Guías antieméticas: ¿hemos incorporado los cambios referentes a carboplatino y antraciclinas? / Antiemetic guidelines: Have we incorporated the changes concerning carboplatin and anthracyclines?

Objetivo: en 2016 se publicaron las guías de la MASCC/ESMO que incorporaron los esquemas de antraciclinas como quimioterapia altamente emetógena (QAE) proponiendo la triple terapia antiemética, así como para los esquemas de carboplatino. Los objetivos fueron analizar el nivel de concordancia entre las guías y la profilaxis antiemética utilizada en el hospital de día de hematooncología, evaluar su efectividad y determinar el ahorro de la inclusión de netupitant/palonosetrón (NEPA) oral con dexametasona intravenosa (NEPAd) respecto a fosaprepitant con ondansetrón y dexametasona (FOD intravenosa). Método estudio observacional prospectivo registrando variables demográficas, esquema de quimioterapia recibido, localización tumoral, riesgo emetógeno del paciente, pauta antiemética prescrita, concordancia con guía MASCC/ESMO y su efectividad, utilización de medicación de rescate y registro de visitas a urgencias o ingresos por emesis.Se llevó a cabo un estudio farmacoeconómico de minimización de costes. Resultados se incluyeron 61 pacientes, 70% mujeres, mediana edad 60,5.Los esquemas de platino fueron más frecuentes en el periodo 1, siendo el 87,5% respecto al 67,6% en el periodo 2. Los esquemas con antraciclinas fueron del 21,6 y 10% respectivamente en cada periodo. Un 21,1% de las pautas antieméticas no coincidían con las recomendaciones MASCC/ESMO, siendo en su totalidad en el periodo 1. La puntuación de los cuestionarios de efectividad fue de protección total en el 90,9% en las náuseas agudas, del 100% en los vómitos agudos y en las náuseas retardadas, y del 72,7% en los vómitos retardados. La frecuencia de uso de medicación de rescate fue del 18,7% en el periodo 1 y no fue necesaria en el periodo 2.No se detectaron visitas a urgencias ni ingresos en ninguno de los periodos. El uso de NEPAd comportó una reducción del 28% de los costes con respecto al empleo de FOD. Conclusiones: ... (AU)

Objective: Latest MASCC/ESMO guidelines of the recommendations for the prophylaxis of acute and delayed emesis induced by moderately emetogenic chemotherapy was published in 2016 incorporating anthracycline schemes as highly emetogenic chemotherapy (HEC), proposing triple antiemetic therapy to control nausea and vomiting. Likewise, they recommend triple therapy for carboplatin. The objectives of this study were to analyze the degree of concordance between guidelines and antiemetic prophylaxis used in the Chemotherapy Outpatient Unit in patients undergoing treatment with HEC and carboplatin, to evaluate its effectiveness and to determine the savings due to the use of netupitant/palonosetron (NEPA) oral (or) with intravenous (iv) dexamethasone (NEPAd) compared to iv Fosaprepitant with ondansetron and dexamethasone (FOD iv).MethodsProspective observational study recording demographic variables, chemotherapy protocol, tumor location, patient emetogenic risk, antiemetic regimen prescribed, concordance with the MASCC/ESMO guideline, and effectiveness, evaluated by MASCC survey, use of rescue medication and visits to the Emergency Department or hospitalization due to emesis.A cost minimization pharmacoeconomic study was carried out. Results 61 patients were included; 70% women; median age 60.5. Platinum schemes were more frequent in period 1, being 87.5% compared to 67.6% in period 2. Anthracycline schemes were 21.6% and 10% respectively in each period.A 21.1% of the antiemetic regimens did not coincide with the MASCC/ESMO recommendations, being entirely in period 1. The score of the effectiveness questionnaires was total protection in 90.9% in acute nausea, from 100% in acute vomiting and delayed nausea, and 72.7% in delayed vomiting.The frequency of use of rescue medication was 18.7% in period 1 and was not necessary in period 2.No visits to the emergency room or admissions were detected in any of the periods. Conclusions: ...(AU)

[Translated article] Have changes concerning carboplatin and anthracyclines been incorporated?

OBJECTIVE: Latest MASCC/ESMO guidelines of the recommendations for the prophylaxis of acute and delayed emesis induced by moderately emetogenic chemotherapy was published in 2016 incorporating anthracycline schemes as highly emetogenic chemotherapy (HEC), proposing triple antiemetic therapy to control nausea and vomiting. Likewise, they recommend triple therapy for carboplatin. The objectives of this study were to analyze the degree of concordance between guidelines and antiemetic prophylaxis used in the Chemotherapy Outpatient Unit in patients undergoing treatment with HEC and carboplatin, to evaluate its effectiveness and to determine the savings due to the use of netupitant/palonosetron (NEPA) oral (or) with intravenous (iv) dexamethasone (NEPAd) compared to iv Fosaprepitant with ondansetron and dexamethasone (FOD iv). METHODS: Prospective observational study recording demographic variables, chemotherapy protocol, tumor location, patient emetogenic risk, antiemetic regimen prescribed, concordance with the MASCC/ESMO guideline, and effectiveness, evaluated by MASCC survey, use of rescue medication and visits to the Emergency Department or hospitalization due to emesis. A cost minimization pharmacoeconomic study was carried out. RESULTS: 61 patients were included; 70% women; median age 60.5. Platinum schemes were more frequent in period 1, being 87.5% compared to 67.6% in period 2. Anthracycline schemes were 21.6% and 10% respectively in each period. A 21.1% of the antiemetic regimens did not coincide with the MASCC/ESMO recommendations, being entirely in period 1. The score of the effectiveness questionnaires was total protection in 90.9% in acute nausea, from 100% in acute vomiting and delayed nausea, and 72.7% in delayed vomiting. The frequency of use of rescue medication was 18.7% in period 1 and was not necessary in period 2. No visits to the emergency room or admissions were detected in any of the periods. CONCLUSIONS: Use of NEPAd led to a 28% reduction in costs with respect to the use of FOD. A high level of concordance was obtained in both periods between the latest published guideline and healthcare practice in our field. Surveys carried out on patients seem to suggest that both antiemetic therapies have similar effectiveness in clinical practice. The inclusion of NEPAd has led to a reduction in costs, positioning itself as an efficient option.

