Stage Race Research Articles

Changes in urinary amino acids excretion in relationship with muscle activity markers over a professional cycling stage race: in search of fatigue markers

The aim of this study was to identify the relationship between metabolic effort, muscular damage/activity indices, and urinary amino acids profile over the course of a strenuous prolonged endurance activity, as a cycling stage race is, in order to identify possible fatigue markers. Nine professional cyclists belonging to a single team, competing in the Giro d'Italia cycling stage race, were anthropometrically characterized and sampled for blood and urine the day before the race started, and on days 12 and 23 of the race. Diet was kept the same over the race, and power output and energy expenditure were recorded. Sera were assayed for muscle markers (lactate dehydrogenase, aspartate aminotransferase, and creatine kinase activities, and blood urea nitrogen), and creatinine, all corrected for plasma volume changes. Urines were profiled for amino acid concentrations, normalized on creatinine excretion. Renal function, in terms of glomerular filtration rate, was monitored by MDRD equation corrected on body surface area. Creatine kinase activity and blood urea were increased during the race as did serum creatinine while kidney function remained stable. Among the amino acids, taurine, glycine, cysteine, leucine, carnosine, 1-methyl histidine, and 3-methyl histidine showed a net decreased, while homocysteine was increased. Taurine and the dipeptide carnosine (β-alanyl-L-histidine) were significantly correlated with the muscle activity markers and the indices of effort. In conclusion, the metabolic profile is modified strikingly due to the effort. Urinary taurine and carnosine seem useful tools to evaluate the muscle damage and possibly the fatigue status on a long-term basis.

The role of SOX-2 on the survival of patients with non-small cell lung cancer.

Lung cancer is the most commonly diagnosed cancer as well as the leading cause of cancer death worldwide. Observational studies on the prognostic role of SOX-2 in non-small-cell lung cancer (NSCLC) are controversial. To clarify the impact of SOX-2 in NSCLC survival, we performed this meta-analysis that included eligible studies. The combined hazard ratios and their corresponding 95% confidence intervals (95% CI) were calculated in terms of overall survival. A total of seven studies with 1,944 patients were evaluable for this meta-analysis. The studies were categorized by histology, disease stage and patient race. Our results suggested that SOX-2 overexpression had a favorable impact on survival of patients with NSCLC, the HR (95% CI) was 0.57 (0.48 to 0.65). However, highly significant heterogeneity was detected among these studies (I(2)=76.7%, P=0.000). SOX-2 overexpression indicates a favorable prognosis for patients with NSCLC.

Osteocartilaginous metabolic markers change over a 3-week stage race in pro-cyclists

Evidence suggests that endurance and even recreational cycling may stimulate bone resorption; however, little is known about cartilage response to endurance cycling exercise. We investigated effort-dependent changes in bone turnover and cartilage biomarkers in blood and urine samples from elite cyclists during a 3-week stage race. Whole blood and urine samples were collected the day before the start of the race, at mid and end-race for serum and urinary CTx-I, NTx-I, PINP, COMP (only in serum), and CTx-II analysis by enzyme-linked immunosorbent assay. The values were corrected for plasma volume or creatinine excretion, respectively, and correlated with power output (corrected for body weight) and net energy expenditure. Bone marker concentrations in both serum and urine were slightly but significantly decreased. Among the cartilage degradation markers, only CTx-II was decreased, while COMP remained unchanged. The changes in bone and cartilage turnover indexes were correlated with the indexes of physical effort and energy consumption.Strenuous physical effort, in the absence of mechanical loading, slows bone metabolism and only minimally affects cartilage turnover. Since changes in plasma and urine volume, which normally occur in exercising athletes, can mask these effects, biomarker concentrations need to be corrected for shifts in plasma volume and urinary creatinine for correct interpretation of the data.

Effect of an intense period of competition on race performance and self-reported illness in elite cross-country skiers.

