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Background: The COVID-19 pandemic caused an unprecedented number of patients requiring veno-venous extracorporeal membrane oxygenation (VV ECMO) therapy. Clinical polyuria was observed at our ECMO center during the pandemic. This study aims to investigate the incidence, potential causes, and implications of polyuria in COVID-19 patients undergoing VV ECMO therapy. Methods: Here, 68 SARS-CoV-2 positive patients receiving VV ECMO were stratified into the following two groups: polyuria (PU), characterized by an average urine output of ≥3000 mL/day within seven days following initiation, and non-polyuria (NPU), defined by <3000 mL/day. Polyuria in ECMO patients occurred in 51.5% (n = 35) within seven days after ECMO initiation. No significant difference in mortality was observed between PU and NPU groups (60.0% vs. 60.6%). Differences were found in the fluid intake (p < 0.01) and balance within 24 h (p = 0.01), creatinine (p < 0.01), plasma osmolality (p = < 0.01), lactate (p < 0.01), urea (p < 0.01), and sodium levels (p < 0.01) between the groups. Plasma osmolality increased (p < 0.01) after ECMO initiation during the observation period. Results: Diuresis and plasma osmolality increased during VV ECMO treatment, while mortality was not affected by polyuria. Conclusions: Polyuria does not appear to impact mortality. Further investigations are warranted to elucidate its underlying mechanisms and clinical implications in the context of VV ECMO therapy and COVID-19 management.
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ABSTRACT: Hemojuvelin (HJV) is a glycosylphosphatidylinositol-anchored protein of the repulsive guidance molecule family acting as a bone morphogenetic protein (BMP) coreceptor to induce the hepatic iron regulatory protein hepcidin. Hepcidin causes ubiquitination and degradation of the sole known iron exporter ferroportin, thereby limiting iron availability. The detailed signaling mechanism of HJV in vivo has yet to be investigated. In the current manuscript, we used an established model of adeno-associated virus (AAV)-mediated liver-specific overexpression of HJV in murine models of hepatocyte-specific deficiency of the BMP type I receptors Alk2 or Alk3. In control mice, HJV overexpression increased hepatic Hamp messenger RNA (mRNA) levels, soluble HJV (sHJV), splenic iron content (SIC), as well as phosphorylated small mothers against decapentaplegic protein (pSMAD1/5/8) levels. In contrast, in Alk2fl/fl;Alb-Cre and Alk3fl/fl;Alb-Cre mice, which present with moderate and severe iron overload, respectively, the administration of AAV-HJV induced HJV and sHJV. However, it did not rescue the iron overload phenotypes of those mice. Serum iron levels were induced in Alk2fl/fl;Alb-Cre mice after HJV overexpression. In phosphate-buffered saline-injected Alk3fl/fl;Alb-Cre mice, serum iron levels and the expression of duodenal ferroportin remained high, whereas Hamp mRNA levels were decreased to 1% to 5% of the levels detected in controls. This was reduced even further by AAV-HJV overexpression. SIC remained low in mice with hepatocyte-specific Alk2 or Alk3 deficiency, reflecting disturbed iron homeostasis with high serum iron levels and transferrin saturation and an inability to induce hepcidin by HJV overexpression. The data indicate that ALK2 and ALK3 are both required in vivo for the HJV-mediated induction of hepcidin.
