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1.
Persistently elevated CK and lysosomal storage myopathy associated with mucolipin 1 defects.
Zambon, AA, Lemaigre, A, Phadke, R, Grunewald, S, Sewry, C, Sarkozy, A, Clement, E, Muntoni, F, ,
Neuromuscular disorders : NMD. 2021;(3):212-217
Abstract
Mucolipidosis type IV is a rare autosomal recessive lysosomal storage disorder caused by bi-allelic pathogenic variants in the gene MCOLN1. This encodes for mucolipin-1 (ML1), an endo-lysosomal transmembrane Ca++ channel involved in vesicular trafficking. Although experimental models suggest that defects in mucolipin-1 can cause muscular dystrophy, putatively due to defective lysosomal-mediated sarcolemma repair, the role of mucolipin-1 in human muscle is still poorly deciphered. Elevation of creatine kinase (CK) had been reported in a few cases in the past but comprehensive descriptions of muscle pathology are lacking. Here we report a 7-year-old boy who underwent muscle biopsy due to persistently elevated CK levels (780-15,000 UI/L). Muscle pathology revealed features of a lysosomal storage myopathy with mild regenerative changes. Next generation sequencing confirmed homozygous nonsense variants in MCOLN1. This is a comprehensive pathological description of ML1-related myopathy, supporting the role of mucolipin-1 in muscle homoeostasis.
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2.
Creatine kinase test diagnostic accuracy in neonatal screening for Duchenne Muscular Dystrophy: A systematic review.
de Freitas Nakata, KC, da Silva Pereira, PP, Salgado Riveros, B
Clinical biochemistry. 2021;:1-9
Abstract
OBJECTIVES to evaluate the accuracy of the creatine kinase test in neonatal screening for Duchenne Muscular Dystrophy. METHODS Investigations were carried out in six databases, gray literature and manual search. All studies and data extraction eligibility processes were carried out in paired mode. The methodological stringency of the studies was assessed using the modified QUADAS 2 tool. The performance measures of the test were calculated using the Meta-DiSc software, version 1.4. RESULTS 11 studies were included, with a total sample of 1,416,123 newborns. The positive likelihood ratio was more than 10 in these studies. On the other hand, the negative likelihood ratio was up to 0.2 in 9/10 studies; however, when considering the upper limit of the confidence interval, only 4/10 studies showed a negative likelihood ratio less than 0.2 and in 6/11 it was greater than 0.5. Specificity was close to 1 in studies. The sensitivity was equal to or greater than 0.81 in 10/11 studies; however, when considering the reliability's minimum interval limit, only 6/10 studies showed sensitivity equal to or greater than 0.7. Ten studies were summarized on a ROC curve indicating good performance (Area under the curve = 0.9980 and Q index = 0.9846). CONCLUSIONS the creatine kinase test showed good accuracy in screening for cases of Duchenne Muscular Dystrophy and may be a useful alternative in the early diagnosis of the disease followed by confirmatory genetic testing.
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3.
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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4.
Muscle manifestations and CK levels in COVID infection: results of a large cohort of patients inside a Pandemic COVID-19 Area.
De Rosa, A, Verrengia, EP, Merlo, I, Rea, F, Siciliano, G, Corrao, G, Prelle, A
Acta myologica : myopathies and cardiomyopathies : official journal of the Mediterranean Society of Myology. 2021;(1):1-7
Abstract
OBJECTIVE To investigate both muscular manifestations and CK levels in a large cohort of patients with COVID-19 infection and to determine whether hyperckemia is associated with morbidity and mortality. METHODS Data of 615 patients discharged from ASST Ovest Milanese (Milan, Lombardy, Italy) with final diagnosis of COVID-19 infection were retrospectively extracted from electronical medical records from 21 February to 1 May 2020. Patients were descriptively analyzed with respect to the following variables: sex, age, muscular manifestations (myalgia and/or arthralgia), fatigue, respiratory involvement (SARS pneumonia or respiratory failure) and history of falls. Association between patients' characteristics and CK levels was investigated. In addition, the proportion of patients who died following access to the ER was calculated. Finally, the effect of CK levels and other patients' features on mortality was estimated using a logistic regression model. RESULTS 176 (28.6%) patients had raised serum CK levels. CK levels were significantly associated with history of falls, male gender, SARS pneumonia, respiratory failure and in-hospital death. No correlation was found between hyperckemia and muscular manifestations. CONCLUSIONS Our study provides preliminary evidence that hyperckemia is associated with respiratory failure and fatal outcome in patients with COVID-19 infection.In these patients, among other testing, CK dosage is recommended.