Antiemetic guidelines: Have we incorporated the changes concerning carboplatin and anthracyclines? / Guías antieméticas: ¿hemos incorporado los cambios referentes a carboplatino y antraciclinas?

OBJECTIVE: Latest MASCC/ESMO guidelines of the recommendations for the prophylaxis of acute and delayed emesis induced by moderately emetogenic chemotherapy was published in 2016 incorporating anthracycline schemes as highly emetogenic chemotherapy (HEC), proposing triple antiemetic therapy to control nausea and vomiting. Likewise, they recommend triple therapy for carboplatin. The objectives of this study were to analyze the degree of concordance between guidelines and antiemetic prophylaxis used in the Chemotherapy Outpatient Unit in patients undergoing treatment with HEC and carboplatin, to evaluate its effectiveness and to determine the savings due to the use of netupitant/palonosetron (NEPA) oral (or) with intravenous (iv) dexamethasone (NEPAd) compared to iv Fosaprepitant with ondansetron and dexamethasone (FOD iv). METHODS: Prospective observational study recording demographic variables, chemotherapy protocol, tumor location, patient emetogenic risk, antiemetic regimen prescribed, concordance with the MASCC/ESMO guideline, and effectiveness, evaluated by MASCC survey, use of rescue medication and visits to the Emergency Department or hospitalization due to emesis. A cost minimization pharmacoeconomic study was carried out. RESULTS: 61 patients were included; 70% women; median age 60.5. Platinum schemes were more frequent in period 1, being 87.5% compared to 67.6% in period 2. Anthracycline schemes were 21.6% and 10% respectively in each period. A 21.1% of the antiemetic regimens did not coincide with the MASCC/ESMO recommendations, being entirely in period 1. The score of the effectiveness questionnaires was total protection in 90.9% in acute nausea, from 100% in acute vomiting and delayed nausea, and 72.7% in delayed vomiting. The frequency of use of rescue medication was 18.7% in period 1 and was not necessary in period 2. No visits to the emergency room or admissions were detected in any of the periods. CONCLUSIONS: Use of NEPAd led to a 28% reduction in costs with respect to the use of FOD. A high level of concordance was obtained in both periods between the latest published guideline and healthcare practice in our field. Surveys carried out on patients seem to suggest that both antiemetic therapies have similar effectiveness in clinical practice. The inclusion of NEPAd has led to a reduction in costs, positioning itself as an efficient option.

Marine communities of the newly created Kawésqar National Reserve, Chile: From glaciers to the Pacific Ocean.

The newly created Kawésqar National Park (KNP) and National Reserve (KNR) in southern Chile consists of diverse terrestrial and marine habitats, which includes the southern terminus of the Andes, the Southern Patagonia Ice Fields, sub-Antarctic rainforests, glaciers, fjords, lakes, wetlands, valleys, channels, and islands. The marine environment is influenced by wide ranging hydrological factors such as glacier melt, large terrigenous inputs, high precipitation, strong currents, and open ocean water masses. Owing to the remoteness, rugged terrain, and harsh environmental conditions, little is known about this vast region, particularly the marine realm. To this end, we conducted an integrated ecological assessment using SCUBA and remote cameras down to 600 m to examine this unique and largely unexplored ecosystem. Kelp forests (primarily Macrocystis pyrifera) dominate the nearshore ecosystem and provide habitat for myriad benthic organisms. In the fjords, salinity was low and both turbidity and nutrients from terrigenous sources were high, with benthic communities dominated by active suspension feeders (e.g., Bivalvia, Ascidiacea, and Bryozoa). Areas closer to the Pacific Ocean showed more oceanic conditions with higher salinity and lower turbidity, with benthic communities experiencing more open benthic physical space in which predators (e.g., Malacostraca and Asteroidea) and herbivorous browsers (e.g., Echinoidea and Gastropoda) were more conspicuous components of the community compared to the inner fjords. Hagfish (Myxine sp.) was the most abundant and frequently occurring fish taxa observed on deep-sea cameras (80% of deployments), along with several taxa of sharks (e.g., Squaliformes, Etmopteridae, Somniosidae, Scyliorhinidae), which collectively were also observed on 80% of deep-sea camera deployments. The kelp forests, deep fjords, and other nearshore habitats of the KNR represent a unique ecosystem with minimal human impacts at present. The KNR is part of the ancestral territory of the indigenous Kawésqar people and their traditional knowledge, including the importance of the land-sea connection in structuring the marine communities of this region, is strongly supported by our scientific findings.

Spatial patterns of continental shelf faunal community structure along the Western Antarctic Peninsula.