The aim of this study was to determine whether participating in a cross-country skiing stage race (Tour de Ski; TDS) affects subsequent illness incidence, training, and race performance. Self-reported training and illness data from 44 male and female elite cross-country skiers were included. In total, 127 years of data were collected (2-3 seasons per athlete). Illness incidence, training load, and performance in international competitions were calculated for athletes who did and did not participate in TDS. Forty-eight percent of athletes reported becoming ill during or in the days immediately after taking part in TDS vs 16% of athletes who did not participate. In both groups, illness incidence was somewhat lower for female athletes. For male athletes, race performance was significantly worse for 6 weeks following TDS vs 6 weeks before TDS. Furthermore, while female athletes who participated in TDS performed relatively better than controls in Olympics/World Championships, male athletes who participated in TDS typically performed worse in subsequent major championships. Participating in TDS appears to result in ∼ 3-fold increase in risk of illness in this period. Male athletes appear more prone to illness and also see a drop in race performance following TDS, possibly linked to differences in training load before and after the event.

Acute protease supplementation effects on muscle damage and recovery across consecutive days of cycle racing

Bromelain, a mixture of proteases obtained from pineapples, has been demonstrated to reduce exercise-induced muscle damage and inflammation, enhancing recovery. This investigation aimed to establish if markers of muscle damage and testosterone were influenced by acute bromelain supplementation in competitive cyclists taking part in a six-day cycle stage race. Fifteen highly trained cyclists [age: 22, = 1.2 years, height: 1.79, = 0.01 m, body mass: 68.69, = 1.97 kg] were supplemented with either bromelain (1000 mg·day−1) (n = 8) or a placebo (n = 7) across six days of competitive racing in a randomised, double-blind, placebo-controlled trial. Blood was collected from each cyclist on days one, three and six of racing and analysed for creatine kinase (CK), myoglobin, lactate dehydrogenase (LDH) and testosterone. CK activity (P < 0.001, d = 17.4–18.8), LDH activity (P < 0.004, d = 0.5–2.5) and myoglobin concentration (P < 0.007, d = 3.4–4.8) were elevated from pre-race on days three and six of racing in both groups. Testosterone concentrations were significantly lower on the final day of racing (P = 0.03, d = 1.3) and there was a trend for bromelain to maintain testosterone concentrations across the race period (P = 0.05, d = 1.04–1.70) when compared to placebo. Fatigue rating was lower in the bromelain group on day four of racing (P = 0.01). Consecutive days of competitive cycling were associated with increased markers of muscle damage and a reduction in circulating testosterone across the race period. Bromelain supplementation reduced subjective feelings of fatigue and was associated with a trend to maintain testosterone concentration.

Risk of marrow neoplasms after adjuvant breast cancer therapy: the national comprehensive cancer network experience.

Outcomes for early-stage breast cancer have improved. First-generation adjuvant chemotherapy trials reported a 0.27% 8-year cumulative incidence of myelodysplastic syndrome/acute myelogenous leukemia. Incomplete ascertainment and follow-up may have underestimated subsequent risk of treatment-associated marrow neoplasm (MN). We examined the MN frequency in 20,063 patients with stage I to III breast cancer treated at US academic centers between 1998 and 2007. Time-to-event analyses were censored at first date of new cancer event, last contact date, or death and considered competing risks. Cumulative incidence, hazard ratios (HRs), and comparisons with Surveillance, Epidemiology, and End Results estimates were obtained. Marrow cytogenetics data were reviewed. Fifty patients developed MN (myeloid, n = 42; lymphoid, n = 8) after breast cancer (median follow-up, 5.1 years). Patients who developed MN had similar breast cancer stage distribution, race, and chemotherapy exposure but were older compared with patients who did not develop MN (median age, 59.1 v 53.9 years, respectively; P = .03). Two thirds of patients had complex MN cytogenetics. Risk of MN was significantly increased after surgery plus chemotherapy (HR, 6.8; 95% CI, 1.3 to 36.1) or after all modalities (surgery, chemotherapy, and radiation; HR, 7.6; 95% CI, 1.6 to 35.8), compared with no treatment with chemotherapy. MN rates per 1,000 person-years were 0.16 (surgery), 0.43 (plus radiation), 0.46 (plus chemotherapy), and 0.54 (all three modalities). Cumulative incidence of MN doubled between years 5 and 10 (0.24% to 0.48%); 9% of patients were alive at 10 years. In this large early-stage breast cancer cohort, MN risk after radiation and/or adjuvant chemotherapy was low but higher than previously described. Risk continued to increase beyond 5 years. Individual risk of MN must be balanced against the absolute survival benefit of adjuvant chemotherapy.

