A Phase Ib/II Study of Sabizabulin, a Novel Oral Cytoskeleton Disruptor, in Men with Metastatic Castration-resistant Prostate Cancer with Progression on an Androgen Receptor-targeting Agent.

PURPOSE: Sabizabulin, an oral cytoskeleton disruptor, was tested in a phase Ib/II clinical study in men with metastatic castration-resistant prostate cancer (mCRPC). PATIENTS AND METHODS: The phase Ib portion utilized a 3+3 design with escalating daily oral doses of 4.5-81 mg and increasing schedule in 39 patients with mCRPC treated with one or more androgen receptor-targeting agents. Prior taxane chemotherapy was allowed. The phase II portion tested a daily dose of 63 mg in 41 patients with no prior chemotherapy. Efficacy was assessed using PCWG3 and RECIST 1.1 criteria. RESULTS: The MTD was not defined in the phase Ib and the recommended phase II dose was set at 63 mg/day. The most common adverse events (>10% frequency) at the 63 mg oral daily dosing (combined phase Ib/II data) were predominantly grade 1-2 events. Grade ≥3 events included diarrhea (7.4%), fatigue (5.6%), and alanine aminotransferase/aspartate aminotransferase elevations (5.6% and 3.7%, respectively). Neurotoxicity and neutropenia were not observed. Preliminary efficacy data in patients treated with ≥1 continuous cycle of 63 mg or higher included objective response rate in 6 of 29 (20.7%) patients with measurable disease (1 complete, 5 partial) and 14 of 48 (29.2%) patients had PSA declines. The Kaplan-Meier median radiographic progression-free survival was estimated to be 11.4 months (n = 55). Durable responses lasting >2.75 years were observed. CONCLUSIONS: This clinical trial demonstrated that chronic oral daily dosing of sabizabulin has a favorable safety profile with preliminary antitumor activity. These data support the ongoing phase III VERACITY trial of sabizabulin in men with mCRPC.

Oral Sabizabulin for High-Risk, Hospitalized Adults with Covid-19: Interim Analysis.

BACKGROUND: Sabizabulin is an oral, novel microtubule disruptor that has dual antiviral and anti-inflammatory activities in preclinical models. METHODS: A randomized, multicenter placebo-controlled phase 3 clinical trial was conducted with hospitalized patients with moderate to severe Covid-19 who were at high risk for acute respiratory distress syndrome (ARDS) and death. Patients were randomly assigned (2:1) to 9 mg of oral sabizabulin or placebo daily (up to 21 days). The primary end point was all-cause mortality up to day 60. Key secondary end points were days in the intensive care unit (ICU), days on mechanical ventilation, and days in the hospital. RESULTS: A total of 204 patients were randomly assigned to treatment: 134 to sabizabulin and 70 to placebo. Baseline characteristics were similar. Sabizabulin superiority was demonstrated by a planned interim analysis for the first 150 randomized patients. Sabizabulin treatment resulted in a 24.9 percentage point absolute reduction and a 55.2% relative reduction in deaths compared with placebo (odds ratio, 3.23; 95% CI confidence interval, 1.45 to 7.22; P=0.0042). The mortality rate was 20.2% (19 of 94) for sabizabulin versus 45.1% (23 of 51) for placebo. For the key secondary end points, sabizabulin treatment resulted in a 43% relative reduction in ICU days (P=0.0013), a 49% relative reduction in days on mechanical ventilation (P=0.0013), and a 26% relative reduction in days in the hospital (P=0.0277) versus placebo. Adverse and serious adverse events were lower in the sabizabulin group compared with the placebo group. CONCLUSIONS: Sabizabulin treatment resulted in a 24.9% absolute reduction in deaths compared with placebo in hospitalized patients with moderate to severe Covid-19 at high risk for ARDS and death, with a lower incidence of adverse and serious adverse events compared with placebo. (Funded by Veru, Inc.; ClinicalTrials.gov number, NCT04842747.)

