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1.
Creatine kinase is associated with bleeding after myocardial infarction.
Brewster, LM, Fernand, J
Open heart. 2020;(2)
Abstract
BACKGROUND The ADP-scavenging enzyme creatine kinase (CK) is reported to reduce ADP-dependent platelet activation. Therefore, we studied whether highly elevated CK after ST-elevation myocardial infarction (STEMI) is associated with bleeding. METHODS Data of the Thrombolysis in Myocardial Infarction Study Group phase II trial on the efficacy of angioplasty, following intravenous recombinant tissue-type plasminogen activator (rt-PA), are used to assess whether peak plasma CK (CKmax) is independently associated with adjudicated fatal or non-fatal bleeding (primary) and combined bleeding/all-cause mortality (secondary) in multivariable binomial logistic regression analysis, adjusting for baseline and treatment allocation covariates. RESULTS The included patients (n=3339, 82% men, 88% white, mean age 57 years, SE 0.2) had a history of angina pectoris (55%), hypertension (38%) and/or diabetes mellitus (13%). CKmax ranged from 16 to 55 890 IU/L (mean 2389 IU/L, SE 41), reached within 8 hours in 51% of the patients (93% within 24 hours). Adjudicated fatal/non-fatal bleeding occurred in 30% of the patients (respectively 26% in the low vs 34% in the high CK tertile), and bleeding/all-cause mortality in 35% (29% in the low vs 40% in the high CK tertile). In multivariable regression analysis, the adjusted OR for fatal/non-fatal bleeding (vs not bleeding and survival) was 2.6 (95% CI 1.8 to 3.7)/log CKmax increase, and 3.1 (2.2 to 4.4) for bleeding/all-cause mortality. CONCLUSION Highly elevated plasma CK after myocardial infarction might be an independent predictor of bleeding and haemorrhagic death. This biologically plausible association warrants further prospective study of the potential role of extracellular CK in ADP-dependent platelet activation and bleeding.
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Cardiotoxicity of anthracycline (ANT) treatment in children with malignant tumors.
Hu, H, Zhang, W, Huang, D, Yang, Q, Li, J, Gao, Y
Pediatric hematology and oncology. 2018;(2):111-120
Abstract
OBJECTIVE To investigate the cardiotoxicity indexes in children with malignant tumors after the administration of anthracycline (ANT) chemotherapy. MATERIALS AND METHODS Data from 131 children with malignant tumors who were treated using ANT chemotherapy at our hospital from January 2011 to December 2015 were collected to analyze the serologic indexes (such as N-terminal pro-brain natriuretic peptide [NT-proBNP] and isoenzyme of creatine kinase [CK-MB]) and changes in corrected QT interval(QT-c) and left ventricular ejection fraction (LVEF) before and after treatment with different ANT cumulative doses. RESULTS General clinical data revealed that 2 of the 131 children developed clinical cardiotoxicity. The ANT cumulative dose range was 12-697 mg/m2. All patients were divided into three groups according to the ANT cumulative dose: group 1 (<100 mg/m2), 2 (≥100 and <200 mg/m2), and 3 (≥200 mg/m2). Although NT-proBNP and LVEF among the three groups differed significantly after chemotherapy (p = 0.022 and 0.035, respectively), no significance was noted for CK-MB and QT-c among the three groups after chemotherapy (p = 0.190 and p = 0.084, respectively). Multiple linear regression analysis revealed that the ANT cumulative dose had the most significant impact on NT-proBNP (standardized coefficient 0.423, p = 0). Pearson correlation analysis revealed that ANT cumulative dose was positively correlated with NT-proBNP post-treatment (correlation coefficient 0.423), but LVEF was negatively correlated with NT-proBNP after chemotherapy (correlation coefficient -0.542). CONCLUSIONS NT-proBNP showed significant changes when the ANT dose was >200 mg/m2. Post-treatment serum NT-proBNP was linearly correlated with ANT cumulative dose, hence strictly controlling the ANT cumulative dose and monitoring serum NT-proBNP may have certain clinical significance in predicting cardiotoxicity.
