A Surgical and Clinical Approach to Persistent Müllerian Duct Syndrome: Laparoscopic, Histological, and Molecular Findings.

BACKGROUND: Persistent müllerian duct syndrome (PMDS) is characterized by the persistence of müllerian duct derivatives in otherwise normally virilized 46,XY males. Biallelic mutations of the anti-müllerian hormone (AMH) and AMH receptor type 2 (AMHR2) genes lead to PMDS type 1 and 2, respectively. AIM: The aims of the study were to report the clinical, hormonal, and genetic findings in a patient with PMDS and discuss surgical strategies to achieve successful orchidopexy. RESULTS: A 4-year-old boy was evaluated after the incidental finding of müllerian derivates during laparoscopy for nonpalpable gonads. Karyotype was 46,XY and laboratory tests revealed normal serum gonadotropin and androgen levels but undetectable serum AMH levels. PMDS was suspected. Molecular analysis revealed a novel variant c.902_929del in exon 5 and a previously reported mutation (c.367C>T) in exon 1 of the AMH gene. Successful orchidopexy was performed in two sequential surgeries in which the müllerian duct structure was preserved and divided to protect the vascular supply to the gonads. Histological evaluation of the testicular biopsy showed mild signs of dysgenesis. Doppler ultrasound showed blood flow in both testes positioned in the scrotum 1.5 years after surgery. CONCLUSION: PMDS is a rare entity that requires a high index of suspicion (from surgeons) when evaluating a patient with bilateral cryptorchidism. Surgical treatment is challenging and long-term follow-up is essential. Histological evaluation of the testis deserves further investigation.

Nuevo modelo de simulador para neuroendoscopía / New simulator model for neuroendoscopy

Introducción: El entrenamiento en simuladores es considerado una herramienta fundamental en las especialidades quirúrgicas, contribuyendo en el aprendizaje de una determinada técnica quirúrgica.Existen modelos de simulación sintéticos que replican la anatomía ventricular con alta fidelidad sin embargo tienen un costo elevado. Algunos centros describieron el uso de cadáveres humanos pero la disponibilidad del material suele ser limitada y la adquisición dificultosa. Otros autores utilizan entrenamiento en modelos biológicos vivos (roedores de laboratorio) que presentan la ventaja de tener alta fidelidad en cuanto a la consistencia de tejidos, sin embargo, la utilización de estos modelos se encuentra cuestionados desde el aspecto ético. Material y Métodos: Se presenta un modelo de simulación que utiliza unidades de cerebro bovino y membrana amniótica. Colocamos el cerebro bovino y las unidades de membrana amniótica dentro de un recipiente esférico de poliestireno expandido. Una vez que se forma la esfera, insertamos dos trocares que nos permitirán insertar el neuroendoscopio y llenarlo con agua. Resultado: Presentamos un nuevo modelo accesible y realista para la simulación neuroendoscópica que reproduce ejercicios de biopsia, coagulación de tejidos, fenestración y dilatación de membrana. Conclusión: Los simuladores para neuroendoscopía descritos hasta ahora son confiables, pero conllevan un alto costo. Los modelos con animales vivos, aunque con menor costo, son cuestionados desde un punto de vista ético.En el trabajo actual, describimos un modelo de simulador neuroendoscópico ventricular de alta fidelidad que, debido a su bajo costo, permite ser replicado en cualquier centro de entrenamiento que tenga un neuroendoscopio.

Objectives: Ventricular endoscopy is considered an excellent technique. However, without an optimal learning curve, it could lead to deadly complications.There are synthetic simulation models that replicate the ventricular anatomy with high fidelity but high costs. Some low-cost models have been published using human corpses for endoscopic training; however, materials' acquisition is difficult. A different option is live biological models (laboratory rodents), although cost is lower, they are questioned from an ethical point of view.The ideal simulator, in addition to aspiring maximum fidelity, must be accessible, affordable and easy to replicate to facilitate repetitive training. Methods: A simulation model using bovine brain and membrane units made by a soda cup covered by an amniotic membrane. We placed the bovine brain and the amniotic membrane units inside an expanded polystyrene spherical container; once the sphere is formed, we inserted two trocars, which will enabled us to insert the neuroendoscope and fill it with water. Result: We introduced an attainable and realistic new model for neuroendoscopic simulation, which replicates biopsy, tissue coagulation, fenestration, and membrane dilatation exercises. Conclusion: Simulators for neuroendoscopy described so far are reliable, but they entail a high cost. Models with live animals, although with lower cost, are questioned from an ethical point of view.In the current work, we describe a high fidelity ventricular neuroendoscopic simulator model that, due to its low cost, allows to be replicated in any training center that has a neuroendoscope

New Simulator for Neuroendoscopy: A Realistic and Attainable Model.