La Alhambra deManguinhos: islamofilia yfunción ornamental en elCastelo Mourisco de Río deJaneiro / The Manguinhos Alhambra: islamophilia and ornamental function in the “Castelo Mourisco” in Rio de Janeiro

El llamado Castelo Mourisco constituye un modelo exacto de la función elevada que corresponde a la arquitectura. Más interesante todavía cuando se trata de la sede de un instituto de ciencias biomédicas de prestigio mundial, cuyo cuidado diseño evidencia el compromiso humanista de Oswaldo Cruz, su impulsor. Solo gracias a la impecable alianza entre promotor y proyectista pueden lograrse realizaciones arquitectónicas como ésta, donde se traspasan los límites constructivos hasta simbolizar la fusión de ciencia, historia y arte. El análisis de los variados recursos estilísticos utilizados en el edificio justifica su elección y vigencia, pues desde hace un siglo no solo ocupa el corazón del campus de Manguinhos, sino que también actualiza el espíritu de la institución que alberga

Mejora coste efectiva en diagnóstico de cáncer endometrial con la incorporación del análisis molecular GynEC(R)-Dx / Cost-effective improvement in endometrial cancer diagnosis by the incorporation of molecular analysis

Objetivo: estimar el número de exploraciones evitables al comparar un algoritmo diagnóstico clásico de la metrorragia posmenopáusica (MPM) frente a un algoritmo que incorpore un test molecular como GynEC(R)-Dx. Material y métodos: estudio de cohortes, prospectivo y aleatorizado por centros realizado en mujeres que presentaron MPM. Las pacientes fueron aleatorizadas a seguir un algoritmo de estudio de MPM clásico vs GynEC(R)-Dx. Se registraron variables demográficas y se comparó el uso de recursos tales como biopsias, ecografías, histeroscopias y visitas entre ambos grupos. Adicionalmente se revalidó la sensibilidad (S), especificidad (E), valor predictivo positivo (VPP) y valor predictivo negativo (VPN) del test. Resultados: se incluyeron un total de 94 pacientes, 51 en grupo clásico y 43 en grupo GynEC(R)-Dx. En el grupo clásico se realizaron 95 exploraciones más respecto al grupo de GynEC(R)-Dx clasificadas en: 11 biopsias, 17 ecografías, 24 histeroscopias y 89 visitas. En el grupo GynEC(R)-Dx se realizaron 92 exploraciones innecesarias consideradas "fuera de protocolo". En la revalidación se observó una S 100%, E 92.5%, VPP 50%, VPN 100%. Conclusiones: la incorporación de un test molecular como GynEC(R)-DX para el estudio de la metrorragia posmenopáusica permite disminuir el número de exploraciones y visitas respecto a los algoritmos convencionales

Objective: The histopathology remains the gold standard to diagnose endometrial cancer (EC) from endometrial biopsy. Molecular tests have recently emerged as a useful tool to classify EC according to its prognosis. However, there is currently no published protocol that includes molecular diagnosis of postmenopausal women with abnormal uterine bleeding (AUB). We hypothesized that the incorporation of a molecular test in the management of postmenopausal women with AUB improves the cost-efectiveness of the diagnostic process. Material and methods: We present a prospective study performed in postmenopausal women who presented AUB between 2009-2014. Seven centers recruited the patients. Three of them follow the classical diagnosis algorithm (group 1) and four centers follow the one that incorporates a molecular test (Gynec(R)-Dx) performed on the remnants of aspirates (group 2). In group 2, when both the endometrial biopsy and the molecular test were negative, the consequent explorations were considered as "out of procotol". Clinical data, number of biopsies, ultrasounds, hysteroscopies and visits were compared between groups. In addition, the sensitivity (S), specificity (E), positive and negative predictive values (PPV and NPV) of the molecular test were calculated. Results: 94 patients were recruited. 51 vs 43 women were included in the classical and the molecular algorithm respectively. There were no differences in age, BMI, parity, use of tamoxifen or hormonal treatment. The detailed outcomes of explorations between classical vs molecular group are shown in Table 1. 324 vs 229 explorations were performed respectively (table 2). In the molecular group, 92 explorations were considered "out of protocol". The test validations showed a 100% S, 92.5% E, 50% PPV and 100% NPV. Conclusions: According to our results, the incorporation of a molecular test for the diagnosis of EC in postmenopausal women who complained with AUB reduces the number of explorations. Consequently, the molecular algorithm is more cost-effective than conventional algorithms

