Estudio de factores de predictibilidad: Expresión de IGF1-R, p73, MMR (MLH-1, MSH-2), COX-2 y VEGF en el cáncer colorrectal estenosante y no estenosante

El cáncer colorrectal (CCR) es la tercera neoplasia más frecuente y la cuarta causa de mortalidad por cáncer en el mundo, con índices de supervivencia que oscilan entre el 30 y el 65%, según la zona geográfica de residencia. El CCR es el responsable del 60- 90% de todos los casos de obstrucción del colon, siendo la estenosis el problema quirúrgico agudo más común, su efecto debe verse afectado por la localización del tumor. El propósito de este estudio fue la búsqueda de dianas potenciales en grupos de alto riesgo, precisando las causas por las que este tipo de neoplasias debutan como obstrucción intestinal y su efecto en el pronóstico vital del enfermo. Para ello, mediante técnicas inmunohistoquímicas, analizamos la expresión de IGF1-R, p73, MMR (MLH1, MSH2), COX-2 y VEGF en especímenes de CCR, pertenecientes a pacientes con un tiempo de seguimiento de 5 años. El CCR obstructivo se ha presentado como un factor predictor clínico y vital del paciente, asociándose a un estadio más avanzado de la enfermedad. Nuestro modelo experimental sugiere que VEGF, COX-2, IGF-1R, p73 e índice de proliferación celular, tienen un impacto potencial en la carcinogénesis y en la historia natural de la neoplasia. La patología obstructiva, con un diámetro ostensiblemente mayor del tumor, la invasión de nodos linfáticos adyacentes, la presencia de valores elevados de VEGF, p73, y Ki- 67, son importantes elementos en el índice de riesgos de la recurrencia de la enfermedad y en la supervivencia. La detección de niveles de antígeno carcinoembrionario postoperatorio fue una buena herramienta suplementaria en el seguimiento oncológico.Colorectal cancer (CRC) is the third most common malignancy and the fourth leading cause of cancer mortality in the world, with survival rates ranging between 30 and 65% depending on the geographical area of residence. The CRC is responsible for 60-90% of all cases of colon obstruction, stenosis being the most common acute surgical problem, its effect should be affected by the location of the tumor. The purpose of this study was to search for potential targets in high-risk groups, specifying the reasons why this type of tumor debut as intestinal obstruction and its effect on the prognosis of the patient. We analysed, using immunohistochemical staining, the expression of IGF1-R, p73, MMR (MLH1, MSH2), COX-2 and VEGF in specimens of CRC, belonging to patients with follow-up time of 5 years. Obstructive CRC has been presented as a clinical and vital predictor of patient, associated to a more advanced stage of the disease. Our experimental model suggests that VEGF, COX-2, IGF-1R, p73 and cell proliferation index, have potential in carcinogenesis and in the natural history of neoplasia. The obstructive disease with a markedly greater tumour diameter, invasion of adjacent lymph nodes, the presence of high levels of VEGF, p73 and Ki-67 are important elements in the index risk of recurrence of the disease and the survival of patients. The detection of carcinoembryonic antigen levels after surgery was a good supplementary tool in monitoring for cancer

Role of age and comorbidities in mortality of patients with infective endocarditis

[Purpose]: The aim of this study was to analyse the characteristics of patients with IE in three groups of age and to assess the ability of age and the Charlson Comorbidity Index (CCI) to predict mortality. [Methods]: Prospective cohort study of all patients with IE included in the GAMES Spanish database between 2008 and 2015.Patients were stratified into three age groups:<65 years,65 to 80 years,and ≥ 80 years.The area under the receiver-operating characteristic (AUROC) curve was calculated to quantify the diagnostic accuracy of the CCI to predict mortality risk. [Results]: A total of 3120 patients with IE (1327 < 65 years;1291 65-80 years;502 ≥ 80 years) were enrolled.Fever and heart failure were the most common presentations of IE, with no differences among age groups.Patients ≥80 years who underwent surgery were significantly lower compared with other age groups (14.3%,65 years; 20.5%,65-79 years; 31.3%,≥80 years). In-hospital mortality was lower in the <65-year group (20.3%,<65 years;30.1%,65-79 years;34.7%,≥80 years;p < 0.001) as well as 1-year mortality (3.2%, <65 years; 5.5%, 65-80 years;7.6%,≥80 years; p = 0.003).Independent predictors of mortality were age ≥ 80 years (hazard ratio [HR]:2.78;95% confidence interval [CI]:2.32–3.34), CCI ≥ 3 (HR:1.62; 95% CI:1.39–1.88),and non-performed surgery (HR:1.64;95% CI:11.16–1.58).When the three age groups were compared,the AUROC curve for CCI was significantly larger for patients aged <65 years(p < 0.001) for both in-hospital and 1-year mortality. [Conclusion]: There were no differences in the clinical presentation of IE between the groups. Age ≥ 80 years, high comorbidity (measured by CCI),and non-performance of surgery were independent predictors of mortality in patients with IE.CCI could help to identify those patients with IE and surgical indication who present a lower risk of in-hospital and 1-year mortality after surgery, especially in the <65-year group

Neuroprotective and reparative effects of carotid body grafts in a chronic MPTP model of Parkinson's disease