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Serum creatine kinase isoenzymes in children with osteogenesis imperfecta.
D'Eufemia, P, Finocchiaro, R, Zambrano, A, Lodato, V, Celli, L, Finocchiaro, S, Persiani, P, Turchetti, A, Celli, M
Osteoporosis international : a journal established as result of cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA. 2017;(1):339-346
Abstract
UNLABELLED This study evaluates serum creatine kinase isoenzyme activity in children with osteogenesis imperfecta to determine its usefulness as a biochemical marker during treatment with bisphosphonate. The changes of creatine kinase (CK) isoenzyme activity during and after discontinuation therapy were observed. These results could be useful in addressing over-treatment risk prevention. INTRODUCTION The brain isoenzyme of creatine kinase (CKbb) is highly expressed in mature osteoclasts during osteoclastogenesis, thus plays an important role in bone resorption. We previously identified high serum CKbb levels in 18 children with osteogenesis imperfect (OI) type 1 treated for 1 year with bisphosphonate (neridronate). In the present study, serum CK isoenzymes were evaluated in the same children with continuous versus discontinued neridronate treatment over a further 2-year follow-up period. METHODS This study included 18 children with OI type 1, 12 with continued (group A) and 6 with ceased (group B) neridronate treatment. Auxological data, serum biochemical markers of bone metabolism, bone mineral density z-score, and serum total CK and isoenzyme activities were determined in both groups. RESULTS Serum CKbb was progressively and significantly increased in group A (p < 0.004) but rapidly decreased to undetectable levels in group B. In both groups, the cardiac muscle creatine kinase isoenzyme (CKmb) showed a marked decrease, while serum C-terminal telopeptide (CTx) levels were almost unchanged. CONCLUSIONS This study provides evidence of the cumulative effect of neridronate administration in increasing serum CKbb levels and the reversible effect after its discontinuation. This approach could be employed for verifying the usefulness of serum CKbb as a biochemical marker in patients receiving prolonged bisphosphonate treatment. Moreover, the decreased serum CKmb levels suggest a systemic effect of these drugs.
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Three-dimensional mapping of the creatine kinase enzyme reaction rate in muscles of the lower leg.
Parasoglou, P, Xia, D, Chang, G, Convit, A, Regatte, RR
NMR in biomedicine. 2013;(9):1142-51
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Abstract
Phosphorus ((31) P) magnetization transfer (MT) techniques enable the non-invasive measurement of metabolic turnover rates of important enzyme-catalyzed reactions, such as the creatine kinase reaction (CK), a major transducing reaction involving adenosine triphosphate and phosphocreatine. Alteration in the kinetics of the CK reaction rate appears to play a central role in many disease states. In this study, we developed and implemented at ultra-high field (7T) a novel three-dimensional (31) P-MT imaging sequence that maps the kinetics of CK in the entire volume of the lower leg at relatively high resolution (0.52 mL voxel size), and within acquisition times that can be tolerated by patients (below 60 min). We tested the sequence on five healthy and two clinically diagnosed type 2 diabetic subjects. Overall, we obtained measurements that are in close agreement with measurements reported previously using spectroscopic methods. Importantly, our spatially resolved method allowed us to measure local CK reaction rate constants and metabolic fluxes in individual muscles in a non-invasive manner. Furthermore, it allowed us to detect variations of the CK rates of different muscles, which would not have been possible using unlocalized MRS methods. The results of this work suggest that 3D mapping of the CK reaction rates and metabolic fluxes can be achieved in the skeletal muscle in vivo at relatively high spatial resolution and with acquisition times well tolerated by patients. The ability to measure bioenergetics simultaneously in large areas of muscles will bring new insights into possible heterogeneous patterns of muscle metabolism associated with several diseases and serve as a valuable tool for monitoring the efficacy of interventions.