[Morbimortalidad de la pancreatoduodenectomía en pacientes con cáncer de páncreas y tumores periampulares en el Hospital de Oncología del Centro Médico Nacional Siglo XXI de 2008 a 2013]. / Morbimortality of pancreatoduenectomy in patients with cancer of pancreas and periampular tumors in the Oncology Hospital of Centro Médico Nacional Siglo XXI from 2008 to 2013.

INTRODUCTION: Pancreatic tumors and periampullary tumors have a similar clinical presentation; pancreatoduodenectomy represents the only possibility of cure or of increasing survival; with an average mortality of 5-10% and a morbidity of 20-40%. OBJECTIVE: To determine the morbidity and mortality secondary to the pancreatoduodenectomy intervention in patients with pancreatic cancer or periampullary tumors in the Oncology Hospital of Centro Médico Nacional Siglo XXI (Mexico City) from 2008 to 2013. METHOD: Historical, observational and descriptive cohort carried out in the department of sarcomas and tumors of the upper digestive tube of the Oncology Hospital of Centro Médico Nacional Siglo XXI, postoperative pancreatoduodenectomy from 2008 to 2013. RESULTS: We included 71 patients who underwent pancreatoduodenectomy, 47 (66.2%) were female and 24 (33.8%) were male. The average age was 60.3 years. The most common histology was cancer of the Vater's ampulla (66.2%). The resections were R0 in 95.8% of the cases. Mortality was 4.22% and morbidity was 69%. The most frequent complication was pancreatic fistula (23.9%). In the statistical analysis, perioperative transfusion was associated with surgical complications (p < 0.007). CONCLUSIONS: The morbidity of pancreatoduodenectomy is greater than that reported in the literature, however, it does not influence mortality that is similar to that reported in other centers. The number of lymph nodes resected; as well as the percentage of negative margins are those accepted worldwide; It is concluded that this is derived from the experience of the center where these procedures are performed. No factor with statistical significance was found, only the transfusion that increased the complications.

INTRODUCCIÓN: Los tumores de páncreas y los tumores periampulares tienen una presentación clínica similar. La pancreatoduodenectomía representa la única posibilidad de curación o de aumentar la sobrevida, con una mortalidad promedio del 5-10% y una morbilidad del 20-40%. OBJETIVO: Determinar la morbilidad y la mortalidad secundarias a la intervención de pancreatoduodenectomía en pacientes con cáncer de páncreas o tumores periampulares en el Hospital de Oncología del Centro Médico Nacional SXXI de 2008 a 2013. MÉTODO: Cohorte histórica, observacional y descriptiva, realizada en el departamento de sarcomas y tumores de tubo digestivo alto del Hospital de Oncología del Centro Médico Nacional Siglo XXI, operados de pancreatoduodenectomía entre 2008 y 2013. RESULTADOS: Se incluyeron 71 pacientes que se sometieron a pancreatoduodenectomía; 47 (66.2%) eran de sexo femenino y 24 (33.8%) de sexo masculino. La edad promedio fue de 60.3 años. La histología más común fue cáncer de ámpula de Vater (66.2%). Las resecciones fueron R0 en el 95.8% de los casos. La mortalidad fue del 4.22% y la morbilidad fue del 69%. La complicación más frecuente fue la fístula pancreática (23.9%). En el análisis estadístico, la transfusión perioperatoria se asoció a complicaciones quirúrgicas (p < 0.007). CONCLUSIONES: La morbilidad de la pancreatoduodenectomía es mayor que lo reportado en la literatura; sin embargo, no influye en la mortalidad, que es similar a lo reportado en otros centros. El número de ganglios resecados, así como el porcentaje de márgenes negativos, son los aceptados internacionalmente. Se concluye que esto se deriva de la experiencia del centro donde se realizan estos procedimientos. No se encontró ningún factor con relevancia estadística, excepto la transfusión, que incrementaba las complicaciones.

