Markers of oxidative stress during post-COVID-19 fatigue: a hypothesis-generating, exploratory pilot study on hospital employees.

Introduction: Post-COVID-19 fatigue is common after recovery from COVID-19. Excess formation of reactive oxygen species (ROS) leading to oxidative stress-related mitochondrial dysfunction is referred to as a cause of these chronic fatigue-like symptoms. The present observational pilot study aimed to investigate a possible relationship between the course of ROS formation, subsequent oxidative stress, and post-COVID-19 fatigue. Method: A total of 21 post-COVID-19 employees of the General Hospital Nuremberg suffering from fatigue-like symptoms were studied during their first consultation (T1: on average 3 months after recovery from COVID-19), which comprised an educational talk on post-COVID-19 symptomatology and individualized outpatient strategies to resume normal activity, and 8 weeks thereafter (T2). Fatigue severity was quantified using the Chalder Fatigue Scale together with a health survey (Patient Health Questionnaire) and self-report on wellbeing (12-Item Short-Form Health Survey). We measured whole blood superoxide anion (O2•-) production rate (electron spin resonance, as a surrogate for ROS production) and oxidative stress-induced DNA strand breaks (single cell gel electrophoresis: "tail moment" in the "comet assay"). Results: Data are presented as mean ± SD or median (interquartile range) depending on the data distribution. Differences between T1 and T2 were tested using a paired Wilcoxon rank sign or t-test. Fatigue intensity decreased from 24 ± 5 at T1 to 18 ± 8 at T2 (p < 0.05), which coincided with reduced O2•- formation (from 239 ± 55 to 195 ± 59 nmol/s; p < 0.05) and attenuated DNA damage [tail moment from 0.67 (0.36-1.28) to 0.32 (0.23-0.71); p = 0.05]. Discussion: Our pilot study shows that post-COVID-19 fatigue coincides with (i) enhanced O2•- formation and oxidative stress, which are (ii) reduced with attenuation of fatigue symptoms.

Changes in hospital staff' mental health during the Covid­19 pandemic: Longitudinal results from the international COPE-CORONA study.

This longitudinal study aimed to explore anxiety and depressive symptoms, individual resources, and job demands in a multi-country sample of 612 healthcare workers (HCWs) during the COVID-19 pandemic. Two online surveys were distributed to HCWs in seven countries (Germany, Andorra, Ireland, Spain, Italy, Romania, Iran) during the first (May-October 2020, T1) and the second (February-April 2021, T2) phase of the pandemic, assessing sociodemographic characteristics, contact with COVID-19 patients, anxiety and depressive symptoms, self-compassion, sense of coherence, social support, risk perception, and health and safety at the workplace. HCWs reported a significant increase in depressive and anxiety symptoms. HCWs with high depressive or anxiety symptoms at T1 and T2 reported a history of mental illness and lower self-compassion and sense of coherence over time. Risk perception, self-compassion, sense of coherence, and social support were strong independent predictors of depressive and anxiety symptoms at T2, even after controlling for baseline depressive or anxiety symptoms and sociodemographic variables. These findings pointed out that HCWs during the COVID-19 outbreak experienced a high burden of psychological distress. The mental health and resilience of HCWs should be supported during disease outbreaks by instituting workplace interventions for psychological support.

Small volume bone marrow aspirates with high progenitor cell concentrations maximize cell therapy dose manufacture and substantially reduce donor hemoglobin loss.

