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ABSTRACT: T-ALL relapse usually occurs early but can occur much later, which has been suggested to represent a de novo leukemia. However, we conclusively demonstrate late relapse can evolve from a pre-leukemic subclone harbouring a non-coding mutation that evades initial chemotherapy.
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Leucemia-Linfoma de Células T do Adulto , Leucemia-Linfoma Linfoblástico de Células T Precursoras , Humanos , Leucemia-Linfoma Linfoblástico de Células T Precursoras/genética , Mutação , Recidiva , Doença Crônica , Células ClonaisRESUMO
BACKGROUND: Pectoralis nerve (Pecs) blocks have been shown to reduce perioperative opioid consumption in patients undergoing mastectomies, but the effectiveness of these blocks in breast reductions has not been established. This trial aims to evaluate the efficacy of Pecs blocks (I and II) on perioperative pain management in patients undergoing breast reductions. METHODS: Thirty-six patients were enrolled in the randomized controlled trial divided into 2 groups. The treatment group (n = 16) received general anesthesia plus postinduction ultrasound-guided Pecs blocks. The control group (n = 20) received general anesthesia alone. The primary outcomes measured were perioperative narcotic requirements, need for postoperative antiemetics, pain scores, and length of time in the operating room (OR). We measured patient and procedural risk factors including pedicle/skin excision patterns, concurrent liposuction, weight of resection, and additional local anesthesia. Risk factors as well as outcomes were analyzed using Fischer exact and t tests. RESULTS: No statistically significant difference was shown between the group receiving the Pecs blocks and the control with regard to narcotic requirements, pain scores, and need for antiemetics. Patients undergoing Pecs blocks had a significantly higher OR time before incision (P = 0.0073). Patient and procedural risk factors were well balanced (P > 0.41). CONCLUSIONS: Pectoralis nerve blocks may be a valuable component of a multimodality pain regimen; however, when performed as a solitary adjunct, they do not seem to decrease perioperative narcotic requirements, pain scores, or the need for antiemetic medication in patients undergoing breast reductions. In addition, postinduction Pecs blocks significantly increase OR times.
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Mamoplastia , Bloqueio Nervoso , Nervos Torácicos , Humanos , Dor Pós-Operatória/prevenção & controle , Estudos ProspectivosRESUMO
Glycogen storage disease is a rare congenital disorder that can lead to hypoglycemic events. This article focuses on a patient in acute distress secondary to hypoglycemia that failed to respond to initial interventions. Because symptoms can be similar to severe hyperglycemia, a thorough history and physical examination are key to prompt diagnosis and appropriate management.
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Doença de Depósito de Glicogênio Tipo I/complicações , Hipoglicemia/diagnóstico , Hipoglicemia/etiologia , Adulto , Biomarcadores/sangue , Glicemia , Diagnóstico Diferencial , Feminino , Gluconeogênese , Glucose/administração & dosagem , Humanos , Hiperglicemia , Hipoglicemia/terapia , Injeções Intravenosas , Insulinoma , Ressuscitação , Tomografia Computadorizada por Raios XRESUMO
Heterotopic pregnancy occurs when a patient has simultaneous intrauterine and ectopic pregnancies. Rates of heterotopic pregnancy have been rising with increased availability and access to in vitro fertilization and other advanced fertility technologies. Symptoms of heterotopic pregnancy are nonspecific, such as vague abdominal pain, so transvaginal ultrasound is a crucial part of the diagnostic process. Laparoscopy is the most commonly performed treatment of the ectopic pregnancy; other options include localized injections of methotrexate and/or potassium chloride. Following definitive termination of the ectopic pregnancy, many patients will successfully deliver the intrauterine pregnancy at term. Early identification of heterotopic pregnancy can reduce maternal morbidity and mortality.
