Serum Creatine Kinase Levels Research Articles

A Case of Non-Progressive Congenital Myopathy: Efficacy and Clinical Outcomes of The Wharton's Jelly Derived Mesenchymal Stem Cell Transplantation

Non-Progressive Congenital Myopathy is a disease characterized by muscle weakness, and unfortunately, there is no conventional treatment. In the last decade, regenerative medicine practices have become a rising value, and Mesenchymal Stem Cells (MSCs) have fascinating outcomes in regenerative medicine with their high regenerative capacities, their ability to regulate with paracrine secretions, and their immunological properties. Based on our experience in our previous clinical studies, Wharton's-Jelly-derived (WJ-)MSCs are the most suitable source for muscle diseases among all MSC sources. In this study, we evaluated the outcomes of 10 doses of WJ-MSC transplantation to the patient diagnosed with Non-Progressive Congenital Myopathy. A 17-year-old female with a SPEN-1 mutation, Non-Progressive Congenital Myopathy patient received 10 times as 1×10⁶/kg in the intra-arterial, intramuscular and intravenous administration of allogenic WJ-MSC. Before and after the treatment, the patient was followed-up with the upper extremity scale, Vignos lower extremity scale, muscle strength scale, functional independence measure, and evaluation of Serum creatine kinase (CK) levels. Improvement in both upper extremity scale and Vignos lower extremity scales, increasing in muscle strength, and decreasing in CK-level were detected. Although transplantation of WJ-MSC cannot treat any genetic-based diseases, they may benefit in alleviating clinical outcomes of disease. More importantly, WJ-MSC transplantation may offer a better quality of life by alleviating the symptoms of this rare disease with no treatment option that can be provided in conventional methods.

Genetic deletion of IL-6 increases CK-MB, a classic cardiac damage marker, and decreases UPRmt genes after exhaustive exercise.

The intensity, duration, type of contraction, and muscle damage influence interleukin-6 (IL-6) response to acute exercise. However, in response to an exhaustive exercise session, the upregulation of IL-6 in the serum and heart is associated with an inflammatory condition and can inhibit autophagy. This study aimed to investigate the role of IL-6 in autophagy pathway responses and mitochondrial function in the heart of mice submitted to acute exhaustive physical exercise. The mice were allocated into three groups, five animals per group, for the wild type (WT) and the IL-6 knockout (IL-6 KO): Basal (sedentary; Basal), 1 h (after 1 h of the acute exercise; 1 h), and 3 h (after 3 h of the acute exercise; 3 h). After the specific time for each group, the blood was collected, each mouse heart was removed, and the left ventricle (LV) was isolated. In summary, under basal conditions, without the influence of the acute exercise, the IL-6 KO group showed lower number of nuclei in the cardiac tissue, but higher collagen deposition; lower messenger RNA(mRNA) levels of Prkaa1 and Mtco1, but higher mRNA levels of Ulk1; and higher protein levels of the ratio p-AMPK/AMPK in the heart when compared to WT at the same time point. After the acute exercise (1and 3 h), the IL-6 KO group had lower mRNA levels of Tfam, Mtnd1, Mtco1, and Nampt in the heart when compared to WT after exercise; higher serum levels of creatine kinase(CK), CK-MB, and lactate dehydrogenase for the IL-6 group when compared to the WT group after the exercise. Specifically, the heat-shock protein 60protein levels in the heart increased 3 h after exhaustive exercise in the WT group, but not in the IL-6 KO group. The study emphasizes that IL-6 may offer cardioprotective effects, including mitochondrial adaptations in response to acute exhaustive exercise.

