Light Scattering by Vitreous of Humans With Vision Degrading Myodesopsia From Floaters.

Purpose: Vision-degrading myodesopsia (VDM) from vitreous floaters significantly degrades vision and impacts visual quality of life (VQOL), but the relationship to light scattering is poorly understood. This study compared in vitro measures of light scatter and transmission in surgically excised human vitreous to preoperative indexes of vitreous structure, visual function, and VQOL. Methods: Pure vitreous collected during vitrectomy from 8 patients with VDM had wide-angle straylight measurements and dark-field imaging, performed within 36 hours of vitrectomy. Preoperative VQOL assessment with VFQ-25, contrast sensitivity (CS) measurements with Freiburg acuity contrast testing, and quantitative ultrasonography were compared to light scattering and transmission in vitro. Results: All indices of vitreous echodensity in vivo correlated positively with straylight at 0.5° (R = 0.708 to 0.775, P = 0.049 and 0.024, respectively). Straylight mean scatter index correlated with echodensity (R = 0.71, P = 0.04) and VQOL (R = -0.82, P = 0.0075). Dark-field measures in vitro correlated with degraded CS in vivo (R = -0.69, P = 0.04). VQOL correlated with straylight mean scatter index (R = -0.823, P = 0.012). Conclusions: Increased vitreous echodensity in vivo is associated with more straylight scattering in vitro, validating ultrasonography as a clinical surrogate for light scattering. Contrast sensitivity in vivo is more degraded in the presence of dark-field scattering in vitro and VQOL is decreased in patients whose vitreous has increased light scattering. These findings could form the basis for the development of optical corrections for VDM or support new laser treatments, as well as novel pharmacotherapy.

Towards a common European ethical and legal framework for conducting clinical research: the GATEKEEPER experience.

This paper examines the ethical and legal challenges encountered during the GATEKEEPER Project and how these challenges informed the development of a comprehensive framework for future Large-Scale Pilot (LSP) projects. GATEKEEPER is a LSP Project with 48 partners conducting 30 implementation studies across Europe with 50,000 target participants grouped into 9 Reference Use Cases. The project underscored the complexity of obtaining ethical approval across various jurisdictions with divergent regulations and procedures. Through a detailed analysis of the issues faced and the strategies employed to navigate these challenges, this study proposes an ethical and legal framework. This framework, derived from a comparative analysis of ethical application forms and regulations, aims to streamline the ethical approval process for future LSP research projects. By addressing the hurdles encountered in GATEKEEPER, the proposed framework offers a roadmap for more efficient and effective project management, ensuring smoother implementation of similar projects in the future.

KIS counteracts PTBP2 and regulates alternative exon usage in neurons.

Alternative RNA splicing is an essential and dynamic process in neuronal differentiation and synapse maturation, and dysregulation of this process has been associated with neurodegenerative diseases. Recent studies have revealed the importance of RNA-binding proteins in the regulation of neuronal splicing programs. However, the molecular mechanisms involved in the control of these splicing regulators are still unclear. Here, we show that KIS, a kinase upregulated in the developmental brain, imposes a genome-wide alteration in exon usage during neuronal differentiation in mice. KIS contains a protein-recognition domain common to spliceosomal components and phosphorylates PTBP2, counteracting the role of this splicing factor in exon exclusion. At the molecular level, phosphorylation of unstructured domains within PTBP2 causes its dissociation from two co-regulators, Matrin3 and hnRNPM, and hinders the RNA-binding capability of the complex. Furthermore, KIS and PTBP2 display strong and opposing functional interactions in synaptic spine emergence and maturation. Taken together, our data uncover a post-translational control of splicing regulators that link transcriptional and alternative exon usage programs in neuronal development.

Anesthetic management of pulmonary artery banding in adult patient with single ventricle and uncorrected transposition of the great arteries.

Pulmonary artery banding (PAB) is a procedure mainly performed during the neonatal period as an initial stage to definitive palliative reconstruction, a scenario in which the criteria for banding adjustment are well defined. However, the indication for BAP in the adult is extraordinarily rare, even more in patients with single ventricle and unrepaired transposition of the great arteries (TGA), and there are no established criteria for banding adjustment. Due to the small number of these procedures, there is limited experience in their anesthetic management and complications. We describe a case of a 29-year-old patient diagnosed with a cyanotic congenital heart disease of double-inlet left ventricle with TGA and unrepaired mitral stenosis, who underwent to a hybrid procedure of PAB and enlargement of the communication between the two atria.

Racial and Ethnic Minorities Underrepresented in Pain Management Guidelines for Total Joint Arthroplasty: A Meta-analysis.

