Hysteroscopic myomectomy for submucosal type 2 fibroids with cold enucleation technique and complete fibroid extraction using a double-lumen intracervical cannula.

OBJECTIVE: To introduce a new double-lumen intracervical cannula designed to allow a single-step hysteroscopic myomectomy with nonfragmented complete fibroid extraction after cold enucleation of submucosal type 2 fibroids, avoiding complications related to the use of energy and hypo-osmolar solutions. DESIGN: Video article depicting the use of a new double-lumen intracervical cannula for single-step hysteroscopic cold myomectomy, according to our institutional care guidelines and after obtaining the patient's informed consent. (The publication of this video has been authorized by the Institutional Ethics Committee of CES University in Medellín, Colombia.) SETTING(S): Private infertility clinic. PATIENT(S): A 45-year-old woman with abnormal uterine bleeding consisting of polymenorrhea and hypermenorrhea, nonresponsive to medical treatment, caused by three type 2 (FIGO leiomyoma subclassification system) submucosal fibroids of 17, 15, and 13 mm with more than 80% of intramyometrial component. INTERVENTION(S): Hysteroscopic enucleation of three submucosal fibroids performed by blunt dissection using the 30° Bettocchi hysteroscope's bevel under continuous observation of the avascular subcapsular plane of the fibroids. Once full enucleation was attained, cervical dilatation to 12 mm with Hegar plugs was performed followed by intracervical placement of a newly designed double-lumen intracervical cannula that allows the concomitant introduction of the Bettocchi diagnostic hysteroscope and a 5-mm laparoscopic tenaculum into the uterine cavity for complete nonfragmented fibroid extraction under direct visualization. MAIN OUTCOME MEASURE(S): Complete and unfragmented fibroid extraction in a single intervention, absence of surgical complications, and postoperative course. RESULT(S): Ambulatory hysteroscopic myomectomy of three submucosal type 2 fibroids was successfully performed by blunt enucleation and complete nonfragmented fibroid extraction using the double-lumen intracervical cannula. The total operative time was 32 minutes, and the total amount of distension media (normal saline) used was 800 mL with a liquid balance of 50 mL. No surgical or anesthesia-related complications occurred. In the postsurgical evaluation, the patient classified her pain as minimal, giving it a score of 1 on a pain scale of 1 to 5 (in which 1 is the lowest and 5 the highest pain perception). When asked about the level of satisfaction with the surgical procedure, the patient reported the highest degree of satisfaction with a score of 5 on a satisfaction scale of 1 to 5 (in which 1 is the lowest and 5 the highest satisfaction). The patient reported having postsurgical regular menstrual cycles every 28 days and 3 bleeding days without hypermenorrhea. CONCLUSION(S): An efficient hysteroscopic myomectomy of submucosal type 2 fibroids with deep intramyometrial component can be performed with complete and nonfragmented fibroid extraction in a single intervention by using a newly designed double-lumen intracervical cannula. This technique allows the completion of the surgery without the need of a resectoscope, electrosurgery, or hypo-osmolar uterine distension media, thus avoiding potential complications such as thermal-induced myometrial injury and hyponatremia; a second surgical intervention will not be required because the fibroid enucleation is complete. The procedure can be performed with the use of a diagnostic hysteroscope that is widely available in gynecologic practices. (Acknowledgment: The authors thank Dr. David Olive for the invaluable help and guidance with this surgical technique and video article.).

Pathway and network analysis of more than 2500 whole cancer genomes.

The catalog of cancer driver mutations in protein-coding genes has greatly expanded in the past decade. However, non-coding cancer driver mutations are less well-characterized and only a handful of recurrent non-coding mutations, most notably TERT promoter mutations, have been reported. Here, as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium, which aggregated whole genome sequencing data from 2658 cancer across 38 tumor types, we perform multi-faceted pathway and network analyses of non-coding mutations across 2583 whole cancer genomes from 27 tumor types compiled by the ICGC/TCGA PCAWG project that was motivated by the success of pathway and network analyses in prioritizing rare mutations in protein-coding genes. While few non-coding genomic elements are recurrently mutated in this cohort, we identify 93 genes harboring non-coding mutations that cluster into several modules of interacting proteins. Among these are promoter mutations associated with reduced mRNA expression in TP53, TLE4, and TCF4. We find that biological processes had variable proportions of coding and non-coding mutations, with chromatin remodeling and proliferation pathways altered primarily by coding mutations, while developmental pathways, including Wnt and Notch, altered by both coding and non-coding mutations. RNA splicing is primarily altered by non-coding mutations in this cohort, and samples containing non-coding mutations in well-known RNA splicing factors exhibit similar gene expression signatures as samples with coding mutations in these genes. These analyses contribute a new repertoire of possible cancer genes and mechanisms that are altered by non-coding mutations and offer insights into additional cancer vulnerabilities that can be investigated for potential therapeutic treatments.