Rhabdomyolysis

Rhabdomyolysis is a condition that results from the breakdown of skeletal muscle. The etiologies can be broken down into three main categories of causes: traumatic, atraumatic exertional, and atraumatic nonexertional. Patients with rhabdomyolysis often present with myalgia and are found to have myoglobinuria with elevations in serum creatine kinase levels. The mainstay in therapy is focused on restoration of intravascular volume with large-volume fluid resuscitation using isotonic fluids. Adequate hydration is necessary to prevent the potential complications of rhabdomyolysis, including the development of acute kidney injury. Practitioners should maintain a high level of suspicion of compartment syndrome in patients with rhabdomyolysis. If extremity compartment syndrome is diagnosed, prompt decompressive fasciotomies should be performed to preserve muscle and nerve viability. The early use of renal replacement therapy in patients with rhabdomyolysis has been described in the literature and may represent another modality of therapy to prevent the adverse sequelae of rhabdomyolysis. This review contains 8 tables and 42 references Keywords: acute kidney injury, compartment syndrome, creatine kinase, disseminated intravascular coagulation, rhabdomyolysis

Rhabdomyolysis in Young Adult Male Stabilized on Mirtazapine and with History of COVID-19 Infection

The purpose of this case study is to review the clinical presentation and medical workup of a young adult male presenting with rhabdomyolysis in the setting of suspected contributing factors, including treatment with mirtazapine and history of COVID-19 infection. This case study involves a 19-year-old male in a residential setting with a psychiatric history of major depressive disorder and post-traumatic stress disorder who had been stabilized on mirtazapine for 9months. Then, the patient exhibited fever, sore throat, cough, nausea, diarrhea, and malaise and was diagnosed with COVID-19 infection; he did not require hospitalization, was treated with supportive care, and signs and symptoms resolved uneventfully. Approximately 2months later, in the winter, the patient presented for clinical assessment due to hematuria and painful urination. History revealed that he had been exercising excessively exercising over the past 24hours, completing hundreds of push-ups and sit-ups. The patient presented to a nearby community hospital and was found to have creatine kinase of over 500,000. He was transferred to a large Midwestern university hospital for further evaluation and management. The patient's serum creatine kinase level was found to be 510,000 U/L. Patient's ALT, AST, and alkaline phosphatase were 283, 79, and 76 IU/L, respectively, while creatinine was 0.92. Patient received vigorous hydration, supportive care, and further evaluation. Treatment with mirtazapine was discontinued. The following week he developed severe nausea and vomiting; creatine kinase had decreased to 920, while hepatic function tests remained mildly elevated. Evaluation for hepatitis, cytomegalovirus, and Epstein-Barr virus were negative, as was Wilson's disease and hemochromatosis. Further medical workup for other potential causes of rhabdomyolysis was negative. The patient recovered and is asymptomatic with return to normal lab values. He remains in psychiatric follow-up. The patient's presentation of rhabdomyolysis may have been attributable to multiple factors. Independently, sustained excessive physical activity, COVID-19 infection, and treatment with mirtazapine have all been implicated in the development of rhabdomyolysis. Caution should be taken when prescribing mirtazapine in individuals at higher risk of developing rhabdomyolysis, including those engaged in excessive exercise or who have had COVID-19 infection. No funding.

Transplantation of umbilical cord blood-derived mesenchymal stem cells as therapy for adriamycin induced-cardiomyopathy

ABSTRACT Umbilical cord blood-derived mesenchymal stem cells (UCBMSCs) have been reported to possess cardioprotective effects in diseases. However, its effects on cardiomyopathy remain unclear. This study aimed to the therapeutic effects of UCBMSC transplantation on adriamycin (ADR)-induced cardiomyopathy. UCBMSCs isolated from human UCB were identified by detecting surface markers (CD29, CD90, CD34, and CD45) using flow cytometry. The effect of UCBMSCs on left ventricular end-diastolic dimension (LVEDD), left ventricular systolic end-diastolic diameter (LVESD), left ventricular ejection fraction (LVEF), and left ventricular fraction shortening (LVFS) were determined by echocardiography. Histological changes were observed by HE and Masson staining. The serum levels of collagen-I (Col-I), brain natriuretic peptide (BNP), aspartate aminotransferase (AST), lactate dehydrogenase (LDH), creatine kinase (CK), CK-MB, interleukin (IL)-6, IL-10, and tumor necrosis factor alpha (TNF-α) were measured by corresponding kits. The protein levels of IL-6, IL-10, and TNF-α were measured by Western blotting. The isolated UCBMSCs manifested the positive expression of CD29 and CD90, and the negative expression of CD34 and CD45. UCBMSC transplantation significantly reduced LVEDD and LVESD, and increased LVEF and LVFS in ADR-induced cardiomyopathy model rats. Cardiac injury and high collagen deposition in model rats were alleviated by UCBMSC treatment. Moreover, UCBMSCs decreased the serum levels of Col-I, BNP, AST, LDH, CK, CK-MB, IL-6, IL-10, and TNF-α in model rats. Overall, UCBMSCs exert the therapeutic effects on ADR-induced cardiomyopathy through recovering the myocadiac function and alleviating the inflammatory response.