BACKGROUND: Total joint arthroplasty aims to improve quality of life and functional outcomes for all patients, primarily by reducing their pain. This goal requires clinical practice guidelines (CPGs) that equitably represent and enroll patients from all racial/ethnic groups. To our knowledge, there has been no formal evaluation of the racial/ethnic composition of the patient population in the studies that informed the leading CPGs on the topic of pain management after arthroplasty surgery. QUESTIONS/PURPOSES: Using papers included in the 2021 Anesthesia and Analgesia in Total Joint Arthroplasty Clinical Practice Guidelines and comparing them with US National census data, we asked: (1) What is the representation of racial/ethnic groups in randomized controlled trials compared with their representation in the US national population? (2) Is there a relationship between the reporting of racial/ethnic groups and year of data collection/publication, location of study, funding source, or guideline section? METHODS: Participant demographic data (study year published, study type, guideline section, year of data collection, study site, study funding, study size, gender, age, and race/ethnicity) were collected from articles cited by this guideline. Studies were included if they were full text, were primary research articles conducted primarily within the United States, and if they reported racial and ethnic characteristics of the participants. The exclusion criteria included duplicate articles, articles that included the same participant population (only the latest dated article was included), and the following article types: systematic reviews, nonsystematic reviews, terminology reports, professional guidelines, expert opinions, population-based studies, surgical trials, retrospective cohort observational studies, prospective cohort observational studies, cost-effectiveness studies, and meta-analyses. Eighty-two percent (223 of 271) of articles met inclusion criteria. Our original literature search yielded 27 papers reporting the race/ethnicity of participants, including 24 US-based studies and three studies conducted in other countries; only US-based studies were utilized as the focus of this study. We defined race/ethnicity reporting as the listing of participants' race or ethnicity in the body, tables, figures, or supplemental data of a study. National census information from 2000 to 2019 was then used to generate a representation quotient (RQ), which compared the representation of racial/ethnic groups within study populations to their respective demographic representation in the national population. An RQ value greater than 1 indicates an overrepresented group and an RQ value less than 1 indicates an underrepresented group, relative to the US population. Primary outcome measures of RQ value versus time of publication for each racial/ethnic group were evaluated with linear regression analysis, and race reporting and manuscript parameters were analyzed with chi-square analyses. RESULTS: Two US-based studies reported race and ethnicity independently. Among the 24 US-based studies reporting race/ethnicity, the overall RQ was 0.70 for Black participants, 0.09 for Hispanic participants, 0.1 for American Indian/Alaska Natives, 0 for Native Hawaiian/Pacific Islanders, 0.08 for Asian participants, and 1.37 for White participants, meaning White participants were overrepresented by 37%, Black participants were underrepresented by 30%, Hispanic participants were underrepresented by 91%, Asian participants were underrepresented by 92%, American Indian/Alaska Natives were 90% underrepresented, and Native Hawaiian Pacific Islanders were virtually not represented compared with the US national population. On chi-square analysis, there were differences between race/ethnicity reporting among studies with academic, industry, and dual-supported funding sources (χ2 = 7.449; p = 0.02). Differences were also found between race/ethnicity reporting among US-based and non-US-based studies (χ2 = 36.506; p < 0.001), with 93% (25 of 27) of US-based studies reporting race as opposed to only 7% (2 of 27) of non-US-based studies. Finally, there was no relationship between race/ethnicity reporting and the year of data collection or guideline section referenced. CONCLUSION: The 2021 Anesthesia and Analgesia in Total Joint Arthroplasty Clinical Practice Guidelines provide evidence-based recommendations that reflect the current standards in orthopaedic surgery, but the studies upon which they are based overwhelmingly underenroll and underreport racial/ethnic minorities relative to their proportions in the US population. As these factors impact analgesic administration, their continued neglect may perpetuate inequities in outcomes after TJA. CLINICAL RELEVANCE: Our study demonstrates that all non-White racial/ethnic groups were underrepresented relative to their proportion of the US population in the 2021 Anesthesia and Analgesia in Total Joint Arthroplasty Clinical Practice Guidelines, underscoring a weakness in the orthopaedic surgery evidence base and questioning the overall external validity and generalizability of these combined CPGs. An effort should be made to equitably enroll and report outcomes for all racial/ethnic groups in any updated CPGs.

Non-clinical toxicity and immunogenicity evaluation of a Plasmodium vivax malaria vaccine using Poly-ICLC (Hiltonol®) as adjuvant.

