Implicaciones de la arginina-vasopresina y de la copeptina en la gestación normal y en la preeclampsia / Implications of arginine-vasopressin and copeptin in normal gestation and in pre-eclampsia

La preeclampsia representa una complicación específica de hipertensión del embarazo, que aparece de novo después de la 20 semana de gestación, acompañada de proteinuria y/o disfunción orgánica materna o útero-placentaria. A pesar de una etiopatogenia incierta, la alteración en el remodelado vascular de la arteria espiral e isquemia placentaria es la hipótesis más generalizada. El hallazgo de niveles elevados de copeptina, en mujeres con preeclampsia respecto a gestantes normales, ha puesto en valor la implicación de la arginina-vasopresina en la etiopatogenia de esta complicación. En este trabajo se considera su utilidad como marcador de preeclampsia a través de la revisión de los principales estudios efectuados con esta molécula.(AU)

Preeclampsia represents a specific complication of pregnancy hypertension, which appears de novo after the 20th week of gestation, accompanied by proteinuria and/or maternal or utero-placental organ dysfunction. Despite an uncertain etiopathogenesis, impaired vascular remodeling of the spiral artery and placental ischemia is the most widespread hypothesis. The finding of elevated levels of copeptin in women with preeclampsia compared to normal pregnant women has valued the involvement of arginine vasopressin in the etiopathogenesis of this complication. In this paper, its usefulness as a marker of preeclampsia is considered through the review of the main studies carried out with this molecule.(AU)

[Implications of arginine-vasopressin and copeptin in normal gestation and in pre-eclampsia]. / Implicaciones de la arginina-vasopresina y de la copeptina en la gestación normal y en la preeclampsia.

Preeclampsia represents a specific complication of pregnancy hypertension, which appears de novo after the 20th week of gestation, accompanied by proteinuria and/or maternal or utero-placental organ dysfunction. Despite an uncertain etiopathogenesis, impaired vascular remodeling of the spiral artery and placental ischemia is the most widespread hypothesis. The finding of elevated levels of copeptin in women with preeclampsia compared to normal pregnant women has valued the involvement of arginine vasopressin in the etiopathogenesis of this complication. In this paper, its usefulness as a marker of preeclampsia is considered through the review of the main studies carried out with this molecule.

Pharmacogenetic biomarkers for secukinumab response in psoriasis patients in real-life clinical practice.

BACKGROUND: Prediction of the response to a biological treatment in psoriasis patients would allow efficient treatment allocation. OBJECTIVE: To identify polymorphisms associated with secukinumab response in psoriasis patients in a daily practice setting. METHODS: We studied 180 SNPs in patients with moderate-to-severe plaque psoriasis recruited from 15 Spanish hospitals. Treatment effectiveness was evaluated by absolute PASI ≤3 and ≤1 at 6 and 12 months. Individuals were genotyped using a custom Taqman array. Multiple logistic regression models were generated. Sensitivity, specificity and area under the curve (AUC) were analysed. RESULTS: A total of 173 patients were studied at 6 months, (67% achieved absolute PASI ≤ 3 and 65% PASI ≤ 1) and 162 at 12 months (75% achieved absolute PASI ≤ 3 and 64% PASI ≤ 1). Multivariable analysis showed the association of different sets of SNPs with the response to secukinumab. The model of absolute PASI≤3 at 6 months showed best values of sensitivity and specificity. Four SNPs were associated with the capability of achieving absolute PASI ≤ 3 at 6 months. rs1801274 (FCGR2A), rs2431697 (miR-146a) and rs10484554 (HLCw6) were identified as risk factors for failure to achieve absolute PASI≤3, while rs1051738 (PDE4A) was protective. AUC including these genotypes, weight of patients and history of biological therapy was 0.88 (95% CI 0.83-0.94), with a sensitivity of 48.6% and specificity of 95.7% to discriminate between both phenotypes. CONCLUSION: We have identified a series of polymorphisms associated with the response to secukinumab capable of predicting the potential response/non-response to this drug in patients with plaque psoriasis.

