Recreational drug use among individuals living with HIV in Europe: review of the prevalence, comparison with the general population and HIV guidelines recommendations.

BACKGROUND: Adherence problems, interactions and higher rate of risk activities have been observed in HIV individuals using recreational drugs. Our aim was to describe recreational drug use in both HIV individuals and general population in Europe, and to assess at what extent HIV guidelines address this issue. METHODS: Data on recreational drug use across Europe were obtained from the European Monitoring Centre for Drugs and Drug Addiction for the general population, and through Pubmed search. for HIV patients. We assessed the incorporation of recreational drug issues in HIV treatment guidelines for the following topics: (a) recreational drugs; (b) adherence to antiretrovirals; (c) interactions; (d) transmission risk. Guidelines included: World Health Organization; European Aids Clinical Society; U.S. Department of Health and Human Services; International Antiviral Society-USA; and seven European national guidelines. RESULTS: 29 countries reported recreational drug use in general population. The highest prevalences were observed for Cannabis (i.e., 8-10% in Spain, France, and Czech Republic) followed by cocaine, amphetamines and ecstasy. The 13 studies selected in the systematic review showed a great variability in recreational drug use on the HIV population. Apart from classical recreational drugs, we found a relevant use of new drugs including sexual experience enhancers. Polydrug consumption was about 50% in some studies. Most guidelines included general information about recreational drugs, showing great variability on the inclusion of the evaluated topics. We found more specific, evidence-based recommendations on interactions, followed by medication adherence and transmission risk. CONCLUSIONS: Available data on the people living with HIV suggest a higher use of recreational drugs than in the general population, which is already relevant. However, recreational drug issues should be included or addressed more thoroughly in most guidelines

Higher metastatic efficiency of KRas G12V than KRas G13D in a colorectal cancer model

Although all KRas (protein that in humans is encoded by the KRas gene) point mutants are considered to have a similar prognostic capacity, their transformation and tumorigenic capacities vary widely. We compared the metastatic efficiency of KRas G12V (Kirsten rat sarcoma viral oncogene homolog with valine mutation at codon 12) and KRas G13D (Kirsten rat sarcoma viral oncogene homolog with aspartic mutation at codon 13) oncogenes in an orthotopic colorectal cancer (CRC) model. Following subcutaneous preconditioning, recombinant clones of the SW48 CRC cell line [Kras wild-type (Kras WT)] expressing the KRas G12V or KRas G13D allele were microinjected in the mouse cecum. The percentage of animals developing lymph node metastasis was higher in KRas G12V than in KRas G13D mice. Microscopic, macroscopic, and visible lymphatic foci were 1.5- to 3.0-fold larger in KRas G12V than in KRas G13D mice (P < 0.05). In the lung, only microfoci were developed in both groups. KRas G12V primary tumors had lower apoptosis (7.0 ± 1.2 vs. 7.4 ± 1.0 per field, P = 0.02), higher tumor budding at the invasion front (1.2 ± 0.2 vs. 0.6 ± 0.1, P = 0.04), and a higher percentage of C-X-C chemokine receptor type 4 (CXCR4)-overexpressing intravasated tumor emboli (49.8 ± 9.4% vs. 12.8 ± 4.4%, P < 0.001) than KRas G13D tumors. KRas G12V primary tumors showed Akt activation, and β5 integrin, vascular endothelial growth factor A (VEGFA), and Serpine-1 overexpression, whereas KRas G13D tumors showed integrin β1 and angiopoietin 2 (Angpt2) overexpression. The increased cell survival, invasion, intravasation, and specific molecular regulation observed in KRas G12V tumors is consistent with the higher aggressiveness observed in patients with CRC expressing this oncogene

Cancer-specific uptake of a liganded protein nanocarrier targeting aggressive CXCR4⁺ colorectal cancer models

Unliganded drug-nanoconjugates accumulate passively in the tumor whereas liganded nanoconjugates promote drug internalization in tumor cells via endocytosis and increase antitumor efficacy. Whether or not tumor cell internalization associates with enhanced tumor uptake is still under debate. We here compared tumor uptake of T22-GFP-H6, a liganded protein carrier targeting the CXCR4 receptor, and the unliganded GFP-H6 carrier in subcutaneous and metastatic colorectal cancer models. T22-GFP-H6 had a higher tumor uptake in primary tumor and metastatic foci than GFP-H6, with no biodistribution or toxicity on normal tissues. T22-GFP-H6 was detected in target CXCR4+ tumor cell cytosol whereas GFP-H6 was detected in tumor stroma. SDF1-α co-administration switched T22-GFP-H6 internalization from CXCR4+ tumor epithelial cells to the stroma. Therefore, the incorporation of a targeting ligand promotes selective accumulation of the nanocarrier inside target tumor cells while increasing whole tumor uptake in a CXCR4-dependent manner, validating T22-GFP-H6 as a CXCR4-targeted drug carrier

Higher metastatic efficiency of KRas G12V than KRas G13D in a colorectal cancer model

Although all KRas (protein that in humans is encoded by the KRas gene) point mutants are considered to have a similar prognostic capacity, their transformation and tumorigenic capacities vary widely. We compared the metastatic efficiency of KRas G12V (Kirsten rat sarcoma viral oncogene homolog with valine mutation at codon 12) and KRas G13D (Kirsten rat sarcoma viral oncogene homolog with aspartic mutation at codon 13) oncogenes in an orthotopic colorectal cancer (CRC) model. Following subcutaneous preconditioning, recombinant clones of the SW48 CRC cell line [Kras wild-type (Kras WT)] expressing the KRas G12V or KRas G13D allele were microinjected in the mouse cecum. The percentage of animals developing lymph node metastasis was higher in KRas G12V than in KRas G13D mice. Microscopic, macroscopic, and visible lymphatic foci were 1.5- to 3.0-fold larger in KRas G12V than in KRas G13D mice (P < 0.05). In the lung, only microfoci were developed in both groups. KRas G12V primary tumors had lower apoptosis (7.0 ± 1.2 vs. 7.4 ± 1.0 per field, P = 0.02), higher tumor budding at the invasion front (1.2 ± 0.2 vs. 0.6 ± 0.1, P = 0.04), and a higher percentage of C-X-C chemokine receptor type 4 (CXCR4)-overexpressing intravasated tumor emboli (49.8 ± 9.4% vs. 12.8 ± 4.4%, P < 0.001) than KRas G13D tumors. KRas G12V primary tumors showed Akt activation, and β5 integrin, vascular endothelial growth factor A (VEGFA), and Serpine-1 overexpression, whereas KRas G13D tumors showed integrin β1 and angiopoietin 2 (Angpt2) overexpression. The increased cell survival, invasion, intravasation, and specific molecular regulation observed in KRas G12V tumors is consistent with the higher aggressiveness observed in patients with CRC expressing this oncogene

Organización y Calidad en el ámbito hospitalario

Editores: Salazar Soler, Albert; Salazar Macian, Ramon // Cada capítulo está escrito por diferentes autores.Este libro recoge los temas/capítulos del camino de la calidad orientada a los estudios de medicina desde la época antigua hasta la actualidad. Se realiza una secuencia de los temas desde el código de Hammurabi, pasando a los estudios generales de la calidad, y finalmente, a los mas específicos de la organización de la calidad en el ámbito hospitalario. En la segunda parte se estudian los temas/capítulos que abarcan el estudio de la organización y aplicación de los trabajos/ funciones que se desarrollan en un hospital