Influence of immunosuppression in patients with severe acute respiratory distress syndrome on veno-venous extracorporeal membrane oxygenation therapy.

Prognosis of patients suffering from acute respiratory distress syndrome (ARDS) is poor. This is especially true for immunosuppressed patients. It is controverisal whether these patients should receive veno-venous extracorporeal membrane oxygenation (VV ECMO) while evidence on this topic is sparse. We report retrospective data of a single-center registry of patients with severe ARDS requiring ECMO support between October 2010 and June 2019. Patients were analyzed by their status of immunosuppression. ECMO weaning success and hospital survival were analyzed before and after propensity score matching (PSM). Moreover, ventilator free days (VFD) were compared. A total of 288 patients were analyzed (age 55 years, 67% male), 88 (31%) presented with immunosuppression. Survival rates were lower in immunosuppressed patients (27% vs. 53%, P < .001 and 27% vs. 48% after PSM, P = .006). VFD (60 days) were lower for patients with immunosuppression (11.9 vs. 22.4, P < .001), and immunosuppression was an independent predictor for mortality in multivariate analysis. Hospital survival was 20%, 14%, 35%, and 46% for patients with oncological malignancies, solid organ transplantation, autoimmune diseases, and HIV, respectively. In this analysis immunosuppression was an independent predictor for mortality. However, there were major differences in the weaning and survival rates between the etiologies of immunosuppression which should be considered in decision making.

Increased Red Cell Volume Is a Relevant Contributing Factor to an Expanded Blood Volume in Compensated Systolic Chronic Heart Failure.

BACKGROUND: In patients with chronic heart failure (CHF), volume overload is usually described as an expansion of plasma volume. Additional red cell volume (RCV) expansion is less commonly recognized. So far, little is known about quantitative differences in blood volume status and its different components in patients with stable CHF compared to healthy controls. METHODS: This study aimed to quantify blood volume and its constituents, RCV and plasma volume, by using an abbreviated carbon monoxide rebreathing method with particular focus on its primary measure total hemoglobin mass in 47 patients (10 women) with systolic CHF and a left ventricular ejection fraction of 29.0 ± 9.4%. These were compared to an age-matched control group of 84 healthy subjects (44 women) using the same method. RESULTS: In both absolute and body-surface-area-corrected analysis, hemoglobin mass (446 ± 81 vs 353 ± 64 g/m2) as well as RCV (1293 ± 231 vs 1033 ± 176 mL/m2) were significantly increased in CHF. In addition, significant plasma volume expansion was observed in CHF (2069 ± 400 vs 1750 ± 231 mL/m2) and, in conjunction with RCV, constituted a significantly increased blood volume (3361 ± 574 vs 2783 ± 369 mL/m2). In 66% of patients with compensated CHF, RCV was excessive compared to 14% in the control group. CONCLUSIONS: An increased RCV is a relevant contributing factor to hypervolemia in stable CHF. This is associated with an increased oxygen-carrying capacity, so it may be regarded as a possible compensatory mechanism for a reduced ejection fraction.

Comparison of three common whole blood platelet function tests for in vitro P2Y12 induced platelet inhibition.