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Proteínas Ligadas a GPI , Proteína de la Hemocromatosis , Hepcidinas , Animales , Ratones , Proteínas Ligadas a GPI/metabolismo , Proteínas Ligadas a GPI/genética , Hepcidinas/metabolismo , Hepcidinas/genética , Proteína de la Hemocromatosis/metabolismo , Proteína de la Hemocromatosis/genética , Receptores de Proteínas Morfogenéticas Óseas de Tipo 1/metabolismo , Receptores de Proteínas Morfogenéticas Óseas de Tipo 1/genética , Hígado/metabolismo , Hierro/metabolismo , Sobrecarga de Hierro/metabolismo , Sobrecarga de Hierro/genética , Receptores de Activinas Tipo I/metabolismo , Receptores de Activinas Tipo I/genética , Receptores de Activinas Tipo IIRESUMEN
BACKGROUND: One of the leading causes of maternal death worldwide is severe obstetric haemorrhage after childbirth. Use of intraoperative cell salvage is strongly recommended by international guidelines on patient blood management. Recent data provide strong evidence that use of cell salvage in obstetrics is effective and safe in women with postpartum haemorrhage resulting in fewer transfusion-related adverse events and shorter hospital stay. We retrospectively analysed the use of cell salvage in bleeding women during delivery for a period of 10 yr in German hospitals. METHODS: Data from the German Federal Statistical Office were used that covers all in-hospital birth deliveries from 2011 to 2020. Prevalence of peripartum haemorrhage (pre-, intra-, and post-partum haemorrhage), comorbidities, peripartum complications, administration of blood products, and use of cell salvage were analysed. RESULTS: Of 6 356 046 deliveries in Germany, 305 610 women (4.8%) suffered from peripartum haemorrhage. Of all women with peripartum haemorrhage, postpartum haemorrhage was the main cause for major obstetric haemorrhage (92.33%). Cell salvage was used in only 228 (0.07%) of all women with peripartum haemorrhage (cell salvage group). In women undergoing Caesarean delivery with postpartum haemorrhage, cell salvage was used in only 216 out of 70 450 women (0.31%). CONCLUSION: Cell salvage during peripartum haemorrhage is rarely used in Germany. There is tremendous potential for the increased use of cell salvage in peripartum haemorrhage nationwide.
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Bases de Datos Factuales , Recuperación de Sangre Operatoria , Hemorragia Posparto , Humanos , Femenino , Alemania/epidemiología , Hemorragia Posparto/terapia , Hemorragia Posparto/epidemiología , Embarazo , Estudios Retrospectivos , Adulto , Recuperación de Sangre Operatoria/estadística & datos numéricos , Cesárea/estadística & datos numéricos , Transfusión de Sangre Autóloga/estadística & datos numéricos , ObstetriciaRESUMEN
BACKGROUND: Approximately 1% to 2% of all hospitalized children receive a transfusion of blood products, in Germany as in other countries. High-quality scientific evidence on transfusions in children is scarce. The available evidence is discussed in this review. METHODS: This review is based on publications on blood product transfusions in children that were retrieved by a literature search, including clinical studies, international guideline recommendations, the recommendations of the German cross-sectional guideline, and results of other recent, relevant publications. RESULTS: A restrictive transfusion strategy is recommended for all children, including those who are critically ill. Randomized controlled trials have shown that a restrictive strategy for erythrocyte concentrate transfusion in the intensive care unit is safe for children, including neonates. No robust data are available to enable the definition of a suitable threshold for the intraoperative administration of red blood cell concentrates in children undergoing extracardiac surgery. On the basis of studies from pediatric intensive care units, transfusions for hemodynamically stable children with a hemoglobin concentration of more than 7 g/dL are recommended only in exceptional cases. Therapeutic plasma is not recommended as volume replacement, except in massive transfusion. Platelet concentrate transfusions are indicated in case of active hemorrhage, and only rarely for prophylaxis. CONCLUSION: There is a broad lack of evidence from randomized controlled trials concerning the indications for transfusions in children. A restrictive transfusion strategy, which has been found safe in the intensive-care setting, is favored by the guidelines in the perioperative setting as well. Further studies are needed to evaluate transfusion triggers and indications for all types of blood products, especially therapeutic plasma. Until more evidence is available, physicians should be aware of what the current evidence supports, and blood products should be given restrictively, and not prophylactically.
