Fatigue visual analogue scale score correlates with quality of life in cancer patients receiving epoetin alfa (Sandoz) for chemotherapy-induced anaemia: The CIROCO study.

PURPOSE: Available tools to measure fatigue and health-related quality of life (HRQoL) in cancer patients are often difficult to use in clinical practice. The fatigue visual analogue scale (VAS) provides a simple method to assess fatigue. This study evaluated the correlation between HRQoL and fatigue perceived by cancer patients undergoing chemotherapy. METHODS: This was a non-interventional prospective study of adult cancer patients in France presenting with chemotherapy-induced anaemia (CIA) treated with epoetin alfa (Sandoz). Data were collected using an electronic case report form at study inclusion (T0), after 2-3 chemotherapy cycles (T1) and after 4-6 cycles (T2). RESULTS: The study included 982 patients from September 2015 to October 2017. Overall, there was a negative correlation between fatigue VAS and HRQoL. The overall haemoglobin (Hb) change between T0 and T2 was +17.8 % (± 18.1 %). Fatigue assessed by both patients and physicians showed a clinically significant improvement during the study. Global HRQoL also increased. CONCLUSION: Treatment of CIA with epoetin alfa (Sandoz) improved Hb levels, fatigue, and HRQoL, with a correlation observed between fatigue VAS score and HRQoL. Fatigue VAS could act as a simple alternative to more complex methods to measure HRQoL; however, further analyses are required to confirm this association.

An updated meta-analysis on the efficacy and safety of hypoxia-inducible factor prolyl hydroxylase inhibitor treatment of anemia in nondialysis-dependent chronic kidney disease.

BACKGROUND: Renal anemia, a common complication and threat factor of chronic kidney disease (CKD), has long been treated with injectable erythropoietin-stimulating agents (ESAs). As concerns regarding cardiovascular safety and erythropoietin resistance to ESAs have emerged, alternative therapies are urgently needed. Hypoxia-inducible factor prolyl hydroxylase inhibitor (HIF-PHI), an oral agent, has been proven to be effective in improving renal anemia. However, the effects of HIF-PHIs on nondialysis-dependent CKD (NDD-CKD) have yet to be supported by updated meta-analyses. METHODS: A meta-analysis of clinical randomized controlled trials (RCTs) on HIF-PHI treatment of NDD-CKD patients based on PubMed, EMBASE, and Cochrane databases as of July 16th, 2023, was conducted. The primary outcomes were the level of hemoglobin (Hb) postintervention and the ratio of Hb responses. Most of the analysis was conducted via RevMan 5.3 software using a random-effects model. Stata (version 15.0) was used to analyze the publication bias. RESULTS: Twenty-two studies with a total of 7178 subjects in the HIF-PHI group, 3501 subjects in the ESA group and 2533 subjects in the placebo group were enrolled. HIF-PHIs increased the level of Hb and improved iron metabolism but were not inferior to ESAs in terms of safety. CONCLUSIONS: HIF-PHIs may be a convenient and safe alternative to ESAs in patients with NDD-CKD and anemia.

Inflammation promotes erythropoietin induced vascular calcification by activating p38 pathway.