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5.
Characterization of Creatine Kinase Levels in Tofacitinib-Treated Patients with Ulcerative Colitis: Results from Clinical Trials.
Panaccione, R, Isaacs, JD, Chen, LA, Wang, W, Marren, A, Kwok, K, Wang, L, Chan, G, Su, C
Digestive diseases and sciences. 2021;(8):2732-2743
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Abstract
BACKGROUND Tofacitinib is an oral, small-molecule JAK inhibitor for the treatment of ulcerative colitis (UC). Creatine kinase (CK) levels and CK-related adverse events (AEs) in tofacitinib-treated patients with UC were evaluated. METHODS Data were analyzed for three UC cohorts: Induction (phase 2 and 3 induction studies); Maintenance (phase 3 maintenance study); Overall [patients who received tofacitinib 5 or 10 mg twice daily (b.d.) in phase 2, phase 3, or open-label, long-term extension studies; data at November 2017]. Clinical trial data for tofacitinib-treated patients with rheumatoid arthritis, psoriasis, and psoriatic arthritis are presented for contextualization. RESULTS Week 8 mean change from baseline CK with tofacitinib 10 mg b.d. induction therapy was 91.1 U/L (95% CI, 48.1-134.1) versus 19.2 U/L (8.5-29.9) with placebo. Among patients completing induction with 10 mg b.d. and re-randomized to 52 weeks of maintenance therapy, mean increases from induction baseline to the end of maintenance were 35.9 (8.1-63.7), 90.3 (51.9-128.7), and 115.6 U/L (91.6-139.7), with placebo, 5 and 10 mg b.d., respectively. The incidence rate (unique patients with events per 100 patient-years) for AEs of CK elevation in the tofacitinib-treated UC Overall cohort was 6.6 versus 2.2, 6.5, and 3.7 for tofacitinib-treated patients with rheumatoid arthritis, psoriasis, and psoriatic arthritis, respectively. No serious AEs of CK elevation or AEs of myopathy occurred in UC studies. CONCLUSIONS In patients with UC, CK elevations with tofacitinib appeared reversible and not associated with clinically significant AEs. UC findings were consistent with tofacitinib use in other inflammatory diseases. TRIAL REGISTRATION NCT00787202; NCT01465763; NCT01458951; NCT01458574; NCT01470612; NCT01262118; NCT01484561; NCT00147498; NCT00413660; NCT00550446; NCT00603512; NCT00687193; NCT01059864; NCT01164579; NCT00976599; NCT01359150; NCT02147587; NCT00960440; NCT00847613; NCT00814307; NCT00856544; NCT00853385; NCT01039688; NCT02187055; NCT00413699; NCT00661661; NCT01710046; NCT00678210; NCT01276639; NCT01309737; NCT01241591; NCT01186744; NCT01163253; NCT01877668; NCT01882439; NCT01976364.
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Investigating raised creatine kinase.
Kim, EJ, Wierzbicki, AS
BMJ (Clinical research ed.). 2021;:n1486
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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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Creatine kinase and bleeding in patients with acute coronary syndromes.
