Assessment of Risk for Ventricular Tachycardia based on Extensive Electrophysiology Simulations.

Patients that have suffered a myocardial infarction are at high risk of developing ventricular tachycardia. Patient stratification is often determined by characterization of the underlying myocardial substrate by cardiac imaging methods. In this study, we show that computer modeling of cardiac electrophysiology based on personalized fast 3D simulations can help to assess patient risk to arrhythmia. We perform a large simulation study on 21 patient digital twins and reproduce successfully the clinical outcomes. In addition, we provide the sites which are prone to sustain ventricular tachycardias, i.e, onset sites around the scar region, and validate if they colocalize with exit sites from slow conduction channels.Clinical relevance- Fast electrophysiological simulations can provide advanced patient stratification indices and predict arrhythmic susceptibility to suffer from ventricular tachycardia in patients that have suffered a myocardial infarction.

Anomalous nucleation of crystals within amorphous germanium nanowires during thermal annealing.

In this work, germanium nanowires rendered fully amorphous via xenon ion irradiation have been annealed within a transmission electron microscope to induce crystallization. During annealing crystallites appeared in some nanowires whilst others remained fully amorphous. Remarkably, even when nucleation occurred, large sections of the nanowires remained amorphous even though the few crystallites embedded in the amorphous phase were formed at a minimum of 200 °C above the temperature for epitaxial growth and 100 °C above the temperature for random nucleation and growth in bulk germanium. Furthermore, the presence of crystallites was observed to depend on the diameter of the nanowire. Indeed, the formation of crystallites occurred at a higher annealing temperature in thin nanowires compared with thicker ones. Additionally, nanowires with a diameter above 55 nm were made entirely crystalline when the annealing was performed at the temperature normally required for crystallization in germanium (i.e. 500 °C). It is proposed that oxygen atoms hinder both the formation and the growth of crystallites. Furthermore, as crystallites must reach a minimum size to survive and grow within the amorphous nanowires, the instability of crystallites may also play a limited role for the thinnest nanowires.

Long-term risk of fibroid recurrence after laparoscopic myomectomy.

OBJECTIVE: The use of laparoscopic myomectomy as a surgical treatment for uterine leiomyoma is associated with low intraoperative morbidity and short hospitalization. Limited data about the long-term outcome of this surgical approach are available. The aims of this study were to estimate the risk of uterine fibroid recurrence after laparoscopic myomectomy and to identify factors contributing to the rate of fibroid relapse. STUDY DESIGN: Between 1996 and 2003, 331 patients underwent laparoscopic myomectomy to treat uterine leiomyoma in our hospital; 224 of these patients consented to participate in our 2009 follow-up survey. Clinical symptomatic uterine leiomyoma recurrence was defined as relapse. Recurrence rates at 24 and 60 months post-operatively were calculated for the study population. Fisher's exact tests were used to examine the impacts of factors previously linked to an increased risk of fibroid recurrence, including (1) patient age at the time of initial surgery, (2) pre-operative body mass index, (3) number and localization of uterine leiomyoma removed, and (4) pregnancy and (5) delivery after laparoscopic myomectomy on fibroid recurrence in our study cohort. RESULTS: We observed 75 recurrences in 224 patients. The cumulative risk of recurrence was 4.9% at 24 months and 21.4% at 60 months post-operatively. An age of 30-40 years and the presence of more than one fibroid at the time of initial laparoscopic myomectomy were identified as factors significantly increasing the risk of symptomatic recurrence after laparoscopic myomectomy (31.25% and 38.71%, respectively; both p<0.01). CONCLUSION: Patients with multiple uterine leiomyoma and those in the third decade of life should be counselled thoroughly about the risk of recurrence prior to laparoscopic myomectomy. The low observed recurrence rate in peri- and postmenopausal patients in our study may support the use of laparoscopic myomectomy as a uterus-preserving surgical alternative beyond the reproductive period.

Sonographic discrimination between benign and malignant adnexal masses in premenopause.