In the context of interventional cardiology, platelet function testing may identify patients treated with P2Y12-inhibitors at an increased risk of mortality, thrombosis and bleeding. Several whole blood point-of-care platelet function analyzers are available; however, inter-device differences have not been examined systematically. To compare three platelet function tests under standardized in vitro conditions. Healthy volunteer (n = 10) blood samples were spiked with increasing concentrations of ticagrelor (0-7500 ng/mL) and/or ASA (0-3280 ng/mL), measured on three platelet function analyzers (TEG®6s, Multiplate®, and VerifyNow®) and respective Effective Concentration (EC) levels EC10, EC50 and EC90 were calculated. Repeatability was assessed in a separate group of pooled blood samples (n = 10) spiked with ticagrelor at EC10, EC50 and EC90. ASA had no impact on ADP-activated channels for all three devices. TEG®6s was able to distinguish (p ≤ 0.05) between all ticagrelor EC zones; VerifyNow® and Multiplate® were able to distinguish between three and two zones, respectively. Multiplate® showed the largest window between EC10 and EC90 (19-9153 ng/mL), followed by TEG®6s (144-2589 ng/mL), and VerifyNow® (191-1100 ng/mL). Drug effect models distribution of disagreements were identified for TEG®6s (5.0%), VerifyNow® (8.3%), and Multiplate® (13.3%). TEG®6s showed the smallest average coefficient of variation between EC conditions (5.1%), followed by Multiplate® (14.1%), and VerifyNow® (17.7%). Linear models could be generated between TEG®6s and Multiplate®, but not VerifyNow®. Significant differences were found between whole blood point-of-care platelet function analyzers and the clinical impact of these differences needs to be further investigated.

Current strategies of blood doping detection.

During the last 30 years, the artificial increase of red blood cell volume ("blood doping") has changed the level of performance in all endurance sports. Many doping scandals have shown the extent of the problem. The detection of blood doping relies on two different approaches: the direct detection of exogenous manipulating substances (erythropoietic stimulants) or red cells (homologous transfusion) and the indirect detection, where not the doping substance or technique itself, but its effect on certain biomarkers is measured. Whereas direct detection using standard laboratory procedures such as isoelectric focusing can identify erythropoietic stimulants, homologous blood transfusion is identified through mismatches in minor blood group antigens by flow cytometry. Indirect methods such as the athlete biological passport are the only means to detect autologous transfusion and may also be used for the detection of erythropoietic stimulants or homologous transfusion. New techniques to unmask blood doping include the use of high-throughput 'omics' technologies (proteomics/metabolomics) and the combination of different biomarkers with the help of mathematical approaches. Future strategies should aim at improving the use of the available data and resources by applying pattern recognition algorithms to recognize suspicious athletes and, on the basis of these findings, use the appropriate testing method. Different types of information should be combined in the quest for a forensic approach to anti-doping.

Altitude training and haemoglobin mass from the optimised carbon monoxide rebreathing method determined by a meta-analysis.

OBJECTIVE: To characterise the time course of changes in haemoglobin mass (Hbmass) in response to altitude exposure. METHODS: This meta-analysis uses raw data from 17 studies that used carbon monoxide rebreathing to determine Hbmass prealtitude, during altitude and postaltitude. Seven studies were classic altitude training, eight were live high train low (LHTL) and two mixed classic and LHTL. Separate linear-mixed models were fitted to the data from the 17 studies and the resultant estimates of the effects of altitude used in a random effects meta-analysis to obtain an overall estimate of the effect of altitude, with separate analyses during altitude and postaltitude. In addition, within-subject differences from the prealtitude phase for altitude participant and all the data on control participants were used to estimate the analytical SD. The 'true' between-subject response to altitude was estimated from the within-subject differences on altitude participants, between the prealtitude and during-altitude phases, together with the estimated analytical SD. RESULTS: During-altitude Hbmass was estimated to increase by ∼1.1%/100 h for LHTL and classic altitude. Postaltitude Hbmass was estimated to be 3.3% higher than prealtitude values for up to 20 days. The within-subject SD was constant at ∼2% for up to 7 days between observations, indicative of analytical error. A 95% prediction interval for the 'true' response of an athlete exposed to 300 h of altitude was estimated to be 1.1-6%. CONCLUSIONS: Camps as short as 2 weeks of classic and LHTL altitude will quite likely increase Hbmass and most athletes can expect benefit.

The distribution of pace adopted by cyclists during a cross-country mountain bike World Championships.

