Treatment of Acute Kidney Injury: A Review of Current Approaches and Emerging Innovations.

Acute kidney injury (AKI) is a complex and life-threatening condition with multifactorial etiologies, ranging from ischemic injury to nephrotoxic exposures. Management is founded on treating the underlying cause of AKI, but supportive care-via fluid management, vasopressor therapy, kidney replacement therapy (KRT), and more-is also crucial. Blood pressure targets are often higher in AKI, and these can be achieved with fluids and vasopressors, some of which may be more kidney-protective than others. Initiation of KRT is controversial, and studies have not consistently demonstrated any benefit to early start dialysis. There are no targeted pharmacotherapies for AKI itself, but some do exist for complications of AKI; additionally, medications become a key aspect of AKI management because changes in renal function and dialysis support can lead to issues with both toxicities and underdosing. This review will cover existing literature on these and other aspects of AKI treatment. Additionally, this review aims to identify gaps and challenges and to offer recommendations for future research and clinical practice.

Blood lead levels in an endangered vulture decline following changes in hunting activity.

Lead ammunition stands out as one of the most pervasive pollutants affecting wildlife. Its impact on bird populations have spurred efforts for the phase-out of leaded gunshot in several countries, although with varying scopes and applications. Ongoing and future policy changes require data to assess the effectiveness of adopted measures, particularly in the current context of biodiversity loss. Here, we assessed the long-term changes in blood lead (Pb) levels of Egyptian vultures from the Canary Islands, Spain, which have been severely affected by Pb poisoning over the past two decades. During this period, the reduction in hunting pressure and changes in legislation regarding firearms usage for small game hunting likely contributed to a decrease in environmental Pb availability. As anticipated, our results show a reduction in Pb levels, especially after the ban on wild rabbit hunting with shotgun since 2010. This effect was stronger in the preadult fraction of the vulture population. However, we still observed elevated blood Pb levels above the background and clinical thresholds in 5.6% and 1.5% of individuals, respectively. Our results highlight the positive impact of reducing the availability of Pb from ammunition sources on individual health. Nonetheless, the continued use of Pb gunshot remains an important source of poisoning, even lethal, mainly affecting adult individuals. This poses a particular concern for long-lived birds, compounding by potential chronic effects associated with Pb bioaccumulation. Our findings align with recent studies indicating insufficient reductions in Pb levels among European birds of prey, attributed to limited policy changes and their uneven implementation. We anticipated further reductions in Pb levels among Egyptian vultures with expanded restrictions on hunting practices, including a blanket ban on Pb shot usage across all small game species.

The trends of interpersonal violence burden in Latin America, 1990 to 2019: secondary data analysis from the global burden of disease study.

OBJECTIVES: We aimed to analyse the trends of interpersonal violence (IV) in Latin America (LA) between 1990 and 2019 for females and males at a national level. STUDY DESIGN: Cross-sectional descriptive study. METHODS: Following the 2019 Global Burden of Disease study we report IV mortality, premature mortality, years lived with disability and disability-adjusted life-years (DALYs) in LA by sex. To estimate the DALYs trends, we conducted a Joinpoint regression analysis. RESULTS: Across all LA countries, IV burden was higher among males. Most of the IV burden was attributable to premature death, with a higher percentage in men than women. The burden of IV was most pronounced within the 15 to 39 age-groups in the majority of countries. Physical violence (PV) by firearm was the main cause of IV in LA, followed by PV by other means. Women in LA experienced at least twice as many sexual violence DALYs as men. IV in LA exhibited heterogeneous trends, with certain countries witnessing a significant decline in the IV DALYs rate, while others displayed a significant increase. CONCLUSIONS: Our results show the great heterogeneity of IV burden present in the region as the trends varied from one country to another. Policing and criminal justice institutions in LA have failed to reduce crime and violence. Thus, tailored preventive measures and public policies that account for the specific context and geographical areas where this phenomenon is prevalent are urgently needed.

MGRN1 depletion promotes intercellular adhesion in melanoma by upregulation of E-cadherin and inhibition of CDC42.