PURPOSE: The aim of this study was to assess the diagnostic value of sonographic pattern recognition by experts, a standardized morphological scoring system, the risk malignancy index (RMI) and CA 125 assay for the preoperative assessment of ovarian lesions in premenopausal patients. MATERIAL AND METHODS: Diagnostic work-up of 1320 patients who underwent surgical exploration due to an adnexal mass at a tertiary referral center were included. We assessed the discriminative value of pattern recognition, a sonographic morphological scoring system, RMI and CA 125 by calculating sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and Cohen's kappa for each diagnostic approach while using histopathology as the reference standard. RESULTS: Pattern recognition showed the highest discriminative power with an observed kappa of 0.53. Sensitivity and specificity yielded 0.76 and 0.97 respectively. Combining pattern recognition with CA 125 serum measurement in the context of a triage system diminished the diagnostic value (kappa: 0.24; sensitivity: 0.29 specificity: 0.97). For the RMI we observed a sensitivity of 0.54 and a specificity of 0.96 and estimated kappa value yielded 0.37. Omitting the CA 125 assay and using a morphological sonographic assessment system increased the kappa value to 0.45 with sensitivity and specificity observed at 0.61 and 0.97 respectively. CONCLUSION: Expert pattern recognition was found to be the method with the highest discriminative power in assessing an adnexal mass during premenopause. Additional assessment of serum CA 125 diminished the diagnostic accuracy. Standardized morphological sonographic assessment resulted in a moderate diagnostic accuracy. Supplementing the morphological sonographic assessment with CA 125 by using the RMI algorithm did not improve the diagnostic value.

Heterogeneity of circulating epithelial tumour cells from individual patients with respect to expression profiles and clonal growth (sphere formation) in breast cancer.

BACKGROUND: The detection of tumour cells circulating in the peripheral blood of patients with breast cancer is a sign that cells have been able to leave the primary tumour and survive in the circulation. However, in order to form metastases, they require additional properties such as the ability to adhere, self-renew, and grow. Here we present data that a variable fraction among the circulating tumour cells detected by the Maintrac(®) approach expresses mRNA of the stem cell gene NANOG and of the adhesion molecule vimentin and is capable of forming tumour spheres, a property ascribed to tumour-initiating cells (TICs). PATIENTS AND METHODS: Between ten and 50 circulating epithelial antigen-positive cells detected by the Maintrac approach were selected randomly from each of 20 patients with breast cancer before and after surgery and were isolated using automated capillary aspiration and deposited individually onto slides for expression profiling. In addition, the circulating tumour cells were cultured without isolation among the white blood cells from 39 patients with breast cancer in different stages of disease using culture methods favouring growth of epithelial cells. RESULTS: Although no epithelial cell adhesion molecule (EpCAM)-positive cells expressing stem cell genes or the adhesion molecule vimentin was detected before surgery, 10%-20% of the cells were found to be positive for mRNA of these genes after surgery. Tumour spheres from circulating cells of 39 patients with different stages of breast cancer were grown without previous isolation in a fraction increasing with the aggressivity of the tumour. SUMMARY: Here we show that among the peripherally circulating tumour cells, a variable fraction is able to express stem cell and adhesion properties and can be grown into tumour spheres, a property ascribed to cells capable of initiating tumours and metastases.

Síndrome neuroléptico maligno y reacción a oxcarbazepina en un paciente pediátrico / Neuroleptic malignant syndrome and adverse reaction to oxcarbazepine in a pediatric patient

Puesto que la prescripción de antipsicóticos o neurolépticos está siendo cada vez más frecuente en la población pediátrica con trastornos neurológicos en politerapia, es interesante tener presente un cuadro tan infrecuente y potencialmente grave como el síndrome neuroléptico maligno, así como otras posibles reacciones adversas a medicamentos. Describimos el caso de un paciente pediátrico que desarrolló un síndrome neuroléptico maligno secundario a haloperidol y/o risperidona, al que pudo sumarse una reacción adversa medicamentosa a oxcarbazepina, con una evolución favorable(AU)