Malaria caused byPlasmodium vivaxis a pressing public health problem in tropical and subtropical areas.However, little progress has been made toward developing a P. vivaxvaccine, with only three candidates being tested in clinical studies. We previously reported that one chimeric recombinant protein (PvCSP-All epitopes) containing the conserved C-terminus of the P. vivax Circumsporozoite Protein (PvCSP), the three variant repeat domains, and aToll-like receptor-3 agonist,Poly(I:C), as an adjuvant (polyinosinic-polycytidylic acid, a dsRNA analog mimicking viral RNA), elicits strong antibody-mediated immune responses in mice to each of the three allelic forms of PvCSP. In the present study, a pre-clinical safety evaluation was performed to identify potential local and systemic toxic effects of the PvCSP-All epitopes combined with the Poly-ICLC (Poly I:C plus poly-L-lysine, Hiltonol®) or Poly-ICLC when subcutaneously injected into C57BL/6 mice and New Zealand White Rabbits followed by a 21-day recovery period. Overall, all observations were considered non-adverse and were consistent with the expected inflammatory response and immune stimulation following vaccine administration. High levels of vaccine-induced specific antibodies were detected both in mice and rabbits. Furthermore, mice that received the vaccine formulation were protected after the challenge with Plasmodium berghei sporozoites expressing CSP repeats from P. vivax sporozoites (Pb/Pv-VK210). In conclusion, in these non-clinical models, repeated dose administrations of the PvCSP-All epitopes vaccine adjuvanted with a Poly-ICLC were immunogenic, safe, and well tolerated.

Head-mounted adaptive optics visual simulator.

Adaptive optics visual simulation is a powerful tool for vision testing and evaluation. However, the existing instruments either have fixed tabletop configurations or, being wearable, only offer the correction of defocus. This paper proposes a novel head-mounted adaptive optics visual simulator that can measure and modify complex ocular aberrations in real-time. The prototype is composed of two optical modules, one for the objective assessment of aberrations and the second for wavefront modulation, all of which are integrated into a wearable headset. The device incorporates a microdisplay for stimulus generation, a liquid crystal on silicon (LCoS) spatial light modulator for wavefront manipulation, and a Hartmann-Shack wavefront sensor. Miniature optical components and optical path folding structures, together with in-house 3D printed mounts and housing, were adapted to realize the compact size. The system was calibrated by characterizing and compensating the internal aberrations of the visual relay. The performance of the prototype was analyzed by evaluating the measurement and compensation of low-order and higher-order aberrations induced through trial lenses and phase masks in an artificial eye. The defocus curves for a simulated bifocal diffractive lens were evaluated in real eyes. The results show high accuracy while measuring and compensating for the induced defocus, astigmatism, and higher-order aberrations, whereas the MTF analysis shows post-correction resolution of up to 37.5 cycles/degree (VA 1.25). Moreover, the subjective test results show the defocus curves closely matched to a commercial desktop visual simulator.

Miastenia gravis y enfermedad de Alzheimer: una asociación a estudio / Association between myasthenia gravis and Alzheimer’s disease

Introducción La miastenia gravis (MG) y la enfermedad de Alzheimer (EA) son dos de las enfermedades neurológicas en cuya fisiopatología interviene la acetilcolina en distintos niveles. En la primera, la alteración de este neurotransmisor se produce en la unión neuromuscular, y en la segunda, en el sistema nervioso central. Objetivo Analizar la posible relación entre dichas patologías estudiando la prevalencia y la odds ratio de la EA dentro de los pacientes diagnosticados de MG con respecto a la prevalencia de EA en la población general. Pacientes y métodos Se han examinado datos de las historias clínicas electrónicas del sistema de salud de Castilla-La Mancha utilizando el procesamiento de lenguaje natural a través de la plataforma clínica de inteligencia artificial Savana Manager?. Resultados Se ha identificado a 970.503 pacientes mayores de 60 años, de los que 1.028 tenían diagnóstico de MG. La proporción de pacientes con diagnóstico de EA dentro de este grupo (4,28%) es mayor que en el resto de la población (2,82%; p = 0,0047), con una odds ratio de 1,54 (intervalo de confianza al 95%: 1,13-2,08; p = 0,0051), sin que se encuentren diferencias significativas en el análisis bivariante del resto de los factores de riesgo para EA más importantes conocidos hasta ahora. Conclusiones Nuestros resultados sugieren que podría existir un aumento de la prevalencia de EA en pacientes con MG. (AU)