BACKGROUND: Bone marrow (BM) transplantation is a life-saving therapy for hematological diseases, and the BM harbors also highly useful (progenitor) cell types for novel cell therapies manufacture. Yet, the BM collection technique is not standardized. METHODS: Benchmarking our collection efficiency to BM collections worldwide (N = 1248), we noted a great variability of total nucleated cell (TNC) yields in BM products (HPC-M) with superior performance of our center, where we have implemented a small volume aspirate policy. Thus, we next prospectively aimed to assess the impact of BM collection technique on HPC-M quality. For each BM collection (N = 20 donors), small volume (3 mL) and large volume (10 mL) BM aspirates were sampled at 3 time points and analyzed for cell composition. RESULTS: Compared to large volume aspirates, small volume aspirates concentrated more TNCs, immune cells, platelets, hematopoietic stem/progenitor cells, mesenchymal stromal cells (MSCs), and endothelial progenitors. Inversely, the hemoglobin concentration was higher in large volume aspirates indicating more hemoglobin loss. Manufacturing and dosing scenarios showed that small volume aspirates save up to 42% BM volume and 44% hemoglobin for HPC-M donors. Moreover, MSC production efficiency can be increased by more than 150%. CONCLUSIONS: We propose to consider small volume BM aspiration as standard technique for BM collection.

German Patient Blood Management Network: effectiveness and safety analysis in 1.2 million patients.

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.

Psychological correlates of perceived loneliness in college students before and during the COVID-19 stay-at-home period: a longitudinal study.

BACKGROUND: Loneliness is increasingly acknowledged as a serious public health issue. This longitudinal study aimed to assess the extent to which psychological distress and alexithymia can predict loneliness among Italian college students before and one year after the COVID-19 outbreak. METHODS: A convenience sample of 177 psychology college students were recruited. Loneliness (UCLA), alexithymia (TAS-20), anxiety symptoms (GAD-7), depressive symptoms (PHQ-9), and somatic symptoms (PHQ-15) were assessed before the COVID-19 outbreak and one year after the spread of COVID-19 worldwide. RESULTS: After controlling for baseline loneliness, students with high levels of loneliness during lockdown showed worsening psychological distress and alexithymic traits over time. Suffering from depressive symptoms before COVID-19 and the aggravation of alexithymic traits independently predicted 41% of perceived loneliness during the COVID-19 outbreak. CONCLUSIONS: College students with higher levels of depression and alexithymic traits both before and one year after the lockdown were more at risk of suffering from perceived loneliness and may constitute the target sample for psychological support and intervention.

Novel evidence that the ABO blood group shapes erythropoiesis and results in higher hematocrit for blood group B carriers.

The ABO blood group (BG) system is of great importance for blood transfusion and organ transplantation. Since the same transcription factors (TFs) and microRNAs (miRNAs) govern the expression of ABO BG antigens and regulate erythropoiesis, we hypothesized functional connections between both processes. We found significantly higher hemoglobin and hematocrit values in BG B blood donors compared to BG A. Furthermore, we observed that erythropoiesis in BG B hematopoietic stem/progenitor cells (HSPCs) was accelerated compared to BG A HSPCs. Specifically, BG B HSPCs yielded more lineage-specific progenitors in a shorter time (B: 31.3 ± 2.2% vs. A: 22.5 ± 3.0%). Moreover, non-BG A individuals exhibited more terminally differentiated RBCs with higher enucleation rates containing more hemoglobin compared to BG A. Additionally, we detected increased levels of miRNA-215-5p and -182-5p and decreased expression of their target TFs RUNX1 and HES-1 mRNAs in erythroid BG B precursor cells compared to BG A. This highlights the important roles of these factors for the disappearance of differentiation-specific glycan antigens and the appearance of cancer-specific glycan antigens. Our work contributes to a deeper understanding of erythropoiesis gene regulatory networks and identifies its interference with BG-specific gene expression regulations particularly in diseases, where ABO BGs determine treatment susceptibility and disease progression.

Burnout among hospital staff during the COVID-19 pandemic: Longitudinal results from the international Cope-Corona survey study.

