Identification of mutations associated with acquired resistance to sunitinib in renal cell cancer.

Sunitinib is one of the most widely used targeted therapeutics for renal cell carcinoma (RCC), but acquired resistance against targeted therapies remains a major clinical challenge. To dissect mechanisms of acquired resistance and unravel reliable predictive biomarkers for sunitinib in RCC, we sequenced the exons of 409 tumor-suppressor genes and oncogenes in paired tumor samples from an RCC patient, obtained at baseline and after development of acquired resistance to sunitinib. From newly arising mutations, we selected, using in silico prediction models, six predicted to be deleterious, located in G6PD, LRP1B, SETD2, TET2, SYNE1, and DCC. Consistently, immunoblotting analysis of lysates derived from sunitinib-desensitized RCC cells and their parental counterparts showed marked differences in the levels and expression pattern of the proteins encoded by these genes. Our further analysis demonstrates essential roles for these proteins in mediating sunitinib cytotoxicity and shows that their loss of function renders tumor cells resistant to sunitinib in vitro and in vivo. Finally, sunitinib resistance induced by continuous exposure or by inhibition of the six proteins was overcome by treatment with cabozantinib or a low-dose combination of lenvatinib and everolimus. Collectively, our results unravel novel markers of acquired resistance to sunitinib and clinically relevant approaches for overcoming this resistance in RCC.

[Design and validation of a satisfaction questionnaire in patients with urolithiasis treated by extracorporeal shock wave lithotripsy (ESWL).] / Diseño y validación de un cuestionario de salud en pacientes con urolitiasis tratados mediante litotricia extracorpórea por ondas de choque (LEOC).

OBJECTIVES: Studying the psychosocial sphere of patients who undergo any treatment allows to have more information about its repercussion and can help the choice of an appropriate and personalized treatment. Due to the absence of specific instruments at present, the objective is to design and validate a health questionnaire regarding the treatment received with ESWL. METHODS: It was carried out in 6 phases using a sampleof 50 patients treated with ESWL in 2015 in ourcenter, whom we interviewed by telephone. In phase1 the items were proposed based on bibliographic review,in phase 2 those that scored below 7 were eliminatedaccording to the evaluation from 0 to 10 on theitems made by specialists. In phase 3, values of 1 to 5were assigned to each item and those with correctedcorrelation more than 0.2 and not significant (p>0.05)discriminant power with U-Mann Whitney were eliminated.In phase 4 the reliability of the questionnaire waschecked with two indexes (Cronbach's alpha and twoGuttman's halves). In phase 5, the factor analysis withVarimax rotation was performed to calculate the constructvalidity and in stage 6, the scores were analyzedto establish reference values. RESULTS: 50 patients (32 men, 18 women). Medianage 59 years (27-79). In phase 1, 35 items were proposed,9 of which were eliminated in phase 2. The initialquestionnaire with 26 items was distributed, with 18being eliminated in phase 3. The final questionnaire wasformed with 8 items. In phase 4 the results of Cronbach'salpha and Guttman's two halves index were 0.44 and0.323 respectively. In phase 5 after factor analysis, wefound 4 factors with 2 items each (background, impactof the acute picture, post-treatment, quality of life) able toexplain 71.19% of the variance. The median scores ofthe scale, extreme values and quartiles studied in phase6 were respectively: P50: 17 (minimum-maximum 9-25),P25: 14 and P75: 20. CONCLUSIONS: The study carried out has provided anew instrument for assessing satisfaction after treatmentwith ESWL with adequate reliability and validity values.Future studies will be necessary to contrast its true clinicalusefulness.