Anemia renal: tratamientos actuales y moléculas emergentes / Renal anemia: current treatments and emerging molecules

La anemia es una complicación frecuente de la enfermedad renal cuya prevalencia aumenta a medida que progresa la enfermedad, empeora la calidad de vida de pacientes y aumenta la morbimortalidad. El fundamento actual para tratar la anemia renal se basa en empleo de agentes estimuladores de eritropoyesis, la suplementación con hierro y en menor medida, el uso de trasfusiones. La estimulación de la síntesis endógena de eritropoyetina y la mejora de la disponibilidad del hierro, a través de la inhibición de prolil-hidroxilasa del factor inducible por la hipoxia (PH-HIF), representa una nueva alternativa oral de tratamiento de la anemia renal. Los ensayos clínicos con inhibidores PH-HIF han demostrado su eficacia en mantener niveles de hemoglobina objetivo. Sin embargo, aspectos concernientes a la seguridad a largo plazo se encuentran pendientes de clarificar. En conclusión, los avances en la patogenia de anemia renal permiten disponer de tratamientos actuales para tratar la anemia renal y el desarrollo de nuevas moléculas, basadas en la inhibición de PH-HIF, representa una nueva alternativa eficaz para anemia asociada con enfermedad renal, especialmente en pacientes con resistencia a agentes estimuladores de eritropoyesis (AU)

Anemia is a common complication of kidney disease and the prevalence increases as the disease progresses. It worsens the quality of life of patients and increases morbidity and mortality. The current rationale for treating renal anemia is based on the use of erythropoiesis-stimulating agents, iron supplementation and, to a lesser extent, the use of transfusions. Stimulation of endogenous erythropoietin synthesis and improvement of iron availability, through inhibition of prolyl-hydroxylase-hypoxia-inducible factor (PH-HIF), represents a new oral alternative for renal anemia treatment. Clinical trials with PH-HIF inhibitors have demonstrated their efficacy in maintaining target hemoglobin levels. However, aspects concerning long-term safety are pending a clarification. In conclusion, advances in the pathogenesis of renal anemia make it possible to have current treatments to treat renal anemia. The development of new molecules, based on the inhibition of PH-HIF, represents a new effective alternative for anemia associated with kidney disease, especially in patients with resistance to erythropoiesis-stimulating agents (AU)

Diagnóstico inesperado de nefronoptisis en estudio genético de hipertensión por diagnóstico histológico de nefroangioesclerosis benigna evolucionada en paciente joven caucásico / Unexpected diagnosis of nephronopthisis in the genetic study of hypertension due to histological diagnosis of benign nephroangioesclerosis evolved in a young caucasian patient

Se presenta el caso de un paciente joven de raza caucásica, con una enfermedad renal de causa no clara, con un diagnóstico final establecido por biopsia renal de nefroangioesclerosis benigna evolucionada. Debido a la posibilidad de haber tenido hipertensión arterial en edad pediátrica (sin estudio ni tratamiento), con los hallazgos de biopsia renal, el estudio genético de hipertensión mostró polimorfismos de riesgo en los genes APOL1 y MYH9 y, además, un diagnóstico inesperado de una deleción completa del gen NPHP1 en homocigosis, asociada al desarrollo de nefronoptisis. En conclusión, este caso ilustra la importancia de hacer estudio genético, sobre todo en pacientes jóvenes con enfermedad renal de causa no clara, incluso teniendo un diagnóstico histológico de nefroangioesclerosis. (AU)

We present the case of a young Caucasian patient with renal disease of unclear cause, with a final diagnosis of advanced benign nephroangiosclerosis established by renal biopsy. Due to the possibility of having hypertension in pediatric age (without study or treatment), with the renal biopsy findings, the genetic study showed polymorphisms risk in the APOL1 and MYH9, and also an unexpected diagnosis of a complete deletion of the NPHP1 gene in homozygosis, associated with the development of nephronophthisis. In conclusion, this case illustrates the importance of carrying out a genetic study in youngs patients with renal disease unclear cause, even having a histological diagnosis of nephroangiosclerosis. (AU)

Recommendations for the prevention of healthcare-associated infections in nursing homes.