OBJECTIVE: Long-term changes in burnout and its predictors in hospital staff during the COVID-19 pandemic were investigated in an international study. METHODS: Two online surveys were distributed to hospital staff in seven countries (Germany, Andorra, Ireland, Spain, Italy, Romania, Iran) between May and October 2020 (T1) and between February and April 2021 (T2), using the following variables: Burnout (emotional exhaustion and depersonalization), job function, age, gender, and contact with COVID-19 patients; individual resources (self-compassion, sense of coherence, social support) and work-related resources and demands (support at the workplace, risk perception, health and safety at the workplace, altruistic acceptance of risk). Data were analyzed using linear mixed models repeated measures, controlled for age. RESULTS: A total of 612 respondents were included (76% women). We found an increase in burnout from T1 to T2. Burnout was high among personnel with high contact with COVID-19 patients. Individual factors (self-compassion, sense of coherence) and work-related factors (support at the workplace, risk perception, health and safety at the workplace) showed associations with burnout. Low health and safety at the workplace at T1 was associated with an increase in emotional exhaustion at T2. Men showed an increase in depersonalization if they had much contact with COVID-19 patients. CONCLUSION: Burnout represents a potential problematic consequence of occupational contact with COVID-19 patients. Special attention should be paid to this group in organizational health management. Self-compassion, sense of coherence, support at the workplace, risk perception, and health and safety at the workplace may be important starting points for interventions. REGISTRATION: Müller, M. M. (2020, August 30). Cope-Corona: Identifying and strengthening personal resources of hospital staff to cope with the Corona pandemic. Open Science Foundation.

Burnout, emotional distress and sleep quality among Chinese psychiatric healthcare workers during the COVID-19 pandemic: a follow-up study.

Background: Different from the very early stages of the COVID-19 pandemic, burnout and chronic mental health problems among health care workers (HCWs) has become a challenge. Research is lacking on the relationship between burnout, stress, emotional distress and sleep quality. Methods: The Chinese center has been involved in the Cope-Corona project since the second survey (T2). Named after the project, a total of three cross-sectional surveys were distributed: T2 (February 16-20, 2021), T3 (May 10-14, 2022), and T4 (December 20-24, 2022). Burnout, depression, anxiety, sleep quality, workplace factors and individual resources were measured. Using the T4 data, we conducted structural equation model (SEM) to examine the mediating role of burnout in predicting emotional distress and sleep quality. Results: 96, 124, and 270 HCWs were enrolled at T2, T3, and T4, respectively. In line with the epidemic trends, the level of perceived COVID-19 related risks was significantly higher at T4, while the feeling of health and safety decreased significantly. At T4, the percentages of participants with clinically significant levels of depression and anxiety symptoms were 18.9% (51/270) and 9.3% (25/270), respectively, while 30.4% (82/270) of them reported poor or very poor sleep quality. According to the SEM, individual resources and workplace factors mainly had an indirect effect in predicting depression and anxiety via burnout. However, neither burnout nor stress was a mediator or predictor of sleep quality. Instead, individual resources, positive workplace factors, and younger age had a direct effect in predicting good sleep quality. Conclusion: Measures designed to enhance workplace factors and individual resources should be implemented to improve psychosomatic wellbeing of HCWs.

Workplace factors can predict the stress levels of healthcare workers during the COVID-19 pandemic: First interim results of a multicenter follow-up study.

Background: Research is lacking on the long-term influence of workplace factors on the mental health of health care workers during the COVID-19 pandemic. Methods: We distributed two online surveys to health care workers between May and October 2020 (T1) and between February and April 2021 (T2). Perceived stress, coronavirus-related risks, and workplace factors were measured via self-report questionnaires at both time points. We conducted hierarchical linear regression to investigate the predictive factors for high stress. Results: A total of 2,110 participants from seven countries and 4,240 participants from nine countries were enrolled at T1 and T2, respectively. Among them, 612 participated in both surveys. We called this cohort T1 + T2. High stress was reported in 53.8 and 61.6% of participants at T1 and T2, respectively. In cohort T1 + T2, compared with the baseline, the level of stress rose significantly (6.0 ± 2.9 vs. 6.4 ± 3.1), as did health/safety in the workplace (3.9 ± 0.8 vs. 4.2 ± 0.7). Unfortunately, we did not detect any significant difference concerning support in the workplace. Among all factors at baseline, being older than 35 [ß (95% CI) = -0.92 (-1.45, -0.40)], support [-0.80 (-1.29, -0.32)], and health/safety in the workplace [-0.33 (-0.65, -0.01)] were independent protective factors, while a positive history of mental disorders [0.81 (0.26, 1.37)] and rejection in private life [0.86 (0.48, 1.25)] were risk factors for high stress at T2. Conclusion: To relieve the high stress of health care workers, organizational-level approaches should be implemented, especially measures designed to enhance support, health/safety in the workplace, and to reduce the rejection of the public.

