The impact of (very) young donor age on euploid rates: An analysis of 1831 trophectoderm biopsies evaluated with 24-chromosome NGS screening in oocyte donation cycles.

RESEARCH QUESTION: Conflicting data exists regarding whether a younger age of donors has a negative influence on the outcomes of oocyte donation cycles. Is there any correlation between a younger age of donors and the rate of embryonic aneuploidy in oocyte donation cycles? DESIGN: Retrospective study including 515 oocyte donation cycles carried out between February 2017 and November 2022. Comprehensive chromosomal screening was performed on 1831 blastocysts. 1793 had a result which were categorised into groups based on the age of the donor: 18-22 (n = 415), 23-25 (n = 600), 26-30 (n = 488), and 31-35 years (n = 290). The analysis aimed to determine the percentage of biopsy samples that were euploid and the number that were aneuploid, relative to the age group of the oocyte donor. Additionally, linear regression was employed to examine the relationship between age and the proportion of aneuploid embryos, while controlling for relevant variables. RESULTS: Aneuploidy increased predictably with donor age: 18-22 years: 27.5 %; 23-25 years: 31.2 %; 26-30 years: 31.8 %; and 31-35 years: 38.6 %. In the donor group aged 31-35 years, a higher percentage of aneuploid embryos was observed compared to younger donors in univariate analysis (OR: 1.66, 95 % CI: 1.21-2.29, p = 0.002) and multivariate logistic analysis (OR: 2.65, 95 % CI: 1.67-4.23, p < 0.001). The rates of embryonic mosaicism revealed no significant differences. CONCLUSION: The lowest risk of embryonic aneuploidy was found among donors aged <22 years. Conversely, an elevated prevalence was evident within the donor group aged 31-35 years, in contrast to the younger cohorts. The incidence of mosaic embryos remained consistent across all age groups.

Comparison of different agents and doses of anti-vascular endothelial growth factors (aflibercept, bevacizumab, conbercept, ranibizumab) versus laser for retinopathy of prematurity: A network meta-analysis.

Laser photocoagulation (LPC) and/or intravitreal anti-vascular endothelial growth factor (anti-VEGF) injections constitute the current standard treatment for retinopathy of prematurity (ROP). This network meta-analysis focus on whether a ranking of interventions may be established for different dose levels of intravitreal injection of anti-VEGF agents (aflibercept, bevacizumab, conbercept, ranibizumab) as primary treatments for ROP versus laser in terms of retreatment rate as primary outcome, and time to retreatment and refractive error as secondary endpoints, since best anti-VEGF dosage remains under debate. Sixty-eight studies (15 randomized control trials and 53 nonrandomized studies) of 12,356 eyes of 6445 infants were retrieved from databases (2005 Jan. - 2023 June). Studies were evaluated for model fit, risk of bias and confidence of evidence in Network Meta-Analysis (CINeMA). Bayesian NMA showed that anti-VEGF drugs were not inferior to laser in terms of retreatment rate. For intravitreal bevacizumab (IVB), doses half of the conventional infant dose showed a low risk of retreatment rate (risk ratio (RR) of 1.43; 95% credible interval (CrI): 0.508, 4.03). On probability ranking as surface under the cumulative ranking curve (SUCRA) plot, half dose of bevacizumab had a better position than conventional and augmented (1.2-2 times the regular dose) doses. A similar probability trend was observed for half vs. conventional doses of aflibercept and ranibizumab. Conventional infant dose of conbercept showed the lowest risk for retreatment (RR 0.846; 95% CrI: 0.245, 2.91). For secondary endpoints, lower doses of anti-VEGF agents were associated with shorter times to retreatment. The largest changes were noted for the augmented doses of bevacizumab and ranibizumab (0.3 mg) with means of 14.1 weeks (95% CrI: 6.65, 21.6) and 12.8 weeks (95% CrI: 3.19, 20.9), respectively. Finally, NMA demonstrated better refractive profile for anti-VEGF than laser therapy, especially for the conventional infant doses of bevacizumab and ranibizumab which exhibited a significantly better refractive profile than LPC, with mean differences of 1.67 (spherical equivalent - diopters) (95% CrI: 0.705, 2.67) and 2.19 (95% CrI: 0.782, 3.59), respectively. In the SUCRA plots, LPC had a markedly different position with a higher probability for myopia. Further clinical trials comparing different intravitreal doses of anti-VEGF agents are needed, but our findings suggest that low doses of these drugs retain efficacy and may reduce ocular and systemic undesired events.

Activation of ductal progenitor-like cells from adult human pancreas requires extracellular matrix protein signaling.

Ductal progenitor-like cells are a sub-population of ductal cells in the adult human pancreas that have the potential to contribute to regenerative medicine. However, the microenvironmental cues that regulate their activation are poorly understood. Here, we establish a 3-dimensional suspension culture system containing six defined soluble factors in which primary human ductal progenitor-like and ductal non-progenitor cells survive but do not proliferate. Expansion and polarization occur when suspension cells are provided with a low concentration (5% v/v) of Matrigel, a sarcoma cell product enriched in many extracellular matrix (ECM) proteins. Screening of ECM proteins identified that collagen IV can partially recapitulate the effects of Matrigel. Inhibition of integrin α1ß1, a major collagen IV receptor, negates collagen IV- and Matrigel-stimulated effects. These results demonstrate that collagen IV is a key ECM protein that stimulates the expansion and polarization of human ductal progenitor-like and ductal non-progenitor cells via integrin α1ß1 receptor signaling.

High risk of coronary artery obstruction during TAVR, how to avoid it?