INTRODUCTION Myasthenia gravis (MG) and Alzheimer’s disease (AD) are two of the most important diseases where the dysregulation of acetylcholine activity plays a crucial role. In the first, this dysregulation happens at the level of the neu­romuscular junction and in the second, in the central nervous system (CNS). AIM To analyze the possible relationship between these two pathologies, analyzing the prevalence and the odds ratio of AD within patients previously diagnosed with MG. We will compare these data with respect to the prevalence of AD in the general population. PATIENTS AND METHODS We examined the data obtained by the electronic medical records of patients in the health care system of Castilla La Mancha using the Natural Language Process provided by a clinical platform of artificial intelligence known as the Savana Manager?. RESULTS We identified 970,503 patients over the age of 60 years, of which 1,028 were diagnosed with MG. The proportion of the patients diagnosed with AD within this group (4.28%) was greater than the rest of the population (2.82%) (p = 0,0047) with an odds ratio of 1.54 (confidence interval at 95% 1.13-2.08; p = 0.0051) without finding significant differences in the bivariate analysis for the rest of the most important actual known risk factors for AD. CONCLUSION. Our results suggest that there might be an increase in the prevalence of AD in patients previously diagnosed with MG. (AU)

Chromosome ends and the theory of marginotomy: implications for reproduction.

Telomeres are the protective structures located at the ends of linear chromosomes. They were first described in the 1930s, but their biology remained unexplored until the early 70s, when Alexey M. Olovnikov, a theoretical biologist, suggested that telomeres cannot be fully copied during DNA replication. He proposed a theory that linked this phenomenon with the limit of cell proliferation capacity and the "duration of life" (theory of marginotomy), and suggested a potential of telomere lenghthening for the prevention of aging (anti-marginotomy). The impact of proliferative telomere shortening on life expectancy was later confirmed. In humans, telomere shortening is counteracted by telomerase, an enzyme that is undetectable in most adult somatic cells, but present in cancer cells and adult and embryonic stem and germ cells. Although telomere length dynamics are different in male and female gametes during gametogenesis, telomere lengths are reset at the blastocyst stage, setting the initial length of the species. The role of the telomere pathway in reproduction has been explored for years, mainly because of increased infertility resulting from delayed childbearing. Short telomere length in ovarian somatic cells is associated to decreased fertility and higher aneuploidy rates in embryos. Consequently, there is a growing interest in telomere lengthening strategies, aimed at improving fertility. It has also been observed that lifestyle factors can affect telomere length and improve fertility outcomes. In this review, we discuss the implications of telomere theory in fertility, especially in oocytes, spermatozoa, and embryos, as well as therapies to enhance reproductive success.

Optimization of a rapid method for screening drugs in blood by liquid chromatography tandem mass spectrometry.

Objectives: In the recent years, liquid chromatography with tandem mass spectrometry has gained popularity in laboratories. This technique has a higher specificity, detects different analytes from a single specimen, measures analytes in distinct matrices, and substantially reduce analytical interference, with respect to immunoassay. The processing and preparation of biological samples are crucial in chromatography. Interferences in blood testing are usually caused by the presence of phospholipids and proteins. The main objective of this study was to improve analytical processes for drug screening by LC-MS/MS using a novel blood sample preparation method based on protein precipitation and removal of phospholipids. Methods: An evaluation was performed of a new method for the preparation of blood samples based on protein precipitation and removal of phospholipids by LC-Q-q-LIT. Results: Limit of detection, limit of quantification and measurement range were determined for 56 molecules. The results of 11 cases were compared with those obtained using standard blood collection methods and instruments. Conclusions: The novel blood preparation and testing method based on LC-Q-q-LIT, a more sensitive technique, has demonstrated to yield comparable results to traditional methods. In addition, this new technique reduces turnaround time and costs.

Dietary Diversity and Its Association with Diet Quality and Health Status of European Children, Adolescents, and Adults: Results from the I.Family Study.

Dietary diversity (DD) plays a crucial role in fostering high-quality diets, but its association with health outcomes, particularly body adiposity and non-communicable diseases (NCDs), is inconsistent. This may be due to a lack of a standardized method for estimating DD. Our study investigates the association between two DD indices, namely the dietary diversity score (DDS) and food variety score (FVS), and anthropometric measures, biochemical parameters, and diet quality in a large population sample from the I.Family study across research centers in eight European countries. In our cross-sectional analysis of 3035 participants, DDSs varied among countries, with a higher prevalence in the third DDS tertile among those with higher education. DDS showed a positive association with diet quality across all age groups. Higher DDS tertile individuals showed increased fiber, fruit, and vegetable intake, greater meal frequency, and lower ultra-processed food consumption. No relevant biochemical differences were observed across DDS tertiles, and a higher DDS was associated with lower overweight/obesity prevalence only in adults. No significant associations were found with FVS. Our findings emphasize the need to consider food groups for a more accurate estimation of diet quality. This aligns with studies suggesting DDS alone is not an independent risk factor for obesity in children and adolescents. Public health programs should prioritize food diversity to promote improved nutrition and overall well-being in communities.

