Systematic elucidation of genetic mechanisms underlying cholesterol uptake.

Genetic variation contributes greatly to LDL cholesterol (LDL-C) levels and coronary artery disease risk. By combining analysis of rare coding variants from the UK Biobank and genome-scale CRISPR-Cas9 knockout and activation screening, we substantially improve the identification of genes whose disruption alters serum LDL-C levels. We identify 21 genes in which rare coding variants significantly alter LDL-C levels at least partially through altered LDL-C uptake. We use co-essentiality-based gene module analysis to show that dysfunction of the RAB10 vesicle transport pathway leads to hypercholesterolemia in humans and mice by impairing surface LDL receptor levels. Further, we demonstrate that loss of function of OTX2 leads to robust reduction in serum LDL-C levels in mice and humans by increasing cellular LDL-C uptake. Altogether, we present an integrated approach that improves our understanding of the genetic regulators of LDL-C levels and provides a roadmap for further efforts to dissect complex human disease genetics.

Bilateral partial thrombosis of the corpus cavernosum associated with the use of a stationary bike. Case report and literature review.

Partial and segmental thrombosis of the corpus cavernosum is a rare pathology not entirely understood, however, there are some triggers that have been associated in its appearance. We present a case of a 36-year-old patient with bilateral partial thrombosis of the corpus cavernosum, without priapism, after use of a stationary exercise bike. Ultrasound and magnetic resonance findings are shown, in which bilateral involvement stands out. The patient received conservative management with good response. This pathology is idiopathic and multiple factors have been associated to its origin, one of them being repetitive trauma due to sports activity.

Systematic elucidation of genetic mechanisms underlying cholesterol uptake.

Genetic variation contributes greatly to LDL cholesterol (LDL-C) levels and coronary artery disease risk. By combining analysis of rare coding variants from the UK Biobank and genome-scale CRISPR-Cas9 knockout and activation screening, we have substantially improved the identification of genes whose disruption alters serum LDL-C levels. We identify 21 genes in which rare coding variants significantly alter LDL-C levels at least partially through altered LDL-C uptake. We use co-essentiality-based gene module analysis to show that dysfunction of the RAB10 vesicle transport pathway leads to hypercholesterolemia in humans and mice by impairing surface LDL receptor levels. Further, we demonstrate that loss of function of OTX2 leads to robust reduction in serum LDL-C levels in mice and humans by increasing cellular LDL-C uptake. Altogether, we present an integrated approach that improves our understanding of genetic regulators of LDL-C levels and provides a roadmap for further efforts to dissect complex human disease genetics.

Nefrectomía parcial single-port apoyada con el uso de pinza magnética robótica / Partial nephrectomy single-port supported by the use of robotic magnetic clamp

La Nefrectomía parcial es la técnica quirúrgica ideal en tumores T1 si técnicamente es posible, preservando una mayor cantidad de tejido renal funcional. El abordaje laparoscópico se asocia a menores tiempos de hospitalización, menor dolor y reinserción laboral precoz. El apoyo del abordaje single-port (LESS) se asocia a menos dolor y mejores resultados estéticos, pero conlleva a una mayor complejidad técnica, sin embargo esta dificultad puede ser eliminada con el apoyo robótico, conservando los beneficios de la técnica single port. La tecnología magnética LEVITA facilita aún mas la técnica, pudiendo ser utilizada también en cirugía laparoscópica convencional. MATERIALES Y MÉTODOS: Presentamos el caso de un paciente de sexo masculino de 64 años, sin antecedentes mórbidos, con hallazgo incidental de tumor renal de 1.6 x 1.5 cm en polo inferior izquierdo, R.E.N.A.L. score 6P. Se realizó nefrectomía parcial robóticamente asistida single port. El tiempo operatorio fue de 270 minutos, sangrado estimado de 200cc. Los márgenes fueron negativos. La creatinina en el último control (1.0 mg/dl) es similar a la preoperatoria inmediata (0.9 mg/dl). CONCLUSIONES: La Nefrectomía parcial robóticamente asistida utilizando solo una incisión permite disminuir la morbilidad perioperatoria y mejorar los resultados cosméticos sin que esto signifique una mayor complejidad en la técnica quirúrgica. La tecnología magnética LEVITA es una herramienta útil a considerar en el arsenal del cirujano robótico / laparoscopista.(AU)