Knowledge of continental shelf faunal biodiversity of Antarctica is patchy and as such, the ecology of this unique ecosystem is not fully understood. To this end, we deployed baited cameras at 20 locations along ~ 500 km of the Western Antarctic Peninsula (WAP) at depths from 90 to 797 m. We identified 111 unique taxa, with mud bottom accounting for 90% of the dominant (≥ 50% cover) habitat sampled. Amphipoda comprised 41% of the total maximum number of individuals per camera deployment (MaxN) and occurred on 75% of deployments. Excluding this taxon, the highest MaxN occurred around King George/25 de Mayo Island and was driven primarily by the abundance of krill (Euphausiidae), which accounted for 36% of total average MaxN among deployments around this island. In comparison, krill comprised 22% of total average MaxN at Deception Island and only 10% along the peninsula. Taxa richness, diversity, and evenness all increased with depth and depth explained 18.2% of the variation in community structure among locations, which may be explained by decreasing ice scour with depth. We identified a number of Vulnerable Marine Ecosystem taxa, including habitat-forming species of cold-water corals and sponge fields. Channichthyidae was the most common fish family, occurring on 80% of all deployments. The Antarctic jonasfish (Notolepis coatsorum) was the most frequently encountered fish taxa, occurring on 70% of all deployments and comprising 25% of total MaxN among all deployments. Nototheniidae was the most numerically abundant fish family, accounting for 36% of total MaxN and was present on 70% of the deployments. The WAP is among the fastest warming regions on Earth and mitigating the impacts of warming, along with more direct impacts such as those from fishing, is critical in providing opportunities for species to adapt to environmental change and to preserve this unique ecosystem.

Significance of pro-angiogenic estrogen metabolites in normal follicular development and follicular growth arrest in polycystic ovary syndrome.

STUDY QUESTION: Do alterations in pro- and anti-angiogenic estrogen metabolites in follicular fluid (FF) contribute to the follicular growth arrest and anovulation associated with polycystic ovary syndrome (PCOS)? SUMMARY ANSWER: FF of PCOS women with anovulation have reduced levels of pro-angiogenic estrogen metabolites (EMs) and vascular endothelial growth factor (VEGF) compared to that of fertile women with regular menstrual cycles, but exogenous gonadotropins increase the pro-angiogenic EMs and VEGF levels in PCOS women. WHAT IS KNOWN ALREADY: PCOS is characterized by the arrest of follicular development that leads to chronic anovulation. Follicular arrest is generally associated with elevated plasma levels of luteinizing hormone (LH), androgens and anti-Mullerian hormone (AMH). There is also reduced angiogenesis in the follicles of PCOS women compared to those of normal cycling women. It is known that angiogenesis is a critical factor during follicular development. We and other investigators have explored the role of EMs in ovarian angiogenesis, particularly in human corpus luteum function, showing that 4-hydroxyestrone (4-OHE1) and 16-ketoestradiol (16-kE2) have pro-angiogenic effects while 2-methoxyestradiol (2-ME2) and 2-methoxyestrone (2-ME1) have anti-angiogenic effects. Additionally, 2-hydroxyestradiol (2-OHE2), which is produced in the ovary, has proliferative and pro-angiogenic properties. We hypothesized that EMs could be involved in angiogenesis necessary for ovarian follicular development in fertile women, and that dysregulation of these factors may contribute to follicular arrest in PCOS. The relationship between EMs, VEGF and AMH in the pathophysiology of follicular arrest in PCOS has not been previously studied at a follicular level in anovulatory women without ovulation induction. STUDY DESIGN, SIZE, DURATION: This is a comparative experimental study of serum and FF collected from different sized follicles (antral ˂10 mm and dominant ˃16 mm) of women with and without ovarian stimulation. The study included women with regular menstrual cycles who were proven to be fertile (n = 20) and PCOS women with follicular arrest who were candidates for ovarian drilling (n = 17), as well as other patients requiring ovarian stimulation, i.e. control women undergoing IVF for male factor infertility (n = 12) and PCOS women undergoing IVF (n = 17). In vitro studies were carried out on granulosa-lutein cells (GCs) obtained from subsets of women undergoing IVF for male factor infertility (n = 6) and PCOS women undergoing IVF (n = 6). GCs were maintained in culture for up to 6 days. PARTICIPANTS/MATERIALS, SETTING, METHODS: Intrafollicular estradiol, estrone and EMs concentrations were determined by high performance liquid chromatography-mass spectrometry. Testosterone in serum was measured by RIA, and LH, FSH and sex hormone-binding globulin in serum were measured with IRMA kits. AMH was determined in serum and FF by enzyme linked immunosorbant assay (ELISA). VEGF levels were measured in FF and conditioned medium by ELISA. Conditioned medium were obtained from cultured GCs. The angiogenic potential was assessed by in vitro angiogenic assays. MAIN RESULTS AND THE ROLE OF CHANCE: Pro-angiogenic EMs (4-OHE1, 16-kE2 and 2-OHE2) and VEGF were lower in FF of antral follicles of PCOS women with follicular arrest compared those of fertile women with ovulatory cycles (P < 0.05). In contrast, higher concentrations of AMH were found in FF of antral follicles from PCOS women with follicular arrest compared to those of fertile women with ovulatory cycles (P < 0.05). Exogenous gonadotropins used in IVF increased pro-angiogenic EMs and VEGF production in PCOS women, reaching similar profiles compared to control women receiving gonadotropins in their IVF treatment for male factor infertility. The pro-angiogenic EM 2-OHE2 increased the angiogenic potential and VEGF levels of GCs from PCOS women compared to the basal condition (P < 0.05). These findings suggest that there is a role for pro-angiogenic EMs in the control of follicular VEGF production. LIMITATIONS, REASONS FOR CAUTION: The limitations include the possibility that in vitro analysis of GCs might not reflect the in vivo mechanisms involved in the pro-angiogenic action of 2-OHE2 since GCs obtained at the time of oocyte retrieval belong to a very early stage of the luteal phase and might not be representative of GCs during follicular growth. Therefore, our findings do not conclusively rule out the possibility that other in vivo mechanisms also account for defective angiogenesis observed in PCOS. WIDER IMPLICATIONS OF THE FINDINGS: The present study highlights the significance of EMs, angiogenic factors and AMH and their interaction in the pathophysiology of follicular development in PCOS. This study provides new insights into the role of pro-angiogenic factors in follicular arrest in PCOS. STUDY FUNDING/COMPETING INTEREST(S): This study was funded by CONICYT/FONDECYT 1140693 and NIH grant R01HD083323. All authors declare no conflict of interest. TRIAL REGISTRATION NUMBER: N/A.

