The effect of erythropoiesis-stimulating agents on systolic and diastolic blood pressure in hemodialysis patients: A systematic review and meta-analysis of clinical trials.

OBJECTIVE: Anemia is a common condition in end-stage renal disease (ESRD) patients. Erythropoiesis-stimulating agents (ESAs) are commonly used to treat anemia in these patients. However, concerns have been raised regarding their potential effects on blood pressure. This systematic review and meta-analysis aim to investigate the relationship between ESAs and changes in systolic and diastolic blood pressure in hemodialysis patients. METHOD: This study is a systematic review and meta-analysis based on clinical trial studies published in various databases, including Web of Science, Cochrane Library, Science Direct, PubMed, Embase, Scopus, and Google Scholar, between 1980 and the end of 2022. We evaluated the quality of articles using the Jadad scale checklist and analyzed the data using Stata 15 software. RESULTS: Our meta-analysis included 34 clinical trial studies. The results showed a significant increase in both systolic blood pressure (SBP) and diastolic blood pressure (DBP) after the consumption of ESAs compared to before consumption. The mean difference in SBP was 4.84mmHg (95% CI: 2.74-6.94; p-value<0.001) and in DBP was 4.69mmHg (95% CI: 2.67-6.71; p-value<0.001). No publication bias was observed. Our meta-regression analysis showed that sample size, quality assessment score, and geographical location of the study were significant factors related to observed heterogenicity in to mean difference of SBP (p-value≤0.20). For DBP, the sample size, quality assessment score and follow-up duration were significant variables (p-value≤0.20). CONCLUSION: Based on the findings of our study, it appears that receiving ESAs is associated with a significant increase in both SBP and DBP in hemodialysis patients, with an increase of about 5mmHg.

Doping and sports endocrinology: growth hormone, IGF-1, insulin, and erythropoietin.

Among the substances prohibited by the World Anti-Doping Agency, "peptide hormones, growth factors, related substances, and mimetics" are classified as prohibited both in- and out-of-competition in section S2. This work reviews growth hormone and its releasing peptides, insulin-like growth factor 1 as the main growth factor, insulin, and erythropoietin and other agents that affect erythropoiesis. This review analyzes the prevalence of use among professional athletes and gym clients, the forms of use, dosing, ergogenic effects and effects on physical performance, as well as side effects and anti-doping detection methods.

[Moderate anaemia refractory to oral iron in a pregnant woman with a history of bariatric surgery]. / Anemia moderada refractaria al hierro oral en una gestante con antecedente de cirugía bariátrica.

INTRODUCTION: Introduction: bariatric surgery involves nutritional and trace element deficiencies that may have a negative impact if not treated properly, especially in situations such as pregnancy. Case report: a patient who underwent biliopancreatic diversion surgery without subsequent therapeutic adherence consults due to edema; findings included 29-week gestation (type 1 intrauterine growth restriction) and moderate anemia. Vitamin supplementation, oligoelements, enteral nutrition, and intravenous iron were restarted. Due to poor hemoglobin response with repleted iron deposits, recombinant human erythropoietin was associated. Discussion: the most frequent nutritional deficiencies after malabsorptive bariatric surgery are sideropenia and hypoproteinemia. Sideropenia and anemia increase the risk of preterm delivery, low weight, and perinatal mortality. In patients with inadequate response to intravenous iron, treatment with recombinant human erythropoietin may be considered, although its use in pregnant women without chronic renal failure has no indication in the prescribing information of this drug.

INTRODUCCIÓN: Introducción: la cirugía bariátrica (CB) implica déficits nutricionales y de oligoelementos que pueden tener una repercusión negativa en caso de no tratarse adecuadamente, especialmente en situaciones como la gestación. Caso clínico: paciente sometida a CB del tipo de la derivación biliopancreática, sin adherencia terapéutica posterior, que acude por edemas, confirmándose la presencia de una gestación de 29 semanas (feto CIR de tipo I) y de anemia moderada. Se reinició la suplementación de vitaminas, oligoelementos, nutrición enteral y hierro intravenoso (FEIV). Debido a la escasa respuesta de la hemoglobina con depósitos de hierro repletados, se asoció eritropoyetina humana recombinante (rHuEPO). Discusión: los déficits nutricionales más frecuentes tras una CB malabsortiva son la ferropenia y la hipoproteinemia. La ferropenia y la anemia incrementan el riesgo del parto pretérmino, el bajo peso y la mortalidad perinatal. En las pacientes sin adecuada respuesta al FEIV puede plantearse el tratamiento con rHuEPO, aunque su uso en gestantes sin insuficiencia renal crónica no dispone de indicación en la ficha técnica.

Human recombinant erythropoietin reduces sensorimotor dysfunction and cognitive impairment in rat models of chronic kidney disease. / La eritropoyetina humana recombinante reduce la disfunción sensoriomotora y el deterioro cognitivo en ratas con enfermedad renal crónica.

INTRODUCTION: Chronic kidney disease (CKD) can cause anaemia and neurological disorders. Recombinant human erythropoietin (rHuEPO) is used to manage anaemia in CKD. However, there is little evidence on the effects of rHuEPO on behaviour and cognitive function in CKD. This study aimed to evaluate the impact of rHuEPO in sensorimotor and cognitive functions in a CKD model. METHODS: Male Wistar rats were randomly assigned to 4 groups: control and CKD, with and without rHuEPO treatment (1050 IU per kg body weight, once weekly for 4 weeks). The Morris water maze, open field, and adhesive removal tests were performed simultaneously to kidney damage induction and treatment. Markers of anaemia and renal function were measured at the end of the study. RESULTS: Treatment with rHuEPO reduced kidney damage and corrected anaemia in rats with CKD. We observed reduced sensorimotor dysfunction in animals with CKD and treated with rHuEPO. These rats also completed the water maze test in a shorter time than the control groups. CONCLUSIONS: rHuEPO reduces kidney damage, corrects anemia, and reduces sensorimotor and cognitive dysfunction in animals with CKD.

