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1.
Cabozantinib-induced serum creatine kinase elevation and musculoskeletal complaints.
Stump, SE, Whang, YE, Crona, DJ
Investigational new drugs. 2018;(6):1143-1146
Abstract
Cabozantinib is a multikinase inhibitor approved for the treatment of metastatic medullary thyroid cancer and advanced renal cell carcinoma (RCC) in patients who have received prior anti-angiogenic therapy. While associations between serum creatine kinase (CK) elevations and other tyrosine kinase inhibitors used for the treatment of solid malignancies have been previously reported, we report a case of cabozantinib-associated CK elevation that was associated with musculoskeletal complaints by an RCC patient. Nine days following initiation of cabozantinib, the patient reported muscle cramps and serum CK had increased from levels 12 months earlier that were within normal limits to a grade 1 elevation of 244 units/L. Despite a dose reduction, her CK continued to rise over the next 2 months, leading to a peak CK of 914 units/L. Due to this grade 3 elevation, cabozantinib was permanently discontinued, and her CK subsequently returned to a grade 1 elevation within one week and then to baseline within 3 weeks. The temporal relationship between drug exposure and CK increase strongly suggests causality. To the authors' knowledge, this is the first reported case of CK elevation attributed to cabozantinib, but cabozantinib-induced CK elevations could be under-reported, and providers should monitor for musculoskeletal complaints during cabozantinib therapy.
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2.
Creatine, Creatine Kinase, and Aging.
Sumien, N, Shetty, RA, Gonzales, EB
Sub-cellular biochemistry. 2018;:145-168
Abstract
With an ever aging population, identifying interventions that can alleviate age-related functional declines has become increasingly important. Dietary supplements have taken center stage based on various health claims and have become a multi-million dollar business. One such supplement is creatine, a major contributor to normal cellular physiology. Creatine, an energy source that can be endogenously synthesized or obtained through diet and supplement, is involved primarily in cellular metabolism via ATP replenishment. The goal of this chapter is to summarize how creatine and its associated enzyme, creatine kinase, act under normal physiological conditions, and how altered levels of either may lead to detrimental functional outcomes. Furthermore, we will focus on the effect of aging on the creatine system and how supplementation may affect the aging process and perhaps reverse it.
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3.
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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4.
Creatine kinase, neuromuscular fatigue, and the contact codes of football: A systematic review and meta-analysis of pre- and post-match differences.
Hagstrom, AD, Shorter, KA
European journal of sport science. 2018;(9):1234-1244
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Abstract
Physiological or performance tests are routinely utilised to assess athletes' recovery. At present, the ideal tool to assess recovery remains unknown. Therefore, the aim of this systematic review was to examine the change in creatine kinase (CK) and neuromuscular function as measured via a countermovement jump (CMJ) following a match in the contact codes of football. A comprehensive search of databases was undertaken with RevMan (V 5.3) used for statistical analysis. Our results demonstrated that CK pre- versus post-match (standardised mean difference (SMD) = 0.90, 95% CI = 0.50 to 1.31, p < .0001), CK pre- versus 24 h post-match (SMD = 1.50, 95% CI = 1.12 to 1.88, p < .00001), and CK pre- versus 48 h post-match all increased significantly (SMD = 0.90, 95% CI = 0.50 to 1.31, p < .0001), while CMJ peak power (PP) pre- versus post-match (SMD = -0.59, 95% CI = -1.12 to -0.06, p = .03), and pre- versus 24 h post-match (SMD = -0.80, 95% CI = -1.31 to -0.28, p = .002) decreased significantly. There was a significant relationship between the change in CK and the change in CMJ PP from immediately pre to immediately post (r = -0.924, p = .025), and between CMJ immediately following a match and 24 h CK change (r = -0.983, p = .017). In conclusion, CK levels increase and performance in the CMJ decreases following a match of a contact code of football. The identification of this relationship may allow coaching staff to implement a standalone measure of recovery.
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Decrements in Neuromuscular Performance and Increases in Creatine Kinase Impact Training Outputs in Elite Soccer Players.
