Training zones in competitive swimming: a biophysical approach.

Since swimming performance depends on both physical conditioning and technical proficiency, training zones should be built based on physiology and biomechanics inputs to dispose of structured and effective training programs. This paper presents a zone-based swimming training, supported by the oxygen uptake (V˙O2) kinetics at low, moderate, heavy, severe and extreme intensities concurrently with lactate and heart rate values. Since technique is vital for efficiently moving through the water, upper limbs frequency and length should also be targeted during the workouts. The index of coordination was also added to our proposal since upper limbs synchronization is a key technical factor. To better establish and characterize a wide range of swimming intensities, the training methods and corresponding contents that better fit each training zone will be suggested. It will be shown that when under/at the anaerobic threshold (at low-to-moderate intensities), swimmers are at homeostasis and can maintain stable internal and external load indicators. However, above that boundary (at heavy and severe intensities), the physiological stable state is no longer observed and the anaerobic metabolism starts contributing significantly, with a technical degradation being more evident when performing near/at the V˙O2max intensity. Then, when performing above aerobic power, on typical anaerobic intensities, V˙O2 kinetics presents a very evident fast rise, ending abruptly due to exhaustion caused by muscle acidosis. This overall knowledge allows advancing toward more objective training programs and highlights the importance of systematic training control and swimmers' evaluation and advice.

Swimming sprint performance depends on upper/lower limbs strength and swimmers level.

Swimming performance is likely influenced by strength, but differences between butterfly, backstroke, breaststroke and front crawl, as well as between novice and expert swimmers, are unclear. We have examined the associations between sprint performances, upper and lower limb strength, and anthropometric characteristics in 14 (six males and eight females) non-elite and 16 (nine males and seven females) elite-level swimmers. After an anthropometric characterisation, participants performed four 25 m maximal swims (one per technique) with 10 min intervals, right and left shoulder flexion/extension isokinetic testing at 90 and 300º/s angular velocities and three countermovement jumps. Pearson correlation analysis showed that sprint times were moderate-largely negatively correlated with upper and lower limb strength and power (r ± 95%CI = 0.39 ± 0.26-0.77 ± 0.13, p < 0.05). Elite swimmers higher strength levels were associated with longer stroke length in butterfly and front crawl, and with higher stroke rate in backstroke and breaststroke (r ± 95%CI = 0.37 ± 0.32-0.68 ± 0.21; p < 0.05). Butterfly, backstroke and front crawl sprint times were moderate-largely negatively related with arm span (r ± 95%CI = 0.37 ± 0.26, 0.39 ± 0.25 and 0.69 ± 0.17, p < 0.05). The predictive model indicated that higher dry-land strength values distinguished elite from non-elite swimmers (r2 = 0.67-0.81; p < 0.001). This association was not observed per performance level and per sex, confirming that sprint swimming performance levels can be differentiated by dry-land strength testing.

Exploring the Applicability of Physiological Monitoring to Manage Physical Fatigue in Firefighters.

Physical fatigue reduces productivity and quality of work while increasing the risk of injuries and accidents among safety-sensitive professionals. To prevent its adverse effects, researchers are developing automated assessment methods that, despite being highly accurate, require a comprehensive understanding of underlying mechanisms and variables' contributions to determine their real-life applicability. This work aims to evaluate the performance variations of a previously developed four-level physical fatigue model when alternating its inputs to have a comprehensive view of the impact of each physiological variable on the model's functioning. Data from heart rate, breathing rate, core temperature and personal characteristics from 24 firefighters during an incremental running protocol were used to develop the physical fatigue model based on an XGBoosted tree classifier. The model was trained 11 times with different input combinations resulting from alternating four groups of features. Performance measures from each case showed that heart rate is the most relevant signal for estimating physical fatigue. Breathing rate and core temperature enhanced the model when combined with heart rate but showed poor performance individually. Overall, this study highlights the advantage of using more than one physiological measure for improving physical fatigue modelling. The findings can contribute to variables and sensor selection in occupational applications and as the foundation for further field research.

Adding protein to a carbohydrate pre-exercise beverage does not influence running performance and metabolism.