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Transfusión Sanguínea , Enfermedad Crítica , Niño , Recién Nacido , Humanos , Enfermedad Crítica/terapia , Estudios Transversales , Transfusión de Eritrocitos/métodos , Periodo PerioperatorioRESUMEN
BACKGROUND: Patient Blood Management (PBM) is a patient-centred, systematic, evidence-based approach to improve patient outcomes by managing and preserving a patient's own blood whilst promoting patient safety and empowerment. The effectiveness and safety of PBM over a longer period have not yet been investigated. METHODS: We performed a prospectively designed, multicentre follow-up study with non-inferiority design. Data were retrospectively extracted case-based from electronic hospital information systems. All in-hospital patients (≥18 yr) undergoing surgery and discharged between January 1, 2010 and December 31, 2019 were included in the analysis. The PBM programme focused on three domains: preoperative optimisation of haemoglobin concentrations, blood-sparing techniques, and guideline adherence/standardisation of allogeneic blood product transfusions. The outcomes were utilisation of blood products, composite endpoint of in-hospital mortality and postoperative complications (myocardial infarction/ischaemic stroke/acute renal failure with renal replacement therapy/sepsis/pneumonia), anaemia rate at admission and discharge, and hospital length of stay. RESULTS: A total of 1 201 817 (pre-PBM: n=441 082 vs PBM: n=760 735) patients from 14 (five university/nine non-university) hospitals were analysed. Implementation of PBM resulted in a substantial reduction of red blood cell utilisation. The mean number of red blood cell units transfused per 1000 patients was 547 in the PBM cohort vs 635 in the pre-PBM cohort (relative reduction of 13.9%). The red blood cell transfusion rate was significantly lower (P<0.001) with odds ratio 0.86 (0.85-0.87). The composite endpoint was 5.8% in the PBM vs 5.6% in the pre-PBM cohort. The non-inferiority aim (safety of PBM) was achieved (P<0.001). CONCLUSIONS: Analysis of >1 million surgical patients showed that the non-inferiority condition (safety of Patient Blood Management) was fulfilled, and PBM was superior with respect to red blood cell transfusion. CLINICAL TRIAL REGISTRATION: NCT02147795.
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Isquemia Encefálica , Accidente Cerebrovascular , Humanos , Transfusión Sanguínea , Estudios de Seguimiento , Estudios Retrospectivos , Adolescente , AdultoRESUMEN
The expression of the iron regulatory hormone hepcidin in hepatocytes is regulated by the BMP-SMAD pathway through the type I receptors ALK2 and ALK3, the type II receptors ACVR2A and BMPR2, and the ligands BMP2 and BMP6. We previously identified the immunophilin FKBP12 as a new hepcidin inhibitor that acts by blocking ALK2. Both the physiologic ALK2 ligand BMP6 and the immunosuppressive drug Tacrolimus (TAC) displace FKBP12 from ALK2 and activate the signaling. However, the molecular mechanism whereby FKBP12 regulates BMP-SMAD pathway activity and thus hepcidin expression remains unclear. Here, we show that FKBP12 acts by modulating BMP receptor interactions and ligand responsiveness. We first demonstrate that in primary murine hepatocytes TAC regulates hepcidin expression exclusively via FKBP12. Downregulation of the BMP receptors reveals that ALK2, to a lesser extent ALK3, and ACVR2A are required for hepcidin upregulation in response to both BMP6 and TAC. Mechanistically, TAC and BMP6 increase ALK2 homo-oligomerization and ALK2-ALK3 hetero-oligomerization and the interaction between ALK2 and the type II receptors. By acting on the same receptors, TAC and BMP6 cooperate in BMP pathway activation and hepcidin expression both in vitro and in vivo. Interestingly, the activation state of ALK3 modulates its interaction with FKBP12, which may explain the cell-specific activity of FKBP12. Overall, our results identify the mechanism whereby FKBP12 regulates the BMP-SMAD pathway and hepcidin expression in hepatocytes, and suggest that FKBP12-ALK2 interaction is a potential pharmacologic target in disorders caused by defective BMP-SMAD signaling and characterized by low hepcidin and high BMP6 expression.