Mahogunin Ring Finger 1 is an E3-ubiquitin ligase encoded by the color gene MGRN1. Our previous in vitro and in vivo studies demonstrated that Mgrn1 deletion in mouse melanoma cells induced cell differentiation and adhesion, and decreased cell motility and invasion on collagen I, and lung colonization in an in vivo model. Here, we investigated the role of MGRN1 on human melanoma cell morphology, adhesion and expression of genes/proteins involved in an EMT-like transition. We demonstrated that wild-type BRAF human melanoma cells adopted a clustering-like morphology on collagen I, with permanent MGRN1 abrogation resulting in bigger cell clusters. Enhanced intercellular adhesion was mostly mediated by induction of E-cadherin and higher co-localization with ß-catenin. Transcriptional upregulation of E-cadherin likely occurred through downregulation of the ZEB1 repressor. Finally, pulldown assays showed reduced activation of CDC42 in the absence of MGRN1, which was reverted after E-cadherin silencing. Overall, these findings highlight a new MGRN1-dependent pathway regulating melanoma cell shape, motility, and invasion potential.

Therapeutic Plasma Exchange: Core Curriculum 2023.

From producing individual blood components for transfusion to the removal of pathogenic substances, apheresis is a cornerstone of modern medical therapies. The use of therapeutic plasma exchange (TPE), in which plasma and its soluble constituents are removed from the body in exchange for a replacement fluid, can be organ- and life-saving in many diseases. Given the notable similarities between TPE and hemodialysis, the nephrologist is often responsible for managing TPE. As such, one must be familiar with the technologies, approach to therapy, indications for use, and complications. TPE uses centrifugation or membrane separation technologies, with the latter able to be performed with certain hemodialysis machines familiar to the nephrologist. Furthermore, primary kidney diseases such as anti-glomerular basement membrane disease are frequently associated with autoantibodies, potentially making them ideal candidates for TPE. Nevertheless, the use of TPE in many kidney diseases is controversial because of the lack of supporting evidence. This review discusses TPE from the perspective of a nephrologist responsible for prescribing and managing TPE, as well as nephrologists engaged in the care of patients undergoing the procedure.

Updates on HIV and Kidney Disease.

PURPOSE OF REVIEW: With the advent of antiretroviral therapy, HIV infection has become a chronic disease in developed countries. RECENT FINDINGS: Non-HIV-driven risk factors for kidney disease, such as APOL1 risk variants and other genetic and environmental factors, have been discovered and are better described. Consequently, the field of HIV-associated kidney disease has evolved with greater attention given to traditional risk factors of CKD and antiretroviral treatment's nephrotoxicity. In this review, we explore risk factors of HIV-associated kidney disease, diagnostic tools, kidney pathology in HIV-positive individuals, and antiretroviral therapy-associated nephrotoxicity.

From screening to treatment: the new landscape of diabetic kidney disease.

Globally, diabetes mellitus is the leading cause of chronic kidney disease (CKD), and it is predicted to increase in the following years. Despite its high prevalence, CKD remains under diagnosed. In this BMC Medicine collection of articles on diabetic kidney disease (DKD), we place in context the importance of screening and early detection of DKD and the most accurate tools to monitor for optimal glycemic control in this his risk population. Further, we address this population's risk for severe complications such as stroke and all-cause mortality. We close this editorial by summarizing recent advances in management of this vulnerable population of patients with DKD, including guideline-directed medical therapy, novel treatments, and predictors of treatment failure.

Utilidad de una aplicación web interactiva en la mejora del control de los factores de riesgo cardiovascular. Proyecto Control-RC / Impact of an interactive web application on the improvement of cardiovascular risk factors control. Control-RCV project