Economic Burden of Contraception Management in Spain.

BACKGROUND: A wide variety of contraceptive methods are available, some of them reimbursed by the Spanish National Health System (SNHS). However, the number of unintended pregnancies (UP) is still significant, leading to a high economic burden, mainly derived from non-adherence to and the incorrect use of contraceptive methods. OBJECTIVES: This study aims to estimate the economic burden associated with reversible contraception management in Spain, from the perspectives of both the SNHS and women, over a 5-year period. METHODS: A survey was performed to identify contraception management in Spain based on the experience of a panel of six expert gynecologists. An economic model was conducted to quantify the current burden of contraception according to healthcare resources use over 5 years. The costs included in the analysis were diagnostic tests, initial and follow-up consultations, methods acquisition costs, and UP derived from therapy failure. RESULTS: Reversible contraception costs in Spain amount to €12.5 billion over a 5-year period. Condoms and combined oral contraceptives (COC) account for 86.8% of the total cost and the other methods only 13.2%. There are differences in contraceptive use according to women's age. Short-acting reversible contraceptives (SARC) such as COC, condom and vaginal ring, are most commonly used by younger women. However, SARC are correlated with the highest failure rate, resulting in over €7.2 billion cost, explained by the high number of UP. Long-acting reversible contraceptives (LARC), such as the levonorgestrel-releasing intrauterine system (LNG-IUS20), implant and copper intrauterine devices (IUD), are selected by women over 35 years of age due to user-independent compliance. SARC methods result in a higher cost per woman over 5 years: vaginal ring €2427.8, patch €2402.6, condom €2060.1 and COC €1895.1; while LARC methods are the most economic option per women: LNG-IUS20 €630.4, copper IUD €658.2, LNG-IUS12 €703.8, intramuscular injectable €907.8 and implant €940.5. CONCLUSIONS: LARC methods result in lower costs compared with SARC options from the perspectives of the SNHS and women, explained by user-independent compliance, preventing a significant number of UP and its elevated economic burden. An increased LARC methods use could avoid UP events, leading to significant cost-savings for the SNHS.

[Prognostic factors for survival in patients with resectable advanced gastric adenocarcinoma]. / Factores pronóstico de sobrevida en adenocarcinoma gástrico avanzado resecable.

BACKGROUND: Patients under 45 years with gastric cancer are associated with a poor prognosis. Recent studies report that the 5-year survival is better in younger patients after curative resection. OBJECTIVE: To determine if prognostic factors such as age under 45 years old, anaemia, weight loss, tumour differentiation, histological sub-type, depth of invasion, and lymph node involvement, reduce the survival of patients with resectable advanced gastric adenocarcinoma undergoing gastrectomy with limited and extended lymphadenectomy. MATERIALS AND METHODS: This study included a cohort of consecutive cases treated in the Sarcomas Department of the Oncology Hospital of the Centro Médico Nacional Siglo XXI, of the Instituto Mexicano del Seguro Social, during the period between January 2000 and December 2006. RESULTS: Of the total of 588 patients evaluated, 112 (19%) were under 45 years, 43% classified as Borrmann IV, and 36% as Borrmann III. Metastatic disease was present in 39.3%, localised diffuse in 12.5%; lower resectability 52.7 vs. 61.3% in older than 45 years. At the end of the study 29.5% of patients under 45 years were alive; no recurrence in 26.8%, with an overall survival of 58.6±4.3 months, compared with 18.3% of patients alive over 45 years, 17.9% disease-free, and with overall survival 35.2±4.3 months resectable disease. CONCLUSIONS: Patients under 45 years have a better survival after a two-year disease-free period.

Toremifene to reduce fracture risk in men receiving androgen deprivation therapy for prostate cancer.