The purpose of this study was to examine the distribution of pace self-selected by cyclists of varying ability, biological age and sex performing in a mountain bike World Championship event. Data were collected on cyclists performing in the Elite Male (ELITEmale; n = 75), Elite Female (ELITEfemale; n = 50), Under 23 Male (U23male; n = 62), Under 23 Female (U23female; n = 34), Junior Male (JNRmale; n = 71) and Junior Female (JNRfemale; n = 30) categories of the 2009 UCI Cross-Country Mountain Bike World Championships. Split times were recorded for the top, middle and bottom 20% of all finishers of each category. Timing splits were positioned to separate the course into technical and non-technical, uphill, downhill and rolling/flat sections. Compared with bottom performers, top performers in all male categories (ELITEmale, U23male, JNRmale) maintained a more even pace over the event as evidenced by a significantly lower standard deviation and range in average lap speed. Top performers, males, and ELITEmale athletes spent a lower percentage of overall race time on technical uphill sections of the course, compared with middle and bottom placed finishers, females, and JNRmale athletes, respectively. Better male performers adopt a more even distribution of pace throughout cross-country mountain events. Performance of lower placed finishers, females and JNRmale athletes may be improved by enhancing technical uphill cycling ability.

Longitudinal observation of Epstein-Barr virus antibodies in athletes during a competitive season.

Epstein-Barr virus (EBV) serology continues to be the first diagnostic test when infectious mononucleosis is suspected. Due to possible mild immunosuppression in competitive athletes, EBV reactivation determined by increases in salivary viral load have been identified as one possible cause in recurrent respiratory infections. The long-term variation in EBV antibody levels in athletes compared to a control group remains unclear. The purpose of the study was to investigate the time course of changes in concentration of EBV antibodies in athletes with special emphasis on antibodies against early antigens (EAs) and avidity determination. During a competition season of approximately 12 months, the serological status of 15 biathletes (age 27 ± 3 years, 7 female, 8 male, international to Olympic level) was compared with 11 controls (age 23 ± 1 years; 1 female 10 male) at multiple time points. In addition, 43 healthy swimmers (age 22 ± 4 years, 18 female, 25 male, national to international level) were tested to validate the results with only two time points interspersed by approximately 6 months of intensive physical exercise. Analysis of quantitative antibody intensity bands revealed stable values during a competition season. In particular, IgG-antibodies against EAs may persist and were found in 15% of past infections in swimmers exhibiting fluctuations in concentration after 6 months. These results provide evidence that positive Anti-EA-IgG may persist in healthy athletes and thus, should not be used to diagnose EBV reactivations or to identify a compromised immune function.

Clinically unrecognized plasma volume expansion predicts long-term all-cause-mortality in chronic heart failure.

INTRODUCTION: Chronic heart failure (CHF) is associated with elevated total blood volume (BV) and distinct phenotypes of total red cell volume (RCV) and plasma volume (PV) elevations. Especially PV expansion during clinical decompensation is linked with adverse clinical outcomes. The role of PV expansion in compensated CHF patients is less clear. Aim of the present study is to investigate the impact of BV parameters on long-term mortality in CHF patients investigated at a compensated state. METHODS AND RESULTS: BV, PV and RCV were determined in 44 (9 female) compensated CHF patients using an abbreviated carbon monoxide method, who were followed up for 6.0 years, (range: 3.7-6.5 years) for all-cause mortality. In univariate analysis PV expansion but not BV and RCV predicted all-cause mortality (p = .021). A cutoff of 1800 ml PV/m² body-surface area allows stratification for all-cause mortality (p = .044). PV expansion but not RCV reduction explains the significantly lower hematocrit values of nonsurvivors. DISCUSSION: In this pilot study, PV expansion, which was unnoticed from a clinician's perspective, but is indicated by significantly lower hematocrit, appears to be a relevant predictor of long-term all-cause mortality. Whether PV expansion constitutes an adverse CHF phenotype and can be targeted by diuretic therapy is currently unclear.