Since the prescription of antipsychotic or neuroleptic medications are becoming more common in the pediatric population under polytherapy with neurological disorders is interesting to take into account this rare and potentially serious neuroleptic malignant syndrome and other possible adverse reactions to drugs. We describe a pediatric patient who developed neuroleptic malignant syndrome secondary to haloperidol/risperidone and a possible adverse reaction to oxcarbazepine(AU)

Leishmaniasis visceral, nuestra experiencia en 30 años / Visceral leishmaniasis, our experience in 30 years

Objetivos. El kala azar o leishmaniasis viscera (LV) es una de las enfermedades más olvidadas del mundo. En los países en desarrollo, 350 millones de personas están en riesgo de contraer LV, habiendo 2 millones de casos nuevos al año, En España, a partir de 1982, se hizo enfermedad de declaración obligatoria, notificándose unos 90 casos/año. A partir de 1995 pasó a ser enfermedad de declaración obligatoria en zonas endémicas, considerándose Aragón una de ellas. Pacientes y métodos. Estudio descriptivo retrospectivo de 14 casos de LV confirmados en edad pediátrica (0 a 14 años) ingresados en la Unidad de Infecciosos del Hospital Infantil Miguel Servet, de Zaragoza, entre enero de 1980 a diciembre de 2010. Resultados. Fueron ingresados 16 niños con el diagnóstico de LV. El estudio se lleva a cabo con datos de 14 pacientes. La edad media de presentación fue 3 años (rango 9 meses-12 años, mediana 19 meses). El 64% de los pacientes procedían del medio rural. Al ingreso presentaban una media de 3.700 leucocitos, con neurtropenia en el 71% de los pacientes. Existían trombopenia (<150.000 plaquetas/mm3) en un 77% de los casos. Presentaban anemia el 100% de los pacientes con una media de hemoglobina de 7,7 mg/dl. Un 64 % de los niños debutaron con pancitopenia. La VSG se elevó por encima de 20 mm/h en el 100% de los casos. En todos los pacientes se realizó aspirado de médula ósea, visualizándose el parásito en todas las muestras, confirmando el diagnóstico de LV. Todos los casos fueron tratados con meglumina antimoniato, excepto el último registrado en 2010 que recibió anfotericina B liposomal, todos con buena respuesta clínica (...) (AU)

Objectives. Kala azar o viscera leishmaniasis (LV) is one of the most neglected disease in the world. In developing countries, 350 million people are at risk of having LV and 2 million cases are reported every year. In Spain, since 1982 LV has become a compulsory notifiable disease with around 90 cases reported every year. In 1995, it was declared notifiable disease in endemic areas and one of them was Aragón. Patients and Methods. Retrospective study of 14 VL cases. All of them in patients between 0-14 years old admitted into the Infectious Diseases Unit at Children´s Hospital Miguel Servet in Zaragoza between January 1980 to December 2010. Results. A total of 16 children were admitted with the diagnosis of I. V. The study was carried out with data of 14 of these patients. The mean age at diagnosis was 3 years (range 9 months-12 years, median 19 months). The 64% of them came from rural areas. At admission, they had 3700 leukocyte average with neutropenia in 71% of those cases. All of them (100%9 were anemic with a 7.7 mg/ld hemoglobin/dl range but only nearly 77% has thrombocytopenia (<150,000 platelets/mm3). The 64% of the children debuted with pancytopenia. ESR rose were more than 20 mm/h in all cases (...) (AU)

Understanding the mechanisms amenable to CRT response: from pre-operative multimodal image data to patient-specific computational models.

This manuscript describes our recent developments towards better understanding of the mechanisms amenable to cardiac resynchronization therapy response. We report the results from a full multimodal dataset corresponding to eight patients from the euHeart project. The datasets include echocardiography, MRI and electrophysiological studies. We investigate two aspects. The first one focuses on pre-operative multimodal image data. From 2D echocardiography and 3D tagged MRI images, we compute atlas based dyssynchrony indices. We complement these indices with presence and extent of scar tissue and correlate them with CRT response. The second one focuses on computational models. We use pre-operative imaging to generate a patient-specific computational model. We show results of a fully automatic personalized electromechanical simulation. By case-per-case discussion of the results, we highlight the potential and key issues of this multimodal pipeline for the understanding of the mechanisms of CRT response and a better patient selection.