The current research aimed to verify the effects of erythropoietin (EPO) on vascular calcification under inflammatory conditions and the molecular regulator of vascular calcification induced by EPO. To induce vascular calcification and systemic chronic inflammation in SD rats, EPO was administered intraperitoneally, and 10% casein was injected subcutaneously. The administration period lasted for 20 consecutive weeks. Blood samples were subsequently collected to detect inflammatory factors and vascular calcification. Additionally, high-dose EPOs were applied to stimulate primary vascular smooth muscle cells (VSMCs), and vascular calcification was measured using alizarin red staining, alkaline phosphatase (ALP) activity, and calcium salt quantification. The probe 2',7'-dichlorofluorescein diacetate (DCFH-DA) was employed to detect cellular reactive oxygen species (ROS) levels. The expressions of bone formation-related protein and anti-calcification protein matrix gla protein (MGP) were determined via Western blot. Compared with the control group, calcium deposits and vascular calcification were increased in the EPO group, tumor necrosis factor-alpha (TNF-α) group and TNF-α+ EPO group, whereas MGP was significantly reduced. Moreover, under the stimulation of TNF-α and EPO+TNF-α, pp38/p38 was increased substantially, the addition of p38 inhibitor SB203580 could significantly reduce calcium deposits and vascular calcification. In vivo experiment, compared with the EPO group, calcium salt deposition and vascular calcification were elevated in the EPO+casein group. The present results revealed that high-dose EPO could cause calcification of the abdominal aorta in rats. The inflammatory response aggravated the vascular calcification induced by EPO via activating p38 and ROS levels.

Hypoxia-inducible factor-prolyl hydroxylase inhibitors for renal anemia in chronic kidney disease: Advantages and disadvantages.

Anemia is a common feature and complication of chronic kidney disease (CKD). Erythropoiesis-stimulating agents (ESAs) and recombinant human erythropoietin have been used widely in renal anemia treatment. Recently, hypoxia-inducible factor-prolyl hydroxylase domain inhibitors (HIF-PHIs) that may improve the treatment of renal anemia patients were launched. Previous studies indicated that HIF-PHIs may decrease hepcidin levels and modulate iron metabolism, thereby increasing total iron-binding capacity and reducing the need for iron supplementation. Furthermore, HIF-PHIs can reduce inflammation and oxidative stress in CKD. Recombinant erythropoietin has become a routine treatment for patients with CKD and end-stage renal disease with relatively few adverse effects. However, higher doses of recombinant erythropoietin have been demonstrated to be an independent predictor of mortality in patients under hemodialysis. Phase III clinical trials of HIF-PHIs in patients with anemia and dialysis-dependent CKD have shown their efficacy and safety in both non-dialysis and dialysis CKD patients. However, HIFα binds to specific hypoxia-response elements in the vascular endothelial growth factor or retinoic acid-related orphan receptor gamma t (RORγt) promoter, which may be involved in the progression of cancer, psoriasis, and rheumatoid arthritis. In this paper, we have summarized the mechanism, clinical application, and clinical trials of HIF-PHIs in the treatment of renal anemia and aimed to provide an overview of the new drugs in clinical practice, as well as reconsider the advantages and disadvantages of HIF-PHIs and ESAs. Presently, there are not enough clinical studies examining the effects of long-term administration of HIF-PHIs. Therefore, further studies will be needed.

How I treat anemia in the perisurgical setting.

Anemia is a common finding in the perioperative setting with significant untoward consequences including worsening of outcomes and diminished quality of life as well as increased risk of allogeneic blood transfusions. Here, we present 3 cases that illustrate how anemia can be perioperatively managed in patients undergoing cardiac, orthopedic, and oncology surgeries. Timely detection of anemia prior to high-blood loss surgeries can allow clinicians to manage it and optimize hemoglobin level, making patients better prepared for the surgery. Treatment of anemia should be guided by the etiology and may include erythropoietic agents, folic acid, B12, and iron preparations. Other blood management strategies geared toward reducing surgical blood loss such as autologous transfusion techniques and agents to optimize hemostasis are used during surgery and in the immediate postoperative period. Patients should be closely monitored following surgery for signs of ongoing bleeding in need of control. Finally, screening for and management of anemia should continue in the postoperative and postdischarge period, as persistence and recurrence of anemia can further undermine patient's outcomes.

Use of preoperative erythropoietin therapy to facilitate autologous blood donation in orthopedic surgery: A meta-analysis.