INTRODUCTION: Partial nephrectomy is the ideal surgical technique in T1 tumors if technically possible, preserving a greater amount of functional renal tissue. The laparoscopic approach is associated to shorter hospitalization time, less pain and early return to work. Support single-port approach is associated with less pain and better cosmetic results but leads to greater technical complexity. However, the latter difficulty can be eliminated with the robotic support, preserving the benefits of the single-port technique. The LEVITA magnetic technology makes it even easier to apply the technique, and can also be used in conventional laparoscopic surgery. MATERIALS AND METHODS: We report the case of a 64-year old male patient without morbid history, with incidental 1.6 x 1.5 cm kidney tumor finding in the left lower pole, R.E.N.A.L. 6P score. Robot-assisted single port partial nephrectomy was performed. The operating time was 270 minutes, estimated blood loss of 200cc. The margins were negative. The ultimate creatinine control (1.0 mg / dl) is similar to the immediate preoperative (0.9 mg / dl). CONCLUSIONS: Robot-assisted partial nephrectomy using only one incision allows reduction of perioperative morbidity and improvement of cosmetic results without greater complexity in surgical technique. The LEVITA magnetic technology is a useful tool to consider in the arsenal of a robotic / laparoscopic surgeon.

Prostatectomía radical retropúbica: experiencia Hospital Padre Hurtado / Radical retropubic prostatectomy: Hospital Padre Hurtado’s experience

Introducción: A través del siguiente reporte damos a conocer nuestra experiencia en el tratamiento quirúrgico del cáncer de próstata. Material y métodos: Se revisó retrospectivamente la ficha clínica de 60 pacientes sometidos durante6 años (2003-2008) a una prostatectomía radical retropúbica (PRR) con o silinfadenectomía ileo obturatriz. Analizamos los resultados desde una perspectiva demográfica, clínica, bioquímica, quirúrgica y patológica. Resultados: El periodo de seguimiento promedio fue de 2,5 años (0,5-5,5). La edad promedio al someterse a la intervención fue de 64,6 años (52-78). El antígeno prostático específico (APE) promedio preoperatorio fue de 10,72 ng/ml (2,5-56,8) con el 57,9 por ciento detectados con APE <10 ng/ml. El estadio preoperatorio fue T1c en 72,5 por ciento, T2 en el 23,5 por ciento y T3 en el 4 por ciento. El tiempo operatorio promedio fue de 197 minutos (120-330). Hubo necesidad de transfusión sanguínea posoperatoria en el 30 por ciento de los operados. En 2 pacientes (3,3 por ciento) hubo lesión de recto. Un paciente tuvo TEP recuperado. No hubo mortalidad perioperatoria. El promedio de días de hospitalización fue de 7 días (4-48) y el promedio de días de sonda de 17 días (7-30). Se comparó el Gleason de la biopsia transrectal con el de la pieza operatoria. La biopsia transrectal subestimó en el 42 porciento de los casos, sobreestimó en el 11,3 por ciento de los casos y en el resto se mantuvo (46,7 por ciento). Hubo 21 por ciento de márgenes quirúrgicos positivos. El estadio TNM fue de 55 por ciento pT2, 45 por ciento pT3 y 5 por ciento pN1. A los 6 meses de seguimiento 82 por ciento de los pacientes había negativizado sus antígenos. En 18,3 por ciento se agregó radioterapia a la cirugía. La sobrevida global libre de enfermedad al momento de hacer el corte en el estudio fue de 73 por ciento. Conclusiones: Presentamos nuestra experiencia en prostatectomía radical. Nuestros resultados oncológicos son comparables a lo reportado...

Introduction: Through this report we expose our experience with the surgical management of prostate cancer. Materials and methods: Retrospective review of 60 patient charts that were submitted to radical retropubic prostatectomy (RRP) with or without ileo-obturatory lymphadenectomy during a 6-year period (2003-2008). Results are analyzed from a demographic, clinic, biochemical, surgical and pathological perspective. Results: follow-up period was 2,5 years (0,5-5,5). Mean age at surgery was 64,6 (52-78). Mean preoperative PSA was 10,72 ng/dl with 57,9 percent of the patients detected with a PSA <10ng/dl. 72,5 percent of the patients had a T1c preoperative staging, 23,5 percent a T2 and 4 percent a T3. Mean surgical time was 197min (120-330). 30 percent of the patients needed a postoperative transfusion. In 2 patients (3,3 percent) there was a rectal lesion. One patient presented a pulmonally embolism and there was no mortality. Mean admission time was 7 days (4-48) and mean duration of catheterization was 17 days (7-30). We compared Gleason score between preoperative biopsy and definitive pathology: trans-rectal biopsy underestimated the Gleason score in 42 percent of the cases, overestimated 11,3 percent and did not change in46,7 percent. We had 21 percent of positive borders. TNM was pT2 55 percent, pT3 45 percent and pN1 5 percent. At a 6 month follow-up 82 percent of the patients had undetectable PSA. Radiotherapy was used in 18,3 percent of the patients. Global disease free survival at the closing of the study was 73 percent. Conclusion: We present our experience with retropubic radical prostatectomy. We show oncological results that are similar to those reported in national literature. A longer follow-up is necessary to confirm them.