OBJETIVO: Estudiar la esfera psicosocial de los pacientes que se someten a algún tratamiento permite tener más información sobre la repercusión del mismo y puede ayudar a la elección de un tratamiento adecuado y personalizado. Debido a la ausencia deinstrumentos específicos actualmente, el objetivo es diseñary validar un cuestionario de salud en pacientes tratados con LEOC.MATERIAL Y MÉTODOS: Se realizó en 6 fases utilizando una muestra de 50 pacientes tratados con LEOC en 2015 en nuestro centro, a los que entrevistamos por vía telefónica. En la fase 1 se propusieron ítems a partir de revisión bibliográfica. En la fase 2 se eliminaron losque puntuaban por debajo de 7 según la valoración de 0-10 sobre los ítems efectuada por especialistas en la materia. En la fase 3 se asignaron valores de 1 a 5 a cada ítem y se eliminaron aquellos cuya correlación corregida fuera mayor de 0,2 y cuya potencia discriminante con U-Mann Whitney no fuera significativa (p>0,05). En la fase 4 se comprobó la fiabilidad del cuestionario con dos índices (alfa de Cronbach y dos mitades de Guttman). En la fase 5 se realizó el análisis factorial con rotación Varimax para el cálculo de la validez de constructo. Finalmente, en la fase 6 se tipificaron de las puntuaciones para establecer valores de referencia. RESULTADOS: 50 pacientes (32 hombres, 18 mujeres). Mediana edad 59 años (27-79). Fase 1: 35 ítems propuestos. Fase 2: 9 ítems eliminados. Distribución de cuestionario con 26 ítems. Fase 3: 18 ítems eliminados.Cuestionario final constituido por 8 ítems. Fase 4: valores de fiabilidad del cuestionario (alfa de Cronbach 0,44 e índice por técnica de dos mitades de Guttman 0,323). Fase 5: análisis factorial hallando 4 factores con 2 ítems cada uno (antecedentes, repercusión delcuadro agudo, post-tratamiento, calidad de vida) capaces de explicar el 71,19% de la varianza. Fase 6: mediana puntuación  50:17(mínimo-máximo 9-25), P25:14 y P75:20. CONCLUSIONES: El trabajo realizado ha proporcionado un nuevo instrumento de evaluación de salud tras tratamiento con LEOC con valores de fiabilidad y validez adecuados. Serán necesarios futuros estudios para contrastar su verdadera utilidad clínica.

Diseño y validación de un cuestionario de salud en pacientes con urolitiasis tratados mediante litotricia extracorpórea por ondas de choque (LEOC) / No disponible

Objetivo: Estudiar la esfera psicosocial de los pacientes que se someten a algún tratamiento permite tener más información sobre la repercusión del mismo y puede ayudar a la elección de un tratamiento adecuado y personalizado. Debido a la ausencia de instrumentos específicos actualmente, el objetivo es diseñar y validar un cuestionario de salud en pacientes tratados con LEOC. Material y métodos: Se realizó en 6 fases utilizando una muestra de 50 pacientes tratados con LEOC en 2015 en nuestro centro, a los que entrevistamos por vía telefónica. En la fase 1 se propusieron ítems a partir de revisión bibliográfica. En la fase 2 se eliminaron los que puntuaban por debajo de 7 según la valoración de 0-10 sobre los ítems efectuada por especialistas en la materia. En la fase 3 se asignaron valores de 1 a 5 a cada ítem y se eliminaron aquellos cuya correlación corregida fuera mayor de 0,2 y cuya potencia discriminante con U-Mann Whitney no fuera significativa (p>0,05). En la fase 4 se comprobó la fiabilidad del cuestionario con dos índices (alfa de Cronbach y dos mitades de Guttman). En la fase 5 se realizó el análisis factorial con rotación Varimax para el cálculo de la validez de constructo. Finalmente, en la fase 6 se tipificaron de las puntuaciones para establecer valores de referencia. Resultados: 50 pacientes (32 hombres, 18 mujeres). Mediana edad 59 años (27-79). Fase 1: 35 ítems propuestos. Fase 2: 9 ítems eliminados. Distribución de cuestionario con 26 ítems. Fase 3: 18 ítems eliminados. Cuestionario final constituido por 8 ítems. Fase 4: valores de fiabilidad del cuestionario (alfa de Cronbach 0,44 e índice por técnica de dos mitades de Guttman 0,323). Fase 5: análisis factorial hallando 4 factores con 2 ítems cada uno (antecedentes, repercusión del cuadro agudo, post-tratamiento, calidad de vida) capaces de explicar el 71,19% de la varianza. Fase 6: mediana puntuación 50:17(mínimo-máximo 9-25), P25:14 y P75:20. Conclusiones: El trabajo realizado ha proporcionado un nuevo instrumento de evaluación de salud tras tratamiento con LEOC con valores de fiabilidad y validez adecuados. Serán necesarios futuros estudios para contrastar su verdadera utilidad clínica