Red Blood Cell-Derived Microparticles Exert No Cancer Promoting Effects on Colorectal Cancer Cells In Vitro.

The biomedical consequences of allogeneic blood transfusions and the possible pathomechanisms of transfusion-related morbidity and mortality are still not entirely understood. In retrospective studies, allogeneic transfusion was associated with increased rates of cancer recurrence, metastasis and death in patients with colorectal cancer. However, correlation does not imply causation. The purpose of this study was to elucidate this empirical observation further in order to address insecurity among patients and clinicians. We focused on the in vitro effect of microparticles derived from red blood cell units (RMPs). We incubated different colon carcinoma cells with RMPs and analyzed their effects on growth, invasion, migration and tumor marker expression. Furthermore, effects on Wnt, Akt and ERK signaling were explored. Our results show RMPs do not seem to affect functional and phenotypic characteristics of different colon carcinoma cells and did not induce or inhibit Wnt, Akt or ERK signaling, albeit in cell culture models lacking tumor microenvironment. Allogeneic blood transfusions are associated with poor prognosis, but RMPs do not seem to convey tumor-enhancing effects. Most likely, the circumstances that necessitate the transfusion, such as preoperative anemia, tumor stage, perioperative blood loss and extension of surgery, take center stage.

Psychiatric and Psychosomatic Consultation-Liaison Services in General Hospitals: A Systematic Review and Meta-Analysis of Effects on Symptoms of Depression and Anxiety.

BACKGROUND: Psychiatric and psychosomatic consultation-liaison services (CL) are important providers of diagnosis and treatment for hospital patients with mental comorbidities and psychological burdens. OBJECTIVE: To perform a systematic review and meta-analysis investigating the effects of CL on depression and anxiety. METHODS: Following PRISMA guidelines, a systematic literature search was conducted until 2017. Included were published randomized controlled trials using CL interventions with adults in general hospitals, treatment as usual as control groups, and depression and/or anxiety as outcomes. Risk of bias was assessed using the Cochrane Risk of Bias Tool. Level of integration was assessed using the Standard Framework for Levels of Integrated Healthcare. Meta-analyses were performed using random effects models and meta-regression for moderator effects. RESULTS: We included 38 studies (9,994 patients). Risk of bias was high in 17, unclear in 15, and low in 6 studies. Studies were grouped by type of intervention: brief interventions tailored to the patients (8), interventions based on specific treatment manuals (19), and integrated, collaborative care (11). Studies showed small to medium effects on depression and anxiety. Meta-analyses for depression yielded a small effect (d = -0.19, 95% CI: -0.30 to -0.09) in manual studies and a small effect (d = -0.33, 95% CI: -0.53 to -0.13) in integrated, collaborative care studies, the latter using mostly active control groups with the possibility of traditional consultation. CONCLUSIONS: CL can provide a helpful first treatment for symptoms of depression and anxiety. Given that especially depressive symptoms in medically ill patients are long-lasting, the results underline the benefit of integrative approaches that respect the complexity of the illness.

Programmes for the management of preoperative anaemia: audit in ten European hospitals within the PaBloE (Patient Blood Management in Europe) Working Group.