Investigation of the Clinical Laboratory Indexes in COVID-19 Patients with Ocular Symptoms in Iran: A Single-Center Experience

Objectives: Ocular symptoms are prevalent in coronavirus infectious disease 2019 (COVID-19) patients, which may be related to clinical/paraclinical conditions. This study investigated the association between laboratory indexes and ocular symptoms in COVID-19 patients. Methods: In this cross-sectional study, 108 polymerase chain reaction (PCR)-confirmed COVID-19 patients admitted to the Rouhani Hospital, Babol, Iran, were enrolled. Ocular symptoms were investigated using standard ophthalmologic examinations. Routine laboratory investigation was done according to the standard management in patients with COVID-19 infection. Results: The erythrocyte sedimentation rate (ESR) and the serum levels of the blood urea nitrogen (BUN) and creatinine (Cr) were significantly higher in COVID-19 patients with ocular discharge and exudate (P = 0.002, 0.045, 0.046, and 0.027, respectively), while the red blood cell (RBC) and albumin were lower in COVID-19 patients with ocular discharge and exudate (P = 0.029 and 0.027, respectively). The serum levels of creatine kinase (CPK) and iron (Fe) were significantly higher in non-photophobic COVID-19 patients than in photophobic patients (P =0.033 and 0.050, respectively). In contrast, the serum level of procalcitonin was lower than photophobic COVID-19 patients (P = 0.024). The serum level of phosphorus (P) was significantly higher in COVID-19 patients with itchy eyes compared to COVID-19 patients without itchy eyes (P = 0.026). Conclusions: The footprint of laboratory indexes was demonstrated in ocular symptoms of COVID-19 patients. The kidney biomarkers were correlated with ocular discharge and exudate, and electrolytes were associated with tear-related symptoms.

Novel SEPN1 Mutations in Exon 1 Are Common in Rigid Spine With Muscular Dystrophy Type 1 in Chinese Patients.

Congenital muscular dystrophy with early rigid spine, also known as the rigid spine with muscular dystrophy type 1 (RSMD1), is caused by SEPN1 mutation. We investigated the clinical manifestations, pathological features, and genetic characteristics of 8 Chinese RSMD1 patients in order to improve diagnosis and management of the disease. Eight patients presented with delayed motor development, muscle weakness, hypotonia, and a myopathic face with high palatine arches. All patients could walk independently, though with poor running and jumping, and most had a rigid spine, lordosis, or scoliosis. The symptoms of respiratory involvement were present early, and upper respiratory tract infections and pneumonia often occurred. Five patients had severe pneumonia, pulmonary hypertension, and respiratory failure. Lung function tests showed variable restrictive ventilation dysfunction. Polysomnography suggested hypoxia and hypoventilation. The serum creatine kinase (CK) level was normal or mildly increased. Muscle biopsy indicated chronic myopathic changes and minicores. Muscle magnetic resonance imaging (MRI) showed diffuse fatty infiltration of the gluteus maximus and thigh muscle. SEPN1 gene analysis revealed 16 compound heterozygous variants, 81.3% of which are unreported, including 7 exon 1 variants. Our study expands the spectrum of clinical and genetic findings in RSMD1 to improve diagnosis, management, and standards of care. SEPN1 mutations in exon 1 are common and easily missed, and exon 1 should be carefully analyzed when RSMD1 is suspected, which will provide valuable genetic counseling for the family and useful information for future natural history studies and clinical trials.