BACKGROUND: Coronary artery obstruction after percutaneous aortic replacement is a complication with high short-term mortality secondary to the lack of timely treatment. There are various predictors of coronary obstruction prior to valve placement such as the distance from the ostia, the degree of calcification, the distance from the sinuses; In such a situation some measures must be taken to prevent and treat coronary obstruction. CASE PRESENTATION: An 84-year-old male, with severe aortic stenosis and high surgical risk, who was treated with TAVR. However, during the deployment of the valve he presented hemodynamic instability secondary to LMCA obstruction. The intravascular image showed obstruction of the ostium secondary to the displacement of calcium that he was successfully treated with a chimney stent technique. CONCLUSIONS: The high degree of calcification and the left ostium near the annulus are conditions for obstruction of the ostium at the time of valve release; In this context, provisional stenting prior to TAVR in patients at high risk of obstruction should be considered as a safe prevention strategy to achieve the success of the procedure.

Relationship between Mental Disorders, Smoking or Alcoholism and Benign Prostate Disease.

INTRODUCTION: Mental disorders, smoking, or alcoholism and benign prostate disease are highly prevalent in men. AIMS: To identify the relationship between mental disorders, smoking, or alcoholism and benign prostate disease. METHODOLOGY: A prospective multicenter study that evaluated prostate health status in 558 men from the community. Groups: GP-men who request a prostate health examination and whose medical history includes a mental disorder, smoking, or alcoholism prior to a diagnosis of benign prostate disease; GU-men who request a prostate health examination and whose medical history includes a benign prostate disease prior to a diagnosis of mental disorder, smoking, or alcoholism. VARIABLES: age, body mass index (BMI), prostate specific antigen (PSA), follow-up of the mental disorder, smoking or alcoholism, time elapsed between urological diagnosis and the mental disorder, smoking or alcoholism diagnosis, status of the urological disease (cured or not cured), concomitant diseases, surgical history, and concomitant treatments. Descriptive statistics, Student's t-test, Chi2, multivariate analysis. RESULTS: There were no mental disorders, smoking, or alcoholism in 51.97% of men. Anxiety, smoking, major depressive disorder, pathological insomnia, psychosis, and alcoholism were identified in 19.71%, 13.26%, 5.73%, 4.30%, 2.87%, and 2.15% of individuals, respectively. Nonbacterial prostatitis (31.54%), urinary tract infection (other than prostatitis, 24.37%), prostatic intraepithelial neoplasia (13.98%), and prostatodynia (1.43%) were prostate diseases. Unresolved symptomatic benign prostate disease was associated with anxiety, depression, and psychosis (p = 0.002). Smoking was the disorder that men managed to eliminate most frequently. The dominant disorder in patients with symptomatic benign prostatic disease was alcoholism (p = 0.006). CONCLUSIONS: Unresolved symptomatic benign prostatic disease is associated with anxiety, depression, and psychosis. Alcoholism is associated with a worse prognosis in the follow-up of symptomatic benign prostatic disease.

Renal cell carcinoma (RCC) spreading to the larynx: an unusual condition.

A man in his mid-70s, heavy smoker with chronic alcohol consumption and a chronic exposure to insecticides and burning of crop residues was referred to the surgical oncology department because of a 4-month onset of hoarseness, dyspnoea and laryngeal stridor. He had a history of left nephrectomy due to Fuhrman IV clear cell renal cancer 2 years ago. The patient underwent a bronchoscopy which identified a deforming tumour of the left vallecula, occlusion of 90% of the lumen and did not allow a safe biopsy. Following discussion between the oncological team, total laryngectomy and bilateral neck dissection of levels II, III, IV and V were performed, finding a transglottic tumour of approximately 4×3 cm with extension to the right anterolateral thyroid cartilage. The pathology report described metastatic RCC. The patient recovered well postoperatively and started systemic therapy with a vascular endothelial growth factor receptors inhibitor.

Capacidad de autocuidado en estudiantes universitarios: estudio longitudinal / Self-care capacity in university students: longitudinal study

Introducción. La etapa universitaria representa un período crucial en la vida de los individuos, donde el desarrollo de hábitos saludables es fundamental. Objetivo. Evaluar la capacidad de autocuidado en estudiantes de una universidad mexicana y su variación a través del tiempo. Materiales y Métodos. Estudio observacional, analítico, prospectivo y longitudinal con 67 estudiantes, bajo muestreo no aleatorio por conveniencia, aplicando en cuatro ocasiones a lo largo de dos años la escala Appraisal of Self-care Agency Scale (ASA) en español, que evalúa la capacidad de autocuidado. El análisis de los datos se realizó a través de la prueba de ANOVA de mediciones repetidas y el modelo lineal de efectos mixtos multinivel. El protocolo fue evaluado y avalado por los Comités de Ética e Investigación de la Institución. Resultados. Se observaron variaciones significativas en la capacidad de autocuidado entre la medida basal y la segunda medición (p=0,001), entre la medida basal y la cuarta medición (p<0,001), pero no entre la medida basal y la tercera medición (p=0,128). Al evaluar las mediciones distintas según el sexo, la facultad, la nacionalidad, el estado civil y el trabajo mientras se estudia, se encontraron diferencias significativas (p<0,001). Conclusión. Existe una variación de la capacidad de autocuidado en estudiantes universitarios a través del tiempo, resaltando la necesidad de intervenciones en Promoción de la Salud. Palabras clave: autocuidado; estudiantes; universidades; salud pública