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Gravidez Heterotópica/diagnóstico , Gravidez Heterotópica/terapia , Dor Abdominal/etiologia , Depressão Pós-Parto , Diagnóstico Precoce , Feminino , Fertilização in vitro/efeitos adversos , Humanos , Dispositivos Intrauterinos/efeitos adversos , Laparoscopia , Laparotomia , Metotrexato/administração & dosagem , Cloreto de Potássio/administração & dosagem , Gravidez , Gravidez Heterotópica/etiologia , Fatores de Risco , Fumar/efeitos adversos , Ultrassonografia Pré-NatalRESUMO
Sickle cell disease (SCD) is a group of inherited blood disorders affecting the hemoglobin, shortening the lifespan of erythrocytes, and causing them to take on a distinctive sickled shape that can lead to vaso-occlusion. Current treatment aims to reduce morbidity and mortality through hydroxyurea, erythrocyte transfusion, and hematopoietic stem cell transplantation. This article reviews the disease process, typical presentations, complications, and acute and chronic treatment options.
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Analgésicos Opioides/uso terapêutico , Anemia Falciforme/terapia , Antidrepanocíticos/uso terapêutico , Transfusão de Eritrócitos , Síndrome Torácica Aguda/diagnóstico , Síndrome Torácica Aguda/etiologia , Síndrome Torácica Aguda/terapia , Doença Aguda , Anemia Falciforme/complicações , Anemia Falciforme/fisiopatologia , Antibacterianos/uso terapêutico , Doença Crônica , Progressão da Doença , Hidratação , Terapia Genética , Glutamina/uso terapêutico , Transplante de Células-Tronco Hematopoéticas , Humanos , Hidroxiureia/uso terapêutico , Recém-Nascido , Controle de Infecções , Infecções , Isquemia Mesentérica/diagnóstico , Isquemia Mesentérica/etiologia , Isquemia Mesentérica/terapia , Triagem Neonatal , Oxigenoterapia , Manejo da Dor , Educação de Pacientes como Assunto , Infecções Pneumocócicas/prevenção & controle , Vacinas Pneumocócicas/uso terapêutico , Acidente Vascular Cerebral/diagnóstico , Acidente Vascular Cerebral/etiologia , Acidente Vascular Cerebral/terapiaRESUMO
With improved survivorship in medulloblastoma, there has been an increasing incidence of late complications. To date, no studies have specifically addressed the risk of radiation-associated diffuse intrinsic pontine glioma (DIPG) in medulloblastoma survivors. Query of the International DIPG Registry identified six cases of DIPG with a history of medulloblastoma treated with radiotherapy. All patients underwent central radiologic review that confirmed a diagnosis of DIPG. Six additional cases were identified in reports from recent cooperative group medulloblastoma trials (total n = 12; ages 7 to 21 years). From these cases, molecular subgrouping of primary medulloblastomas with available tissue (n = 5) revealed only non-WNT, non-SHH subgroups (group 3 or 4). The estimated cumulative incidence of DIPG after post-treatment medulloblastoma ranged from 0.3-3.9%. Posterior fossa radiation exposure (including brainstem) was greater than 53.0 Gy in all cases with available details. Tumor/germline exome sequencing of three radiation-associated DIPGs revealed an H3 wild-type status and mutational signature distinct from primary DIPG with evidence of radiation-induced DNA damage. Mutations identified in the radiation-associated DIPGs had significant molecular overlap with recurrent drivers of adult glioblastoma (e.g. NRAS, EGFR, and PTEN), as opposed to epigenetic dysregulation in H3-driven primary DIPGs. Patients with radiation-associated DIPG had a significantly worse median overall survival (median 8 months; range 4-17 months) compared to patients with primary DIPG. Here, it is demonstrated that DIPG occurs as a not infrequent complication of radiation therapy in survivors of pediatric medulloblastoma and that radiation-associated DIPGs may present as a poorly-prognostic distinct molecular subgroup of H3 wild-type DIPG. Given the abysmal survival of these cases, these findings provide a compelling argument for efforts to reduce exposure of the brainstem in the treatment of medulloblastoma. Additionally, patients with radiation-associated DIPG may benefit from future therapies targeted to the molecular features of adult glioblastoma rather than primary DIPG.