Detection of autologous blood doping with adaptively evaluated biomarkers of doping: a longitudinal blinded study.

BACKGROUND: Since no direct detection method for autologous blood transfusions exists, the most promising attempt is the Athlete Biological Passport (ABP) and its adaptive model that enables a longitudinal monitoring of hematologic measures to identify patterns of blood manipulations. The purpose therefore was to evaluate the performance of this adaptive model for the detection of autologous blood transfusions in a longitudinal blinded setting. STUDY DESIGN AND METHODS: Twenty-one subjects were divided into a doped group (multiple transfusions of 1-2 units of red blood cells, n = 11) and a control group (n = 10). The time course of a cycling season (42 weeks) was simulated including three major competitions (Classics, Grand Tour, World Championships). Up to 10 venous blood samples were ordered per subject by a blinded investigator mimicking the intelligent approach in obtaining hematologic data for the adaptive model (hemoglobin [Hb] concentration, reticulocyte percentage, OFF-score). RESULTS: Retrospective analysis allowed identification of four (probability >99%) or three (probability >99.9%) abnormal samples for Hb and eight (probability >99%) or five (probability >99.9%) abnormal samples for OFF-hr in doped subjects. Four doped subjects (36%) presented an abnormal OFF-hr sequence and three doped subjects (27%) an abnormal Hb sequence; there were no false-positive sequence results. The best possible sensitivity was 82% when a combination of all tests was used. CONCLUSIONS: This investigation provides evidence that the adaptive model allows detection of autologous blood transfusions with a good sensitivity. An intelligent testing approach and the adherence to World Anti-Doping Agency's ABP operating guidelines are nevertheless determinant in the success.

The contribution of haemoglobin mass to increases in cycling performance induced by simulated LHTL.

We sought to determine whether improved cycling performance following 'Live High-Train Low' (LHTL) occurs if increases in haemoglobin mass (Hb(mass)) are prevented via periodic phlebotomy during hypoxic exposure. Eleven, highly trained, female cyclists completed 26 nights of simulated LHTL (16 h day(-1), 3000 m). Hb(mass) was determined in quadruplicate before LHTL and in duplicate weekly thereafter. After 14 nights, cyclists were pair-matched, based on their Hb(mass) response (ΔHb(mass)) from baseline, to form a response group (Response, n = 5) in which Hb(mass) was free to adapt, and a Clamp group (Clamp, n = 6) in which ΔHb(mass) was negated via weekly phlebotomy. All cyclists were blinded to the blood volume removed. Cycling performance was assessed in duplicate before and after LHTL using a maximal 4-min effort (MMP(4min)) followed by a ride time to exhaustion test at peak power output (T (lim)). VO(2peak) was established during the MMP(4min). Following LHTL, Hb(mass) increased in Response (mean ± SD, 5.5 ± 2.9%). Due to repeated phlebotomy, there was no ΔHb(mass) in Clamp (-0.4 ± 0.6%). VO(2peak) increased in Response (3.5 ± 2.3%) but not in Clamp (0.3 ± 2.6%). MMP(4min) improved in both the groups (Response 4.5 ± 1.1%, Clamp 3.6 ± 1.4%) and was not different between groups (p = 0.58). T (lim) increased only in Response, with Clamp substantially worse than Response (-37.6%; 90% CL -58.9 to -5.0, p = 0.07). Our novel findings, showing an ~4% increase in MMP(4min) despite blocking an ~5% increase in Hb(mass), suggest that accelerated erythropoiesis is not the sole mechanism by which LHTL improves performance. However, increases in Hb(mass) appear to influence the aerobic contribution to high-intensity exercise which may be important for subsequent high-intensity efforts.

Time course of red cell volume and plasma volume over six months in compensated chronic heart failure.

