Elevated Serum Creatine Kinase Research Articles

Duchenne Muscular Dystrophy: An Overview of Diagnosis, Management, and Pharmacological Treatment

Background: Duchenne muscular dystrophy (DMD) is a severe inherited neuromuscular disorder, primarily affecting males, characterized by progressive muscle weakness due to mutations in the dystrophin gene. This gene encodes dystrophin, a protein crucial for maintaining muscle cell integrity. DMD leads to the progressive loss of muscle function, cardiac complications, and intellectual disability. The disease typically results in wheelchair dependence by the early teens and early mortality due to respiratory or cardiac complications in the twenties. Aim: This overview aims to examine the diagnosis, management strategies, and pharmacological treatments for Duchenne muscular dystrophy. Methods: The article reviews current literature on the genetic basis, epidemiology, pathophysiology, and clinical manifestations of DMD. It also explores diagnostic methods including serum biomarkers, genetic testing, and muscle biopsy, as well as treatment options, particularly glucocorticoid therapy, and ongoing pharmacological interventions. Results: Early detection of elevated serum creatine kinase (CK) levels, along with genetic testing, is key to confirming DMD. Current pharmacological treatments primarily focus on corticosteroids to slow muscle degeneration, and new investigational therapies are exploring gene editing and protein restoration. Additionally, cardiomyopathy, a major complication, requires regular monitoring and management. Conclusion: Duchenne muscular dystrophy remains a challenging condition with significant impact on patients and their families. Early diagnosis and intervention are essential for improving outcomes, while ongoing research offers hope for more effective therapies. Effective management includes a multidisciplinary approach focusing on pharmacological, physical, and cardiac care.

Early Biomarkers for Detecting Subclinical Exposure to Fumonisin B1, Deoxynivalenol, and Zearalenone in Broiler Chickens.

Identifying biomarkers of mycotoxin effects in chickens will provide an opportunity for early intervention to reduce the impact of mycotoxicosis. This study aimed to identify whether serum enzyme concentrations, gut integrity, and liver miRNAs can be potential biomarkers for fumonisin B1 (FB1), deoxynivalenol (DON), and zearalenone (ZEA) toxicity in broiler birds as early as 14 days after exposure. A total of 720 male broiler chicks were distributed to six treatment groups: T1: control group (basal diet), T2 (2 FB1 + 2.5 DON + 0.9 ZEA), T3 (5 FB1 + 0.4 DON + 0.1 ZEA), T4 (9 FB1 + 3.5 DON + 0.7 ZEA), T5 (17 FB1 + 1.0 DON + 0.2 ZEA), and T6 (21 FB1 + 3.0 DON + 1.0 ZEA), all in mg/kg diet. On d14, there were no significant differences in the body weight gain (BWG) of mycotoxin treatment groups when compared to the control (p > 0.05), whereas on d21, T6 birds showed significantly reduced BWG compared to the control (p < 0.05). On d14, birds in T6 showed significant upregulation of liver miRNAs, gga-let-7a-5p (14.17-fold), gga-miR-9-5p (7.05-fold), gga-miR-217-5p (16.87-fold), gga-miR-133a-3p (7.41-fold), and gga-miR-215-5p (6.93-fold) (p < 0.05) and elevated serum fluorescein isothiocyanate-dextran (FITC-d) concentrations, aspartate aminotransferase (AST), and creatine kinase (CK) levels compared to the control (p < 0.05). On d21, T2 to T6 birds exhibited reduced serum phosphorus, glucose, and potassium, while total protein, FITC-d, AST, and CK levels increased compared to control (p < 0.05). These findings suggest that serum FITC-d, AST, CK, and liver miRNAs could serve as biomarkers for detecting mycotoxin exposure in broiler chickens.

Inflammasomes and idiopathic inflammatory myopathies.