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Comparison of serum cardiac specific biomarker release after non-cardiac thoracic surgery.
Muley, T, Kurz, M, Männle, C, Alekozai, A, Winteroll, S, Dienemann, H, Schmidt, W, Pfannschmidt, J
Clinical laboratory. 2011;(11-12):925-32
Abstract
BACKGROUND The detection of postoperative myocardial infarction can be difficult in patients after lung surgery. The aim of this study was to verify the clinical significance of elevated Troponin I (cTnI), N-terminal pro-natriuretic peptide (NT-pro-BNP), lactate dehydrogenase (LDH), creatine kinase (CK), and CK-MB in the perioperative course. METHODS Between 2007 and 2010, 64 patients (36 men, 28 women) were includeded in this prospective study and underwent thoracotomy and wedge lung resection (n = 20, group I), lobectomy/bilobectomy (n = 24, group II), and pneumonectomy (n = 20, group III). Peri-operative measurements were done for the serum markers: cTnI, NT-pro-BNP, LDH, CK, and CK-MB preoperatively and at 4 hours, 8 hours, and 24 hours postoperatively. Patients were followed over a 90-day period to evaluate postoperative cardiac mortality. RESULTS No basal troponin I elevation (or CK-MB) was found prior to surgery. Elevation in concentrations of troponin I (> 0.32 ng/mL) occurring after the procedure were seen in 9 patients. However, there was neither association with 90-day survival, postoperative ECG changes, nor with elevated levels of the other cardiac serum markers. cTnI correlated significantly with intrapericardial procedures in 7 out of 20 patients (Spearman's rank correlation coefficient: 0.406; p < 0.0001). Additionally, of the 20 patients within the pneumonectomy group, 8 patients had postoperative elevated serum cTnI. The grouping of patients into groups I through III was significantly associated with cTnI elevation (Spearman's rank correlation coefficient: 0.455; p < 0.0001). CONCLUSIONS Despite the excellent sensitivity of troponin I for detection of acute myocardial infarction the fact remains that troponin I elevations were common after intrapericardial procedures and pneumonectomies. Thus, to differentiate between cardiac ischemia provoked chest pain and wound pain related to thoracotomy remains most difficult. Patients with only marginally elevated cTnI concentrations after intrapericardial resections or pneumonectomy should remain in the intensive care unit and should be followed-up carefully by cardiologists.
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Monitoring markers of muscle damage during a 3 week periodized drop-jump exercise programme.
Kamandulis, S, Skurvydas, A, Snieckus, A, Masiulis, N, Aagaard, P, Dargeviciute, G, Brazaitis, M
Journal of sports sciences. 2011;(4):345-53
Abstract
The aim of this study was to examine changes in indirect markers of muscle damage during 3 weeks of stretch-shortening exercise with a progressively increasing load and continued modulation of various key training variables. Eight healthy untrained men performed a drop-jump programme involving a progressive increase in load impact with respect to the number of jumps performed, drop (platform) height, squat depth amplitude, and addition of weights. Maximal concentric and isometric knee extensor strength were assessed immediately before and 10 min after each training session. Voluntary and 100 Hz-stimulation-evoked torque decreased acutely after each training session relative to pre-exercise values (P < 0.05) but recovered before the subsequent training session. Post-exercise plasma creatine kinase activity increased from 162.2 ± 56.2 IU · l(-1) to 284.3 ± 116.3 IU · l(-1) at 48 h after the first training session (P < 0.05) and remained marginally elevated throughout the training period. The present results indicate that detrimental muscle damage can be avoided with drop-jump training even with the gradual introduction of more demanding exercise induced by increasing the volume, intensity, and muscle stretch amplitude. These findings suggest that the human neuromuscular system is highly adaptable to progressively varied loading demands during stretch-shortening exercise training.
