Corrigendum: A modified formula using energy system contributions to calculate pure maximal rate of lactate accumulation during a maximal sprint cycling test.

[This corrects the article DOI: 10.3389/fphys.2023.1147321.].

A modified formula using energy system contributions to calculate pure maximal rate of lactate accumulation during a maximal sprint cycling test.

Purpose: This study aimed at comparing previous calculating formulas of maximal lactate accumulation rate ( ν La.max) and a modified formula of pure ν La.max (P ν La.max) during a 15-s all-out sprint cycling test (ASCT) to analyze their relationships. Methods: Thirty male national-level track cyclists participated in this study (n = 30) and performed a 15-s ASCT. The anaerobic power output (Wpeak and Wmean), oxygen uptake, and blood lactate concentrations (La-) were measured. These parameters were used for different calculations of ν La.max and three energy contributions (phosphagen, W PCr; glycolytic, W Gly; and oxidative, W Oxi). The P ν La.max calculation considered delta La-, time until Wpeak (tPCr-peak), and the time contributed by the oxidative system (tOxi). Other ν La.max levels without tOxi were calculated using decreasing time by 3.5% from Wpeak (tPCr -3.5%) and tPCr-peak. Results: The absolute and relative W PCr were higher than W Gly and W Oxi (p < 0.0001, respectively), and the absolute and relative W Gly were significantly higher than W Oxi (p < 0.0001, respectively); ν La.max (tPCr -3.5%) was significantly higher than P ν La.max and ν La.max (tPCr-peak), while ν La.max (tPCr-peak) was lower than P ν La.max (p < 0.0001, respectively). P ν La.max and ν La.max (tPCr-peak) were highly correlated (r = 0.99; R 2 = 0.98). This correlation was higher than the relationship between P ν La.max and ν La.max (tPCr -3.5%) (r = 0.87; R 2 = 0.77). ν La.max (tPCr-peak), P ν La.max, and ν La.max (tPCr -3.5%) were found to correlate with absolute Wmean and W Gly. Conclusion: P ν La.max as a modified calculation of ν La.max provides more detailed insights into the inter-individual differences in energy and glycolytic metabolism than ν La.max (tPCr-peak) and ν La.max (tPCr -3.5%). Because W Oxi and W PCr can differ remarkably between athletes, implementing their values in P ν La.max can establish more optimized individual profiling for elite track cyclists.

Lactate Thresholds and the Simulation of Human Energy Metabolism: Contributions by the Cologne Sports Medicine Group in the 1970s and 1980s.

Today, researchers, practitioners, and physicians measure the concentration of lactate during a graded exercise test to determine thresholds related to the maximal lactate steady state (maxLass) as a sensitive measure of endurance capacity. In the 1970s and 1980s, a group of Cologne-based researchers around Wildor Hollmann, Alois Mader, and Hermann Heck developed the methodology for systematic lactate testing and introduced a 4 mmol.L-1 lactate threshold. Later, they also developed the concept of the maxLass, and Mader designed a sophisticated mathematical model of human energy metabolism during exercise. Mader`s model simulates metabolic responses to exercise based on individual variables such as maximum oxygen uptake ( V ˙ O2max) and the maximal rate of lactate formation (νLa.max). Mader's model predicts that the νLa.max reduces the power at the anaerobic threshold and endurance performance but that a high νLa.max is required for events with high power outputs in elite athletes. Mader's model also assumed before the millennium that the rate of fat oxidation is explained by the difference between glycolytic pyruvate synthesis and the actual rate of pyruvate oxidation which is consistent with current opinion. Mader's model also simulated the V ˙ O2max slow component in the mid-1980s. Unfortunately, several landmark studies by the Cologne group were only published in German, and as a result, contributions by the Cologne group are under-appreciated in the English-speaking world. This narrative review aims to introduce key contributions of the Cologne group to human metabolism research especially for readers who do not speak German.

The ability of energy recovery in professional soccer players is increased by individualized low-intensity exercise.