SSA-ME Detection of cancer driver genes using mutual exclusivity by small subnetwork analysis.

Because of its clonal evolution a tumor rarely contains multiple genomic alterations in the same pathway as disrupting the pathway by one gene often is sufficient to confer the complete fitness advantage. As a result, many cancer driver genes display mutual exclusivity across tumors. However, searching for mutually exclusive gene sets requires analyzing all possible combinations of genes, leading to a problem which is typically too computationally complex to be solved without a stringent a priori filtering, restricting the mutations included in the analysis. To overcome this problem, we present SSA-ME, a network-based method to detect cancer driver genes based on independently scoring small subnetworks for mutual exclusivity using a reinforced learning approach. Because of the algorithmic efficiency, no stringent upfront filtering is required. Analysis of TCGA cancer datasets illustrates the added value of SSA-ME: well-known recurrently mutated but also rarely mutated drivers are prioritized. We show that using mutual exclusivity to detect cancer driver genes is complementary to state-of-the-art approaches. This framework, in which a large number of small subnetworks are being analyzed in order to solve a computationally complex problem (SSA), can be generically applied to any problem in which local neighborhoods in a network hold useful information.

EXPLoRA-web: linkage analysis of quantitative trait loci using bulk segregant analysis.

Identification of genomic regions associated with a phenotype of interest is a fundamental step toward solving questions in biology and improving industrial research. Bulk segregant analysis (BSA) combined with high-throughput sequencing is a technique to efficiently identify these genomic regions associated with a trait of interest. However, distinguishing true from spuriously linked genomic regions and accurately delineating the genomic positions of these truly linked regions requires the use of complex statistical models currently implemented in software tools that are generally difficult to operate for non-expert users. To facilitate the exploration and analysis of data generated by bulked segregant analysis, we present EXPLoRA-web, a web service wrapped around our previously published algorithm EXPLoRA, which exploits linkage disequilibrium to increase the power and accuracy of quantitative trait loci identification in BSA analysis. EXPLoRA-web provides a user friendly interface that enables easy data upload and parallel processing of different parameter configurations. Results are provided graphically and as BED file and/or text file and the input is expected in widely used formats, enabling straightforward BSA data analysis. The web server is available at http://bioinformatics.intec.ugent.be/explora-web/.

Frequency-based haplotype reconstruction from deep sequencing data of bacterial populations.

Clonal populations accumulate mutations over time, resulting in different haplotypes. Deep sequencing of such a population in principle provides information to reconstruct these haplotypes and the frequency at which the haplotypes occur. However, this reconstruction is technically not trivial, especially not in clonal systems with a relatively low mutation frequency. The low number of segregating sites in those systems adds ambiguity to the haplotype phasing and thus obviates the reconstruction of genome-wide haplotypes based on sequence overlap information.Therefore, we present EVORhA, a haplotype reconstruction method that complements phasing information in the non-empty read overlap with the frequency estimations of inferred local haplotypes. As was shown with simulated data, as soon as read lengths and/or mutation rates become restrictive for state-of-the-art methods, the use of this additional frequency information allows EVORhA to still reliably reconstruct genome-wide haplotypes. On real data, we show the applicability of the method in reconstructing the population composition of evolved bacterial populations and in decomposing mixed bacterial infections from clinical samples.

Improved linkage analysis of Quantitative Trait Loci using bulk segregants unveils a novel determinant of high ethanol tolerance in yeast.