Platelet-to-lymphocyte and neutrophil-to-lymphocyte ratios as markers of erythropoietin resistance in chronic haemodialysis patients: a multicentre cross-sectional study. / Índices plaquetas-linfocito y neutrófilo-linfocito como marcadores de resistencia a la eritropoyetina en pacientes en hemodiálisis crónica: estudio transversal-multicéntrico.

INTRODUCTION: The platelet-to-lymphocyte (PLR) and neutrophil-to-lymphocyte (NLR) ratios are emerging markers of inflammation. Erythropoietin resistance is associated with increased morbidity and mortality in patients with chronic kidney disease and is influenced by inflammation, among other factors. Therefore, it would be reasonable to expect a relationship between these markers and erythropoietin resistance. METHODS: Multicentre cross-sectional study. The records of the haemodialysis sessions of 534 patients belonging to four of our dialysis centres were studied. 137 patients were excluded, so the final number of patients studied was 397. NLR, PLR and the erythropoietin resistance index (ERI) were calculated. RESULTS: The ERI was divided into quartiles and compared with the mean NLR and PLR of the four groups, with these differences being statistically significant (p=0.00058). In the regression analysis, the NLR value was able to predict ERI significantly (p<0.0001) (R2=0.029). The PLR value also predicted ERI significantly (p<0.0001) (R2=0.103). The ability of PLR to predict erythropoietin resistance was measured with the area under the ROC curve (AUC=0.681) (95% CI, 0.541-0.821). A PLR cut-off point of 125.5 would result in a sensitivity of 80.95% and 42.82% specificity. CONCLUSIONS: Both PLR and NLR could be considered acceptable markers of erythropoietin resistance. The PLR was a better predictor for the ERI than the NLR.

La obesidad como factor riesgo para eritrocitosis secundaria / Obesity as a risk factor for secondary erythrocytosis

Introducción. La obesidad es un problema de salud pública, está asociada exponencialmente al aumento del riesgo de desarrollar patologías como diabetes, cáncer, enfermedades cardiovasculares y pulmonares. En la altitud, la hipoxia hipobárica conllevaría una repercusión importante en personas con obesidad involucrando disminución de la funcionalidad pulmonar, incremento de HIF y de eritropoyetina que pueden condicionar el desarrollo de una eritrocitosis secundaria. Objetivo. Determinar el rol de la obesidad en la presentación de la eritrocitosis en un ambiente de hipoxia hipobárica. Material y métodos. Estudio descriptivo transversal con carácter retrospectivo que consideró 615 pacientes con eritrocitosis (EPA, ES) residentes a 3650 y 4150 m s. n. m., ciudades de La Paz y El Alto (Bolivia). Se analizó datos demográficos, clínicos y laboratoriales, considerando características del IMC según grados de obesidad. Resultados. Se observó que, el 7% que reflejaron IMC normal correlacionaron con EPA, mientras que el 93% distribuidos por grados de sobrepeso u obesidad correlacionaron con ES. Los eventos trombóticos estuvieron relacionados con el incremento eritropoyetina, no así con la obesidad. A mayor IMC, mayores fueron las concentraciones de eritropoyetina. La presentación de eritrocitosis fue representativa en varones (80 %), adicionalmente, la edad de presentación fue después de los 50 años de edad. Conclusiones. La obesidad constituye un factor de riesgo importante en la presentación de la eritrocitosis secundaria en grandes altitudes, su etiopatogenia está representada por el incremento de eritropoyetina sérica.

Introduction. Obesity is a public health problem, it is associated with an increased risk of developing pathologies such as diabetes, cancer, cardiovascular or lung diseases. At high-altitude, hypobaric hypoxia may imply a significant impact in people with obesity, it involves a decrease in lung functionality, an increase of HIF and erythropoietin conditioning the development of secondary erythrocytosis. Objective. To determine the role of obesity in the occurrence of erythrocytosis at a hypobaric hypoxia environment. Material and methods. Retrospective cross-sectional descriptive study that considered 615 patients with erythrocytosis (EPA, ES) residing at 3650 and 4150 m, La Paz and El Alto cities from Bolivia. Demographic, clinical and laboratory data by considering patients BMI characteristics as well as degrees of obesity were analyzed. Results. 7% corresponding to a normal BMI displayed correlation with CMS- erythrocytosis, while 93% distributed by degrees of overweight or obesity correlated with ES. Thrombotic events were related to increased erythropoietin, but not to obesity. The higher BMI, the higher erythropoietin concentrations were. Occurrence of erythrocytosis was representative in men (80%), likewise the occurrence age was after 50 years old. Conclusions. Obesity constitutes an important risk factor in the occurrence of secondary erythrocytosis at high altitude, its etiopathogenesis is represented by increased serum erythropoietin.