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Daptomycin exposure and the probability of elevations in the creatine phosphokinase level: data from a randomized trial of patients with bacteremia and endocarditis.
Bhavnani, SM, Rubino, CM, Ambrose, PG, Drusano, GL
Clinical infectious diseases : an official publication of the Infectious Diseases Society of America. 2010;(12):1568-74
Abstract
BACKGROUND The objective of this analysis was to evaluate the relationship between daptomycin exposure and the probability of an elevation in the creatine phosphokinase (CPK) level (hereafter, "CPK elevation") in patients with Staphylococcus aureus bacteremia with or without infective endocarditis. METHODS Phase 3 data for patients with S. aureus bacteremia, with or without infective endocarditis, who received intravenous daptomycin (6 mg/kg daily) and in whom pharmacokinetic data were collected were evaluated. On the basis of univariate logistic regression, the relationship between Bayesian post hoc exposure estimates and the probability of a CPK elevation was evaluated. Time to CPK elevation was examined with Kaplan-Meier analysis and Cox proportional hazards regression. RESULTS Significant relationships between the minimum concentration of drug (C(min)) and area under the plasma concentration time curve and probability of CPK elevation were observed in 108 evaluable patients. Of the 108 patients evaluated, 6 (5.56%) demonstrated a defined CPK elevation, regardless of treatment relationship. C(min) (breakpoint of 24.3 mg/L) was most significantly associated with CPK elevation (P = .002). The probabilities of a CPK elevation with a C(min) 24.3 mg/L and <24.3 mg/L were 0.5 and 0.029, respectively. Increases in C(min), evaluated as a continuous variable, were also significantly associated with CPK elevation (P = .01). Stratified Kaplan-Meier analysis and Cox proportional hazards regression demonstrated C(min) to be a significant predictor of time to a CPK elevation (P .003). The probability of a CPK elevation was 0 and 0.01 after 7 days of treatment in patients with a C(min) 24.3 mg/L or <24.3 mg/L, respectively. After 14 days, the probabilities were 0.5 and 0.025, respectively. CONCLUSIONS This analysis demonstrated that a daptomycin C(min) 24.3 mg/L was associated with an increased probability of a CPK elevation. Clinical trials registration. Clinical trials.gov NCT00093067 .
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Relationship between serum creatine kinase activity following exercise-induced muscle damage and muscle fibre composition.
Magal, M, Dumke, CL, Urbiztondo, ZG, Cavill, MJ, Triplett, NT, Quindry, JC, McBride, JM, Epstein, Y
Journal of sports sciences. 2010;(3):257-66
Abstract
In this study, we examined the relationship between serum creatine kinase activity following exercise-induced muscle damage and muscle fibre composition. Seventeen untrained males volunteered and underwent a .[Vdot]O2max test, Wingate test, and an exercise-induced muscle damage protocol. Muscle soreness and blood samples were recorded before, immediately after, and 24, 48, 72, and 96 h after exercise. Biopsy samples from the vastus lateralis were collected one week after exercise-induced muscle damage and were assessed for muscle fibre composition. There was no significant relationship (P > 0.05) between muscle fibre composition and creatine kinase activity. A significant positive correlation (P < 0.05) was observed between soreness 48 h after exercise and type II and IIb fibres, and a significant negative correlation (P < 0.05) was observed between soreness 48 h after exercise and type I muscle fibres. Significant positive correlations were observed between soreness 48 h after exercise and the fatigue index, relative average power, and relative anaerobic capacity. Our results suggest that creatine kinase activity following exercise-induced muscle damage may not be related to muscle fibre proportions, and higher post-exercise muscular pain may be related to a predominance of type II muscle fibres and higher anaerobic capabilities.
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Should high creatine kinase discourage the initiation or continuance of statins for the treatment of hypercholesterolemia?