BACKGROUND: In patients with chronic heart failure (CHF), volume overload is usually described as an expansion of plasma volume (PV). Additional red cell volume (RCV) expansion also occurs in a relevant fraction of compensated CHF patients. So far, little is known about the stability of these vascular volumes and possible volume excess in compensated CHF patients over time. METHODS AND RESULTS: This study aims at quantification of blood volume and its components, RCV and PV (raw values and adjusted for sex and anthropometric characteristics, expressed as per cent of the expected normal value), using an abbreviated carbon monoxide (CO) rebreathing method (aCORM) in 14 patients (two women) with systolic CHF at baseline and at a follow-up visit after approximately 6 months. While a vast heterogeneity was observed concerning RCV (82% to 134% of normalized alues) and PV (72% to 131% of normalized values), the vascular volumes showed a mean change of 1.2% and -1.3% after a mean follow-up of 183 days. CONCLUSIONS: The vascular volumes including individual volume excess appear to be stable in compensated CHF patients. The reason for this individual volume response concerning both RCV and PV in CHF remains unclear and deserves further clarification.

Estimated plasma volume status is a modest predictor of true plasma volume excess in compensated chronic heart failure patients.

Plasma volume and especially plasma volume excess is a relevant predictor for the clinical outcome of heart failure patients. In recent years, estimated plasma volume based on anthropometric characteristics and blood parameters has been used whilst direct measurement of plasma volume has not entered clinical routine. It is unclear whether the estimation of plasma volume can predict a true plasma volume excess. Plasma volume was measured in 47 heart failure patients (CHF, 10 female) using an abbreviated carbon monoxide rebreathing method. Plasma volume and plasma volume status were also estimated based on two prediction formulas (Hakim, Kaplan). The predictive properties of the estimated plasma volume status to detect true plasma volume excess > 10% were analysed based on logistic regression and receiver operator characteristics. The area under the curve (AUC) to detect plasma volume excess based on calculation of plasma volume by the Hakim formula is 0.65 (with a positive predictive value (PPV) of 0.62 at a threshold of - 16.5%) whilst the AUC for the Kaplan formula is 0.72 (PPV = 0.67 at a threshold of - 6.3%). Only the estimated plasma volume status based on prediction of plasma volume by the Kaplan formula formally appears as an acceptable predictor of true plasma volume excess, whereas calculation based on the Hakim formula does not sufficiently predict a true plasma volume excess. The low positive predictive values for both methods suggest that plasma volume status estimation based on these formulas is not suitable for clinical decision making.

Blood volume and hemoglobin mass in long-term heart transplant recipients with and without Anemia.

BACKGROUND: In systolic chronic heart failure, a heterogeneous blood volume (BV) regulation can be found with plasma volume expansion in many cases, possibly leading to pseudoanemia. Little is known about the volume status after heart transplantation (HTX). So far, anemia of HTX recipients was solely investigated using hemoglobin-concentration that may be misleading in a clinical context. The objective of the study was whether a difference in plasma volume and red cell volume can be observed in clinically stable heart transplant recipients compared to matched control subjects. Secondary, the aim was to describe anemia in the long-term after HTX based on quantitative data. METHODS: Blood volume and its constituents red cell volume and plasma volume were quantified using an abbreviated carbon monoxide rebreathing method (aCORM) with focus on its primary measure total hemoglobin mass (Hbmass) and coincidental anemia in 36 (7 women) heart transplant recipients. For comparison, a matched control group of 46 (5 women) healthy subjects was selected. RESULTS: Neither Hbmass nor blood volumes were significantly different in HTX patients compared to matched healthy control group subjects. The prevalence of anemia 6.3 ± 4.3 years after transplantation was 19%. Hbmass and red cell volume were significantly lower in anemic HTX patients compared to non-anemic patients while plasma volume was not expanded. Various immunosuppressant regimens did not have an effect on Hbmass, plasma volume or red cell volume. CONCLUSIONS: There was no difference in blood volumes and Hbmass between HTX patients and control subjects. The pathophysiologic blood volume regulation in chronic heart failure does not seem to be longer active in long-term HTX recipients. However, in the long-term after HTX, anemia occurs in a considerable number of patients as true anemia without a clear association with immunosuppression. TRIAL REGISTRATION: German registry for clinical studies, DRKS00006078. Registered 09 May 2014, https://www.drks.de/drks_web/navigate.do?navigationId=trial . HTML&TRIAL_ID=DRKS00006078.