Efecto de la hemodiálisis de alto flujo en la dosis de eritropoyetina en pacientes con enfermedad renal crónica

Objetivo: Evaluar el requerimiento de eritropoyetina (EPO) tras el cambio de membrana de bajo a alto flujo en pacientes prevalentes en hemodiálisis. Secundariamente determinar la variación de β2-microglobulina, Proteína C reactiva (PCR) y ferritina. Material y métodos: Estudio retrospectivo observacional en pacientes prevalentes en hemodiálisis en dos centros de diálisis en Perú. Se determinaron las características clínicas y demográficas de los pacientes. Se determinó hemoglobina, porcentaje de saturación de transferrina, ferritina, Kt/V y dosis de EPO basal y cada 3 meses durante los 12 meses posteriores al cambio de dializador. Adicionalmente se determinó la PCR y β2-microglobulina a los 3, 6 y 12 meses. Resultados: Se incluyeron 58 pacientes que cumplieron con los criterios de inclusión y exclusión. La dosis de EPO basal fue 5 763,55 ± 3 000,69 UI/semana y a los 12 meses, 4031,18 ± 2 663,95 UI/semana (p=0,000) y la hemoglobina basal 11,10 ± 1,24 g/dl y a los 12 meses 11,69 ± 1,28 g/dl (p=0, 077). La β2-microglobulina disminuyó de 45,64 ± 11,39 mg/l a 26,26 ± 8,02 mg/l a los 12 meses (p=0,000). Conclusiones: En la población de estudio la dosis de EPO disminuyó 30% a los 12 meses sin cambios en la hemoglobina. La β2-microglobulina disminuyó 42,5% al año.

SUMMARY Objective: To evaluate the requirements of erythropoietin (EPO) after changing low membrane flow to high in patients on hemodialysis. Secondly, to evaluate changes in serum levels of beta 2 microglobulin, C-reactive protein (CRP) and ferritin. Methods: A retrospective-observational study was carried-out in patients on hemodialysis in two centers in Peru. Clinical and demographic characteristics of patients were reported. Levels of hemoglobin, ferritin saturation percentage, ferritin, Kt/V and EPO baseline doses and each three months for one year after changing the dialyzer were measured. Additionally, serum levels of C-reactive protein and beta 2 microglobulin at 3, 6 and 12 months were obtained. Results: A total of 58 were included; baseline EPO levels were 5 763.55 ± 3 000.69 UI/week and at 12 months were 4 031.18 ± 2663.95 UI/week (p=0.000); baseline hemoglobin was 11.10 ± 1.24 g/dl and 11.69 ± 1.28 g/dl (p=0.077) after 12 months. Serum levels of beta 2 microglobulin dropped from 45.64 ± 11.39 mg/l at baseline to 26.26 ± 8.02 mg/l at one year (p=0.000). Conclusions: EPO doses dropped 30% at 12 months with no changes in hemoglobin. Beta 2 microglobulin dropped 42.5% after one year.

Pitiriasis liquenoide varioliforme aguda posterior al inicio de eritropoyetina / Acute varioliform lichenoid pityriasis following the initiation of erythropoietin

Resumen La pitiriasis liquenoide varioliforme aguda (PLEVA) pertenece a un grupo de enfermedades categorizadas como pitiriasis liquenoides, junto con la enfermedad febril úlcero-necrótica de Mucha-Habermann y la pitiriasis liquenoide crónica (PLC). Se caracteriza por la aparición aguda de múltiples pápulas eritemato-violáceas con posterior necrosis, discromía residual y cicatrices varioliformes. Dentro de las teorías patogénicas propuestas se encuentra el posible papel de agentes infecciosos, trastornos linfoproliferativos, complejos inmunes e incluso, asociación a medicamentos. Se presenta un casode una mujer adulta con un cuadro típico de PLEVA con confirmación histopatológica, cuyas lesiones aparecieron posteriormente al inicio de eritropoyetina.

Abstract Pityriasis lichenoides et varioliformes acuta (PLEVA) is part of a group of diseases clustered as pityriasis lichenoides, next to febrile ulceronecrotic Mucha-Habermann disease and pityriasis lichenoides chronica. It's characterized by a sudden onset of multiple erythematous and violaceous papules which develop necrosis, leaving residual dyschromia and varioliform scars. It's been hypothesized the possible role of infectious agents, lymphoproliferative diseases, immune complexes and drugs. We present the case of a woman with a typical PLEVA with histopathological confirmation, whose lesions appeared after therapy with erythropoietin.

Electrochemical biosensor for erythropoietin detection in athletes / Biossensor eletroquímico para detecção de eritropoietina em atletas / Biosensor electroquímico para detección de eritropoyetina en deportistas

ABSTRACT Introduction: The cytokine erythropoietin (EPO) is a crucial hormone for producing RBCs, which carry oxygenated blood to the rest of the body. Objective: This paper aimed to create an electrochemical detection based on Fe2O3-NiO nanoparticles and graphene oxide to measure EPO levels in athletes' blood. Methods: On a glassy carbon electrode, Fe2O3-NiO@GO was synthesized using the electrochemical deposition method. Results: The Fe2O3-NiO@GO/GCE was validated by structural characterizations using scanning electron microscopy (SEM). The Fe2O3-NiO@GO/GCE was found to be a suitable and stable erythropoietin biosensor with a linear range of 0-500 ng/l and a detection limit of 0.03ng/l in electrochemical tests using the DPV technique. Fe2O3-NiO@GO/erythropoietin was investigated as a biosensor for erythropoietin in athlete's plasma. Conclusion: The results showed that the values obtained for recovery (94.56% to 98.40) and RSD (2.01% to 3.22%) were acceptable, indicating that the suggested technique can be used as a practical erythropoietin biosensor in blood samples. Level of evidence II; Therapeutic studies - investigation of treatment outcomes.