Objetivo Valorar la utilidad de una aplicación web interactiva en la mejora del control del riesgo cardiovascular (CV). Métodos Estudio observacional en el que médicos de Atención Primaria, incluyeron consecutivamente a pacientes con un riesgo CV elevado/muy elevado y al menos uno de los siguientes factores de riesgo mal controlado: hipertensión, dislipidemia o diabetes. Al introducir los datos, la aplicación generaba un informe indicando los objetivos recomendados y los reales, y el médico podía modificar la actitud terapéutica. El estudio consistió en 2visitas: basal y a los 4-6 meses. Resultados Se incluyó a 379 pacientes (66,4 ± 9,0 años; 67,3% varones; 67,5/32,5% con un riesgo CV elevado/muy elevado). Basalmente, la mayoría recibió recomendaciones sobre la restricción de sal (90,2%), dieta (94,2%) y actividad física (94,5%). En cuanto al tratamiento farmacológico, el 53,6% no tomaba combinaciones fijas. Solo el 35,1% cumplía siempre con el tratamiento. En el 95,8% se realizó educación sanitaria, en el 29,8% se empleó la polipíldora y en el 24,3% se incidió sobre los cambios en hábitos de vida. En la segunda visita se objetivó una mejoría significativa de los cambios en el estilo de vida (menor tabaquismo y consumo de alcohol, y mayor actividad física, restricción de sal, dieta), factores de riesgo CV (menor obesidad, presión arterial, lípidos, HbA1c), así como una reducción del riesgo CV. El cumplimiento terapéutico mejoró. Conclusiones El empleo de la aplicación permite mejorar los estilos de vida y el control de los factores de riesgo, reduciendo el riesgo CV y mejorando el cumplimiento terapéutico (AU)

Objective To ascertain the utility of an interactive web application in the improvement of cardiovascular (CV) risk control. Methods Observational study in which primary care physicians consecutively included high/very high CV risk patients with at least one of the following risk factors poorly controlled: hypertension, dyslipidemia or diabetes. After the introduction of data, the application generated a report comparing the recommended and the real targets. Then, the physicians could modify the therapeutic approach. The study consisted of 2 visits, at baseline and after 4-6 months. Results A total of 379 patients (66.4±9.0 years; 67.3% male; 67.5/32.5% with high/very high CV risk) were included. At baseline, most patients received recommendations about salt restriction (90.2%), diet (94.2%), and physical activity (94.5%). With regard to pharmacological treatments, 53.6% of patients were not taking fixed-dose combinations. Only 35.1% met always with treatment. In 95.8% of patients sanitary education was given, in 29.8% the polypill was prescribed and in 24.3% lifestyle changes were recommended. During the second visit, a significant improvement in lifestyle changes (less smoking and alcohol consumption, and more physical activity, salt restriction and diet), CV risk factors (less obesity, blood pressure, lipids, HbA1c), as well as CV risk reduction were observed. The therapeutic compliance also improved. Conclusions The use of the application allows improving lifestyle and CV risk factors control, leading to a reduction of CV risk and an improvement of therapeutic compliance (AU)

[Impact of an interactive web application on the improvement of cardiovascular risk factors control. Control-RCV project]. / Utilidad de una aplicación web interactiva en la mejora del control de los factores de riesgo cardiovascular. Proyecto Control-RCV.

OBJECTIVE: To ascertain the utility of an interactive web application in the improvement of cardiovascular (CV) risk control. METHODS: Observational study in which primary care physicians consecutively included high/very high CV risk patients with at least one of the following risk factors poorly controlled: hypertension, dyslipidemia or diabetes. After the introduction of data, the application generated a report comparing the recommended and the real targets. Then, the physicians could modify the therapeutic approach. The study consisted of 2 visits, at baseline and after 4-6 months. RESULTS: A total of 379 patients (66.4±9.0 years; 67.3% male; 67.5/32.5% with high/very high CV risk) were included. At baseline, most patients received recommendations about salt restriction (90.2%), diet (94.2%), and physical activity (94.5%). With regard to pharmacological treatments, 53.6% of patients were not taking fixed-dose combinations. Only 35.1% met always with treatment. In 95.8% of patients sanitary education was given, in 29.8% the polypill was prescribed and in 24.3% lifestyle changes were recommended. During the second visit, a significant improvement in lifestyle changes (less smoking and alcohol consumption, and more physical activity, salt restriction and diet), CV risk factors (less obesity, blood pressure, lipids, HbA1c), as well as CV risk reduction were observed. The therapeutic compliance also improved. CONCLUSIONS: The use of the application allows improving lifestyle and CV risk factors control, leading to a reduction of CV risk and an improvement of therapeutic compliance.