Introduction. The university stage represents a crucial period in individuals' lives, where the development of healthy habits is fundamental. Objective.To evaluate self-care capacity in students from a Mexican university and its variation over time. Materials and Methods.An observational, analytical, prospective, and longitudinal study with 67 students, using convenience sampling, applying the Appraisal of Self-care Agency Scale (ASA) in Spanish on four occasions over two years, which assesses self-care capacity. Dataanalysis was performed through the repeated measures ANOVA test and the multilevel mixed-effects linear model. The protocol was evaluated and endorsed by the Institution's Ethics and Research Committees. Results.Significant variations in self-care capacity were observed between the baseline measurement and the second measurement (p=0.001), between the baseline measurement and the fourth measurement (p<.001), but not between the baseline measurement and the third measurement (p=0.128). When evaluating different measurements according to sex, faculty, nationality, marital status, and working while studying, significant differences were found (p<0.001). Conclusion.There exists a variation in self-care capacity among university students over time, emphasizing the need for Health Promotion interventions. Key words:self-care; students; universities;public health

Rare, Tightly-Bound, Multi-Cellular Clusters in the Pancreatic Ducts of Adult Mice Function Like Progenitor Cells and Survive and Proliferate After Acinar Cell Injury.

Pancreatic ductal progenitor cells have been proposed to contribute to adult tissue maintenance and regeneration after injury, but the identity of such ductal cells remains elusive. Here, from adult mice, we identify a near homogenous population of ductal progenitor-like clusters, with an average of 8 cells per cluster. They are a rare subpopulation, about 0.1% of the total pancreatic cells, and can be sorted using a fluorescence-activated cell sorter with the CD133highCD71lowFSCmid-high phenotype. They exhibit properties in self-renewal and tri-lineage differentiation (including endocrine-like cells) in a unique 3-dimensional colony assay system. An in vitro lineage tracing experiment, using a novel HprtDsRed/+ mouse model, demonstrates that a single cell from a cluster clonally gives rise to a colony. Droplet RNAseq analysis demonstrates that these ductal clusters express embryonic multipotent progenitor cell markers Sox9, Pdx1, and Nkx6-1, and genes involved in actin cytoskeleton regulation, inflammation responses, organ development, and cancer. Surprisingly, these ductal clusters resist prolonged trypsin digestion in vitro, preferentially survive in vivo after a severe acinar cell injury and become proliferative within 14 days post-injury. Thus, the ductal clusters are the fundamental units of progenitor-like cells in the adult murine pancreas with implications in diabetes treatment and tumorigenicity.

Implicit bias in diagnosing mosaicism amongst preimplantation genetic testing providers: results from a multicenter study of 36 395 blastocysts.

STUDY QUESTION: Does the diagnosis of mosaicism affect ploidy rates across different providers offering preimplantation genetic testing for aneuploidies (PGT-A)? SUMMARY ANSWER: Our analysis of 36 395 blastocyst biopsies across eight genetic testing laboratories revealed that euploidy rates were significantly higher in providers reporting low rates of mosaicism. WHAT IS KNOWN ALREADY: Diagnoses consistent with chromosomal mosaicism have emerged as a third category of possible embryo ploidy outcomes following PGT-A. However, in the era of mosaicism, embryo selection has become increasingly complex. Biological, technical, analytical, and clinical complexities in interpreting such results have led to substantial variability in mosaicism rates across PGT-A providers and clinics. Critically, it remains unknown whether these differences impact the number of euploid embryos available for transfer. Ultimately, this may significantly affect clinical outcomes, with important implications for PGT-A patients. STUDY DESIGN, SIZE, DURATION: In this international, multicenter cohort study, we reviewed 36 395 consecutive PGT-A results, obtained from 10 035 patients across 11 867 treatment cycles, conducted between October 2015 and October 2021. A total of 17 IVF centers, across eight PGT-A providers, five countries and three continents participated in the study. All blastocysts were tested using trophectoderm biopsy and next-generation sequencing. Both autologous and donation cycles were assessed. Cycles using preimplantation genetic testing for structural rearrangements were excluded from the analysis. PARTICIPANTS/MATERIALS, SETTING, METHODS: The PGT-A providers were randomly categorized (A to H). Providers B, C, D, E, F, G, and H all reported mosaicism, whereas Provider A reported embryos as either euploid or aneuploid. Ploidy rates were analyzed using multilevel mixed linear regression. Analyses were adjusted for maternal age, paternal age, oocyte source, number of embryos biopsied, day of biopsy, and PGT-A provider, as appropriate. We compared associations between genetic testing providers and PGT-A outcomes, including the number of chromosomally normal (euploid) embryos determined to be suitable for transfer. MAIN RESULTS AND THE ROLE OF CHANCE: The mean maternal age (±SD) across all providers was 36.2 (±5.2). Our findings reveal a strong association between PGT-A provider and the diagnosis of euploidy and mosaicism. Amongst the seven providers that reported mosaicism, the rates varied from 3.1% to 25.0%. After adjusting for confounders, we observed a significant difference in the likelihood of diagnosing mosaicism across providers (P < 0.001), ranging from 6.5% (95% CI: 5.2-7.4%) for Provider B to 35.6% (95% CI: 32.6-38.7%) for Provider E. Notably, adjusted euploidy rates were highest for providers that reported the lowest rates of mosaicism (Provider B: euploidy, 55.7% (95% CI: 54.1-57.4%), mosaicism, 6.5% (95% CI: 5.2-7.4%); Provider H: euploidy, 44.5% (95% CI: 43.6-45.4%), mosaicism, 9.9% (95% CI: 9.2-10.6%)); and Provider D: euploidy, 43.8% (95% CI: 39.2-48.4%), mosaicism, 11.0% (95% CI: 7.5-14.5%)). Moreover, the overall chance of having at least one euploid blastocyst available for transfer was significantly higher when mosaicism was not reported, when we compared Provider A to all other providers (OR = 1.30, 95% CI: 1.13-1.50). Differences in diagnosing and interpreting mosaic results across PGT-A laboratories raise further concerns regarding the accuracy and relevance of mosaicism predictions. While we confirmed equivalent clinical outcomes following the transfer of mosaic and euploid blastocysts, we found that a significant proportion of mosaic embryos are not used for IVF treatment. LIMITATIONS, REASONS FOR CAUTION: Due to the retrospective nature of the study, associations can be ascertained, however, causality cannot be established. Certain parameters such as blastocyst grade were not available in the dataset. Furthermore, certain platform-related and clinic-specific factors may not be readily quantifiable or explicitly captured in our dataset. As such, a full elucidation of all potential confounders accounting for variability may not be possible. WIDER IMPLICATIONS OF THE FINDINGS: Our findings highlight the strong need for standardization and quality assurance in the industry. The decision not to transfer mosaic embryos may ultimately reduce the chance of success of a PGT-A cycle by limiting the pool of available embryos. Until we can be certain that mosaic diagnoses accurately reflect biological variability, reporting mosaicism warrants utmost caution. A prudent approach is imperative, as it may determine the difference between success or failure for some patients. STUDY FUNDING/COMPETING INTEREST(S): This work was supported by the Torres Quevedo Grant, awarded to M.P. (PTQ2019-010494) by the Spanish State Research Agency, Ministry of Science and Innovation, Spain. M.P., L.B., A.R.L., A.L.R.d.C.L., N.P.P., M.P., D.S., F.A., A.P., B.M., L.D., F.V.M., D.S., M.R., E.P.d.l.B., A.R., and R.V. have no competing interests to declare. B.L., R.M., and J.A.O. are full time employees of IB Biotech, the genetics company of the Instituto Bernabeu group, which performs preimplantation genetic testing. M.G. is a full time employee of Novagen, the genetics company of Cegyr, which performs preimplantation genetic testing. TRIAL REGISTRATION NUMBER: N/A.