Idiopathic inflammatory myopathies (IIM) are a group of systemic autoimmune diseases characterized by muscle weakness and elevated serum creatine kinase levels. Recent research has highlighted the role of the innate immune system, particularly inflammasomes, in the pathogenesis of IIM. This review focuses on the role of inflammasomes, specifically NLRP3 and AIM2, and their associated proteins in the development of IIM. We discuss the molecular mechanisms of pyroptosis, a programmed cell death pathway that triggers inflammation, and its association with IIM. The NLRP3 inflammasome, in particular, has been implicated in muscle fiber necrosis and the subsequent release of damage-associated molecular patterns (DAMPs), leading to inflammation. We also explore the potential therapeutic implications of targeting the NLRP3 inflammasome with inhibitors such as glyburide and MCC950, which have shown promise in reducing inflammation and improving muscle function in preclinical models. Additionally, we discuss the role of caspases, particularly caspase-1, in the canonical pyroptotic pathway associated with IIM. The understanding of these mechanisms offers new avenues for therapeutic intervention and a better comprehension of IIM pathophysiology.

Asymptomatic and oligosymptomatic states of dysferlinopathy

Dysferlinopathy is a phenotypically heterogeneous, inherited, progressive muscular dystrophy caused by mutations in the DYSF gene. Dysferlinopathy is marked by elevated serum creatine kinase (CK) and can in some cases manifest as hyperCKemia in asymptomatic or low-symptom states. Here, we describe the clinical signs and symptoms and laboratory and imaging results with quantitative MRI analysis of eight pediatric patients at asymptomatic and oligosymptomatic states of dysferlinopathy (aged 3–14 years). Seven of them with a same homozygous mutation and one with a compound heterozygous mutation in the DYSF gene. Based on this case series, we propose two stages of dysferlinopathy disease progression. The first state is asymptomatic hyperCKemia laboratory syndrome of myocytolysis, which is marked by an increase in CK (&gt;1.5 times the upper limit of normal (ULN)) and lactic dehydrogenase (LDH). Second state (oligosymptomatic): increasing CK (2.7–12.6 × ULN), LDH, alanine aminotransferase (ALT), and myoglobin; minimal or moderate signs of fatty muscle infiltration, displacement of the center of support to the back of the foot during plantography; slight afterload fatigue of the calf muscles; slight decrease in muscle strength (imperceptible to the patient) and decrease in Achilles reflexes. Taken together, isolated hyperCKemia (asymptomatic stage) and oligosymptomatic patients form a single continuum of pre-manifest cases.

Case Report: Urinary Proteomic Analysis of Exercise-Induced Rhabdomyolysis with Acute Kidney Injury

Exertional rhabdomyolysis (ER) is a frequently observed consequence following sustained strenuous exercise. The incidence of exercise-induced rhabdomyolysis has risen in the healthy population in recent decades, posing potential systemic, life-threatening complications like acute kidney injury (AKI). Early diagnosis requires prompt identification and management to prevent morbidity. This case report details the presentation of a 24-year-old male military member from the amphibious command specialization course, who attended the hospital emergency room with symptoms of nausea and dark brown urine 24 hours after strenuous military physical training. Laboratory results revealed a significant elevation in serum creatine kinase (CK) and creatinine (Cre) levels, reaching 9300 IU/L and 5.7 mg/dL, respectively. Concurrently, liver enzymes and urea levels were elevated, leading to the diagnosis of both ER and AKI. The individual exhibited a polygenic risk profile for ER, increasing susceptibility to inflammation and muscle damage. Further investigation through urine proteomic analysis unveiled the presence of various proteins associated with muscle damage, including creatine kinase M (CKM), myoglobin (MB), carbonic anhydrase (CA1), titin (TTN), as well as proteins linked to AKI, such as alpha-2-macroglobulin (A2MG), beta-2-microglobulin (B2MG), insulin-like growth factor-binding protein 7 (IBP7), metalloproteinase inhibitor 1 (TIMP1), and uromodulin (UROM), among others. Following a 12-day intensive care unit (ICU) treatment, a notable reduction in CK and MB levels was observed, accompanied by the restoration of renal function to normal levels. Subsequent laboratory tests during outpatient follow-up, two weeks after discharge, confirmed the normalization of relevant markers. The utilization of urinary proteomics emerged as a non-invasive method for monitoring pathophysiological changes, offering valuable insights into the mechanisms underlying ER and associated AKI.