RESUMO Introdução: A citocina eritropoietina (EPO), é referida como um hormônio crucial para a produção de hemácias, que transportam o sangue oxigenado para o resto dos corpos. Objetivos: O objetivo deste trabalho foi criar uma detecção eletroquímica baseada em nanopartículas de Fe2O3-NiO e óxido de grafeno para medir os níveis de EPO no sangue dos atletas. Métodos: Em um eletrodo de carbono vítreo, o Fe2O3-NiO@GO foi sintetizado usando o método de deposição eletroquímica. Resultados: O Fe2O3-NiO@GO/GCE foi validado por caracterizações estruturais utilizando microscopia eletrônica de varredura (SEM). O Fe2O3-NiO@GO/GCE foi considerado um biosensor eritropoietina adequado e estável com uma faixa linear de 0-500 ng/l e um limite de detecção de 0,03ng/l em testes eletroquímicos utilizando a técnica DPV. O Fe2O3-NiO@GO/extropoietina foi investigado como um biosensor de eritropoietina no plasma do atleta. Conclusão: Os resultados mostraram que os valores obtidos para recuperação (94,56% a 98,40) e RSD (2,01% a 3,22%) foram aceitáveis, indicando que a técnica sugerida pode ser usada como um prático biosensor de eritropoietina em amostras de sangue. Nível de evidência II; Estudos terapêuticos - investigação dos resultados do tratamento.

RESUMEN Introducción: La citoquina eritropoyetina (EPO), se conoce como una hormona crucial para la producción de glóbulos rojos, que transportan la sangre oxigenada al resto del cuerpo. Objetivos: El objetivo de este trabajo fue crear una detección electroquímica basada en nanopartículas de Fe2O3-NiO y óxido de grafeno para medir los niveles de EPO en la sangre de los deportistas. Métodos: Sobre un electrodo de carbono vítreo, se sintetizó Fe2O3-NiO@GO mediante el método de deposición electroquímica. Resultados: El Fe2O3-NiO@GO/GCE fue validado por caracterizaciones estructurales mediante microscopía electrónica de barrido (SEM). El Fe2O3-NiO@GO/GCE resultó ser un biosensor de eritropoyetina adecuado y estable con un rango lineal de 0-500 ng/l y un límite de detección de 0,03ng/l en ensayos electroquímicos mediante la técnica DPV. Se investigó el uso de Fe2O3-NiO@GO/extropoietina como biosensor de eritropoyetina en el plasma de atletas. Conclusión: Los resultados mostraron que los valores obtenidos para la recuperación (94,56% a 98,40) y la RSD (2,01% a 3,22%) fueron aceptables, lo que indica que la técnica sugerida puede ser utilizada como un biosensor práctico de eritropoyetina en muestras de sangre. Nivel de evidencia II; Estudios terapéuticos - investigación de los resultados del tratamiento.

Increased Urinary Erythropoietin Excretion in Severe Sleep Apnea-Hipoapnea Syndrome: The Effect of CPAP. / El síndrome de apneas-hipoapneas del sueño (SAHS) grave incrementa la excreción urinaria de eritropoyetina. Efecto del tratamiento con CPAP.

INTRODUCTION: Tissue hypoxia stimulates the production of erythropoietin (EPO), the main effect of which is, in turn, to stimulate erythropoiesis. Sleep apnea-hypopnea syndrome (SAHS) is an entity characterized by repeated episodes of hypoxemia during sleep. OBJECTIVE: To analyze whether hypoxemia stimulated increased urinary excretion of EPO, and if so, to evaluate if treatment with continuous positive airway pressure (CPAP) can inhibit this phenomenon. METHODS: We studied 25 subjects with suspected SAHS who underwent a polysomnography study (PSG). EPO levels in first morning urine (uEPO) and blood creatinine and hemoglobin were determined in all patients. Patients with severe SAHS repeated the same determinations after CPAP treatment. RESULTS: Twelve subjects were diagnosed with severe SAHS (mean ± SD, AHI 53.1 ± 22.7). Creatinine and hemoglobin levels were normal in all subjects. uEPO was 4 times higher in the SAHS group than in the control group (1.32 ± 0.83 vs. 0.32 ± 0.35 UI/l, p <.002). CPAP treatment reduced uEPO to 0.61 ± 0.9 UI/l (p <.02), levels close to those observed in healthy subjects. No dose-response relationship was observed between severity of PSG changes and uEPO values. CONCLUSIONS: Patients with severe SAHS show increased uEPO excretion, but this normalizes after treatment with CPAP.

The anaemia control model: Does it help nephrologists in therapeutic decision-making in the management of anaemia? / El modelo de control de anemia: ¿ayuda al nefrólogo en la decisión terapéutica para el manejo de la anemia?