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Hepcidinas , Proteína 1A de Unión a Tacrolimus , Humanos , Ratones , Animales , Hepcidinas/genética , Hepcidinas/metabolismo , Proteína 1A de Unión a Tacrolimus/genética , Proteína 1A de Unión a Tacrolimus/metabolismo , Ligandos , Receptores de Proteínas Morfogenéticas Óseas/metabolismo , Hepatocitos/metabolismo , Proteína Morfogenética Ósea 6/genéticaRESUMEN
BACKGROUND: Preoperative intravenous iron administration is a frequently used patient blood management procedure. If the timeframe of intravenous iron administration before surgery is short, (1) the concentration of the intravenous iron compound might still be high in patients' plasma when undergoing surgery and (2) this iron in patients' plasma is at risk to be lost due to blood loss. The aim of the current study was, therefore, to track the iron compound ferric carboxymaltose (FCM) before, during, and after cardiac surgery requiring cardiopulmonary bypass, with an emphasis on intraoperative iron losses in shed blood and potential recovery through autologous cell salvage. METHODS: Concentrations of FCM were analyzed in patients' blood using a hyphenation of liquid chromatography and inductively coupled plasma-mass spectrometry to distinguish between pharmaceutical compound FCM and serum iron. In this prospective, single-center pilot trial, 13 anemic and 10 control patients were included. Anemic patients with hemoglobin levels ≤12/13 g/dL in women and men were treated with 500 milligrams (mg) intravenous FCM 12 to 96 hours before elective on-pump cardiac surgery. Patients' blood samples were collected before surgery and at days 0, 1, 3, and 7 after surgery. One sample each was taken of the cardiopulmonary bypass, the autologous red blood cell concentrate generated by cell salvage, and the cell salvage disposal bag. RESULTS: Patients who had received FCM <48 hours before surgery had higher FCM serum levels (median [Q1-Q3], 52.9 [13.0-91.6]) compared to ≥48 hours (2.1 [0.7-5.1] µg/mL, P = .008). Of 500-mg FCM administered <48 hours, 327.37 (257.96-402.48) mg were incorporated compared to administration ≥48 hours with 493.60 (487.78-496.70) mg. After surgery, patients' plasma FCM concentration in the FCM <48 hours group was decreased (-27.1 [-30 to -5.9] µg/mL). Little FCM was found in the cell salvage disposal bag (<48 hours, 4.2 [3.0-25.8] µg/mL, equivalent to 29.0 [19.0-40.7] mg total; equivalent to 5.8% or 1/17th of the 500 mg FCM initially administered), almost none in the autologous red blood cell concentrate (<48 hours, 0.1 [0.0-0.43] µg/mL). CONCLUSIONS: The data generate the hypotheses that nearly all FCM is incorporated into iron stores with administration ≥48 hours before surgery. When FCM is given <48 hours of surgery, the majority is incorporated into iron stores by the time of surgery, although a small amount may be lost during surgical bleeding with limited recovery by cell salvage.
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Anemia , Procedimientos Quirúrgicos Cardíacos , Masculino , Humanos , Femenino , Hierro , Estudios Prospectivos , Proyectos Piloto , Compuestos Férricos , Administración Intravenosa , MaltosaRESUMEN
Background and aims: Germany uses more blood transfusions than the majority of other countries. The objective of this study was to detect the degree of Patient Blood Management (PBM) implementation within Germany and to identify obstacles to establishing PBM programs. Methods: An electronical questionnaire containing 21 questions and 4 topics was sent in 2018 to the members of the German interdisciplinary hemotherapy (IAKH) society in Germany. The degree of PBM (described as pre-, intra-, postoperative period) was established via questions within the topics "management of preoperative anemia" (PA) (n = 5), "preoperative management and transfusion preparation" (n = 3), PBM organization and structure (n = 5), coagulation management (n = 3), perioperative transfusion performance and habits (n = 3), best practices and problems (n = 2). Results: 533 German hospitals with transfusion activity received the questionnaire with a 32.5% response rate to the survey. A dedicated PBM program had not been established in a quarter of all small and medium sized institutions. Red blood cell transfusion was the only therapeutic option in a third of institutions. Approximately half of the hospitals did not use knowledge of PA rates or transfusion needs of surgical procedures. Institutions failed to implement PBM because of a lack of profit, workload, personnel shortage, and administrative support. Conclusion: PBM was not present in at least a quarter of the hospitals interrogated. Factors for improvement were the relationship between health care disciplines and sectors, economic incentives, inclusion of relevant disciplines, and the structure of the blood industry. To improve BPM implementation, hospitals need support to implement top-down PBM projects.