Left anterior descending artery hyper dominance giving rise to the posterior descending artery: an extremely rare coronary anomaly and its clinical implications.

The prevalence of congenital coronary artery anomalies is approximately 1% in the general population. They are a common cause of sudden death in younger persons. The origination of the posterior descending artery (PDA) from left anterior descending (LAD) artery is an extremely rare anomaly. We present a case of a 54-year-old female who presented with diabetic ketoacidosis with co-existing non-ST elevation myocardial infarction, therefore, had an invasive angiogram that identified the anomalous origin of PDA from LAD. It is vital to define coronary anatomy as anomalies dictate which cardiac intervention should be attempted in cases of ischemia.

Kelp forests at the end of the earth: 45 years later.

The kelp forests of southern South America are some of the least disturbed on the planet. The remoteness of this region has, until recently, spared it from many of the direct anthropogenic stressors that have negatively affected these ecosystems elsewhere. Re-surveys of 11 locations at the easternmost extent of Tierra del Fuego originally conducted in 1973 showed no significant differences in the densities of adult and juvenile Macrocystis pyrifera kelp or kelp holdfast diameter between the two survey periods. Additionally, sea urchin assemblage structure at the same sites were not significantly different between the two time periods, with the dominant species Loxechinus albus accounting for 66.3% of total sea urchin abundance in 2018 and 61.1% in 1973. Time series of Landsat imagery of the region from 1998 to 2018 showed no long-term trends in kelp canopy over the past 20 years. However, ~ 4-year oscillations in canopy fraction were observed and were strongly and negatively correlated with the NOAA Multivariate ENSO index and sea surface temperature. More extensive surveying in 2018 showed significant differences in benthic community structure between exposed and sheltered locations. Fish species endemic to the Magellanic Province accounted for 73% of all nearshore species observed and from 98-100% of the numerical abundance enumerated at sites. Fish assemblage structure varied significantly among locations and wave exposures. The recent creation of the Yaganes Marine Park is an important step in protecting this unique and biologically rich region; however, the nearshore waters of the region are currently not included in this protection. There is a general lack of information on changes in kelp forests over long time periods, making a global assessment difficult. A complete picture of how these ecosystems are responding to human pressures must also include remote locations and locations with little to no impact.

Androgens Profile in Blood Serum and Follicular Fluid of Women With Poor Ovarian Response During Controlled Ovarian Stimulation Reveals Differences Amongst POSEIDON Stratification Groups: A Pilot Study.

Patients with poor ovarian response (POR) to exogenous gonadotropins stimulation for assisted reproductive technology (ART) have decreased circulating androgens during spontaneous cycles. The Patient-Oriented Strategies Encompassing Individualized Oocyte Number (POSEIDON) is a 4-tier stratification of women with POR to controlled ovarian stimulation (COH) based on age and biomarkers of ovarian reserve has been proposed to maximize the clinical management of this group for ART. The aim of the present study was to characterize the levels of androgens during COH in follicular fluid (FF) and serum in POSEIDON subgroups and compared them with women of normal ovarian response. Sixty nine consecutive patients undergoing ART were included and testosterone, androstenedione, dehydroepiandrosterone sulfate (DHEA-S), estradiol, sex hormone-binding globulin (SHBG), and insulin-like growth factor 1 (IGF-1) were measured in serum and FF collected at the time of oocyte pick-up. The number of retrieved oocytes was registered for each patient for their allocation to the respective POSEIDON subgroup. The control group comprised 19 women and the POSEIDON group 1 (age < 35, normal ovarian reserve biomarkers) n = 14, group 2 (age ≥ 35, normal ovarian reserve biomarkers) n = 8, group 3 (age < 35, poor ovarian reserve biomarkers) n = 6 and group 4 (age ≥ 35, poor ovarian reserve biomarkers) n = 22. Serum levels of total testosterone, androstenedione and DHEA-S were not different in group 1 vs. control but significantly decreased in group 3 vs. control. DHEA-S in FF was also significantly decreased in group 3 vs. control. In addition, serum testosterone was decreased in groups 2 and 4 vs. control; and serum androstenedione and estradiol were reduced in group 4 vs. control. No differences were observed for estradiol, SHBG and IGF-1 in FF. Finally, a high correlation between serum and FF DHEA-S was observed when data from samples of all groups were pooled. Group 1 did not show hypoandrogenemia however group 3 had low levels of all measured androgens in serum and DHEA-S in FF. Such differences might help to better characterize and/or improve the clinical management of women with POR according to their respective POSEIDON stratification.