High altitude, prolonged exercise, and the athlete biological passport.

The Athlete Biological Passport (ABP) detects blood doping in athletes through longitudinal monitoring of erythropoietic markers. Mathematical algorithms are used to define individual reference ranges for these markers for each athlete. It is unclear if altitude and exercise can affect the variables included in these calculations in a way that the changes might be mistaken for blood manipulation. The aim of this study was to investigate the influence of the simultaneous strenuous exercise and low to high altitude exposure on the calculation algorithms of the ABP. 14 sea level (SL) and 11 altitude native (ALT) highly trained athletes participated in a 14-day cycling stage race taking place at an average altitude of 2496 m above sea level (min. 1014 m, max. 4120 m), race distances ranged between 96 and 227 km per day. ABP blood measures were taken on days -1,3,6,10,14 (SL) and -1,9,15 (ALT) of the race. Four results from three samples of two different SL athletes exceeded the individual limits at the 99% specificity threshold and one value at 99.9%. In ALT, three results from three samples of three different athletes were beyond the individual limits at 99%, one at 99.9%. The variations could be explained by the expected physiological reaction to exercise and altitude. In summary, the abnormalities observed in the haematological ABP´s of well-trained athletes during extensive exercise at altitude are limited and in line with expected physiological changes.

Can intensive exercise harm the heart? You can get too much of a good thing.

Can intensive exercise harm the heart? You can get too much of a good thing.

Effect of environmental temperature on pacing during a simulated 16 km cycling time trial

Background: In cycling time trials (TT) the aim is to produce greatest average power possible for the duration of the effort; to do this an athlete must distribute their effort efficiently to ensure that they do not fatigue early but finish the event having exhausted their energy stores (Atkinson et al, 2007: Sports Medicine, 37, 647-667). This distribution of effort is initially determined by conscious control (selection of a pacing strategy), but is influenced by afferent feedback from both internal sensations and environmental factors (St. Clair Gibson & Noakes, 2004: British Journal of Sports Medicine, 38, 797-806). Performance in prolonged endurance exercise is inversely related to environmental temperature; this is thought to be due to central nervous system regulation of effort in response to increased core temperature. While this negative effect of hot conditions on TT performance is well established, less is known about the effect of environmental temperature on pacing during TT efforts, in particular in short time trials which are common in amateur cycling as well as in professional stage races such as the Grand Tours. Purpose: The aim of this study was to examine the effect of environmental temperature on performance and pacing during a simulated 16 km cycling time trial.Methods: After familiarisation, six moderately trained male cyclists (age (mean ± s) 20 ± 1 year; VO2max 45.3 ± 7.3 ml.kg-1.min-1, power at VO2max 312 ± 28 W) completed self-paced 22-minute trials on an electromagnetically-braked cycle ergometer in hot (30ÂoC, HOT) and temperate (15ÂoC, COOL) conditions. Participants were instructed to complete as much work as possible during the trial and the only feedback provided was cadence and time with 5 and 1 minute remaining. Heart rate, core temperature and rate of perceived exertion were recorded at two minute intervals.Results: Mean power was slightly lower in HOT than COOL (201 ± 38 W vs. 209 ± 43 W); the difference was not significant.  Core temperature and heart rate were both significantly higher in HOT than COOL (temperature: 37.3 ± 0.5 ÂoC vs. 36.4 ± 0.9 ÂoC; heart rate: 173 ± 7 bpm vs. 166 ± 11 bpm); rating of perceived exertion did not differ between the two conditions. Pacing appeared to differ slightly: when power output was compared across four quarters of the time trial the athletes adopted a positive split with end-spurt in HOT (Q1: 103% overall mean power, Q2: 100%, Q3: 97%, Q4: 100%) and a negative split with end-spurt in COOL (Q1: 97% overall mean power, Q2: 98%, Q3: 99%, Q4: 107%); the difference was significant in the last quarter.Discussion: The main outcome of this study was that pacing strategy differed slightly with environmental conditions, despite relatively similar overall performances in both trials. The effect of environmental conditions on pacing and the mechanisms involved warrant further investigation, given the important of pacing in successful time trial performance for athletes who train and compete under a range of environmental conditions.

