RESUMEN
BACKGROUND: Vaccination of cancer patients with p53-expressing modified vaccinia Ankara virus (p53MVA) has shown in our previous studies to activate p53-reactive T cells in peripheral blood but without immediate clinical benefit. We hypothesized that the immunological responses to p53MVA vaccine may require additional immune checkpoint blockade to achieve clinically beneficial levels. We therefore conducted a phase I trial evaluating the combination of p53MVA and pembrolizumab (anti-PD-1) in patients with advanced solid tumors. PATIENTS AND METHODS: Eleven patients with advanced breast, pancreatic, hepatocellular, or head and neck cancer received up to 3 triweekly vaccines in combination with pembrolizumab given concurrently and thereafter, alone at 3-week intervals until disease progression. The patients were assessed for toxicity and clinical response. Correlative studies analyzed p53-reactive T cells and profile of immune function gene expression. RESULTS: We observed clinical responses in 3/11 patients who remained with stable disease for 30, 32, and 49 weeks. Two of these patients showed increased frequencies and persistence of p53-reactive CD8+ T cells and elevation of expression of multiple immune response genes. Borderline or undetectable p53-specific T cell responses in 7/11 patients were related to no immediate clinical benefit. The first study patient had a grade 5 fatal myocarditis. After the study was amended for enhanced cardiac monitoring, no additional cardiac toxicities were noted. CONCLUSION: We have shown that the combination of p53MVA vaccine with pembrolizumab is feasible, safe, and may offer clinical benefit in select group of patients that should be identified through further studies.
Asunto(s)
Anticuerpos Monoclonales Humanizados/uso terapéutico , Antineoplásicos Inmunológicos/uso terapéutico , Vacunas contra el Cáncer/uso terapéutico , Terapia Combinada/métodos , Neoplasias/terapia , Adulto , Anciano , Linfocitos T CD8-positivos/inmunología , Vacunas contra el Cáncer/inmunología , Femenino , Vectores Genéticos , Humanos , Masculino , Persona de Mediana Edad , Neoplasias/inmunología , Proteína p53 Supresora de Tumor/administración & dosificación , Proteína p53 Supresora de Tumor/inmunologíaRESUMEN
A Check-up is characterized as a medical examination and a counselling of asymptomatic persons. The aim of such a Check-up is the identification of modifiable risk factors for different illnesses and/or the detection of a treatable, latent disease. The value and the cost-effectiveness of regular Check-up examinations can be assessed in scientific enquiries. However, the question whether regular Check-up examinations are or are not of value from an individual or societal point of view cannot be answered by the results of evaluative studies alone. This question should be discussed between an individual person and a physician or, in general, on a societal level. In addition, in this paper we discuss various tests recommended for a patient who requires a Check-up examination.
Asunto(s)
Examen Físico , Adulto , Factores de Edad , Anciano , Diagnóstico Diferencial , Femenino , Humanos , Masculino , Persona de Mediana Edad , Pronóstico , Radiografía Torácica , Factores de Riesgo , Factores de Tiempo , Frotis VaginalRESUMEN
Acute fatty liver is a rare but usually severe and frightening complication of the last trimester of pregnancy. Many patients therefore do not want or are warned against having another child. This report adds another case of successful consecutive pregnancy to the 28 documented cases in 24 patients. On the other hand, only 2 recurrences have been reported. Therefore, the wish for another pregnancy may be supported, provided the gravida is well informed and the necessary (bi)weekly clinical and laboratory checks are carried out in the last trimester (liver tests, uric acid, prothrombin time and, in case of doubt, further coagulation tests including antithrombin III).
Asunto(s)
Hígado Graso/complicaciones , Complicaciones del Embarazo , Resultado del Embarazo , Adulto , Femenino , Humanos , Recién Nacido , Pruebas de Función Hepática , Embarazo , Embarazo Múltiple , Atención Prenatal , GemelosRESUMEN
After major abdominal surgery 32 patients received a parenteral nutrition for 6 days with 360 g of a carbohydrate mixture (levulose:glucose:xylitol = 2:1:1) and 100 g of an L-amino acid mixture/24 h. 16 patients with benign disease showed positive nitrogen balances, 16 patients with malignant diseases balanced or slightly negative nitrogen balances. Postoperatively, blood glucose levels did not require insulin. Less than 1.5% of the infused levulose, 2.0% of glucose and 2.4-4.1% of xylitol were found in urine. C3- and C4- complement levels in serum were below normal, transferrin showed a pathological decrease in carcinoma patients.
Asunto(s)
Abdomen/cirugía , Dieta , Ingestión de Energía , Cuidados Posoperatorios , Aminoácidos/administración & dosificación , Carbohidratos/orina , Complemento C3/análisis , Complemento C4/análisis , Carbohidratos de la Dieta/administración & dosificación , Electrólitos/sangre , Femenino , Humanos , Persona de Mediana Edad , Nitrógeno/orina , Nutrición Parenteral , Periodo Posoperatorio , Transferrina/análisisRESUMEN
32 patients with major abdominal surgery received parenteral nutrition with 360 g carbohydrate mixture (levulose: glucose: xylitol = 2:1:1)/24 hours and 1000 ml of a 10% L-amino acid mixture (potato-egg-pattern)/24 hours. Daily nitrogen balances were balanced or slightly negative. Daily we determined serum amino acid concentration; essential amino acid levels were normal. Of non-essential amino acid levels glutamine acid and aspartic acid were elevated. Amino acid loss in urine was 0.2 to 3%, only tryptophan and histidine were excreted in 6.6 and 7.0%.
Asunto(s)
Aminoácidos/sangre , Carbohidratos de la Dieta/metabolismo , Nutrición Parenteral , Aminoácidos/orina , Glucemia/análisis , Humanos , Procedimientos Quirúrgicos OperativosRESUMEN
Infusion of a 3% amino acid solution after moderate abdominal surgery for 4 - 6 days postoperatively results in a nitrogen-saving effect as compared with an infusion of carbohydrates or a combination of carbohydrates and amino acids. Patients who received only amino acids showed the lowest blood glucose levels, but a significant increase of ketone bodies and triglycerides in serum, which is an indication of lipolysis.
Asunto(s)
Aminoácidos/uso terapéutico , Nitrógeno/metabolismo , Nutrición Parenteral , Abdomen/cirugía , Adulto , Anciano , Aminoácidos/administración & dosificación , Fructosa/administración & dosificación , Glucosa/administración & dosificación , Humanos , Persona de Mediana Edad , Periodo PosoperatorioRESUMEN
This, the fourth part of a synopisis of cutaneous side effects of drugs, covers the drugs affecting the central nervous system: antiepileptics, hypnotics, narcotics and psychopharmaceutics; the myorelaxants and antiallergics follow, and lastly there is a section on drug addiction and placebo. The various cutaneous side effects are listed in chart form referring to more than 500 sources. A drug index is attached for handy reference. The reviews of certain drug induced skin disorders are continued with tables covering photosensitivity and changes in skin colour. Phototoxicity, photoallergy and light sensitivity by porphyria are differentiated. The various pigmentation disorders, colour changes due to metal deposits as well as different localisations are included.