BACKGROUND: Autologous blood transfusion helps to avoid or reduce the need for allogenic blood transfusion in patients undergoing major surgery. We examined the value of erythropoietin therapy to support preoperative autologous blood donation (PABD) in patients undergoing orthopedic surgery. METHODS: For this systematic review and meta-analysis, Medline, Cochrane, EMBASE, and Google Scholar databases were searched from October 26th, 1989 until September 30th, 2017. Primary outcomes were percentages of patients able to donate ≥4 units of blood for autologous transfusion, amount of allogeneic blood transfused, changes in hematocrit and hemoglobin levels from before PABD to immediately before surgery, and adverse events. RESULTS: Of 256 studies identified, 18 studies met the inclusion criteria with a total of 1914 patients (mean age 51-69 years), of whom 1153 were treated with erythropoietin. Erythropoietin was associated with a greater percentage of patients able to donate ≥4 units of blood for autologous use compared to controls (OR = 6.00, 95% CI = 3.97 to 9.09, P < .001). Patients receiving preoperative erythropoietin had significantly less of a reduction in hematocrit and hemoglobin levels from before PABD to immediately before surgery compared with controls (hematocrit: mean differences = -1.438, 95% CI = -2.14 to -0.73, P < .001; hemoglobin: mean differences = -1.426, 95% CI = -1.78 to -1.07, P < .001). No significant differences were observed in the amount of allogenic blood transfused between patients receiving erythropoietin and controls (difference in means = -0.220, 95% CI = -0.536 to 0.097, P = .174). Patients who received erythropoietin were less likely to experience dizziness than controls, but the incidence of nausea or fatigue were similar between groups. CONCLUSION: Erythropoietin therapy during the PABD period results in less of a reduction in hematocrit and hemoglobin levels and an increase in the percentage of patients able to donate blood preoperatively.

[Cardiovascular complications of doping products]. / Complications cardiovasculaires des produits dopants.

Doping is the use of a substance that artificially increases an individual's physical ability for competition purpose. Products and methods used in doping are not without risk, especially at cardiovascular level. Here we review the most common doping substances in sport and their cardiovascular consequences.

Randomized trial of early erythropoietin supplementation after preterm birth: Iron metabolism and outcome.

BACKGROUND: Excess of iron and oxidant injury shortly after birth may be associated with neonatal morbidities in preterm infants. AIMS: The aim was to determine whether administration of erythropoietin without iron supplementation decreases iron load and morbidity. STUDY DESIGN AND SUBJECTS: In a randomized trial, we administered erythropoietin (EPO 250IU/kg daily during the first 6days of life) or placebo to 39 preterm infants (BW 700-1500g, GA≤30.0weeks). OUTCOME MEASURES: The iron status, postnatal morbidities and follow-up at the age of two years were investigated. RESULTS: In all, 21 EPO- and 18 placebo-treated infants were recruited. A requirement of red blood cell transfusions during first 28days was similar between the study groups. EPO treatment decreased total serum iron concentration (p=0.035). EPO supplementation had no significant effect on serum transferrin receptors or reactive non-protein-bound iron. There were no differences in neonatal morbidity or in survival without major neurological abnormality at two years of age. CONCLUSIONS: A 6-day course of EPO decreased the iron load in preterm infants. There was no change in reactive, non-protein bound iron plasma levels and no influence on the outcomes during early childhood. Whether the neurocognitive effects of early EPO treatment can be detectable later in childhood remained to be verified.

Efficacy and safety of adjuvant recombinant human erythropoietin and ferrous sulfate as treatment for iron deficiency anemia during the third trimester of pregnancy.