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Acute brain injuries such as intracerebral hemorrhage (ICH) and ischemic stroke have been reported in critically ill COVID-19 patients as well as in patients treated with veno-venous (VV)-ECMO independently of their COVID-19 status. The purpose of this study was to compare critically ill COVID-19 patients with and without VV-ECMO treatment with regard to acute neurological symptoms, pathological neuroimaging findings (PNIF) and long-term deficits. The single center study was conducted in critically ill COVID-19 patients between February 1, 2020 and June 30, 2021. Demographic, clinical and laboratory parameters were extracted from the hospital's databases. Retrospective imaging modalities included head computed tomography (CT) and magnetic resonance imaging (MRI). Follow-up MRI and neurological examinations were performed on survivors > 6 months after the primary occurrence. Of the 440 patients, 67 patients received VV-ECMO treatment (15%). Sixty-four patients (24 with VV-ECMO) developed acute neurological symptoms (pathological levels of arousal/brain stem function/motor responses) during their ICU stay and underwent neuroimaging with brain CT as the primary modality. Critically ill COVID-19 patients who received VV-ECMO treatment had a significantly lower survival during their hospital stay compared to those without (p < 0.001). Among patients treated with VV-ECMO, 10% showed acute PNIF in one of the imaging modalities during their ICU stay (vs. 4% of patients in the overall COVID-19 ICU cohort). Furthermore, 9% showed primary or secondary ICH of any severity (vs. 3% overall), 6% exhibited severe ICH (vs. 1% overall) and 1.5% were found to have non-hemorrhagic cerebral infarctions (vs. < 1% overall). There was a weak, positive correlation between patients treated with VV-ECMO and the development of acute neurological symptoms. However, the association between the VV-ECMO treatment and acute PNIF was negligible. Two survivors (one with VV-ECMO-treatment/one without) showed innumerable microhemorrhages, predominantly involving the juxtacortical white matter. None of the survivors exhibited diffuse leukoencephalopathy. Every seventh COVID-19 patient developed acute neurological symptoms during their ICU stay, but only every twenty-fifth patient had PNIF which were mostly ICH. VV-ECMO was found to be a weak risk factor for neurological complications (resulting in a higher imaging rate), but not for PNIF. Although logistically complex, repeated neuroimaging should, thus, be considered in all critically ill COVID-19 patients since ICH may have an impact on the treatment decisions and outcomes.
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COVID-19 , Oxigenación por Membrana Extracorpórea , Humanos , Oxigenación por Membrana Extracorpórea/métodos , Enfermedad Crítica/terapia , Estudios Retrospectivos , Prevalencia , COVID-19/complicaciones , COVID-19/diagnóstico por imagen , COVID-19/terapia , Neuroimagen , Hemorragia Cerebral/diagnóstico por imagen , Hemorragia Cerebral/epidemiología , Hemorragia Cerebral/etiologíaRESUMEN
PURPOSE OF REVIEW: The particular fields within patient blood management (PBM) and patient safety reviewed here include novel insights into bleeding therapy, autologous cell salvage, and perioperative anemia therapy. RECENT FINDING: World Health Organization has published that implementation of PBM is important but has not yet been performed in all hospitals. Two antibodies that mimic the function of FVIII, Emicizumab, and Mim8 have been developed. Tranexamic acid (TXA) has been investigated further in patients with hip surgery and shows reduction of bleeding. Thrombocytopenia in patients undergoing cardiac surgery is a particular concern that has been investigated in another trial. The use of autologous cell salvage was updated in form of a review and meta-analysis. And last but not least, intravenous iron in preoperative anemia therapy can reduce the number of transfusions, but especially iron carboxymaltose can cause hypophosphatemia. SUMMARY: PBM should be further implemented in more hospitals. Emicizumab and Mim8 are indicated in acquired hemophilia or hemophilia A with inhibitors. TXA was confirmed to reduce bleeding. Autologous cell salvage is state of the art to reduce transfusion requirements in major cardiac and noncardiac surgery. Serum phosphate concentrations should be monitored after administration of intravenous iron compounds.
