[Adverse events of immune checkpoint inhibitors]. / Nebenwirkungen der Immun-Checkpoint-Inhibitoren.

After immune checkpoint inhibitor therapy was approved for renal cell carcinoma last year, this new immune therapy has spread to urology. Further approvals (atezolizumab, nivolumab, pembrolizumab) are expected in 2017 for metastatic urothelial carcinoma that has progressed following treatment with platinum-based chemotherapy. With expanding use of immune checkpoint inhibitors, experience in diagnosing and managing immune-mediated adverse events increases. Although of low incidence, grade 3/4 toxicities play a central role. Organs most common for immune-mediated adverse events are skin, liver (hepatitis), kidneys (nephritis), gastrointestinal tract (diarrhea and colitis), lungs (pneumonitis), and endocrine organs (hyper-, hypothyroidism and hypophysitis). Diagnostic workup includes routine laboratory tests (including liver function tests) and may be supplemented with hormone values. In cases of pneumonitis or hypophysitis, imaging (high-resolution CT, MRI) can confirm diagnoses. Immune-mediated toxicities are treated with therapy interruption and administration of corticosteroids (and in individual cases additional immunosuppression). Dose modification is not intended!

[Renaissance of immuno-oncology for urological tumors : Current status]. / Renaissance der Immunonkologie bei urologischen Tumoren : Eine Bestandsaufnahme.

With the advent of immune checkpoint inhibitors, immunotherapy has gained new importance in oncology. Current research is focused on the cytotoxic T­lymphocyte antigen 4 (CTLA4), programmed cell death 1 (PD-1) and programmed death ligand 1 (PD-L1) immune checkpoints. The CTLA4 antibody ipilimumab (melanoma) as well as the PD-1 antibodies nivolumab (melanoma, non-small cell lung cancer and renal cell carcinoma) and pembrolizumab (melanoma) are approved for the treatment of metastatic disease in Europe. Immune checkpoint inhibitors (re)activate the immune system against cancer cells and appear to be more effective than current standards for many tumors. The toxicity profile is favorable but involves new so-called immune-related side effects, which need to be recognized and treated in time. Immune checkpoint inhibitors are also currently being tested in uro-oncology in phase 3 trials relevant for approval status. Based on this it is to be expected that immune checkpoint inhibitors will become a new standard (as monotherapy or as part of combination therapy) in the early lines of therapy in the near future and replace the previous standard therapies, particularly for metastasized renal cell carcinoma and urothelial cancer.

SNAP-25 requirement for dendritic growth of hippocampal neurons.

Structure and dimension of the dendritic arbor are important determinants of information processing by the nerve cell, but mechanisms and molecules involved in dendritic growth are essentially unknown. We investigated early mechanisms of dendritic growth using mouse fetal hippocampal neurons in primary culture, which form processes during the first week in vitro. We detected a key component of regulated exocytosis, SNAP-25 (synaptosomal associated protein of 25 kDa), in axons and axonal terminals as well as in dendrites identified by the occurrence of the dendritic markers transferrin receptor and MAP2. Selective inactivation of SNAP-25 by botulinum neurotoxin A (BoNTA) resulted in inhibition of axonal growth and of vesicle recycling in axonal terminals. In addition, dendritic growth of hippocampal pyramidal and granule neurons was significantly inhibited by BoNTA. In contrast, cleavage of synaptobrevin by tetanus toxin had an effect on neither axonal nor dendritic growth. Our observations indicate that SNAP-25, but not synaptobrevin, is involved in constitutive axonal growth and dendrite formation by hippocampal neurons.

[The validation of qualitative nutritional indicators: the Guttman Scale vs the customary diet]. / Validación de indicadores cualitativos de alimentación: Escala de Guttman vs dieta habitual.

The purpose of this study was to assess the validity and feasibility of using the Guttman Scale as an indicator of usual dietary intake. Validation was done by comparing the results of dietary intake of a population obtained by using the Guttman Scale with a well-known method for evaluating dietary intake: the dietary history (one week). The study was done in seven communities in the state of Puebla, Mexico. Results from this study showed a weak correlation between the Guttman Scale with socioeconomic status and nutritional status. However, the results obtained with the dietary history method had a significant relationship with socioeconomic status and nutritional status. The conclusions are that the Guttman Scale has limitations when it is used as an alternative to the dietary history method for evaluating the total caloric intake, though it can be useful to determine dietary patterns of the individual.

Determination of the extent of heat treatment in canned hams by use of the phosphatase test.

In determining the core temperature in canned hams by Lind's phosphatase test, residual activity depends, in general, on the integral heat treatment of the core. The concept of heat treatment equivalent is a clearer description of the phenomenon. The heat treatment equivalents were determined at constant temperatures to give a residual activity as proposed by Lind (69°C for 12-lb cans): T versus log t(69) gives a linear relationship with a z value of 5·85° C allowing the classical F(0) and z concept to be used.