Clinicopathological biomarker patterns, venom detection and venom proteomics in canine Vipera berus envenomation

Vipera berus (V. berus) bites are associated with high morbidity, including kidney injury, in dogs. Although antivenom is often used and perceived effective to treat this type of snakebite, it is costly and associated with adverse events and specific diagnostics for this type of snakebite are lacking. We sought to improve diagnostics in V. berus envenomation by using currently available tools, including evaluating urinary albumin as a biomarker for snakebite-associated kidney injury. Additionally, we planned to adapt a method from human medicine for venom detection in clinical samples from bitten dogs and describe the composition of Norwegian V. berus venom. Serum biochemical analytes and urine albumin (ELISA) were measured in samples collected at 24 hours and two weeks after bite in 29 envenomated dogs. An adapted ELISA was applied to detect venom in urine and plasma collected from 25 cases between presentation and 24 hours after bite, using a commercial antivenom as the capture and detection antibody. Proteomic analysis of venom collected from 11 V. berus was performed using liquid chromatography-tandem mass spectrometry. Elevated serum C-reactive protein, creatine kinase, and aspartate aminotransferase were common for the case group. Although no case dogs showed acute kidney injury with azotemia and/or reduced urine output, elevated urinary albumin concentrations may indicate early or mild kidney injury in some case dogs. The venom ELISA detected positive signals in both plasma and urine for up to 24 hours after bite. However, with false positives detected in plasma, urine seemed to be the most appropriate body fluid for this assay. The venom proteome identified L-amino acid oxidases as the dominant component. In conclusion, serum biochemical and urinary albumin analyses are useful tools for evaluating canine V. berus envenomation. The venom ELISA is proposed as a promising tool for studies of V. berus envenomation and future diagnostic test development. Venom from the studied Norwegian V. berus was shown to differ considerably from previous reports from other countries, implying geographical variation in composition.

Variability in Disease Severity in Siblings With Homozygous Missense Variant of ADSSL1: Clinical Genetic Study and Review of Literatures.

Distal myopathies are genetic muscle disorders caused by mutations in various genes. A study found that mutations in adenylosuccinate synthetase-like 1 (ADSSL1) are associated with distal myopathy in nine patients from six unrelated families in South Korea. Previous research showed that affected individuals experienced distal muscle weakness starting in adolescence, along with mild facial muscle weakness, slightly elevated or normal serum creatine kinase (CK) levels, and the presence of a few rimmed vacuoles in muscle fibers or minimal chronic myopathic damage. Previously reported patients in this category exhibited an early age of symptom onset and severe muscle weakness. In this study, we present a case of two sisters who share the same mutation locus but display distinct disease phenotypes. A literature review was conducted on distal myopathies in patients with ADSSL1 mutations, alongside a retrospective analysis of disease severity variability among siblings with a homozygous missense variant of ADSSL1. The study focuses on two sisters with differing disease manifestations despite carrying the same genetic mutation. The older sister showed lower ability in running and jumping compared to her peers at age 7 and experienced notable muscle weakness and atrophy by age 27, whereas the younger sister remained free of symptoms at age 30. These findings suggest that mutations at the same locus can result in varying disease outcomes, emphasizing the complexity of predicting disease progression based solely on genetic mutations.

Serum creatine kinase elevation following tyrosine kinase inhibitor treatment in cancer patients: Symptoms, mechanism, and clinical management.

Molecular targeted tyrosine kinase inhibitors (TKIs) have produced unprecedented treatment response in cancer therapy for patients harboring specific oncogenic mutations. While the TKIs are mostly well tolerated, they were reported to increase serum levels of creatine kinase (CK) and cause muscle metabolism-related toxicity. CK is an essential enzyme involved in cellular energy metabolism and muscle function. Elevated serum CK levels can arise from both physiological and pathological factors, as well as triggered by specific drug classes. The incidence of serum CK elevation induced by a few approved TKIs (brigatinib, binimetinib, cobimetinib-vemurafenib combination [Food and Drug Administration, United States]; aumolertinib, and sunvozertinib [only approved by National Medical Products Administration, China]) were over 35%. CK elevation-related symptoms include myopathy, myositis, inclusion body myositis (IBM), cardiotoxicity, rhabdomyolysis, rash, and acneiform dermatitis. High-level or severe symptomatic CK elevation may necessitate dose reduction and indirectly dampen TKI efficacy. This review presents an updated summary about the prevalence rate and recent research about mechanisms leading to TKI-induced serum CK elevation in cancer patients. The utility of monitoring serum CK levels for predicting TKI-induced adverse effects and their management will also be discussed.