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Anemia , Pérdida de Sangre Quirúrgica , Ácido Tranexámico , Humanos , Anemia/prevención & control , Antifibrinolíticos/uso terapéutico , Pérdida de Sangre Quirúrgica/prevención & control , Seguridad del Paciente , Ácido Tranexámico/uso terapéuticoRESUMEN
Background: Allogeneic blood transfusions in oncologic surgery are associated with increased recurrence and mortality. Adverse effects on outcome could be reduced or avoided by using intraoperative autologous blood cell salvage (IOCS). However, there are concerns regarding the safety of the autologous IOCS blood. Previous meta-analyses from 2012 and 2020 did not identify increased risk of cancer recurrence after using autologous IOCS blood. The objective of this review was to reassess a greater number of IOCS-treated patients to present an updated and more robust analysis of the current literature. Methods: This systematic review includes full-text articles listed in PubMed, Cochrane, Cochrane Reviews, and Web of Science. We analyzed publications that discussed cell salvage or autotransfusion combined with the following outcomes: cancer recurrence, mortality, survival, allogeneic transfusion rate and requirements, length of hospital stay (LOS). To rate the strength of evidence, a Grading of Recommendations Assessment, Development and Evaluation (GRADE) of the underlying evidence was applied. Results: In the updated meta-analysis, 7 further observational studies were added to the original 27 observational studies included in the former 2020 analysis. Studies compared either unfiltered (n = 2,311) or filtered (n = 850) IOCS (total n = 3,161) versus non-IOCS use (n = 5,342). Control patients were either treated with autologous predonated blood (n = 484), with allogeneic transfusion (n = 4,113), or did not receive a blood transfusion (n = 745). However, the current literature still contains only observational studies on these topics, and the strength of evidence remains low. The risk of cancer recurrence was reduced in recipients of autologous salvaged blood with or without LDF (odds ratio [OR] 0.76, 95% confidence interval [CI]: 0.64-0.90) compared to nontransfused patients or patients with allogeneic transfusion. There was no difference in mortality (OR 0.95, 95% CI: 0.71-1.27) and LOS (mean difference -0.07 days, 95% CI: -0.63 to 0.48) between patients treated with IOCS blood or those in whom IOCS was not used. Due to high heterogeneity, transfusion rates or volumes could not be analyzed. Conclusion: Randomized controlled trials comparing mortality and cancer recurrence rate of IOCS with or without LDF filtration versus allogeneic blood transfusion were not found. Outcome was similar or better in patients receiving IOCS during cancer surgery compared to patients with allogeneic blood transfusion or nontransfused patients.
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Hereditary hemochromatosis (HH) is a genetic disorder in which mutations affect systemic iron homeostasis. Most subtypes of HH result in low hepcidin levels and iron overload. Accumulation of iron in various tissues can lead to widespread organ damage and to various complications, including liver cirrhosis, arthritis, and diabetes. Osteoporosis is another frequent complication of HH, and the underlying mechanisms are poorly understood. Currently, it is unknown whether iron overload in HH directly damages bone or whether complications associated with HH, such as liver cirrhosis or hypogonadism, affect bone secondarily. This review summarizes current knowledge of bone metabolism in HH and highlights possible implications of metabolic dysfunction in HH-driven bone loss. We further discuss therapeutic considerations managing osteoporosis in HH.