PURPOSE: Androgen deprivation therapy is associated with fracture risk in men with prostate cancer. We assessed the effects of toremifene, a selective estrogen receptor modulator, on fracture incidence in men receiving androgen deprivation therapy during a 2-year period. MATERIALS AND METHODS: In this double-blind, placebo controlled phase III study 646 men receiving androgen deprivation therapy for prostate cancer were assigned to toremifene (80 mg by mouth daily) and 638 were assigned to placebo. Subjects were followed for 2 years. The primary study end point was new vertebral fractures. Secondary end points included fragility fractures, bone mineral density and lipid changes. RESULTS: The 2-year incidence of new vertebral fractures was 4.9% in the placebo group vs 2.5% in the toremifene group, a significant relative risk reduction of 50% (95% CI -1.5 to 75.0, p = 0.05). Toremifene significantly increased bone mineral density at the lumbar spine, hip and femoral neck vs placebo (p <0.0001 for all comparisons). There was a concomitant decrease in markers of bone turnover (p <0.05 for all comparisons). Toremifene also significantly improved lipid profiles. Venous thromboembolic events occurred more frequently with toremifene than placebo with 7 subjects (1.1%) in the placebo group experiencing a venous thromboembolic event vs 17 (2.6%) in the toremifene group. Other adverse events were similar between the groups. CONCLUSIONS: Toremifene significantly decreased the incidence of new vertebral fractures in men receiving androgen deprivation therapy for prostate cancer. It also significantly improved bone mineral density, bone turnover markers and serum lipid profiles.

La biotecnología como herramienta para la propagación, conservación y el mejoramiento genético del guayabo / Biotechnology as a tool for propagation, con-servation and genetic breeding in guava

Las técnicas biotecnológicas contribuyen positiva y significativamente en los programas de propagación, conservación y mejoramiento de las especies vegetales. Dentro de éstas, el cultivo de tejidos, el desarrollo de mapas de ligamientos genéticos y de QTLs y la detección de genes de interés han demostrado ser de gran utilidad para los mencionados propósitos. En este sentido, se estandarizó una técnica para la multiplicación in vitro de la forma silvestre de guayabo en tres fases de cultivo: establecimiento, multiplicación de propágulos y enraizamiento. La misma constituye una vía de utilidad para la propagación, la conservación de germoplasma y el mejoramiento genético en la especie. Además, se estandarizó un método de conservación a corto-mediano plazo. Por otra parte, se construyó un mapa de ligamiento genético para la especie empleando marcadores AFLP y SSR. Los 11 grupos del mapa de ligamiento genético y los 50 QTLs relacionados con caracteres vegetativos y de calidad interna y externa del fruto, constituyen el punto de partida para el clonaje de genes de interés agrícola y la implementación futura de la selección asistida por marcadores en el guayabo. De igual forma, las 176 secuencias candidatas a genes de resistencia (RGL) y del desarrollo de la planta (MADS-box y HOMEO-box) detectadas pueden ser de gran utilidad en la saturación del mapa de ligamiento referido, el estudio de la variabilidad presente en el cultivo, así como en la solución de problemas relacionados con el rendimiento, la producción y la resistencia a estrés biótico y abiótico

Biotechnologies contribute positively and signifi¬cantly in the propagation, conservation and breeding programs of many plant species. From them, tissue culture, linkage maps and QTLs detection for interesting genes have been proved to be of great utility for these purposes. In this sense, a technique for in vitro multiplication of wild guava was standardized in three culture phases: establishment, multiplication and rooting. This technique constituted a useful way for propagation, germplasm conservation and genetic breeding in the specie. A method for short-medium term conservation was also standardized. On the other hand, a genetic linkage map was constructed for the specie using AFLP and SSR markers. The 11 groups of the genetic linkage map and the 50 QTLs related with vegetative and internal/external fruit characters constitute the starting point for genes cloning of agricultural interest and the future imple¬mentation of markers assisted selection in guava. Also, the 176 candidate sequences for resistance-gene-like (RGL) and plant development (MADS-box and HOMEO-box) genes detected can be of great utility in linkage map saturation, variability studies in this crop, as well as in the solution of problems rela¬ted with yielding and resistance to biotic and abiotic stresses.

