Trastuzumab deruxtecan in patients with previously treated HER2-low advanced breast cancer and active brain metastases: the DEBBRAH trial.

BACKGROUND: Trastuzumab deruxtecan (T-DXd) is approved for human epidermal growth factor receptor 2 (HER2)-positive and HER2-low advanced breast cancer (ABC). T-DXd has shown encouraging intracranial activity in HER2-positive ABC patients with stable or active brain metastases (BMs); however, its efficacy in patients with HER2-low ABC with BMs is not well established yet. METHODS: DEBBRAH is a single-arm, five-cohort, phase II study evaluating T-DXd in patients with central nervous system involvement from HER2-positive and HER2-low ABC. Here, we report results from patients with heavily pretreated HER2-low ABC and active BMs, enrolled in cohorts 2 (n = 6, asymptomatic untreated BMs) and 4 (n = 6, progressing BMs after local therapy). Patients received 5.4 mg/kg T-DXd intravenously once every 21 days. The primary endpoint was intracranial objective response rate per Response Assessment in Neuro-Oncology Brain Metastases (RANO-BM) for both cohorts. RESULTS: Intracranial objective response rate per RANO-BM was 50.0% [3/6 patients; 95% confidence interval (CI) 11.8% to 88.2%] and 33.3% [2/6 patients; 95% CI 4.3% to 77.7%; P = 0.033 (one-sided)] in cohorts 2 and 4, respectively. All responders had partial responses. Median time to intracranial response was 2.3 months (range, 1.5-4.0 months) and median duration of intracranial response was 7.2 months (range, 2.8-16.8 months). Median progression-free survival per RECIST v.1.1. was 5.4 months (95% CI 4.1-10.0 months). Treatment-emergent adverse events occurred in all patients included (16.7% grade 3). Three patients (25.0%) had grade 1 interstitial lung disease/pneumonitis. CONCLUSIONS: T-DXd demonstrated promising intracranial activity in pretreated HER2-low ABC patients with active BMs. Further studies are needed to validate these results in larger cohorts. This trial is registered with ClinicalTrials.gov, NCT04420598.

Haplotype characterization of Ceraeochrysa cubana (Hagen) and Ceraeochrysa valida (Banks) (Neuroptera: Chrysopidae) from the state of Colima, Mexico.

The larvae of Ceraeochrysa cubana and Ceraeochrysa valida, green lacewing species widely spread in Mexico, have been described as natural enemies of Diaphorina citri (Hemiptera: Liviidae), vector of the bacteria Candidatus Liberibacter spp. causing Huanglongbing disease. To develop an effective biological control program, the establishment of the genetic structure of the biocontrol agent species is mandatory. Consequently, the goal of this work was to obtain reliable DNA barcoding regions of the two species, and then by sequence analysis of the mitochondrial gene cytochrome c oxidase subunit I, evaluate the genetic structure of Mexican lime populations of C. cubana and C. valida from the state of Colima. This research produced the first barcode region of C. cubana and C. valida with morphological and molecular confirmation. The genetic parameters revealed the presence of 15 and 10 haplotypes, and haplotype diversity values of 0.889 and 0.838 for C. cubana and C. valida, respectively. The populations showed high diversity and gene flow, and AMOVA analysis demonstrated no genetic structure in the two populations. Consequently, these single populations of C. cubana and C. valida could be used as unique genetic source for mass production and release in the Mexican lime-producing state of Colima to control D. citri.

Peptide functionalized magneto-plasmonic nanoparticles obtained by microfluidics for inhibition of ß-amyloid aggregation.

In the present work, we report on the synthesis of peptide functionalized magneto-plasmonic nanoparticles in a simple microfluidic platform. Superparamagnetic nanoparticles and gold nanorods were selected for this study. Magnetic nanoparticles were functionalized with peptide D1, which can bind selectively to toxic aggregates of the ß-amyloid peptide associated with Alzheimer's disease. Gold nanorods were functionalized with chitosan replacing the surfactant cetyltrimethylammonium bromide to reduce the cytotoxic effect. The selected microfluidic strategy yields structures with plasmonic and magnetic properties in a nanostructure. Cytotoxic assays with SH-SY5Y cells demonstrate that nanoparticles obtained by microfluidics do not affect cell viability at the studied concentrations. Additionally, these magneto-plasmonic nanoparticles inhibit fibril formation demonstrating that the magneto-plasmonic nanoparticles obtained by microfluidics could be applied for a potential treatment and diagnosis of Alzheimer's disease.