HGH isoform differential immunoassays applied to blood samples from athletes: Decision limits for anti-doping testing

ObjectiveTo detect hGH doping in sport, the World Anti-Doping Agency (WADA)-accredited laboratories use the ratio of the concentrations of recombinant hGH (‘rec’) versus other ‘natural’ pituitary-derived isoforms of hGH (‘pit’), measured with two different kits developed specifically to detect the administration of exogenous hGH. The current joint compliance decision limits (DLs) for ratios derived from these kits, designed so that they would both be exceeded in fewer than 1 in 10,000 samples from non-doping athletes, are based on data accrued in anti-doping labs up to March 2010, and later confirmed with data up to February–March 2011. In April 2013, WADA asked the authors to analyze the now much larger set of ratios collected in routine hGH testing of athletes, and to document in the peer-reviewed literature a statistical procedure for establishing DLs, so that it be re-applied as more data become available. DesignWe examined the variation in the rec/pit ratios obtained for 21,943 screened blood (serum) samples submitted to the WADA accredited laboratories over the period 2009–2013. To fit the relevant sex- and kit-specific centiles of the logs of the ratios, we classified ‘rec/pit’ ratios based on low ‘rec’ and ‘pit’ values as ‘negative’ and fitted statistical distributions to the remaining log-ratios. The flexible data-driven quantile regression approach allowed us to deal with the fact that the location, scale and shape of the distribution of the modeled ‘rec/pit’ ratios varied with the concentrations of the ‘rec’ and ‘pit’ values. The between-kit correlation of the ratios was included in the fitting of the DLs, and bootstrap samples were used to quantify the estimation error in these limits. We examined the performance of these limits by applying them to the data obtained from investigator-initiated hGH administration studies, and in athletes in a simulated cycling stage race. ResultsThe mean and spread of the distribution of the modeled log-ratios depended in different ways on the magnitude of the rec and pit concentrations. Ultimately, however, the estimated limits were almost invariant to the concentrations, and similar to those obtained by fitting simpler (marginal) log-normal and Box–Cox transformed distributions. The estimated limits were similar to the (currently-used) limits fitted to the smaller datasets analyzed previously. In investigator-initiated instances, the limits distinguished recent use of rec-hGH from non-use. ConclusionsThe distributions of the rec/pit ratios varied as a function of the rec and pit concentrations, but the patterns in their medians and spreads largely canceled each other. Thus, ultimately, the kit- and sex-specific ratio DL obtained from the simpler model was very close to the ‘curve of DLs’ obtained from the more complex one. Both were close to previously established limits.

The effect of a period of intense exercise on the marker approach to detect growth hormone doping in sports.