Laparoscopic lymphocele fenestration in gynaecological cancer patients after retroperitoneal lymph node dissection as a first-line treatment option.

OBJECTIVE: To evaluate laparoscopic lymphocele fenestration (LLF) as a first-line treatment in gynaecological cancer patients with a history of retroperitoneal lymph node dissection (LND). DESIGN: Retrospective cohort study. SETTING: A tertiary referral centre. POPULATION: Patients who underwent LLF between January 2001 and December 2010 for a symptomatic lymphocele following retroperitoneal LND. METHODS: Surgical outcomes of 102 patients who underwent LLF at our hospital between January 2001 and December 2010 were analysed. Patients were identified using hospital database search software, and hand-written and electronic charts were reviewed. MAIN OUTCOME MEASURES: Outcomes included operating time, blood loss, conversion rate, intra- and postoperative complication rates, hospital stay and relapse rate. RESULTS: A total of 132 lymphoceles were fenestrated in 102 patients. The mean duration of surgery was 115.6 minutes and the average intraoperative blood loss per patient was 146 ml. The overall conversion rate to laparotomy was 7.8%. Intra- and postoperative complication rates were estimated at 9.8 and 5.9%, respectively. The rate of intraoperative and postoperative complications was significantly higher in patients after pelvic plus paraaortic LND (23.8%), compared with those after pelvic LND only (3.6%; P > 0.01). The mean follow-up time was 60.4 months and a total of seven symptomatic recurrences of lymphoceles were observed (a recurrence rate of 6.9%). CONCLUSIONS: For the treatment of symptomatic lymphoceles, LLF has previously been established as an efficient first-line treatment option in a post-transplant context. Our data suggest that these favourable results for LLF may be transferable to gynaecological cancer patients.

Casos de paludismo en un Hospital Terciario, Revisión de los últimos 10 años / Retrospective descriptive study of the meningitis admitted to our hospital

Objetivos. El paludismo sigue siendo un problema de salud pública a nivel global. Según la OMS, 108 países son endémicos en el mundo. En España, el número de casos importados ha crecido paulatinamente desde los años 70 debido al aumento de la inmigración, el turismo y trabajadores estacionales en países endémicos. Pacientes y métodos. Estudio descriptivo retrospectivo de los casos de paludismo confirmado en niños ingresados en la unidad de Infecciosos de nuestro Hospital, entre enero del 200 y enero 2010. Resultados. Fueron ingresados 51 niños con el diagnóstico de paludismo. La edad media de presentación fue de 6 años (rango: 11 meses y los 13 años). El 92,3% de los pacientes procedían del África SubSahariana con predominio de Guinea Ecuatorial (17 casos: 43,6%). En 35 casos (89,7%) constaba un viaje reciente a su país de origen, habiendo recibido profilaxis antipalúdica 2 casos. Presentaron fiebre en el 71,8% de los casos, hepatomegalia en el 59%, el plenomegalia en el 56,4% y 3 casos requirieron ingreso en UCI. Todos los casos se diagnosticaron mediante el método de gota gruesa. El Plasmodium falciparum fue el más frecuente 871,8%), seguido de Plasmodium vivax (12,8%) y de Plamodium malarie (5,1%). La detección de antígeno de Plasmodium en sangre se realizó en 21 casos (53,8%) y en ninguno se realizó la determinación genómica con PCR. La combinación de quinina con pirimetamina y sulfadioxina se aplicó en el 61,5% de la muestra. Se encontró parasitación intestinal concomitante en 8 casos. Conclusiones. En nuestra casuística, como en otras series publicadas en nuestro país, el 92,3% de los pacientes procedían del África Subsahariana con predominio de Guinea Ecuatorial y en el 89,7% constaba un viaje reciente a su país de origen. La gota gruesa fue el método diagnóstico más útil. Hay que destacar la importancia de efectuar una profilaxis antipalúdica adecuada antes de realizar un viaje a zonas endémicas (en nuestro estudio únicamente 2 caos la habían realizado). Es importante realizar en todos los casos un despistaje de otra parasitosis intestinales asociadas (AU)