Caveolin-3 and Arrhythmias: Insights into the Molecular Mechanisms.

Caveolin-3 is a muscle-specific protein on the membrane of myocytes correlated with a variety of cardiovascular diseases. It is now clear that the caveolin-3 plays a critical role in the cardiovascular system and a significant role in cardiac protective signaling. Mutations in the gene encoding caveolin-3 cause a broad spectrum of clinical phenotypes, ranging from persistent elevations in the serum levels of creatine kinase in asymptomatic humans to cardiomyopathy. The influence of Caveolin-3(CAV-3) mutations on current density parallels the effect on channel trafficking. For example, mutations in the CAV-3 gene promote ventricular arrhythmogenesis in long QT syndrome 9 by a combined decrease in the loss of the inward rectifier current (IK1) and gain of the late sodium current (INa-L). The functional significance of the caveolin-3 has proved that caveolin-3 overexpression or knockdown contributes to the occurrence and development of arrhythmias. Caveolin-3 overexpression could lead to reduced diastolic spontaneous Ca2+ waves, thus leading to the abnormal L-Type calcium channel current-induced ventricular arrhythmias. Moreover, CAV-3 knockdown resulted in a shift to more negative values in the hyperpolarization-activated cyclic nucleotide channel 4 current (IHCN4) activation curve and a significant decrease in IHCN4 whole-cell current density. Recent evidence indicates that caveolin-3 plays a significant role in adipose tissue and is related to obesity development. The role of caveolin-3 in glucose homeostasis has attracted increasing attention. This review highlights the underlining mechanisms of caveolin-3 in arrhythmia. Progress in this field may contribute to novel therapeutic approaches for patients prone to developing arrhythmia.

Creatine Kinase Is Associated With Recurrent Stroke and Functional Outcomes of Ischemic Stroke or Transient Ischemic Attack.

BackgroundMany patients after stroke are found to have elevated serum creatine kinase (CK). This study aimed to investigate the associations between serum CK levels and clinical outcomes in patients with acute ischemic stroke or transient ischemic attack.Methods and ResultsThe study included 8910 patients with acute ischemic stroke or transient ischemic attack from the CNSR‐III (Third China National Stroke Registry). Baseline serum CK levels after admission were measured. The associations between CK and clinical outcomes (stroke recurrence, death, and disability, defined as modified Rankin scale score 3–6 or 2–6) were analyzed. Patients with elevated CK levels had higher risks of recurrent stroke (hazard ratio [HR], 1.53; 95% CI, 1.21–1.93), death (HR, 1.68; 95% CI, 1.10–2.58), and disability (modified Rankin scale score, 3–6; odds ratio, 1.57; 95% CI, 1.29–1.90) at 3 months after adjusting confounding factors. Similar results were found at 1 year. The effects of CK on death and disability were more significant in male patients than female patients (P value for interaction <0.05). Elevated CK‐MB levels were not associated with clinical outcomes in this study.ConclusionsElevated serum CK after ischemic stroke or transient ischemic attack is associated with higher risks of recurrent stroke, death, and disability at 3 months and 1 year. Serum CK may act as a useful predictor for recurrent stroke and poor functional outcomes in patients with acute ischemic stroke or transient ischemic attack. Sex modifies the relationship between elevated CK and disability or death.

Clinical implications and current perspectives of statin-induced rhabdomyolysis syndrome – case presentation

Abstract Though rare, statins can produce serious adverse effects with clinical implications that urge prompt intervention. However, in high-risk patients that require intense hypolipemiant treatment, such situations can be challenging and require complimentary therapies. We report the case of a 82-year-old hypertensive female patient admitted for diffuse myalgia, mainly in the lower limbs, fatigue and shortness of breath. The patient is known with a recent myocardial infarction (MI) treated by primary stent implantation. The electrocardiogram and transthoracic echocardiography confirmed the recent MI, with non-dilated left ventricle mildly reduced ejection fraction. Initial laboratory studies revealed elevated NT-proBNP, moderate renal impairment and increased serum levels of creatine kinase (CK), CK-MB fraction and transaminases. After stopping statin and receiving supportive treatment, the patient's paraclinical test results and symptoms improved: CK levels and transaminase dropped significantly and both myalgia and general fatigue resolved mostly within 4 days. PCSK9 inhibitor has been introduced with favourable results at follow-ups. Even though statins are effective and safe, they may still generate potential dangerous adverse effects in rare cases. Statin dose adjustment or replacement and adding other lipid lowering therapies represent current therapeutical options, especially in high-risk populations.