The major objective of this study was to investigate the effects of several days of intense exercise on the growth hormone marker approach to detect doping with human growth hormone (hGH). In addition we investigated the effect of changes in plasma volume on the test. Fifteen male athletes performed a simulated nine-day cycling stage race. Blood samples were collected twice daily over a period of 15 days (stage race + three days before and after). Plasma volumes were estimated by the optimized CO Rebreathing method. IGF-1 and P-III-NP were analyzed by Siemens Immulite and Cisbio Assays, respectively. All measured GH 2000 scores were far below the published decision limits for an adverse analytical finding. The period of exercise did not increase the GH-scores; however the accompanying effect of the increase in Plasma Volume yielded in essentially lower GH-scores. We could demonstrate that a period of heavy, long-term exercise with changes in plasma volume does not interfere with the decision limits for an adverse analytical finding.

Mean speed in professional cycling: No evidence of decline

The aim of this article was to evaluate the mean speed progression of the three major cycling stage races in order to empirically establish whether excellent in performance in professional cycling is to some extent correlated with the trend of blood doping and anti-doping throughout more than a century of official cycling competitions. We retrieved data about the mean speed of the winners of the Tour de France, Giro d’Italia and Vuelta a Espana, since their beginning. A linear correlation has then been calculated between the years and the mean speed in km/h for each single major cycling stage race, as well as for the mean speed of the winners of the three major cycling stage races in the same year. Although a highly significant correlation was found between years and mean speed of the winners of each single major cycling stage race during the same year (r=0.941; p<0.001), a number of differential trends were observed. More specifically, from 1903 to 1925 the association was inverse, between 1926 and 2000 the relationship was positive, whereas in the period 2001–2013 the relationship became virtually flat. This data suggests that a strengthened policy of anti-doping testing may have been effective in the past 15 years for curbing the use of performance-enhancing substances.

Energy and Macronutrient Intake of a Female Vegan Cyclist During an 8-Day Mountain Bike Stage Race

This report describes the dietary intake of a vegan mountain biker (height, 161 cm; weight, 49.6 kg; body mass index, 19.1 kg/m(2); relative peak power output, 4.6 W/kg) during the Transalp Challenge 2004 (altitude climbed, 22,500 m; total distance, 662 km), illustrating an aggressive dietary strategy that allowed the cyclist to be competitive. She finished the 8-stage event in 42 hours (mixed category, rank 16; 514 minutes behind the winners of this category), cycling with an average heart rate of 79.5% of laboratory-determined maximum, spending 892 minutes and 1627 minutes at intensities below and above 80%, respectively. During racing, the consumption of energy was 69.3 MJ (1.65 MJ/h), 65.76 MJ from carbohydrates (92 g/h), which was 35% of calories and 40% of carbohydrate total intake, and the fluid ingested was 3 L/day (570 mL/h), 55% of the total fluid consumed.

Body composition changes in professional cyclists during the 2011 Giro d’Italia, a 3-week stage race

Body composition changes in professional cyclists during the 2011 Giro d’Italia, a 3-week stage race

Variability of serum markers of erythropoiesis during a cycling stage race

Introduction: The Athlete Biological Passport for the fight against doping is currently based on longitudinal monitoring for abnormal changes in cellular blood parameters. Serum parameters related to altered erythropoiesis could be considered for inclusion in the passport. The aim of this study was to quantify the changes in such parameters in athletes during a period of intense exercise.

Bone‐muscle unit activity, salivary steroid hormones profile, and physical effort over a 3‐week stage race

Muscle traction and bone metabolism are functionally linked and co-regulated by a series of factors. Although a role for steroid hormones was hypothesized, a clear definition of the bone-muscle interconnection still lacks. To investigate this relationship, we studied bone metabolism, muscle activity, and salivary steroid hormones profile in relation with the physical effort across a cycling stage race, a model of effort in absence of load. Nine pro-cyclists were recruited; body weight and power output/energy expenditure were recorded. Diet was kept constant. Saliva was collected at days -1, 4, 8, 12, 14, 19, and 23; blood and urine were collected at days -1, 12, and 23. Salivary steroid hormones [cortisol, dehydroepiandrosterone (DHEA), testosterone, and estradiol], serum lactate dehydrogenase (LDH), aspartate aminotransferase (AST) and creatine kinase (CK) activities, plasma sclerostin, and urinary calcium and phosphorous were measured. Cortisol remained constant, testosterone decreased at day 4, and estradiol and DHEA firstly increased and then returned to basal levels. Hormone concentrations were not correlated with plasma volume shifts. LDH, CK, AST, sclerostin, and urinary calcium and phosphorous increased. DHEA and estradiol correlated with the physical effort and the bone-muscular markers. A relationship between muscle activity, in absence of load, and bone resorption emerged under a putative regulation by DHEA and estradiol.