Role of the glucose tolerance test as a predictor of preeclampsia.

OBJECTIVE: To determine whether oral glucose tolerance tests (OGTT) play a role as predictors of preeclampsia (PET) in pregnant women. METHODS: A retrospective case-control study was conducted in 2,002 singleton pregnancies that had a uterine artery (UtA) Doppler at 22-25 weeks and an OGTT. The UtA Doppler and OGTT were adjusted based on maternal characteristics, and the results were expressed as multiples of the expected normal median and compared between groups. Logistic regression analysis was used to determine whether maternal characteristics, OGTT, and UtA Doppler significantly contribute to the prediction of early- (<34 weeks), intermediate- (34-37 weeks), or late-onset (>37 weeks) PET. The performance of the screening was determined by ROC curves. RESULTS: Women who developed PET were characterized by an older maternal age, an increased body mass index, and an altered UtA Doppler. The group with intermediate-onset PET was the only one associated with higher 2-hour OGTT levels compared to controls. Combined models were developed via logistic regression analysis using maternal characteristics, UtA Doppler, and OGTT to predict PET. These combined models were able to detect around 74, 42, and 21% of women who later developed early-, intermediate-, or late-onset PET, respectively, with only a 5% false-positive rate. CONCLUSIONS: This study shows that the combination of maternal characteristics, second-trimester UtA Doppler, and OGTT is a predictor of the development of PET in healthy pregnant women.

Is there a role for cervical assessment and uterine artery Doppler in the first trimester of pregnancy as a screening test for spontaneous preterm delivery?

OBJECTIVE: To evaluate the role of cervical length (CL) and uterine artery pulsatility index (UtA-PI) at 11+0 to 13+6 weeks as predictors of spontaneous preterm delivery (sPTD) in a Chilean population. METHODS: This was a prospective study of asymptomatic women with singleton pregnancies attending for a nuchal translucency scan at 11+0 to 13+6 weeks' gestation and who underwent a transvaginal scan for evaluation of CL and UtA-PI. Exclusion criteria were fetal and pregnancy complications (other than sPTD) and iatrogenic delivery at<34 weeks. Measurements of CL and UtA-PI were adjusted for fetal crown-rump length and maternal characteristics and expressed as multiples of the median (MoM) of the unaffected group. Prediction of sPTD using maternal and pregnancy characteristics was studied using logistic regression analysis. RESULTS: A total of 3480 women were recruited into the study and, after application of exclusion criteria, 3310 were included in the analysis. The rate of sPTD at<34 weeks was 0.9% (n=31). A previous PTD had occurred in 7.4% of parous women. Patients with sPTD in the index pregnancy were characterized by a significantly higher prevalence of previous PTD (12.9% vs 3.7%, P<0.05). No significant difference was found in either CL or UtA-PI between pregnancies with and without subsequent sPTD. Logistic regression analysis showed that smoking and previous PTD were significantly associated with sPTD at<34 weeks. The combination of these characteristics provided a detection rate of 26% with a false-positive rate of 8%. CONCLUSIONS: Neither UtA-PI nor CL during the first trimester was shown to be a useful predictor of early sPTD. However, a combined model that includes smoking and previous PTD predicts approximately one-quarter of those women destined to deliver at<34 weeks, with a false-positive rate of 8%.

[Monitoring indicators of the program "Chile Grows with You" 2008-2011]. / Monitoreo de los indicadores del Programa "Chile Crece Contigo" 2008-2011.

OBJECTIVE: To monitor coverage and outcomes associated with the activities of the integrated protection system for early childhood Chile Grows with You (CHCC), which includes the comprehensive psychosocial development of children between 18 months and 3 years old, in each of the 29 Health Services of the country, as well as the changes observed after 4 years. MATERIAL AND METHOD: Database analysis of all local public networks in the country between 2008 and 2011 was performed. The application of the test regarding psychomotor development, prevalence of development delay and risk, participation of mothers in educational workshops, home visits and recovery rate of deficient children by age were studied. Median and observed changes of each indicator were analyzed developing a ranking based on the results observed. RESULTS: Approximately 75% of children were evaluated, with a prevalence of delay or risk of about 5% and a rate of recovery close to 50%. The participation of mothers in educational workshops increased from 7.6 to 11.0% (p<0.001) and home visits to developmentally delayed children increased 6 times between 2009 and 2011 (p<0.001). Most changes were positive, although the prevalence of developmentally delayed children under 2 years slightly increased (0.6%), and the recovery of 3 year olds decreased (-14.4%). A great variability was observed among the Health Services. CONCLUSIONS: There are some positive results in relation to psychomotor development, with significant regional differences. A lower than expected deficit rate regarding psychomotor development was observed, which implies the need to further analyze the instrument used or the conditions of application.