Objectives. Malaria remains a public health problema worldwide. According to WHO, 108 countries are endemic in the world. In Spain, the number of imported cases has grown steadily since the 70's due to increased immigration, tourism and seasonal working in endemic countries. Patients and methods. A retrospective of confirmed malaria cases in children admitted to the Infectious Diseases Unit of our hospital, between January 2000 and January 2010. Results. 51 children were admitted with the diagnosis of malaria. The mean age at diagnosis was 6 years (range; 11 months to 13 years). 92,3% of patients came from sub-Saharan Africa with prevalence of Equatorial Guinea (17 cases: 43,6%). In 35 cases (89,7%) a recent trip to his home country has been made, two of them having received antimalarial prophylaxis. There was fever in 71,8% of the cases, hepatomegaly in 59%, splenomegaly in 56,4% and 3 patients required admission to ICU. Thick smear was carried out as diagnostic initial method in 100% of the cases. Plasmodium falciparum stands out among the other affecting 71,8% of cases, followed by Plasmodium vivax (12,8%) and Plasmodium malaria (5.1%). Antigen detection of Plamodium in blood was performed in 21 cases (53,8%) and none was performed to determine genomic PCR. The combination of quinine and pyrimethamine with sulfadioxine was applied n 61,5% of the sample. Concomitant intestinal parasitism was found in 8 cases. Conclusiones. In our series, as in other series in our country, 92,3% of patients came from sub-Saharan Africa with prevalence of Equatorial Guinea and 89,7% comprised a recent trip to their country of origin. The thick smear was the most useful diagnostic method. An adequate prophylaxis (it had been performed just in 2 cases in our study) and a thorough screening of other associated parasitosis would be instrumental in fighting this disease (AU)

A systematic comparison of two pulse sequences for edema assessment in MR-mammography.

OBJECTIVE: Perifocal edema, defined as high T2w signal intensity around an enhancing lesion has been described as a specific feature of malignancy. In clinical MR-mammography (MRM), both fatsat and non-fatsat T2w sequences are available. However, there is no consensus on which technique should be used for edema assessment. Consequently, this investigation was performed to compare two commonly used pulse sequences for edema assessment in MRM. MATERIALS AND METHODS: 321 consecutive patients from a 22 month period were included in this investigation. Further selection criteria were histopathological verification of enhancing lesions and absence of presurgical chemotherapy or biopsy, resulting in 108 malignant and 107 benign lesions. All underwent MRM according to international guidelines including a non-fatsat T2w-TSE sequence (TR/TE: 8900/207 ms) and a short tau inversion recovery fatsat sequence (STIR, TR/TE: 8420/70 ms). All images were acquired in the same orientation (axial) and slice thickness. Two experienced radiologists in consensus rated presence of perifocal edema according to an ordinal scale: 0 = not present, 1 = little, 2 = intermediate, and 3 = distinct. Data analysis was performed using crosstabs and Visual Grading Characteristics (VGC) analysis. RESULTS: Overall sensitivity/specificity was calculated with 53.7%/94.4% (T2w-TSE) and 52.8%/95.3% (STIR). VGC revealed an area under the VGC curve of 0.502 (standard error 0.026), P = 0.814. CONCLUSION: Perifocal edema is a specific feature of malignancy with moderate sensitivity. VGC analysis did not reveal significant differences between both pulse sequences analysed. Consequently, both T2w-TSE and STIR images are suitable for assessment of perifocal edema.

Efficacy control of therapy using circulating epithelial tumor cells (CETC) as "liquid biopsy": trastuzumab in HER2/neu-positive breast carcinoma.