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Neoplasias do Tronco Encefálico/etiologia , Neoplasias do Tronco Encefálico/genética , Glioma/etiologia , Glioma/genética , Histonas/genética , Mutação/genética , Radioterapia/efeitos adversos , Adolescente , Neoplasias Cerebelares/radioterapia , Criança , Estudos de Coortes , Exoma , Feminino , Proteínas Hedgehog/metabolismo , Humanos , Cooperação Internacional , Masculino , Meduloblastoma/radioterapia , Sistema de Registros , Transdução de Sinais/fisiologia , Estatísticas não Paramétricas , Transcriptoma , Proteínas Wnt/metabolismo , Adulto JovemRESUMO
BACKGROUND: Viral infection of the bronchial epithelium disrupts the barrier properties of the epithelium in healthy individuals and those with lung disease. Repair of the bronchial epithelium is dependent of the formation of a provisional fibrin matrix and migration of epithelial cells to cover denuded areas, followed by proliferation and differentiation. OBJECTIVE: The objective was to test the hypothesis that poly I:C, a model of viral infection, limits epithelial repair through the stimulated release of matrix metalloproteinase-13 (MMP-13). METHODS: Confluent layers of cultured normal human primary bronchial epithelial cells (NHBE) and SV-40 virus-transformed 16HBE14o- bronchial epithelial cells were mechanically wounded, and video microscopy used to measure the rate of wound closure over 2 hours, in the absence and presence of poly I:C (1-20 µg/mL). MMP-13, tissue factor and endothelin release were measured by ELISA. The effect of inhibitors of MMP-13 activity and expression and a nonspecific endothelin receptor antagonist, bosentan, on the rate of epithelial repair was investigated. RESULTS: Poly I:C limited the rate of epithelial repair, and NHBE were significantly more sensitive to poly I:C effects than 16HBE14o- cells. NHBE, but not 16HBE14o-, released MMP-13 in response to poly I:C. Inhibitors of MMP-13 activity (WAY 170523) and expression (dimethyl fumarate) significantly enhanced the rate of repair. Bosentan enhanced the rate of bronchial epithelial repair by a mechanism that was independent of MMP-13. CONCLUSIONS AND CLINICAL RELEVANCE: Bronchial epithelial repair is limited by endothelin and by MMP-13, a protease that degrades coagulation factors, such as fibrinogen, and matrix proteins essential for epithelial repair. Further studies with primary cells from patients are needed to confirm whether repurposing bosentan and inhibitors of MMP-13 expression or activity, for inhalation may be a useful therapeutic strategy in diseases where repeated cycles of epithelial injury and repair occur, such as asthma and COPD.
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Brônquios/efeitos dos fármacos , Brônquios/metabolismo , Metaloproteinase 13 da Matriz/metabolismo , Inibidores de Metaloproteinases de Matriz/farmacologia , Mucosa Respiratória/efeitos dos fármacos , Mucosa Respiratória/metabolismo , Cicatrização/efeitos dos fármacos , Brônquios/patologia , Brônquios/virologia , Diferenciação Celular/efeitos dos fármacos , Linhagem Celular , Proliferação de Células/efeitos dos fármacos , Células Cultivadas , Células Epiteliais/efeitos dos fármacos , Células Epiteliais/metabolismo , Células Epiteliais/virologia , Humanos , Poli I-C/imunologia , Poli I-C/farmacologia , Mucosa Respiratória/patologia , Mucosa Respiratória/virologia , Infecções Respiratórias/imunologia , Infecções Respiratórias/metabolismo , Infecções Respiratórias/virologiaRESUMO
Abdominal aortic aneurysm (AAA) is a clinical challenge in risk assessment, recognition, treatment, and prevention. This article explores the pathogenesis, presentation, diagnosis, treatment, and prevention of AAA.
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Aneurisma da Aorta Abdominal/terapia , Procedimentos Cirúrgicos Vasculares , Conduta Expectante , Fatores Etários , Angiografia , Aorta/diagnóstico por imagem , Aneurisma da Aorta Abdominal/diagnóstico , Aneurisma da Aorta Abdominal/epidemiologia , Aneurisma da Aorta Abdominal/prevenção & controle , Aterosclerose/epidemiologia , Aterosclerose/terapia , Doença da Artéria Coronariana/epidemiologia , Humanos , Hiperlipidemias/epidemiologia , Hiperlipidemias/terapia , Hipertensão/tratamento farmacológico , Hipertensão/epidemiologia , Imageamento por Ressonância Magnética , Programas de Rastreamento , Fatores de Risco , Comportamento de Redução do Risco , Fatores Sexuais , Fumar/epidemiologia , Abandono do Hábito de Fumar , Tomografia Computadorizada por Raios X , UltrassonografiaRESUMO
Patients with cancer are at higher risk for venous thromboembolism than patients without cancer due to hypercoagulability associated with malignancy. This article describes a patient with metastatic renal cell carcinoma who had chest pain over several weeks caused by multiple pulmonary emboli.
