Tyrosine kinase inhibitors reprogramming immunity in renal cell carcinoma: rethinking cancer immunotherapy.

The immune system regulates angiogenesis in cancer by way of both pro- and antiangiogenic activities. A bidirectional link between angiogenesis and the immune system has been clearly demonstrated. Most antiangiogenic molecules do not inhibit only VEGF signaling pathways but also other pathways which may affect immune system. Understanding of the role of these pathways in the regulation of immunosuppressive mechanisms by way of specific inhibitors is growing. Renal cell carcinoma (RCC) is an immunogenic tumor in which angiogenesis and immunosuppression work hand in hand, and its growth is associated with impaired antitumor immunity. Given the antitumor activity of selected TKIs in metastatic RCC (mRCC), it seems relevant to assess their effect on the immune system. The confirmation that TKIs improve cell cytokine response in mRCC provides a basis for the rational combination and sequential treatment of TKIs and immunotherapy.

[Gastric bypass in the surgical treatment of the morbid obesity and super obesity: comparative study]. / Bypass gástrico en el tratamiento de la obesidad mórbida y la superobesidad: estudio comparativo.

INTRODUCTION: Gastric Bypass (GB) constitutes the surgical treatment of election of morbid obesity (BMI < 50) at the present time, however doubts exist about its effectiveness in super obesity patients (BMI > 50). OBJECTIVE: The purpose of this work is one of to analyze the results of loss of weight of the first 52 open GB of our series, and to compare the losses of weight in morbid obesity (MO) and super obesity (SO), to determine if the superobese patient looses enough weight with this technique or if it would be more indicated another technique more malabsorptive, like some authors recommend. MATERIALS AND METHOD: Retrospective study of the first 52 patients operated of open GB pathway. The weight loss of 32 patients' with MO are compared with the weight loss of 20 patients with super obesity after five year follow-up. The parameters analyzed are: age, sex, height, initial weight, current weight, initial BMI, current BMI, % BMI lost, % overweight lost, incidence of incisional hernia, acceptable oral tolerance and metabolic alterations. The malabsorptive procedure associated in patients with super obesity was a 200 cm Roux-en-Y and a patients with BMI between 40 and 50 was a 150 cm Roux-en-Y. The results are compared by means of the X2 and Mann Whitney statistical test. RESULTS: The age, the sex and the stature are homogeneous in the two groups. In the group of MO the initial weight was of 121.5 kg; initial BMI, 45; current BMI; 28.9, the median loss of weight in 5 years was of 48 kg; the percentage loss of the excess of BMI is of 80% and the percentage loss of the excess of weight is of 74.6%. In the group of SO the initial weight was of 142.,7 kg; initial BMI, 54.9; current BMI, 34.,9; the median loss of weight in 5 years was of 54 kg; the percentage loss of the excess of BMI was of 65,3% and the percentage loss of the excess of weight was of 63.2%. The analysis of the results ponders shows that it exists statistically significant differences (P < 0.05) among the two groups, however the rate of success, according to the classic parameter of loss of more than 50% of the excess of weight, was superior to 90% in both groups. The results of the study about the presence of incisional postoperative hernia, alimentary tolerance and metabolic alterations, indicate that it doesn't exist differences statistically significant between both groups. CONCLUSIONS: GB is an effective surgical technique in patients with morbid obesity and with super obesity, provided that in these patients is realized a procedure more malabsorptive. There are not differences between both groups, in morbidity, improvement in the associate disease, alimentary tolerance and necessity of nutritional supplements.

Experimental equations to calculate aminoglycoside clearances through cuprophan dialyzers.

Aminoglycosides are a group of antibiotics of particular interest because of their widespread use in the treatment of infections caused by gram-negative bacteria. However, they are difficult to dose accurately because of their narrow therapeutic range and overdosing produces a large number of toxic effects. This paper describes a study carried out with the aim of ensuring the accurate administration of these antibiotics in end-stage renal disease patients undergoing hemodialysis, by developing equations which enable the dosage for individual patients to be calculated according to the dialyzer being used and the operational conditions set up during the dialysis session.

An in vitro study of the influence of a drug's molecular weight on its overall (Clt), diffusive (Cld) and convective (Clc) clearance through dialysers.

The dialyser clearance of a drug is the sum of two components: one diffusive, arising from the concentration gradient across the membrane, and the other convective, arising from the ultrafiltration of plasma water, produced by the increases in hydraulic pressure that the membrane undergoes. To demonstrate the importance of these clearances during haemodialysis, this study analyses the influence of a drug's molecular weight on them. To this end, an experimental study of dialysis in vitro was carried out to determine the clearances, in aqueous solution, of five drugs of increasing molecular weights (theophylline, quinidine, tobramycin, digoxin, and vancomycin), using two series of dialysers with the same type of membrane (Cuprophan), differing in effective surface area and ultrafiltration coefficient. From the data obtained in this study, the importance of quantifying convective clearance during haemodialysis becomes apparent since if it is not taken into account errors of up to 20% and more may be made. This is particularly so if the drug is of high molecular weight and if a high filtration rate is being used.