[Surgical prognostic factors of gastroenteropancreatic neuroendocrine tumors (GEP NET)]. / Tumor neuroendocrino gastroenteropancreático. Factores pronósticos quirúrgicos.

OBJECTIVE: to determine surgical prognostic variables from a retrospective cohort of histopathologically confirmed gastroenteropancreatic neuroendocrine tumors (GEP-NET) in Mexican subjects. METHODS: consecutive patients treated for GEP-NET from 1999 through 2007 at Oncological Hospital were included. Demographic, clinical variables, disease-free survival were retrieved. RESULTS: forty-eight patients were included, 29 (60.4 %) female with a mean age of 54 years. Overall survival time was 43.7 months and disease-free survival was 33 months. Negative statistically significant overall survival time predictors were 2 and 3 histological types (HR 5.5. CI 2.0-21, p = 0.0001), tumor size > 2 cm (HR 8.8, CI 1 .29-75, p = 0.002), the presence of metastasis (HR 2.4, CI 1.2-9.6, p = 0.0001) and tumor resectability (HR 9.8, CI 2.9-40.2, p = 0.0001). For the disease-free period, only the histological type (2 or 3) was a negative outcome variable. CONCLUSIONS: histological type, tumor size, the presence of metastasis, and tumor non resectability were significant survival predictors.

Resectability of primary gastroenteropancreatic neuroendocrine tumor as a prognostic factor for survival.

BACKGROUND: Gastroenteropancreatic neuroendocrine tumors (GEP-NETs) originate from gastrointestinal cells and pancreas; most are benign or well-differentiated. GEP-NET treatment objectives are tumor resection and reduction of tumor growth and dissemination, as well as symptom amelioration. We undertook this study to identify prognostic factors among patients with GEP-NETs. METHODS: A total of 48 patients with histopathological diagnosis of GEP-NET were examined. Dependent variables were disease-free survival (DFS) and overall survival rates. Independent variables were age, gender, primary tumor size, resectability, metastatic disease, and histological degree. RESULTS: In 48 patients (60.4% female, 39.6% male, median age 54 years), overall survival rate was 43.7%, and DFS was 33 months. The most common location was gastric. Factors related with the poorest prognosis were histological degree types 2 and 3, tumors >2 cm, metastatic disease, and primary tumor irresectability. For DFS, the only adverse factor was histological degree. CONCLUSIONS: Patients with recurrence of GEP-NET had a poorer prognosis. Complete resection of the lesion with negative margins is the most determining prognostic factor for overrall survival in patients with GEP-NET.

The selective androgen receptor modulator GTx-024 (enobosarm) improves lean body mass and physical function in healthy elderly men and postmenopausal women: results of a double-blind, placebo-controlled phase II trial.

BACKGROUND: Cachexia, also known as muscle wasting, is a complex metabolic condition characterized by loss of skeletal muscle and a decline in physical function. Muscle wasting is associated with cancer, sarcopenia, chronic obstructive pulmonary disease, end-stage renal disease, and other chronic conditions and results in significant morbidity and mortality. GTx-024 (enobosarm) is a nonsteroidal selective androgen receptor modulator (SARM) that has tissue-selective anabolic effects in muscle and bone, while sparing other androgenic tissue related to hair growth in women and prostate effects in men. GTx-024 has demonstrated promising pharmacologic effects in preclinical studies and favorable safety and pharmacokinetic profiles in phase I investigation. METHODS: A 12-week double-blind, placebo-controlled phase II clinical trial was conducted to evaluate GTx-024 in 120 healthy elderly men (>60 years of age) and postmenopausal women. The primary endpoint was total lean body mass assessed by dual energy X-ray absorptiometry, and secondary endpoints included physical function, body weight, insulin resistance, and safety. RESULTS: GTx-024 treatment resulted in dose-dependent increases in total lean body mass that were statistically significant (P < 0.001, 3 mg vs. placebo) and clinically meaningful. There were also significant improvements in physical function (P = 0.013, 3 mg vs. placebo) and insulin resistance (P = 0.013, 3 mg vs. placebo). The incidence of adverse events was similar between treatment groups. CONCLUSION: GTx-024 showed a dose-dependent improvement in total lean body mass and physical function and was well tolerated. GTx-024 may be useful in the prevention and/or treatment of muscle wasting associated with cancer and other chronic diseases.

