Mitochondrial redox impairment and enhanced autophagy in peripheral blood mononuclear cells from type 1 diabetic patients.

Type 1 diabetes (T1D) involves critical metabolic disturbances that contribute to an increased cardiovascular risk. Leukocytes are key players in the onset of atherosclerosis due to their interaction with the endothelium. However, whether mitochondrial redox impairment, altered bioenergetics and abnormal autophagy in leukocytes contribute to T1D physiopathology is unclear. In this study we aimed to evaluate the bioenergetic and redox state of peripheral blood mononuclear cells (PBMCs) from T1D patients in comparison to those from healthy subjects, and to assess autophagy induction and leukocyte-endothelial interactions. T1D patients presented lower levels of fast-acting and total antioxidants in their blood, and their leukocytes produced higher amounts of total reactive oxygen species (ROS) and superoxide radical with respect to controls. Basal and ATP-linked respiration were similar in PBMCs from T1D and controls, but T1D PBMCs exhibited reduced spare respiratory capacity and a tendency toward decreased maximal respiration and reduced non-mitochondrial respiration, compared to controls. The autophagy markers P-AMPK, Beclin-1 and LC3-II/LC3-I were increased, while P62 and NBR1 were decreased in T1D PBMCs versus those from controls. Leukocytes from T1D patients displayed lower rolling velocity, higher rolling flux and more adhesion to the endothelium versus controls. Our findings show that T1D impairs mitochondrial function and promotes oxidative stress and autophagy in leukocytes, and suggest that these mechanisms contribute to an increased risk of atherosclerosis by augmenting leukocyte-endothelial interactions.

Crioterapia frente a high intensity focused ultrasound en el tratamiento del cáncer de próstata: resultados oncológicos y funcionales / Cryotherapy versus high-intensity focused ultrasound for treating prostate cancer: Oncological and functional results

Contexto y objetivo: El diagnóstico cada vez más precoz del cáncer de próstata obliga a buscar alternativas terapéuticas con buenos resultados oncológicos, que a su vez faciliten una buena calidad de vida a largo plazo. La presente revisión analiza los resultados de 2 terapias mínimamente invasivas en el tratamiento del cáncer localizado de próstata en cuanto a resultados oncológicos y funcionales, así como las complicaciones derivadas de los mismos. Adquisición de la evidencia: Revisión sistemática de la literatura referida al tratamiento del cáncer localizado de próstata con 2 técnicas ablativas como terapia primaria: la criocirugía o crioterapia y el high intensity focused ultrasound (HIFU). Se incluyen pacientes con procedimientos que incluían la totalidad de la glándula, con hemiablación o con terapia focal e indicados en cáncer de próstata de bajo riesgo o riesgo intermedio según criterios D'Amico. Se excluyen pacientes con cáncer de próstata de alto riesgo, o aquellos que hayan recibido cualquier tratamiento previo para el cáncer de próstata. Síntesis de la evidencia: Tras la búsqueda y exclusión de estudios que no cumplían los criterios del protocolo, se revisan un total de 14 estudios, con un total de 350 pacientes tratados mediante crioterapia, y un total de 1.107 pacientes tratados con HIFU. En todos los casos se trataron de estudios prospectivos o retrospectivos, no aleatorizados. La edad media de los pacientes fue de menos de 75 años. En global la tasa de recidiva anatomopatológica en los pacientes tratados con crioterapia oscila entre el 13,2% y el 26%, mientras que en el HIFU oscilan entre el 7,3% y el 67,9%. La continencia global mostrada fue de un 97,6-100% en el caso de la crioterapia, y un 96-100% en el HIFU a los 12 meses. Respecto a las tasas de potencia sexual la crioterapia muestra una potencia completa del 86-100% a los 12 meses en pacientes tratados con crioterapia focal, y algo menores en la hemiablación (76,9-100%) y en la terapia total (39%). El HIFU reporta tasas de potencia del 89% 52-80% y 33-78% en terapia focal, hemiablación y terapia total respectivamente. Conclusiones: Ambas técnicas presentan unos resultados funcionales equiparables, si bien los resultados oncológicos algo más pobres en el HIFU son reflejo de una curva de aprendizaje más complicada, que puede abocar su uso a centros con alto volumen de pacientes