Perioperative Rhabdomyolysis in Obese Individuals Undergoing Bariatric Surgery: Current Status.

One potential complication in bariatric surgery is rhabdomyolysis, which is a condition involving muscle tissue damage that can significantly impact a patient's health. The causes of rhabdomyolysis can be broadly classified into two major categories: traumatic and non-traumatic. Early investigations into the development of intraoperative rhabdomyolysis in bariatric surgery identified the main risk factors as tissue compression-primarily affecting the lower extremities, gluteal muscles, and lumbar region-as well as prolonged periods of immobilization. Clinically, rhabdomyolysis is typically suspected when a patient presents with muscle pain, weakness, and potentially dark urine or even anuria. However, the most reliable biomarker for rhabdomyolysis is elevated serum creatine kinase levels. The primary goal in managing hydration is to correct intravascular volume depletion, with solutions such as Lactated Ringer's or 0.9% saline being appropriate options for resuscitation. Perioperative diagnosis of rhabdomyolysis poses a significant challenge for anesthesiologists, requiring a high degree of clinical suspicion, particularly in bariatric patients. In this vulnerable population, prevention is crucial. The success of treatment depends on its early initiation; however, there are still significant limitations in the therapies available to prevent renal injury secondary to rhabdomyolysis.

Clinical and Genetic Profile of Chinese Children With Danon Disease: A Single-Center Retrospective Cohort Study

BackgroundDanon disease (DD) is a rare X-linked dominant lysosomal storage disorder. Studies on DD paediatric patients are limited owing to the small number of cases and challenges in early detection. MethodsWe retrospectively analysed clinical and genetic data of 29 paediatric patients who visited our hospital for treatment of or genetic counselling for DD from July 2014 to December 2023. ResultsThe mean age at diagnosis was 7.2 ± 5.9 years for boys (n = 21) and 9.4 ± 5.0 years for girls (n = 8). Asymptomatic elevated liver transaminase or creatine kinase (CK) levels were initial manifestations detected in 10 male patients (48%) and absent in female patients. Hypertrophic cardiomyopathy (HCM) was observed in 20 male patients (95%) and 7 female patients (88%), whereas dilated cardiomyopathy (DCM) was not detected. Ventricular preexcitation (VP) was observed initially in 10 patients (36%) and in 15 (54%) at latest evaluation. Patients with VP had higher left ventricular posterior wall thickness in end-diastole z-scores than those without VP (5.6 ± 2.2 vs 3.5 ± 2.1; P = 0.029). During a median 2.7 years of follow-up, 2 male patients received heart transplants. One boy and 1 girl died of heart failure and sudden cardiac arrest, respectively. Twenty-three pathogenic LAMP2 variants were identified, including 7 novel variants. ConclusionsA retrospective review of 29 DD cases suggests an underrecognised asymptomatic period in male DD patients, characterised by elevations in serum CK and transaminases. HCM appears to be the only cardiac manifestation in paediatric female patients, unlike a high incidence of DCM in adult female patients. The incidence of VP may increase with disease progression.

Dominant stop-loss HNRNPA1 variants in juvenile-onset myopathy.