EP380: Sequencing of entire 2.2 MB DMD gene facilitates diagnostic testing and aids selection of patients for therapeutic intervention

Duchenne Muscular Dystrophy (DMD) is an X-linked inherited neuromuscular disorder caused by pathogenic variants in the DMD gene. The variant spectrum of DMD is unique including 60% intragenic deletions, 5% duplications and 35% sequence variants. The clinical presentation of DMD includes progressive weakness of the skeletal muscles that leads to loss of ambulation by age 10-12 years. Affected individuals also have significantly elevated creatine kinase (CK) levels in blood. Present mean age of diagnosis of DMD is about 5 years; however, it can be diagnosed as early as immediately after birth through newborn screening (NBS) by measuring serum CK levels followed by confirmatory molecular testing.

Remote ischemic postconditioning protects against crush-induced acute kidney injury via down-regulation of apoptosis and senescence

BackgroundAcute renal failure due to crush syndrome is one of the leading causes of death in disasters. Ischemic Postconditioning (IPC) is a potentially effective strategy to protect against ischemic reperfusion injury, but a few studies noted its protective effect in crush induced acute kidney injury (AKI). Hence, this study investigated the optimal IPC strategy to prevent crush induced AKI and reveal related cellular mechanisms. MethodsThe right lower extremities of rabbits were constantly compressed for 8 h and then performed five cycles of clamping and releasing the femoral artery and vein before depression using a clip. In terms of the duration of clamping and releasing, the animals were randomly divided into 5 groups, Control, IPC-5sec, IPC-30sec, IPC-1min, and IPC-5min groups; 6 rabbits for each group. Biomarkers of inflammation, renal function, renal tubular injury, and muscular injury, apoptosis, and cellular senescence in kidney were detected. ResultsSix hours after decompression, the levels of Serum Creatine (SCr), Blood Urea Nitrogen (BUN), K+, and Interleukin-6 (IL-6) in IPC-1min and IPC-5min groups were lower than Control, with a statistically significant difference. The morphological study of Periodic Acid-Schiff (PAS) staining demonstrated that 6 h after decompression, IPC-1min can attenuate renal tubular damage renal tubule. Meanwhile, the level of Neutrophil Gelatinase-Associated Lipocalin (NGAL) in circulation in the IPC-30sec, IPC-1min, and IPC-5min groups was significantly decreased compared with the Control group, 2 h after decompression. On the other hand, the levels of serum Creatine Kinase (CK) and Myoglobin (Mb), and the morphological change of muscular damage detected by hematoxylin and eosin (H&E) staining in IPC-1min-treated group were significantly lower than Control group 6 hours after decompression. Further results of the cellular mechanism showed that the apoptotic markers of Terminal deoxynucleotidyl Transferase-mediated dUTP Nick End Labeling (TUNEL) and Caspase3 and the cell senescent markers of senescence-associated β-galactosidase (SA-β-Gal) and nuclear LAMNB1 have changed significantly in the IPC-1min group, compared with the control group. ConclusionsPerforming 5 cycles of 1-min IPC would be a convenient, time-saving, and effective method to prevent crush-induced AKI by attenuating the release of nephrotoxic substances after decompression and downregulation of the expression of apoptosis and cellular senescence biomarkers.

Anti-Fatigue and Exercise Performance Improvement Effect of Glossogyne tenuifolia Extract in Mice.