A Unique and Rare Presentation of Adult Congenital Heart Disease: Common Atrium Associated with Coronary Aneurysms and Fistula.

An atrial septal defect is the second most common congenital heart disease found in adults with a female to male ratio of 4 : 1. However, it is rare to have a complete absence of the interatrial septum (IAS) to be diagnosed in an elderly patient associated with other coexisting anomalies. We present a case of a 60-year-old female presenting with common atrium, coronary arteriovenous fistula, and coronary artery aneurysms. This case highlights rare adult congenital cardiac anomalies and the importance of thorough workup to evaluate for the intracardiac shunt in a patient who has right heart enlargement and development of pulmonary disease in adulthood without a significant history of chronic smoking. A 60-year-old female patient presented with substernal chest pain. The nuclear stress test showed no reversible ischemia; however, right ventricle (RV) dilation was present. The patient underwent further evaluation for RV dilation with a transthoracic echocardiogram that demonstrated a complete absence of IAS and was confirmed by a positive bubble study. The patient had an invasive angiography that showed severely elevated RV pressure. Oxygen saturation in the right atrium was higher than in the inferior vena cava. Hence, an intracardiac shunt with a 10% increase in oxygen saturation was identified. It also identified aneurysmal coronary arteries (measuring 0.8 to 1.0 cm). Cardiac computed tomography angiogram was performed that identified all coronary arteries to be ectatic/aneurysmal measuring up to 8-10 mm, an absence of IAS, and a possible fistula between the distal left anterior descending and a coronary vein. To our knowledge, this is the first-ever presentation of a complete congenital absence of IAS in a patient who has survived into adulthood with the development of severe pulmonary hypertension without Eisenmenger syndrome. It is unclear at this point if surgical treatment to correct the anatomical defect (which would be probably palliative) would be superior to conservative medical therapy. Besides, the presence of coronary arteriovenous fistula would make the decision-making process more complex regarding surgical versus conservative management.

Molecular modelling predicts that 2-methoxyestradiol disrupts HIF function by binding to the PAS-B domain.

An estradiol metabolite, 2-methoxyestradiol (2ME), has emerged as an important regulator of ovarian physiology. 2ME is recognized as a potent anti-angiogenic agent in clinical trials and laboratory studies. However, little is known about its molecular actions and its endogenous targets. 2ME is produced by human ovarian cells during the normal menstrual cycle, being higher during regression of the corpus luteum, and is postulated to be involved in the anti-angiogenic process that plays out during luteolysis. We utilized cell biology techniques to understand the molecular mechanism of 2ME anti-angiogenic effects on human granulosa luteal cells. The principal effect of 2ME was to alter Hypoxia Inducible Factor 1A (HIF1A) sub-cellular localization. Molecular modelling and multiple bioinformatics tools indicated that 2ME impairs Hypoxia Inducible Factor complex (HIF) nuclear translocation by binding to a buried pocket in the HIF1A Per Arnt Sim (PAS)-B domain. Binding of 2ME to HIF1A protein is predicted to perturb HIF1A-Hypoxia Inducible Factor B (HIFB) interaction, a key step in HIF nuclear translocation, preventing the transcriptional actions of HIF, including Vascular Endotelial Growth Factor (VEGF) gene activation. To our knowledge, 2ME is the first putative HIF endogenous ligand characterized with anti-angiogenic activity. This postulate has important implications for reproduction, because angiogenic processes are critical for ovarian follicular development, ovulation and corpus luteum regression. The present research could contribute to the development of novel pharmacological approaches for controlling HIF activity in human reproductive diseases.

Ovarian Function in Adolescents Conceived Using Assisted Reproductive Technologies.

STUDY OBJECTIVE: To compare ovarian function between adolescents conceived using assisted reproductive technology (AcART) and adolescents who were conceived spontaneously (AcSP). DESIGN: Multicenter study of ovarian function in AcART because of male or tubal infertility. SETTING: University Hospital. PARTICIPANTS: We evaluated 22 AcART and 53 AcSP at 1-2 years after menarche. The participants were born at term (≥37 weeks of gestation) with normal birth weights (≥2500 g) from singleton pregnancies. INTERVENTIONS: None. MAIN OUTCOME MEASURES: Differences in ovulation, reproductive hormones, and ovarian morphology. RESULTS: AcART had an older age of menarche than that of AcSP, even after adjusting for maternal age at menarche, gestational age, and birth weight (P = .027). AcART had lower incidence of ovulation (P = .021) and higher luteinizing hormone serum levels (P = .01) than those of AcSP. The incidence of oligomenorrhea and the cycle length were similar between AcART and AcSP. AcART had levels of anti-Müllerian hormone, inhibin B, follicle-stimulating hormone, estradiol, and androgens similar to those of AcSP. The ovarian morphology, ovarian volume, and follicle counts were similar in both groups. CONCLUSION: AcART had later menarche, lower ovulation rates, and higher luteinizing hormone levels than those of AcSP. Future studies should investigate whether these findings are indicative of a risk of ovarian dysfunction later in life for AcART.

Marine biodiversity at the end of the world: Cape Horn and Diego Ramírez islands.