Nursing homes (NH) conceptually should look as much like a home as possible. However NH have unquestionable similarities with a nosocomium as they are places where many patients with underlying diseases and comorbidities accumulate. There is evidence of transmission of microorganisms between residents and between residents and caregivers. We have not found any recommendations specifically aimed at the prevention of nosocomial infections in NH by the major Public Health Agencies and, therefore, the Health Sciences Foundation (Fundación de Ciencias de la Salud) has convened a series of experts and 14 Spanish scientific societies to discuss recommendations that could guide NH personnel in establishing written programs for the control and reduction of these infections. The present document is the result of these deliberations and contains suggestions for establishing such control programs on a voluntary and flexible basis in NH. We also hope that the document can help the health authorities to encourage this control activity in the different territorial areas of Spain. In our opinion, it is necessary to draw up a written plan and establish the figure of a coordinator or person responsible for implementing these projects. The document includes measures to be implemented and ways of quantifying the reality of different problems and of monitoring the impact of the measures established.

Renal anemia: current treatments and emerging molecules.

Anemia is a common complication of kidney disease and the prevalence increases as the disease progresses. It worsens the quality of life of patients and increases morbidity and mortality. The current rationale for treating renal anemia is based on the use of erythropoiesis-stimulating agents, iron supplementation and, to a lesser extent, the use of transfusions. Stimulation of endogenous erythropoietin synthesis and improvement of iron availability, through inhibition of prolil-hydroxilase-hypoxia-inducible factor (PH-HIF), represents a new oral alternative for renal anemia treatment. Clinical trials with PH-HIF inhibitors have demonstrated their efficacy in maintaining target hemoglobin levels. However, aspects concerning long-term safety are pending a clarification. In conclusion, advances in the pathogenesis of renal anemia make it possible to have current treatments to treat renal anemia. The development of new molecules, based on the inhibition of PH-HIF, represents a new effective alternative for anemia associated with kidney disease, especially in patients with resistance to erythropoiesis-stimulating agents.

Nephroangiosclerosis: an update / Nefroangioesclerosis: actualización

Nephroangiosclerosis or kidney disease that accompanies chronic essential arterial hypertension has been known for more than a hundred years. The definitive diagnosis is established by renal biopsy, which is reserved for doubtful cases or atypical presentation, being in most cases a presumptive clinical diagnosis. The objective of this review is to analyse the main controversies that currently exist related to nephroangiosclerosis: inaccuracy in epidemiological aspects (prevalence and incidence unknown), diagnostic difficulties and lack of correlation studies between clinical data and histopathology, progression factors in Caucasians. Currently, with advances in genetic studies in hypertension, not using or redefining the term hypertensive kidney disease for another condition such as nephropathy related to the present genetic alteration is being considered. (AU)

La nefroangioesclerosis o enfermedad renal que acompaña a la hipertensión arterial esencial crónica, es una entidad conocida desde hace más de 100 años. El diagnóstico definitivo se establece por biopsia renal, la cual se reserva para casos dudosos o presentación atípica, siendo en la mayoría de casos un diagnóstico clínico de presunción. El objetivo de esta revisión es analizar las principales controversias que existen actualmente relacionadas con la nefroangioesclerosis: inexactitud en aspectos epidemiológicos (prevalencia e incidencia real desconocida), dificultades diagnósticas y falta de estudios de correlación entre datos clínicos e histopatología, factores de progresión en raza caucásica. Actualmente con los avances en estudios genéticos en hipertensión se está planteando abandonar o redefinir el término de enfermedad renal hipertensiva por otro como nefropatía relacionada con la alteración genética presente. (AU)

[Unexpected diagnosis of nephronopthisis in the genetic study of hypertension due to histological diagnosis of benign nephroangioesclerosis evolved in a young caucasian patient]. / Diagnóstico inesperado de nefronoptisis en estudio genético de hipertensión por diagnóstico histológico de nefroangioesclerosis benigna evolucionada en paciente joven caucásico.