PURPOSE: Gestational anemia increases the incidence of maternal and fetal complications. Adjuvant recombinant human erythropoietin (rHuEPO) has been used in patients who refuse blood transfusions, have a low response to treatment with iron sulfate, have limited time before birth, or have other illnesses that complicate the anemia. We demonstrated that the use of adjuvant rHuEPO with iron sulfate reduces the anemia time period and is innocuous to the fetus. METHOD: An experimental longitudinal prospective study; 100 pregnant women in their third trimester were included. Group 1 (n=50) was set as control for prevalence of anemia and establish hematological maternal and fetal parameters at delivery for our population; 50 women diagnosed with iron deficiency anemia were randomly assigned to treatment groups. Group 2 (n=25) third trimester women with a hemoglobin of <11g/dL were treated with iron sulfate, 600mg administered orally daily for 4 weeks, evaluating the hematologic response for the mother weekly and for both mother and fetus at birth; Group 3 (n=25) women similar to group 2, treated in addition with adjuvant rHuEPO, 4000 units subcutaneously, three times a week, for 4 weeks evaluating the same parameters. RESULTS: Group 2 and 3 showed a corrected anemia before delivery (mean 11.1 vs 11.4g/dL), but Group 3 showed a statistically broader and more rapid increase in hemoglobin (1.22 vs 1.92g/dL, p value 0.013) with an rHuEPO dose of 4000 units, three times a week for 1 month. No clinical or hematologic difference or changes in growth were observed in the fetus. CONCLUSIONS: Erythropoietin is safe and effective for both mother and fetus, although an ideal pregnancy dose has not yet been established.

New horizons for newborn brain protection: enhancing endogenous neuroprotection.

Intrapartum-related events are the third leading cause of childhood mortality worldwide and result in one million neurodisabled survivors each year. Infants exposed to a perinatal insult typically present with neonatal encephalopathy (NE). The contribution of pure hypoxia-ischaemia (HI) to NE has been debated; over the last decade, the sensitising effect of inflammation in the aetiology of NE and neurodisability is recognised. Therapeutic hypothermia is standard care for NE in high-income countries; however, its benefit in encephalopathic babies with sepsis or in those born following chorioamnionitis is unclear. It is now recognised that the phases of brain injury extend into a tertiary phase, which lasts for weeks to years after the initial insult and opens up new possibilities for therapy.There has been a recent focus on understanding endogenous neuroprotection and how to boost it or to supplement its effectors therapeutically once damage to the brain has occurred as in NE. In this review, we focus on strategies that can augment the body's own endogenous neuroprotection. We discuss in particular remote ischaemic postconditioning whereby endogenous brain tolerance can be activated through hypoxia/reperfusion stimuli started immediately after the index hypoxic-ischaemic insult. Therapeutic hypothermia, melatonin, erythropoietin and cannabinoids are examples of ways we can supplement the endogenous response to HI to obtain its full neuroprotective potential. Achieving the correct balance of interventions at the correct time in relation to the nature and stage of injury will be a significant challenge in the next decade.

Algoritmo para el tratamiento de la anemia preoperatoria / Algorithm for treating preoperative anemia

La optimización de la hemoglobina o el tratamiento de la anemia preoperatoria en cirugía con riesgo moderado-alto de sangrado quirúrgico reduce la tasa de transfusión y puede mejorar la evolución postoperatoria, así como la hemoglobina al alta. Para ello se requiere programar una visita preoperatoria con suficiente antelación para poderla corregir. El algoritmo de tratamiento que proponemos se acompaña de un «check list» sencillo para saber si debemos remitir al paciente al especialista o podemos tratarlo en ese mismo momento. Con el hemograma, algún test complementario del metabolismo del hierro, un parámetro de inflamación y la tasa de filtrado glomerular podremos decidir si iniciar el tratamiento con hierro intravenoso solo o asociar eritropoyetina, con o sin hierro. En la anemia importante puede ser necesaria alguna visita de control a los 15 días, para ver la respuesta y complementar el tratamiento, si el paciente lo precisa. La hemoglobina objetivo dependerá del tipo de cirugía y las características del paciente (AU)