Heterogeneous nuclear ribonucleoprotein A1 is involved in nucleic acid homeostatic functions. The encoding gene HNRNPA1 has been associated with several neuromuscular disorders including an amyotrophic lateral sclerosis-like phenotype, distal hereditary motor neuropathy, multisystem proteinopathy, and various myopathies. We report two unrelated individuals with monoallelic stop loss variants affecting the same codon of HNRNPA1. Two individuals with unsolved juvenile-onset myopathy were enrolled under approved institutional protocols. Phenotype data were collected and genetic analyses were performed, including whole-exome sequencing (WES). The two probands (MNOT002-01 and K1440-01) showed a similar onset of slowly progressive extremity and facial weakness in early adolescence. K1440-01 presented with facial weakness, winged scapula, elevated serum creatine kinase (CK) levels, and mild neck weakness. MNOT002-01 also exhibited elevated CK levels along with facial weakness, cardiomyopathy, respiratory dysfunction, pectus excavatum, a mildly rigid spine, and loss of ambulation. On quadriceps muscle biopsy, K1440-01 displayed rounded myofibers, mild variation in fiber diameter, and type 2 fiber hypertrophy, while MNOT002-01 displayed rimmed vacuoles. Monoallelic stop-loss variants in HNRNPA1 were identified for both probands: c.1119A>C p.*373Tyrext*6 (K1440-01) and c.1118A>C p.*373Serext*6 (MNOT002-01) affect the same codon and are both predicted to lead to the addition of six amino acids before termination at an alternative stop codon. Both stop-loss variants in our probands are likely pathogenic. Our findings contribute to the disease characterization of pathogenic variants in HNRNPA1. This gene should be screened in clinical diagnostic testing of unsolved cases of sporadic or dominant juvenile-onset myopathy.

Benefits of Early Versus Late Initiation of Intravenous Immunoglobulin in the Treatment of Patients With Anti-3-Hydroxy-3-Methylglutaryl-Coenzyme A Reductase Immune-Mediated Necrotizing Myopathy.

No clinical trials have been conducted to establish optimal and effective treatment in patients with immune-mediated necrotizing myopathy (IMNM), which can have a refractory course with increased morbidity from permanent muscle damage, especially in patients who experience delay in diagnosis and treatment. A subset of autoimmune necrotizing myopathy is associated with antibodies against 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR). Treatment involves withdrawing statins and using a combination of immunosuppressant and immunomodulatory treatment. Our study aims to provide longitudinally collected data on outcomes of early versus late initiation of intravenous Ig (IVIG) using our myositis center cohort of patients with anti-HMGCR IMNM. We conducted a retrospective chart review of 31 adult patients of the Oregon Health and Science University Myositis Center who were diagnosed with anti-HMGCR IMNM from September 2016 through October 2022 and reviewed physical examination, serologic laboratory data, and their treatment including prednisone reception as well as treatment response at 0 (the evaluation immediately before IVIG initiation), 3, 6, and 12 months on treatment. We divided this cohort into those who received IVIG at or before six months after receiving the diagnosis of anti-HMGCR IMNM and refer this as the cohort with nondelayed treatment, and those who received IVIG after six months following their diagnosis, which we referred to as the cohort with delayed treatment. Diagnosis of anti-HMGCR IMNM was defined as per the 2016 European Neuromuscular Centre criteria as having all three of elevated serum creatine kinase (CK), proximal muscle weakness, and anti-HMGCR antibodies. We evaluated the response to treatment by using a limited total improvement score (TIS) as per 2016 American College of Rheumatology/EULAR myositis response criteria. Among the 31 total patients, 19 were included within the cohort with nondelayed treatment, and 12 within the cohort with delayed treatment. The two cohorts had a comparable amount of time between the onset of symptoms and diagnosis; however, the cohort with delayed treatment had a significantly longer time between diagnosis and IVIG treatment (P < 0.001). At disease onset, cohorts had a comparable serum CK (P > 0.999), but patients with delayed treatment had an expected lower serum CK (P = 0.016) at the 0-month time point. At the 0-month time point, nine of the patients with nondelayed treatment (47%) required the use of a walker or wheelchair, whereas eight of the cohort with delayed treatment (66%) did. Patients who received nondelayed treatment demonstrated significant improvement in manual muscle testing 8 at the 12-month intervals (P < 0.001). Average serum CK values of all patients measured at the 3, 6, and 12 months did not significantly differ between the groups with nondelayed and delayed treatment. TIS improved more in the group with nondelayed treatment than in the group with delayed treatment (P = 0.002 at 3 months, P = 0.019 at 6 months, and P = 0.001 at 12 months). Seven patients in the group with delayed treatment had permanent residual muscle weakness requiring walker or wheelchair use at 12 months, whereas none of the patients in the group with nondelayed treatment did. Though our results have limitations, they contribute to a growing body of evidence that suggests that IVIG may prove to be a valuable addition to an early and aggressive induction regimen in patients afflicted by anti-HMGCRIMNM, particularly those with moderate to severe weakness requiring the use of a wheelchair or walking aids. Delay in IVIG treatment may lead to the development of permanent residual weakness and long-term disability.