INTRODUCTION: Anaemia is common in haemodialysis patients and treating it with erythropoiesis-stimulating agents (ESAs) is complex due to many factors. OBJECTIVES: To assess the usefulness of the Anaemia Control Model (ACM) in the treatment of anaemia in haemodialysis. METHODS: ACM is a software that predicts the optimal dose of darbepoetin and iron sucrose to achieve target haemoglobin (Hb) and ferritin levels, and makes prescription suggestions. Study conducted in dialysis clinics lasting 18months with two intervention phases (IPs) with ACM (IP1, n:213; IP2, n:218) separated by a control phase (CP, n:219). The primary outcome was the percentage of Hb in range and the median dose of ESAs, and the secondary outcomes were transfusion, hospitalisation and cardiovascular events. Clinical and patient analyses were performed. Hb variability was assessed by the standard deviation (SD) of the Hb. We also analysed the patients with most of the suggestions confirmed (ACM compliant group). RESULTS: ACM increased the percentage of Hb in range: 80.9% in IP2, compared with 72.7% in the CP and reduced the intake of darbepoetin (IP1: 20 [70]; CP 30 [80] µg P=0.032) with less Hb fluctuation (0.91±0.49 in the CP to 0.82±0.37g/dl in IP2, P<0.05), improving in the ACM compliant group. The secondary outcomes decreased with the use of ACM. CONCLUSIONS: ACM helps to obtain better anaemia results in haemodialysis patients, minimising the risks of treatment with ESAs and reducing costs.

Eritrocitosis patológicas con niveles de eritropoyetina baja e incrementada: características clínicas y laboratoriales / Pathological erythrocytosis with low and increased erythropoietin levels: clinical and laboratory characteristics

RESUMEN: Introducción: Los pacientes con eritrocitosis patológicas en la altura, Eritrocitosis Secundaria o Eritrocitosis Patológica de Altura, ocasionalmente suelen presentar niveles de eritropoyetina (EPO) con variaciones notables respecto de los parámetros normales, reflejando ya sea concentraciones muy bajas o muy altas de EPO. Objetivo: Analizar la prevalencia de las eritrocitosis con EPO disminuida y de las eritrocitosis con EPO incrementada, así como, las características laboratoriales y clínicas inmiscuidas entre ellas. Material y Métodos: Se realizó un estudio descriptivo transversal de tipo retrospectivo. Se analizó historias clínicas de 44 pacientes eritrocíticos; de estos, 22 pacientes (5 mujeres, 17 varones) con registros de EPO sérica disminuida (100 mUI/ml) que constituyeron el Grupo 2. Todos ellos residentes a una altura >3650 m s. n. m. Se recolectó datos demográficos, clínicos y laboratoriales; asimismo, datos referentes a los tratamientos administrados, seguimiento y respectivas respuestas en ambos grupos. Resultados: La frecuencia de las eritrocitosis patológicas con EPO disminuida representó 5 % y de aquellas con EPO elevada 5 %.: Se debe considerar estudios específicos en pacientes eritrocíticos con EPO baja para descartar Policitemia Vera, asimismo, los pacientes con EPO incrementada implican mayor complejidad en el manejo médico.

ABSTRACT: Introduction: Patients with pathological erythrocytosis at high altitude, Secondary Erythrocytosis or High Altitude Pathological Erythrocytosis, occasionally present notable variations of erythropoietin (EPO) levels regarding normal parameters, reflecting either very low or very high EPO concentrations. Objective: To analyze the prevalence of erythrocytosis with decreased EPO and erythrocytosis with increased EPO, as well as the laboratory and clinical characteristics involved between them. Material and methods: A retrospective cross-sectional descriptive study was conducted. Clinical records of 44 patients with erythrocytosis were analyzed; of these, 22 (5 women, 17 men) with records of decreased serum EPO (100 mIU/ml) ml) specified as Group 2. All of them were high altitude dwellers (>3650 m a. s. l). Demographic, clinical and laboratory data were collected, including data about administered treatments, follow-up and responses in both groups. Results: Frequency of pathological erythrocytosis with decreased EPO was 5% and with elevated EPO 5%. There were no representative differences between both groups concerning the CBC variables. Patients with increased EPO showed more complications of erythrocytosis (27%) compared to those with decreased EPO (0%). Two types of treatment regimen were evidenced in each group: a) ATV+ASA, and b) ATV+ASA+HU. Erythrocytosis patients with decreased EPO receiving ATV+ASA had higher favorable responses 90% versus those with elevated EPO (80%). The ATV+ASA+HU regimen reflected better applicability in the increased EPO group. Conclusion: Specific studies should be considered in erythrocytosis patients with decreased EPO to rule out Polycythemia Vera, similarly, patients with increased EPO imply more complexity at medical management.

Anaemia in the elderly. / Anemia del anciano.

Anaemia is common in the elderly and is associated with an increased risk of physical, functional, and cognitive impairment, hospitalisation and mortality. Although it is unknown whether anaemia is a causal factor or a subrogated marker of worse health status, its correction can improve the patients' physical and functional capacity. Detection, classification, and treatment of anaemia should be a priority for the health system. The main causes of anaemia in the elderly are nutritional deficiencies and chronic disease, with or without kidney failure, although some cases are of indeterminate origin. Medical history and physical examination help to clarify its aetiology. A diagnostic algorithm based on data from the lab allows anaemia classification with a therapeutic orientation. Supplements of iron and maturation factors, as well as erythropoiesis-stimulating agents, constitute the mainstay of treatment, along with that of the underlying disease, whereas red blood cell transfusion should be reserved for severe cases.