OBJECTIVE: To present an attainable and realistic model for neuroendoscopic simulation which replicates exercises of tissue biopsy and coagulation and membrane fenestration. METHODS: We presented a stepwise method to create a neuroendoscopic simulation model using bovine brain and membrane units made by a soda cup covered by an amniotic membrane inside an expanded polystyrene spherical container. We used face validation for preliminary evaluation. We also rated the students before and after training with the NEVAT global rating scale (GRS) and recorded the time required to complete all 3 procedures (third ventriculostomy, tissue biopsy, and coagulation). The total cost of the model was $5. RESULTS: The experts consider this new model as capable of reproducing real surgical situations with great similarity to the human brain. We tested the model in 20 trainees. The median GRS score before the training was 9 (range, 7-12). After repeated training and performance feedback, the final median GRS score was 41 (range, 37.5-45; P < 0.0001). The time needed to finish the exercises before training was 33 minutes (range, 30.5-42.5 minutes), and after using the model the final median time was 20 minutes (range, 17.5-22 minutes; P < 0.0001). CONCLUSIONS: Simulators for neuroendoscopy described so far are reliable, but they entail a high cost. Models with live animals, although of lower cost, are questioned from an ethical point of view. In the current work, we describe a high fidelity ventricular neuroendoscopic simulator model that, because of its low cost, can be replicated in any training center that has a neuroendoscope.

Modelo de neuroendoscopia ventricular "INARUS" / Ventricular neuroendoscopy model "INARUS"

Introducción: La simulación es una herramienta de educación indispensable para un entrenamiento progresivo en un ámbito seguro, no solo para el paciente sino para el educando. La misma fue incorporada en la curricula de nuestras especialidades quirúrgicas a partir del 2013. Las habilidades neuroquirúrgicas requieren de un experticio que implica un periodo prolongado de tiempo de práctica. En la actualidad, dicho periodo, se tiende a disminuir con la enseñanza de ensayo y error, repetición de los procedimientos y automatización de maniobras que la simulación facilita con el agregado de la posibilidad de un feedback de retroalimentación entre el profesional en formación y el educador en un ambiente seguro. Objetivo: Describir un modelo de simulador físico sintético de bajo costo como herramienta inicial para mejorar la curva de aprendizaje de las técnicas de neuroendoscopia intraventricular. Descripción del simulador: es un modelo físico sintético realizado a través de técnicas de mordería con gel autoportante. El simulador ofrece la posibilidad de practicar técnicas básicas neuroendoscópicas intraventriculares, ofreciendo la particularidad de poder repetir las maniobras y gestos quirúrgicas con un coste beneficio muy elevado debido al muy bajo precio de realización del simulador. A su vez, se trata de un modelo de simulación que se puede fabricar de forma casera en cualquier centro de simulación. Discusión: Presentamos un modelo inédito de bajo costo y alta fidelidad para simulación neuroendoscópica. Consta de un cerebro sintético físico que permite replicar ejercicios de navegación intraventricular con maniobras endoscópicas, toma de biopsia de lesiones quísticas o sólidas, sección de tabiques, lavado ventricular y desobstrucción de catéteres intraventriculares. Lo consideramos una herramienta básica y de amplia ayuda para profesionales que decidan iniciar su curva de aprendizaje en la neuroendoscopia intraventricular. Planeamos su validación en futuros congresos de neurocirugía.

Introduction: Simulation is an indispensable educational tool for progressive training in a safe environment, for both patients and learning neurosurgeons. It was incorporated into the curricula of our surgical specialties as of 2013. Neurosurgical skills require an expertise that involves a prolonged period of practice time. Currently, this period tends to decrease with the teaching of trial and error, repetition of procedures and automation of maneuvers that the simulation facilitates with the addition of the possibility of feedback between the professional in training and the educator, all doing in a safe environment. Objective: To describe a low cost synthetic physical simulator model as an initial tool to improve the learning curve of intraventricular neuroendoscopy techniques. Description of the simulator: it is a synthetic physical model realized through self-supporting gel biting techniques. The simulator offers the possibility of practicing intraventricular neuroendoscopic basic techniques, offering the peculiarity of being able to repeat maneuvers and surgical gestures with a very high benefit-cost due to a very low price of its creation. At the same time, it is a simulation model that can be manufactured at home in any simulation center. Discussion: We present an unprecedented model of low cost and high fidelity for neuroendoscopic simulation. It consists of a physical synthetic brain that allows the replication of intraventricular navigation exercises with endoscopic maneuvers, a biopsy of solid or cystic lesions, the section of the ventricular septum, ventricular lavage and unblocking of intraventricular catheters. We consider this simulator as a basic tool of wide assistance for professionals who decide to start their learning curve in intraventricular neuroendoscopy. We're planning its validation in a future neurosurgery congress.

Malpractice in paediatric minimally invasive surgery - a current concept: Results of an international survey.