[Satisfaction rating in a group of women from Granada on birthing care, support and breastfeeding length]. / Valoración del nivel de satisfacción en un grupo de mujeres de Granada sobre atención al parto, acompañamiento y duración de la lactancia.

INTRODUCTION: The satisfaction's analysis is being used as an instrument to create different sanitary reforms to improve the quality and numerous studies aim to the increase the mother's satisfaction directly related to the maternity care. OBJECTIVES: [corrected] Identify the woman satisfaction's degree about birth attention, accompaniment during nativity and the breastfeeding's term. MATERIAL AND METHOD: [corrected] Descriptive transversal study in the university hospital San Cecilio in Granada (España), during the time of August 2011 to 2012, it performed with a second prospective tracing phase to a N = 60 mothers. It used a protocol (Annex 1) after 24 hours in hospital and at 14 days by telephone. After 3 months, it performed a tracing pertaining to the baby food. RESULTS: The global satisfaction's level about birth is high in study population. It has been shown that breastfeeding (P = 0,514) and vaginal birth without epidural (P = 0,320) creates higher satisfaction for mother. On the other hand, birth satisfaction related with duration of breastfeeding. CONCLUSION: Satisfactory mothers' opinion related with birth care and accompaniment during nativity increases in women whose birth happened in a uncomplicated way without epidural and they started early breastfeeding.

Introducción: El análisis de la satisfacción se está utilizando como instrumento para crear diferentes reformas sanitarias para la mejora de la calidad y numerosos estudios apuntan al incremento de la satisfacción de la madre en relación directa con el cuidado en la maternidad. Objetivos: Identificar el grado de satisfacción de la mujer sobre la atención al parto, el acompañamiento durante el nacimiento y la duración de la lactancia materna. Material y método: Estudio descriptivo transversal en el Hospital Universitario San Cecilio de Granada (España), durante el periodo de tiempo Agosto del 2011 al 2012, se realizo con una segunda fase de seguimiento prospectivo a una N = 60 madres. Se utilizó un protocolo (Anexo 1) a las 24 horas en el hospital y a los 14 días por teléfono. A los 3 meses, se realizó un seguimiento relacionado con la alimentación del bebe. Resultados: El nivel de satisfacción global sobre el parto es alto en la población estudiada. Se ha demostrado que la lactancia materna (P = 0,514) y el parto vía vaginal sin epidural (P = 0,320) crea una mayor satisfacción en la madre. Por otro lado, la satisfacción sobre el parto guarda relación con la duración de la lactancia materna. Conclusión: La opinión satisfactoria de las madres relacionadas con la atención al parto y el acompañamiento durante el nacimiento se incrementa en aquellas mujeres cuyo parto ocurrió de forma eutócica sin epidural e iniciaron la lactancia materna precoz.

Prediction of early and late pre-eclampsia from maternal characteristics, uterine artery Doppler and markers of vasculogenesis during first trimester of pregnancy.