The vast and complex coast of the Magellan Region of extreme southern Chile possesses a diversity of habitats including fjords, deep channels, and extensive kelp forests, with a unique mix of temperate and sub-Antarctic species. The Cape Horn and Diego Ramírez archipelagos are the most southerly locations in the Americas, with the southernmost kelp forests, and some of the least explored places on earth. The giant kelp Macrocystis pyrifera plays a key role in structuring the ecological communities of the entire region, with the large brown seaweed Lessonia spp. forming dense understories. Kelp densities were highest around Cape Horn, followed by Diego Ramírez, and lowest within the fjord region of Francisco Coloane Marine Park (mean canopy densities of 2.51 kg m-2, 2.29 kg m-2, and 2.14 kg m-2, respectively). There were clear differences in marine communities among these sub-regions, with the lowest diversity in the fjords. We observed 18 species of nearshore fishes, with average species richness nearly 50% higher at Diego Ramírez compared with Cape Horn and Francisco Coloane. The number of individual fishes was nearly 10 times higher at Diego Ramírez and 4 times higher at Cape Horn compared with the fjords. Dropcam surveys of mesophotic depths (53-105 m) identified 30 taxa from 25 families, 15 classes, and 7 phyla. While much of these deeper habitats consisted of soft sediment and cobble, in rocky habitats, echinoderms, mollusks, bryozoans, and sponges were common. The southern hagfish (Myxine australis) was the most frequently encountered of the deep-sea fishes (50% of deployments), and while the Fueguian sprat (Sprattus fuegensis) was the most abundant fish species, its distribution was patchy. The Cape Horn and Diego Ramírez archipelagos represent some of the last intact sub-Antarctic ecosystems remaining and a recently declared large protected area will help ensure the health of this unique region.

Endocarditis infecciosa asociada a catéter de hemodiálisis: hallazgos clínicos y ecocardiográficos / Infective endocarditis associated with hemodialysis catheters: clinical and ehocardiographic findings

Resumen: Hallazgos clínicos y ecocardiográficos en pacientes con endocarditis infecciosa (E.I.) asociada a catéter de hemodiálisis (CHD) fueron comparados con sujetos controles con E.I. "habitual". Pacientes y métodos: Del total de registros ecocardiográficos de una Clínica privada de Antofagasta entre 2009 y 2014, 4 pacientes presentaban E.I. asociada CHD (E.I.-CHD) y 16 otro tipo de E.I. (controles). Se compararon ambos grupos clínicamente y en las distintas modalidades de ecografía, para evaluar el aporte de cada una de ellas en el diagnóstico, manejo y comprensión del mecanismo de producción de la E.I. Resultados: El periodo del inicio de los síntomas hasta la hospitalización y el comprendido entre ésta hasta el fallecimiento fue variable, con tendencia a fallecimiento más precoz en el grupo E.I.-CHD (promedio 14,6 vs 20,6 días en el grupo control). La edad en E.I.-CHD fue mayor (65 versus 62.2 años), con mayor incidencia de las 3 comorbilidades más frecuentes: hipertensión arterial (100% versus 56,25%), diabetes mellitus (75% versus 50%) e insuficiencia cardíaca (75% versus 31,25%). La mortalidad fue 18.75% en el grupo control y 75% en la E.I.-CHD. En los pacientes con E.I.-CHD se aisló: Cándida (50%), Bacilos gram negativo (Stenotrophomonas maltophilia) (25%) y SAMR (25%) mientras que en el grupo control fueron aislados Enterococcus faecalis (25%), Streptococcus viridans (12.5%), Streptococcus spp (6.25%), Staphylococcus aureus (6.25%), Streptococcus grupo C (6.25%), Abiotrophia defectiva (6.25%) y Streptococcus pneumoniae (6.25). En 31.25% de los casos los hemocultivos fue-ron negativos. La localización más frecuente de las vegetaciones en los pacientes con E.I.-CHD correspondió a la pared de AD, sitio de impacto del jet del CHD, en un 100%, seguida por CHD 50%, tricúspide 25% y aórtica 25%. En los controles las localizaciones fueron 75% en válvula aórtica y 25% en válvula mitral. En el grupo de E.I.-CHD, la mitad presentó disfunción sistólica e insuficiencia valvular, mientras que en el grupo control fue predominante la insuficiencia valvular (62,5%) seguida por la perforación de velo (25%). Conclusión: En las E.I.-CHD se aislaron gérmenes asociados a un peor pronóstico (hongos o bacterias atípicas), con altísima mortalidad. La localización principal de las vegetaciones fue en la pared de la aurícula derecha (AD), alrededor de la desembocadura de la vena cava inferior (VCI), sitio de impacto del jet del CHD, y en el tercio distal del catéter. Clinical and echocardiographic findings in patients with infective endocarditis (I.E.) associated to the presence of hemodialysis catheters (HDC) were compared to those in subjects with other types of I.E.

Abstracts: Methods: Between 2009 and 2014 an echocardiographic diagnosis of I.E. was established in 4 subjects with a hemodialysis catheter in place and 16 patients had a common variety of I.E. (controls). Clinical and echocardiographic findings, including echocardiographic modalities were compared between groups. Results: Time from onset of symptoms and time to patient death were shorter in I.E.-HDC patients compared to controls (mean 14.6 vs 20.6 days, respectively. I.E. -HDC patients tended to be older (65.0 vs 62.2 years old). The incidence of main comorbidities was higher in I.E.-HDC: hypertension (100% vs 56.2%), diabetes (75 vs 59%) and heart failure (75% vs 31.2%), respectively. Mortality was much higher in I.E-HDC (74% vs 18%). Infective agents also differed between groups: I.E.-HDC was associate to C albicans (50%), Gram negative rods (Stenotrophomonas maltophilia) (25%) y SAMR (25%). In contrast, the agents involved in controls were E faecalis (25%), S viridans (12.5%), S. group C (6.25%), S aureus (6,25%), group C Streptococcus (6.25%), Abiotrophic defectiva (6.25%) and S pneumoniae (6.25%). Overall, blood cultures were negative in 31.2% patients. Among patients with I.E.-HDC vegetations were most commonly found at the right atrial wall (100%), on the catheter (50%), at the tricuspid valve (25%) and at the aortic valve (25%). In non I.E.-HDC, vegetations were located at the aortic valve (75%) and the mitral valve (25%). Half the patients with I.E.- HDC patients presented ventricular dysfunction and valvular regurgitation while control patients had predominantly valvular insufficiency (62.5%) or leaflet perforation (25%). Conclusion: Mortality in I.E.-HDC patients was very high, associated to the presence of aggressive microbial or fungal agents. Vegetations were most commonly located at the right atrial wall, around de junction with the inferior vena cava and on the catheter itself.