Identificación de Factores Clínicos Relacionados a una Mayor Mortalidad Asociada a Insuficiencia Renal Aguda en pacientes de Terapia Intensiva

La insuficiencia renal aguda (IRA) es una de las complicaciones más frecuentes en los pacientes hospitalizados, siendo un factor de riesgo de mortalidad. Es de suma importancia identificar la asociación de factores clínicos que empeoran la mortalidad en pacientes con IRA internados en una unidad de terapia intensiva (UTI). Se incluyeron 218 pacientes, de los cuales el 63,7% (n=139) correspondieron a hombres con un promedio de edad de 43±19 años. El análisis de correlación de variables de control, dependiente e independiente fue a través del coeficiente de Spearman y el OR fue analizado mediante regresión logística. De los 218 pacientes, falleció el 33% (n=72) de los pacientes internados en UTI. La IRA ocurrió en 28,4% (n=62) del total de pacientes y de estos, el 61,3% (n=38) fallecieron, con un OR de 4,94 (p 0,0001). La mayor proporción de fallecidos perteneció a la categoría AKIN 3. Las variables clínicas de ventilación mecánica (PR 3,57, IC 95%, 0,34-37,93), uso de drogas vasoactivas (PR 8,32, IC 95%, 3,20-21,64), puntuación APACHE III (PR 1,12, IC 95%, 1,03-1,23), edad (PR 1,01, IC 95%, 0,99-1,04) y los sometidos a cirugía (PR 0,28, IC 95%, 0,10-0,80) tuvieron asociación positiva y aumentaron la mortalidad. La presencia de variables clínicas de ventilación mecánica, la utilización de drogas vasoactivas, sepsis, el estudio APACHE III, la edad, la categoría AKIN 3, y el antecedente de cirugía previo al ingreso a UTI aumentan significativamente la mortalidad en pacientes con IRA en UTI.

Acute renal failure (ARF) is one of the most frequent complications in hospitalized patients and is a risk factor for mortality. It is extremely important to identify the association of clinical factors that worsen mortality in patients with ARF admitted to an intensive care unit (ICU). A total of 218 patients were included, of which 63.7% (n=139) were men with a mean age of 43±19 years. The correlation analysis of control, dependent, and independent variables was done through Spearman's coefficient and the OR was analyzed through logistic regression. Of the 218 patients, 33% (n=72) died in the ICU. ARF occurred in 28.4% (n=62) of all patients and of these, 61.3% (n=38) died, with an OR of 4.94 (p 0.0001). The highest proportion of deceased patients were in the AKIN 3 category. The clinical variables of mechanical ventilation (PR 3.57, 95% CI, 0.34-37.93), use of vasoactive drugs (PR 8.32, 95% CI, 3.20-21.64), APACHE III score (PR 1.12, 95% CI, 1.03-1.23), age (PR 1.01, 95% CI, 0.99-1.04) and those who underwent surgery (PR 0.28, 95% CI, 0.10-0.80) had a positive association and increased mortality. The presence of clinical variables of mechanical ventilation, the use of vasoactive drugs, sepsis, APACHE III stage, age, AKIN 3 category, and a history of surgery before admission to the ICU significantly increase mortality in patients with ARF in ICU.