Hemoglobin optimization and treatment of preoperative anemia in surgery with a moderate to high risk of surgical bleeding reduces the rate of transfusions and improves hemoglobin levels at discharge and can also improve postoperative outcomes. To this end, we need to schedule preoperative visits sufficiently in advance to treat the anemia. The treatment algorithm we propose comes with a simple checklist to determine whether we should refer the patient to a specialist or if we can treat the patient during the same visit. With the blood count test and additional tests for iron metabolism, inflammation parameter and glomerular filtration rate, we can decide whether to start the treatment with intravenous iron alone or erythropoietin with or without iron. With significant anemia, a visit after 15 days might be necessary to observe the response and supplement the treatment if required. The hemoglobin objective will depend on the type of surgery and the patient’s characteristics (AU)

[Perioperative anemia management: a systematic review and meta-analysis]. / Perioperatives Anämiemanagement - Systematischer Review und Meta-Analyse.

Anemia is a risk factor for increased postoperative morbidity and mortality. International guidelines, therefore, recommend preoperative diagnostic work up and causal treatment of anemia. Iron therapy, however, is suspected to negatively affect disease progression in patients with cancer-associated anemia. The objective of our systematic review was to assess the efficacy and safety of perioperative diagnosis and causal therapy of anemia, and to determine the effect of iron supplement on disease progression of cancer.We systematically searched multiple electronic databases. Two persons independently reviewed abstracts and full-text articles. We rated the risk of bias using the Cochrane Risk of Bias Tool and assessed the quality of the evidence using GRADE (Grading of Recommendations Assessment, Development and Evaluation). Meta-Analyses were performed using the DerSimonian&Laird random effects method. Results indicate that preoperative therapy of anemia could reduce the need for blood transfusions (relative risk: 0,78; 95% confidence interval 0,61-1,02; number needed to treat: 6) For other patient-relevant outcomes the number of events were too small to detect clinically relevant differences. We could not find any evidence that iron supplements have an influence on the progression of tumors.

A randomized, masked, placebo-controlled study of darbepoetin alfa in preterm infants.

BACKGROUND: A novel erythropoiesis stimulating agent (ESA), darbepoetin alfa (Darbe), increases hematocrit in anemic adults when administered every 1 to 3 weeks. Weekly Darbe dosing has not been evaluated in preterm infants. We hypothesized that infants would respond to Darbe by decreasing transfusion needs compared with placebo, with less-frequent dosing than erythropoietin (Epo). METHODS: Preterm infants 500 to 1250 g birth weight and ≤48 hours of age were randomized to Darbe (10 µg/kg, 1 time per week subcutaneously), Epo (400 U/kg, 3 times per week subcutaneously) or placebo (sham dosing) through 35 weeks' gestation. All received supplemental iron, folate, and vitamin E, and were transfused according to protocol. Transfusions (primary outcome), complete blood counts, absolute reticulocyte counts (ARCs), phlebotomy losses, and adverse events were recorded. RESULTS: A total of 102 infants (946 ± 196 g, 27.7 ± 1.8 weeks' gestation, 51 ± 25 hours of age at first dose) were enrolled. Infants in the Darbe and Epo groups received significantly fewer transfusions (P = .015) and were exposed to fewer donors (P = .044) than the placebo group (Darbe: 1.2 ± 2.4 transfusions and 0.7 ± 1.2 donors per infant; Epo: 1.2 ± 1.6 transfusions and 0.8 ± 1.0 donors per infant; placebo: 2.4 ± 2.9 transfusions and 1.2 ± 1.3 donors per infant). Hematocrit and ARC were higher in the Darbe and Epo groups compared with placebo (P = .001, Darbe and Epo versus placebo for both hematocrit and ARCs). Morbidities were similar among groups, including the incidence of retinopathy of prematurity. CONCLUSIONS: Infants receiving Darbe or Epo received fewer transfusions and fewer donor exposures, and fewer injections were given to Darbe recipients. Darbepoetin and Epo successfully serve as adjuncts to transfusions in maintaining red cell mass in preterm infants.

More clearly defining the risks of erythrocyte transfusion in the NICU.