The aim of this study was to investigate whether individualized low-intensity exercise (ILIE) within the recovery domain before lactate threshold 1 (LT 1) improves energetic recovery and general endurance capacity in professional soccer players. Twenty-four professional soccer players (age: 24.53 ± 4.85 years, height: 180 ± 6.30 cm, body mass: 75.86 ± 8.01 kg, body fat: 12.19 ± 2.69%) participated in the study (n = 24). The 1-h ILIE intervention involved 27 jogging sessions spanning nine weeks and jogging speed corresponding to 72% of LT 1 (7.15 ± 0.95 km∙h-1). Pre-ILIE and post-ILIE LT testing variables measured within 9 weeks included blood lactate concentrations (La-) and heart rate (HR) at specific exercise intensities during ILIE LT test. The jogging/running speeds (S), delta (Δ) S, HR, and ΔHR were measured at 1.5, 2.0, 3.0, and 4.0 mmol∙L-1 La-, respectively. Values of La- and HR at the same exercise intensities (5.4-16.2 km∙h-1) in the post-ILIE LT test compared with pre-ILIE LT test were significantly decreased (P < 0.05 and P < 0.01, respectively). Furthermore, S at all specific La- levels (1.5, 2.0, 3.0, and 4.0) were significantly increased, while HR at 2.0, 3.0, and 4.0 La- decreased significantly (P < 0.05 and P < 0.01, respectively). Low to moderate positive correlations were observed between ΔS and ΔHR at 1.5 and 2.0 La- (r = 0.52 and r = 0.40, respectively). The nine-week ILIE improved energy recovery and general endurance of professional soccer players. This relates to repeated high-intensity intermittent sprints during the 90-min soccer game.

Decreased Blood Glucose and Lactate: Is a Useful Indicator of Recovery Ability in Athletes?

During low-intensity exercise stages of the lactate threshold test, blood lactate concentrations gradually diminish due to the predominant utilization of total fat oxidation. However, it is unclear why blood glucose is also reduced in well-trained athletes who also exhibit decreased lactate concentrations. This review focuses on decreased glucose and lactate concentrations at low-exercise intensity performed in well-trained athletes. During low-intensity exercise, the accrued resting lactate may predominantly be transported via blood from the muscle cell to the liver/kidney. Accordingly, there is increased hepatic blood flow with relatively more hepatic glucose output than skeletal muscle glucose output. Hepatic lactate uptake and lactate output of skeletal muscle during recovery time remained similar which may support a predominant Cori cycle (re-synthesis). However, this pathway may be insufficient to produce the necessary glucose level because of the low concentration of lactate and the large energy source from fat. Furthermore, fatty acid oxidation activates key enzymes and hormonal responses of gluconeogenesis while glycolysis-related enzymes such as pyruvate dehydrogenase are allosterically inhibited. Decreased blood lactate and glucose in low-intensity exercise stages may be an indicator of recovery ability in well-trained athletes. Athletes of intermittent sports may need this recovery ability to successfully perform during competition.

Safety Analysis of Iobitridol as a Nonionic Contrast Medium: A Postmarketing Multicenter Surveillance Study With 94,960 Patients Almost 20 Years After Introduction.

OBJECTIVES: Our study sought to reevaluate the safety and diagnostic efficacy of iobitridol as a nonionic contrast medium after almost 20 years of use. MATERIALS AND METHODS: This noninterventional postmarketing surveillance noncontrolled, multicenter (168 centers in Germany) study enrolled 94,960 patients receiving intravenous or intra-arterial iobitridol. The majority of the adjusted population (n = 92,550, 98.2%) underwent either computed tomography examination (n = 46,502, 49.3%) or intravenous urography (n = 46,048, 48.8%). A standardized questionnaire was used to ascertain patient's information, known risk factors, renal function status, premedication, type of examination, injection of contrast agent, imaging quality, diagnostic value, and safety. RESULTS: A total of 469 patients (0.49%) experienced an adverse event (AE), and 24 patients (0.025%) reported a serious AE (SAE). All patients recovered and no fatal event occurred. The prevalence of AE was significantly higher in patients with at least one risk factor, with premedication, with a history of AE, in female and patients younger than 60 years old (P < 0.05). Presence of at least one risk factor is the only predictive factor for the prevalence of SAE (P = 0.042). In patients with a history of AE, premedication did not significantly lower the AE rate (P = 0.737). No statistically significant difference in the prevalence of AE between the different combination of cortisone and/or antihistamines as pretreatment was found. CONCLUSIONS: Iobitridol is a safe contrast medium with a high tolerability and efficacy. Presence of risk factors such as cardiovascular diseases, allergies, or asthma was the only significant predictive factor for an AE and an SAE. Premedication did not significantly lower the occurrence of an AE and an SAE.

Baseline characteristics, diagnostic efficacy, and peri-examinational safety of IV gadoteric acid MRI in 148,489 patients.

