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BACKGROUND: Although androgen receptor-targeted agents prolong the lives of patients with metastatic prostate cancer, patients develop therapy resistance and most ultimately succumb to the disease. The PI3K/AKT/PTEN pathway has been associated with the development of resistance, raising the possibility that pathway inhibitors may produce a clinical benefit. This open-label phase Ib study examined the safety, tolerability, pharmacokinetics (PK) and preliminary clinical activity of adding capivasertib - a potent, selective inhibitor of AKT1/2/3 - to approved abiraterone acetate therapy. METHODS: Twenty-seven patients with metastatic castration-resistant prostate cancer who had undergone at least 1 prior line of systemic therapy received abiraterone acetate 1000 mg (orally administered once daily), plus oral prednisone 5 mg (twice daily) with capivasertib 400 mg (orally, twice daily, with an intermittent schedule of 4 days on, 3 days off). RESULTS: No dose-limiting toxicity was observed. The most frequent adverse events (all grade) were diarrhea (30%), anemia (26%), asthenia (22%), and nausea (22%). The most frequent grade 3 or higher adverse events were acute kidney injury (19%), hyperglycemia (7%), rash (7%), abdominal pain (7%), and asthenia (7%). Capivasertib and abiraterone PK were consistent with previously reported results from monotherapy dosing. Nine participants (33%) showed a 20% or greater decrease in prostate-specific antigen during study treatment. CONCLUSION: The combination of capivasertib and abiraterone acetate had an acceptable tolerability profile consistent with the known profile of each agent. These data support further evaluation of capivasertib and abiraterone acetate in patients with advanced prostate cancer.
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Acetato de Abiraterona , Neoplasias de la Próstata Resistentes a la Castración , Masculino , Humanos , Neoplasias de la Próstata Resistentes a la Castración/tratamiento farmacológico , Neoplasias de la Próstata Resistentes a la Castración/patología , Astenia/inducido químicamente , Fosfatidilinositol 3-Quinasas , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , PrednisonaRESUMEN
BACKGROUND: Vascular injuries occur in approximately 25% of all penetrating neck traumas, with carotid artery injuries being particularly lethal. Penetrating neck injuries are potentially fatal. Vascular injuries occur in approximately 25% of cases, which can lead to the formation of arteriovenous fistulas. CASE DESCRIPTION: The authors present a case of delayed open surgery to repair a carotid-jugular fistula that resulted in an unprecedented complication, as well as a brief review of the condition's diagnosis and treatment options. CONCLUSION: This case report suggests us that, penetrating neck injuries should be thoroughly evaluated for arteriovenous fistulae. To avoid complications, common carotid-jugular fistulas must be treated as soon as possible. Postoperative complications can be effectively managed with prompt action.
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PURPOSE: To examine the benefit of telehealth over current delivery options in oncology practices without genetic counselors. METHODS: Participants meeting cancer genetic testing guidelines were recruited to this multi-center, randomized trial comparing uptake of genetic services with remote services (telephone or videoconference) to usual care in six predominantly community practices without genetic counselors. The primary outcome was the composite uptake of genetic counseling or testing. Secondary outcomes compare telephone versus videoconference services. RESULTS: 147 participants enrolled and 119 were randomized. Eighty percent of participants in the telehealth arm had genetic services as compared to 16% in the usual care arm (OR 30.52, p < 0.001). Five genetic mutation carriers (6.7%) were identified in the telehealth arm, compared to none in the usual care arm. In secondary analyses, factors associated with uptake were lower anxiety (6.77 vs. 8.07, p = 0.04) and lower depression (3.38 vs. 5.06, p = 0.04) among those who had genetic services. There were no significant differences in change in cognitive or affective outcomes immediately post-counseling and at 6 and 12 months between telephone and videoconference arms. CONCLUSION: Telehealth increases uptake of genetic counseling and testing at oncology practices without genetic counselors and could significantly improve identification of genetic carriers and cancer prevention outcomes.