Effect of intranasal administration of NeuroEPO in the histological structure of the olfactory mucosa of Wistar rats / Efecto de la administración intranasal de NeuroEPO en la estructura histológica de la mucosa olfatoria de ratas Wistar

Introduction: Strokes and neurodegenerative diseases are major global health problems, not only because they cause high mortality and disability, but due to the lack of effective therapies. NeuroEPO, a variant of recombinant human erythropoietin (rHu-EPO) with a low sialic acid content, has shown encouraging results as a potential neuroprotective agent when administered intranasally. Objective: To determine the effect of intranasal administration of NeuroEPO on the histological structure of the olfactory mucosa of Wistar rats. Materials and Methods: An experimental, prospective, and longitudinal study was conducted on Wistar rats. Ten healthy animals were randomly distributed into two groups of five each. The control group received a vehicle (0.3 μl/g/day) and the treated group received NeuroEPO (300 μg/kg/day). Both treatments were administered intranasally for 28 days. The histological characteristics of the olfactory mucosa were evaluated. The medians between the study groups were compared using the Mann-Whitney U test. Results: There were no alterations in the histological characteristics of the olfactory epithelium. However, slight hypertrophy and hyperplasia of the Bowman's glands were observed at the level of the lamina propria in the group treated with NeuroEPO. Conclusions: The administration of the nasal formulation of NeuroEPO did not induce histological alterations of the olfactory mucosa of Wistar rats under the experimental conditions of this research.

Introducción: Los accidentes cerebrovasculares y las enfermedades neurodegenerativas constituyen un importante problema de salud mundial. No solo porque causan una alta mortalidad y discapacidad, sino por la falta de terapias eficaces para tratarlos. La NeuroEPO, una variante de la eritropoyetina humana recombinante (rHu-EPO) con bajo contenido en ácido siálico, ha mostrado resultados alentadores como potencial agente neuroprotector al ser administrada por vía intranasal. Objetivo: Determinar el efecto de la administración intranasal de NeuroEPO en la estructura histológica de la mucosa olfatoria de ratas Wistar. Materiales y Métodos: Se realizó un estudio experimental, prospectivo y de corte longitudinal en ratas Wistar. Se utilizaron diez animales sanos distribuidos aleatoriamente en dos grupos de cinco cada uno. El grupo control recibió vehículo (0,3 μl/g/día) y el grupo tratado recibió NeuroEPO (300 μg/kg/día). Ambos tratamientos fueron administrados por vía intranasal durante 28 días. Fueron evaluadas las características histológicas de la mucosa olfatoria. Las medianas de los grupos del estudio fueron comparadas mediante la prueba U de Mann-Whitney. Resultados: No se evidenciaron alteraciones en las características histológicas del epitelio olfatorio. Sin embargo, a nivel de la lámina propia en el grupo tratado con NeuroEPO, se observó una ligera hipertrofia e hiperplasia de las glándulas de Bowman. Conclusiones: La administración de la formulación nasal de NeuroEPO no indujo alteraciones histopatológicas de la mucosa olfatoria de ratas Wistar en las condiciones experimentales de esta investigación.

Efecto hipoglicemiante de la NeuroEPO en ratas con y sin diabetes mellitus / Hypoglycemic effect of NeuroEPO in diabetic and non-diabetic rats

RESUMEN Introducción: La NeuroEPO es una variante no-hematopoyética de la eritropoyetina recombinante humana, que pudiera tener efecto hipoglicemiante. Objetivo: Evaluar la influencia de la NeuroEPO sobre la glicemia de ratas con diabetes mellitus y ratas no-diabéticas. Material y Métodos: Se realizaron experimentos en ratas Wistar con diabetes inducida por estreptozotocina, con y sin tratamiento con insulina, y en ratas no-diabéticas con una sobrecarga de glucosa. En cada experimento, un grupo recibió una inyección subcutánea de NeuroEPO (0,5 mg/kg) y otro el vehículo, y se determinó la glicemia durante 120 minutos. Se realizaron comparaciones mediante análisis de varianza de una y dos vías, seguidas por la prueba de Bonferroni. Las diferencias se consideraron significativas con valores de p < 0,05. Resultados: En las ratas diabéticas sin tratamiento con insulina, los niveles de glicemia del grupo con NeuroEPO disminuyeron de forma significativa. En las ratas no-diabéticas que recibieron NeuroEPO y una sobrecarga de glucosa, la glicemia fue similar al grupo control. En las ratas diabéticas que recibieron NeuroEPO e insulina la reducción de la glicemia fue mayor que en el grupo que solo recibió insulina. Conclusiones: La NeuroEPO tiene un efecto hipoglicemiante en ratas diabéticas, por un mecanismo insulinotrópico que muestra sinergismo con la insulina en el tratamiento de la hiperglicemia. Sin embargo, la NeuroEPO no influye en la tolerancia a la glucosa de ratas no-diabéticas, al menos de forma inmediata. Es necesario profundizar en los mecanismos mediante los cuales la NeuroEPO puede reducir la hiperglicemia, y la influencia de esta sustancia en condiciones de normoglicemia.

ABSTRACT Introduction: NeuroEPO is a non-hematopoietic variant of human recombinant erythropoietin, which may have a hypoglycemic effect. Objectives: To evaluate the influence of NeuroEPO on glycemia in diabetic and non-diabetic rats. Material and Methods: The experiments were conducted in Wistar rats with streptozotocin-induced diabetes with and without insulin treatment, and in non-diabetic rats with glucose overload. In each experiment, one group received a subcutaneous injection of NeuroEPO (0.5 mg/kg) and the other group received a vehicle. Glycemia was determined in 120 min. Comparisons were made using one-and two-way analysis of variance, followed by the Bonferroni test. The differences were considered significant with p values < 0,05. Results: In diabetic rats without insulin treatment, glycemic levels decreased significantly in the group that received NeuroEPO. In nondiabetic rats that received NeuroEPO and a glucose overload, glycemia was similar to that in the control group. In diabetic rats that received NeuroEPO and insulin, the glycemia reduction was greater than in the group that only received insulin. Conclusions: NeuroEPO has a hypoglycemic effect in diabetic rats due to an insulinotropic mechanism that shows synergism with insulin in the treatment of hyperglycemia. However, NeuroEPO does not influence the glucose tolerance in non-diabetic rats, at least immediately. It is necessary to delve into the mechanisms by which NeuroEPO can reduce hyperglycemia and the influence of this substance under conditions of normoglycemia.