Hipertensión arterial pulmonar en pacientes con dermatomiositis juvenil y esclerosis sistémica en un centro pediátrico de tercer nivel

INTRODUCCIÓN: La hipertensión arterial pulmonar puede estar asociada secundariamente a enfermedades del tejido conectivo. Entre estas enfermedades, predominan la esclerosis sistémica y la dermatomiositis juvenil. MATERIALES Y MÉTODOS: Se realizó un estudio retrospectivo, descriptivo y transversal. Se incluyeron todos los pacientes con diagnóstico de dermatomiositis juvenil y esclerosis sistémica que acudieron a nuestro hospital. Posteriormente se verificaron los niveles de presión arterial pulmonar mediante ecocardiografía. RESULTADOS: Se incluyeron 58 pacientes, de los cuales sólo 17 pacientes tuvieron ecocardiografía diagnóstica. Entre ellos, dos pacientes presentaron hipertensión arterial pulmonar. CONCLUSIÓN: La detección oportuna de la hipertensión arterial pulmonar en las enfermedades del tejido conectivo es esencial. Generalmente es asintomático. Es necesario adherirse al protocolo internacional que sugiere realizar ecocardiografía en todos los pacientes con dermatomiositis juvenil y esclerosis sistémica.

INTRODUCTION: Pulmonary arterial hypertension may be secondary associated with connective tissue diseases. Among these diseases, systemic sclerosis and juvenile dermatomyositis predominate. MATERIALS AND METHODS: A retrospective, descriptive and cross-sectional study was carried out. All patients with a diagnosis of juvenile dermatomyositis and systemic sclerosis who attended our hospital were included. Pulmonary arterial pressure levels were subsequently verified by echocardiography. RESULTS: 58 patients were included, of which only 17 patients had a diagnostic echocardiography. Among them, two patients presented pulmonary arterial hypertension. CONCLUSION: Timely detection of pulmonary arterial hypertension in connective tissue diseases is essential. It is generally asymptomatic. It is necessary to adhere to the international protocol that suggests performing echocardiography in all patients with juvenile dermatomyositis and systemic sclerosis.

Effects of Virtual Health Messages on Maternal Therapeutic Adherence for Childhood Anemia

Introduction: Therapeutic adherence for childhood anemia is addressed in health services with unsatisfactory results. Therefore, the implementation of this strategy will favor greater adherence to treatment with ferrous sulfate. Objective: To evaluate the effect of virtual health messages on maternal therapeutic adherence for childhood anemia. Materials and Methods: A pre-experimental and longitudinal study was developed between November and December 2022, in which 24 mothers of children diagnosed with anemia participated. Adherence was determined using a test and inferential analysis through the Wilcoxon test. Results: The mothers were between 18 and 29 years old (50.0 %), of rural origin (66.7 %), who completed primary school (33.3 %), housewives (83.3 %), and cohabitants (79.2 %). In the pre-test, high adherence was observed in social factors (50 %), health personnel (75 %), illness (87.5 %), and person supplementing the ferrous sulfate and the patient (75.5 %). The overall adherence was medium in the pretest (50.0 %) and high in the post-test (100.0 %). Message reception was high for the overall test (62.6 %), reminder (79.2 %), informational (79.2 %), and motivational (75.0 %) messages. Conclusion: Virtual health messages have a positive effect on maternal therapeutic adherence for childhood anemia (p < 0.05) and their inclusion in primary health services will contribute favorably to obtaining optimal results.

Introducción: la adherencia terapéutica de anemia infantil es un tópico abordado en los servicios de salud, con resultados poco satisfactorios; por lo tanto, la implementación de esta estrategia favorecerá una mayor adherencia al tratamiento con sulfato ferroso. Objetivo: evaluar el efecto de los mensajes virtuales en salud sobre la adherencia terapéutica materna de anemia infantil. Materiales y Métodos: se desarrolló un estudio preexperimental y longitudinal entre noviembre y diciembre de 2022, en el cual participaron 24 madres de niños diagnosticados con anemia; la adherencia se determinó mediante un test y el análisis inferencial por medio de la prueba de Wilcoxon. Resultados: Las madres tenían entre 18 y 29 años (50,0 %), procedencia rural (66,7 %), primaria completa (33,3 %), amas de casa (83,3 %) y convivientes (79,2 %). En el pretest, se observó alta adherencia en factores sociales (50 %), personal de salud (75 %), enfermedad (87,5 %), persona que suplementa y paciente (75,5 %), y adherencia media en factores relacionados a la suplementación (54,2 %); en el postest, la adherencia alta se presentó en factores sociales (100,0 %), personal de salud (100,0 %), enfermedad (87,5 %), suplementación (95,8 %), persona que suministra el sulfato ferroso y paciente (100,0 %). La adherencia global fue media en el pretest (50,0 %) y alta en el postest (100,0 %). La recepción de mensajes fue alta para el test global (62,6 %), mensajes recordatorios (79,2 %), informativos (79,2 %) y motivacionales (75,0 %). Conclusión: los mensajes virtuales en salud tienen un efecto positivo en la adherencia terapéutica materna de anemia infantil (p < 0,05) y su inclusión en los servicios primarios de salud contribuirá favorablemente en la obtención de resultados óptimos.