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Servicios Genéticos/estadística & datos numéricos , Oncología Médica/estadística & datos numéricos , Telemedicina/estadística & datos numéricos , Ansiedad/epidemiología , Consejeros , Depresión/epidemiología , Femenino , Tamización de Portadores Genéticos/estadística & datos numéricos , Asesoramiento Genético/estadística & datos numéricos , Pruebas Genéticas/estadística & datos numéricos , Humanos , Masculino , Persona de Mediana Edad , Tasa de Mutación , Factores Socioeconómicos , Telemedicina/métodos , Teléfono/estadística & datos numéricos , Factores de Tiempo , Comunicación por Videoconferencia/estadística & datos numéricosRESUMEN
The current coronavirus disease 2019 pandemic has been particularly challenging for the clinician because of the unclear nature of the underlying disease mechanisms. One of the hallmarks of the disease involves an increased risk of thrombosis and hypercoagulable state. Here, we describe 2 cases of patients admitted with submassive pulmonary embolism in the setting of positive tests for severe acute respiratory syndrome coronavirus 2.
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COVID-19/diagnóstico por imagen , Pandemias , Embolia Pulmonar/diagnóstico por imagen , SARS-CoV-2/aislamiento & purificación , Adolescente , COVID-19/complicaciones , COVID-19/patología , COVID-19/virología , Angiografía por Tomografía Computarizada , Femenino , Humanos , Embolia Pulmonar/etiología , Embolia Pulmonar/patología , Embolia Pulmonar/virologíaAsunto(s)
Betacoronavirus , Infecciones por Coronavirus , Síndrome Mucocutáneo Linfonodular , Pandemias , Neumonía Viral , COVID-19 , Niño , Humanos , SARS-CoV-2RESUMEN
OBJECTIVES: Tissue factor overexpression is associated with tumor progression, venous thromboembolism, and worsened survival in patients with cancer. Tissue factor and activated factor VII (FVIIa) complex may contribute to tumor invasiveness by promoting cell migration and angiogenesis. The study objective was to evaluate safety, pharmacokinetics, and efficacy of PCI-27483, a selective FVIIa inhibitor. METHODS: This was an open-label, multicenter phase 2 trial of patients with advanced pancreatic cancer. Part A of the study was an intrapatient dose escalation lead-in portion in patients concurrently receiving gemcitabine, and in part B, patients were randomized 1: 1 to the recommended phase 2 dose combination PCI-27483-gemcitabine versus gemcitabine alone. RESULTS: Target international normalized ratio (between 2.0-3.0) was achieved following PCI-27483 treatment. Overall safety of PCI-27483-gemcitabine (n = 26) was similar to gemcitabine alone (n = 16), with a higher incidence of mostly low-grade bleeding events (65% vs. 19%). Progression-free survival (PFS) and overall survival (OS) were not significantly different between patients treated with PCI-27483-gemcitabine (PFS: 3.7 months, OS: 5.7 months) and those treated with gemcitabine alone (PFS: 1.9 months, OS: 5.6 months). CONCLUSIONS: Targeted inhibition of the coagulation cascade was achieved by administering PCI-27483. PCI-27483-gemcitabine was well tolerated, but superiority to single agent gemcitabine was not demonstrated.