PURPOSE: The majority of targeted personalized cancer therapies are effective only in part of the patients, and most of these drugs are excessively expensive. Therefore, methods are urgently required, which reveal already early during treatment, whether the therapy is effective. In the present report, monitoring of circulating epithelial tumor cells (CETC) was used as a timely control of trastuzumab therapy in patients with HER2/neu-positive breast cancer. METHODS: Seventy-nine sequential HER2/neu-positive breast cancer patients, 35 without trastuzumab, and 36 treated with 1 year of trastuzumab treatment were included. CETC from unseparated white blood cells stained with FITC-anti-EpCAM were analyzed repeatedly during chemotherapy and between 2 and 10 times during 1 year of maintenance treatment or observation. RESULTS: Patients treated with trastuzumab had a better relapse-free survival than patients without trastuzumab treatment during the first 2-4 years of follow-up. Decrease in numbers or no change versus highly variable numbers or increase (fivefold or more) allowed to discriminate highly significantly and clearly (P < 0.0001, hazard ratio 5.5) between patients with a low or high risk of relapse. An increase in CETC was accompanied by an increasing portion of cells containing a very high number of HER2/neu gene amplificates. CONCLUSIONS: Analysis of the behavior of CETC can, in the future, contribute to evaluate the efficacy of targeted therapy early during the course of the disease, sparing patients unnecessary treatment but also to reduce the costs for the health system and to downsize the extent and length of clinical studies.

Inter-model consistency and complementarity: learning from ex-vivo imaging and electrophysiological data towards an integrated understanding of cardiac physiology.

Computational models of the heart at various scales and levels of complexity have been independently developed, parameterised and validated using a wide range of experimental data for over four decades. However, despite remarkable progress, the lack of coordinated efforts to compare and combine these computational models has limited their impact on the numerous open questions in cardiac physiology. To address this issue, a comprehensive dataset has previously been made available to the community that contains the cardiac anatomy and fibre orientations from magnetic resonance imaging as well as epicardial transmembrane potentials from optical mapping measured on a perfused ex-vivo porcine heart. This data was used to develop and customize four models of cardiac electrophysiology with different level of details, including a personalized fast conduction Purkinje system, a maximum a posteriori estimation of the 3D distribution of transmembrane potential, the personalization of a simplified reaction-diffusion model, and a detailed biophysical model with generic conduction parameters. This study proposes the integration of these four models into a single modelling and simulation pipeline, after analyzing their common features and discrepancies. The proposed integrated pipeline demonstrates an increase prediction power of depolarization isochrones in different pacing conditions.

[Investigation of epidemiology of neurotrauma in the Republic of Guinea].

The paper focuses on analysis of incidence of neurotrauma in economically underdeveloped country such as Republic of Guinea. It is found that leading etiology of central nervous system injuries are road accidents and indoor traumatism. Investigation of system of medical care revealed its poor condition and severe defects which prevent practical application of evidence-based recommendations for management of traumatic brain injury in underdeveloped countries including Republic of Guinea. Development of multiplanar strategy of control of neurotrauma is required which can be achieved only in case of massive governmental and international aid.

Clinical MR mammography: impact of hormonal status on background enhancement and diagnostic accuracy.