BACKGROUND AND OBJECTIVES: Preoperative anaemia is an independent risk factor for a higher morbidity and mortality, a longer hospitalization and increased perioperative transfusion rates. Managing preoperative anaemia is the first of three pillars of Patient Blood Management (PBM), a multidisciplinary concept to improve patient safety. While various studies provide medical information on (successful) anaemia treatment pathways, knowledge of organizational details of diagnosis and management of preoperative anaemia across Europe is scarce. MATERIALS AND METHODS: To gain information on various aspects of preoperative anaemia management including organization, financing, diagnostics and treatment, we conducted a survey (74 questions) in ten hospitals from seven European nations within the PaBloE (Patient Blood Management in Europe) working group covering the year 2016. RESULTS: Organization and activity in the field of preoperative anaemia management were heterogeneous in the participating hospitals. Almost all hospitals had pathways for managing preoperative anaemia in place, however, only two nations had national guidelines. In six of the ten participating hospitals, preoperative anaemia management was organized by anaesthetists. Diagnostics and treatment focused on iron deficiency anaemia which, in most hospitals, was corrected with intravenous iron. CONCLUSION: Implementation and approaches of preoperative anaemia management vary across Europe with a primary focus on treating iron deficiency anaemia. Findings of this survey motivated the hospitals involved to critically evaluate their practice and may also help other hospitals interested in PBM to develop action plans for diagnosis and management of preoperative anaemia.

Treatment Options in Hemophilia.

BACKGROUND: Approximately 4550 persons were under treatment for hemophilia in Germany in 2017. The condition is currently treated with intravenous supplementa- tion of the missing clotting factor, either prophylactically or as needed. Newer treat- ment options rely on novel mechanisms of action. METHODS: This review is based on pertinent publications retrieved by a selective search in MEDLINE/PubMed, as well as on expert opinions and the recommenda- tions of specialty societies. RESULTS: Randomized controlled trials have shown that, in children aged 30 months to 6 years, prophylactic clotting-factor supplementation yields a markedly lower an- nual rate of hemorrhage than supplementation as needed: 3.27 (standard deviation [SD] 6.24) for the former vs. 17.69 (SD 9.25) for the latter. A similar large effect was seen in patients aged 12 to 50 years, with hemorrhage rates of 1.9 (SD 4.1) vs. 28.7 (SD 18.8). Clotting-factor preparations with longer half-lives make it possible to lessen the frequency of administration and to prevent subtherapeutic factor levels. A number of alternatives to clotting-factor supplementation have recently been approved or are currently being clinically tested. These new drugs are injected sub- cutaneously and have a longer half-life, possibly enabling better protection against bleeding than the current standard treatment. A further advantage of some of these drugs is that they can be given even in the presence of inhibitors to factor VIII. In addition, initial (phase I) clinical trials of gene therapy have been performed suc- cessfully for both hemophilia A and hemophilia B. CONCLUSION: Now that new alternatives to classic supplementation therapy are be- coming available, pertinent treatment algorithms for patients with hemophilia will have to be developed. It is still unclear to what extent the new drugs might supplant clotting factor supplementation as the first line of treatment.

[Blood Transfusion: a Guide to Clinical Decision Making]. / Bluttransfusion: ein Leitfaden für die klinische Entscheidungsfindung.

Nowadays, management of hemotherapy is regulated in Germany by the transfusion act and several guidelines while the transfusing physician is responsible for correct implementation at the bedside. Indications for blood products have to be carefully adapted to the patient's current clinical situation and pre-existing diseases have to be considered as well. Today, for most perioperative elective surgeries, evidence-based transfusion thresholds for packed red blood cell concentrates (RBC) have been defined and should be considered. Platelet concentrates (PC) have to be transfused in bleeding patients with thrombocytopenia or -pathy. In addition, PC are indicated prophylactically in clinically stable, not bleeding patients with a platelet trough count of less than 10/nl. Therapeutic plasma or fresh frozen plasma (FFP) is indicated for balanced substitution of coagulation factors, coagulation inhibitors and fibrinolysis factors in massive transfusion settings, where dilution of coagulation factors takes place. Plasma exchange in adults with thrombotic-thrombocytopenic purpura (TTP) or adult hemolytic-uremic syndrome (HUS) also requires FFP. In addition, FFP might be indicated, if no coagulation factor concentrate is available (e.g. FV deficiency). Adverse transfusion reactions are rare nowadays; however, hemolytic and allergic reactions are not too uncommon. For severe hemolytic transfusion reactions, in almost all cases, wrong blood in tube (WBIT) at the diagnostic bedside blood withdrawal or a mix-up of blood components before transfusion is causative. Massive transfusion situations require a proactive management, which includes RBC, FFP and potentially also PC and coagulation factor concentrates. Prior to elective surgery, anemic patients should be diagnosed and treated for the cause of their anemia, if possible.

