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1.
Serum creatine kinase and creatinine in adult spinal muscular atrophy under nusinersen treatment.
Freigang, M, Wurster, CD, Hagenacker, T, Stolte, B, Weiler, M, Kamm, C, Schreiber-Katz, O, Osmanovic, A, Petri, S, Kowski, A, et al
Annals of clinical and translational neurology. 2021;(5):1049-1063
Abstract
OBJECTIVE To determine whether serum creatine kinase activity (CK) and serum creatinine concentration (Crn) are prognostic and predictive biomarkers for disease severity, disease progression, and nusinersen treatment effects in adult patients with 5q-associated spinal muscular atrophy (SMA). METHODS Within this retrospective, multicenter observational study in 206 adult patients with SMA, we determined clinical subtypes (SMA types, ambulatory ability) and repeatedly measured CK and Crn and examined disease severity scores (Hammersmith Functional Motor Scale Expanded, Revised Upper Limb Module, and revised Amyotrophic Lateral Sclerosis Functional Rating Scale). Patients were followed under nusinersen treatment for 18 months. RESULTS CK and Crn differed between clinical subtypes and correlated strongly with disease severity scores (e.g., for Hammersmith Functional Motor Scale Expanded: (CK) ρ = 0.786/ (Crn) ρ = 0.558). During the 18 months of nusinersen treatment, CK decreased (∆CK = -17.56%, p < 0.0001), whereas Crn slightly increased (∆Crn = +4.75%, p < 0.05). INTERPRETATION Serum creatine kinase activity and serum creatinine concentration reflect disease severity of spinal muscular atrophy and are promising biomarkers to assess patients with spinal muscular atrophy during disease course and to predict treatment response. The decrease of creatine kinase activity, combined with the tendency of creatinine concentration to increase during nusinersen treatment, suggests reduced muscle mass wasting with improved muscle energy metabolism.
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2.
Elevation of creatine kinase is associated with acute kidney injury in hospitalized patients infected with seasonal influenza virus.
Ishibuchi, K, Fukasawa, H, Kaneko, M, Yasuda, H, Furuya, R
Clinical and experimental nephrology. 2021;(4):394-400
Abstract
BACKGROUND Although acute kidney injury (AKI) is known as a potential complication of influenza infections, there is limited information concerning the association between influenza and AKI. The aim of this study is to evaluate the incidence, the mortality, and risk factors of AKI in hospitalized patients by seasonal influenza viral infections. METHODS We performed a single center, retrospective observational study. 123 patients admitted to Iwata City Hospital due to influenza for 3 seasons were included. We examined the association between the incidence of AKI and clinical parameters using Spearman's correlation analyses, receiver-operating characteristic (ROC) curves, and multivariate logistic regression analyses. RESULTS Of 123 patients, AKI developed in 46 patients (37.4%). Patients with AKI showed higher serum creatine kinase (CK, P < 0.001), higher creatinine (Cr, P < 0.001), and higher C-reactive protein (CRP) levels (P < 0.001) at admission and higher mortality rate (P < 0.05) compared with patients without AKI. The severity of kidney injuries was well correlated with serum CK levels (P < 0.001). By ROC curve analysis, 186 U/L was the most predictive value of CK levels for AKI (sensitivity, 0.674; specificity, 0.688; and area under the curve [AUC], 0.714). Multivariate logistic regression analyses revealed that elevated CK levels (> 186 U/L) were significantly associated with AKI (P < 0.01). CONCLUSIONS The incidence of AKI and the mortality were high in hospitalized patients infected with seasonal influenza. The slight elevation of CK levels (> 186 U/L) at admission was associated with the development of AKI.
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3.
Biological markers and follow-up after discharge home of patients with COVID-19 pneumonia.
Gutiérrez Gabriel, S, Domínguez García, MJ, Pérez Mañas, G, Moreno García, N, Silvan Domínguez, M, Andrés, EM
Emergencias : revista de la Sociedad Espanola de Medicina de Emergencias. 2021;(3):174-180
Abstract
OBJECTIVES We aimed to analyze the clinical course of patients discharged from our emergency departament (ED) with pneumonia symptoms compatible with a diagnosis of COVID-19. MATERIAL AND METHODS We followed 102 patients discharged home with a diagnosis of pneumonia compatible with COVID19 between March 12 and 21, 2020, in our hospital in the southern part of the autonomous community of Madrid. Descriptive statistics (medians and interquartile ranges or frequencies, as appropriate) were compiled for the main variables. Treatments and prognoses were compared with 2, Kruskal-Wallis, or Mann-Whitney tests. The data then underwent logistic regression analysis. RESULTS Most patients (accounting for 74.5% of the discharges) were treated with hydroxychloroquine alone. The readmission rate was 15.7%; the ED revisiting rate was 25.7%. Admission was associated with an elevated lactate dehydrogenase (LDH) level (P=.011), elevated creatine kinase (CK) (P=.004), and lymphopenia (P=.034). Hypertension and chronic obstructive pulmonary disease were also related to admission. Ischemic heart disease was associated with longer duration of symptoms. CONCLUSION Lymphopenia, and elevated LDH and CK levels predicted the need for hospital admission better than other traditional biological markers in patients with mild to moderate symptoms. Telephone follow-up proved useful for dealing with the overloading of health care services.