Toremifene to reduce fracture risk in men receiving androgen deprivation therapy for prostate cancer.

PURPOSE: Androgen deprivation therapy is associated with fracture risk in men with prostate cancer. We assessed the effects of toremifene, a selective estrogen receptor modulator, on fracture incidence in men receiving androgen deprivation therapy during a 2-year period. MATERIALS AND METHODS: In this double-blind, placebo controlled phase III study 646 men receiving androgen deprivation therapy for prostate cancer were assigned to toremifene (80 mg by mouth daily) and 638 were assigned to placebo. Subjects were followed for 2 years. The primary study end point was new vertebral fractures. Secondary end points included fragility fractures, bone mineral density and lipid changes. RESULTS: The 2-year incidence of new vertebral fractures was 4.9% in the placebo group vs 2.5% in the toremifene group, a significant relative risk reduction of 50% (95% CI -1.5 to 75.0, p = 0.05). Toremifene significantly increased bone mineral density at the lumbar spine, hip and femoral neck vs placebo (p <0.0001 for all comparisons). There was a concomitant decrease in markers of bone turnover (p <0.05 for all comparisons). Toremifene also significantly improved lipid profiles. Venous thromboembolic events occurred more frequently with toremifene than placebo with 7 subjects (1.1%) in the placebo group experiencing a venous thromboembolic event vs 17 (2.6%) in the toremifene group. Other adverse events were similar between the groups. CONCLUSIONS: Toremifene significantly decreased the incidence of new vertebral fractures in men receiving androgen deprivation therapy for prostate cancer. It also significantly improved bone mineral density, bone turnover markers and serum lipid profiles.

Probabilistic PCA self-organizing maps.

In this paper, we present a probabilistic neural model, which extends Kohonen's self-organizing map (SOM) by performing a probabilistic principal component analysis (PPCA) at each neuron. Several SOMs have been proposed in the literature to capture the local principal subspaces, but our approach offers a probabilistic model while it has a low complexity on the dimensionality of the input space. This allows to process very high-dimensional data to obtain reliable estimations of the probability densities which are based on the PPCA framework. Experimental results are presented, which show the map formation capabilities of the proposal with high-dimensional data, and its potential in image and video compression applications.

Riesgo cardiovascular absoluto en hipertensos y su evolución con el tratamiento antihipertensivo / Absolute cardiovascular risk in hypertensive patients and evolution with antihypertensive treatment