We present the case of a young Caucasian patient with renal disease of unclear cause, with a final diagnosis of advanced benign nephroangiosclerosis established by renal biopsy. Due to the possibility of having hypertension in pediatric age (without study or treatment), with the renal biopsy findings, the genetic study showed polymorphisms risk in the APOL1 and MYH9, and also an unexpected diagnosis of a complete deletion of the NPHP1 gene in homozygosis, associated with the development of nephronophthisis. In conclusion, this case illustrates the importance of carrying out a genetic study in youngs patients with renal disease unclear cause, even having a histological diagnosis of nephroangiosclerosis.

High SARS-CoV-2 Seroprevalence after Second COVID-19 Wave (October 2020-April 2021), Democratic Republic of the Congo.

Serologic surveys are important tools for estimating the true burden of COVID-19 in a given population. After the first wave of SARS-CoV-2 infections, a household-based survey conducted in Kinshasa, Democratic Republic of the Congo, estimated >292 infections going undiagnosed for every laboratory-confirmed case. To ascertain the cumulative population exposure in Kinshasa after the second wave of COVID-19, we conducted a prospective population-based cross-sectional study using a highly sensitive and specific ELISA kit. The survey included 2,560 consenting persons from 585 households; 55% were female and 45% male. The overall population-weighted, test kit-adjusted SARS-CoV-2 seroprevalence was 76.5% (95% CI 74.5%-78.5%). The seroprevalence was 4-fold higher than during the first wave, and positivity was associated with age, household average monthly income, and level of education. Evidence generated from this population-based survey can inform COVID-19 response, especially vaccination campaign strategies in the context of vaccine shortages and hesitancy.

Nephroangiosclerosis: an update.

Nephroangiosclerosis or kidney disease that accompanies chronic essential arterial hypertension has been known for more than a hundred years. The definitive diagnosis is established by renal biopsy, which is reserved for doubtful cases or atypical presentation, being in most cases a presumptive clinical diagnosis. The objective of this review is to analyse the main controversies that currently exist related to nephroangiosclerosis: inaccuracy in epidemiological aspects (prevalence and incidence unknown), diagnostic difficulties and lack of correlation studies between clinical data and histopathology, progression factors in Caucasians. Currently, with advances in genetic studies in hypertension, not using or redefining the term hypertensive kidney disease for another condition such as nephropathy related to the present genetic alteration is being considered.

High Prevalence of Anti-Severe Acute Respiratory Syndrome Coronavirus 2 (Anti-SARS-CoV-2) Antibodies After the First Wave of Coronavirus Disease 2019 (COVID-19) in Kinshasa, Democratic Republic of the Congo: Results of a Cross-sectional Household-Based Survey.