Objectives: Studying the psychosocial sphere of patients who undergo any treatment allows to have more information about its repercussion and can help the choice of an appropriate and personalized treatment. Due to the absence of specific instruments at present, the objective is to design and validate a health questionnaire regarding the treatment received with ESWL. Methods: It was carried out in 6 phases using a sample of 50 patients treated with ESWL in 2015 in our center, whom we interviewed by telephone. In phase 1 the items were proposed based on bibliographic review, in phase 2 those that scored below 7 were eliminated according to the evaluation from 0 to 10 on the items made by specialists. In phase 3, values of 1 to 5 were assigned to each item and those with corrected correlation more than 0.2 and not significant (p>0.05) discriminant power with U-Mann Whitney were eliminated. In phase 4 the reliability of the questionnaire was checked with two indexes (Cronbach’s alpha and two Guttman's halves). In phase 5, the factor analysis with Varimax rotation was performed to calculate the construct validity and in stage 6, the scores were analyzed to establish reference values. Results: 50 patients (32 men, 18 women). Median age 59 years (27-79). In phase 1, 35 items were proposed, 9 of which were eliminated in phase 2. The initial questionnaire with 26 items was distributed, with 18 being eliminated in phase 3. The final questionnaire was formed with 8 items. In phase 4 the results of Cronbach’s alpha and Guttman’s two halves index were 0.44 and 0.323 respectively. In phase 5 after factor analysis, we found 4 factors with 2 items each (background, impact of the acute picture, post-treatment, quality of life) able to explain 71.19% of the variance. The median scores of the scale, extreme values and quartiles studied in phase 6 were respectively: P50: 17 (minimum-maximum 9-25), P25: 14 and P75: 20. Conclusions: The study carried out has provided a new instrument for assessing satisfaction after treatment with ESWL with adequate reliability and validity values. Future studies will be necessary to contrast its true clinical usefulness

[Assessment and prevalence of urinary incontinence after radical prostatectomy: Analysis of a historical series]. / EVALUACIÓN Y PREVALENCIA DE INCONTINENCIA URINARIA TRAS PROSTATECTOMÍA RADICAL: ANÁLISIS DE UNA SERIE HISTÓRICA.

OBJECTIVES: Prostate cancer can be treated by radical prostatectomy and provoke urinary incontinence as secondary effect. Our aim is to calculate the prevalence of urinary incontinence, characteristics of leakage and influential factors, through a historical series. METHODS: We perform a descriptive, observational and retrospective study of 1310 patients who received treatment for PCa between 1989 and 2011. Prevalence was obtained after 12 months of recovery and using ICS definition. To complete ICIQ-SF and number of pads/day used we perform a cross-sectional study. The series is studied globally and divided in two groups according to oncologic characteristics. We perform a descriptive, comparative and predictive analysis. RESULTS: Prevalence of the series was 23.5%, 296 patients. 279 incontinent patients completed ICIQ-SF with a mean score of 11.1±4.03. 16.4% of the patients use 1 pad/day or none, 69% (11.4% of the total) use compress and 22% diapers. 8% of the total use more than 1 pad/day. Clinico-pathological factors divide series in two groups: 1989-1999 with a prevalence of 24.6% and 2000-2011 with 22.8%. Multivariate analysis shows influential factors: age (65 years) (OR:1.65, p=0.013) and prostate volume (50cc) (OR:1.49, p=0.029). CONCLUSIONS: Urinary incontinence is a disease with some prevalence that varies depending on definition. The most common situation was to leak several times a day (42.2%), a small amount (59.1%), using compress (69%) most of incontinents with a mild (0-7: 88.2%) impact on quality of life. Predictive factors were age (65 years) and prostate volume (50cc). The historical changes does not influence over prevalence.

Case of emphysematous pyelonephritis in kidney allograft: Conservative treatment.

Emphysematous pyelonephritis is an acute necrotizing infection with gas in the kidney and perinephric space that carries a bad prognosis. Apart from its predisposing clinical entities, diabetes mellitus and immune-incompetence are quite common in patients with this infection. We report a case of a 53-year-old kidney transplant recipient diabetic male, suffering from recurrent fever, abdominal pain and nausea episodes. Immediate broad-spectrum antibiotics were administered and percutaneous drainage was performed after the diagnosis. The bacteria involved were Stahpylococcus epidermidis and Escherichia coli. After 4 weeks of antibiotic treatment and abscesses drainage, the case was resolved. Consecutives urine cultures and ultrasonographies confirm the complete resolution of the disease. We discuss the predisposing factors, clinical presentation and management.