The relationship between attachment orientations and the course of depression in coronary artery disease patients: A secondary analysis of the SPIRR-CAD trial.

OBJECTIVE: The relationship between attachment orientations and the recovery from depressive symptoms in patients diagnosed with coronary artery disease (CAD) with and without a psychotherapeutic intervention was examined in this study. METHODS: In a multicenter trial of 570 depressed CAD patients (SPIRR-CAD), assigned to usual care plus either a stepwise psychotherapy intervention or one information session, 522 patients provided attachment data at baseline. Attachment was measured with the Relationship Scales Questionnaire (RSQ), yielding four attachment orientations. The primary outcome was change in Hospital Anxiety and Depression Scale depression (HADS-D) scores from baseline to follow-up at 18 months. Secondary outcomes were HADS-D scores at 1, 6, 12, and 24 months. RESULTS: Independent of treatment assignment, attachment was related to change in depression at 18 months (p < 0.01) with secure attachment resulting in a significant reduction (-2.72, SE = 0.27) in depression compared to dismissive-avoidant (-1.51, SE = 0.35, p = 0.040) and fearful-avoidant (-0.65, SE = 0.61, p = 0.012) attachment. Patients with anxious-preoccupied attachment showed changes similar to secure attachment (-2.01, SE = 0.47). An explorative subgroup analysis across all assessment time points revealed patients with a dismissive-avoidant attachment benefitted from psychotherapy (average mean difference = 0.93, SE = 0.47, p = 0.048). CONCLUSION: Attachment played an important role for improvement in depressive symptoms. Only dismissive-avoidant patients seemed to benefit from the intervention. The lack of improvement in fearful-avoidant patients shows a need for specific interventions for this group. TRIAL REGISTRATION: www.clinicaltrials.govNCT00705965; www.isrctn.com ISRCTN76240576.

Red blood cells treated with the amustaline (S-303) pathogen reduction system: a transfusion study in cardiac surgery.

BACKGROUND: Nucleic acid-targeted pathogen inactivation technology using amustaline (S-303) and glutathione (GSH) was developed to reduce the risk of transfusion-transmitted infectious disease and transfusion-associated graft-versus-host disease with red blood cell (RBC) transfusion. STUDY DESIGN AND METHODS: A randomized, double-blind, controlled study was performed to assess the in vitro characteristics of amustaline-treated RBCs (test) compared with conventional (control) RBCs and to evaluate safety and efficacy of transfusion during and after cardiac surgery. The primary device efficacy endpoint was the postproduction hemoglobin (Hb) content of RBCs. Exploratory clinical outcomes included renal and hepatic failure, the 6-minute walk test (a surrogate for cardiopulmonary function), adverse events (AEs), and the immune response to amustaline-treated RBCs. RESULTS: A total of 774 RBC unis were produced. Mean treatment difference in Hb content was -2.27 g/unit (95% confidence interval, -2.61 to -1.92 g/unit), within the prespecified equivalence margins (±5 g/unit) to declare noninferiority. Amustaline-treated RBCs met European guidelines for Hb content, hematocrit, and hemolysis. Fifty-one (25 test and 26 control) patients received study RBCs. There were no significant differences in RBC usage or other clinical outcomes. Observed AEs were within the spectrum expected for patients of similar age undergoing cardiovascular surgery requiring RBCs transfusion. No patients exhibited an immune response specific to amustaline-treated RBCs. CONCLUSION: Amustaline-treated RBCs demonstrated equivalence to control RBCs for Hb content, have appropriate characteristics for transfusion, and were well tolerated when transfused in support of acute anemia. Renal impairment was characterized as a potential efficacy endpoint for pivotal studies of RBC transfusion in cardiac surgery.