BACKGROUND: To analyze whether pre-exercise CHO+PRO vs. CHO intake distinctly influences running performance and metabolic biomarkers along a various of exercise intensities. METHODS: In a randomized, double blind, counterbalanced, crossover and placebo control design, 10 middle distance runners were tested in 3 occasions. After 10 h of fasting, participants ingested isovolumic beverages (0.75+0.25g·BW-1 of CHO+PRO, 1.0g·BW-1 of CHO and placebo control) 30 min before a treadmill running incremental protocol of 4 min steps until exhaustion. Venous blood was collected at fasting, 30 min after beverage ingestion and after the 3rd and 7th running steps. Oxygen uptake-related variables, including respiratory exchange ratio, heart rate, plasma glucose, insulin, glucagon, free fatty acids, blood lactate concentrations, gastrointestinal discomfort and rate of perceived exertion were measured. RESULTS: The addition of PRO to CHO had no influence on the measured variables, which did not differ between conditions along all incremental protocol intensities. The intake of CHO+PRO (compared to CHO) tended to decrease glycemia (106.5±21.3 vs. 113.6±26.5) and to increase insulinemia (14.4±15.1 vs. 12.7±10.8) at intensities close to maximum oxygen uptake. CONCLUSIONS: The addition of PRO to a pre-exercise CHO beverage had no impact on running performance and related metabolic variables at a wide spectrum of exercise intensities.

Shoulder Torque Production and Muscular Balance after Long and Short Tennis Points.

Tennis is an asymmetric sport characterized by a systematic repetition of specific movements that may cause disturbances in muscular strength, power, and torque. Thus, we assessed (i) the torque, power, ratio production, and bilateral asymmetries in the shoulder's external and internal rotations at 90 and 180°/s angular velocities, and (ii) the point duration influence of the above-mentioned variables. Twenty competitive tennis players performed external and internal shoulder rotations; an isokinetic evaluation was conducted of the dominant and non-dominant upper limbs before and after five and ten forehands. A higher torque production in the shoulder's internal rotations at 90 and 180°/s was observed for the dominant vs. non-dominant sides (e.g., 63.1 ± 15.6 vs. 45.9 ± 9.8% and 62.5 ± 17.3 vs. 44.0 ± 12.6% of peak torque/body mass, p < 0.05). The peak torque decreased only after ten forehands (38.3 ± 15.8 vs. 38.2 ± 15.8 and 39.3 ± 16.1 vs. 38.1 ± 15.6 Nm, respectively, p < 0.05), but without impacting speed or accuracy. Unilateral systematic actions of tennis players caused contralateral asymmetries, evidencing the importance of implementing compensatory training. The forehand kinematic assessment suggests that racket and wrist amplitude, as well as speed, are important success determinants in tennis.

Influenza vaccination strategy in acute coronary syndromes: the VIP-ACS trial.

AIMS: To evaluate whether a strategy of double-dose influenza vaccination during hospitalization for an acute coronary syndrome (ACS) compared with standard-dose outpatient vaccination (as recommended by current guidelines) would further reduce the risk of major cardiopulmonary events. METHODS AND RESULTS: Vaccination against Influenza to Prevent cardiovascular events after Acute Coronary Syndromes (VIP-ACS) was a pragmatic, randomized, multicentre, active-comparator, open-label trial with blinded outcome adjudication comparing two strategies of influenza vaccination following an ACS: double-dose quadrivalent inactivated vaccine before hospital discharge vs. standard-dose quadrivalent inactivated vaccine administered in the outpatient setting 30 days after randomization. The primary outcome was a hierarchical composite of all-cause death, myocardial infarction, stroke, unstable angina, hospitalization for heart failure, urgent coronary revascularization, and hospitalization for respiratory causes, analysed by the win ratio method. Patients were followed for 12 months. During two influenza seasons, 1801 participants were included at 25 centres in Brazil. The primary outcome was not different between groups, with 12.7% wins in-hospital double-dose vaccine group and 12.3% wins in the standard-dose vaccine group {win ratio: 1.02 [95% confidence interval (CI): 0.79-1.32], P = 0.84}. Results were consistent for the key secondary outcome, a hierarchical composite of cardiovascular death, myocardial infarction and stroke [win ratio: 0.94 (95% CI: 0.66-1.33), P = 0.72]. Time-to-first event analysis for the primary outcome showed results similar to those of the main analysis [hazard ratio 0.97 (95% CI: 0.75-1.24), P = 0.79]. Adverse events were infrequent and did not differ between groups. CONCLUSION: Among patients hospitalized with an ACS, double-dose influenza vaccination before discharge did not reduce cardiopulmonary outcomes compared with standard-dose vaccination in the outpatient setting. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov number: NCT04001504.