Upscaling the effect of traits in response to drought: The relative importance of safety-efficiency and acquisitive-conservation functional axes.

We tested the idea that functional trade-offs that underlie species tolerance to drought-driven shifts in community composition via their effects on demographic processes and subsequently on shifts in species' abundance. Using data from 298 tree species from tropical dry forests during the extreme ENSO-2015, we scaled-up the effects of trait trade-offs from individuals to communities. Conservative wood and leaf traits favoured slow tree growth, increased tree survival and positively impacted species abundance and dominance at the community-level. Safe hydraulic traits, on the other hand, were related to demography but did not affect species abundance and communities. The persistent effects of the conservative-acquisitive trade-off across organizational levels is promising for generalization and predictability of tree communities. However, the safety-efficient trade-off showed more intricate effects on performance. Our results demonstrated the complex pathways in which traits scale up to communities, highlighting the importance of considering a wide range of traits and performance processes.

Predictors of Preexposure Prophylaxis Eligibility among Pregnant People with Opioid Use Disorder.

OBJECTIVE: We seek to evaluate risk factors for eligibility for preexposure prophylaxis (PrEP) among pregnant people with opioid use disorder (OUD). STUDY DESIGN: This is a single-site retrospective cohort study of pregnant people admitted for management of OUD at an urban, tertiary care center from 2013 to 2022. PrEP eligibility was defined based on (1) modified American College of Obstetricians and Gynecologists' (ACOG) 2014 criteria: diagnosis of a sexually transmitted infection (STI), engagement in transactional sex work, intravenous drug use (IVDU), or incarceration and (2) modified 2021 Centers for Disease Control (CDC) criteria: diagnosis of bacterial STI (e.g., gonorrhea or syphilis) or transactional sex work. Risk factors associated with PrEP eligibility were evaluated using chi- square or Fischer's exact tests for categorical variables and t-tests or Wilcoxon rank-sum tests for continuous variables. Multivariable regression was used to control for confounding covariates, defined as p < 0.10 on bivariate analysis. p < 0.05 was used to indicate statistical significance. RESULTS: A total of 132 individuals met inclusion criteria, of whom 101 (76.5%) were deemed eligible for PrEP by meeting one or more modified 2014 ACOG criteria: 42 (31.8%) were incarcerated or had one or more STIs, while 30 (22.7%) endorsed engaging in transactional sex work and 68 (58.6%) endorsed IVDU. Using modified 2021 CDC criteria, 37 (28%) met PrEP eligibility, with 12 (9.1%) diagnosed specifically with a bacterial STI and 30 (22.7%) engaging in transactional sex work. Only comorbid psychiatric illness was associated with an increased risk for PrEP eligibility based on 2014 criteria, which persisted after controlling for maternal race/ethnicity (aRR 1.52, 95% confidence interval [CI] 1.24-1.86), and 2021 criteria, which persisted after controlling for nulliparity (aRR 2.12, 95% CI 1.30-3.57). CONCLUSION: A significant number of pregnant people with OUD meet one or more criteria for PrEP, with comorbid psychiatric conditions increasing the risk of meeting criteria. KEY POINTS: · Comorbid psychiatric illness is significantly associated with high risk of PrEP eligibility.. · A large proportion of pregnant individuals with active OUD meet criteria for PrEP prescribing.. · Risk-based screening algorithms for PrEP eligibility have limitations..

Comparing Mitochondrial Activity, Oxidative Stress Tolerance, and Longevity of Thirteen Ascomycota Yeast Species.

Aging is characterized by a number of hallmarks including loss of mitochondrial homeostasis and decay in stress tolerance, among others. Unicellular eukaryotes have been widely used to study chronological aging. As a general trait, calorie restriction and activation of mitochondrial respiration has been proposed to contribute to an elongated lifespan. Most aging-related studies have been conducted with the Crabtree-positive yeasts Saccharomyces cerevisiae and Schizosaccharomyces pombe, and with deletion collections deriving from these conventional yeast models. We have performed an unbiased characterization of longevity using thirteen fungi species, including S. cerevisiae and S. pombe, covering a wide range of the Ascomycota clade. We have determined their mitochondrial activity by oxygen consumption, complex IV activity, and mitochondrial redox potential, and the results derived from these three methodologies are highly overlapping. We have phenotypically compared the lifespans of the thirteen species and their capacity to tolerate oxidative stress. Longevity and elevated tolerance to hydrogen peroxide are correlated in some but not all yeasts. Mitochondrial activity per se cannot anticipate the length of the lifespan. We have classified the strains in four groups, with members of group 1 (Kluyveromyces lactis, Saccharomyces bayanus and Lodderomyces elongisporus) displaying high mitochondrial activity, elevated resistance to oxidative stress, and elongated lifespan.

