Search

Understanding persistence of humoral immune responses elicited by vaccination against coronavirus disease 2019 (COVID-19) is critical for informing the duration of protection and appropriate booster timing. We developed a mechanistic model to characterize the time course of humoral immune responses in severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2)-seronegative adults after primary vaccination with the Janssen COVID-19 vaccine, Ad26.COV2.S. The persistence of antibody responses was quantified through mechanistic modeling-based simulations. Two biomarkers of humoral immune responses were examined: SARS-CoV-2 neutralizing antibodies determined by wild-type virus neutralization assay (wtVNA) and spike protein-binding antibodies determined by indirect spike protein enzyme-linked immunosorbent assay (S-ELISA). The persistence of antibody responses was defined as the period of time during which wtVNA and S-ELISA titers remained above the lower limit of quantification. A total of 442 wtVNA and 1,185 S-ELISA titers from 82 and 220 participants, respectively, were analyzed following administration of a single dose of Ad26.COV2.S (5 × 10

Several factors such as low therapeutic index, large interindividual variability in systemic exposure, and the relationships between exposure and toxicity for sorafenib could justify its therapeutic drug monitoring (TDM). To support TDM, a selective and precise high-performance liquid chromatography with ultraviolet detection (HPLC-UV) method was developed and validated for the determination of sorafenib in human plasma.After protein precipitation with acetonitrile, sorafenib and lapatinib (internal standard) were separated using isocratic elution on a Kromasil C18 column using a mobile phase of acetonitrile and 20 mmol/L ammonium acetate in a proportion 53:47 (vol/vol) pumped at a constant flow rate of 1.2 mL/min. Quantification was performed at 260 nm. Validation experiments were carried out after the guidelines for Bioanalytical Method Validation published by the Food and Drug Administration and the European Medicines Agency.Calibration curves were linear over the range 0.1-20 mcg/mL. Inter- and intra-day coefficients of variation were3%. The limit of detection and the lower limit of quantification were 0.06 and 0.1 mcg/mL, respectively. Recoveries of sorafenib from plasma were99% in all cases.This method was successfully applied to the determination of the drug in the plasma of 2 patients with cancer receiving sorafenib 200 and 400 mg orally twice daily, respectively, and could be useful for TDM of sorafenib in routine clinical practice.

Peritoneal carcinomatosis is a relatively frequent situation in the natural history of colorectal cancer and is associated with a dismal prognosis. Promising results have been shown after radical cytoreduction followed by intraperitoneal chemohyperthermic perfusion. The aim our study was to assess the outcomes after treating patients with peritoneal carcinomatosis of colonic origin by means of cytoreductive surgery and intraoperative hyperthermic intraperitoneal chemotherapy (HIPEC) followed by early postoperative intraperitoneal chemotherapy (EPIC).Tumour resection was performed in accordance with the guidelines for oncologic surgery. Selective peritonectomies and remnant nodule electroevaporation were performed with the aim of achieving a complete cytoreduction. Peritoneal perfusion was carried out according to the Coliseum technique at 0.5-1 L/min, and chemotherapy was administered at 42oC for 40-90 min. Mitomycin C 10-12.5 mg/m(2) or oxaliplatin 360 mg/m(2) was used. Postoperative intraperitoneally administered 5-fluorouracil (5-FU) (650 mg/m(2) per day) was given for 5 consecutive days.Twenty patients were treated from 2001 to 2008. The mean peritoneal cancer index was 11 (range 2-39). Fifteen patients had undergone complete cytoreductive surgery. The morbidity was 40%. There was one case of death due to bone marrow aplasia. Ten patients had recurrence; five of them underwent salvage surgery. Two patients were treated with a second HIPEC. Actuarial overall survival and progression-free survival were 36% and 30% at 5 years, respectively, with a median follow-up of 18 (range 8-28) months.Cytoreductive surgery combined with HIPEC is a feasible technique that might increase patient survival. It represents a potential cure for selected patients who have no other alternatives.

Nuestro objetivo es comparar la efectividad del inicio del tratamiento con rHu-GCSF transcurridas 24 ho-ras (dia +1) desde la reinfusion de celulas precursoras hematopoyeticas de sangre periferica (CPHSP) con la administracion de rHu-GCSF 5 dias (dia +5) despues de la reinfusion de CPHSP en pacientes con cancer de mama de alto riesgo. Cuarenta y una pacientes de 47±9 anos, peso 70±12 kg, y talla 158±5 cm, que recibieron el esquema STAMP-V de quimioterapia se dividieron y fueron asignadas aleatoriamente al grupo A (n=21) cuando el inicio del rHu-GCSF es el dia +1 y al grupo B cuando el tratamiento se inicio el dia +5; la efectividad del trata-miento se establecio en funcion del tiempo transcurrido desde la reinfusion de CPHSP hasta alcanzar cifras de neutrofilos superiores a 500·106/1 durante 3 dias seguidos. La efectividad del tratamiento se analizo, mediante regresion de Cox, en relacion con la edad, peso, talla, superficie corporal, aclaramiento plasmatico de carboplatino y ciclofosfamida, dosis de celulas CD34+, e inicio del tratamiento con rHu-GCSF.

The external administration of recombinant human erythropoietin is the chosen treatment for those patients with secondary anemia due to chronic renal failure undergoing periodic hemodialysis. The goal is to carry out an individualised prediction of the erythropoietin dosage to be administered. It is justified because of the high cost of this medication, its secondary effects and the phenomenon of potential resistance which some individuals suffer. One hundred and ten patients were included in this study and several factors were collected in order to develop the neural models. Since the results obtained were excellent, an easy-to-use decision-aid computer application was implemented.

This paper proposes the use of neural networks ensemble for predicting the cyclosporine A (CyA)concen tration in kidney transplant patients. In order to optimize clinical outcomes and to reduce the cost associated with patient care, accurate prediction of CyA concentrations is the main objective of therapeutic drug monitoring. Thirty-two renal allograft patients and different factors (age, weight, gender, creatinine and post-transplantation days, together with past dosages and concentrations)w ere studied to obtain the best models. Three kinds of networks (multilayer perceptron, FIR network, Elman recurrent network) and the formation of neural-network ensembles were used. The FIR network, yielding root-mean-squared errors (RMSE)of 41.61 ng/mL in training (22 patients)and 52.34 ng/mL in validation (10 patients)sho wed the best results. A committee of trained networks improved accuracy (RMSE = 44.77 ng/mL in validation).