This study aimed to assess malpractice in paediatric minimally invasive surgery (MIS), and attitudes, prevention strategies and mechanisms to support surgeons while they are under investigation. An observational, multicentric, questionnaire-based study was conducted. The survey questionnaire was sent via mail, and it comprised four sections. Twenty-four paediatric surgeons (average age 54.6 years), from 13 different countries, participated in this study. The majority had >15 years of experience in MIS. Three (12.5%) surgeons reported a total of five malpractice claims regarding their MIS activity. The reasons for the claims were a postoperative complication in 3/5 (60%) cases, a delayed/failed diagnosis in 1/5 (20%) cases and the death of the patient in 1/5 (20%) cases. The claims concluded with the absolution of the surgeon in all cases, and monetary compensation to the claimant in two (40%) cases. Eleven (45.8%) surgeons were invited as expert counsels in medico-legal actions. Medico-legal aspects have a minimal impact on the MIS activity of paediatric surgeons. In this series, claims concluded with the absolution of the surgeon in all cases, but they had a negative effect on the surgeon's reputation and finances. A key element in supporting surgeons while they are under investigation is always to choose a surgeon who is an expert in paediatric MIS as legal counsel. A constant update on innovations in paediatric MIS and appropriate professional liability insurance may also play a key role in reducing medico-legal consequences.

Androgen Insensitivity Syndrome at Prepuberty: Marked Loss of Spermatogonial Cells at Early Childhood and Presence of Gonocytes up to Puberty.

Androgen insensitivity syndrome (AIS) is a hereditary condition in patients with a 46,XY karyotype in which loss-of-function mutations of the androgen receptor (AR) gene are responsible for defects in virilization. The aim of this study was to investigate the consequences of the lack of AR activity on germ cell survival and the degree of testicular development reached by these patients by analyzing gonadal tissue from patients with AIS prior to Sertoli cell maturation at puberty. Twenty-three gonads from 13 patients with AIS were assessed and compared to 18 testes from 17 subjects without endocrine disorders. The study of the gonadal structure using conventional microscopy and the ultrastructural characteristics of remnant germ cells using electron microscopy, combined with the immunohistochemical analysis of specific germ cell markers (MAGE-A4 for premeiotic germ cells and of OCT3/4 for gonocytes), enabled us to carry out a thorough investigation of germ cell life in an androgen-insensitive microenvironment throughout prepuberty until young adulthood. Here, we show that germ cell degeneration starts very early, with a marked decrease in number after only 2 years of life, and we demonstrate the permanence of gonocytes in AIS testis samples until puberty, describing 2 different populations. Additionally, our results provide further evidence for the importance of AR signaling in peritubular myoid cells during prepuberty to maintain Sertoli and spermatogonial cell health and survival.

Malignant extra-cranial germ cell tumors in children and adolescents. Results following the guidelines of SFOP/SFCE 95 Protocol.

Between September 1995 and December 2010, 99 new consecutive assessable patients with extra-cranial MGCT were treated according to SFOP/SFCE TGM95 Protocol. A "watch and wait" strategy for completely resected stage I-II was observed in cases with preoperative high tumor markers levels. Metastatic disease or alpha fetoprotein levels > 15 000 ng/ml cases were treated by VIP chemotherapy (etoposide, ifosfamide and CDDP) 4-6-courses. All other cases were treated by VBP (vinblastine, bleomycin, and CDDP) 3-5 courses. Median age for the whole group was 11.1 (r: 0-17) years. Males: 49, females: 50. Stage I: 19 patients, stage II: 16, stage III: 31 and stage IV: 3. Gonadal disease occurred in 77 cases. Of 21 completely resected stage I-II patients with MGCT who did not receive chemotherapy after surgery, 6 presented disease progression and were successfully treated by chemotherapy and remained disease-free. There were no significant differences in outcome according to age, gender, initial site, staging, and histological variant or high levels of alpha-fetoprotein. Initial non-responsiveness to VIP chemotherapy was the only significant unfavorable prognostic feature. With a median follow-up of 64 (r: 5-204) months, at 10 years EFS and OS estimates for the whole group were 0.82 (SE = 0.05) and 0.90 (SE = 0.03) respectively. Therapy results of MGCT treated with the SFOP/SFCE 95 strategy were excellent. Initial non-response to front line chemotherapy was the only significant adverse prognostic feature. The "watch and wait" strategy for completely resected disease with initial positive markers proved to be safe with optimal outcome.

Malignant extra-cranial germ cell tumors in children and adolescents: Results following the guidelines of SFOP/SFCE 95 Protocol

Between September 1995 and December 2010, 99 new consecutive assessable patients with extra-cranial MGCT were treated according to SFOP/SFCE TGM95 Protocol. A "watch and wait" strategy for completely resected stage I-II was observed in cases with preoperative high tumor markers levels. Metastatic disease or alpha fetoprotein levels > 15 000 ng/ml cases were treated by VIP chemotherapy (etoposide, ifosfamide and CDDP) 4-6-courses. All other cases were treated by VBP (vinblastine, bleomycin, and CDDP) 3-5 courses. Median age for the whole group was 11.1 (r: 0-17) years. Males: 49, females: 50. Stage I: 19 patients, stage II: 16, stage III: 31 and stage IV: 3. Gonadal disease occurred in 77 cases. Of 21 completely resected stage I-II patients with MGCT who did not receive chemotherapy after surgery, 6 presented disease progression and were successfully treated by chemotherapy and remained disease-free. There were no significant differences in outcome according to age, gender, initial site, staging, and histological variant or high levels of alpha-fetoprotein. Initial non-responsiveness to VIP chemotherapy was the only significant unfavorable prognostic feature. With a median follow-up of 64 (r: 5-204) months, at 10 years EFS and OS estimates for the whole group were 0.82 (SE = 0.05) and 0.90 (SE = 0.03) respectively. Therapy results of MGCT treated with the SFOP/SFCE 95 strategy were excellent. Initial non-response to front line chemotherapy was the only significant adverse prognostic feature. The "watch and wait" strategy for completely resected disease with initial positive markers proved to be safe with optimal outcome.