Perioperative Myocardial Infarction Following Dabigatran Reversal With Idarucizumab in a Patient Undergoing Orthotopic Liver Transplantation.

Insufficient information is available regarding the administration of anticoagulants, specifically direct oral anticoagulants, in individuals with cirrhosis awaiting liver transplantation. In this report, we present a case of a 66-year-old male with atrial fibrillation treated with dabigatran who received idarucizumab prior to orthotopic liver transplantation. Hemostatic status was monitored throughout the procedure with both conventional hemostatic tests and point-of-care viscoelastic hemostatic assays. The patient suffered an intraoperative myocardial infarction, which could be related to the use of idarucizumab.

The impact of mutational clonality in predicting the response to immune checkpoint inhibitors in advanced urothelial cancer.

Immune checkpoint inhibitors (ICI) have revolutionized cancer treatment and can result in complete remissions even at advanced stages of the disease. However, only a small fraction of patients respond to the treatment. To better understand which factors drive clinical benefit, we have generated whole exome and RNA sequencing data from 27 advanced urothelial carcinoma patients treated with anti-PD-(L)1 monoclonal antibodies. We assessed the influence on the response of non-synonymous mutations (tumor mutational burden or TMB), clonal and subclonal mutations, neoantigen load and various gene expression markers. We found that although TMB is significantly associated with response, this effect can be mostly explained by clonal mutations, present in all cancer cells. This trend was validated in an additional cohort. Additionally, we found that responders with few clonal mutations had abnormally high levels of T and B cell immune markers, suggesting that a high immune cell infiltration signature could be a better predictive biomarker for this subset of patients. Our results support the idea that highly clonal cancers are more likely to respond to ICI and suggest that non-additive effects of different signatures should be considered for predictive models.

Desenlaces maternos y neonatales en gestantes con cardiopatía con evaluación única vs. evaluación semiestructurada por un equipo cardio-obstétrico / Maternal and neonatal outcomes in pregnant women with heart disease with single evaluation vs. semi-structured evaluation by a cardio-obstetric team

Resumen Introducción: Las enfermedades cardiovasculares en las gestantes son desafiantes, con alta morbimortalidad materna y perinatal, por lo que se recomienda un equipo cardio-obstétrico para su atención. Aun así, pocos datos evalúan el impacto de estos equipos. Por lo tanto, el presente estudio tiene como objetivo comparar los resultados obstétricos, maternos y neonatales del seguimiento semiestructurado (SSE) en una clínica cardio-obstétrica con respecto a un seguimiento usual o seguimiento no estructurado (SNE) en gestantes con enfermedad cardiaca. Métodos: Se realizó un registro prospectivo de gestantes con cardiopatías. Se compararon las pacientes con SSE por un equipo cardio-obstétrico, contra aquellas con evaluación única o SNE. Se calculó el riesgo de eventos según la clasificación de la Organización Mundial de la Salud modificado (OMSm) y la escala del Cardiac Disease in Pregnancy Study II (CARPREG-II) y se evaluaron los desenlaces cardiacos, obstétricos y neonatales. Resultados: Se evaluaron 168 pacientes, 37 con SSE y 131 con evaluación única (SNE). Los principales diagnósticos fueron cardiopatía congénita, arritmias y valvulopatías. La media del CARPREG-II en pacientes de SNE fue 2.48 (DE: 2.3) y en pacientes de SSE fue 3.37 (DE: 2.45; p = 0.041). La media de la OMSm en pacientes de SNE fue 2.1 (DE: 1.6) y con SSE fue 2.65 (DE: 0.95; p = 0.0052). No hubo diferencias significativas en los desenlaces cardiacos primarios (13.8% en SNE vs. 5.4% en SSE; p = 0.134), cardiacos secundarios (5.3 en SNE vs. 2.7 en SSE; p = 0.410), obstétricos (10% en SNE vs. 16.2% en SSE; p = 0.253) y neonatales (35.9% en SNE y 40.5% en SSE; p = 0.486) a pesar de que las pacientes con SSE tenían un riesgo mayor que las pacientes con SNE según las escalas de la OMSm y el CARPREG-II. Conclusiones: En gestantes con cardiopatía, un SSE comparado con un SNE por un equipo cardio-obstétrico no mostró diferencias estadísticamente significativas en los desenlaces cardiovasculares, obstétricos y neonatales, a pesar de que las pacientes con SSE tenían un riesgo significativamente más alto de desenlaces adversos por las escalas de la OMSm y el CARPREG-II. Esto sugiere que el SSE logra al menos equiparar los desenlaces a pesar del mayor riesgo de eventos adversos que tenían las pacientes de este grupo.

