RESUMEN
INTRODUCTION: Neoadjuvant endocrine therapy is often utilized to downstage Estrogen Receptor-positive (ER+) breast cancer prior to surgery. However, this approach is sometimes met with endocrine resistance mechanisms within the tumor. This trial examines the safety and efficacy of tamoxifen in combination with an mTORC1/2 inhibitor, TAK-228, in the neoadjuvant treatment of ER+ breast cancer. METHODS: In this single-arm, open-label trial, pre- and post-menopausal women were enrolled to receive neoadjuvant tamoxifen (20 mg daily) with TAK-228 (30 mg weekly) for 16 weeks prior to surgery. Patient had tissue sampling at baseline, week 6, and week 16. The primary endpoint was change in Ki-67 from baseline to 6 weeks. The toxicity, change in tumor size, pathologic complete response rate, PEPI score, and baseline Oncotype Dx score were also assessed. RESULTS: Twenty-eight women were enrolled on the trial, and 25 completed the entire study course. The combination of tamoxifen and TAK-228 resulted in a significant reduction in Ki-67 from 18.3 to 15.2% (p = 0.0023). The drug was also found to be safe and tolerable. While nausea and hyperglycemia were common side effects, these were manageable. The tumor size also significantly decreased with the treatment, with a median decrease of 0.75 cm (p < 0.0001). There were no pathologic complete responses. CONCLUSION: Tamoxifen and TAK-228 was safe and well tolerated neoadjuvant treatment for ER+ breast cancer, preliminary evidence of activity with significant reduction in both Ki-67 and tumor size, warranting further evaluation in a larger study.
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Neoplasias de la Mama , Terapia Neoadyuvante , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Benzoxazoles , Neoplasias de la Mama/tratamiento farmacológico , Femenino , Hormonas/uso terapéutico , Humanos , Nitrilos/uso terapéutico , Pirimidinas , Receptor ErbB-2/genética , Receptores de Estrógenos , Tamoxifeno/uso terapéutico , Resultado del Tratamiento , Triazoles/uso terapéuticoRESUMEN
BACKGROUND: Rasburicase is commonly used in patients with hematologic malignancies for tumor lysis syndrome prophylaxis and management. Methemoglobinemia is a serious rare adverse effect of rasburicase, more common in patients with G6PD deficiency. Prompt diagnosis and appropriate management of this condition can make the difference between successful recovery and significant morbidity. Here we discuss the link of rasburicase with methemoglobinemia and the pathophysiology behind increased incidence of this side effect in G6PD deficient patients. METHODS: We report the case of a 73-year-old African American man who developed methemoglobinemia on rasburicase treatment, who was later confirmed to be G6PD deficient. We reviewed the literature using Pubmed and Google Scholar using the following key words: "methemoglobinemia", "rasburicase", "urate oxidase", tumor lysis syndrome", G6PD deficiency", "hemolytic anemia" and "hyperuricemia". RESULTS: Rasburicase-induced methemoglobinemia is more common in patients with G6PD deficiency, and rasburicase is therefore contraindicated in these patients. Clinical presentation includes cyanosis, pallor, methemoglobin levels of 8-12%, and oxygen saturation gap which is evident from ABG analysis, though pulse oximetry is normal. Treatment consists of oxygen supplementation, ascorbic acid and blood transfusion. Importantly, methylene blue is avoided as therapy in G6PD deficiency as it can worsen the methemoglobinemia. CONCLUSION: Rasburicase-induced methemoglobinemia is a serious concern, especially in African- American patients. It should be considered when clinical signs and symptoms are present. Knowledge of this side effect is important in early diagnosis and successful management of the condition.