Entre septiembre de 1995 y diciembre 2010 se registraron 99 nuevos pacientes evaluables consecutivos con tumores germinales malignos (TGM) extra-cerebrales. Los pacientes fueron tratados prospectivamente según los lineamientos del Protocolo SFOP/SFCE TGM95. Se siguió una estrategia de watch and wait para la enfermedad estadio I-II completamente resecada. La enfermedad con metástasis y los casos con niveles de alfa fetoproteína > 15 000 ng/ml fueron tratados con etopósido, ifosfamida y CDDP, 4-6 cursos. El resto fue tratado con vinblastina, bleomicina y CDDP, 3-5 ciclos. La mediana de edad fue de 11.1 (r: 0-17) años. Varones: 49, niñas: 50. Estadio I: 19 casos; II: 16; III: 31y IV: 33. De 21 enfermos con estadios tumorales I y II con resección completa inicial que no tuvieron tratamiento adyuvante, seis progresaron, todos fueron exitosamente tratados con quimioterapia y permanecieron libres de enfermedad. No hubo diferencias significativas en los resultados de supervivencia según edad, género, sitio inicial, estadificación, variante histológica o niveles elevados de alfa-fetoproteína. La resistencia primaria a la quimioterapia VIP fue el único factor pronóstico desfavorable significativo. Con una mediana de seguimiento de 64 (r: 5-204) meses, a 10 años las probabilidades de supervivencia libre de eventos y supervivencia global para todo el grupo fueron respectivamente de 0.82 (EE = 0.05) y 0.90 (EE = 0.03). Los resultados con la estrategia SFOP/SFCE 95 fueron excelentes. La ausencia de respuesta a la quimioterapia de primera línea fue el único factor pronóstico adverso significativo. La estrategia de watch and wait probó ser segura y eficaz.

Neurosurgical training with simulators: a novel neuroendoscopy model.

PURPOSE: The aim of this study is to present a novel neuroendoscopy simulation model in live animals, with the objective of enhancing patient safety with realistic surgical training. METHODS: A simulation model using live Wistar rats was designed after the approval of the Institutional Committee for the Care and Use of Laboratory Animals. Under anesthesia, a hydroperitoneum was created in order to simulate a cavity with mesenteric membranes and vessels, viscera, and a solid and bleeding tumor (the liver) floating in a liquid environment. For validation purposes, we evaluated trainees' basal and final skills for each neuroendoscopic procedure, and we also acknowledged trainees' and instructors' opinion on the model's realism. RESULTS: This model is simple and low cost effective for complete and real-life training in neuroendoscopy, with the possibility of performing all the basic and advanced endoscopic procedures, such as endoscopic exploration, membrane fenestration, vessel coagulation, hematoma evacuation, and endoscopic tumor biopsy and resection using a ventricular neuroendoscopy set. Although the model does not represent human ventricular anatomy, a reliable simulation is possible in real living tissue in a liquid environment. Trainees' skills improvements were notorious. CONCLUSION: Minimally invasive endoscopic techniques require specific training. Simulation training can improve and accelerate the learning curve. The presented training model allows simulating the different neuroendoscopic procedures. We believe that due to its practical possibilities, its simplicity, low cost, reproducibility, and reality, being live animal tissue, it can be considered a fundamental model within a complete training program on neuroendoscopy.

Three novel IGF1R mutations in microcephalic patients with prenatal and postnatal growth impairment.

BACKGROUND: IGF1R gene mutations have been associated with varying degrees of intrauterine and postnatal growth retardation, and microcephaly. OBJECTIVE: To identify and characterize IGF1R gene variations in a cohort of 28 Argentinean children suspected of having IGF-1 insensitivity, who were selected on the basis of the association of pre/postnatal growth failure and microcephaly. METHODS: The coding sequence and flanking intronic regions of IGF1R gene were amplified and directly sequenced. Functional characterization was performed by two in vitro assays: 1) [Methyl-(3) H] thymidine incorporation into DNA in fibroblast cell primary cultures from patients and controls treated with IGF-1 for 16-24 h. 2) PI3K/Akt pathway was evaluated with phospho-Akt (Ser473) STAR ELISA Kit (Millipore) in fibroblast cultures from patients and controls stimulated with IGF-1 for 10 min. Prepubertal clinical and GH-IGF-1 axis evaluation was followed up. RESULTS: We identified three novel heterozygous missense mutations in three unrelated patients, de novo p.Arg1256Ser, de novo p.Asn359Tyr and p.Tyr865Cys. In control cells, proliferation assay showed that IGF-1 significantly induced DNA synthesis at 20 h and Akt phosphorylation assay that it significantly stimulated phosphorylation after 10 min (P < 0·05 by anova and Bonferroni Tests). However, no significant increase was observed in any of the three patient fibroblasts in both functional studies. GH therapy growth response in two patients was inconsistent. CONCLUSION: These variations led to failure of the IGF1R function causing pre- and postnatal growth retardation and microcephaly. Microcephaly should be considered in the evaluation of SGA patients, because it seems to favour the frequency of detection of IGF1R mutations.