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Anticoagulantes/administración & dosificación , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Ácido Aspártico/análogos & derivados , Bencimidazoles/administración & dosificación , Coagulación Sanguínea/efectos de los fármacos , Carcinoma Ductal Pancreático/tratamiento farmacológico , Desoxicitidina/análogos & derivados , Factor VIIa/antagonistas & inhibidores , Neoplasias Pancreáticas/tratamiento farmacológico , Anciano , Anciano de 80 o más Años , Anticoagulantes/efectos adversos , Anticoagulantes/farmacocinética , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Ácido Aspártico/administración & dosificación , Ácido Aspártico/efectos adversos , Ácido Aspártico/farmacocinética , Bencimidazoles/efectos adversos , Bencimidazoles/farmacocinética , Carcinoma Ductal Pancreático/sangre , Carcinoma Ductal Pancreático/mortalidad , Carcinoma Ductal Pancreático/secundario , Desoxicitidina/administración & dosificación , Desoxicitidina/efectos adversos , Monitoreo de Drogas/métodos , Factor VIIa/metabolismo , Femenino , Hemorragia/inducido químicamente , Humanos , Relación Normalizada Internacional , Masculino , Persona de Mediana Edad , Neoplasias Pancreáticas/sangre , Neoplasias Pancreáticas/mortalidad , Neoplasias Pancreáticas/patología , Supervivencia sin Progresión , Factores de Tiempo , GemcitabinaAsunto(s)
Debilidad Muscular , Insuficiencia Respiratoria , Extubación Traqueal , Niño , Humanos , Fósforo , Músculos Respiratorios , Factores de RiesgoRESUMEN
OBJECTIVE: To determine the prevalence of vitamin D deficiency in critically ill children, and to study its association with parathyroid response, severity of illness and clinical outcomes. DESIGN: Prospective observational study. SETTING: Medical Pediatric Intensive Care Unit of a tertiary care centre of Northern India. PARTICIPANTS: 154 children in-patients: August 2011-January 2013. MAIN OUTCOME MEASURES: Vitamin D deficient children were (serum 25-hydroxy vitamin D <20 ug/mL) divided into parathyroid-responder [serum parathyroid hormone >65 pg/mL with 25(OH)D<20 ug/mL and/or calcium corrected for albumin <8.5 mg/dL] and non parathyroid-responder. Illness severity was assessed by Pediatric Index of Mortality-2 (PIM-2) score at admission. Biochemical parameters, illness severity scores and clinical outcomes were compared between parathyroid-responders and non-parathyroid-responders. RESULTS: Vitamin D deficiency and hypocalcemia were observed in 125 (83.1%) and 91 (59%) children, respectively at admission. There were no differences in illness severity score at admission, mortality rate and length of stay between vitamin D-deficient children and 19.8% of non-vitamin D-deficient children. Among Vitamin D-deficient children, parathyroid-responders had higher PIM-2 score at admission compared to non-parathyroid-responder [12.8 (7.4,20.6) vs. 6.5 (2.5,12.2), P=0.01]. However, there were no differences in other clinical outcomes between two groups. CONCLUSION: Critically ill children have high prevalence of vitamin D deficiency. Parathyroid gland response secondary to hypocalcemia or vitamin D defiency is impaired in critical illness.
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Enfermedad Crítica/epidemiología , Hipocalcemia/complicaciones , Hipocalcemia/epidemiología , Deficiencia de Vitamina D/complicaciones , Deficiencia de Vitamina D/epidemiología , Niño , Preescolar , Humanos , India , Lactante , Recién Nacido , Hormona Paratiroidea/sangre , Estudios Prospectivos , Índice de Severidad de la Enfermedad , Resultado del TratamientoRESUMEN
OBJECTIVES: To determine the prevalence of hypophosphatemia in critically ill children and its association with clinical outcomes; to determine risk factors and mechanism of hypophosphatemia. METHODS: Levels of serum phosphate, phosphate intake, renal phosphate handling indices and blood gases were measured on days 1, 3, 7 and 10 of pediatric intensive care unit (PICU) stay. Hypophosphatemia was defined as any serum phosphorus <3.8 mg/dl for children younger than 2 y and <3.5 mg/dl for children 2 y or older. Renal phosphate loss was assessed using the ratio of tubular maximum reabsorption of phosphate (TmP) to glomerular filtration rate (GFR) [TmP/GFR]. RESULTS: Prevalence of hypophosphatemia was 71.6 % (95 % CI: 64.6-78.6). On adjusted analysis, hypophosphatemia was associated with prolonged PICU length of stay (PICU LOS > 6 d) (adjusted OR: 3.0 [95 % CI: 1.4-6.7; p = 0.005]) but not associated with increased mortality. Renal phosphate threshold was significantly lower on all the days in hypophosphatemic group compared to that of non-hypophosphatemic group. No statistically significant difference in the amount of phosphate intake was seen in both the groups. CONCLUSIONS: Hypophosphatemia is highly prevalent in critically ill children and is associated with prolonged PICU LOS. Increased phosphate loss in urine is one of the mechanism responsible for hypophosphatemia in critically ill children.