Cardiogenic shock: incidence, survival and mechanical circulatory support usage 2007-2017-insights from a national registry.

BACKGROUND: A central element in the management of cardiogenic shock (CS) comprises mechanical circulatory support (MCS) systems to maintain cardiac output (CO). This study aims to quantify incidence, outcome and influence of MCS in CS over the last decade. METHODS: All patients hospitalized with CS in a tertiary university hospital in Germany between 2007 and 2017 were identified utilizing the international coding system ICD-10 with code R57.0. Application of MCS was identified via German procedure classification codes (OPS). RESULTS: 383,983 cases of cardiogenic shock were reported from 2007 to 2017. Patients had a mean age of 71 years and 38.5% were female. The incidence of CS rose by 65.6% from 26,828 cases in 2007 (33.1 per 100,000 person-years, hospital survival 39.2%) to 44,425 cases in 2017 (53.7 per 100,000 person-years, survival 41.2%). In 2007, 16.0% of patients with CS received MCS (4.6 per 100,000 person-years, survival 46.6%), dropping to 13.9% in 2017 (6.6 per 100,000 person-years, survival 38.6%). Type of MCS changed over the years, with decreasing use of the intra-aortic balloon pump (IABP), an increase in extracorporeal membrane oxygenation (VA-ECMO) and percutaneous ventricular assist device (pVAD) usage. Significant differences regarding in-hospital survival were observed between the devices (survival: overall: 40.2%; medical treatment = 39.5%; IABP = 49.5%; pVAD = 36.2%; VA-ECMO = 30.5%; p < 0.001). CONCLUSIONS: The incidence of CS is increasing, but hospital survival remains low. MCS was used in a minority of patients, and the percentage of MCS usage in CS has decreased. The use rates of the competing devices change over time.

Total haemoglobin mass but not cardiac volume adapts to long-term endurance exercise in highly trained spinal cord injured athletes.

The oxygen transport system is an important component in the limitation of endurance performance in able-bodied and paraplegic athletes. The aim of the present study was to investigate the total haemoglobin mass (tHb, carbon monoxide rebreathing method) and cardiac volume (HV, echocardiography) in 25 highly endurance trained male spinal cord injured (mainly paraplegic) athletes (SCI-TRAINED) and to compare the results with those of 10 untrained spinal cord injured controls (SCI-UNTRAINED) and in 25 able-bodied elite endurance athletes (TRAINED). tHb and tHb/kg were higher in SCI-TRAINED than in SCI-UNTRAINED (748 +/- 110 vs. 629 +/- 209 g (464 +/- 68 vs. 390 +/- 130 mmol) (mean +/- SD), P = 0.02 and 10.3 +/- 1.3 vs. 7.9 +/- 2.0 g/kg (6.4 +/- 0.8 vs. 4.9 +/- 1.2 mmol/kg), P < 0.0001), while HV and HV/kg showed no significant differences between the two groups (765 +/- 93 vs. 793 +/- 164 ml and 10.6 +/- 1.4 vs. 10.3 +/- 2.5 ml/kg). No difference between SCI-TRAINED and TRAINED was found for septal diameter (9.5 +/- 1.0 mm vs. 9.7 +/- 0.7 mm). However, tHb and tHb/kg in SCI-TRAINED was lower than in TRAINED [896 +/- 123 g (556 +/- 76 mmol), P = 0.0003 and 12.6 +/- 1.3 g/kg (7.8 +/- 0.8 mmol), P < 0.0001]. In spinal cord injured athletes, tHb but not HV adapts moderately to chronic endurance exercise, although tHb in spinal cord injured athletes does not reach the level of able-bodied-trained persons.