Ndrepepa, G, Holdenrieder, S, Cassese, S, Kastrati, A
European journal of clinical investigation. 2021;(7):e13514
Abstract
BACKGROUND The association between elevated creatine kinase (CK) and bleeding in patients with acute coronary syndrome (ACS) remains incompletely investigated. We undertook this study to assess whether there is an association between elevated CK activity and the risk for bleeding in contemporary patients with ACS. MATERIALS AND METHODS This post hoc analysis of a randomized trial included 3368 patients with ACS undergoing percutaneous coronary intervention. CK was measured serially in all patients until hospital discharge. The main outcome was 30-day incidence of major bleeding (type 3 to 5 bleeding according to the Bleeding Academic Research Consortium criteria). RESULTS Patients were categorized in groups according to the peak CK tertiles: 1st tertile (CK ≤259 U/L; n = 1127 patients), 2nd tertile (CK ≥260 to 990 U/L; n = 1119 patients), and 3rd tertile (CK ≥ 991 U/L; n = 1122 patients). Peak CK activity was higher in patients with bleeding than those without bleeding (771 [316-1845] U/L vs. 496 [190-1357] U/L; P <.001). Bleeding occurred in 26 patients (2.3%) with peak CK within 1st tertile, 39 patients (3.5%) with peak CK within 2nd tertile, and 54 patients (4.8%) with peak CK within 3rd tertile (univariable hazard ratio [HR]=1.39, 95% confidence interval [CI] 1.08 to 1.81, P =.012, per tertile increment in CK values). After adjustment, peak CK activity remained significantly associated with the 30-day bleeding (HR = 1.67 [1.16-2.41]; P =.006 per unit increment in logarithmic CK values). The C statistic of the multivariable model with CK activity was 0.807 [0.770-0.842]. CONCLUSIONS In patients with ACS, peak CK activity was independently associated with increased 30-day incidence of bleeding.
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Is alectinib-induced elevation of creatine phosphokinase a predictive factor for response? Report of two cases and review of the literature.
Shalata, W, Massalha, I, Agbarya, A
Anti-cancer drugs. 2021;(4):456-459
Abstract
We aim to describe two cases of creatine phosphokinase (CPK) and liver enzymes elevation occurring as adverse effects of alectinib (Alecensa) treatment for anaplastic lymphoma kinase (ALK)-mutated metastatic nonsmall cell lung cancer (NSCLC). A 56-year-old female and a 59-year-old male diagnosed with NSCLC exhibiting ALK gene rearrangements were treated by alectinib administration. The former had a complete response of widespread metastatic disease within 3 months, and the latter also had a substantial response. Both patients initially experienced an episode of CPK elevation and neither had dose modifications. At the end of the treatment, CPK and liver enzymes returned to normal range despite the continuation of alectinib full dose. A transient elevation of CPK and liver enzymes may take place during the alectinib treatment, indicating a tumor tissue damage thus contributing to a significant response.
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Severe acute myopathy following SARS-CoV-2 infection: a case report and review of recent literature.
Islam, B, Ahmed, M, Islam, Z, Begum, SM
Skeletal muscle. 2021;(1):10
Abstract
BACKGROUND SARS-CoV2 virus could be potentially myopathic. Serum creatinine phosphokinase (CPK) is frequently found elevated in severe SARS-CoV2 infection, which indicates skeletal muscle damage precipitating limb weakness or even ventilatory failure. CASE PRESENTATION We addressed such a patient in his forties presented with features of severe SARS-CoV2 pneumonia and high serum CPK. He developed severe sepsis and acute respiratory distress syndrome (ARDS) and received intravenous high dose corticosteroid and tocilizumab to counter SARS-CoV2 associated cytokine surge. After 10 days of mechanical ventilation (MV), weaning was unsuccessful albeit apparently clear lung fields, having additionally severe and symmetric limb muscle weakness. Ancillary investigations in addition with serum CPK, including electromyogram, muscle biopsy, and muscle magnetic resonance imaging (MRI) suggested acute myopathy possibly due to skeletal myositis. CONCLUSION We wish to stress that myopathogenic medication in SARS-CoV2 pneumonia should be used with caution. Additionally, serum CPK could be a potential marker to predict respiratory failure in SARS-CoV2 pneumonia as skeletal myopathy affecting chest muscles may contribute ventilatory failure on top of oxygenation failure due to SARS-CoV2 pneumonia.