[Novel heterozygous mutation in the steroidogenic acute regulatory protein gene in a 46,XY patient with congenital lipoid adrenal hyperplasia]. / Nueva mutación heterocigota en el gen de la proteína regulatoria aguda de la esteroideogénesis (StAR) en un paciente 46,XY con hiperplasia adrenal congénita lipoidea.

StAR facilitates cholesterol entry into the mitochondria as part of the transduceosome complex. Recessive mutations in the gen STAR cause classic and nonclassic congenital lipoid adrenal hyperplasia. The aim of the study was to analyze the molecular consequences of a novel heterozygous STAR mutation in a 46,XY patient with ambiguous genitalia and adrenal insufficiency. We found a de novo heterozygous IVS-2A>G STAR mutation and the reported heterozygous p.G146A SF1 polymorphism with normal CYP11A1, FDXR, FDX1, VDAC1 and TSPO genes. RT-PCR and sequencing from patient's testicular RNA showed a -exon2 transcript and the wild-type (WT) transcript. Both 37 kDa precursor and 30 kDa mature protein were detected in COS-7 cell transfected with mutant and WT plasmids. Immunofluorescence showed almost no co-localization of mitochondria and mutant protein (delta22-59StAR). Delta22-59StAR activity was 65±13% of WT. Cotransfection with WT and delta22-59StAR plasmids reduced WT activity by 62.0% ± 13.9. Novel splice-junction heterozygous STAR mutation (IVS-2A>G) resulted in the in-frame loss of amino acids 22 to 59 in the N-terminal mitochondrial targeting signal. A misfolded p.G22_L59delStAR might interfere with WT StAR activity by blocking the transduceosome complex, causing an autosomal dominant form of StAR deficiency, explaining the clinical phenotype.

Work-related upper limb musculoskeletal disorders in paediatric laparoscopic surgery. A multicenter survey.

BACKGROUND: Surgeons are at risk for developing work-related musculoskeletal symptoms (WMS). The present study aims to examine the physical factors and their association with WMS among pediatric laparoscopic surgeons. METHODS: A questionnaire consisting of 21 questions was created and mailed to 25 pediatric laparoscopic surgeons (LG). 23/25 surgeons (92%) completed the survey. The questionnaire was analyzed and then split into 2 groups. Group 1 (LG1) included surgeons with greater laparoscopic experience, and group 2 (LG2) included surgeons with less important laparoscopic experience. In addition, we constructed and sent to the same surgeons a similar questionnaire focused on WMS after an open procedure (OG) with the aim to compare results of LG with OG. RESULTS: The prevalence rate of WMS with shoulder symptoms was 78.2% in surgeons that performed laparoscopy for more than 10 years, with 60.8% also reporting other pain. In 66.6% this pain is evident only after a long-lasting procedure. Forty-four percent of these surgeons require painkillers at least twice a week. Fifty percent of these surgeons also suffer at home. Fifty-five and one half percent of surgeons indicate that this pain is related to their laparoscopic activity. Forty-three and a half percent think that laparoscopy is beneficial only for the patient but has a bad ergonomic effect for surgeons. Sixty-five and two-tenths percent think that robotic surgery can be helpful to improve ergonomics. Comparing the groups, WMS occur more frequently in LG (78.2%) than in OG (56.5%), but this difference was not statistically significant (χ(2)=0.05). In addition, WMS occur more frequently in LG1 (84.6%) than in LG2 (70%), but this difference was not statistically significant (χ(2)=0.05). CONCLUSIONS: These results confirmed a strong association between WMS and the number of laparoscopic procedures performed. Skilled laparoscopic surgeons have more pain than less skilled laparoscopic surgeons. WMS in the same group of surgeons are more frequent after laparoscopy than after open procedures. The majority of surgeons refer to shoulder symptoms.

Nueva mutación heterocigota en el gen de la proteína regulatoria aguda de la esteroideogénesis (StAR) en un paciente 46,XY con hiperplasia adrenal congénita lipoidea / [Novel heterozygous mutation in the steroidogenic acute regulatory protein gene in a 46,XY patient with congenital lipoid adrenal hyperplasia].