El control de los factores de riesgo es la clave para la prevención primaria de las enfermedades cardiovasculares, por ello el concepto de riesgo cardiovascular absoluto debería ser la guía para iniciar el tratamiento antihipertensivo. El objetivo de este estudio fue calcular el riesgo cardiovascular absoluto para ictus y cardiopatía isquémica basal y tras un año de intervención médica en dos poblaciones de hipertensos: en asistencia primaria (CS) y en la Unidad de Hipertensión de referencia (UH). Material y métodos. Se realizó un estudio retrospectivo en el que se realizaron dos cortes transversales con un año de intervalo en los mismos pacientes. Utilizamos las tablas de predicción de riesgo del Framingham Heart Study, expresándolo como probabilidad porcentual de padecer incidente en 10 años. Se valoraron un total de 216 pacientes, 105 de la UH y 111 del CS. Resultados. Los pacientes de la UH presentan mayor riesgo absoluto basal tanto para ictus como para cardiopatía isquémica que los de CS. Con la práctica clínica habitual en el paciente hipertenso el riesgo de ictus se redujo significativamente en la UH (15,1 ñ 12,8 frente a 11,7 ñ 4,3, p < 0,05), pero no en el CS (11,7 ñ 10,5 frente a 9,6 ñ 7,9). La reducción del riesgo absoluto de cardiopatía isquémica fue significativa tanto en la UH como en el CS (19,4 ñ 12 frente a 16,5 ñ 12, p < 0,01 en la UH, y 18 ñ 10 frente a 14,8 ñ 9,5, p < 0,05 en CS). Conclusión. El tratamiento de la hipertensión arterial reduce los niveles de presión arterial y también el riesgo cardiovascular tanto en pacientes con riesgo menos elevado como son los del CS como en pacientes de mayor riesgo cardiovascular como son los remitidos a la UH. La utilización de un método de medida del riesgo es importante para conocer tanto el riesgo inicial del paciente y valorar la eficacia de la actuación médica (AU)

Reintervención para completar el tratamiento quirúrgico en cáncer de tiroides. Indicaciones y hallazgos histopatológicos / Reintervention to complete thyroid cancer surgical treatment. Indications and histopathological findings

En México, de 158 pacientes operados por cáncer de tiroides 39 por ciento requiere ser reintervenido para completar su tratamiento quirúrgico. Se revisaron las indicaciones y los hallazgos histopatológicos de 60 pacientes reoperados por: a) sospecha clínica de persistencia o recurrencia tumoral, b) pacientes con alto riesgo sometidos a lobectomía, c) histología diferente, d) carencia de información y e) metástasis distentes. La cirugía inicial correspondió en 53 casos (88 por ciento) a nodulectomía o lobectomía, en siete (11 por ciento) a tiroidectomía subtotal. En la reintervención se completó la tiroidectomía total en 50 casos y en 10 tiroidectomía "casi" total. Se les hizo además disección de cuello a 27 casos (45 por ciento). El estudio histopatológico mostró cáncer tiroideo en 32 casos (53 por ciento) y metástasis a ganglios en 28 (47 por ciento). Hubo seis casos (9 por ciento) de parálisis del nervio recurrente después de la primera intervención y dos (1.75 por ciento) en las reoperaciones. En cuatro pacientes reoperados (6.6 por ciento) se presentó hipoparatiroidismo permanente. Es indispensable completar la tiroidectomía y la disección de cuello en una alta proporción de pacientes con cáncer de tiroides operados inicialmente en los hospitales generales, debido al criterio inadecuado en la selección de la extensión de la tiroidectomía y en el tratamiento de las metástasis a ganglios cervicales. Los hallazgos histopatológicos justifican reintervenir para completar el tratamiento quirúrgico

Disfunción pulmonar en pacientes diabéticos no insulino dependientes / Pulmonar dysfunction in patients with diabetes mellitus non insulin dependent

Por tratarse de Diabetes Mellius (DM) de una enfermedad sistémica, los pulmones pueden afectarse. Es por ello que se trata de demostrar la existencia de alterciones funcionales pulmonares como complicación crónica en la Diabetes Mellitus No Insulino Dependiente (DMNID) y su asociación con la evolución de la enfermedad y otras comlicaciones. Se incluyeron 12 pacienes portadores de DMNID y 9 controles sanos, sin historia de enfermedad pulmonar, tabaquismo o descompensación metabólica aguda, admitidos en la consulta externa y emergencia del Hospital General del Oeste; a todos se realizó historia clínica, exámenes de laboratorio, RX de tórax, electrocardiograma, test de RINES VALCARDI, gasometría y pruebas de función pulmonar (espirometría, pletismografía, difusión de CO y oclusión bucal). La inferencia estadística fue realizada mediante dócimas del Chi Cuadrado y t de Student; obteniéndose inexistencia de diferencia significativa entre los dos grupos en ninguna de las variables, así como tampoco su asociación con la evolución de la enfermedad y/o comlicaciones crónicas