BACKGROUND: Bulk segregant analysis (BSA) coupled to high throughput sequencing is a powerful method to map genomic regions related with phenotypes of interest. It relies on crossing two parents, one inferior and one superior for a trait of interest. Segregants displaying the trait of the superior parent are pooled, the DNA extracted and sequenced. Genomic regions linked to the trait of interest are identified by searching the pool for overrepresented alleles that normally originate from the superior parent. BSA data analysis is non-trivial due to sequencing, alignment and screening errors. RESULTS: To increase the power of the BSA technology and obtain a better distinction between spuriously and truly linked regions, we developed EXPLoRA (EXtraction of over-rePresented aLleles in BSA), an algorithm for BSA data analysis that explicitly models the dependency between neighboring marker sites by exploiting the properties of linkage disequilibrium through a Hidden Markov Model (HMM). Reanalyzing a BSA dataset for high ethanol tolerance in yeast allowed reliably identifying QTLs linked to this phenotype that could not be identified with statistical significance in the original study. Experimental validation of one of the least pronounced linked regions, by identifying its causative gene VPS70, confirmed the potential of our method. CONCLUSIONS: EXPLoRA has a performance at least as good as the state-of-the-art and it is robust even at low signal to noise ratio's i.e. when the true linkage signal is diluted by sampling, screening errors or when few segregants are available.

Evolutionary algorithm for vehicle driving cycle generation.

Modeling transit bus emissions and fuel economy requires a large amount of experimental data over wide ranges of operational conditions. Chassis dynamometer tests are typically performed using representative driving cycles defined based on vehicle instantaneous speed as sequences of "microtrips", which are intervals between consecutive vehicle stops. Overall significant parameters of the driving cycle, such as average speed, stops per mile, kinetic intensity, and others, are used as independent variables in the modeling process. Performing tests at all the necessary combinations of parameters is expensive and time consuming. In this paper, a methodology is proposed for building driving cycles at prescribed independent variable values using experimental data through the concatenation of "microtrips" isolated from a limited number of standard chassis dynamometer test cycles. The selection of the adequate "microtrips" is achieved through a customized evolutionary algorithm. The genetic representation uses microtrip definitions as genes. Specific mutation, crossover, and karyotype alteration operators have been defined. The Roulette-Wheel selection technique with elitist strategy drives the optimization process, which consists of minimizing the errors to desired overall cycle parameters. This utility is part of the Integrated Bus Information System developed at West Virginia University.

Factores de riesgo de enfermedad cardiovascular de universitarios voluntarios en un proyecto de control de colesterol sérico / Cardiovascular disease risk factors of university volunteers in a serum cholesterol control project. Salta. 2007

Objetivo: Estudiar los factores de riesgo cardiovascular del personal docente y administrativo de la Universidad Nacional de Salta interesados en participar en un ensayo clínico para evaluar el efecto de un suplemento dietario “naringina” sobre los niveles de colesterolemia. Metodología: Se realizó una convocatoria por correo electrónico. Se realizó una revisión clínica, antropométrica, impedancia bioeléctrica y estudio bioquímico en dos etapas para preseleccionar la muestra del ensayo clínico con criterios de inclusión y exclusión pre-establecidos. Los resultados se analizaron estadísticamente con diferencia de medias, chi2 y prueba de Fisher. Resultados: Se incluyeron 38 mujeres y 16 varones de 40 a 60 años. 50 por ciento refirió tener antecedentes familiares de hipercolesterolemia. 61 por ciento de los participantes no realizó actividad física. 16% y el 93% respectivamente presentó patologías asociadas e Índice de cintura cadera (ICC) en riesgo y 69% índice de masa corporal (IMC) superior a lo normal. 32 mujeres y 12 hombres presentaron grasa intrabdominal en exceso. En la segunda etapa (n=45), 15% presentó valores de colesterol superiores a 240 mg/dl (alto riesgo) y 55 por ciento hasta 219 mg/dl (bajo riesgo). 62 por ciento HDL colesterol a 100 mg/dl (alto riesgo). 37,8 por ciento mostró valores de triglicéridos superiores a 160 mg/dl. 50 por ciento presentó más de 6 factores de riesgo. Los índices antropométricos se relacionaron entre sí y el IMC es el único que se vinculó con las fracciones HDL y LDL colesterol. El sedentarismo y antecedentes familiares mostraron correspondencia con las fracciones lipídicas HDL y LDL colesterol. Conclusiones: Casi la totalidad del grupo mostró factores de riesgo, destacándose entre ellos las fracciones HDL y LDL colesterol elevado, ICC elevado y exceso de grasa corporal, los que deben ser abordados tanto desde lo personal como desde lo institucional.

Espondiloartropatía ocronótica: reporte de un caso / Ochronotic spondyloarthropathy: a case report

Se presenta el caso de un hombre de 40 años con artropatía en la rodilla derecha y la columna lumbar secundaria a ocronosis confirmada. Esta enfermedad es infrecuente pero se la debe tener en cuenta en el diagnóstico diferencial en pacientes jóvenes con artropatía y compromiso espondiloarticular. Se revisan brevemente los aspectos histórico, bioquímico, clínico y terapéutico de la enfermedad.