In-vitro study of gonadotrophin signaling pathways in human granulosa cells in relation to progesterone receptor expression.

In humans, data on gonadotrophin-activated (LH, HCG and FSH) progesterone receptor expression and signalling pathways involved in matrix metalloproteinases (MMPs) expression presumably linked to the follicle rupture, are limited. Our hypothesis is LH, HCG and FSH increase progesterone receptor expression in granulosa cells through different signalling pathways, leading to an increased expression of ADAMTS-1 and MMP3/10, which may mediate follicular rupture through the transcription factor, HIF1A. Human granulosa cells were isolated from follicular aspirates obtained from 22 healthy women participating in our IVF programme for male-factor infertility. Progesterone receptor and HIF1A expression was assessed by immunofluorescence, and PKA-PKC-PI3K- ERK1/2, ADAMTS-1 and MMP3/10 expression by Western blot in pre-ovulatory and in cultured granulosa cells. Results show that HCG, LH and FSH regulate progesterone receptor expression and activate PKA, PKC, PI3K and ERK1/2 signalling pathways in granulosa cells but progesterone receptor expression is only mediated by PKA, PKC and ERK pathways. HCG, FSH and LH regulated MMPs expression through progesterone receptors. Moreover, HCG-progesterone-receptor-dependent HIF1A expression stimulated MMP3/10 expression but not that of ADAMTS-1. These results suggest differential downstream progesterone receptor signalling, as progesterone receptor regulates MMP3/10 expression via HIF1A, which is not involved in ADAMTS-1 expression.

Medición del NGAL urinario en el donante para detectar función retardada del injerto renal en el receptor / NGAL as a marker to detect donor risk factors for delayed graft function

Resumen Introducciónen el trasplante renal de donante fallecido es importante tener marcadores tempranos que ayuden a predecir la funcionalidad adecuada del injerto renal. La medición de creatinina continóa siendo el marcador de elección para definir si los riñones de un posible donante son aptos para ser trasplantados. La lipocalina asociada a la gelatinasa del neutrófilo urinaria (NGALu) es un biomarcador que ha sido utilizado para el diagnóstico temprano de lesión renal aguda, pero su comportamiento es incierto en el donante fallecido. Este estudio tiene como objetivo determinar si los niveles de NGALu del donante pueden predecir la función retardada del injerto (FRI) en los receptores. Métodología: cohorte prospectiva en la que se evaluaron los niveles de NGALu del donante al momento de la extracción renal; se aplicó estadística descriptiva y pruebas no paramétricas. Se exploró el comportamiento de este biomarcador en el donante del injerto renal para determinar si es un factor predictivo de función retardada del injerto. Resultados: se evaluaron 27 donantes de criterios óptimos; el 74,1 % eran hombres, la edad tuvo una mediana de 27 años (rango: 18,8-43,3); la principal causa de muerte fue trauma encefalocraneano, seguido por el accidente cerebrovascular. La creatinina tuvo una mediana de 0,8 mg/dl y los valores de NGALu tuvieron una mediana de 11,1ng/ml (4,2-33,6). En total se realizaron 46 trasplantes, de los cuales el 15,2 % presentaron función retardada del injerto y dos pacientes necesitaron terapia de reemplazo renal en la primera semana luego del trasplante. Los valores de NGALu agrupados de acuerdo a presencia o no de función retardada del injerto fueron de 11,1 ng/ml (3-17,3) en los pacientes sin función retardada del injerto y 11,2 ng/ml en los pacientes con dicha función (7,7-39,4) (p=0,40). En el análisis multivariado no se encontró ningón factor asociado al desarrollo de función retardada del injerto. Conclusión: en este estudio la medición de uNGAL en donantes fallecidos de criterios óptimos no predijo función retardada del injerto.

Abstract Introduction: For deceased donor renal transplantation, it is important to have early markers that can predict the functional outcome of the transplant. Currently, creatinine is the marker of choice for determining whether a potential donor's kidneys are suitable for transplantation. Urine neutrophil gelatinase-associated lipocalin (uNGAL) is a biomarker that has been utilized to diagnose early-stage acute kidney injury, but its behavior in deceased donors is uncertain. The objective of this study was to determine whether donor uNGAL levels can predict delayed graft function in recipients. Methodology: A prospective cohort utilizing descriptive statistics and non-parametric median tests was carried out to evaluate donor uNGAL levels at the time of kidney removal. The behavior of this biomarker was analyzed in kidney transplant donors to evaluate its use as a predictive factor for DGF. Results: A total of 27 standard criteria transplants were evaluated, including 7 (25.9%) women and 20 (74.1%) men with a median age of 27 years (18.75-43.25). The principal cause of death was traumatic head injury, followed by stroke. The median creatinine level was 0.8 mg/dl (0.57-1), and the median uNGAL level was 11.1 ng/ml (4.2-33.6). In total, 46 transplants were performed, of which 15.22% (7 patients) presented with delayed graft function and 2 patients needed renal replacement therapy within the first week after transplantation. The patients were grouped according to the presence of DGF, with median uNGAL values of 11.1 ng/ml (3-17.3) in patients without DGF and median values of 11.2 ng/ml (7.7-39.4) (p=0.4) in those with delayed graft function. No factors were found to be associated with the development of delayed graft function in the multivariate analysis. Discussion: in this study, uNGAL measurements in deceased standard criteria donors did not predict delayed graft function.