Context and objective: The increasingly early diagnosis of prostate cancer requires a search for therapeutic alternatives with good oncological results that in turn facilitate a good long-term quality of life. This review analyses 2 minimally invasive therapies for treating localised prostate cancer in terms of oncological and functional results, as well as the complications resulting from the therapies. Acquisition of evidence: A systematic literature review was conducted of the treatment of localised prostate cancer with 2 ablative techniques as the primary therapy: cryosurgery or cryotherapy and high intensity focused ultrasound (HIFU). We included patients who underwent procedures that included the entire gland, with hemiablation or focal therapy, which were indicated for low to intermediate-risk prostate cancer according to the D’Amico criteria. We excluded patients with high-risk prostate cancer and those who underwent any prior treatment for prostate cancer. Synthesis of the evidence: After conducting the literature search and excluding the studies that did not meet the protocol criteria, we reviewed a total of 14 studies, with a total of 350 patients treated using cryotherapy and 1107 treated with HIFU. All studies were either prospective or retrospective and were not randomised. The patients' mean age was younger than 75 years. Overall, the rate of disease recurrence in the patients treated with cryotherapy varied between 13.2% and 26%, while the rate for those treated with HIFU varied between 7.3% and 67.9%. The overall demonstrated continence at 12 months was 97.6-100% for cryotherapy and 96-100% for HIFU. In terms of sexual potency rates, cryotherapy showed complete potency at 12 months for 86-100% of the patients treated with focal cryotherapy and slightly lower rates for hemiablation (76.9-100%) and total therapy (39%). HIFU showed potency rates of 89%, 52-80% and 33-78% for focal therapy, hemiablation and total therapy, respectively. Conclusions: Both techniques have comparable functional results, although the somewhat poorer oncological results for HIFU reflect a steeper learning curve, which could lead to its use in centres with high volumes of patients

Cryotherapy versus high-intensity focused ultrasound for treating prostate cancer: Oncological and functional results. / Crioterapia frente a high intensity focused ultrasound en el tratamiento del cáncer de próstata: resultados oncológicos y funcionales.

CONTEXT AND OBJECTIVE: The increasingly early diagnosis of prostate cancer requires a search for therapeutic alternatives with good oncological results that in turn facilitate a good long-term quality of life. This review analyses 2 minimally invasive therapies for treating localised prostate cancer in terms of oncological and functional results, as well as the complications resulting from the therapies. ACQUISITION OF EVIDENCE: A systematic literature review was conducted of the treatment of localised prostate cancer with 2 ablative techniques as the primary therapy: cryosurgery or cryotherapy and high intensity focused ultrasound (HIFU). We included patients who underwent procedures that included the entire gland, with hemiablation or focal therapy, which were indicated for low to intermediate-risk prostate cancer according to the D'Amico criteria. We excluded patients with high-risk prostate cancer and those who underwent any prior treatment for prostate cancer. SYNTHESIS OF THE EVIDENCE: After conducting the literature search and excluding the studies that did not meet the protocol criteria, we reviewed a total of 14 studies, with a total of 350 patients treated using cryotherapy and 1107 treated with HIFU. All studies were either prospective or retrospective and were not randomised. The patients' mean age was younger than 75 years. Overall, the rate of disease recurrence in the patients treated with cryotherapy varied between 13.2% and 26%, while the rate for those treated with HIFU varied between 7.3% and 67.9%. The overall demonstrated continence at 12 months was 97.6-100% for cryotherapy and 96-100% for HIFU. In terms of sexual potency rates, cryotherapy showed complete potency at 12 months for 86-100% of the patients treated with focal cryotherapy and slightly lower rates for hemiablation (76.9-100%) and total therapy (39%). HIFU showed potency rates of 89%, 52-80% and 33-78% for focal therapy, hemiablation and total therapy, respectively. CONCLUSIONS: Both techniques have comparable functional results, although the somewhat poorer oncological results for HIFU reflect a steeper learning curve, which could lead to its use in centres with high volumes of patients.