BACKGROUND: Magnetic resonance imaging (MRI) examinations with intravenous (IV) contrast are performed worldwide in routine daily practice. In order to detect and enumerate even rare adverse events (AE) and serious adverse events (SAE), and to relate them with patients' baseline characteristics and diagnostic effectiveness, high quantity sample size is necessary. PURPOSE: To assess safety, diagnostic effectiveness, and baseline characteristics of patients undergoing IV gadoteric acid (Dotarem®) MRI in routine practice. MATERIAL AND METHODS: Data from two observational post-marketing surveillance (PMS) databases compiled by 139 and 52 German centers in 2004-2011 and 2011-2013, respectively, were pooled, yielding data on a total of 148,489 patients examined over a 10-year period. Radiologists used a standardized questionnaire to report data including patient demographics, characteristics of MR examinations, and results in terms of diagnosis and patient safety. RESULTS: Overall, 712 AEs were reported in 467 (0.3%) patients, mainly nausea (n = 224, 0.2%), vomiting (n = 29, <0.1%), urticaria (n = 20, <0.1%), and feeling hot (n = 13, <0.1%). AEs were considered related to gadoteric acid in 362 (0.2%) patients. Higher frequencies of AEs were observed among patients with a previous reaction to a contrast agent (2.0%), liver dysfunction (0.7%), bronchial asthma (0.7%), and a history of allergies (0.6%). There were 49 SAEs in 18 (<0.1%) patients, including two children. No fatal SAE was reported. Examinations were diagnostic in 99.8% of all patients, and image quality was excellent or good in 97.7% of the patients. CONCLUSION: Gadoteric acid is a safe peri-examinational and effective contrast agent for MRI in routine practice.

Rapid weight reduction does not impair athletic performance of Taekwondo athletes - A pilot study.

In combat sports such as taekwondo (TKD), athletes rapidly reduce body weight to achieve a desired weight category. Competition takes place 16-24 h after weigh-in and thus, the recovery time is an important factor for competition performance. The purpose of this study was to investigate the impact of rapid weight reduction (RWR) on athletic performance and associated hemorheological properties considering relevant recovery time. Five male TKD athletes reduced body weight by 5% within 3½ days. A simulated competition day (SCD) was carried out after a 16 h recovery period. Parameters were measured before RWR, at weigh-in and before and after three TKD simulation matches (SMs) at SCD. Same set-up was conducted but without RWR as control. Basal blood parameters, red blood cells (RBC) deformability and aggregation, serum glucose and fibrinogen were determined. During SMs, heart rate (HRpeak, HRmean), oxygen uptake (VO2peak, VO2mean), peak lactate (Peak La-), difference of lactate (ΔLa) and energy systems (anaerobic-alactic, -lactic and aerobic) were analyzed. Basal blood parameters remained unaltered during the interventions. RBC deformability was reduced and aggregation was increased after RWR but values returned to baseline after recovery and were not affected by the SMs. Glucose level was not affected by the interventions. Kick frequency in SMs was higher after RWR which might be responsible for higher HRpeak, VO2peak, VO2mean, Peak La-, ΔLa- and aerobic demand. The 16 h recovery is sufficient to regenerate measured physiological and hemorheological parameters. TKD-specific performance was not negatively affected during SMs after RWR.

Diagnostic efficacy and safety of gadoteric acid MR mammography in 1537 patients.

OBJECTIVES: To perform a large-scale multicenter post-marketing surveillance study for analyzing diagnostic effectiveness and safety of intravenous (IV) gadoteric acid (Dotarem®) in magnetic resonance (MR) mammography under daily practice conditions. MATERIALS AND METHODS: Patients underwent high-resolution MR mammography with gadoteric acid in 15 German centers. Radiologists used a standardized questionnaire to report data including patient demographics and medical history, characteristics of MR examination and results in terms of diagnosis and safety for the patient. RESULTS: A total of 1537 patients were examined. In 99.2% of all patients, a diagnosis was established. In 91.6% of all patients, image quality was excellent or good. Histopathological examinations were performed for 232 of 1537 patients (15.1%) with invasive ductal carcinoma being the most frequent diagnosis (109 patients, 47.0%). Based on histopathology as the standard of reference, IV gadoteric acid-enhanced MR mammography confirmed diagnoses of invasive ductal carcinoma in 93.5% of the patients. Adverse drug reactions occurred in 5 of 1537 patients (0.3%) and were classified as serious in one case (tachycardia, dysphagia, urticaria, rash). All patients with adverse drug reactions fully recovered after the examination. CONCLUSION: This noninterventional surveillance study shows IV gadoteric acid to be a safe and effective contrast agent for use in MR mammography.