Glossogyne tenuifolia (GT) is a native perennial plant growing across the coastline areas in Taiwan. The current study aimed to examine the efficacy of GT extract in ameliorating physical fatigue during exercise and increasing exercise performance. Fifty male Institute of Cancer Research (ICR) mice were randomly segregated into five groups (n = 10) to GT extract orally for 4 weeks, at different concentrations (50, 100, 250, and 500 mg/kg BW/day): LGT 1X, MGT 2X, HGT 5X, and HGT 10X groups. Forelimb grip strength, endurance swimming time, serum biochemical marker levels, blood lipid profile and histological analysis of various organs were performed to assess the anti-fatigue effect and exercise performance of GT extract. The forelimb-grips strength and endurance-swimming time of GT-administered mice were increased significantly in a dose-dependent manner when compared to the control. Serum glucose, creatine kinase, and lactate levels were increased significantly in the HGT 10X group. Liver marker serum glutamic-oxaloacetic transaminase (GOT) was increased in the HGT 5X and HGT 10X groups, whereas Serum Glutamic Pyruvic Transaminase (GPT) was not altered. Renal markers, creatinine and uric acid levels, were not altered. Muscle and hepatic glycogen levels, which are essential for energy sources during exercise, were also significantly increased in a dose-dependent manner in all GT extract groups. No visible histological aberrations were observed in the vital organs after GT extract administration. The supplementation with GT extract could have beneficial effects on exercise performance and anti-fatigue function without toxicity at a higher dose.

Involvement of Abnormal Gut Microbiota Composition and Function in Doxorubicin-Induced Cardiotoxicity

ObjectivesDoxorubicin (Dox), a chemotherapeutic anthracycline agent for the treatment of a variety of malignancies, has a limitation in clinical application for dose-dependent cardiotoxicity. The purpose of this study was to explore the relationship between the composition/function of the gut microbiota and Dox-induced cardiotoxicity (DIC).MethodsC57BL/6J mice were injected intraperitoneally with 15 mg/kg of Dox, with or without antibiotics (Abs) administration. The M-mode echocardiograms were performed to assess cardiac function. The histopathological analysis was conducted by H&E staining and TUNEL kit assay. The serum levels of creatine kinase (CK), CK-MB (CK-MB), lactic dehydrogenase (LDH), and cardiac troponin T (cTnT) were analyzed by an automatic biochemical analyzer. 16S rRNA gene and metagenomic sequencing of fecal samples were used to explore the gut microbiota composition and function.Key FindingsDox caused left ventricular (LV) dilation and reduced LV contractility. The levels of cardiomyocyte apoptosis and myocardial enzymes were elevated in Dox-treated mice compared with the control (Con) group. 16S rRNA gene sequencing results revealed significant differences in microbial composition between the two groups. In the Dox group, the relative abundances of Allobaculum, Muribaculum, and Lachnoclostridium were significantly decreased, whereas Faecalibaculum, Dubosiella, and Lachnospiraceae were significantly increased compared with the Con group at the genus level. Functional enrichment with Cluster of orthologous groups of proteins (COG) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses showed that the Dox mice displayed different clusters of cellular processes and metabolism from the Con mice. The different species and their functions between the two groups were associated with the clinical factors of cardiac enzymes. Moreover, depletion of the gut microbiota could alleviate Dox-induced myocardial injury and cardiomyocyte apoptosis.ConclusionsThe study here shows that composition imbalance and functional changes of the gut microbiota can be one of the etiological mechanisms underlying DIC. The gut microbiota may serve as new targets for the treatment of cardiotoxicity and cardiovascular diseases.

Neuroleptic malignant-like syndrome associated multiple system atrophy: report on three cases

BackgroundMultiple system atrophy (MSA) associated with neuroleptic malignant-like syndrome (NMLS) is rare and few cases have been described in the literature.Case presentationIn the present study, three patients with MSA associated with NMLS were analyzed from January 2012 to January 2020 to characterize their clinical presentations. Data collected from the patients for analysis included general patient history, the fluctuation and severity of disease symptoms, the indicated therapies and disease progression at follow-up. All patients had histories of sudden withdrawal or reduction of levodopa prior to the onset of symptoms. Clinical presentations were characterized by hyperthermia, autonomic dysfunction, worsening of extrapyramidal symptoms, and elevated serum creatine kinase (CK) levels. During hospitalization, one patient rapidly progressed and died, while the other two patients were successfully treated.ConclusionsEarly diagnosis and treatment are very important for patient outcomes in NMLS. Notably, the correct dose and time of administration of dopaminergic medication may be key in treating NMLS.