We report the case of a male patient, aged 40 years, with knee and lumbar spine arthropathy secondary to confirmed ochronosis. Although this is an infrequent disease, it is necessary to take it into account in the differential diagnosis of articular lesions and spondyloarthropathy in young patients. Historic, biochemical, clinical and therapeutic aspects of the disease are briefly reviewed.

Isquemia coronaria y mesenterica: novedoso enfoque quirúrgico combinado / Coronary and mesenteric isquemia: a combine surgical procedure

La isquemia mesenterica cronica (IMC) se encuentran mas frecuentemente en pacientes que presentan un compromiso plurifocal de la enfermedad ateromatosa. teniendo en cuenta la comorbilidad asociada, la coronariopatia ocupa un lugar preponderante, complicando el enfoque terapeútico de esta patología. Nosotros reportamos el caso de un paciente que presentaba una IMC severa asociada a una coronariopatia recidivante, en quien se practico, en el curso del mismo tiempo operatorio una revascularizacion miocardiaca y mesenterica, por puentes venosos a partir de la aorta ascendente, por compromiso ateromatoso extenso de la aorta. Esta elección terapéutica fue impuesta por las condiciones anatómicas de las lesiones arteriosclerosas. La evolución postoperatoria faboreble con un seguimiento actual de dos a±os justifica la indicación quirúrgica.ABSTRACT: Chronic mesenteric ischemia (CMI) is found most frequently among patients who present a multifocal compromise of the atheromastosis disease. Taking into account the associated comorbility, coronarypathy occupies a remarkable place, complicating the therapeutic approach of this pathology. We report the case of a patient who presented a severe chronic mesenteric ischemia associated to a recidiving coronarypathy. While he was being operated on a myocardial and mesenteric revascularization was performed hrough venous bypasses from the ascending aorta, due to the extended atheromatosis compromise of the aorta. This therapeutic choice was lead by the anatomic conditions of the arteriosclerosis lesions. The favorable post-surgical evolution, with a two year follow-up to date, justifies the surgical indication

Medistinoscopia: su utilidad y bajo riesgo / Mediastinoscopy: your utility and low risk

RESUMEN: Análisis retrospectivo de 48 pacientes sometidos a mediastinoscopía para diagnóstico de patología mediastinal aislada o asociada a enfermedad pulmonar o sistémica. Los diagnósticos preoperatorios fueron: metástasis de carcinoma pulmonar 29, linfoma 7, sarcoidosis 5, adenomegalia mediastinal 3, esclerodermia, transformación sarcomatosa de Leucemia Mieloide Crónica (LMC), metástasis de carcinoma de tiroides sin diagnóstico en 1 caso respectivamente. No hubo mortalidad relacionada al procedimiento y la única compilación fue tumefacción de herida operatoria en un caso. Se obtuvo diagnóstico de patología espacífica en 38/48(79.2 por ciento), confirmado el diagnóstico peroperatorio en 25/48(52 por ciento). En 10/48(20.8 por ciento) el diagnóstico fue estructura ganglionar normal o inflamación inespecífica. El tiempo de internación fue de 24 hs. En 44/48 (91.6 por ciento) de los pacientes. En conclusión, la mediastinoscopíames un método simple, seguro, efectivo y de muy baja morbimortalidad para el diagnóstico de patologías mediastinales.

Protocolo de asistencia circulatoria mecánica: balon de contrapulsión aórtico / Protocol of circulatory mechanics assistance: aortic ballon contrapulsation

RESUMEN: El tratamiento del síndrome de bajo gasto cardíaco, mantiene elevados porcentajes de mortalidad a pesar de los importantes avances en el tratamiento farmacológico. Por ello, se han realizado grandes esfuerzos para mejorar la función ventricular izquierda y el aporte miócardico de oxígeno. Durante años se han ideado y experimentado diversos sistemas de asistencia circulatoria, como dispositivos capaces de sustituir o mejorar la función cardíaca. Estos son; la bomba de circulación extracorpórea, ventriculos artificiales y otros que modifican la dinámica cardíaca como el balón de contrapulsión intra-aórtico. Se revisa la fisiología, hemodinamia, usos manejos y complicaciones en el contexto clínico, así como guía básica para la correcta utilización del balón de contrapulsación.