Carcinoma de células renales con invasión vascular: mortalidad y factores pronósticos / Renal cell carcinoma with vascular invasion: mortality and prognostic factors

Objetivo. Análisis de los resultados obtenidos en el seguimiento de los pacientes intervenidos de carcinoma renal con invasión vascular en nuestro centro, evaluación de los factores pronósticos y de las complicaciones. Material y métodos. Estudio observacional retrospectivo de 37 pacientes diagnosticados de carcinoma renal con invasión vascular intervenidos entre mayo de 1999 y julio de 2013. Se emplean el método de Kaplan-Meier para el análisis de supervivencias y la prueba de Mantel-Haenszel (LogRank) y el modelo de riesgos proporcionales de Cox para el análisis de los factores de riesgo de mortalidad. Resultados. La mediana de edad fue de 60 años. El tiempo de seguimiento medio de 42,1 meses. Las medianas de supervivencia global y supervivencia libre de enfermedad fueron de 53,8 y 36,3 meses respectivamente. Existe asociación estadística entre supervivencia global y el ASA (p=0,047), estadio tumoral (p=0,003), la afectación ganglionar (p=0,024), la presencia de metástasis (p=0,013), el nivel de trombo tumoral (p=0,05) y el tipo histológico (p=0,001). Catorce pacientes presentaron complicaciones grado IIIb o mayor según la clasificación de Clavien-Dindo, siendo la más frecuente el sangrado. Conclusiones. El carcinoma renal con invasión vascular es una enfermedad con alta tasa de mortalidad. La cirugía es una opción terapéutica que puede resultar curativa. El número de complicaciones es importante. La supervivencia está condicionada por el ASA, el estadio tumoral, el nivel de trombo tumoral, la afectación ganglionar, las metástasis y el tipo histológico (AU)

Objective. Analysis of the results of patients who had been operated of renal cell carcinoma with vascular invasion in our institution, evaluation of prognostic factors and complications. Methods. Retrospective observational study of 37 patients diagnosed of renal cell carcinoma with vascular invasion operated between May 1999 and July 2013. We used the method of Kaplan-Meier survival analysis and the Mantel-Haenszel's test (log rank) and the Cox's proportional hazards analysis test to analyse the risk factors of mortality. Results. The median age was 60 years. Mean follow-up period was 42.1 months. The median overall survival and disease-free survival were 53.8and 36.3 months, respectively. There was statistical association between overall survival and ASA (p=0.047), tumor stage (p=0.003), lymph node involvement (p=0.024), presence of metastases (p=0.013), level of tumor thrombus (p=0, 05) and histological type (p=0.001). 14 patients had grade IIIb complications or higher according to the Clavien Dindo classification, the most frequent was bleeding. Conclusions. Renal cell carcinoma with vascular invasion is a disease with high rate of mortality. Surgery is a therapeutic option that can be curative. The number of complications is important. Survival is conditioned by the ASA, tumor stage, the level of tumor thrombus, lymph node involvement, metastasis and histological type (AU)

Renal cell carcinoma with vascular invasion: Mortality and prognostic factors. / Carcinoma de células renales con invasión vascular: mortalidad y factores pronósticos.