Fluid Balance, Carbohydrate Ingestion, and Body Temperature During Men’s Stage-Race Cycling in Temperate Environmental Conditions

To observe voluntary fluid and carbohydrate intakes and thermoregulatory characteristics of road cyclists during 2 multiday, multiple-stage races in temperate conditions. Ten internationally competitive male cyclists competed in 2 stage races (2009 Tour of Gippsland, T1, n = 5; 2010 Tour of Geelong, T2, n = 5) in temperate conditions (13.2-15.8°C; 54-80% relative humidity). Body mass (BM) was recorded immediately before and after each stage. Peak gastrointestinal temperature (TGI peak) was recorded throughout each stage. Cyclists recalled the types and volumes of fluid and food consumed throughout each stage. Although fluid intake varied according to the race format, there were strong correlations between fluid intake and distance across all formats of racing, in both tours (r = .82, r = .92). Within a stage, the relationship between finishing time and fluid intake was trivial. Mean BM change over a stage was 1.3%, with losses >2% BM occurring on 5 out of 43 measured occasions and the fastest competitors incurring lower BM changes. Most subjects consumed carbohydrate at rates that met the new guidelines (30-60 g/h for 2-3 h, ~90 g/h for >3 h), based on event duration. There were consistent observations of TGI peak >39°C during stages of T1 (67%) and T2 (73%) despite temperate environmental conditions. This study captured novel effects of high-intensity stage racing in temperate environmental conditions. In these conditions, cyclists were generally able to find opportunities to consume fluid and carbohydrate to meet current guidelines. We consistently observed high TGI peak, which merits further investigation.

Increasing Pretreatment Tumor SUVmean Is Associated With Local Regional Failure After Chemoradiation for Locally-Advanced Non-Small Cell Lung Cancer

Local regional failure (LRF) after definitive chemoradiation for stage IIIA and IIIB non-small cell lung cancer (NSCLC) remains high. The purpose of this study was to determine if pre-treatment [F-18] fluoro-D-glucose-positron emission tomography (FDG PET) parameters are associated with LRF after chemoradiation. This IRB-approved retrospective study analyzed patients with stage IIIA and IIIB NSCLC treated with definitive chemoradiation between the years of 2006 and 2011 at Emory University Hospital. Patient and treatment characteristics were collected from electronic charts. The SUVmean, SUVmax, and SUVpeak of the primary tumor and involved lymph nodes were extracted from the pre-treatment FDG PET CT by a single user. Locoregional failure was defined as failure within the ipsilateral lung, hilum or mediastinum. Multivariate analysis for factors associated with LRF was performed using the Cox proportional hazard method. SUV parameters were analyzed as continuous variables. Sixty-one patients were identified. Median follow-up was 19 months. Eighteen percent of patients were treated with Intensity Modulated Radiation therapy (IMRT), 10% with 3D and IMRT techniques, and 72% with 3D conformal technique. Thirty-nine percent of patients received daily on board imaging (OBI). Median total RT dose for all patients was 66 Gy. Concurrent chemotherapy was delivered to 90% of patients. The median pre-treatment SUVmax, SUVmean, and SUVpeak values were 15.2 (6.6-50.1), 4.52 (2.2-9.04), and 13.7 (4.85-44), respectively. A LRF occurred in 36% of patients. Median time to LRF was 11.4 months. On multivariate analysis, increasing pre-treatment tumor SUV mean was significantly associated with LRF (HR: 1.77; 95% CI, 1.18-2.65; p < 0.01). Lower T stage (HR: 0.04; 95% CI, 0.004-0.51; p = 0.013), lower N stage (HR 0.038, 95% CI, 0.004-0.34, p < 0.01) and white race (HR: 0.266; 95% CI, 0.076-0.931; p = 0.04) were associated with a decreased risk of LRF. Other factors, including radiation technique, use of OBI, SUVmax, and SUVpeak were not significantly associated with LRF on multivariate analysis. Pretreatment FDG PET tumor SUVmean is associated with LRF after chemoradiation for stage III NSCLC, and warrants further investigation.