Efficient drug development of oseltamivir capsules based on process control, bioequivalence and PBPK modeling.

Oseltamivir phosphate is used to treat influenza. For registration of a generic product, bioequivalence studies are crucial, however, in vitro studies can sometimes replace the conventional human pharmacokinetic. To assess whether the dissolution profile is comparable with the in vivo release, physiologically based pharmacokinetic absorption models (PBPK) are being used. The aim of the study was to develop a generic capsule of oseltamivir phosphate 30 mg with process understanding and control, development of PBPK model and comparison of virtual bioequivalence study (VBE) to the real bioequivalence study that was also performed. For that, 30 mg capsules were prepared by wet granulation according to 22 full factorial design. The biobatch was prepared with the selected process and a batch was made with the API from the second manufacture. Both manufactures presented polymorph A and the second manufacture showed higher particle size. Product batches produced without adding water during granulation showed higher dissolution. The addition of water associated with higher conical mill speed, lowered the average weight of the capsules. The biobatch dissolution was similar to Tamiflu; also, they were bioequivalent. The crossover VBE between the biobatch and Tamiflu corroborated with the real bioequivalence study. The same result was found for the batch with higher particle size. PBPK model showed that computer simulations can help pharmaceutical companies to replace in vivo studies.

Repeatability of ventilatory, metabolic and biomechanical responses to an intermittent incremental swimming protocol.

Objective. This study aimed to determine the repeatability of ventilatory, metabolic and biomechanical variables assessed at a large spectrum of front crawl swimming intensities. We hypothesized a strong agreement (combined with a small range of variation) between a typical step protocol performed in two experimental moments.Approach. Forty competitive swimmers performed a 7 × 200 m front crawl intermittent incremental protocol (0.05 m·s-1velocity rises and 30 s intervals) on two different occasions (48-72 h apart). Pulmonary gas exchange and ventilation were continuously measured breath-by-breath, metabolic variables were assessed during the intervals and biomechanical analysis was done at every protocol step.Main results. Concomitantly with the velocity increment, oxygen uptake, carbon dioxide production, ventilation, respiratory frequency, respiratory exchange ratio, averaged expiratory concentrations, end tidal oxygen and ventilatory equivalents for oxygen and carbon dioxide and blood lactate concentrations rose (p < 0.001), averaged expiratory concentrations and end tidal carbon dioxide and duration of inspiration, expiration and total breathing cycle decreased (p < 0.001), while tidal volume and volumes of oxygen and carbon dioxide expired maintained constant. Stroke frequency and stroke length increased and decreased (respectively) with the swimming velocity raise. No differences between experimental moments were observed in most of the assessed variables (p > 0.05), with a low dispersion (0.49%-9.94%) except for lactate concentrations and inspiration and expiration durations (11.00%-17.16%). Moderate-nearly perfect direct relationships and a good-excellent degree of reliability between moments were verified for all the assessed variables (r = 0.50-1.00, ICC = 0.76-1.00,p < 0.001), except for respiratory exchange ratio.Significance. The reliability analysis confirmed the repeatability of the assessed ventilatory, metabolic and biomechanical variables, with the obtained data well representing swimmers physiological condition when monitoring performance through a commonly used step protocol.

Morphine and clinical outcomes in patients with ST segment elevation myocardial infarction treated with fibrinolytic and antiplatelet therapy: Insights from the TREAT trial.