OBJECTIVE: To develop a predictive model for pre-eclampsia using clinical, biochemical and ultrasound markers during the first trimester of pregnancy. METHODS: This was a nested case-control study within a pre-eclampsia screening project that involved 5367 asymptomatic pregnant women undergoing routine transvaginal uterine artery (UtA) Doppler at 11 + 0 to 13 + 6 weeks. Following exclusions, there were 70 pregnant women who later developed pre-eclampsia and 289 control patients enrolled during the first trimester who had serum or plasma samples taken at enrolment available for the purposes of this study. Of these, 17 pregnancies were diagnosed with early-onset (delivery < 34 weeks) pre-eclampsia and 53 with late-onset (delivery ≥ 34 weeks) pre-eclampsia. The lowest, highest and mean of left and right UtA pulsatility indices (PI) were calculated. Blood samples were stored at -84 °C until biochemical analysis for markers of vasculogenesis was performed. The distributions of the lowest UtA-PI and the biochemical markers were adjusted for maternal characteristics, expressed as multiples of the median (MoM), and compared between groups. Logistic regression analysis was used to evaluate if any variable was significantly associated with pre-eclampsia. RESULTS: Pregnancies that later developed pre-eclampsia were associated with higher maternal prepregnancy body mass index. An increased lowest UtA-PI was significantly associated with both early- and late-onset disease. Placental growth factor (PlGF) MoM was significantly reduced in women who later developed early- or late-onset pre-eclampsia compared with controls (median (interquartile range), 0.69 (0.33-1.46) and 1.10 (0.39-1.56), respectively, vs 1.19 (0.65-1.84), P < 0.05). Different combined models were generated by logistic regression analysis, and the detection rate with a fixed 10% false-positive rate was 47% and 29% for early- and late-onset pre-eclampsia, respectively. CONCLUSION: Pregnancies that later developed early or late pre-eclampsia were characterized by impaired placentation and an anti-angiogenic state during the first trimester of pregnancy. Regression models which include maternal characteristics, UtA Doppler and PlGF can apparently predict approximately half of pregnancies that will be complicated by early-onset pre-eclampsia. We believe more research in several areas is needed to aid in the creation of a better and more population-specific screening test for pre-eclampsia during the first trimester of pregnancy.

[Anthropometric study and evaluation of the nutritional status of a population school children in Granada; comparison of national and international reference standards]. / Estudio antropométrico y valoración del estado nutricional de una población de escolares de Granada; comparación con los estándares nacionales e internacionales de referencia.

Recent studies show an alarming increase in levels of overweight and obesity among children and adolescents. The main objectives of this research were the following: (i) to carry out an anthropometric evaluation of the nutritional status and body composition of school children in the city and province of Granada; (ii) to compare the nutritional status of this population sample with national and international reference standards. The results obtained in this study showed that the general prevalence of overweight in both sexes was 22.03% and that 9.12% of the children were obese. Statistically significant differences were found between the variable, weight for age and sex (p < 0.05) and the variable, height for age and sex (p < 0.05). Regarding the body mass index, no statistically significant differences were found for the variable, sex (p = 0.182). This contrasted with the variable, age, which did show statistically significant differences (p < 0.05). As a conclusion, the results of our study highlighted the fact that these anthropometric values were much higher than national and international reference standards.

Prenatal exposure to androgen excess increases LH pulse amplitude during postnatal life in male sheep.

Prenatal exposure to excess testosterone has a profound impact on reproductive and metabolic functions in young and adult female sheep. Nevertheless, few studies have addressed the impact of prenatal exposure to an excess of androgens on reproductive and metabolic functions in males. The aim of the present study was to assess the impact of prenatal exposure to an excess of testosterone or dihydrotestosterone on the luteinizing hormone (LH) pulse characteristics during sexual development in male sheep. Control male sheep (C-males) and males born to mothers exposed to twice weekly injections of 30 mg testosterone or dihydrotestosterone from day 30-90 and 40 mg from day 90-120 of gestation (T-males, DHT-males) were studied at 5, 10, and 20 weeks of age, ages that represent infancy, early prepubertal, and late prepubertal stages of sexual development in this species, respectively. Patterns of LH pulsatility showed that T- and DHT-males exhibited a higher secretion of LH during the 6-h study and a higher amplitude of the LH pulses compared with C-males. Moreover, nadir of the pulses was higher in T- and DHT-males compared with C-males. Frequency of LH pulses, however, was not different within ages or between groups. These results show that males can be responsive to prenatal androgenization and suggest that treatment transiently alters the amplitude of LH pulses probably as the result of defects in the pituitary responsiveness pattern or in the gonadotropin-releasing hormone (GnRH) release pattern.

[Prenatal stimulation: results in the peripartum period]. / La estimulación prenatal: resultados relevantes en el periparto.

UNLABELLED: During pregnancy, the prolonged stress and worry felt by mothers can alter the development and function of the right brain hemisphere. For this reason, importance is given to prenatal stimulation programs for pregnant women. OBJECTIVES: To determine the perinatal results in the moment of childbirth in mothers who had participated in prenatal stimulation programs. MATERIAL: An experimental study was conducted in five health districts in the town of Cienfuegos (Cuba) with a view to identifying the perinatal results at the moment of childbirth in women that had participated in prenatal stimulation programs. METHODOLOGY: The study consisted of an intentional sampling of all of the subjects (n = 200 women who were 20-28 weeks pregnant). The variables studied were the following: duration of labor, baby's birth weight, Apgar score at birth, type of childbirth, and opinion of the subjects about the prenatal stimulation program. RESULTS: Of the population sample, 36% of the subjects gave birth in less than six hours; 67.5% had babies weighing 2,500-3,000 grams; and 96.5% had babies whose Apgar scores were between 8 and 9. Finally, 68.5% of the subjects had natural childbirths and 96% were satisfied with the prenatal stimulation program. CONCLUSIONS: The results obtained showed that these new prenatal stimulation programs were well received by the subjects in this study.