Epidemiología del ictus cardioembólico y su asociación con la penetración de los ACOD en España: primer estudio poblacional 2005-2018 / Epidemiology of atrial fibrillation-related ischemic stroke and its association with DOAC uptake in Spain: first national population-based study 2005 to 2018

Introducción y objetivos: La prevalencia y la incidencia de la fibrilación auricular (FA), un importante factor de riesgo de ictus cardioembólico, han aumentado sustancialmente en los últimos años. Sin embargo, varios estudios europeos han observado una disminución en la tasa de ictus cardioembólico asociada con un aumento de la penetración de los anticoagulantes orales de acción directa (ACOD). Este estudio ecológico evalúa la asociación entre la penetración de los ACOD y la tasa de incidencia de ictus cardioembólicos en España. Métodos: Los datos se obtuvieron del Registro de Actividad Sanitaria Especializada del Ministerio de Sanidad de España (RAE-CMBD). Los ictus cardioembólicos se identificaron mediante códigos ICD. Las tasas de incidencia se estandarizaron por edad y se ajustaron a la población estándar europea de 2013. Se utilizaron modelos de regresión de Poisson para estimar la asociación entre la penetración de los ACOD y la tasa de ictus cardioembólico en pacientes de 65 o más años. Resultados: La tasa de incidencia ajustada (TI) del ictus cardioembólico aumentó desde 2005 (2,20/100.000 personas/año) hasta 2012 (2,67). A partir de 2012, tras la introducción de los ACOD para la prevención del ictus cardioembólico en España, la TI se ha mantenido constante o ha disminuido ligeramente (en 2018, 2,66). Los resultados del modelo de regresión de Poisson indican que la penetración de los ACOD tiene una influencia estadísticamente significativa en la tasa de ictus cardioembólicos de los mayores de 65 años (RDI=0,995; IC95%, 0,995-0,996). Conclusiones: Los resultados de este estudio muestran una asociación entre la penetración de los ACOD y una menor incidencia de ictus cardioembólicos. A pesar de que esta asociación no implica causalidad, indica que una mayor penetración de los ACOD podría llevar a un mayor beneficio clínico para los pacientes con FA en España (AU)

Introduction and objectives: The incidence and prevalence of atrial fibrillation (AF), a major risk factor for stroke, has increased substantially in the past few years. However, several studies have reported a decline in AF-related stroke rates associated with higher uptake of direct oral anticoagulants (DOACs). This ecological study evaluated the association between DOAC uptake in Spain and the incidence rate (IR) of AF-related ischemic stroke. Methods: Data were obtained from the Registry of Activity of Specialized Healthcare of the Spanish Ministry of Health (RAE-MDS). AF-related ischemic strokes were identified using International Classification of Diseases codes. IR were age-standardized and adjusted to the 2013 European standard population. Poisson regression models were used to identify the association between DOAC uptake and AF-related ischemic stroke in patients aged ≥ 65 years. Results: Before the use of DOACs, the adjusted IR of AF-related ischemic stroke increased steadily from 2005 (IR=2.20 per 100 000 person/y) to 2012 (IR=2.67). Upon DOAC uptake in Spain from 2012 onwards for AF-related ischemic stroke prevention, the IR remained constant or decreased slightly (IR in 2018=2.66). Poisson regression showed that DOAC uptake was a significant predictor for the rate of AF-related ischemic stroke in patients older than 65 years (IRR=0.995; 95%CI, 0.995-0.996). Conclusions: This study shows an association between DOAC use and a reduced incidence of AF-related ischemic stroke. While this association is based on aggregate data and cannot demonstrate causality, these findings suggest that higher DOAC uptake could improve health outcomes in AF patients in Spain (AU)

Evaluation of prophylaxis in primary prevention with acetylsalicylic acid in people with diabetes: A scoping review

Background: The efficacy and safety of acetylsalicylic acid (ASA) prophylaxis for the primary prevention of atherosclerotic cardiovascular disease (ACVD) remain controversial in people with diabetes (DM) without ACVD, because the possible increased risk of major bleeding could outweigh the potential reduction in the risk of mortality and of major adverse cardiovascular events (MACE) considered individually or together. Objective: To evaluate the overall risk-benefit of ASA prophylaxis in primary prevention in people with DM and to compare the recommendations of the guidelines with the results of the meta-analyses (MA) and systematic reviews (SR). Material and methods: We searched Medline, Google Scholar, Embase, and the Cochrane Library for SR and MA published from 2009 to 2020 which compared the effects of ASA prophylaxis versus placebo or control followed up for at least one year in people with DM without ACVD. Heterogeneity among the randomized clinical trials (RCT) included in the SR and MA was assessed. Cardiovascular outcomes of efficacy (all-cause mortality [ACM], cardiovascular mortality [CVM], myocardial infarction [MI], stroke and MACE) and of safety (major bleeding events [MBE], major gastrointestinal bleeding events [MGIBE], and intracranial and extracranial bleeding) were shown. Results: The recommendations of 12 guidelines were evaluated. The results of 25 SR and MA that included a total of 20 RCT were assessed. None of the MA or SR showed that ASA prophylaxis decreased the risk of ACM, CVM or MI. Only two of the 19 SR and MA that evaluated ischemic stroke showed a decrease in the stroke risk (mean 20.0% [SD±5.7]), bordering on statistical significance. Almost half of the MA and SR showed, bordering on statistical significance, a risk reduction for the MACE composite endpoint (mean 10.5% [SD±3.3]). The significant increases in MGIBE risk ranged from 35% to 55% (AU)