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4.
Leisure physical exercise and creatine kinase activity. The Tromsø study.
Bekkelund, SI
Scandinavian journal of medicine & science in sports. 2020;(12):2437-2444
Abstract
Creatine kinase (CK) is an enzyme catalyzing energy reaction in muscle cells and has proven to modify cardiovascular risks. The influence of skeletal muscle activity on CK concentrations is a potential study confounder but is mainly reported in connection with sport activities. This study investigated the association between leisure physical exercise and CK and estimated the effect of physical exercise on the CK values. CK and leisure physical exercise defined as intensity, frequency, and duration subsets were measured in the population-based Tromsø study. Comparisons of CK at different exercise levels, multivariate analyses, and relative differences in CK between "never exercise" and "heavy exercise" (moderate or hard exercise ≥2 hours per week) subgroups were analyzed age- and sex-stratified in 12 796 men and women. CK increased significantly with higher levels of physical exercise intensity and frequency in both sexes analyzed by ANOVA. In a multivariate analysis, CK was independently associated with heavy exercise after adjusting for age, BMI, and blood pressure; OR 9.38 (95% CI 5.32-16.53), P < .0001 in men and OR 5.20 (95% CI 2.53-10.69), P < .0001 in women. The differences in CK between physically inactive and participants performing heavy exercise varied between 3.1% (women) and 6.4% (men) and was also larger in participants ≥50 years. In conclusion, CK was positively and independently associated with increasing leisure physical exercise in a general population. CK values associated with exercise were approximately twice as high in men than women, but exercise altered CK only modestly.
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5.
Monitoring training and recovery responses with heart rate measures during standardized warm-up in elite badminton players.
Schneider, C, Wiewelhove, T, McLaren, SJ, Röleke, L, Käsbauer, H, Hecksteden, A, Kellmann, M, Pfeiffer, M, Ferrauti, A
PloS one. 2020;(12):e0244412
Abstract
PURPOSE To investigate short-term training and recovery-related effects on heart rate during a standardized submaximal running test. METHODS Ten elite badminton players (7 females and 3 males) were monitored during a 12-week training period in preparation for the World Championships. Exercise heart rate (HRex) and perceived exertion were measured in response to a 5-min submaximal shuttle-run test during the morning session warm-up. This test was repeatedly performed on Mondays after 1-2 days of pronounced recovery ('recovered' state; reference condition) and on Fridays following 4 consecutive days of training ('strained' state). In addition, the serum concentration of creatine kinase and urea, perceived recovery-stress states, and jump performance were assessed before warm-up. RESULTS Creatine kinase increased in the strained compared to the recovered state and the perceived recovery-stress ratings decreased and increased, respectively (range of average effects sizes: |d| = 0.93-2.90). The overall HRex was 173 bpm and the observed within-player variability (i.e., standard deviation as a coefficient of variation [CV]) was 1.3% (90% confidence interval: 1.2% to 1.5%). A linear reduction of -1.4% (-3.0% to 0.3%) was observed in HRex over the 12-week observational period. HRex was -1.5% lower (-2.2% to -0.9%) in the strained compared to the recovered state, and the standard deviation (as a CV) representing interindividual variability in this response was 0.7% (-0.6% to 1.2%). CONCLUSIONS Our findings suggest that HRex measured during a standardized warm-up can be sensitive to short-term accumulation of training load, with HRex decreasing on average in response to consecutive days of training within repeated preparatory weekly microcycles. From a practical perspective, it seems advisable to determine intra-individual recovery-strain responses by repeated testing, as HRex responses may vary substantially between and within players.
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6.
Prognostic Impact of B-Type Natriuretic Peptide on Long-Term Clinical Outcomes in Patients with Non-ST-Segment Elevation Acute Myocardial Infarction Without Creatine Kinase Elevation.
Takahashi, N, Ogita, M, Suwa, S, Nakao, K, Ozaki, Y, Kimura, K, Ako, J, Noguchi, T, Yasuda, S, Fujimoto, K, et al
International heart journal. 2020;(5):888-895
Abstract
Although B-type natriuretic peptide (BNP) has gradually gained recognition as an indicator in risk stratification for patients with acute myocardial infarction (AMI), the prognostic impact on long-term clinical outcomes in patients with non-ST-segment elevation acute myocardial infarction (NSTEMI) without creatine kinase (CK) elevation remains unclear.This prospective multicenter study assessed 3,283 consecutive patients with AMI admitted to 28 institutions in Japan between 2012 and 2014. We analyzed 218 patients with NSTEMI without CK elevation (NSTEMI-CK) for whom BNP was available. In the NSTEMI-CK group, patients were assigned to high- and low-BNP groups according to BNP values (cut-off BNP, 100 pg/mL). The primary endpoint was defined as a composite of all-cause death, non-fatal myocardial infarction, non-fatal stroke, cardiac failure, and urgent revascularization for unstable angina up to 3 years. Primary endpoints were observed in 60 (33.3%) events among patients with NSTEMI-CK. Kaplan-Meier analysis revealed a significantly higher event rate for primary endpoints among patients with high BNP (log-rank P < 0.001). After adjusting for covariates, a higher BNP level was significantly associated with long-term clinical outcomes in NSTEMI-CK (adjusted hazard ratio, 4.86; 95% confidence interval, 2.18-12.44; P < 0.001).The BNP concentration is associated with adverse long-term clinical outcomes among patients with NSTEMI-CK who are considered low risk. Careful clinical management may be warranted for secondary prevention in patients with NSTEMI-CK with high BNP levels.