PURPOSE: Hormonal stimulation can induce background enhancement (BE) in MR mammography (MRM). This fact has been assumed to decrease the accuracy of MRM. Consequently, this report investigates: 1. The prevalence of BE in postmenopausal vs. premenopausal women in correlation to hormonal cycle phase (CP). 2. The impact of hormonal status (HS) and BE on diagnostic accuracy. MATERIALS AND METHODS: Consecutive patients over 22 months with complete HS information (week of CP or postmenopausal) were included in this prospective investigation. Exclusion criteria were any hormonal therapy, hysterectomy as well as cancer proven by biopsy. The standard of reference was histopathology. All MRM scans were acquired using the same protocol (1.5 T, dynamic T 1w GRE after 0.1 mmol/kg bw Gd-DTPA i. v.). Two radiologists rated all examinations in consensus according to BI-RADS. BE was defined as: 0 = missing, 1 = moderate, 2 = distinct. RESULTS: 224 patients (150 postmenopausal, 74 premenopausal, 45 in the second week of CP) were included in this study (83 benign and 141 malignant findings). BE was more frequent in premenopausal women (p = 0.006), but did not differ between CP (p = 0.460). Neither HS nor BE had a significant impact on the diagnostic parameters of MRM (p ≥ 0.375). However, regarding BE, the relative number of false positive (FP) findings was highest (5 / 10; 50 %) in the distinct BE group. Regarding HS, 17 % more FP findings were observed in premenopausal women examined outside the second week of CP. CONCLUSION: In premenopausal women, HS leads to increased BE of breast tissue, independent of CP. Distinct BE and less pronounced, non-optimal CP may lead to an increased number of false positive findings.

A geographical approach to identify sleeping sickness risk factors in a mangrove ecosystem.

OBJECTIVES: To provide a better understanding of sleeping sickness transmission and spread in mangrove areas to optimize its control. METHODS: In the Forecariah mangrove area, Guinea, 19 sleeping sickness cases and 19 matched controls were followed up in their living areas (at home, in fields and at water points). All occupational sites and pathways were mapped and then placed in their environmental context. RESULTS: The sleeping sickness cases displayed a significantly broader and more diverse spatial occupation than the controls. They covered double the daily walking distances of controls and had on average two more occupational sites, most of which were located in mangrove forests. Activities with a higher transmission risk (rice culture, attendance of pirogue jetties) were identified as well as high-risk areas and pathways. CONCLUSIONS: An entomological control strategy targeting transmission risk areas is proposed. Its implementation in a control programme would reduce by 86% the efforts needed for a classical vector control programme throughout the area. Medical surveys set up at specific locations, such as pirogue jetties and high-risk paths, should also enable better targeting of the population at highest risk.

Prognostic role of platinum sensitivity in patients with brain metastases from ovarian cancer: results of a German multicenter study.

BACKGROUND: Ovarian cancer is the leading cause of death in women with gynecological malignancies. Brain metastases are considered an uncommon metastatic site. Only few data exist on prognostic factors for this patient collective. PATIENTS AND METHODS: A multicenter retrospective chart review was carried out including all patients with histologically confirmed ovarian cancer from six different German hospitals from 1981 to 2008. Overall, 4277 cases of patients with ovarian cancer were screened and patients with brain metastasis were identified and analyzed regarding various clinical variables and survival. RESULTS: A total of 74 women with brain metastases were identified, resulting in an incidence of 1.73%. In multivariate analysis, the following clinical parameters had a significant impact on overall survival: multiple lesions [hazard ratio (HR) 4.4, 95% confidence interval (CI) 2.0-9.7] and low grading (HR 3.1, 95% CI 1.7-5.8) were associated with a negative impact. Platinum sensitivity (HR 0.23, 95% CI 0.12-0.48) was significantly associated with a favorable outcome. Good performance status (60%-80% HR 0.48, 95% CI 0.23-0.99 and 90%-100% HR 0.21, 95% CI 0.08-0.53) also had a positive impact on overall survival. CONCLUSIONS: Platinum sensitivity is the most important prognostic factor in patients with ovarian cancer metastatic to the brain. This novel finding should be considered in the strategy of multimodal therapy for brain metastases in ovarian cancer.

Toward integrated management of cerebral aneurysms.

In the last few years, some of the visionary concepts behind the virtual physiological human began to be demonstrated on various clinical domains, showing great promise for improving healthcare management. In the current work, we provide an overview of image- and biomechanics-based techniques that, when put together, provide a patient-specific pipeline for the management of intracranial aneurysms. The derivation and subsequent integration of morphological, morphodynamic, haemodynamic and structural analyses allow us to extract patient-specific models and information from which diagnostic and prognostic descriptors can be obtained. Linking such new indices with relevant clinical events should bring new insights into the processes behind aneurysm genesis, growth and rupture. The development of techniques for modelling endovascular devices such as stents and coils allows the evaluation of alternative treatment scenarios before the intervention takes place and could also contribute to the understanding and improved design of more effective devices. A key element to facilitate the clinical take-up of all these developments is their comprehensive validation. Although a number of previously published results have shown the accuracy and robustness of individual components, further efforts should be directed to demonstrate the diagnostic and prognostic efficacy of these advanced tools through large-scale clinical trials.