BACKGROUND: In October 2020, after the first wave of coronavirus disease 2019 (COVID-19), only 8290 confirmed cases were reported in Kinshasa, Democratic Republic of the Congo, but the real prevalence remains unknown. To guide public health policies, we aimed to describe the prevalence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) immunoglobulin G (IgG) antibodies in the general population in Kinshasa. METHODS: We conducted a cross-sectional, household-based serosurvey between 22 October 2020 and 8 November 2020. Participants were interviewed at home and tested for antibodies against SARS-CoV-2 spike and nucleocapsid proteins in a Luminex-based assay. A positive serology was defined as a sample that reacted with both SARS-CoV-2 proteins (100% sensitivity, 99.7% specificity). The overall weighted, age-standardized prevalence was estimated and the infection-to-case ratio was calculated to determine the proportion of undiagnosed SARS-CoV-2 infections. RESULTS: A total of 1233 participants from 292 households were included (mean age, 32.4 years; 764 [61.2%] women). The overall weighted, age-standardized SARS-CoV-2 seroprevalence was 16.6% (95% CI: 14.0-19.5%). The estimated infection-to-case ratio was 292:1. Prevalence was higher among participants ≥40 years than among those <18 years (21.2% vs 14.9%, respectively; P < .05). It was also higher in participants who reported hospitalization than among those who did not (29.8% vs 16.0%, respectively; P < .05). However, differences were not significant in the multivariate model (P = .1). CONCLUSIONS: The prevalence of SARS-CoV-2 is much higher than the number of COVID-19 cases reported. These results justify the organization of a sequential series of serosurveys by public health authorities to adapt response measures to the dynamics of the pandemic.

Using models to advance medicine: mathematical modeling of post-myocardial infarction left ventricular remodeling.

The heart is an organ with limited capacity for regeneration and repair. The irreversible cell death and corresponding diminished ability of the heart to repair after myocardial infarction (MI), is a leading cause of morbidity and mortality worldwide. In this paper, a new mathematical model is presented to study the left ventricular (LV) remodeling and associated events after MI. The model accurately describes and predicts the interactions among heart cells and the immune system post-MI in the absence of medical interventions. The resulting system of nonlinear ordinary differential equations is studied both analytically and numerically in order to demonstrate the functionality and performance of the new model. To the best of our knowledge, this model is the only one of its kind to consider and correctly apply all of the known factors in diseased heart LV modeling. This model has the potential to provide researchers with a predictive computational tool to better understand the MI pathology and develop various cell-based treatment options, with benefits of lowering the cost and reducing the development time.

[Acute myocardial infarction and severe hypokalaemia due to liquorice consumption during COVID-19 confinement]. / Infarto agudo de miocardio e hipopotasemia severa por consumo de regaliz durante el confinamiento por COVID-19.

Liquorice is one of the oldest known herbs with medicinal properties and comprises up to 300 active compounds. It has been used for millennia for its digestive, anti-inflammatory and anti-infective properties. However, its possible toxic effects were described only a few years ago and there is growing interest in the side effects associated with chronic consumption. The main active component of liquorice is the prodrug glycyrrhizin and its active metabolite glycyrrhetic acid. It is a rare cause of hypokalaemia due to suppression of the renin-angiotensin-aldosterone axis, causing pseudohyperaldostenonism (PHA). We describe a rare case of secondary acute myocardial infarction in a patient with chronic consumption of liquorice.

Epigenetics in Non-tumor Immune-Mediated Skin Diseases.

Epigenetics is the study of the mechanisms that regulate gene expression without modifying DNA sequences. Knowledge of and evidence about how epigenetics plays a causative role in the pathogenesis of many skin diseases is increasing. Since the epigenetic changes present in tumor diseases have been thoroughly reviewed, we believe that knowledge of the new epigenetic findings in non-tumor immune-mediated dermatological diseases should be of interest to the general dermatologist. Hence, the purpose of this review is to summarize the recent literature on epigenetics in most non-tumor dermatological pathologies, focusing on psoriasis. Hyper- and hypomethylation of DNA methyltransferases and methyl-DNA binding domain proteins are the most common and studied methylation mechanisms. The acetylation and methylation of histones H3 and H4 are the most frequent and well-characterized histone modifications and may be associated with disease severity parameters and serve as therapeutic response markers. Many specific microRNAs dysregulated in non-tumor dermatological disease have been reviewed. Deepening the study of how epigenetic mechanisms influence non-tumor immune-mediated dermatological diseases might help us better understand the role of interactions between the environment and the genome in the physiopathogenesis of these diseases.