OBJECTIVE: Red blood cell (RBC) transfusions convey benefits but they also carry risks. Among NICU patients, some transfusion risks are well defined and their occurrence odds can be estimated and weighed against benefits. However other risks are poorly defined and it is not currently possible to estimate their occurrence adds or weigh these against benefits. METHODS: We reviewed publications in the past 15 years, listed in PubMed, dealing with risks and benefits of RBC transfusions to newborn infants. RESULTS: Risks of RBC transfusion to adult patients decreased significantly with the advent of nucleic acid testing for viral pathogens. However, new or previously unknown risks of transfusions have been suggested for neonatal recipients. These include developmental delay, intraventricular hemorrhage, and necrotizing enterocolitis. These potential transfusion risks are all currently in the form of statistical associations, and cause-and-effect relationships have not been proven. Mean of reducing transfusions, tested during the past 15 years, include adopting transfusions guidelines, erythropoietic stimulating agents, delayed cord clamping, cord stripping, drawing all NICU admission blood tests from the placenta, and limiting phlebotomy losses for blood testing. DISCUSSION: We advocate always attempt to weigh benefits and risks when ordering a transfusion for a neonatal patient. Certainly some such are life-saving or otherwise clearly beneficial. Perhaps others carry risks unbalanced by meager benefit. Efforts to improve NICU transfusion practice have been proposed and appear to be working to diminish costs and improve outcomes.

Safety of preoperative erythropoietin in surgical calvarial remodeling: an 8-year retrospective review and analysis.

BACKGROUND: Calvarial remodeling is typically associated with significant blood loss. Although preoperative erythropoiesis-stimulating agents have proven to significantly decrease the need for blood transfusions, recent data in adults have raised concerns that elevating hemoglobin levels greater than 12.5 g/dl may increase the risk of thrombotic events. This study was designed to assess the risks of erythropoietin in the pediatric population. METHODS: Records were retrospectively reviewed from 2000 to 2008 at three major metropolitan children's hospitals of all children undergoing calvarial remodeling after receiving preoperative erythropoietin. Demographic and perioperative outcome data were reviewed, including transfusion reactions, pressure ulcer secondary to prolonged positioning, pneumonia, infection, deep vein thrombosis, cerebrovascular accident, pulmonary embolism, sagittal sinus thrombosis, pure red cell aplasia, and myocardial infarction. RESULTS: A total of 369 patients met the inclusion criteria (mean age, 0.86±1.1 years). On average, three preoperative doses of erythropoietin were administered (600 U/kg). Iron was also supplemented. No complications associated with dosing were noted, there were no thrombotic events identified, and no other major complications were seen (i.e., death or blindness). Thirty-one patients (8.40 percent) experienced one or more postoperative complications. There was no significant correlation between hemoglobin levels greater than 12.5 g/dl and the occurrence of any noted complication. CONCLUSIONS: With zero thrombotic postoperative complications, the authors estimate the risk of a thrombotic event in the pediatric population to be less than 0.81 percent (95 percent confidence). These data suggest that preoperative administration of erythropoietin in children undergoing calvarial remodeling does not appear to increase the incidence of thrombotic events or other significant complications. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, IV.

[Treatment of anaemia in medical oncology]. / A vérszegénység kezelésének onkológiai szempontjai.

Development of cytotoxic chemotherapy, which has several side effects, has resulted in the development in supportive care as well. Two families of novel drugs have spread in the care of chemotherapy induced anaemia: human recombinant erythropoietin and intravenous iron. They were praised for the decreased transfusion demand and the increased quality of life. However, if we read the literature critically, our enthusiasm should be decreased. New data show an unfavourable impact of erythropoietin on life expectancy. Furthermore, the health care policy has changed since the introduction of erythropoietin 25 years ago. Transfusion control has improved and cost awareness in health care has increased. Recommendations of the American Societies of Haematology and Clinical Oncology reflect on these considerations. Erythropoietin is not recommended in adjuvant settings. The choice between erythropoietin and transfusion is conferred to the clinician in case of the development of metastases. No sufficient scientific argument was found to support the use of intravenous iron supplementation.