Intrastriatal transplantation of dopaminergic carotid body (CB) cells ameliorates parkinsonism in animal models and, with less efficacy, in Parkinson's disease patients. CB-based cell therapy was initially proposed because of its high dopamine content. However, later studies suggested that its beneficial effect might be due to a trophic action exerted on nigrostriatal neurons. Compatible with this concept are the high levels of neurotrophic factors encountered in CB cells. To test experimentally this idea, unilateral striatal transplants were performed with a sham graft in the contralateral striatum, as a robust internal control. Thereafter, the dopaminergic neurotoxin 1-methyl-4-phenyl-1,2,3,6, -tetrahydropyridine was injected during 3 months. CB grafts protected from degeneration ipsilateral nigral dopaminergic neurons projecting to the transplant in a dose-dependent manner regarding size and glial cell line-derived neurotrophic factor expression. Grafts performed at different times after the onset of the neurotoxic treatment demonstrated with histological and behavioral methods protection and repair of the nigrostriatal pathway by CB transplants. This study provides a mechanistic explanation for the action of CB transplants on parkinsonian models. It should also help to improve cell therapy approaches to Parkinson's disease. © 2013 Elsevier Inc.This study was supported by grants from the Spanish Government (FIS, Red TERCEL, CIBERNED, MEC, and MICINN), the Andalusian Government (Excellence projects) and the Marcelino Botín Foundation.Peer Reviewe

Prosthetic Valve Candida spp. Endocarditis: New Insights Into Long-term Prognosis—The ESCAPE Study

International audienceBackground: Prosthetic valve endocarditis caused by Candida spp. (PVE-C) is rare and devastating, with international guidelines based on expert recommendations supporting the combination of surgery and subsequent azole treatment.Methods: We retrospectively analyzed PVE-C cases collected in Spain and France between 2001 and 2015, with a focus on management and outcome.Results: Forty-six cases were followed up for a median of 9 months. Twenty-two patients (48%) had a history of endocarditis, 30 cases (65%) were nosocomial or healthcare related, and 9 (20%) patients were intravenous drug users. "Induction" therapy consisted mainly of liposomal amphotericin B (L-amB)-based (n = 21) or echinocandin-based therapy (n = 13). Overall, 19 patients (41%) were operated on. Patients <66 years old and without cardiac failure were more likely to undergo cardiac surgery (adjusted odds ratios [aORs], 6.80 [95% confidence interval [CI], 1.59-29.13] and 10.92 [1.15-104.06], respectively). Surgery was not associated with better survival rates at 6 months. Patients who received L-amB alone had a better 6-month survival rate than those who received an echinocandin alone (aOR, 13.52; 95% CI, 1.03-838.10). "Maintenance" fluconazole therapy, prescribed in 21 patients for a median duration of 13 months (range, 2-84 months), led to minor adverse effects.Conclusion: L-amB induction treatment improves survival in patients with PVE-C. Medical treatment followed by long-term maintenance fluconazole may be the best treatment option for frail patients

Contemporary use of cefazolin for MSSA infective endocarditis: analysis of a national prospective cohort

Objectives: This study aimed to assess the real use of cefazolin for methicillin-susceptible Staphylococcus aureus (MSSA) infective endocarditis (IE) in the Spanish National Endocarditis Database (GAMES) and to compare it with antistaphylococcal penicillin (ASP). Methods: Prospective cohort study with retrospective analysis of a cohort of MSSA IE treated with cloxacillin and/or cefazolin. Outcomes assessed were relapse; intra-hospital, overall, and endocarditis-related mortality; and adverse events. Risk of renal toxicity with each treatment was evaluated separately. Results: We included 631 IE episodes caused by MSSA treated with cloxacillin and/or cefazolin. Antibiotic treatment was cloxacillin, cefazolin, or both in 537 (85%), 57 (9%), and 37 (6%) episodes, respectively. Patients treated with cefazolin had significantly higher rates of comorbidities (median Charlson Index 7, P <0.01) and previous renal failure (57.9%, P <0.01). Patients treated with cloxacillin presented higher rates of septic shock (25%, P = 0.033) and new-onset or worsening renal failure (47.3%, P = 0.024) with significantly higher rates of in-hospital mortality (38.5%, P = 0.017). One-year IE-related mortality and rate of relapses were similar between treatment groups. None of the treatments were identified as risk or protective factors. Conclusion: Our results suggest that cefazolin is a valuable option for the treatment of MSSA IE, without differences in 1-year mortality or relapses compared with cloxacillin, and might be considered equally effective

Role of age and comorbidities in mortality of patients with infective endocarditis.

The aim of this study was to analyse the characteristics of patients with IE in three groups of age and to assess the ability of age and the Charlson Comorbidity Index (CCI) to predict mortality. Prospective cohort study of all patients with IE included in the GAMES Spanish database between 2008 and 2015.Patients were stratified into three age groups: A total of 3120 patients with IE (1327  There were no differences in the clinical presentation of IE between the groups. Age ≥ 80 years, high comorbidity (measured by CCI),and non-performance of surgery were independent predictors of mortality in patients with IE.CCI could help to identify those patients with IE and surgical indication who present a lower risk of in-hospital and 1-year mortality after surgery, especially in th