High-risk screening for late-onset Pompe disease in China: An expanded multicenter study.

Late-onset Pompe disease (LOPD) is caused by a genetic deficiency of the lysosomal enzyme acid alpha-glucosidase (GAA), leading to progressive limb-girdle weakness and respiratory impairment. The insidious onset of non-specific early symptoms often prohibits timely diagnosis. This study aimed to validate the high-risk screening criteria for LOPD in the Chinese population. A total of 726 patients were included, including 96 patients under 14 years of age. Dried blood spots (DBS) and tandem mass spectrometry (MS/MS) were employed to evaluate serum GAA activity. Forty-four patients exhibited a decreased GAA activity, 16 (2.2%) of which were confirmed as LOPD by genetic testing. Three previously unreported GAA mutations were also identified. The median diagnostic delay was shortened to 3 years, which excelled the previous retrospective studies. At diagnosis, most patients exhibited impaired respiratory function and/or limb-girdle weakness. Elevated serum creatine kinase (CK) levels were more frequently observed in patients who manifested before age 16. Overall, high-risk screening is a feasible and efficient method to identify LOPD patients at an early stage. Patients over 1 year of age with either weakness in axial and/or proximal limb muscles, or unexplained respiratory distress shall be subject to GAA enzymatic test, while CK levels above 2 times the upper normal limit shall be an additional criterion for patients under 16. This modified high-risk screening criteria for LOPD requires further validation in larger Chinese cohorts.

‘Escápula voadora’ em bovino – relato de caso

The objective of this report was to describe the clinical and laboratory findings in an eight-month-old Holstein crossbred cow diagnosed with flying scapula. During anamnesis, the owner informed that the cow was placed in a pasture with other animals of different age groups. Three days after the environment change, he noticed the animal showed abnormal position of the scapulae, reduced appetite, and apathy. He suspected another animal had tried to mount it. The owner also reported it had never happened on his property. Clinical examination revealed difficulty in getting up and reluctance to move. The scapulae seemed to be loose (flying scapula) in a level above the thoracic vertebrae, with noticeable deepening of the rib cage between the front limbs. Laboratory tests showed hypoproteinaemia (5.2 g/dL), selenium values below normal (0.0094 μmol/L), elevated serum creatine kinase (CK) activity (898 U/L), and normal vitamin E levels (7.8 μg/ml) for the species. These findings confirm the diagnosis of flying scapula, having as a triggering factor the trauma associated with selenium deficiency.

Expert panel curation of 31 genes in relation to limb girdle muscular dystrophy.

Limb girdle muscular dystrophies (LGMDs) are a group of genetically heterogeneous autosomal conditions with some degree of phenotypic homogeneity. LGMD is defined as having onset >2 years of age with progressive proximal weakness, elevated serum creatine kinase levels and dystrophic features on muscle biopsy. Advances in massively parallel sequencing have led to a surge in genes linked to LGMD. The ClinGen Muscular Dystrophies and Myopathies gene curation expert panel (MDM GCEP, formerly Limb Girdle Muscular Dystrophy GCEP) convened to evaluate the strength of evidence supporting gene-disease relationships (GDR) using the ClinGen gene-disease clinical validity framework to evaluate 31 genes implicated in LGMD. The GDR was exclusively LGMD for 17 genes, whereas an additional 14 genes were related to a broader phenotype encompassing congenital weakness. Four genes (CAPN3, COL6A1, COL6A2, and COL6A3) were split into two separate disease entities, based on each displaying both dominant and recessive inheritance patterns, resulting in curation of 35 GDRs. Of these, 30 (86%) were classified as definitive, 4 (11%) as moderate, and 1 (3%) as limited. Two genes, POMGNT1 and DAG1, though definitively related to myopathy, currently have insufficient evidence to support a relationship specifically with LGMD. The expert-reviewed assertions on the clinical validity of genes implicated in LGMDs form an invaluable resource for clinicians and molecular geneticists. We encourage the global neuromuscular community to publish case-level data that help clarify disputed or novel LGMD associations.