Efficacy and safety of combined administration of erythropoietin and iron in comparison to iron therapy alone in orthopaedic surgery: systematic review and metanalysis / Eficacia y seguridad de la administración combinada de eritropoyetina y hierro en comparación con el tratamiento con hierro solo en cirugía ortopédica: revisión sistemática y metaanálisis

Abstract: Introduction: Iron deficiency anaemia in orthopaedic surgery is common and there is increased risk of blood transfusion and associated adverse reactions. The management involves administration of iron (oral or intravenous) and erythropoietin stimulating agents. Material and methods: We searched for PubMed, Embase, Google Scholar and Cochrane database to identify the studies from inception to April 2021. Randomized controlled trials with adult patients undergoing orthopedic surgery were included. The metanalysis compared patients who were administered combination of erythropoietin stimulating agents and iron in one group and iron alone. The primary outcome was the rate of blood transfusion and the secondary outcome studied were postoperative hemoglobin concentration, after treatment hemoglobin levels, and complications like mortality, stroke, myocardial infarction, deep vein thrombosis, pulmonary embolism and renal dysfunction. Results: Eleven studies were included. The combination of ESA and iron decreased number of patients who required blood transfusion in comparison to patients treated with iron therapy alone (RR, 0.73; 95% CI, 0.59 to 0.91, I(2) = 65%; p = 0.005). In subgroup analysis with oral and intravenous iron, the difference was not statistically significant (p = 0.24). Administration of erythropoietin either in high (≥ 80,000 IU) or low dose (≤ 80,000 IU) resulted in lower blood transfusion rates (p = 0.0007) with no significant difference between groups. The risk of mortality, myocardial infarction, stroke, deep vein thrombosis or pulmonary embolism did not significantly increase. Conclusion: Combined administration of ESA and iron versus iron only reduces the number of red blood cell transfusions in the postoperative period in orthopedic procedures with minimal risk of complications.

Resumen: Introducción: La anemia por deficiencia de hierro en la cirugía ortopédica es común y existe un mayor riesgo de transfusión de sangre y reacciones adversas asociadas. El tratamiento implica la administración de hierro (oral o intravenoso) y agentes estimulantes de la eritropoyetina. Material y métodos: Se realizaron búsquedas en PubMed, Embase, Google Académico y la base de datos Cochrane para identificar los estudios desde su inicio hasta Abril de 2021. Se incluyeron ensayos controlados aleatorios con pacientes adultos sometidos a cirugía ortopédica. El metaanálisis comparó pacientes a los que se les administró una combinación de agentes estimulantes de la eritropoyetina y hierro en un grupo y hierro solo. El resultado primario fue la tasa de transfusión de sangre y el resultado secundario estudiado fue la concentración de hemoglobina postoperatoria, los niveles de hemoglobina después del tratamiento y complicaciones como mortalidad, accidente cerebrovascular, infarto de miocardio, trombosis venosa profunda, embolia pulmonar y disfunción renal. Resultados: Se incluyeron 11 estudios. La combinación de AEE y hierro disminuyó el número de pacientes que requirieron transfusión de sangre en comparación con los pacientes tratados con tratamiento con hierro solo (RR, 0.73; IC del 95%, 0.59 a 0.91, I(2) = 65%; p = 0.005). En el análisis de subgrupos con hierro oral e intravenoso, la diferencia no fue estadísticamente significativa (p = 0.24). La administración de eritropoyetina en dosis altas (≥ 80,000 UI) o bajas (≤ 80,000 UI) dio lugar a tasas de transfusión de sangre más bajas (p = 0.0007) sin diferencias significativas entre los grupos. El riesgo de mortalidad, infarto de miocardio, accidente cerebrovascular, trombosis venosa profunda o embolia pulmonar no aumentó significativamente. Conclusión: La administración combinada de AEE y hierro frente al hierro solo reduce el número de transfusiones de glóbulos rojos en el período postoperatorio en procedimientos ortopédicos con un riesgo mínimo de complicaciones.

Implementation of a patient blood management program in pediatric scoliosis surgery.

OBJECTIVES: To determine whether the implementation of a blood conservation program, and the adoption and progressive association of different methods, reduces transfusion requirements in pediatric patients undergoing scoliosis surgery of different origins. MATERIAL AND METHOD: Quasi-experimental, nonrandomized, descriptive study, approved by the Ethics Committee for Research of our institution. 50 pediatric patients (ASA I-III) aged 5 to 18 years, undergoing scoliosis surgery of any etiology by a single posterior or double approach (anterior and posterior) were included. A historical group with no alternatives to transfusion: Group No ahorro=15 patients (retrospective data collection) was compared with another 3 prospective study groups: Group HNA (acute normovolemic hemodilution)=9 patients; Group HNA+Rec (intraoperative blood salvage)=14 patients, and Group EPO (HNA+Rec+erythropoietin±preoperative donation)=12 patients; according with the implementation schedule of the transfusion alternatives in our institution. RESULTS: The rate of transfusion in different groups (No ahorro, HNA, HNA+Rec, EPO) was 100, 66, 57, and 0% of the patients, respectively, with a mean±SD of 3.40±1.59; 1.33±1.41; 1.43±1.50; 0±0 RBC units transfused per patient, respectively. Statistically significant differences (P<.001) were found in both the transfusion rate and number of RBC units. CONCLUSIONS: The application of a multimodal blood transfusion alternatives program, individualized for each pediatric patient undergoing scoliosis surgery can avoid transfusion in all cases.