Effects of gadolinium-based contrast agent concentrations (0.5 M or 1.0 M) on the diagnostic performance of magnetic resonance imaging examinations: systematic review of the literature.

Background To date there is no agreement as to what is the optimal concentration for gadolinium-based contrast agents (GBCAs). Purpose To assess whether diagnostic performance differences exist between 0.5 M and 1.0 M GBCAs used for magnetic resonance imaging (MRI). Material and Methods A PubMed literature search identified 21 clinical studies published between 2005 and 2013 which evaluated the diagnostic efficacy of both types of GBCAs. Study design, type of procedure, GBCA administration mode, imaging performances, impact on patient management, study limitations, and biases were analyzed. No statistical test was performed on pooled data. Results Sixteen comparative and five non-comparative studies were analyzed, involving 2183 patients who underwent MRI procedures for various indications. In 67% of the studies, 0.5 M and 1.0 M GBCAs were injected at equimolar gadolinium amounts per kg body weight. Only 33% applied the same molar flow rate for delivery of the GBCAs. No significant differences between GBCAs were reported for 23 out of 27 qualitative endpoints (mainly image quality, lesion, and vessel visualization) and 29 out of 40 quantitative endpoints. Three out of four studies with non-equimolar delivery rates showed better contrast-to-noise and signal-to-noise ratios for 1.0 M gadobutrol, without showing an impact on diagnostic performance. Methodological biases were identified in several studies impairing the interpretation of comparisons. Conclusion Imaging differences between 0.5 M and 1.0 M GBCAs were essentially observed under non-equimolar delivery rates. However, they did not result into greater diagnostic efficacy when performed under equimolar conditions.

Rapid rather than gradual weight reduction impairs hemorheological parameters of Taekwondo athletes through reduction in RBC-NOS activation.

PURPOSE: Rapid weight reduction is part of the pre-competition routine and has been shown to negatively affect psychological and physiological performance of Taekwondo (TKD) athletes. This is caused by a reduction of the body water and an electrolyte imbalance. So far, it is unknown whether weight reduction also affects hemorheological properties and hemorheology-influencing nitric oxide (NO) signaling, important for oxygen supply to the muscles and organs. METHODS: For this purpose, ten male TKD athletes reduced their body weight by 5% within four days (rapid weight reduction, RWR). After a recovery phase, athletes reduced body weight by 5% within four weeks (gradual weight reduction, GWR). Each intervention was preceded by two baseline measurements and followed by a simulated competition. Basal blood parameters (red blood cell (RBC) count, hemoglobin concentration, hematocrit, mean corpuscular volume, mean cellular hemoglobin and mean cellular hemoglobin concentration), RBC-NO synthase activation, RBC nitrite as marker for NO synthesis, RBC deformability and aggregation parameters were determined on a total of eight investigation days. RESULTS: Basal blood parameters were not affected by the two interventions. In contrast to GWR, RWR decreased activation of RBC-NO synthase, RBC nitrite, respective NO concentration and RBC deformability. Additionally, RWR increased RBC aggregation and disaggregation threshold. CONCLUSION: The results point out that a rapid weight reduction negatively affects hemorheological parameters and NO signaling in RBC which might limit performance capacity. Thus, GWR should be preferred to achieve the desired weight prior to a competition to avoid these negative effects.

Erythropoiesis-stimulating agents for the treatment of chemotherapy-induced anemia: comparisons from real-world clinical experience.

BACKGROUND: The purpose of this paper is to report real-world data on the relative effectiveness of a biosimilar erythropoiesis-stimulating agent (ESA; Binocrit(®)), and other available ESAs for the treatment of chemotherapy-induced anemia. METHODS: Data were collected retrospectively from single centers in Spain (n=284) and Germany (n=145). Hemoglobin outcomes, transfusion requirements, and serious drug-related adverse events were assessed for each ESA. RESULTS: Hemoglobin outcomes and transfusion requirements were generally similar in the different ESA treatment groups assessed. No serious drug-related adverse events were recorded in any of the treatment groups. CONCLUSION: These data confirm the real-world effectiveness and safety of a biosimilar ESA (Binocrit(®)) for the treatment of cancer patients with chemotherapy-induced anemia.

Tolerability and diagnostic value of gadoteric acid in the general population and in patients with risk factors: results in more than 84,000 patients.