StAR facilitates cholesterol entry into the mitochondria as part of the transduceosome complex. Recessive mutations in the gen STAR cause classic and nonclassic congenital lipoid adrenal hyperplasia. The aim of the study was to analyze the molecular consequences of a novel heterozygous STAR mutation in a 46,XY patient with ambiguous genitalia and adrenal insufficiency. We found a de novo heterozygous IVS-2A>G STAR mutation and the reported heterozygous p.G146A SF1 polymorphism with normal CYP11A1, FDXR, FDX1, VDAC1 and TSPO genes. RT-PCR and sequencing from patient’s testicular RNA showed a -exon2 transcript and the wild-type (WT) transcript. Both 37 kDa precursor and 30 kDa mature protein were detected in COS-7 cell transfected with mutant and WT plasmids. Immunofluorescence showed almost no co-localization of mitochondria and mutant protein (delta22-59StAR). Delta22-59StAR activity was 65±13

of WT. Cotransfection with WT and delta22-59StAR plasmids reduced WT activity by 62.0

± 13.9. Novel splice-junction heterozygous STAR mutation (IVS-2A>G) resulted in the in-frame loss of amino acids 22 to 59 in the N-terminal mitochondrial targeting signal. A misfolded p.G22_L59delStAR might interfere with WT StAR activity by blocking the transduceosome complex, causing an autosomal dominant form of StAR deficiency, explaining the clinical phenotype.

Health-related quality of life in children and adolescents undergoing surgery for Hirschsprung's disease and anorectal malformations.

PURPOSE: The objective was to describe health related quality of life (HRQoL) after surgery for Hirschsprung's disease (HD) and anorectal malformations (ARMs) in children according to their own perception and that of their parents, by different age groups, the presence of functional disorders, and diet indication. METHODS: This is a cross-sectional descriptive study. Participants were patients aged 2-18 years old and their parents. The study was conducted from June 2008 to May 2009. The instrument used was the PedsQL TM 4.0. Data were analyzed with SPSS version 11.5. RESULTS: A total of 93 families gave their consent to participate. Higher scores indicated a better HRQoL. Parents showed a trend towards obtaining higher scores in the three scales analyzed. There were no differences observed in the various age groups. The lowest scores were obtained in incontinent, pseudo-incontinent and constipated patients with statistically significant differences according to the parents' reports when compared to the patients who had no functional disorders. When analyzing dietary therapy, patients who were on a controlled protein and low sodium diet together with a suitable intestinal function obtained lower scores. CONCLUSION: The presence of postoperative functional disorders had a negative impact on the scores. Incontinent, pseudo-incontinent and constipated patients had the lowest scores, as well as those who had a stricter diet.

Health-related quality of life in children and adolescents undergoing surgery for Hirschsprung´s disease and anorectal malformations / Calidad de vida relacionada con la salud en niños y adolescentes con cirugía de enfermedad de Hirschsprung y malformaciones anorrectales

Purpose. The objective was to describe health related quality of life (HRQoL) after surgery for Hirschsprungs disease (HD) and anorectal malformations (ARMs) in children according to their own perception and that of their parents, by different age groups, the presence of functional disorders, and diet indication. Methods. This is a cross-sectional descriptive study. Participants were patients aged 2-18 years old and their parents. The study was conducted from June 2008 to May 2009. The instrument used was the PedsQL TM 4.0. Data were analyzed with SPSS version 11.5. Results. A total of 93 families gave their consent to participate. Higher scores indicated a better HRQoL. Parents showed a trend towards obtaining higher scores in the three scales analyzed. There were no differences observed in the various age groups. The lowest scores were obtained in incontinent, pseudo-incontinent and constipated patients with statistically significant differences according to the parents´ reports when compared to the patients who had no functional disorders. When analyzing dietary therapy, patients who were on a controlled protein and low sodium diet together with a suitable intestinal function obtained lower scores. Conclusion. The presence of postoperative functional disorders had a negative impact on the scores. Incontinent, pseudo-incontinent and constipated patients had the lowest scores, as well as those who had a stricter diet.(AU)

Introducción/Objetivos. Los resultados postoperatorios de la enfermedad de Hirschsprung y malformaciones anorrectales son satisfactorios, pero muchos pacientes mantienen disfunciones intestinales. Estudiar la calidad de vida relacionada con la salud facilita el conocimiento del estado de salud y mejora la elección de estrategias de tratamiento. Los objetivos del estudio fueron describir la CVRS en niños luego de la cirugía correctora definitiva, según su propia percepción y la de sus padres. A su vez, evaluar la calidad de vida relacionada con la salud según grupo etario, presencia de trastornos funcionales postoperatorios y la indicación dietoterápica. Materiales y métodos. Estudio descriptivo, transversal. Participaron niños de 2-18 años y sus padres al concurrir al consultorio en el período de junio 2008-mayo 2009. Una vez obtenidos el consentimiento y asentimiento informado se aplicó el cuestionario genérico PedsQLtm. Paquete estadístico SPSS11.5. Resultados. Participaron 93 pacientes, 32% con enfermedad de Hirschsprung y 68% con malformaciones anorrectales. La mediana de edad fue de 7 años (intervalo 2-18). Puntuaciones más altas indican mejor calidad de vida. Los padres obtuvieron puntuaciones superiores a las de los niños en todas las escalas analizadas. No se observaron diferencias según los distintos grupos etarios. Se obtuvieron puntuaciones más bajas, con diferencias estadísticamente significativas según los padres, en los pacientes incontinentes y constipados. Resultados similares se observaron en pacientes con indicación dietoterápica, especialmente las dietas adecuadas a patologías renal y digestiva. Las puntuaciones más bajas se encontraron en los dominios total y psicosocial. Conclusión. La presencia de incontinencia y constipación repercute negativamente sobre la calidad de vida de los niños, así como la realización de dietas con las puntuaciones más bajas cuanto más restrictivas son aquéllas.(AU)