BACKGROUND: Morphine is commonly used to relieve pain, anxiety and dyspnea in STEMI but it lowers blood pressure and delays the activity of oral antiplatelet agents. The impact of morphine on clinical outcomes remains unknown. This analysis was performed to determine if morphine use was associated with increased risk of adverse clinical events among STEMI patients treated with fibrinolytic therapy and clopidogrel or ticagrelor. METHODS: In the Ticagrelor in Patients with ST Elevation Myocardial Infarction Treated with Pharmacological Thrombolysis (TREAT) study, 3799 STEMI patients treated with fibrinolysis were randomized to receive clopidogrel or ticagrelor. Morphine use was left to the discretion of the treating physicians. In this pre-specified analysis, we evaluated clinical outcomes based on the use and timing of morphine administration. Outcomes were stratified by randomized treatment group. Multivariable analysis was performed using Inverse Probability Treatment Weighting (IPTW) weighting. RESULTS: Morphine was used in 53% of patients. After adjustment using IPTW weighting, morphine use was associated with higher hazard of reinfarction at 7 days (HR 4.9, P = .0006) and 30 days (HR 1.7, P = .04), and lower hazard of major bleeding (HR 0.37, P = .006). There was no significant difference in mortality at any time point. CONCLUSIONS: Among patients with STEMI treated with fibrinolytic therapy, morphine use was associated with a higher risk of early reinfarction and a lower risk of major bleeding but no difference in mortality. CLINICAL TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT02298088.

How Anthropometrics of Young and Adolescent Swimmers Influence Stroking Parameters and Performance? A Systematic Review.

The purpose of this systematic review was to investigate the relationship between anthropometric characteristics, biomechanical variables and performance in the conventional swimming techniques in young and adolescent swimmers. A database search from 1 January 2001 to 30 June 2021 was done according to the PRISMA statement, with 43 studies being selected for analysis. Those manuscripts were divided in butterfly, backstroke, breaststroke and front crawl techniques as main categories. The results showed the importance of the anthropometric variables for the performance of the young swimmer, although there was a lack of variables common to the studies that analysed the butterfly, backstroke and breaststroke techniques. For the front crawl technique there is a consensus among studies on the advantage of having higher height and arm span values, variables that concurrently with high body mass and lean body mass values, contribute positively to better stroke length and stoke index values.

Dapagliflozin in patients with cardiometabolic risk factors hospitalised with COVID-19 (DARE-19): a randomised, double-blind, placebo-controlled, phase 3 trial.

BACKGROUND: COVID-19 can lead to multiorgan failure. Dapagliflozin, a SGLT2 inhibitor, has significant protective benefits for the heart and kidney. We aimed to see whether this agent might provide organ protection in patients with COVID-19 by affecting processes dysregulated during acute illness. METHODS: DARE-19 was a randomised, double-blind, placebo-controlled trial of patients hospitalised with COVID-19 and with at least one cardiometabolic risk factor (ie, hypertension, type 2 diabetes, atherosclerotic cardiovascular disease, heart failure, and chronic kidney disease). Patients critically ill at screening were excluded. Patients were randomly assigned 1:1 to dapagliflozin (10 mg daily orally) or matched placebo for 30 days. Dual primary outcomes were assessed in the intention-to-treat population: the outcome of prevention (time to new or worsened organ dysfunction or death), and the hierarchial composite outcome of recovery (change in clinical status by day 30). Safety outcomes, in patients who received at least one study medication dose, included serious adverse events, adverse events leading to discontinuation, and adverse events of interest. This study is registered with ClinicalTrials.gov, NCT04350593. FINDINGS: Between April 22, 2020 and Jan 1, 2021, 1250 patients were randomly assigned with 625 in each group. The primary composite outcome of prevention showed organ dysfunction or death occurred in 70 patients (11·2%) in the dapagliflozin group, and 86 (13·8%) in the placebo group (hazard ratio [HR] 0·80, 95% CI 0·58-1·10; p=0·17). For the primary outcome of recovery, 547 patients (87·5%) in the dapagliflozin group and 532 (85·1%) in the placebo group showed clinical status improvement, although this was not statistically significant (win ratio 1·09, 95% CI 0·97-1·22; p=0·14). There were 41 deaths (6·6%) in the dapagliflozin group, and 54 (8·6%) in the placebo group (HR 0·77, 95% CI 0·52-1·16). Serious adverse events were reported in 65 (10·6%) of 613 patients treated with dapagliflozin and in 82 (13·3%) of 616 patients given the placebo. INTERPRETATION: In patients with cardiometabolic risk factors who were hospitalised with COVID-19, treatment with dapagliflozin did not result in a statistically significant risk reduction in organ dysfunction or death, or improvement in clinical recovery, but was well tolerated. FUNDING: AstraZeneca.