[Blunted erythropoietic response in the anemia of anorexia nervosa]. / Disminución de la respuesta eritropoyética en pacientes con anorexia nerviosa y anemia.

BACKGROUND AND OBJECTIVE: The cause of the anemia in anorexia nervosa (AN) has not been fully ascertained. Ferritin, folate and cobalamin values are usually within normal ranges. Anemia does not have a relationship with bone marrow changes and erythropoietin (EPO) levels have not been investigated. The objective of this study was to evaluate the EPO response in a small group of AN patients. PATIENTS AND METHODS: EPO levels were measured in serum samples of 41 female AN patients (11 with anemia, and 30 with normal blood cell count). The adequacy of EPO response was assessed by comparing the increase observed in a group of normal weight patients with anemia. RESULTS: EPO concentrations in anemic AN patients were higher than in non-anemic: 20.63mU/mL (4.04-28.46) vs 8.7mU/mL (3.9-20.93), P=.0088, but the increase in EPO was lower than expected (27.85mU/mL [17.7-118.9]), P=.014. BMI and the difference between actual and expected EPO were inversely correlated. CONCLUSIONS: Inadequate EPO response may partly explain anemia in AN, but further studies are necessary.

Utilidad de la eritropoyetina en el paciente quemado grave con anemia. Revisión del tema / Usefulness of erythropoietin in seriously burned patient with anemia. Topic review

La quemadura grave representa el tipo de agresión biológica más severo que puede sufrir el organismo y ponen en peligro la vida del paciente por el permanente riesgo de sepsis y falla multisistémica progresiva. La anemia incide en la morbilidad y mortalidad del quemado en estado grave; su tratamiento ha pasado por diversos momentos en la historia y su corrección depende de las transfusiones sanguíneas que aumentan el riesgo de complicaciones y reacciones adversas. Actualizar los conocimientos sobre la utilidad de la eritropoyetina en el tratamiento de la anemia en el quemado grave. La gravedad de la quemadura está determinada por la intensidad de la temperatura y la duración de la exposición. La anemia es una de las complicaciones más frecuentes en los quemados graves y su tratamiento en ocasiones se limita al uso de transfusiones de sangre, sin embargo la eritropoyetina es una alternativa terapéutica; pertenece a la familia de las citoquinas, alcanza la médula ósea, donde estimula células progenitoras cuyo objetivo es lograr su transformación en eritrocitos. La administración de eritropoyetina humana recombinante en el paciente quemado grave con anemia se considera eficaz, ya que al estimular los mecanismos de la eritropoyesis, produce una elevación paulatina pero mantenida del hematocrito acompañándose de otros efectos beneficios(AU)

The serious burn represents the most severe type of biological aggression the body can suffer and endangers the patient's life due to the permanent risk of sepsis and progressive multisystem failure. Anemia affects the morbidity and mortality of seriously burned patient in serious condition; its treatment has gone through different moments in history and its correction depends on blood transfusions that increase the risk of complications and adverse reactions. To update knowledge about the usefulness of erythropoietin in the treatment of anemia in seriously burned patient.The severity of the burn is determined by the intensity of the temperature and the duration of the exposure. Anemia is one of the most frequent complications in seriously burned patient and its treatment is sometimes limited to the use of blood transfusions. However, erythropoietin is a therapeutic alternative; it belongs to the family of cytokines, reaches the spinal cord, where it stimulates progenitor cells with the objective of achieving their transformation into erythrocytes. The administration of recombinant human erythropoietin in seriously burned patient with anemia is considered effective, since by stimulating the mechanisms of erythropoiesis, it produces a gradual but sustained elevation of the hematocrit accompanied by other beneficial effects(AU)

Eritropoyetina (EPO) / Erythropoietin (EPO)

La eritropoyetina (EPO) es una hormona glucoproteica producida principalmente en las células peritubulares de los riñones, que regula la producción y diferenciación eritrocitaria. La síntesis de eritropoyetina está regulada por cambios en la disponibilidad del oxígeno, es decir, a mayor cantidad de oxígeno, menor producción de EPO, y a la inversa. La EPO se une a los receptores en las células madre hematopoyéticas CD34+, promoviendo la activación de los genes para estimular su proliferación y diferenciación hasta eritrocitos maduros [1]. La medición de eritropoyetina en suero es de gran utilidad para el diagnóstico de eritrocitosis y el establecimiento de su etiología. Su determinación en suero permite identificar si la producción eritrocitaria es autónoma (primaria), como en el caso de la producida en la policitemia vera, o secundaria, mediada por la eritropoyetina. En pacientes con eritrocitosis secundaria, los niveles de eritropoyetina están aumentados como un mecanismo compensatorio cuando es por hipoxia [2], o pueden ser el resultado de una patología que estimula su producción, como ocurre con ciertos tumores, entre otros factores. De acuerdo con la clasificación vigente de neoplasias hematolinfoides de la Organización Mundial de la Salud, los niveles disminuidos de eritropoyetina son un criterio menor para el diagnóstico de policitemia vera [2], y los niveles normales o elevados de eritropoyetina descartan que se trate de esta entidad e indican al médico tratante que debe explorar otras causas de eritrocitosis [2].