PURPOSE: To review the tolerability and diagnostic effectiveness of gadoteric acid under daily practice conditions in the general population and at-risk patients. MATERIALS AND METHODS: A total of 84,621 patients (45.4% men, 54.6% women, mean age 52.0 ± 16.9 years) were studied in 129 German centers. Patients underwent contrast-enhanced magnetic resonance imaging (MRI) using gadoteric acid (Gd-DOTA, Dotarem(®), Guerbet, Roissy CdG, France) as IV contrast medium (mean volume, 16.4 ml). 22.9% of the patients had at least one risk factor (e.g., allergies, previous allergic reaction to a contrast medium, and renal impairment). 554 patients received pretreatment before contrast medium administration (0.7%). Adverse events were documented and image quality was assessed. RESULTS: A diagnosis was possible in 99.7% of all cases. Image quality was rated good or excellent in 97.1%. Adverse events (e.g., nausea, vomiting, and urticaria) were observed in 0.34% of the examinations and were mostly rated as minor. There were 8 patients with serious adverse events. The adverse event rate was significantly higher in patients with a history of allergies (0.62%; p<0.001) and in patients with a previous allergic reaction to contrast medium (1.23%; p<0.001). There was no elevated incidence of adverse events in patients with renal impairment. CONCLUSION: Gadoteric acid is a well-tolerated MRI contrast medium in patients with and without risk factors that is associated with a low rate of adverse events and good or excellent image quality in most patients.

Safety and tolerability of iobitridol in general and in patients with risk factors: results in more than 160,000 patients.

OBJECTIVE: To review the safety, the tolerability and the diagnostic effectiveness of iobitridol under daily practice conditions in the general population and at-risk patients in a post-marketing surveillance study. MATERIALS AND METHODS: A total of 160,639 patients (55.1% male, 43.6% female, mean age 58.6 years) were analysed in 555 centers. Patients underwent X-ray examinations using iobitridol (Xenetix®, Guerbet, Sulzbach, Germany) as IV contrast medium (mean volume 85.6 ml). 21.8% of all patients had at least one risk factor (e.g., renal impairment), 7.3% were at-risk patients with allergies or who had previously reacted to contrast medium. Antiallergic pretreatment before contrast medium administration was given in 1144 patients (0.7%). Adverse events were documented and the image quality was assessed. RESULTS: A diagnosis was possible in 99.5% of all cases. The image quality was rated good or excellent in 92.2%. The adverse event rate (e.g., nausea, urticaria) observed was 0.6% in all patients, 1.6% in patients with allergies and 6.0% in patients with a previous reaction to contrast medium. Adverse events occurred more often in women than in men (p<0.001). Pretreatment did not decrease the rate of adverse events. The rate of adverse events was not increased in higher doses of iobitridol, even if administered to high-risk patients. CONCLUSIONS: Iobitridol was shown to be a safe and well-tolerated contrast medium with a low incidence of adverse events in patients with and without risk factors resulting in a good or excellent image quality in most patients.

[Quality assurance in palliative medicine--results of the core documentation of 1999-2002]. / Qualitätssicherung in der Palliativmedizin--Ergebnisse der Kerndokumentation 1999-2002.

Quality assurance has been started in palliative care units since 1999, using a documentation project based on yearly documentation periods. The project was developed by a working party of palliative care specialists in cooperation with the German Cancer Society and the German Association for Palliative Medicine. The aim was a concise but meaningful standard documentation, able to describe the special therapeutic situation of palliative care patients and the interdisciplinary and multi-professional care they receive. In this paper, data of 4693 in-patient treatment periods relating to structural, procedural and outcome quality of palliative care units are presented from the beginning of the core documentation in 1999 through 2001. In 2002, data from palliative care units were compared with those from oncologic and geriatric wards, as well as hospices. Palliative care units show constant traits since the beginning of the core documentation in 1999, in spite of the rising number of participants. At the same time, there are distinct differences among the groups of participants due to the scope of their therapeutic setting. These relate to structure quality in the functional status of the patients (ECOG), which is worst in hospices (> palliative care units > geriatric wards > oncologic wards); to process quality in intensified pain treatment concerning incidence and intensity of pain, which is most frequent and severe in palliative care units (> hospices > geriatric > oncologic wards); and outcome quality in the rate of discharge home, which is highest in oncologic wards (> geriatric > palliative care units > hospices). Quality assurance in palliative care is difficult due to complex indicators, which should be assessed in a standardised documentation. The core documentation was established as a quality assurance programme for palliative care patients. The results of the previous evaluations have enabled the development of a standard documentation. The continuous application of such a standard documentation will prove the quality improvement and development of the participating units.