Tofacitinib in Patients Hospitalized with Covid-19 Pneumonia.

BACKGROUND: The efficacy and safety of tofacitinib, a Janus kinase inhibitor, in patients who are hospitalized with coronavirus disease 2019 (Covid-19) pneumonia are unclear. METHODS: We randomly assigned, in a 1:1 ratio, hospitalized adults with Covid-19 pneumonia to receive either tofacitinib at a dose of 10 mg or placebo twice daily for up to 14 days or until hospital discharge. The primary outcome was the occurrence of death or respiratory failure through day 28 as assessed with the use of an eight-level ordinal scale (with scores ranging from 1 to 8 and higher scores indicating a worse condition). All-cause mortality and safety were also assessed. RESULTS: A total of 289 patients underwent randomization at 15 sites in Brazil. Overall, 89.3% of the patients received glucocorticoids during hospitalization. The cumulative incidence of death or respiratory failure through day 28 was 18.1% in the tofacitinib group and 29.0% in the placebo group (risk ratio, 0.63; 95% confidence interval [CI], 0.41 to 0.97; P = 0.04). Death from any cause through day 28 occurred in 2.8% of the patients in the tofacitinib group and in 5.5% of those in the placebo group (hazard ratio, 0.49; 95% CI, 0.15 to 1.63). The proportional odds of having a worse score on the eight-level ordinal scale with tofacitinib, as compared with placebo, was 0.60 (95% CI, 0.36 to 1.00) at day 14 and 0.54 (95% CI, 0.27 to 1.06) at day 28. Serious adverse events occurred in 20 patients (14.1%) in the tofacitinib group and in 17 (12.0%) in the placebo group. CONCLUSIONS: Among patients hospitalized with Covid-19 pneumonia, tofacitinib led to a lower risk of death or respiratory failure through day 28 than placebo. (Funded by Pfizer; STOP-COVID ClinicalTrials.gov number, NCT04469114.).

Post-swim oxygen consumption: assessment methodologies and kinetics analysis.

OBJECTIVE: This study aimed at comparing different recovery-based methods to assess the highest exercise oxygen uptake value ([Formula: see text]O2peak) when swimming at low-moderate, heavy and severe intensities. Complementarily, the different recovery curve kinetics were analysed. APPROACH: Eighteen competitive swimmers performed a 5 × 200 m front crawl intermittent protocol (0.05 m · s-1 increments and 3 min intervals), with respiratory gas exchange being continuously measured breath-by-breath during and post-exercise using a portable gas analyser. The directly determined [Formula: see text]O2peak ([Formula: see text]O2dir) was compared with the values obtained by linear and exponential backward extrapolations (of different intervals) and the recovery curve mathematical modelling. MAIN RESULTS: [Formula: see text]O2dir rose with intensity increase: 41.96 ± 6.22, 46.36 ± 6.89 and 50.97 ± 7.28 ml · kg-1 min-1 for low-moderate, heavy and severe swims. Linear and exponential regressions applied to the first 20 s of recovery presented the [Formula: see text]O2peak values closest to [Formula: see text]O2dir at low-moderate (42.80 ± 5.54 vs 42.88 ± 5.58 ml kg-1 min-1), heavy (47.12 ± 4.91 vs 47.48 ± 5.09 ml kg-1 min-1) and severe intensity domains (51.24 ± 6.89 vs 53.60 ± 8.54 ml kg-1 · min-1, respectively; r = 0.5-0.8, p < 0.05). The mono-exponential function was the best fit at low-moderate and heavy intensities, while the bi-exponential function better characterized the severe exercise domain (with a slow component amplitude, time delay and time constant of 6.2 ± 2.3 ml kg-1 min-1, 116.6 ± 24.3 and 39.9 ± 15.2 s, respectively). SIGNIFICANCE: The backward extrapolation of the first 20 s of recovery is the best method to assess the [Formula: see text]O2peak for a large spectrum of swimming intensities. Complementarily, intensity increases imply different recovery curve kinetics, particularly a mono-exponential behaviour for low-moderate and heavy exertions and a bi-exponential dynamics for severe paces.