Introdução: a adesão ao tratamento da anemia infantil é um tema abordado nos serviços de saúde, com resultados insatisfatórios; portanto, a implementação dessa estratégia favorecerá uma maior adesão ao tratamento com sulfato ferroso. Objetivo: avaliar o efeito das mensagens virtuais de saúde na adesão materna ao tratamento da anemia infantil. Materiais e método: foi realizado um estudo pré-experimental e longitudinal entre novembro e dezembro de 2022, do qual participaram 24 mães de crianças diagnosticadas com anemia; a adesão foi determinada por meio de um teste e a análise inferencial, por meio do teste de Wilcoxon. Resultados: as mães tinham entre 18 e 29 anos de idade (50 %), eram de áreas rurais (66,7 %), concluíram o ensino fundamental (33,3 %), eram donas de casa (83,3 %) e viviam juntas (79,2 %). No pré-teste, foi observada alta adesão em fatores sociais (50 %), equipe de saúde (75 %), doença (87,5 %), pessoa que suplementa e paciente (75,5 %), e adesão média em fatores relacionados à suplementação (54,2 %); no pós-teste, foi observada alta adesão em fatores sociais (100 %), equipe de saúde (100 %), doença (87,5 %), suplementação (95,8 %), pessoa que fornece sulfato ferroso e paciente (100 %). A adesão geral foi média no pré-teste (50 %) e alta no pós-teste (100 %). A recepção das mensagens foi alta para o teste geral (62,6 %), lembretes (79,2 %), mensagens informativas (79,2 %) e motivacionais (75 %). Conclusões: as mensagens virtuais de saúde têm um efeito positivo na adesão materna ao tratamento da anemia infantil (p < 0,05) e sua inclusão nos serviços de saúde primários contribuirá favoravelmente para a otimização dos resultados.

Valve-in-valve as a rescue treatment in retrograde migration of the transcatheter aortic valve to the left ventricle: a case report.

Background: The treatment of choice for patients with severe symptomatic pure native aortic valve regurgitation (PNAVR) is surgical aortic valve replacement (SAVR). However, not all patients are candidates for surgery because of comorbidities or are deemed high risk for surgery. In such cases, transcatheter aortic valve replacement (TAVR) has proved to be better than medical treatment. Case summary: A 78-year-old male with a history of ankylosing spondylitis was admitted with New York Heart Association III heart failure. The echocardiogram showed severe aortic regurgitation and a left ventricular ejection fraction of 52%. Because of high surgical risk and being refractory to medical RX, he was accepted for TAVR. The tomography of anatomical characteristics reported the absence of calcium and dilation of the aortic ring and aortic root. During the TAVR procedure, the patient experienced valve migration, but it was autonomously repositioned in the aortic annulus. As a rescue measure, a second valve was placed. Here, we present a case of valve migration to the left ventricle treated with a valve-in-valve procedure without the need for surgical treatment. Discussion: The absence of annulus calcification in PNAVR increases the risk of post-TAVR paravalvular leak and device embolization. Valve migration generally requires valve recovery and conversion to SAVR.

Diagnosis of patients with Lynch syndrome lacking the Amsterdam II or Bethesda criteria.

BACKGROUND: Lynch Syndrome (LS) is an autosomal dominant inheritance disorder characterized by genetic predisposition to develop cancer, caused by pathogenic variants in the genes of the mismatch repair system. Cases are detected by implementing the Amsterdam II and the revised Bethesda criteria, which are based on family history. MAIN BODY: Patients who meet the criteria undergo posterior tests, such as germline DNA sequencing, to confirm the diagnosis. However, these criteria have poor sensitivity, as more than one-quarter of patients with LS do not meet the criteria. It is very likely that the lack of sensitivity of the criteria is due to the incomplete penetrance of this syndrome. The penetrance and risk of developing a particular type of cancer are highly dependent on the affected gene and probably of the variant. Patients with variants in low-penetrance genes have a lower risk of developing a cancer associated with LS, leading to families with unaffected generations and showing fewer clear patterns. This study focuses on describing genetic aspects of LS cases that underlie the lack of sensitivity of the clinical criteria used for its diagnosis. CONCLUSION: Universal screening could be an option to address the problem of underdiagnosis.

Simultaneous Targeting of IL-1-Signaling and IL-6-Trans-Signaling Preserves Human Pulmonary Endothelial Barrier Function During a Cytokine Storm-Brief Report.

BACKGROUND: Systemic inflammatory diseases, such as sepsis and severe COVID-19, provoke acute respiratory distress syndrome in which the pathological hyperpermeability of the microvasculature, induced by uncontrolled inflammatory stimulation, causes pulmonary edema. Identifying the inflammatory mediators that induce human lung microvascular endothelial cell barrier dysfunction is essential to find the best anti-inflammatory treatments for critically ill acute respiratory distress syndrome patients. METHODS: We have compared the responses of primary human lung microvascular endothelial cells to the main inflammatory mediators involved in cytokine storms induced by sepsis and SARS-CoV2 pulmonary infection and to sera from healthy donors and severely ill patients with sepsis. Endothelial barrier function was measured by electric cell-substrate impedance sensing, quantitative confocal microscopy, and Western blot. RESULTS: The human lung microvascular endothelial cell barrier was completely disrupted by IL (interleukin)-6 conjugated with soluble IL-6R (IL-6 receptor) and by IL-1ß (interleukin-1beta), moderately affected by TNF (tumor necrosis factor)-α and IFN (interferon)-γ and unaffected by other cytokines and chemokines, such as IL-6, IL-8, MCP (monocyte chemoattractant protein)-1 and MCP-3. The inhibition of IL-1 and IL-6R simultaneously, but not separately, significantly reduced endothelial hyperpermeability on exposing human lung microvascular endothelial cells to a cytokine storm consisting of 8 inflammatory mediators or to sera from patients with sepsis. Simultaneous inhibition of IL-1 and JAK (Janus kinase)-STAT (signal transducer and activator of transcription protein), a signaling node downstream IL-6 and IFN-γ, also prevented septic serum-induced endothelial barrier disruption. CONCLUSIONS: These findings strongly suggest a major role for both IL-6 trans-signaling and IL-1ß signaling in the pathological increase in permeability of the human lung microvasculature and reveal combinatorial strategies that enable the gradual control of pulmonary endothelial barrier function in response to a cytokine storm.