Abstract Introduction: Cardiovascular diseases in pregnant women are challenging, with high maternal and perinatal morbidity and mortality, so a cardio-obstetric team is recommended for their care. Even so, little data evaluates the impact of these teams. Therefore, the present study aims to compare the obstetric, maternal, and neonatal outcomes of semi-structured follow-up (SSF) in a Cardio-obstetric clinic concerning regular or unstructured follow-up (USF) in pregnant women with heart disease. Methods: A prospective registry of pregnant women with heart disease was carried out. Patients with SSF by a cardio-obstetric team were compared with those with single evaluation or USF. The risk of events was calculated according to the modified World Health Organization (mWHO) classification and the CARPREG-II scale, and cardiac, obstetric, and neonatal outcomes were evaluated. Results: One hundred sixty-eight patients were evaluated, 37 with SSF and 131 with single evaluation (USF). The primary diagnoses were congenital heart disease, arrhythmias, and valve disease. The average CARPREG-II in USF patients was 2.48 (SD 2.3); in SSF patients, it was 3.37 (SD 2.45; p = 0.041). The average of the mWHO in patients with USF was 2.1 (SD 1.6), and with SSF, it was 2.65 (SD 0.95; p = 0.0052). There were no significant differences in primary cardiac outcomes (13.8% in USF vs. 5.4% in SSF; p = 0.134), secondary cardiac (5.3% in USF vs. 2.7% in SSF; p = 0.410), obstetric (10% in USF vs. 16.2% in SSF; p = 0.253) and neonatal (35.9% in USF and 40.5% in SSF; p = 0.486) even though patients with SSF had a higher risk than patients with USF according to the mWHO and CARPREG-II scales. Conclusions: In pregnant women with heart disease, an SSF compared with a USF by a cardio-obstetric team did not show statistically significant differences in cardiovascular, obstetric, and neonatal outcomes. However, patients with SSF had a significantly higher risk of adverse outcomes due to the mWHO and CARPREG-II scales. This result suggests that the SSF achieves at least equal outcomes despite the higher risk of adverse events that patients in this group had.

Maternal and neonatal outcomes in pregnant women with heart disease with single evaluation vs. semi-structured evaluation by a cardio-obstetric team.

INTRODUCTION: Cardiovascular diseases in pregnant women are challenging, with high maternal and perinatal morbidity and mortality, so a cardio-obstetric team is recommended for their care. Even so, little data evaluates the impact of these teams. Therefore, the present study aims to compare the obstetric, maternal, and neonatal outcomes of semi-structured follow-up (SSF) in a Cardio-obstetric clinic concerning regular or unstructured follow-up (USF) in pregnant women with heart disease. METHODS: A prospective registry of pregnant women with heart disease was carried out. Patients with SSF by a cardio-obstetric team were compared with those with single evaluation or USF. The risk of events was calculated according to the modified World Health Organization (mWHO) classification and the CARPREG-II scale, and cardiac, obstetric, and neonatal outcomes were evaluated. RESULTS: One hundred sixty-eight patients were evaluated, 37 with SSF and 131 with single evaluation (USF). The primary diagnoses were congenital heart disease, arrhythmias, and valve disease. The average CARPREG-II in USF patients was 2.48 (SD 2.3); in SSF patients, it was 3.37 (SD 2.45; p = 0.041). The average of the mWHO in patients with USF was 2.1 (SD 1.6), and with SSF, it was 2.65 (SD 0.95; p = 0.0052). There were no significant differences in primary cardiac outcomes (13.8% in USF vs. 5.4% in SSF; p = 0.134), secondary cardiac (5.3% in USF vs. 2.7% in SSF; p = 0.410), obstetric (10% in USF vs. 16.2% in SSF; p = 0.253) and neonatal (35.9% in USF and 40.5% in SSF; p = 0.486) even though patients with SSF had a higher risk than patients with USF according to the mWHO and CARPREG-II scales. CONCLUSIONS: In pregnant women with heart disease, an SSF compared with a USF by a cardio-obstetric team did not show statistically significant differences in cardiovascular, obstetric, and neonatal outcomes. However, patients with SSF had a significantly higher risk of adverse outcomes due to the mWHO and CARPREG-II scales. This result suggests that the SSF achieves at least equal outcomes despite the higher risk of adverse events that patients in this group had.