OBJECTIVE: Analysis of the results of patients who had been operated of renal cell carcinoma with vascular invasion in our institution, evaluation of prognostic factors and complications. METHODS: Retrospective observational study of 37 patients diagnosed of renal cell carcinoma with vascular invasion operated between May 1999 and July 2013. We used the method of Kaplan-Meier survival analysis and the Mantel-Haenszel's test (log rank) and the Cox's proportional hazards analysis test to analyse the risk factors of mortality. RESULTS: The median age was 60 years. Mean follow-up period was 42.1 months. The median overall survival and disease-free survival were 53.8and 36.3 months, respectively. There was statistical association between overall survival and ASA (p=0.047), tumor stage (p=0.003), lymph node involvement (p=0.024), presence of metastases (p=0.013), level of tumor thrombus (p=0, 05) and histological type (p=0.001). 14 patients had grade IIIb complications or higher according to the Clavien Dindo classification, the most frequent was bleeding. CONCLUSIONS: Renal cell carcinoma with vascular invasion is a disease with high rate of mortality. Surgery is a therapeutic option that can be curative. The number of complications is important. Survival is conditioned by the ASA, tumor stage, the level of tumor thrombus, lymph node involvement, metastasis and histological type.

[The use of ureteral stents and catheters in renal transplantation.] / Empleo de catéteres y stents ureterales en el trasplante renal.

Mayor urological complications, fistulae and stenosis, mainly affect the vesicoureteral anastomosis and present in the early post-transplant period. The systematic use of ureteral catheters keeps selecbeing controversial with many groups using them only selectively depending on the existence of pretransplant or intraoperative risk factors. METHODS: We performed a bibliographic review through automatized search in the Medline bibliographic database, as the main bibliographic source, and also in Clinical Key. The search strategy included the following terms: "stent" AND "kidney transplantation". RESULTS: The bibliographic search revealed the protective effect of the use of ureteral catheters in the transplant ureteroneocystostomy for both development of fistulae (RR 0.29, 0.12 to 0.74, p=0.009) and stenosis (RR 0.27, 0.09 to 0.81, p=0.02). The use of catheters in immunosuppressed patients was associated with significant increase of the incidence of post-transplant urinary tract infections (RR 1.49 IC 95% 1.04 to 2.15, p=0.03) that was prevented by antibiotic prophylaxis with cotrimoxazole directed against pneumocistis carinii. The rates of permeability of self-expandable metallic stents and extra-anatomic bypasses in the treatment of ureteral stenosis after renal transplantation in high surgical risk patients or after the failure of previous surgery, has varied from 50% to 100%, with a limited number of patients included. CONCLUSIONS: The use of ureteral catheters in the extravesical ureteroneocystostomy reduces the incidence of anastomotic complications. Surgery is the treatment of choice of post-transplant ureteral stenosis. The use of metallic stents and extra-anatomic bypasses should be limited to complex ureteral stenosis when primary therapy has failed, in high surgical risk patients or chronic graft dysfunction.

Evaluation of intra-abdominal pressure after laparoscopic and open gastric bypass.

BACKGROUND: Increased intra-abdominal pressure (IAP) postoperatively can adversely affect cardiovascular, pulmonary, and renal function. In this prospective, randomized trial, we compared the IAP in morbidly obese patients after laparoscopic and open gastric bypass (GBP) surgery. METHODS: 64 patients with a body mass index of 40 to 60 kg/m2 were randomized to undergo laparoscopic or open GBP. IAPs were obtained at baseline (after induction of anesthesia), immediately after the operation, and on post-operative day (POD) 1, 2, and 3. Intraoperative and postoperative fluid requirements, urine output, and creatinine clearance were recorded. RESULTS: Demographics of the two groups were similar. IAP increased from baseline immediately after laparoscopic and open GBP (p < 0.05). IAP returned to baseline by POD 2 after laparoscopic GBP but remained elevated through POD 3 after open GBP. In fact, IAP was lower after laparoscopic GBP than after open GBP on POD 1, 2 and 3 (p < 0.05). The amount of intraoperative IV fluid was similar between groups, but laparoscopic GBP required less IV fluid and facilitated higher urine output postoperatively than open GBP. There was no significant difference in creatinine clearance between groups. CONCLUSIONS: Laparoscopic GBP resulted in significantly lower IAP, less postoperative fluid required, and greater postoperative urine output than open GBP.