Malone, S, Mendes, B, Hughes, B, Roe, M, Devenney, S, Collins, K, Owen, A
Journal of strength and conditioning research. 2018;(5):1342-1351
Abstract
Malone, S, Mendes, B, Hughes, B, Roe, M, Devenney, S, Collins, K, and Owen, A. Decrements in neuromuscular performance and increases in creatine kinase impact training outputs in elite soccer players. J Strength Cond Res 32(5): 1342-1351, 2018-The aim of the current investigation was to understand the impact of pretraining neuromuscular performance and creatine kinase (CK) status on subsequent training performance in elite soccer players. Thirty soccer players (age: 25.3 ± 3.1 years; height: 183 ± 7 cm; mass: 72 ± 7 kg) were involved in this observational study. Each morning before training, players completed assessments for neuromuscular performance (countermovement jump; CMJ) and CK levels. Global positioning technology provided external load: total distance, high-speed distance, sprint distance, accelerations, decelerations, average metabolic power, explosive distance, and high metabolic power distance (>25.5 W·kg). Mixed-effect linear models revealed significant effects for CK and CMJ Z-score on total high-speed distance, very high-speed distance, accelerations, decelerations, explosive distance, and maximal velocity. Effects are reported with 90% confidence limits. A CK Z-score of +1 corresponded to a -5.5 ± 1.1, -3.9 ± 0.5, -4.3 ± 2.9%, -4.1 ± 2.9%, -3.1 ± 2.9%, and -4.6 ± 1.9%, reduction in total high-speed distance, very high-speed distance, accelerations, decelerations, explosive distance, and maximal velocity, respectively. Countermovement jump Z-score of -1 corresponded to a -3.5 ± 1.1, -2.9 ± 0.5, -2.1 ± 1.4, -5.3 ± 2.9%, -3.8 ± 2.9%, -1.1 ± 2.9%, and -5.6 ± 1.2% reduction in these external load measures. Magnitude-based analysis revealed that the practical size of the effect of a pretraining CMJ Z-score of -1 and CK Z-score of +1 would have on total high-speed distance, very high-speed distance, high metabolic power distance (>25.5 W·kg), accelerations, decelerations, explosive distance, and maximal velocity was likely negative. The results of this study suggest that systematic pretraining monitoring of neuromuscular and muscle stress within soccer cohorts can provide coaches with information about the training output that can be expected from individual players during a training session.
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6.
Effects of lymphatic drainage and cryotherapy on indirect markers of muscle damage.
Behringer, M, Jedlicka, D, Mester, J
The Journal of sports medicine and physical fitness. 2018;(6):903-909
Abstract
BACKGROUND Muscle enzymes are cleared from the extracellular space by the lymphatic system, while smaller proteins enter the bloodstream directly. We investigated if manual lymphatic drainage (MLD), local cryotherapy (CRY), and rest (RST) differently affect the time course of creatine kinase (CK, 84 kDa) and heart-type fatty acid binding protein (h-FABP, 15 kDa) in the blood. METHODS Randomized controlled trial. After 4x20 unilateral, eccentric accentuated knee extensions (with one-third of the maximal isometric force) 30 sports students randomly received either a 30 min MLD, CRY or they rested (RST) for the same amount of time. CK, h-FABP, neutrophil granulocytes, and the perceived muscle soreness were assessed before, immediately after, and 1 hour, 4 hours, and 24 hours after the exercise. RESULTS All measures increased significantly (P<0.001) after the protocol indicating that muscle damage was induced. However, the responses did not differ between the treatments. CONCLUSIONS Large and small damage markers were not affected differently by MLD, CRY, or RST, when applied for 30 min and no beneficial effects on inflammation or muscle soreness could be found for MLD and CRY when compared to RST. This information is particularly important for those sports physicians and conditioning specialists who use biochemical muscle damage markers to adjust the training load and volume of athletes.
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Implication of peripheral blood miRNA-124 in predicting acute myocardial infarction.
Guo, ML, Guo, LL, Weng, YQ
European review for medical and pharmacological sciences. 2017;(5):1054-1059
Abstract
OBJECTIVE This study aimed to determine the expression of miR-124 in the patients with acute myocardial infarction (AMI) and elucidated the role of miR-124 on early diagnosis of AMI. PATIENTS AND METHODS A total of 90 AMI patients were recruited, along with 45 healthy individuals as the control group. Blood samples were collected at different time points (0 h at admission, 6 h, 12 h and 24 h of disease onset). Real-time PCR was used to test miRNA-124 level. ELISA was used to test serum troponin (cTnI) and creatine kinase-MB isoenzyme (CK-MB) levels. The correlation between miRNA-124, cTnI and CK-MB was analyzed. Receiver operating characteristic curve (ROC) was used to analyze sensitivity and specificity of AMI. RESULTS MiRNA-124 expression in experimental group was significantly elevated in peripheral blood of AMI patients. It can reach the peak at 6h after onset. AMI patients had significantly elevated cTnI and CK-MB expression level (p<0.05 compared to control group). The expression of miRNA-124 reached the peak earlier than cTnI and CK-MB. miRNA-124 was positively correlated with cTnI and CK-MB (p<0.05). The area under the curve of ROC of miRNA-124 was 0.86 (95% CI: 0.815-0.937), with 52% sensitivity and 91% specificity. CONCLUSIONS AMI patients presented a significantly elevated level of miRNA-124 in peripheral blood. Our data suggested that miR-124 contributed to an earlier detection than other diagnostic markers for AMI. Therefore, peripheral miRNA-124 can serve as a novel biological marker for early diagnosis of AMI.
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Posterolateral vs Direct Anterior Approach in Total Hip Arthroplasty (POLADA Trial): A Randomized Controlled Trial to Assess Differences in Serum Markers.