[Clinical consequences of using the new cardiovascular risk tables SCORE OP in patients aged over 65 years]. / Consecuencias clínicas de la utilización de las nuevas tablas de riesgo cardiovascular SCORE OP para pacientes mayores de 65 años.

BACKGROUND AND OBJECTIVE: Estimating cardiovascular risk with SCORE is not recommended in persons over 65 years. SCORE investigators have recently published specific tables for older people (SCORE Older Persons [SCORE OP]). The aim of this study is to assess the impact of using SCORE OP tables on a Spanish population aged over 64 years, and compare it with the use of SCORE in patients aged 65-69 years. PATIENTS AND METHOD: Cross-sectional study carried out in 2 urban primary health care centres. Individuals between 65 and 85 years old without diabetes or established cardiovascular diseases were included. Cardiovascular risk using SCORE and the new SCORE OP tables for low risk countries was calculated. RESULTS: Cardiovascular risk was estimated in 3,425 patients. Mean values of the original SCORE and SCORE OP were 4.08 and 3.83, respectively in the group of patients aged 65-69 years old (n=974, 22.44%) (P< .001). The percentage of patients at high or very high risk was 25.46% and 22.90% with the original SCORE and the SCORE OP, respectively (P<.001). Using the original SCORE, 16.43% of the total patients should potentially be treated with lipid lowering drugs, while using the SCORE OP, 13.45% of the patients aged 65-69 years should potentially be treated. Using SCORE OP in patients older than 69 years, 61.49% patients should potentially be treated with lipid lowering drugs. CONCLUSIONS: SCORE OP identifies fewer patients at high or very high risk than the original SCORE, therefore, its utilization would imply treating fewer patients of this age with lipid lowering drugs.

Estrogen metabolites in human corpus luteum physiology: differential effects on angiogenic activity.

OBJECTIVE: To determine tissue concentrations of E2, estrone, P, and estrogens metabolites (EMs) 2-methoxyestradiol, 2-methoxyestrone, 4-hydroxyestrone, and 16-ketoestradiol in corpus luteum (CL) of different ages, and after hCG administration; and to examine the effects of EMs on vascular endothelial growth factor (VEGF) secretion and angiogenic activity released by cultured luteinizing granulosa cells in the presence and absence of hCG. DESIGN: Experimental study. SETTING: University. PATIENT(S): Thirty-two healthy women of reproductive age. INTERVENTION(S): Corpus luteum was collected at the time of minilaparotomy for tubal sterilization, at varying stages of the luteal phase (LP). Late-LP CL was collected 24 hours after IM administration of 10,000 IU hCG. Granulosa cells were isolated from follicular aspirates obtained from healthy women participating in our IVF program for male factor infertility. MAIN OUTCOMES MEASURE(S): Estrogen metabolite concentrations were determined in CL tissue, and VEGF was assessed in conditioned medium. The angiogenic activity was analyzed by bioassay. RESULT(S): Concentrations of EMs with proangiogenic activity (16-ketoestradiol and 4-hydroxyestrone) were higher in early and mid-LP CL vs. late-LP CL. These EMs and hCG increased VEGF production and angiogenic activity. Conversely, late-LP CL had significantly higher levels of 2-methoxyestrone and 2-methoxyestradiol, which have antiangiogenic activity. Administration of hCG reduced the production of these EMs. CONCLUSION(S): Our findings suggest that the EMs are important paracrine modulators of CL function. Administration of hCG increases the production of EMs with proangiogenic activity and reduces the secretion of those EMs with antiangiogenic action, suggesting a novel mechanism by which the late-LP CL is rescued in conception cycles.

Silencing of tumor suppressor genes RASSF1A, SLIT2, and WIF1 by promoter hypermethylation in hereditary breast cancer.

Promoter hypermethylation is gaining strength as one of the main mechanisms through which tumor suppressor genes are silenced during tumor progression. Three tumor suppressor genes are frequently found methylated in their promoter, in concordance with absence of expression, RASSF1A, SLIT2, and WIF1. In addition, a previous array-CGH analysis from our group showed that these genes are found in deleted genomic regions observed in hereditary breast cancer tumors. In the present work we analyzed the methylation status of these three tumor suppressor gene promoters in 47 hereditary breast cancer tumors. Promoter methylation status analysis of hereditary breast tumors revealed high methylation frequencies for the three genes (67% RASSF1A, 80% SLIT2, and 72% WIF1). Additionally, the presence of methylated PCR products was associated with absence of protein expression for the three genes and statistically significant for RASSF1A and WIF1. Interestingly, methylation of all the three genes was found in 4 out of 6 grade I invasive ductal carcinoma tumors. Association between RASSF1A methylation and DCIS tumors was found. These results suggest that silencing of these tumor suppressor genes is an early event in hereditary breast cancer, and could be a marker for pre-malignant phenotypes.