Hodgkin's Lymphoma in an elite endurance athlete.

Cancer is a life-threatening condition. We describe the case of a 22-yr-old world-class endurance athlete who presented with mild local lymphadenopathy but without any systemic complaints or impaired performance. He was subsequently diagnosed with stage III A (S) Hodgkin's lymphoma. A complete physiological workup before the diagnosis revealed high aerobic capacity. Immediately after six courses of escalated BEACOPP chemotherapy in an identical test setting, aerobic capacity was markedly reduced (-42%), mainly because of a decrease in total hemoglobin mass (-37%), despite maintaining a certain amount of endurance training. Other potentially performance-limiting systems such as heart, lung, or aerobic metabolism did not show any signs of impairment. Two months after chemotherapy, the athlete had recovered his hemoglobin mass, and his aerobic performance was almost back to pretherapy levels. This case illustrates that advanced malignancies can be present in elite athletes without affecting performance, and that aerobic capacity can be regained within a short time after systemic chemotherapy.

Applying the Optimized CO Rebreathing Method for Measuring Blood Volumes and Hemoglobin Mass in Heart Failure Patients.

Introduction: Determination of blood volume, red cell volume, and plasma volume contributes to the understanding of the pathophysiology in heart failure, especially concerning anemia and volume load. The optimized carbon monoxide (CO)-rebreathing method (oCORM) is used to determine these parameters and hemoglobin mass (Hbmass) in exercise physiology. The applicability of oCORM to determine the intravascular volumes and Hbmass in heart failure patients is currently undetermined because assumptions concerning CO kinetics with oCORM rely on healthy subjects with a normal ejection fraction. Therefore, the aim of the present study is to determine the applicability and the systematic error of oCORM arising from a reduced EF when oCORM is used for measurement of intravascular volumes and Hbmass in heart failure patients. Methods: oCORM was performed in 21 patients with heart failure and a reduced ejection fraction (EF) of < 30% (EFsev) and 25 controls (CONT). CO kinetics in capillary blood was studied 3-15 min after commencement of CO rebreathing. Differences in CO kinetics between the groups were assessed using a generalized linear model. The systematic error for determination of Hbmass with oCORM arising from differences in CO kinetics was assessed using the Monte Carlo method. Results: The CO kinetics was significantly different between EFsev and CONT. In both groups, exposure to CO led to a COHb increase to 6.0 ± 1.0% 3 min after CO rebreathing. There were no CO related side effects or any clinical symptoms. Monte Carlo simulation quantifies the systematic error for determination of Hbmass arising from an impaired ejection fraction to be -0.88%. Conclusion: Our results indicate an impaired vascular mixing of CO when EF is severely reduced. When Hbmass is determined using the original oCORM protocol in heart failure patients with a reduced EF, the systematic underestimation of about 1% should be considered. However, the error arising from this impaired vascular mixing appears small and clinically negligible. Furthermore, application of oCORM was safe and not related to any side effects resulting from CO exposure. In conclusion, oCORM can be used for assessing intravascular volumes and Hbmass in patients with a reduced EF.

Hb mass measurement suitable to screen for illicit autologous blood transfusions.