Chamomile Extract Reduces Cardiac Toxicity in Female Mice with Ehrlich Solid Carcinoma.

Cancer is the most serious disorder that may affect a person and is also the leading cause of mortality. Worldwide, breast cancer continues to be the leading cause of cancer-related deaths in women. The popularity of treating diseases using alternative and complementary medicines has increased in recent decades; many of these are derived from plants. Chamomile has a beneficial effect in treating many diseases, there for the purpose of this work is to study how chamomile protect against cardiac damage and toxicity brought on by Ehrlich solid tumor (EST) in adult female mice. 40 female mice were distributed in 4 groups (control, chamomile, EST, EST+chamomile). The research results indicated that EST caused significant alterations in cardiac function and structure. EST induced a significant elevation in serum creatine kinase (CK), creatine kinase MB (CK-MB), lactate dehydrogenase (LDH), alkaline phosphatase (ALP), and myoglobin (MB), potassium, chloride ions, cholesterol, triglycerides, low-density lipoprotein (LDL), cardiac tissue damage, apoptotic P53 and Caspase 3 expressions while levels of sodium ions and high-density lipoprotein (HDL) were significantly decreased. Treatments of EST with chamomile improved the biochemical, histopathological, and Immunohistochemical alterations. This suggests that chamomile may be useful as an adjuvant for the treatment and prevention of cardiac toxicity.

Acute Kidney Injury in Hospitalized Patients With Exertional Rhabdomyolysis

An association between serum creatine kinase (CK) levels and the risk of kidney failure in patients with exertional rhabdomyolysis (ERM) has been suggested. However, the actual incidence of AKI in hospitalized patients with ERM along with the contributing cofactors that may increase the risk of AKI have rarely been investigated. To examine the incidence of kidney injury in hospitalized patients with ERM and to identify additional cofactors that might contribute to the development of kidney injury in patients with ERM. This retrospective cohort study was conducted in a diverse community population of patients 18 years or older with ERM who were hospitalized across Kaiser Permanente Northern California between January 1, 2009, and December 31, 2019. Patients were initially identified through electronic screening for all-cause rhabdomyolysis admissions, followed by manual medical record reviews to verify their eligibility for the study. The diagnosis of AKI and chronic kidney disease (CKD) was determined using KDIGO (Kidney Disease Improving Global Outcomes) criteria and confirmed by medical record review. Data analysis was performed from October 1, 2023, to January 31, 2024. History of strenuous physical exercise before hospitalization for ERM. Development of AKI, CKD, and compartment syndrome and number of deaths. Among 3790 patients hospitalized for rhabdomyolysis between 2009 and 2019 in Kaiser Permanente Northern California, 200 (mean [SD] age, 30.5 [8.5] years; 145 [72.5%] male) were confirmed to have ERM via medical record review. Seventeen patients (8.5%) developed AKI, none developed CKD, 1 (0.5%) developed compartment syndrome, and there were no fatalities. There was no association between serum CK levels and the risk of AKI. However, the risk of AKI was significantly higher in patients with ERM who used nonsteroidal anti-inflammatory drugs (NSAIDs) before admission (11 of 17 with AKI [64.7%] vs 40 of 183 without AKI [21.9%], P < .001) or experienced dehydration (9 of 183 without AKI [52.9%] vs 9 of 17 with AKI [4.9%], P < .001). This analysis suggests that eliminating preadmission NSAID use and dehydration could reduce the risk of potential AKI in patients with ERM by 92.6% (95% CI, 85.7%-96.1%) in this population. The findings of this cohort study of hospitalized patients with ERM suggest that serum CK elevation alone is insufficient as an indicator of AKI in patients with ERM. Concurrent risk factors, such as NSAID use or dehydration, may be associated with AKI development in patients with ERM.