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Carcinoma de Células Renais/secundário , Neoplasias Renais/patologia , Neoplasias Pulmonares/diagnóstico por imagem , Embolia Pulmonar/diagnóstico por imagem , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma de Células Renais/complicações , Carcinoma de Células Renais/tratamento farmacológico , Dor no Peito/etiologia , Doxorrubicina/administração & dosagem , Eletrocardiografia , Enoxaparina/uso terapêutico , Fibrinolíticos/uso terapêutico , Humanos , Medula Renal , Neoplasias Renais/complicações , Neoplasias Renais/tratamento farmacológico , Neoplasias Hepáticas/secundário , Neoplasias Pulmonares/complicações , Neoplasias Pulmonares/secundário , Masculino , Estadiamento de Neoplasias , Paclitaxel/administração & dosagem , Embolia Pulmonar/complicações , Embolia Pulmonar/tratamento farmacológico , Tomografia Computadorizada por Raios XRESUMO
First-time seizures are frightening to children and their families, but the practice parameter recommends minimal evaluation in the emergency department (ED) for the child who presents in a neurologically normal state. We report a 12-year-old girl with seizure whose evaluation in the ED included a computed tomographic scan, largely because of parental anxiety. Computed tomography demonstrated a cerebral cavernous hemangioma or cavernoma. Because of the high recurrence risk of seizures with cavernomas, she was discharged from the ED with a prescription for an antiepileptic drug.
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Hemangioma Cavernoso do Sistema Nervoso Central/diagnóstico por imagem , Lobo Parietal/diagnóstico por imagem , Convulsões/etiologia , Anticonvulsivantes/uso terapêutico , Tronco Encefálico/irrigação sanguínea , Hemorragia Cerebral/diagnóstico , Criança , Diagnóstico Diferencial , Suscetibilidade a Doenças , Diagnóstico Precoce , Emergências , Epilepsias Parciais/tratamento farmacológico , Epilepsias Parciais/etiologia , Saúde da Família , Feminino , Hemangioma Cavernoso do Sistema Nervoso Central/complicações , Hemangioma Cavernoso do Sistema Nervoso Central/etnologia , Humanos , México/etnologia , Pais/psicologia , Lobo Parietal/irrigação sanguínea , Guias de Prática Clínica como Assunto , Fatores de Risco , Tomografia Computadorizada por Raios XRESUMO
The hormone leptin modulates a diverse range of biological functions, including energy homeostasis and reproduction. Leptin promotes GnRH function via an indirect action on forebrain neurons. We tested whether leptin deficiency or leptin resistance due to a high-fat diet (HFD) can regulate the potent reproductive neuropeptide kisspeptin. In mice with normalized levels of estradiol, leptin deficiency markedly reduced kisspeptin gene expression, particularly in the arcuate nucleus (ARC), and kisspeptin immunoreactive cell numbers in the rostral periventricular region of the third ventricle (RP3V). The HFD model was used to determine the effects of diet-induced obesity and central leptin resistance on kisspeptin cell number and gene expression. DBA/2J mice, which are prone to HFD-induced infertility, showed a marked decrease in kisspeptin expression in both the RP3V and ARC and cell numbers in the RP3V after HFD. This is the first evidence that kisspeptin can be regulated by HFD and/or increased body weight. Next we demonstrated that leptin does not signal (via signal transducer and activator of transcription 3 or 5, or mammalian target of rapamycin) directly on kisspeptin-expressing neurons in the RP3V. Lastly, in leptin receptor-deficient mice, neither GnRH nor kisspeptin neurons were activated during a preovulatory-like GnRH/LH surge induction regime, indicating that leptin's actions on GnRH may be upstream of kisspeptin neurons. These data provide evidence that leptin's effects on reproductive function are regulated by kisspeptin neurons in both the ARC and RP3V, although in the latter site the effects are likely to be indirect.