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Enfermedad Crítica , Hipofosfatemia , Niño , Femenino , Tasa de Filtración Glomerular , Humanos , Unidades de Cuidado Intensivo Pediátrico , Masculino , Factores de RiesgoAsunto(s)
Deficiencia de Vitamina D , Vitamina D , Niño , Enfermedad Crítica , Humanos , Hormona ParatiroideaRESUMEN
OBJECTIVE: To assess the impact of nutritional status on outcomes like mortality rate, length of mechanical ventilation and length of Pediatric Intensive Care Unit (PICU) stay, in critically ill children. METHODS: In this retrospective study conducted at a tertiary care center, records of 332 critically ill children between 1 mo to 15 y of age for whom anthropometric parameters were available were included. Anthropometric parameters for the study subjects were used to assess the nutritional status using the WHO growth charts as the reference. The study subjects were categorized as non-malnourished, moderately, and severely malnourished, defined by Body mass index (BMI) for age 0 to -2 SD, -2 to -3 SD and less than -3 SD of WHO growth charts, respectively. Various outcomes like mortality, duration of PICU stay and duration of mechanical ventilation were assessed in the 3 groups based on the nutritional status. RESULTS: The prevalence of malnutrition in the index study was 51.2 % with an overall mortality of 38.8 %. No difference was found between mortality rates and proportion of ventilated children in the three study groups. However, more children who were severely malnourished had significantly prolonged ICU stay (>7 d) as well as duration of mechanical ventilation (>7 d). When the outcome variables were compared after adjusting for PIM2 scores, there were increasing odds of mortality, ventilation, prolonged PICU stay and duration of mechanical ventilation with increasing severity of malnutrition. CONCLUSIONS: After stabilization of the initial critical phase, PICU outcome is influenced by the nutritional status of the children.
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Enfermedad Crítica/mortalidad , Desnutrición/epidemiología , Estado Nutricional , Respiración Artificial , Adolescente , Niño , Preescolar , Femenino , Humanos , Lactante , Unidades de Cuidado Intensivo Pediátrico , Tiempo de Internación , Masculino , Evaluación Nutricional , Estado Nutricional/fisiología , PrevalenciaRESUMEN
BACKGROUND: Angiogenesis is a key element in solid-tumor growth, invasion, and metastasis. VEGF is among the most potent angiogenic factor thus far detected. The aim of the present study is to explore the potential of VEGF (also known as VEGF-A) as a prognostic and predictive biomarker among men with locally advanced prostate cancer. METHODS: The analysis was performed using patients enrolled on RTOG 8610, a phase III randomized control trial of radiation therapy alone (Arm 1) versus short-term neoadjuvant and concurrent androgen deprivation and radiation therapy (Arm 2) in men with locally advanced prostate carcinoma. Tissue samples were obtained from the RTOG tissue repository. Hematoxylin and eosin slides were reviewed, and paraffin blocks were immunohistochemically stained for VEGF expression and graded by Intensity score (0-3). Cox or Fine and Gray's proportional hazards models were used. RESULTS: Sufficient pathologic material was available from 103 (23%) of the 456 analyzable patients enrolled in the RTOG 8610 study. There were no statistically significant differences in the pre-treatment characteristics between the patient groups with and without VEGF intensity data. Median follow-up for all surviving patients with VEGF intensity data is 12.2 years. Univariate and multivariate analyses demonstrated no statistically significant correlation between the intensity of VEGF expression and overall survival, distant metastasis, local progression, disease-free survival, or biochemical failure. VEGF expression was also not statistically significantly associated with any of the endpoints when analyzed by treatment arm. CONCLUSIONS: This study revealed no statistically significant prognostic or predictive value of VEGF expression for locally advanced prostate cancer. This analysis is among one of the largest sample bases with long-term follow-up in a well-characterized patient population. There is an urgent need to establish multidisciplinary initiatives for coordinating further research in the area of human prostate cancer biomarkers.