Value of ductal obstruction sign in the differentiation of benign and malignant breast lesions at MR imaging.

PURPOSE: MR-Mammography (MRM) is regarded as the most sensitive method for detection of breast cancer without a broad consensus on specificity. There is room for improvement of the existing ACR BIRADS lexicon by adding new and specific descriptors. Dilated ducts have been described in association with papillomas. However, the differential diagnostic value of this finding has not been investigated yet. MATERIALS AND METHODS: 316 consecutive patients, undergoing histopathologic workup after MR-Mammography were included in this prospective, ethical review board approved study. Two blinded radiologists rated the images in consensus. Ductal obstruction was defined as dilated liquid filled ducts proximal an enhancing lesion. Sensitivity, specificity as well as positive and negative likelihood ratio (LR+, LR-) were calculated. RESULTS: Dilated ducts were found in 60 cases (19%), 20 of these showed an association with enhancing lesions and were categorized as ductal obstruction (6.3%). Malignancy was found in two cases (one invasive ductal carcinoma and one DCIS) and benign tissue in 18 cases (15 papillomas). The difference of ductal obstruction between these groups was found to be highly significant in two-sided Fisher's exact test (p<0.001). Because of the clear association with benign lesions, benign lesions showing ductal obstruction were characterized as true positive findings. Therefore, following diagnostic parameters were calculated: sensitivity 15.4%, specificity 99.0%, LR+ 15.3, LR- 0.9. DISCUSSION: If ductal obstruction is found to be positive, the associated lesion is most likely benign. Therefore, though a rare finding, this descriptor should be taken into account for improved lesion differentiation.

Sequential chemotherapy with carboplatin followed by weekly paclitaxel in advanced ovarian cancer: results of a multicenter phase II study of the northeastern German society of gynecological oncology.

BACKGROUND: For the adjuvant setting of advanced ovarian cancer (AOC) after primary radical surgery the combination of paclitaxel and platinum in a 3-week schedule has emerged as the current standard. In preclinical studies additional anti-angiogenic effects of low dose paclitaxel infusion were demonstrated. A sequential schedule of carboplatin and paclitaxel has the potential to improve the therapeutic index. METHODS: In this multicenter phase II trial four cycles of carboplatin at a dose of AUC 5 (d1/q21d) followed by 12 cycles of weekly paclitaxel at a dose of 80 mg/m(2) (d1/q7d) were applied after primary radical surgery. Eligible were all optimally or sub-optimally debulked patients with FIGO IA-IV ovarian cancer. All patients with hemoglobin levels <12 mg/dl received erythropoietin additionally. RESULTS: Between July 2003 and May 2005, 105 patients from 27 institutions were enrolled. The median age was 60 years (range: 23-80 years). A median number of 16 courses (range 1-16) were applied. The incidence of non-hematological toxicities was very low. Only 41% of patients experienced alopecia (grade 1-2). Neurotoxicity (grade 3-4) was not observed. Grade 3-4 hematological toxicity (43% of all patients) included thrombocytopenia (17%), anemia (3%), leucopenia (23%), and neutropenic fever (0%). Ninety-seven percent received erythropoietin. Thromboembolic events (4%) were not increased in patients who received erythropoietin. After a median time of 23 months (range: 1-42 months) 32 patients had died, and the median overall survival was not reached. The progression-free survival was 25.4 months (95% CI: 18.8-40+). CONCLUSION: These results suggest that this sequential regimen using weekly paclitaxel represents an efficacious and well-tolerated regimen. A randomized study comparing this new schedule with the conventional 3-week protocol is warranted.