Síndrome de compresión medular de etiología infecciosa

El síndrome de compresión medular es una urgencia neuroquirúrgica debido a que un diagnóstico precoz y un tratamiento temprano podría revertir las incapacitantes secuelas ocasionadas por esta enfermedad. Las causas de este síndrome pueden ser traumática, metastásica, infecciosa y vascular (hematomas). La etiología infecciosa no es frecuente y el principal germen involucrado suele ser Staphylococcus aureus. A continuación presentamos el caso de una paciente de 58 años con síndrome de compresión medular de etiología infecciosa quien fue ingresada en el Servicio de Clínica Médica del Centro Médico Nacional.

Spinal cord compression syndrome is a neurosurgical emergency because early diagnosis and early treatment could reverse the disabling consequences caused by this disease. The causes of this syndrome can be traumatic, metastatic, infectious, and vascular (hematomas). Infectious etiology is not frequent and the main germ involved is usually Staphylococcus aureus. Below we present the case of a 58-year-old patient with spinal cord compression syndrome of infectious etiology who was admitted to the Medical Clinic Service of the National Medical Center.

Remimazolam: ¿el agente ideal para sedación, inducción y mantenimiento de la anestesia? / Remimazolam: the ideal agent for sedation, induction and maintenance of anesthesia?

Resumen: El remimazolam es una nueva benzodiacepina que combina las propiedades farmacológicas de dos agentes utilizados en la anestesia: el efecto hipnótico del midazolam y el metabolismo del remifentanilo. El remimazolam se hidroliza por esterasas tisulares inespecíficas a metabolitos inactivos, permitiendo una alta depuración y recuperación rápida. Por sus propiedades farmacológicas, se ha propuesto su uso como un agente de acción ultracorta en procedimientos de sedación fuera de quirófano, inducción, mantenimiento de la anestesia y de sedación en la unidad de terapia intensiva. El perfil de seguridad del remimazolam es amplio, ya que sus efectos hemodinámicos y cardiorrespiratorios son menos marcados que otros fármacos empleados en dichos procedimientos. Como otras benzodiacepinas, los efectos del remimazolam pueden ser revertidos con flumazenil. Hasta el momento, el remimazolam ha demostrado ser un agente hipnótico eficaz; sin embargo, se requiere mayor investigación para establecer su utilidad clínica.

Abstract: Remimazolam is a new benzodiacepine that combines the pharmacological properties of two agents used in anesthesia: the hypnotic effect of midazolam and the metabolism of remifentanyl. Remimazolam is hydrolized by nonspecific tissue esterases into inactive metabolytes, allowing high clearance and fast recovery. Due to its pharmacological characteristics, it has been proposed as an ultra- short acting agent for sedation out operating room, induction and maintenance of anesthesia, as well as for sedation in the Intensive Care Unit. Remimazolam has an elevated safety profile, as it might that, it has less pronounced hemodynamic and cardiorespiratory effects in contrast to other drugs used in the same procedures. Like other benzodiacepines, remimazolam effects can be reversed with flumazenil. Remimazolam has proven to be an effective hypnotic agent, however further research and clinical evaluation is required to establish its use.

Microbiota composition and its impact on DNA methylation in colorectal cancer.

Colorectal cancer is a complex disease resulting from the interaction of genetics, epigenetics, and environmental factors. DNA methylation is frequently found in tumor suppressor genes to promote cancer development. Several factors are associated with changes in the DNA methylation pattern, and recently, the gastrointestinal microbiota could be associated with this epigenetic change. The predominant phyla in gut microbiota are Firmicutes and Bacteroidetes; however, an enrichment of Bacteroides fragilis, Fusobacterium nucleatum, and Streptococcus bovis, among others, has been reported in colorectal cancer, although the composition could be influenced by several factors, including diet, age, sex, and cancer stage. Fusobacterium nucleatum, a gram-negative anaerobic bacillus, is mainly associated with colorectal cancer patients positive for the CpG island methylator phenotype, although hypermethylation in genes such as MLH1, CDKN2A, MTSS1, RBM38, PKD1, PTPRT, and EYA4 has also been described. Moreover, Hungatella hathewayi, a gram-positive, rod-shaped bacterium, is related to hypermethylation in SOX11, THBD, SFRP2, GATA5, ESR1, EYA4, CDX2, and APC genes. The underlying epigenetic mechanism is unclear, although it could be implicated in the regulation of DNA methyltransferases, enzymes that catalyze the transfer of a methyl group on cytosine of CpG sites. Since DNA methylation is a reversible event, changes in gut microbiota could modulate the gene expression through DNA methylation and improve the colorectal cancer prognosis.