Azithromycin in addition to standard of care versus standard of care alone in the treatment of patients admitted to the hospital with severe COVID-19 in Brazil (COALITION II): a randomised clinical trial.

BACKGROUND: The efficacy and safety of azithromycin in the treatment of COVID-19 remain uncertain. We assessed whether adding azithromycin to standard of care, which included hydroxychloroquine, would improve clinical outcomes of patients admitted to the hospital with severe COVID-19. METHODS: We did an open-label, randomised clinical trial at 57 centres in Brazil. We enrolled patients admitted to hospital with suspected or confirmed COVID-19 and at least one additional severity criteria as follows: use of oxygen supplementation of more than 4 L/min flow; use of high-flow nasal cannula; use of non-invasive mechanical ventilation; or use of invasive mechanical ventilation. Patients were randomly assigned (1:1) to azithromycin (500 mg via oral, nasogastric, or intravenous administration once daily for 10 days) plus standard of care or to standard of care without macrolides. All patients received hydroxychloroquine (400 mg twice daily for 10 days) because that was part of standard of care treatment in Brazil for patients with severe COVID-19. The primary outcome, assessed by an independent adjudication committee masked to treatment allocation, was clinical status at day 15 after randomisation, assessed by a six-point ordinal scale, with levels ranging from 1 to 6 and higher scores indicating a worse condition (with odds ratio [OR] greater than 1·00 favouring the control group). The primary outcome was assessed in all patients in the intention-to-treat (ITT) population who had severe acute respiratory syndrome coronavirus 2 infection confirmed by molecular or serological testing before randomisation (ie, modified ITT [mITT] population). Safety was assessed in all patients according to which treatment they received, regardless of original group assignment. This trial was registered at ClinicalTrials.gov, NCT04321278. FINDINGS: 447 patients were enrolled from March 28 to May 19, 2020. COVID-19 was confirmed in 397 patients who constituted the mITT population, of whom 214 were assigned to the azithromycin group and 183 to the control group. In the mITT population, the primary endpoint was not significantly different between the azithromycin and control groups (OR 1·36 [95% CI 0·94-1·97], p=0·11). Rates of adverse events, including clinically relevant ventricular arrhythmias, resuscitated cardiac arrest, acute kidney failure, and corrected QT interval prolongation, were not significantly different between groups. INTERPRETATION: In patients with severe COVID-19, adding azithromycin to standard of care treatment (which included hydroxychloroquine) did not improve clinical outcomes. Our findings do not support the routine use of azithromycin in combination with hydroxychloroquine in patients with severe COVID-19. FUNDING: COALITION COVID-19 Brazil and EMS.

Portland Cement/Acrocomia Aculeata Endocarp Bricks: Thermal Insulation and Mechanical Properties.

In the last few decades, Portland/residue composites have been researched due to their technological and environmental advantages. In this study, residues of Acrocomia aculeata (Jacq.) Lodd endocarp (AE) were introduced in the Portland cement-soil (PC) matrix in different concentrations (0, 5, 10, 15, 20, and 50 wt%) to produce PC/AE bricks. The characterization of the microstructures of the bricks indicate agglomerates of AE particles with increased humidity in small regions distributed throughout the matrix. Mid-infrared and laser-induced breakdown spectroscopy, along with thermogravimetry, indicated that AE contained mainly lignin and cellulose, as well as inorganic chemical elements such as Mg and Si. X-ray studies revealed that AE did not affect the crystallographic properties of the Portland/AE bricks. The findings indicate that the use of AE improved the thermal insulation capability of the composites with a small impact on the compressive strength.

In-Water and On-Land Swimmers' Symmetry and Force Production.