PURPOSE: An increase of hemoglobin (Hb) mass is the key target of blood doping practices to enhance performance as it is a main determinant of maximal oxygen uptake. Although detection methods exist for doping with recombinant EPO and homologous blood transfusions, autologous transfusions remain virtually undetectable. In this context, the most sensitive parameter would be a determination of Hb mass itself. The purpose therefore was to establish whether Hb mass measurements by the optimized CO-rebreathing method allow screening for the withdrawal and reinfusion of autologous red blood cells. METHODS: The optimized CO-rebreathing method was used for evaluation of Hb mass in two groups at three time points (duplicate measurements: 1) baseline, 2) after donation, and 3) after reinfusion). Group I (N = 6) was to donate and receive 1 unit of packed red cells (PRC) in contrast to two PRC in group II (N = 4). The time span between withdrawal and reinfusion was 2 d. RESULTS: The mean Hb content of the blood units was 59.0 +/- 3.9 g (group I) and 108.3 +/- 1.3 g (group II). Hb mass decreased significantly after blood withdrawal (-89 +/- 16 g in group I and -120 +/- 14 g in group II) and increased significantly after reinfusion (group I: 70 +/- 16 g; group II: 90 +/- 9 g) but was lower than at baseline (group I: -19 +/- 17 g; group II: -30 +/- 14 g). The total error of measurements for the duplicate measures ranged between 0.8 and 3.1% (Hb mass: 6.4-22.1 g). CONCLUSION: Hb mass determination with the optimized CO-rebreathing method has sufficient precision to detect the absolute differences in Hb mass induced by blood withdrawal and autologous reinfusion. Thus, it may be suited to screen for artificially induced alterations in Hb mass.

Epstein-Barr virus serostatus: no difference despite aberrant patterns in athletes and control group.

PURPOSE: To investigate the Epstein-Barr virus (EBV) serostatus in an athletic endurance population, especially the prevalence of complex aberrant EBV antibody patterns. In addition, the purpose was to determine whether serology in athletes is more complex than in the general population. METHODS: The study protocol included serological testing of 202 advanced endurance athletes (biathlon, cycling, nordic skiing (state to international level); mean age 19 +/- 4) and 200 control subjects (mean age 23 +/- 2). Twenty-microliter serum samples were examined using a strip immunoassay with antigens produced by recombinant techniques for detection of EBV IgG antibodies: anti-EBNA-1 (anti-EBV nuclear antigen-1), anti-p18, anti-p23, anti-p138, anti-p54, and anti-BZLF-1. Avidity determination was used to differentiate further between acute, recent, and past infections. RESULTS: Athletes showed 35 negative (17%), 6 unresolvable (3%), 1 acute (0.5%), 11 recent (5%), 122 past (61%), and 27 aberrant past (mainly anti-EBNA-1 negative) (13.5%) cases. The control group showed 31 negative (16%), 4 unresolvable (2%), 1 acute (0.5%), 1 recent (0.5%), 135 past (68%), and 28 (14.0%) aberrant past cases. Although endurance athletes included more recent infections (several months since acute infection), there was no significant difference (P = 0.144) in the total constellation of EBV serostatus between the groups. CONCLUSION: No evidence was found for the assumption that endurance athletes are more susceptible to EBV infections than the general population. In addition, no differences were found with respect to serological classical and aberrant complicated patterns between athletes and the control group. Those cases that may lead to false diagnoses of acute EBV infection in previously used test systems because of a negative anti-EBNA-1 are common in both groups but were unambiguously resolved by the Recomline EBV IgG test applied here.

Therapeutic Depletion of Iron Stores Is Not Associated with a Reduced Hemoglobin Mass in a Hemochromatosis Patient.

INTRODUCTION: Hereditary hemochromatosis features a dysregulated iron absorption leading to iron overload and organ damage. The regulation of total hemoglobin mass during depletion of iron deposits by therapeutic phlebotomy has not been studied. CASE PRESENTATION: The initial ferritin level of the 52-year-old male subject was 1,276 µg/l. Despite successful depletion of iron stores (ferritin_min: 53 µg/l) through phlebotomies, total hemoglobin mass stabilized at the pretherapy level. However, regeneration of total hemoglobin mass was accelerated (up to 10.8 g/day). CONCLUSION: In this hemochromatosis patient, the total hemoglobin mass was not altered in the long term, but regeneration was accelerated, possibly due to elevated body iron content.