La viruela símica, alcances sobre lo que se conoce / Monkeypox, insights into what is known / Monkeypox, escopo do que é conhecido

La viruela símica es una enfermedad zoonótica endémica de África occidental y central, pero el actual brote está presentado una inusual propagación por el mundo a pesar de su limitada capacidad para trasmitirse de humano a humano, situación que ha generado una preocupación sanitaria a nivel mundial. Objetivo. Identificar la viruela símica, descripción del monkeypox virus, brote actual de la viruela símica, etiología, trasmisión, signos y síntomas, diagnóstico, vacunación y tratamiento antiviral. Metodología. Se llevó a cabo una revisión sistemática en PubMed, Ovid y LILACS, empleando operadores booleanos como, "monkeypox" OR "MPXV" OR "human monkeypox" OR "virus monkeypox", en total se identificaron 986 registros, en inglés y español. La fase de cribado recabo 59 registros entre artículos científicos y literatura gris publicados entre el 2010 y el 2022. El proceso de revisión se desarrolló bajo los estándares del método PRISMA; la elegibilidad, incluyó valoración de la calidad científica por listas de comprobación, y la inclusión contempló los criterios de calidad de la evidencia y graduación de la fuerza de recomendación. Resultados. Se encontraron 287 registros en PubMed, 699 en Ovid Medline®, se localizaron en total 986 registros electrónicos. Conclusión. El incremento de la trasmisión de humano a humano pone en peligro al entorno familiar y a quienes brindan el cuidado de salud. Las erupciones cutáneas son el signo patognomónico durante la valoración clínica. La inmunidad colectiva alcanzada durante la vacunación contra la viruela humana se ha reducido, contribuyendo en el aumento de casos y la propagación.

Smallpox is a zoonotic disease endemic to West and Central Africa, but the current outbreak is showing an unusual spread throughout the world despite its limited ability to transmit from human to human, a situation that has raised global health concern. Objective. To identify monkeypox, description of monkeypox virus, current outbreak of monkeypox, etiology, transmission, signs and symptoms, diagnosis, vaccination and antiviral treatment. Methodology. A systematic review was carried out in PubMed, Ovid and LILACS, using Boolean operators such as, "monkeypox" OR "MPXV" OR "human monkeypox" OR "monkeypox virus", a total of 986 records were identified, in English and Spanish. The screening phase collected 59 records between scientific articles and grey literature published between 2010 and 2022. The review process was developed under the standards of the PRISMA method; eligibility included assessment of scientific quality by checklists, and inclusion contemplated the criteria of quality of evidence and grading of the strength of recommendation. Results. A total of 287 records were found in PubMed, 699 in Ovid Medline®, and 986 electronic records were located. Conclusion. The increase in human-to-human transmission endangers the family environment and health care providers. Skin rashes are the pathognomonic sign during clinical assessment. The herd immunity achieved during human smallpox vaccination has been reduced, contributing to the increase in cases and spread.

A varíola é uma doença zoonótica endêmica da África Ocidental e Central, mas o surto atual está mostrando uma disseminação global incomum, apesar de sua capacidade limitada de transmissão de pessoa para pessoa, uma situação que levantou preocupações com a saúde global. Objetivo. Identificar a varíola do macaco, a descrição do vírus da varíola do macaco, o atual surto de varíola do macaco, a etiologia, a transmissão, os sinais e sintomas, o diagnóstico, a vacinação e o tratamento antiviral. Metodologia. Foi realizada uma revisão sistemática no PubMed, Ovid e LILACS, usando operadores booleanos como "monkeypox" OR "MPXV" OR "human monkeypox" OR "monkeypox virus", no total foram identificados 986 registros, em inglês e espanhol. A fase de triagem coletou 59 registros de artigos científicos e literatura cinzenta publicados entre 2010 e 2022. O processo de revisão foi desenvolvido de acordo com os padrões do método PRISMA; a elegibilidade incluiu a avaliação da qualidade científica por meio de listas de verificação, e a inclusão contemplou os critérios de qualidade de evidência e graduação da força de recomendação. Resultados. Foram encontrados 287 registros no PubMed, 699 no Ovid Medline® e um total de 986 registros eletrônicos. Conclusões. O aumento da transmissão de pessoa para pessoa coloca em risco o ambiente doméstico e os prestadores de serviços de saúde. Erupções cutâneas são o sinal patognomônico durante a avaliação clínica. A imunidade de rebanho obtida durante a vacinação contra a varíola humana foi reduzida, contribuindo para o aumento dos casos e da disseminação.

Deconstructing the role of MALAT1 in MAPK-signaling in melanoma: insights from antisense oligonucleotide treatment.

The long non-coding RNA (lncRNA) MALAT1 is a regulator of oncogenesis and cancer progression. MAPK-pathway upregulation is the main event in the development and progression of human cancer, including melanoma and recent studies have shown that MALAT1 has a significant impact on the regulation of gene and protein expression in the MAPK pathway. However, the role of MALAT1 in regulation of gene and protein expression of the MAPK-pathway kinases RAS, RAF, MEK and ERK in melanoma is largely unknown. We demonstrate the impacts of antisense oligonucleotide (ASO)-based MALAT1-inhibition on MAPK-pathway gene regulation in melanoma. Our results showed that MALAT1-ASO treatment decreased BRAF RNA expression and protein levels, and MALAT1 had increased correlation with MAPK-pathway associated genes in melanoma patient samples compared to healthy skin. Additionally, drug-induced MAPK inhibition upregulated MALAT1-expression, a finding that resonates with a paradigm of MALAT1-expression presented in this work: MALAT1 is downregulated in melanoma and other cancer types in which MALAT1 seems to be associated with MAPK-signaling, while MALAT1-ASO treatment strongly reduced the growth of melanoma cell lines, even in cases of resistance to MEK inhibition. MALAT1-ASO treatment significantly inhibited colony formation in vitro and reduced tumor growth in an NRAS-mutant melanoma xenograft mouse model in vivo, while showing no aberrant toxic side effects. Our findings demonstrate new insights into MALAT1-mediated MAPK-pathway gene regulation and a paradigm of MALAT1 expression in MAPK-signaling-dependent cancer types. MALAT1 maintains essential oncogenic functions, despite being downregulated.