Antecedentes: La eficacia y la seguridad de la profilaxis con ácido acetilsalicílico (AAS) para la prevención primaria de la enfermedad cardiovascular arteriosclerótica (ECVA) siguen siendo controvertidas en personas con diabetes (DM) sin ECVA, ya que el posible aumento del riesgo de hemorragias graves podría superar la posible disminución del riesgo de mortalidad y de los principales episodios adversos cardiovasculares (MACE) considerados individualmente o en conjunto. Objetivo: Evaluar el riesgo-beneficio de la profilaxis con AAS en prevención primaria en personas con DM y comparar las recomendaciones de las guías de práctica clínica con los resultados de los metaanálisis (MA) y revisiones sistemáticas (RS). Material y métodos: Se realizaron búsquedas en Medline, Google Scholar, Embase y Biblioteca Cochrane de RS y MA publicados desde 2009 hasta 2020 que compararan los efectos de AAS versus placebo o control en seguimiento durante al menos un año en personas con DM sin ECVA. Se valoraron la heterogeneidad entre los ensayos clínicos aleatorizados (ECA) incluidos en las RS y MA. Se mostraron los resultados cardiovasculares de eficacia (muerte por cualquier causa [MCC], muerte cardiovascular [MCV], infarto de miocardio [IM], ictus y MACE) y de seguridad (episodios hemorrágicos importantes [EHI], episodios hemorrágicos gastrointestinales importantes [EHGI], hemorragias intracraneales y extracraneales). Resultados: Se valoraron las recomendaciones de 12 guías de práctica clínica. Se evaluaron los resultados de 25 RS y MA que incluyeron un total de 20ECA. Ningún MA ni RS mostró que la profilaxis con AAS disminuyera el riesgo de MCC, MCV o IM. Solo dos de los 19 SR y MA que evaluaron el ictus isquémico mostraron una disminución en el riesgo de ictus (media 20,0% [DE±5,7]), rozando la significación estadística (AU)

Posicionamiento SEMERGEN en el abordaje de la insuficiencia cardíaca crónica en atención primaria / SEMERGEN positioning on approaching chronic heart failure in primary care

La insuficiencia cardíaca (IC) es un problema de salud pública que genera una gran carga asistencial tanto hospitalaria como en atención primaria (AP). La publicación de numerosos estudios sobre IC durante los últimos años ha supuesto un cambio de paradigma en el abordaje de este síndrome, en el que la labor de los equipos de AP va adquiriendo un protagonismo mayor. Las recientes guías publicadas por la Sociedad Europea de Cardiología han introducido cambios fundamentalmente en el manejo del paciente con IC. La nueva estrategia propuesta, con fármacos que reducen las hospitalizaciones y frenen la progresión de la enfermedad, debe ser ya una prioridad para todos los profesionales implicados. En este documento de posicionamiento se analiza una propuesta de abordaje basada en equipos multidisciplinares con el liderazgo de los médicos de familia, clave para proporcionar una atención de calidad a lo largo de todo el proceso de la enfermedad, desde su prevención hasta el final de la vida (AU)

Heart failure (HF) is a public health problem that generates a large healthcare burden both in hospitals and in Primary Care (PC). The publication of numerous studies about HF in recent years has led to a paradigm shift in the approach to this syndrome, in which the work of PC teams is gaining greater prominence. The recent guidelines published by the European Society of Cardiology have fundamentally introduced changes in the management of patients with HF. The new proposed strategy, with drugs that reduce hospitalizations and slow the progression of the disease, should now be a priority for all professionals involved. This position document analyzes a proposal for an approach based on multidisciplinary teams with the leadership of family doctors, key to providing quality care throughout the entire process of the disease, from its prevention to the end of the life (AU)

Evaluation of prophylaxis in primary prevention with acetylsalicylic acid in people with diabetes: A scoping review.