Workflow for Target-Oriented Parametrization of an Enhanced Mechanistic Cell Culture Model.

The goal of this study is to develop a macroscopic mechanistic model describing growth and production within fed-batch cultivations of CHO cells. The model should be used for process characterization as well as for process monitoring including real-time parameter adaptations. The model proved to be able to describe a data-set of 40 processes differing in clones, scales, and process conditions with a normalized root mean square error of approximately 10%. However, due to limited parameter identifiability and limited knowledge about physiologically meaningful parameter values, a broad range of parameters could describe the data with similar quality. This hampered comparison of the model parameters as well as their real-time estimation. Therefore an iterative workflow combining techniques like sensitivity and identifiability analysis, analysis of the specific rates as well as structural adaptations of the parameter space is developed. By applying it the parameter variability could be reduced by 80% with similar predictive power as the original parameters. Summing up, based on a mechanistic CHO model, a generic and transferrable workflow is created for target-oriented parameter estimation in case of limited parameter identifiability. Finally, we suggest a methodology, which fits ideally into the frame of Process Analytical Technology aiming to increase process understanding.

[Preoperative Preparation: Patient Blood Management - What is Optimal?] / Präoperative Vorbereitung: Patient Blood Management ­ Was ist optimal?

Patient Blood Management (PBM) focusses on anemia management, the minimization of (unnecessary) iatrogenic blood loss and the exhaustion of natural tolerance to anemia with rational use of red blood cell transfusion. The focus of the current review article is now the preoperative phase with the following PBM components: management of anemia, pre-transfusion analytics and management of anticoagulants. Preoperative anemia is an independent risk factor for increased perioperative morbidity and mortality. In elective surgery, the causes of anemia should be diagnosed prior to surgery as early as possible, and if indicated, a specific treatment for treatable causes should be initiated. Preoperative pre-transfusion analytics should be performed by a step-wise approach depending on the transfusion probability (and the baseline hemoglobin) and current in-house data. Management of (oral) anticoagulants needs to consider an individual risk stratification for bleeding and thromboembolic events, should be initiated in the preoperative phase, and should specify whether the anticoagulant needs to be continued, stopped or bridged. Long-term success of the preoperative PBM program can only be guaranteed with clearly defined responsibilities in the preoperative PBM team, communication and training of all those involved in the process of care.

Transfusion of Packed Red Cells: Indications, Triggers and Adverse Events.

BACKGROUND: About four million units of packed red cells are transfused in Germany every year. The safety of blood transfusions is further improved by modern production methods and molecular diagnostic techniques. METHODS: This review is based on selected publications,including the German guidelines and regulations and the German Transfusion Act. RESULTS: Packed red blood cells are transfused to prevent tissue hypoxia. As the clinical manifestations of anemia are nonspecific, the indication for transfusion is based on surrogate parameters, such as the hemoglobin (Hb) concentration, in addition to clinical criteria. For patients with unimpaired cardiopulmonary and vascular function, transfusion is generally indicated at hemoglobin values of 6 g/dL (3.7 mmol/L) or less. Randomized controlled trials have shown that a restrictive transfusion strategy (trigger: Hb 7-8 g/dL) in certain patient groups is as effective as a more liberal strategy (trigger: Hb about 10 g/dL). The most frequent causes for transfusion errors are lack of informed consent, lack of identity checking and/or AB0 identity testing, and the drawing of blood samples in unlabelled tubes. CONCLUSION: Overtransfusion, undertransfusion, as well as other transfusion errors can be markedly reduced by means of appropriate organizational measures and training.