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Hemocromatosis , Sobrecarga de Hierro , Osteoporosis , Hemocromatosis/complicaciones , Hemocromatosis/genética , Hemocromatosis/metabolismo , Humanos , Hierro/metabolismo , Sobrecarga de Hierro/complicaciones , Sobrecarga de Hierro/genética , Cirrosis Hepática/complicaciones , Osteoporosis/genéticaRESUMEN
PURPOSE: Anaemia is common in patients presenting with aneurysmal subarachnoid (aSAH) and intracerebral haemorrhage (ICH). In surgical patients, anaemia was identified as an idenpendent risk factor for postoperative mortality, prolonged hospital length of stay (LOS) and increased risk of red blood cell (RBC) transfusion. This multicentre cohort observation study describes the incidence and effects of preoperative anaemia in this critical patient collective for a 10-year period. METHODS: This multicentre observational study included adult in-hospital surgical patients diagnosed with aSAH or ICH of 21 German hospitals (discharged from 1 January 2010 to 30 September 2020). Descriptive, univariate and multivariate analyses were performed to investigate the incidence and association of preoperative anaemia with RBC transfusion, in-hospital mortality and postoperative complications in patients with aSAH and ICH. RESULTS: A total of n = 9081 patients were analysed (aSAH n = 5008; ICH n = 4073). Preoperative anaemia was present at 28.3% in aSAH and 40.9% in ICH. RBC transfusion rates were 29.9% in aSAH and 29.3% in ICH. Multivariate analysis revealed that preoperative anaemia is associated with a higher risk for RBC transfusion (OR = 3.25 in aSAH, OR = 4.16 in ICH, p < 0.001), for in-hospital mortality (OR = 1.48 in aSAH, OR = 1.53 in ICH, p < 0.001) and for several postoperative complications. CONCLUSIONS: Preoperative anaemia is associated with increased RBC transfusion rates, in-hospital mortality and postoperative complications in patients with aSAH and ICH. TRIAL REGISTRATION: ClinicalTrials.gov , NCT02147795, https://clinicaltrials.gov/ct2/show/NCT02147795.
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Anemia , Hemorragia Subaracnoidea , Adulto , Anemia/complicaciones , Anemia/epidemiología , Anemia/terapia , Hemorragia Cerebral/complicaciones , Hemorragia Cerebral/terapia , Transfusión de Eritrocitos/efectos adversos , Humanos , Sistema de Registros , Estreptotricinas , Hemorragia Subaracnoidea/complicaciones , Hemorragia Subaracnoidea/diagnóstico , Hemorragia Subaracnoidea/terapiaRESUMEN
Acute respiratory distress syndrome (ARDS) is a major cause of patient mortality in intensive care units (ICUs) worldwide. Considering that no causative treatment but only symptomatic care is available, it is obvious that there is a high unmet medical need for a new therapeutic concept. One reason for a missing etiologic therapy strategy is the multifactorial origin of ARDS, which leads to a large heterogeneity of patients. This review summarizes the various kinds of ARDS onset with a special focus on the role of reactive oxygen species (ROS), which are generally linked to ARDS development and progression. Taking a closer look at the data which already have been established in mouse models, this review finally proposes the translation of these results on successful antioxidant use in a personalized approach to the ICU patient as a potential adjuvant to standard ARDS treatment.
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The adult human body contains about 4 g of iron. About 1-2 mg of iron is absorbed every day, and in healthy individuals, the same amount is excreted. We describe a patient who presents with severe iron deficiency anemia with hemoglobin levels below 6 g/dL and ferritin levels below 30 ng/mL. Although red blood cell concentrates and intravenous iron have been substituted every month for years, body iron stores remain depleted. Diagnostics have included several esophago-gastro-duodenoscopies, colonoscopies, MRI of the liver, repetitive bone marrow biopsies, psychological analysis, application of radioactive iron to determine intact erythropoiesis, and measurement of iron excretion in urine and feces. Typically, gastrointestinal bleeding is a major cause of iron loss. Surprisingly, intestinal iron excretion in stool in the patient was repetitively increased, without gastrointestinal bleeding. Furthermore, whole exome sequencing was performed in the patient and additional family members to identify potential causative genetic variants that may cause intestinal iron loss. Under different inheritance models, several rare mutations were identified, two of which (in CISD1 and KRI1) are likely to be functionally relevant. Intestinal iron loss in the current form has not yet been described and is, with high probability, the cause of the severe iron deficiency anemia in this patient.