BACKGROUND: The efficacy and safety of acetylsalicylic acid (ASA) prophylaxis for the primary prevention of atherosclerotic cardiovascular disease (ACVD) remain controversial in people with diabetes (DM) without ACVD, because the possible increased risk of major bleeding could outweigh the potential reduction in the risk of mortality and of major adverse cardiovascular events (MACE) considered individually or together. OBJECTIVE: To evaluate the overall risk-benefit of ASA prophylaxis in primary prevention in people with DM and to compare the recommendations of the guidelines with the results of the meta-analyses (MA) and systematic reviews (SR). MATERIAL AND METHODS: We searched Medline, Google Scholar, Embase, and the Cochrane Library for SR and MA published from 2009 to 2020 which compared the effects of ASA prophylaxis versus placebo or control followed up for at least one year in people with DM without ACVD. Heterogeneity among the randomized clinical trials (RCT) included in the SR and MA was assessed. Cardiovascular outcomes of efficacy (all-cause mortality [ACM], cardiovascular mortality [CVM], myocardial infarction [MI], stroke and MACE) and of safety (major bleeding events [MBE], major gastrointestinal bleeding events [MGIBE], and intracranial and extracranial bleeding) were shown. RESULTS: The recommendations of 12 guidelines were evaluated. The results of 25 SR and MA that included a total of 20 RCT were assessed. None of the MA or SR showed that ASA prophylaxis decreased the risk of ACM, CVM or MI. Only two of the 19 SR and MA that evaluated ischemic stroke showed a decrease in the stroke risk (mean 20.0% [SD±5.7]), bordering on statistical significance. Almost half of the MA and SR showed, bordering on statistical significance, a risk reduction for the MACE composite endpoint (mean 10.5% [SD±3.3]). The significant increases in MGIBE risk ranged from 35% to 55%. The significant increases in the risk of MBE and extracraneal bleeding were 33.4% (SD±14.9) and 54.5% (SD±0.7) respectively. CONCLUSION: The overall risk-benefit assessment of ASA prophylaxis in primary prevention suggests that it should not be applied in people with DM.

Preliminary survey of the occurrence of mycotoxins in cereals and estimated exposure in a northwestern region of Mexico.

Mycotoxins have several toxicological implications. In the present study, we evaluate the presence of aflatoxin B1 (AFB1), ochratoxin A (OTA), and fumonisin (FB1) in paddy rice, polished rice, and maize from the fields and markets in Nayarit State (Mexico). The results indicated the presence of AFB1 in 21.21% of paddy rice samples and 11.11% of market maize samples. OTA was present in only 3.03% (one sample) of paddy rice samples. FB1 was detected in 87.50% and 88.88% of maize samples from field and market, respectively. The estimated human exposure was calculated for FB1 using the probable daily intake (PDI), which suggested that FB1 could contribute to the development of diseases through the consumption of contaminated maize. Positive samples indicated that some rice and maize samples were not suitable for human consumption. Further efforts are needed to continue monitoring mycotoxins and update national legislation on mycotoxins accordingly.

[SEMERGEN positioning on approaching chronic heart failure in primary care]. / Posicionamiento SEMERGEN en el abordaje de la insuficiencia cardíaca crónica en atención primaria.

Heart failure (HF) is a public health problem that generates a large healthcare burden both in hospitals and in Primary Care (PC). The publication of numerous studies about HF in recent years has led to a paradigm shift in the approach to this syndrome, in which the work of PC teams is gaining greater prominence. The recent guidelines published by the European Society of Cardiology have fundamentally introduced changes in the management of patients with HF. The new proposed strategy, with drugs that reduce hospitalizations and slow the progression of the disease, should now be a priority for all professionals involved. This position document analyzes a proposal for an approach based on multidisciplinary teams with the leadership of family doctors, key to providing quality care throughout the entire process of the disease, from its prevention to the end of the life.