Recombinant human erythropoietin in combination with chemotherapy increases breast cancer metastasis in preclinical mouse models.

PURPOSE: Erythropoiesis-stimulating agents (ESA) are used clinically for treating cancer-related anemia. Recent clinical trials have reported increased adverse events and reduced survival in ESA-treated breast cancer patients receiving chemotherapy, potentially related to erythropoietin (EPO)-induced cancer progression. However, minimal preclinical data are available about the impact of EPO on metastatic cell behavior and/or the metastatic process, and this was the goal of our study. EXPERIMENTAL DESIGN: Breast cancer cell lines were treated with recombinant human EPO (rHuEPO) and screened for expression of EPO receptors (EPOR). MDA-MB-231 and MDA-MB-435 cell lines were used for functional assays in vitro (two-dimensional/three-dimensional growth and survival) and in vivo (tumorigenicity and metastasis), in the presence or absence of EPO and/or cytotoxic agents. RESULTS: A large variation in EPOR expression across cell lines was observed. In vitro, rHuEPO had a protective effect on radiation-treated MDA-MB-435 cells (P < 0.05); however, rHuEPO treatment alone or combined with chemotherapy or hypoxia did not influence cell survival. In vivo, rHuEPO increased lung metastases in immunocompromised mice injected with MDA-MB-231 or MDA-MB-435 cells and treated with chemotherapy relative to mice treated with chemotherapy alone (P < 0.05). CONCLUSIONS: The lack of an in vitro effect of rHuEPO highlights the importance of in vivo studies to delineate the effects of EPO on the metastatic process. These studies may begin to uncover the underlying functional explanation for the observed EPO-related adverse events and decreased survival in ESA-treated metastatic breast cancer patients undergoing chemotherapy.

Administración precoz de eritropoyetina en el prematuro extremo, ¿factor de riesgo de la retinopatía del prematuro? / Early administration of erythropoietin in the extreme premature, a risk factor for retinopathy of prematurity?

Introducción: La eritropoyetina (EPO) estimula la angiogénesis y podría favorecer la retinopatía del prematuro (ROP). El objetivo fue determinar si la EPO más hierro (Fe) administrada a partir del quinto día de vida era un factor de riesgo independiente para el desarrollo de ROP y su gravedad. Pacientes y métodos: 718 prematuros supervivientes con peso al nacer (PN) ≤1.500g o edad gestacional (EG) ≤32 semanas (y 6 días), ingresados entre 2001 y 2008. Los objetivos de SaO2 durante estos años fueron mantenerla entre el 88 y el 93%. El tratamiento con EPO se inició a los 5–7 días de vida, a 250UI/kg/3 veces a la semana vía subcutánea, asociada a Fe 5–6mg/kg/día, hasta las 34 semanas de edad corregida o el alta. Resultados: 493 prematuros (68,7%) no presentaron ROP, 139 (19,4%) tuvieron una ROP grado 1, 50 (7,0%) una grado 2 y 36 (5,0%) una grado 3. 27 precisaron láser. Una mayor gravedad de la ROP se asoció con menor PN y EG, más patología neonatal y mayor agresividad terapéutica (duración de la oxigenoterapia o ventiloterapia, número de transfusiones de hematíes). Los factores de riesgo asociados de manera independiente y significativa con la presencia de cualquier estadio de ROP fueron: menor PN, ausencia de cesárea, administración de EPO y necesidad de transfusión de hematíes. La administración de EPO aumentó 2,4 veces el riesgo de ROP, pero la influencia de la EPO sólo se observó en la aparición de ROP grado 1 (odds ratio: 5,50). Conclusiones: La administración de EPO+Fe se asocia y quizás favorece la aparición de ROP grado 1 (AU)