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Anemia Ferropénica/etiología , Anemia Ferropénica/genética , Tracto Gastrointestinal/metabolismo , Hemorragia/complicaciones , Hemorragia/genética , Deficiencias de Hierro/etiología , Deficiencias de Hierro/genética , Anciano , Anciano de 80 o más Años , Anemia Ferropénica/sangre , Eritropoyesis/genética , Femenino , Variación Genética/genética , Humanos , Hierro/sangre , Hierro/metabolismo , Hierro/orina , Masculino , Persona de Mediana Edad , Mutación/genéticaRESUMEN
BACKGROUND: Iron deficiency (ID) is one of the most common nutritional deficiencies in children worldwide and may result in iron deficiency anemia (IDA). The reticulocyte hemoglobin equivalent (Ret-He) provides information about the current availability of iron in erythropoiesis. This study aims to examine the validation of Ret-He as a screening marker for ID and IDA in children. METHODS: Blood samples were retrospectively obtained from medical records. Anemia was defined according to the definition provided by the World Health Organization (WHO) for children. ID was defined by transferrin saturation (TSAT) < 20% and ferritin < 100 ng/mL. Children were classified into four groups: IDA, non-anemia iron deficiency (NAID), control and others. RESULTS: Out of 970 children, 332 (34.2%) had NAID and 278 (28.7%) presented with IDA. Analysis revealed that Ret-He significantly correlates with ferritin (rho = 0.41; p < 0.001), TSAT (rho = 0.66; p < 0.001) and soluble transferrin receptor (sTfR) (rho = -0.72; p < 0.001). For ROC analysis, the area under the curve (AUC) was 0.771 for Ret-He detecting ID and 0.845 for detecting IDA. The cut-off value for Ret-He to diagnose ID was 33.5 pg (sensitivity 90.7%; specificity 35.8%) and 31.6 pg (sensitivity 90.6%; specificity 50.4%) to diagnose IDA. CONCLUSIONS: The present study demonstrates Ret-He to be a screening marker for ID and IDA in children. Furthermore, Ret-He can be used as a single screening parameter for ID and IDA in children without considering other iron parameters. Economically, the use of Ret-He is highly relevant, as it can save one blood tube per patient and additional costs.
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PURPOSE OF REVIEW: Multisystem inflammatory syndrome in children (MIS-C)/pediatric inflammatory multisystem syndrome (PIMS) is a new and serious disease that occurs in temporal association with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. We describe the clinical presentation, diagnosis, and treatment recommendations. RECENT FINDING: To date, no randomized prospective studies have been published; recommendations are based on some observational studies, case reports, and expert opinions. The article provides an overview of the most important publications, presents the current results of the German Registry for PIMS and expert recommendations for treatment. SUMMARY: MIS-C PIMS is a new syndrome that is associated with a variety of virus infections, and also with SARS-CoV-2. The main characteristics are fever, multiple organ dysfunction due to a hyper-inflammatory state. In particular, cardiac dysfunction and severe shock. A high proportion of patients require intensive medical care, but the absolute number of children with SARS-CoV-2 MIS-C is low. Medical therapy is based on pathophysiologic considerations and is not evidence-based. Immunoglobulins, steroids and biologics are used and lead to effective treatment. Therefore, the mortality rate is very low. Patients usually recover within days, sequelae are reported only in a minority of cases.
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COVID-19 , Niño , Humanos , Estudios Prospectivos , SARS-CoV-2 , Síndrome de Respuesta Inflamatoria SistémicaRESUMEN
Matriptase-2, a serine protease expressed in hepatocytes, is a negative regulator of hepcidin expression. The purpose of the study was to investigate the interaction of matriptase-2 with hemojuvelin protein in vivo. Mice lacking the matriptase-2 proteolytic activity (mask mice) display decreased content of hemojuvelin protein. Vice versa, the absence of hemojuvelin results in decreased liver content of matriptase-2, indicating that the two proteins interact. To further characterize the role of matriptase-2, we investigated iron metabolism in mask mice fed experimental diets. Administration of iron-enriched diet increased liver iron stores as well as hepcidin expression. Treatment of iron-overloaded mask mice with erythropoietin increased hemoglobin and hematocrit, indicating that the response to erythropoietin is intact in mask mice. Feeding of an iron-deficient diet to mask mice significantly increased spleen weight as well as the splenic content of erythroferrone and transferrin receptor proteins, indicating stress erythropoiesis. Liver hepcidin expression was decreased; expression of Id1 was not changed. Overall, the results suggest a complex interaction between matriptase-2 and hemojuvelin, and demonstrate that hepcidin can to some extent be regulated even in the absence of matriptase-2 proteolytic activity.