Health-related quality of life in children and adolescents undergoing surgery for Hirschsprung´s disease and anorectal malformations / Calidad de vida relacionada con la salud en niños y adolescentes con cirugía de enfermedad de Hirschsprung y malformaciones anorrectales

Purpose. The objective was to describe health related quality of life (HRQoL) after surgery for Hirschsprung's disease (HD) and anorectal malformations (ARMs) in children according to their own perception and that of their parents, by different age groups, the presence of functional disorders, and diet indication. Methods. This is a cross-sectional descriptive study. Participants were patients aged 2-18 years old and their parents. The study was conducted from June 2008 to May 2009. The instrument used was the PedsQL TM 4.0. Data were analyzed with SPSS version 11.5. Results. A total of 93 families gave their consent to participate. Higher scores indicated a better HRQoL. Parents showed a trend towards obtaining higher scores in the three scales analyzed. There were no differences observed in the various age groups. The lowest scores were obtained in incontinent, pseudo-incontinent and constipated patients with statistically significant differences according to the parents´ reports when compared to the patients who had no functional disorders. When analyzing dietary therapy, patients who were on a controlled protein and low sodium diet together with a suitable intestinal function obtained lower scores. Conclusion. The presence of postoperative functional disorders had a negative impact on the scores. Incontinent, pseudo-incontinent and constipated patients had the lowest scores, as well as those who had a stricter diet.

Introducción/Objetivos. Los resultados postoperatorios de la enfermedad de Hirschsprung y malformaciones anorrectales son satisfactorios, pero muchos pacientes mantienen disfunciones intestinales. Estudiar la calidad de vida relacionada con la salud facilita el conocimiento del estado de salud y mejora la elección de estrategias de tratamiento. Los objetivos del estudio fueron describir la CVRS en niños luego de la cirugía correctora definitiva, según su propia percepción y la de sus padres. A su vez, evaluar la calidad de vida relacionada con la salud según grupo etario, presencia de trastornos funcionales postoperatorios y la indicación dietoterápica. Materiales y métodos. Estudio descriptivo, transversal. Participaron niños de 2-18 años y sus padres al concurrir al consultorio en el período de junio 2008-mayo 2009. Una vez obtenidos el consentimiento y asentimiento informado se aplicó el cuestionario genérico PedsQLtm. Paquete estadístico SPSS11.5. Resultados. Participaron 93 pacientes, 32% con enfermedad de Hirschsprung y 68% con malformaciones anorrectales. La mediana de edad fue de 7 años (intervalo 2-18). Puntuaciones más altas indican mejor calidad de vida. Los padres obtuvieron puntuaciones superiores a las de los niños en todas las escalas analizadas. No se observaron diferencias según los distintos grupos etarios. Se obtuvieron puntuaciones más bajas, con diferencias estadísticamente significativas según los padres, en los pacientes incontinentes y constipados. Resultados similares se observaron en pacientes con indicación dietoterápica, especialmente las dietas adecuadas a patologías renal y digestiva. Las puntuaciones más bajas se encontraron en los dominios total y psicosocial. Conclusión. La presencia de incontinencia y constipación repercute negativamente sobre la calidad de vida de los niños, así como la realización de dietas con las puntuaciones más bajas cuanto más restrictivas son aquéllas.

Unique dominant negative mutation in the N-terminal mitochondrial targeting sequence of StAR, causing a variant form of congenital lipoid adrenal hyperplasia.