[Analysis of the nutritional state and body composition of school children in Granada (Spain)]. / Análisis del estado nutricional y composición corporal de una población de escolares de Granada.

The objective of this study was to first determine the nutritional state of a sample population of school children, and then analyze the distribution pattern of their subcutaneous fat layer. The sample was composed of 977 school children from the city and province of Granada (Spain). All of the children (524 girls and 452 boys) were 9-17 years of age. To study their nutritional state and the distribution of the subcutaneous fat layer, they were given a complete anthropometric evaluation, which included measuring their weight, height, body mass index, skin folds, and body perimeters. The results obtained showed a 23.01% prevalence of overweight in the female subjects and 20.81% in the male subjects. Furthermore, the female subjects had an obesity prevalence of 12.70% in comparison to the male subjects, whose obesity prevalence was 4.98%. The distribution pattern of subcutaneous fat was found to be mainly located in the central part of body. The high percentage of overweight and obesity along with the development of a central fat distribution pattern (neck, chest, and abdomen) in these school children is clear evidence of potential cardiovascular risk.

[Risk factors in the development of breast cancer, state of Mexico]. / Factores de riesgo como pronóstico de padecer cáncer de mama en un estado de México.

INTRODUCTION: Breast cancer is one of the most frequent diseases in women today, and its social impact is devastating. The risk factors focused on in recent research are mainly hormonal, genetic, and environmental though toxic habits, overweight, and obesity have also been studied. In contrast, protective factors against breast cancer include breastfeeding and daily exercise. OBJECTIVE: To ascertain the risk factors for the women with breast cancer in our study sample. MATERIAL AND METHODS: A study of cases and controls was performed on 115 women diagnosed with breast cancer and on 115 healthy women, who had been patients at the National Cancer Institute ISSEMYM in Mexico from January to December 2011. Information was collected from the women in the sample pertaining to their family history of cancer, personal background, life style, and body mass index (BMI). Breast cancer risk was estimated with multivariate logistic regression models and the chi-square test. RESULTS: It was found that there was a greater risk of breast cancer in overweight or obese women who did not do any physical exercise and either who had breastfed their children for a very short time or who had not breastfed them at all. No significant differences were found between breast cancer and toxic habits. CONCLUSIONS: The results of our study found a direct relation between breast cancer and overweight, obesity, and physical inactivity. Breastfeeding during the first months of the baby's life was found to be a protective factor against breast cancer.

[Overweight/obesity in women and its implication in breast cancer: age of diagnosis]. / Sobrepeso/obesidad en mujeres y su implicación en el cáncer de mama: edad de diagnóstico.

UNLABELLED: Overweight, obesity, and breast cancer are three pathologies that are endemic in the world today and which have a great impact on society. Many research studies are currently trying to discover possible associations between these factors and to specify the links between them. OBJECTIVE: To verify whether there is a direct connection between overweight/obesity in women with breast cancer and its relation to age of diagnosis. MATERIALS AND METHODS: The sample population in this study was composed of 118 women (32-76 years of age) who had been diagnosed and treated for breast cancer in 2009-2011 at the Centro Oncológico Estatal ISSEMyM [National Cancer Institute of Mexico]. An observational, descriptive, and transversal study was performed in which a random sample of n = 60 women was divided into two groups. The first group was composed of women with breast cancer, but who were of normal weight. The second group was composed of women with breast cancer, but who were either overweight or obese. In both groups, the Patient-Generated Subjective Global Assessment (PG-SGA) was applied, and the BMI (weight and height) was determined as well as waist circumference. RESULTS: A statistically significant relation was found between age of diagnosis and weight (normal/overweight/obese) of the subjects (p < 0.05). CONCLUSIONS: The results obtained show that overweight and obesity are directly linked to breast cancer and age of diagnosis. Breast cancer was diagnosed earlier in women of normal weight.