INTRODUCCIÓN: Las enfermedades cardiovasculares en las gestantes son desafiantes, con alta morbimortalidad materna y perinatal, por lo que se recomienda un equipo cardio-obstétrico para su atención. Aun así, pocos datos evalúan el impacto de estos equipos. Por lo tanto, el presente estudio tiene como objetivo comparar los resultados obstétricos, maternos y neonatales del seguimiento semiestructurado (SSE) en una clínica cardio-obstétrica con respecto a un seguimiento usual o seguimiento no estructurado (SNE) en gestantes con enfermedad cardiaca. MÉTODOS: Se realizó un registro prospectivo de gestantes con cardiopatías. Se compararon las pacientes con SSE por un equipo cardio-obstétrico, contra aquellas con evaluación única o SNE. Se calculó el riesgo de eventos según la clasificación de la Organización Mundial de la Salud modificado (OMSm) y la escala del Cardiac Disease in Pregnancy Study II (CARPREG-II) y se evaluaron los desenlaces cardiacos, obstétricos y neonatales. RESULTADOS: Se evaluaron 168 pacientes, 37 con SSE y 131 con evaluación única (SNE). Los principales diagnósticos fueron cardiopatía congénita, arritmias y valvulopatías. La media del CARPREG-II en pacientes de SNE fue 2.48 (DE: 2.3) y en pacientes de SSE fue 3.37 (DE: 2.45; p = 0.041). La media de la OMSm en pacientes de SNE fue 2.1 (DE: 1.6) y con SSE fue 2.65 (DE: 0.95; p = 0.0052). No hubo diferencias significativas en los desenlaces cardiacos primarios (13.8% en SNE vs. 5.4% en SSE; p = 0.134), cardiacos secundarios (5.3 en SNE vs. 2.7 en SSE; p = 0.410), obstétricos (10% en SNE vs. 16.2% en SSE; p = 0.253) y neonatales (35.9% en SNE y 40.5% en SSE; p = 0.486) a pesar de que las pacientes con SSE tenían un riesgo mayor que las pacientes con SNE según las escalas de la OMSm y el CARPREG-II. CONCLUSIONES: En gestantes con cardiopatía, un SSE comparado con un SNE por un equipo cardio-obstétrico no mostró diferencias estadísticamente significativas en los desenlaces cardiovasculares, obstétricos y neonatales, a pesar de que las pacientes con SSE tenían un riesgo significativamente más alto de desenlaces adversos por las escalas de la OMSm y el CARPREG-II. Esto sugiere que el SSE logra al menos equiparar los desenlaces a pesar del mayor riesgo de eventos adversos que tenían las pacientes de este grupo.

A Randomized Controlled Intervention Trial with Danazol to Improve Telomeric and Fertility Parameters in Women with Diminished Ovarian Reserve: A Pilot Study.

Background: Most women who are treated at in vitro fertilization (IVF) clinics have trouble conceiving due to ovarian failure (OF), which seems to be associated to short telomeres and reduced or absent telomerase activity in their granulosa cells. Indeed, telomere pathways are involved in organ dysfunction. However, sexual steroids can stimulate the expression of the telomerase gene and have been successfully used to prevent telomere attrition. Thus, a strategy to improve IVF outcomes in women with OF could be telomerase reactivation using sexual steroids. Methods: We conducted a double-blind, placebo-controlled study. Patients with diminished ovarian reserve were randomized to Danazol or placebo for 3 months. We included patients with normal ovarian reserve in the study as untreated controls. Patients and controls underwent several ovarian stimulations (OSs). Telomere and IVF parameters were assessed. Results: We found that the mean telomere length in blood and the percentage of short and long telomeres were similar throughout the 3 months of treatment with Danazol. Remarkably, while the number of cells with one telomeric repeat-containing RNA (TERRA) focus decreased (p = 0.04) after the first month of Danazol treatment, the number of cells with 2 to 4 TERRA foci increased (p = 0.02). Regarding fertility, no differences were found in the antral follicle count. Interestingly, in OS performed after the trial, all Danazol-treated patients had a better MII oocyte rate compared to OS performed before the pilot study.EudraCT number: 2018-004400-19. Conclusions: Danazol treatment seemed to affect telomere maintenance, since both the number of TERRA foci and the ratio of MII oocytes changed. However, further research is needed to confirm these results.