Feasibility of aligning creatine kinase MB activity and mass data in multicentre trials using generalized additive modelling.

Elevated serum creatine kinase isoenzyme MB (CK-MB) levels indicate myocardial ischaemia and periprocedural myocardial injury during treatment of heart diseases. We established a method to predict CK-MB mass from activity data based on a prospective pilot study in order to simplify multicentre trials. 38 elective cardiac surgery patients without acute myocardial ischaemia and terminal renal failure were recruited. CK-MB mass and activity were determined in venous blood samples drawn preoperatively, postoperatively, 6 h post-op, and 12 h post-op. Linear regression and generalized additive models (GAMs) were applied to describe the relationship of mass and activity. Influences of demographic and perioperative factors on the fit of GAMs was evaluated. The agreement of predicted and measured CK-MB masses was assessed by Bland-Altman analyses. Linear regression provided an acceptable overall fit (r2 = 0.834) but showed deviances at low CK-MB levels. GAMs did not benefit from the inclusion of age, body mass index and surgical times. The minimal adequate model predicted CK-MB masses from activities, sex and sampling time with an r2 of 0.981. Bland-Altman analyses confirmed narrow limits of agreement (spread: 8.87 µg/l) and the absence of fixed (P = 0.41) and proportional (P = 0.21) biases. GAM-based modelling of CK-MB data in a representative patient cohort allowed to predict CK-MB masses from activities, sex and sampling time. This approach simplifies the integration of study centres with incompatible CK-MB data into multicentre trials in order to facilitate inclusion of CK-MB levels in statistical models.

A case control study of the relationship between persistent serum creatine kinase elevation and polyneuropathy

Creatine kinase (CK) has been associated with neuropathy, but the mechanisms are uncertain. We hypothesized that peripheral nerve function is impaired in subjects with persistent CK elevation (hyperCKemia) compared to age- and sex matched controls in a general population. The participants were recruited from the population based Tromsø study in Norway. Neuropathy impairment score (NIS), nerve conduction studies (NCS) and electromyography (EMG) in subjects with persistent hyperCKemia (n = 113; 51 men, 62 women) and controls (n = 128; 61 men, 67 women) were performed. The hyperCKemia group had higher NIS score than the controls (p = 0.050). NCS of the tibial nerve showed decreased compound motor action potential amplitude (p < 0.001), decreased motor conduction velocity (p < 0.001) and increased F-wave latency (p = 0.044). Also, reduced sensory amplitudes of the median, ulnar, and sural nerves were found. EMG showed significantly increased average motor unit potential amplitude in all examined muscles. CK correlated positively with glycated hemoglobin and non-fasting glucose in the hyperCKemia group, although not when controlled for covariates. The length dependent polyneuropathy demonstrated in the hyperCKemia group is unexplained, but CK leakage and involvement of glucose metabolism are speculated on.

Pregabalin-induced rhabdomyolysis: a case series and literature analysis.

Pregabalin is a prescription medicine that has recently been approved for individuals who suffer from fibromyalgia, neuropathic pain, anxiety disorder, or epilepsy. Pregabalin has the side effects of dizziness, sleepiness, and angioedema. Pregabalin-induced rhabdomyolysis has been rarely reported, with only four reports to date. We report two cases of rhabdomyolysis after pregabalin treatment. A man aged older than 90 years presented with exhaustion, muscle aches, and a high serum creatine kinase concentration after taking 75 mg of pregabalin on the first day of treatment. A woman in her 90s with long-term use of pregabalin presented with considerably elevated serum creatine kinase concentrations. Both patients had a long history of taking statins. Pregabalin therapy was stopped, high-volume intravenous fluids were administered, and serum electrolytes were frequently checked. Alkalinisation was performed with excellent outcomes. The Naranjo Adverse Drug Reaction scale and previous research suggest an association between pregabalin and rhabdomyolysis. Clinicians should be alert to the possibility of rhabdomyolysis occurring with the use of pregabalin, especially when taking statins.