Although performance and biomechanical evaluations are becoming more swimming-specific, dryland testing permits monitoring of a larger number of performance-related variables. However, as the degree of comparability of measurements conducted in-water and on land conditions is unclear, we aimed to assess the differences between force production in these two different conditions. Twelve elite swimmers performed a 30 s tethered swimming test and four isokinetic tests (shoulder and knee extension at 90 and 300°/s) to assess peak force, peak and average torque, and power symmetry index. We observed contralateral symmetry in all the tests performed, e.g., for 30 s tethered swimming and peak torque shoulder extension at 90°/s: 178 ± 50 vs. 183 ± 56 N (p = 0.38) and 95 ± 37 vs. 94 ± 35 N × m (p = 0.52). Moderate to very large direct relationships were evident between dryland testing and swimming force production (r = 0.62 to 0.96; p < 0.05). Swimmers maintained similar symmetry index values independently of the testing conditions (r = -0.06 to -0.41 and 0.04 to 0.44; p = 0.18-0.88). Asymmetries in water seems to be more related to technical constraints than muscular imbalances, but swimmers that displayed higher propulsive forces were the ones with greater force values on land. Thus, tethered swimming and isokinetic evaluations are useful for assessing muscular imbalances regarding propulsive force production and technical asymmetries.

Influence of Ischemia Time in Injury of Deep Peribiliary Glands of the Bile Ducts Graft: A Prospective Study.

The deep peribiliary glands (DPBG) are a niche of progenitor cells in the wall of the biliary duct (BD) and are the second line of multiplication when severe lesion of the epithelium occurs. Previous studies have identified DPBG injury as a cause of post-liver transplant (LT) biliary stenosis; this complication is a major cause of post-LT morbidity. The incidence of biliary stenosis in our center is high (38.1%). This study evaluates the lesion of DPBG in response to ischemia. Graft BD was collected in adult LT between August 2016-July 2017, from donation after brain death. Samples of 45 grafts were collected at 2 moments: BD1-during graft preparation and BD2-before biliary anastomosis. Histological analysis of the samples was performed and then classified according to degree of lesion (0, ≤50%, and >50%). A comparison was made between the degree of lesion and graft ischemia, graft histology, donor, and procurement variables. The DPBG lesion was more frequent in BD2 (20.9% vs 7%, P = .079). BD2 lesions with DPBG lesions had higher medians and means at all times of ischemia. The difference was greater in the warm ischemia time (0: 43.3 ± 12.53 minutes vs ≤50%: 52.4 ± 14.38 minutes, P = .068). The group of BD1 with DPBG lesion presented superior median cold ischemia time (CIT). In the analysis of the remaining variables there were also no statistically significant differences. We concluded that during the period of CIT there is already lesion of the DPBG, which increases after reperfusion of the graft, in greater association with longer warm ischemia time.

Ticagrelor Versus Clopidogrel in Patients With STEMI Treated With Fibrinolysis: TREAT Trial.

BACKGROUND: The efficacy of ticagrelor in the long-term post-ST-segment elevation myocardial infarction (STEMI) treated with fibrinolytic therapy remains uncertain. OBJECTIVES: The purpose of this study was to evaluate the efficacy of ticagrelor when compared with clopidogrel in STEMI patients treated with fibrinolytic therapy. METHODS: This international, multicenter, randomized, open-label with blinded endpoint adjudication trial enrolled 3,799 patients (age <75 years) with STEMI receiving fibrinolytic therapy. Patients were randomized to ticagrelor (180-mg loading dose, 90 mg twice daily thereafter) or clopidogrel (300- to 600-mg loading dose, 75 mg daily thereafter). The key outcomes were cardiovascular mortality, myocardial infarction, or stroke, and the same composite outcome with the addition of severe recurrent ischemia, transient ischemic attack, or other arterial thrombotic events at 12 months. RESULTS: The combined outcome of cardiovascular mortality, myocardial infarction, or stroke occurred in 129 of 1,913 patients (6.7%) receiving ticagrelor and in 137 of 1,886 patients (7.3%) receiving clopidogrel (hazard ratio: 0.93; 95% confidence interval: 0.73 to 1.18; p = 0.53). The composite of cardiovascular mortality, myocardial infarction, stroke, severe recurrent ischemia, transient ischemic attack, or other arterial thrombotic events occurred in 153 of 1,913 patients (8.0%) treated with ticagrelor and in 171 of 1,886 patients (9.1%) receiving clopidogrel (hazard ratio: 0.88; 95% confidence interval: 0.71 to 1.09; p = 0.25). The rates of major, fatal, and intracranial bleeding were similar between the ticagrelor and clopidogrel groups. CONCLUSION: Among patients age <75 years with STEMI, administration of ticagrelor after fibrinolytic therapy did not significantly reduce the frequency of cardiovascular events when compared with clopidogrel. (Ticagrelor in Patients With ST Elevation Myocardial Infarction Treated With Pharmacological Thrombolysis [TREAT]; NCT02298088).