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7.
Effect of lansoprazole on DNA integrity of human spermatozoa and activity of seminal creatine kinase.
Banihani, SA, Khasawneh, FH
Andrologia. 2020;(5):e13564
Abstract
Although lansoprazole (brand name Prevacid) is a commonly used dug to manage various acid-related gastrointestinal diseases, little is known about its effects on human semen quality and sperm parameters. Here, we aimed to investigate the effect of lansoprazole on DNA integrity of human spermatozoa and activity of seminal creatine kinase. DNA integrity of human spermatozoa was assessed by the Apo-Direct™ kit followed by flow cytometry. The activity of creatine kinase was measured by kinetic spectrophotometric method using commercially available kits following the International Federation of Clinical Chemistry recommendations. Lansoprazole at 3 µg/ml, after 1-hr incubation period, did not show any significant increase in fluorescein isothiocyanate fluorescence (p > .05) and hence on the content of DNA breaks of human spermatozoa. In addition, there was no significant change (p = .8113) in the activity of seminal creatine kinase by the effect of lansoprazole. In conclusion, lansoprazole at 3 µg/ml did not alter DNA integrity of human spermatozoa or activity of seminal creatine kinase after 1-hr incubation period.
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8.
Observational retrospective single-centre study in Japan to assess the clinical significance of serum daptomycin levels in creatinine phosphokinase elevation.
Ando, M, Nishioka, H, Nakasako, S, Kuramoto, E, Ikemura, M, Kamei, H, Sono, Y, Sugioka, N, Fukushima, S, Hashida, T
Journal of clinical pharmacy and therapeutics. 2020;(2):290-297
Abstract
WHAT IS KNOWN AND OBJECTIVE Daptomycin-induced creatinine phosphokinase (CPK) elevation is reported to be associated with its trough level (Ctrough ; breakpoint of 24.3 μg/mL). However, even with high-dose treatment (ie, > 8 mg/kg), the safety of daptomycin treatment is widely demonstrated with low or no significant incidence of CPK elevation or other adverse effects, despite the possibility of Ctrough above 24.3 μg/mL. Therefore, we questioned the clinical significance of Ctrough levels of 24.3 μg/mL. In this study, we retrospectively evaluated the significance of Ctrough in the clinical setting, in addition to completing a retrospective safety assessment of daptomycin utilizing electronic health records. METHODS Patients who had received daptomycin treatment for > 4 days from July 2011 to June 2015 were enrolled. Serum daptomycin levels, including Ctrough and peak (Cpeak ), were measured by high-performance liquid chromatography equipped with a photodiode array. To evaluate the safety, patients' characteristics and relevant laboratory test values were reviewed retrospectively using an electronic medical record system. RESULTS AND DISCUSSION A total of 52 therapeutic cases for 46 patients were identified; of these, Ctrough and Cpeak levels were measured in 27 and 28 cases, respectively, and 6 patients received multiple courses of daptomycin treatment. The median age of the 52 patients was 68 years (range: 19-88 years), and 14 patients initially had an estimated creatinine clearance of less than 30 mL/min. Seven cases indicated a Ctrough of above 24.3 μg/mL; however, none of these presented CPK elevation, which meets with the study definition for abnormality. Furthermore, of the two patients with abnormal CPK elevations, only one patient had a measured Ctrough (of 10.9 μg/mL). Their CPK abnormalities were temporal and did not result in treatment discontinuation. The other four patients discontinued daptomycin treatment due to suspicions of adverse effects. Of the discontinued patients, two had measured Ctrough levels; these were 8.6 and 8.1 μg/mL. All patients with abnormal CPK elevation or treatment discontinuation exhibited Ctrough levels lower than 24.3 μg/mL. In this study, two patients receiving high-dose daptomycin (ie, 9.4 and 10.0 mg/kg) had observed Ctrough levels similar to patients who received doses of daptomycin < 9 mg/kg. WHAT IS NEW AND CONCLUSIONS The safety of daptomycin treatment was suggested in this study. Ctrough level of 24.3 μg/mL was not suggested as a significant clinical index for the incidence of CPK elevation, adverse effects or treatment discontinuation. Thus, acceptable tolerability towards higher Ctrough levels than 24.3 μg/mL was also suggested, though further studies are required. On the other hand, low levels of daptomycin in blood were unexpectedly observed in two cases, despite the high-dose treatments. Accordingly, the monitoring of serum daptomycin levels may also be useful to assess cases in which subtherapeutic levels were achieved.
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9.
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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10.
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.