Introduction: Erythropoietin (EPO) stimulates angiogenesis and may favour the appearance of retinopathy of prematurity (ROP). The objective was to determine if EPO+Fe administered from the 5th day of life could be an independent risk factor for ROP appearance and its severity. Patients and method: The study included 718 preterm newborns with a birth weight ≤1,500g or a gestational age ≤32 weeks (and 6 days), admitted between 2001 and 2008. During these years, the target SaO2 was between 88% and 93%. EPO treatment began at 5–7 days of life, with a dose of 250 UI/Kg, 3 times a week, subcutaneously, together with Fe, 5–6mg/kg/day, both until 34 weeks of corrected age or discharge. Results: A total of 493 preterms (68.7%) did not have ROP, 139 (19.4%) had a grade 1 ROP, 50 (7.0%) a grade 2 ROP and 36 (5.0%) a grade 3 ROP. Laser therapy was required by 27 severe ROP was associated with lower birth weight and gestational age, more neonatal morbidity and a more aggressive treatment (duration of oxygen supplements or mechanical ventilation, number of blood transfusions). Risk factors independently and significantly associated with any ROP grade were: lower birth weight, no caesarean section, EPO administration and need for blood transfusion. EPO administration increased the risk of ROP by 2.4, but this only happened in case of grade 1 ROP (OR: 5.50). Conclusions: EPO+Fe administration is associated and perhaps stimulates the appearance of grade 1 ROP (AU)

[Use of recombinant human erythropoietin preparations as a blood-saving method in neurosurgery].

The paper gives the results of the first clinical use of recombinant human erythropoietin (rhEPO) within the blood-saving program in neurosurgical patients with preoperative anemia of various genesis and predictable massive intraoperative blood loss. A course of effective therapy with rhEPO is shown to increase hemoglobin and packed cell volume rather rapidly in all patients prior to surgery. This made it possible to effectively apply other blood-saving procedures (isovolemic hemodilution and instrumental reinfusion of washed red blood cells) and to reduce the volume required for the use of donor transfused media in these patients. Various clinical aspects of the use of rhEPO in these patients are discussed.

[Early administration of erythropoietin in the extreme premature, a risk factor for retinopathy of prematurity?]. / Administración precoz de eritropoyetina en el prematuro extremo, ¿factor de riesgo de la retinopatía del prematuro?

INTRODUCTION: Erythropoietin (EPO) stimulates angiogenesis and may favour the appearance of retinopathy of prematurity (ROP). The objective was to determine if EPO+Fe administered from the 5th day of life could be an independent risk factor for ROP appearance and its severity. PATIENTS AND METHOD: The study included 718 preterm newborns with a birth weight ≤1,500g or a gestational age ≤32 weeks (and 6 days), admitted between 2001 and 2008. During these years, the target SaO2 was between 88% and 93%. EPO treatment began at 5-7 days of life, with a dose of 250 UI/Kg, 3 times a week, subcutaneously, together with Fe, 5-6mg/kg/day, both until 34 weeks of corrected age or discharge. RESULTS: A total of 493 preterms (68.7%) did not have ROP, 139 (19.4%) had a grade 1 ROP, 50 (7.0%) a grade 2 ROP and 36 (5.0%) a grade 3 ROP. Laser therapy was required by 27 severe ROP was associated with lower birth weight and gestational age, more neonatal morbidity and a more aggressive treatment (duration of oxygen supplements or mechanical ventilation, number of blood transfusions). Risk factors independently and significantly associated with any ROP grade were: lower birth weight, no caesarean section, EPO administration and need for blood transfusion. EPO administration increased the risk of ROP by 2.4, but this only happened in case of grade 1 ROP (OR: 5.50). CONCLUSIONS: EPO+Fe administration is associated and perhaps stimulates the appearance of grade 1 ROP.