Worst outcomes according to RAS mutation variants: an analysis in patients with metastatic colorectal adenocarcinoma.

PURPOSE: Over 50% of metastatic colorectal cancers harbor RAS mutations. It is unclear if different mutation variants have an impact on survival. The purpose of this study was to evaluate the impact of these mutations on colorectal cancer survival. METHODS: The charts of all cases of metastatic colorectal cancer diagnosed between January 2005 and January 2016 in a tertiary hospital in Brazil were reviewed. Inclusion criteria were complete data on clinical staging, treatments received and all-RAS testing. Multivariate Cox proportional survival models were used to evaluate the impact of specific RAS variants on survival. RESULTS: There were 151 eligible patients and 61.6% had RAS alterations, the most common G12D (11.9%) and G12A (8.6%). Most patients received chemotherapy, including oxaliplatin (79%), irinotecan (53%) and bevacizumab (59%). Among RAS-wild type patients, 46% received anti-EGFR therapy. Median survival was 39.2 months for RAS-wildtype, 18.8 months for RAS G12A and 34.6 for other RASmutant patients (multivariate analysis for G12A vs RASwild type HR 1.94; 95% CI 0.83-5.51; p=0.12). CONCLUSION: Patients with metastatic colorectal cancer who have RAS mutations have shorter overall survival. Regarding the impact of specific KRAS alterations, G12A mutations have a worse prognosis.

Ticagrelor versus clopidogrel after fibrinolytic therapy in patients with ST-elevation myocardial infarction: Rationale and design of the ticagrelor in patients with ST elevation myocardial infarction treated with thrombolysis (TREAT) trial.

BACKGROUND: The safety and efficacy of ticagrelor in patients with ST-elevation myocardial infarction (STEMI) treated with fibrinolytic therapy remain uncertain. OBJECTIVES: The primary objective of the TicagRElor in pAtients with ST elevation myocardial infarction treated with Thrombolysis (TREAT) trial is to evaluate the short-term safety of ticagrelor when compared with clopidogrel in STEMI patients treated with fibrinolytic therapy. Key secondary objectives are to assess the safety and efficacy of ticagrelor compared with clopidogrel at 12-months. DESIGN: The TREAT trial is a multicenter, randomized, phase III, Prospective randomized open blinded end-point (PROBE) study that enrolled 3,799 patients in 152 sites from 10 countries. Following administration of fibrinolytic therapy patients were randomized to a loading dose of ticagrelor 180 mg or clopidogrel 300 mg followed by a maintenance dose of ticagrelor 90 mg twice daily or clopidogrel 75 mg/day for 12-months. The primary outcome is the rate of TIMI major bleeding at 30-days and will be assessed for non-inferiority using an intention-to-treat analysis. Co-treatments include aspirin and anticoagulants. Other evidence based therapies are also recommended. Secondary efficacy outcome include a composite of death from vascular causes, myocardial infarction, stroke, severe recurrent ischemia, transient ischemic attack or other arterial thrombotic event. All-cause mortality as well as individual components of the combined efficacy endpoint will also be ascertained. SUMMARY: TREAT is an international randomized controlled trial comparing ticagrelor with clopidogrel in STEMI patients treated with fibrinolytic therapy. The results of this trial will inform clinical practice and international guidelines.