CONTEXT: Steroid acute regulatory (StAR) protein is a mitochondria-targeted protein that is part of the transduceosome complex crucial for transport of cholesterol to mitochondria. Recessive mutations cause classic and nonclassic congenital lipoid adrenal hyperplasia. OBJECTIVE: The aim of this study was to report the clinical, hormonal, genetic, and functional data of a novel heterozygous mutation in the StAR gene found in a 46,XY patient with ambiguous genitalia and neonatal severe steroidogenic deficiency. PATIENT: Undetectable serum steroids with high ACTH and plasma renin activity but normal acute GnRH response were found in infancy. After gonadectomy (at 3 yr of age), serum LH and testosterone were undetectable, whereas FSH was normal but increased slowly afterward. Estrogen replacement therapy, started at 10.2 yr of age, suppressed gonadotropins (for 2 yr). However, after 1 month off estrogens, the patient showed castrated levels. At 11.9 yr old, after fludrocortisone withdrawal because of hypertension, plasma renin activity and aldosterone remained normal, suggesting mineralocorticoid recovery by a StAR-independent mechanism. RESULTS: We found a de novo heterozygous IVS-2A>G StAR mutation and the reported heterozygous p.G146A SF1 polymorphism with normal CYP11A1, FDXR, FDX1, VDAC1, and TSPO genes. The mutant StAR transcript lacked exon 2, resulting in the in-frame loss of amino acids 22 to 59 in the N-terminal mitochondrial targeting signal. In vitro, the mutant protein exhibited reduced StAR activity in a dominant-negative manner and almost no mitochondria localization. CONCLUSIONS: A misfolded p.G22_L59del StAR might interfere with wild-type StAR activity by blocking the transduceosome complex, causing an autosomal dominant form of StAR deficiency, explaining the clinical phenotype. We speculated that estrogen might have modulated mineralocorticoid function and pubertal maturation in a human natural model lacking endogenous steroid production.

Health-related quality of life in children and adolescents undergoing surgery for Hirschsprungs disease and anorectal malformations. / Health-related quality of life in children and adolescents undergoing surgery for Hirschsprungs disease and anorectal malformations.

PURPOSE: The objective was to describe health related quality of life (HRQoL) after surgery for Hirschsprungs disease (HD) and anorectal malformations (ARMs) in children according to their own perception and that of their parents, by different age groups, the presence of functional disorders, and diet indication. METHODS: This is a cross-sectional descriptive study. Participants were patients aged 2-18 years old and their parents. The study was conducted from June 2008 to May 2009. The instrument used was the PedsQL TM 4.0. Data were analyzed with SPSS version 11.5. RESULTS: A total of 93 families gave their consent to participate. Higher scores indicated a better HRQoL. Parents showed a trend towards obtaining higher scores in the three scales analyzed. There were no differences observed in the various age groups. The lowest scores were obtained in incontinent, pseudo-incontinent and constipated patients with statistically significant differences according to the parents reports when compared to the patients who had no functional disorders. When analyzing dietary therapy, patients who were on a controlled protein and low sodium diet together with a suitable intestinal function obtained lower scores. CONCLUSION: The presence of postoperative functional disorders had a negative impact on the scores. Incontinent, pseudo-incontinent and constipated patients had the lowest scores, as well as those who had a stricter diet.

Nueva mutación heterocigota en el gen de la proteína regulatoria aguda de la esteroideogénesis (StAR) en un paciente 46,XY con hiperplasia adrenal congénita lipoidea. / [Novel heterozygous mutation in the steroidogenic acute regulatory protein gene in a 46,XY patient with congenital lipoid adrenal hyperplasia].

StAR facilitates cholesterol entry into the mitochondria as part of the transduceosome complex. Recessive mutations in the gen STAR cause classic and nonclassic congenital lipoid adrenal hyperplasia. The aim of the study was to analyze the molecular consequences of a novel heterozygous STAR mutation in a 46,XY patient with ambiguous genitalia and adrenal insufficiency. We found a de novo heterozygous IVS-2A>G STAR mutation and the reported heterozygous p.G146A SF1 polymorphism with normal CYP11A1, FDXR, FDX1, VDAC1 and TSPO genes. RT-PCR and sequencing from patients testicular RNA showed a -exon2 transcript and the wild-type (WT) transcript. Both 37 kDa precursor and 30 kDa mature protein were detected in COS-7 cell transfected with mutant and WT plasmids. Immunofluorescence showed almost no co-localization of mitochondria and mutant protein (delta22-59StAR). Delta22-59StAR activity was 65±13

of WT. Cotransfection with WT and delta22-59StAR plasmids reduced WT activity by 62.0

± 13.9. Novel splice-junction heterozygous STAR mutation (IVS-2A>G) resulted in the in-frame loss of amino acids 22 to 59 in the N-terminal mitochondrial targeting signal. A misfolded p.G22_L59delStAR might interfere with WT StAR activity by blocking the transduceosome complex, causing an autosomal dominant form of StAR deficiency, explaining the clinical phenotype.

[Achievements and challenges in implementing the surgical checklist in a pediatric hospital]. / Lista de verificación de seguridad de la cirugía: logros y dificultades de su implementación en un hospital pediátrico.

Patient safety in the operating room is a topic of universal concern. Several studies support the existence of a high percentage of complications and a high mortality rate in surgical procedures (0.5 to 5%). The World Health Organization (WHO) has proposed the implementation of surgical check list in order to improve patient safety in the operating room. In Hospital Garrahan, 9600 surgeries and surgical anesthesia for more than 8000 studies and other invasive procedures are performed per year. WHO checklist adaptation and implementation was considered an institutional priority. We describe difficulties and solutions in implementing the surgical checklist. Surgical team involvement in project planning and development was essential.