Rykov, K, Reininga, IHF, Sietsma, MS, Knobben, BAS, Ten Have, BLEF
The Journal of arthroplasty. 2017;(12):3652-3658.e1
Abstract
BACKGROUND The direct anterior approach (DAA) for total hip arthroplasty has claimed to be a true tissue-sparing minimally invasive approach that has less tissue damage and a faster recovery when compared to the posterolateral approach (PLA). The aim of this randomized controlled trial is to measure the differences in serum markers and functional outcomes between the DAA and PLA for total hip arthroplasty. METHODS Forty-six patients were prospectively included and randomized for either the DAA (n = 23) or PLA (n = 23). All surgical procedures were performed by 3 well-trained orthopedic surgeons. The degree of tissue damage was assessed by measuring creatine kinase (CK) and C-reactive protein levels (CRP) preoperatively and 2 hours, 1 day, 2 weeks, and 6 weeks postoperatively. Generalized linear mixed models analyses were used to assess differences between serum markers over time; correction for possible confounding factors was performed. The Hip disability and Osteoarthritis Outcome Score and the Harris Hip Score were assessed preoperatively and 6 weeks postoperatively. RESULTS There were no differences in patient demographics. The DAA had a longer operative time (P = .001). CK and CRP levels increased postoperatively, but no significant differences between the groups were found on any of the time points. Functional outcomes were also similar in both approaches. CONCLUSION No difference in tissue damage measured with serum markers CK and CRP were found between the DAA and PLA for total hip arthroplasty.
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9.
Effects on Energy Metabolism of Two Guanidine Molecules, (Boc)2 -Creatine and Metformin.
Garbati, P, Ravera, S, Scarfì, S, Salis, A, Rosano, C, Poggi, A, Damonte, G, Millo, E, Balestrino, M
Journal of cellular biochemistry. 2017;(9):2700-2711
Abstract
Several enzymes are involved in the energy production, becoming a possible target for new anti-cancer drugs. In this paper, we used biochemical and in silico studies to evaluate the effects of two guanidine molecules, (Boc)2 -creatine and metformin, on creatine kinase, an enzyme involved in the regulation of intracellular energy levels. Our results show that both drugs inhibit creatine kinase activity; however, (Boc)2 -creatine displays a competitive inhibition, while metformin acts with a non-competitive mechanism. Moreover, (Boc)2 -creatine is able to inhibit the activity of hexokinase with a non-competitive mechanism. Considering that creatine kinase and hexokinase are involved in energy metabolism, we evaluated the effects of (Boc)2 -creatine and metformin on the ATP/AMP ratio and on cellular proliferation in healthy fibroblasts, human breast cancer cells (MDA-MB-468), a human neuroblastoma cell line (SH-SY5Y), a human Hodgkin lymphoma cell line (KMH2). We found that healthy fibroblasts were only partially affected by (Boc)2 -creatine, while both ATP/AMP ratio and viability of the three cancer cell lines were significantly decreased. By inhibiting both creatine kinase and hexokinase, (Boc)2 -creatine appears as a promising new agent in anticancer treatment. Further research is needed to understand what types of cancer cells are most suitable to treatment by this new compound. J. Cell. Biochem. 118: 2700-2711, 2017. © 2017 Wiley Periodicals, Inc.
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Lactate dehydrogenase and creatine kinase as poor prognostic factors in lung cancer: A retrospective observational study.
Liu, L, He, Y, Ge, G, Li, L, Zhou, P, Zhu, Y, Tang, H, Huang, Y, Li, W, Zhang, L
PloS one. 2017;(8):e0182168
Abstract
PURPOSE Circulating molecules play important roles in lung cancer diagnosis. In addition, plasma lactate dehydrogenase (LDH) and creatine kinase (CK) have been shown to be closely related to tumor progression in breast cancer, prostate cancer, and colonel cancer. However, the relationships between LDH and CK levels with metastasis occurrence and the survival status of lung cancer patients remain unclear. EXPERIMENTAL DESIGN A total of 1142 lung cancer patients were enrolled in this study and were separated into negative or positive groups, according to the plasma levels of CK or LDH. Patients in both groups were assessed for clinical characteristics, metastasis occurrence, and survival status. The Cox regression model was then introduced to confirm whether CK and LDH could act as independent factors for predicting a poor prognosis. RESULTS The results indicated that CK had a close relationship with bone (p < 0.05) and lymph node (p < 0.05) metastases. In addition, LDH was strongly related with bone (p < 0.05), adrenal gland (p < 0.05), and lymph node (p < 0.05) metastases. CK and LDH were also correlated with the survival status of the lung cancer patients (all p < 0.001). According to specific histological classification analysis, it was found that CK was closely related to the survival status of adenocarcinoma (ADC) and squamous cell carcinoma (SCC) patients, while LDH was only correlated with that of ADC patients. Cox regression analysis confirmed that CK and LDH could act as independent factors for predicting a poor prognosis in ADC but not SCC patients. CONCLUSIONS For the first time, our study confirmed the role of CK in metastasis occurrence and the survival status of lung cancer patients. In addition, it also demonstrated that CK and LDH could be used as independent factors to predict a poor prognosis in ADC patients. The identification of CK and LDH will play important roles in lung cancer diagnosis and poor outcome prediction in the future.