Glueck, CJ, Rawal, B, Khan, NA, Yeramaneni, S, Goldenberg, N, Wang, P
Metabolism: clinical and experimental. 2009;(2):233-8
Abstract
Patients with high low-density lipoprotein cholesterol (LDLC) and asymptomatic high creatine kinase (CK) (>or=250 but <2500 IU/L, 10x the laboratory upper normal limit [UNL]) are often not started on statins or have statins stopped because of concern about myositis-rhabdomyolysis. In the current report, we prospectively examined the hypothesis that asymptomatic patients with high CK (>or=250 but <2500 IU/L) tolerate statins well at doses reducing LDLC to target, less than 100 mg/dL, without development of myalgia-myositis. We assessed outcomes of 3 groups of patients referred to us because of asymptomatic high CK (>or=250 but <2500 IU/L)--1 group (n = 29) on statins at referral and continued on statins, 1 group (n = 20) not on statins and started on statins, and 1 group (n = 19) not on statins and not given statins--all restudied 1 month after entry and then every 3 months. Of the 68 patients, 59 (87%) had CK greater than 1 to 3 times the UNL, 7 (10%) had CK greater than 3 to 5 times the UNL, and 2 (3%) had CK greater than 5 to 10 times the UNL. After 1.2 months of follow-up in 29 statin-->statin patients, median CK fell from 353 to 301 (P = .0018) and was 287 (P = .015) after 4 months. After 1.3 months of follow-up in 20 no statin-->statin patients, median CK fell from 397 to 292 (P = .0094) and was 419 after 4.1 months. After 1.1 months of follow-up in 19 no statin-->no statin patients, median CK fell from 392 to 323 (P = .14) and was 271 (P = .029) after 4.2 months. By repeated-measures analysis, there were no differences in entry CK among the 3 treatment groups; CK fell (P = .04) in the no statin-->no statin patients. Despite high baseline CK (48 patients with CK 1-5x the UNL, 1 with CK 5-10x UNL), no patients during follow-up on statins developed CK greater than 10 times the UNL (2500 IU/L), none discontinued statins or reduced statin dose because of myalgia-myositis, and there was no rhabdomyolysis. High pretreatment CK, particularly 1 to 5 times the UNL, should not be an impediment to start or continue statins to lower LDLC.
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The effects of compression garments on intermittent exercise performance and recovery on consecutive days.
Duffield, R, Edge, J, Merrells, R, Hawke, E, Barnes, M, Simcock, D, Gill, N
International journal of sports physiology and performance. 2008;(4):454-68
Abstract
PURPOSE The aim of this study was to determine whether compression garments improve intermittent-sprint performance and aid performance or self-reported recovery from high-intensity efforts on consecutive days. METHODS Following familiarization, 14 male rugby players performed two randomized testing conditions (with or without garments) involving consecutive days of a simulated team sport exercise protocol, separated by 24 h of recovery within each condition and 2 weeks between conditions. Each day involved an 80-min high-intensity exercise circuit, with exercise performance determined by repeated 20-m sprints and peak power on a cart dynamometer (single-man scrum machine). Measures of nude mass, heart rate, skin and tympanic temperature, and blood lactate (La-) were recorded throughout each day; also, creatine kinase (CK) and muscle soreness were recorded each day and 48 h following exercise. RESULTS No differences (P=.20 to 0.40) were present between conditions on either day of the exercise protocol for repeated 20-m sprint efforts or peak power on a cart dynamometer. Heart rate, tympanic temperature, and body mass did not significantly differ between conditions; however, skin temperature was higher under the compression garments. Although no differences (P=.50) in La- or CK were present, participants felt reduced levels of perceived muscle soreness in the ensuing 48 h postexercise when wearing the garments (2.5+/-1.7 vs 3.5+/-2.1 for garment and control; P=.01). CONCLUSIONS The use of compression garments did not improve or hamper simulated team-sport activity on consecutive days. Despite benefits of reduced self-reported muscle soreness when wearing garments during and following exercise each day, no improvements in performance or recovery were apparent.