Therapeutic delays lead to worse survival among patients with hepatocellular carcinoma.

Although prior studies have shown underuse of appropriate therapy in patients with hepatocellular carcinoma (HCC), no studies to date have assessed the prevalence and clinical impact of therapeutic delays among patients with HCC. The goal of this study was to characterize and identify factors associated with underuse and delays in treatment of these patients. A retrospective cohort study was conducted of patients with cirrhosis diagnosed with HCC at a large urban safety net hospital between January 2005 and June 2012. Dates for HCC diagnosis and any treatments were recorded. Univariate and multivariate analysis was used to determine factors associated with treatment underuse and delayed treatment, which was defined as time from diagnosis to treatment exceeding 3 months. The authors identified 267 treatment-eligible patients with HCC, of whom only 62% received HCC therapy. On multivariate analysis, tumor stage (odds ratio [OR], 0.48; 95% CI, 0.36-0.65), Child-Pugh class (OR, 0.49; 95% CI, 0.28-0.84), and black race (OR, 0.55; 95% CI, 0.31-0.99) were associated with lower rates of treatment use. The median time to treatment was 1.7 months, with 31% of patients experiencing delayed treatment. Delayed treatment was associated with the presence of ascites (hazard ratio [HR], 2.8; 95% CI, 1.3-6.1) and current treatment with transarterial chemoembolization (HR, 4.8; 95% CI, 1.8-12.5). After adjusting for tumor stage and Child-Pugh class, treatment underuse (HR, 0.33; 95% CI, 0.24-0.46) and delayed treatment (HR, 0.50; 95% CI, 0.30-0.84) were both associated with significantly worse survival. Results showed that, in addition to one-third of patients not receiving HCC-directed therapy, another 30% experienced significant therapeutic delays, leading to worse survival.

Variability of Serum Markers of Erythropoiesis during 6 Days of Racing in Highly Trained Cyclists

The athlete biological passport for the fight against doping is currently based on longitudinal monitoring for abnormal changes in cellular blood parameters. Serum parameters related to altered erythropoiesis could be considered for inclusion in the passport. The aim of this study was to quantify the changes in such parameters in athletes during a period of intense exercise.12 highly trained cyclists tapered for 3 days before 6 days of simulated intense stage racing. Morning and afternoon blood samples were taken on most days and analysed for total protein, albumin, soluble transferrin receptor and ferritin concentrations. Plasma volume was determined via total haemoglobin mass measured by carbon-monoxide rebreathing. Percent changes in means from baseline and percent standard errors of measurement (analytical error plus intra-athlete variation) on each measurement occasion were estimated with mixed linear modelling of log-transformed measures. Means of all variables changed substantially in the days following the onset of racing, ranging from -13% (haemoglobin concentration) to +27% (ferritin). After the second day, errors of measurement were generally twice those at baseline. Plasma variables were affected by heavy exercise, either because of changes in plasma volume (total protein, albumin, haemoglobin), acute phase/inflammatory reactions (ferritin) or both (soluble transferrin receptor). These effects need to be taken into consideration when integrating a plasma parameter into the biological passport model for athletes.