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Deficiencia de Glucosafosfato Deshidrogenasa/diagnóstico , Supresores de la Gota/efectos adversos , Metahemoglobinemia/inducido químicamente , Metahemoglobinemia/diagnóstico , Urato Oxidasa/efectos adversos , Anciano , Deficiencia de Glucosafosfato Deshidrogenasa/sangre , Humanos , Masculino , Metahemoglobinemia/sangreRESUMEN
OBJECTIVE: To compare case-mix, health care practices, and outcome in obstetric ICU admissions in inner-city teaching hospitals in economically developed and developing countries. DESIGN: Retrospective study. SETTING: Ben Taub General Hospital (BTGH), Houston, Texas, and King Edward Memorial Hospital (KEMH), Mumbai, India. PATIENTS: Women admitted during pregnancy or 6 weeks postpartum between 1992 and 2001. MEASUREMENTS AND RESULTS: Patients from BTGH (n=174) and KEMH (n=754) had comparable age, number of organs affected, incidence of medical disorders (30%), liver dysfunction, and thrombocytopenia. Fewer KEMH patients received prenatal care (27 vs 86%) and came to hospital within 24 h of onset of symptoms (60 vs 90%). They had higher APACHE II scores (median 16 vs 10), greater incidence of neurological (63 vs 36%), renal (50 vs 37%), and cardiovascular dysfunction (39 vs 29%). Severe malaria, viral hepatitis, cerebral venous thrombosis, and poisoning were common medical disorders. The BTGH group had higher incidence of respiratory dysfunction (59 vs 46%) and disseminated intravascular coagulation (40 vs 23%), placental anomalies, HELLP syndrome, chorioamnionitis, peripartum cardiomyopathy, puerperal sepsis, urinary infection, bacteremia, substance abuse, and asthma. More BTGH patients required mechanical ventilation and blood component therapy, whereas more KEMH patients needed dialysis. Of BTGH patients, 78.2% were delivered by cesarean section (vs 15.4%). Maternal (2.3 vs 25%) and fetal (13 vs 51%) mortality were lower in BTGH patients. CONCLUSIONS: There were marked differences in medical diseases, organ failure, and intensive care needs. Higher mortality in the Indian ICU may be due to difference in case mix, inadequate prenatal care, delay in reaching hospital, and greater severity of illness.
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Enfermedad Crítica , Complicaciones del Embarazo/terapia , Adulto , Cuidados Críticos/economía , Femenino , Edad Gestacional , Hospitales Públicos , Humanos , India , Unidades de Cuidados Intensivos , Insuficiencia Multiorgánica/etiología , Insuficiencia Multiorgánica/terapia , Embarazo , Complicaciones del Embarazo/clasificación , Complicaciones del Embarazo/diagnóstico , Estudios Retrospectivos , Trombocitopenia/etiología , Trombocitopenia/terapia , Resultado del Tratamiento , Estados UnidosRESUMEN
BACKGROUND: Imatinib mesylate has become one of the main chemotherapeutic agents currently used to treat patients with chronic myeloid leukemia (CML). Although cutaneous reactions to this drug have been documented before, this is the first time that Sweet syndrome has been reported with its use. OBSERVATIONS: We report a case of Sweet syndrome secondary to the administration of imatinib to treat CML. On 2 separate occasions, a 53-year-old African American woman with CML developed neutrophilic dermatosis consistent with Sweet syndrome after chemotherapy with imatinib. CONCLUSION: Greater awareness of the adverse effects of imatinib and the characterization of its cutaneous adverse effects will lead to improved surveillance for and treatment of those adverse effects.
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Antineoplásicos/efectos adversos , Leucemia Mielógena Crónica BCR-ABL Positiva/diagnóstico , Leucemia Mielógena Crónica BCR-ABL Positiva/tratamiento farmacológico , Piperazinas/efectos adversos , Pirimidinas/efectos adversos , Síndrome de Sweet/inducido químicamente , Síndrome de Sweet/patología , Antineoplásicos/uso terapéutico , Benzamidas , Biopsia con Aguja , Femenino , Estudios de Seguimiento , Humanos , Mesilato de Imatinib , Inmunohistoquímica , Persona de Mediana Edad , Piperazinas/uso terapéutico , Pirimidinas/uso terapéutico , Medición de Riesgo , Índice de Severidad de la EnfermedadRESUMEN
Pneumococcal bacteremia secondary to acute epiglottitis is relatively rare, and all previously reported cases occurred in immunocompromised patients. We report a case of pneumococcal bacteremia associated with acute epiglottitis and retropharyngeal soft-tissue inflammation with upper airway narrowing that occurred in an otherwise healthy patient. In light of our unique finding, we recommend that pneumococcal bacteremia be suspected in an otherwise healthy patient who has systemic manifestations associated with acute epiglottitis.