Immune-checkpoint inhibition in first-line treatment of advanced non-small cell lung cancer patients: Current status and future approaches.

Immune checkpoint inhibitors are considered standard second-line treatment in advanced non-small cell lung cancer patients. This strategy has also become standard in first-line setting for a subgroup of patients with strongly positive PD-L1 tumors; therefore, PD-L1 status might be considered a new biomarker that deserves upfront testing. New combinations of immune checkpoint inhibitors and with chemotherapy have been tested in first-line treatment. However, some questions remain unanswered such as the best treatment strategy or the real upfront efficacy of these therapeutic strategies in the whole lung cancer population. In this review we summarize the main results in the first-line setting of recent phase III trials with immune checkpoint inhibitors in advanced non-small cell lung cancer patients.

Application of genomic tools in plant breeding.

Plant breeding has been very successful in developing improved varieties using conventional tools and methodologies. Nowadays, the availability of genomic tools and resources is leading to a new revolution of plant breeding, as they facilitate the study of the genotype and its relationship with the phenotype, in particular for complex traits. Next Generation Sequencing (NGS) technologies are allowing the mass sequencing of genomes and transcriptomes, which is producing a vast array of genomic information. The analysis of NGS data by means of bioinformatics developments allows discovering new genes and regulatory sequences and their positions, and makes available large collections of molecular markers. Genome-wide expression studies provide breeders with an understanding of the molecular basis of complex traits. Genomic approaches include TILLING and EcoTILLING, which make possible to screen mutant and germplasm collections for allelic variants in target genes. Re-sequencing of genomes is very useful for the genome-wide discovery of markers amenable for high-throughput genotyping platforms, like SSRs and SNPs, or the construction of high density genetic maps. All these tools and resources facilitate studying the genetic diversity, which is important for germplasm management, enhancement and use. Also, they allow the identification of markers linked to genes and QTLs, using a diversity of techniques like bulked segregant analysis (BSA), fine genetic mapping, or association mapping. These new markers are used for marker assisted selection, including marker assisted backcross selection, 'breeding by design', or new strategies, like genomic selection. In conclusion, advances in genomics are providing breeders with new tools and methodologies that allow a great leap forward in plant breeding, including the 'superdomestication' of crops and the genetic dissection and breeding for complex traits.

Genetic diversity of Brazilian strains of porcine circovirus type 2 (PCV-2) revealed by analysis of the cap gene (ORF-2).

Porcine circovirus 2 (PCV-2) is associated with a broad range of syndromes. In this study, 19 of 870 samples from pigs from different Brazilian states were found to be positive for PCV-2 by polymerase chain reaction (PCR). A fragment of 700 nt of the cap gene (ORF-2) from the 19 PCV-2-positive samples were sequenced using three pairs of primers (Fa/Ra, Fb/Rb and Fc/Rc). Maximum parsimony genealogy with a heuristic algorithm using the 19 field strain studied here, 21 sequences from GenBank and PCV-1 as an out-group showed the existence of two major clusters (A and B) and the Brazilian strains segregating in both of them. PCV-2 was found in pigs with various clinical signs. No association between clusters of PCV-2 and different states or clinical signs were observed, demonstrating that the exact role of PCV-2 in porcine circovirus diseases (PCVD) in Brazil still needs to be clarified. These results contribute to the molecular characterization of PCV-2, which serve as a basis for the epimiology of PCV-2 infection.

Efficacy of fenfluramine and dexfenfluramine in the treatment of obesity: a meta-analysis.

A meta-analysis was conducted to estimate the difference of weight loss among patients treated with placebo and with fenfluramine or dexfenfluramine after 1, 2, 3, 6, and 12 months of treatment. Placebo-controlled, double-blind, randomized clinical trials, whose results were presented as weight loss by the placebo group and the drug-treated patient group, were selected for the analysis. For the pooled estimations, the method of the weighted means by the inverse of the variance was used. The association between the difference of means and several predictive variables was studied by means of weighted linear regression. Patients treated with fenfluramine or dexfenfluramine achieved a higher weight loss than those receiving placebo in all the periods studied. The greatest efficacy was observed after 3 months of treatment. Beyond this time, there is a decline in the effectiveness. Based on the efficacy data, treatments longer than 3 months would not be justified.

Opioid consumption in Spain--the significance of a regulatory measure.

OBJECTIVE: To investigate the impact of new regulatory measures on opioid consumption in Spain during the period 1985-1998. METHODS: A search in the ECOM (Especialidades Consumo de Medicamentos) database of the Ministry of Health was made for the 1985-1998 period. This database contains information about drug preparations prescribed in primary care in the National Health System in Spain. RESULTS: Since 1985-1998, the overall opioid consumption has increased tenfold, from 94.7 DDD (defined daily dose) per million inhabitants per day to more than 1000 DDD. For the five drugs that require a special prescription form (morphine, methadone, pethidine, tilidine and fentanyl), the consumption has increased 13.5-fold. CONCLUSION: A huge increase in opioid consumption has occurred. In this increase, changes in supply and, to a lesser extent, regulatory measures have played an important role.

Aztreonam/clavulanic acid in the treatment of serious infections caused by Stenotrophomonas maltophilia in neutropenic patients: case reports.

Two seriously neutropenic patients (a 23-year-old man with a promyelocytic acute myeloid leukemia [AML-M3] and a 77-year old male with an immature acute myeloid leukemia [AML-M1] diagnosis) with severe infections caused by Stenotrophomonas maltophilia were treated with aztreonam/clavulanic acid (2:1) combination. In the first patient the infection was caused by a multiresistant strain and in the second, by a strain with poor response to trimethoprim-sulfamethoxazole and other antimicrobial agents. After treatment with aztreonam/clavulanic acid both patients evolved favorably.

Comparative evaluation of selective and nonselective media for primary isolation of Helicobacter pylori from gastric biopsies.

BACKGROUND: In this study, we compared and evaluated the efficacy of five culture media for the primary isolation of Helicobacter pylori from gastric biopsies. MATERIALS AND METHODS: A total of 1,174 biopsies (antrum and corpus) taken from 587 patients were plated in parallel on two selective media--Skirrow's medium and brain-heart infusion (BHI) agar supplemented with 10% sheep blood, polymyxin B, vancomycin, trimethoprim, and amphotericin B (HPA medium), and on three nonselective media--chocolate agar with Isovitalex, Columbia blood agar, and BHI-10% sheep blood agar. RESULTS: An isolation rate of 57.9% (680 of 1,174) was obtained with a combination of all media. HPA medium gave the highest isolation rate, 99.4% (676 of 680). Chocolate agar, Columbia blood agar, brain-heart blood agar, and Skirrow's medium showed very poor performance (23.5%, 28.5%, 65.9%, and 71% of all isolates, respectively). The number of cultures in HPA medium discarded due to contamination was only 2 (0.32%). There was no difference in the positive rate of culture in HPA medium between the antrum and the corpus of the stomach. CONCLUSIONS: The HPA medium is superior to Skirrow's medium and nonselective media in promoting growth of H. pylori and, on the basis of these results, we recommended the use of HPA medium for primary isolation of H. pylori from gastric biopsies.