Motor Vehicle Collision and Acute Kidney Injury in Children.

Our study aimed to determine the prevalence of acute kidney injury (AKI) in pediatric patients who sustained trauma due to motor vehicle collision (MVC) and identify factors associated with its development. We retrospectively reviewed the clinical information and laboratory tests of pediatric patients who were admitted because of MVC from January 2014 to April 2021. The occurrence of AKI was our primary outcome, which was defined by the Kidney Disease Improving Global Outcomes criteria. A serum creatine kinase (CK) level of 1000 IU/L or greater was defined as rhabdomyolysis. Sixty-four patients (median age, 9.6 years) were included in the study. Twenty three of the patients (35.9%) developed AKI: stage 1 AKI in 18 (78.3%) and stage 2 AKI in 5 (21.7%) patients. Acute kidney injury patients had higher injury severity scores (no AKI: 5.0; stage 1 AKI: 10.5; stage 2 AKI: 26.0). Rhabdomyolysis was present in 21.1% of the patients and was associated with the overall AKI risk (odds ratio [OR], 7.3; 95% confidence interval [CI], 1.6-32.6) and stage 2 AKI (OR, 15.0; 95% CI, 1.4-163.2). Blood tests from AKI patients showed lower serum bicarbonate and base excess, higher leukocyte and CK levels on admission, and a higher peak CK in the first 72 hours of admission. Intubation in emergency department (OR, 11.1; 95% CI, 1.2-102.1) and surgical interventions (OR, 3.2; 95% CI, 1.0-9.8) were associated with AKI. Acute kidney injury patients required longer stay in pediatric intensive care unit (median 1.0 vs 2.3 days, P < 0.001) and hospital (median 4.1 vs 7.0 days, P = 0.010). Approximately one third of pediatric patients who sustained trauma from MVC developed AKI. Initial blood results, including higher CK and leukocyte count, and lower bicarbonate and base excess, were associated with the development of AKI. Rhabdomyolysis occurred in approximately one fifth of the patients and was significantly associated with AKI.

Serum cytokine and chemokine profiles in patients with immune-mediated necrotizing myopathy

Immune-mediated necrotizing myopathy (IMNM) is a pathologically defined diagnosis of idiopathic inflammatory myopathies. Adequate studies on cytokines of IMNM is lacking. We measured serum levels of 27 cytokines/chemokines in 22 IMNM patients, 10 sporadic inclusion body myositis (IBM) patients, and 23 other neurological disorders (ONDs) patients. In IMNM patients, the correlations between clinical features and cytokine/chemokine levels, and changes in cytokine/chemokine levels after immunosuppressive therapy were examined. Compared with ONDs patients, IMNM patients had significantly increased serum levels of several cytokines. In particular, IP-10 and MIP-1α levels were prominently increased, decreased after immunosuppressive-therapy, and correlated with serum creatine kinase levels. IP-10 and MIP-1α could play important roles in the IMNM pathogenesis.

HP42: EMG is a potential biomarker for myositis in patients with antisynthetase syndrome without muscle symptoms

Anti-aminoacyl-tRNA synthetase (ARS) antibodies positive patients sometimes present interstitial lung disease (ILD) without muscle symptoms. We investigated needle electromyography (nEMG) to explore whether there are some myogenic changes or not in patients with antisynthetase syndrome without muscle symptoms. Method: We enrolled three patients who fulfilled anti ARS antibodies positive and ILD of the Connor's criteria for antisynthetase syndrome, and not fulfill the PM/DM criteria. We investigated the nEMG, and magnetic resonance imaging (MRI) of muscles to explore whether there are some myogenic changes or not. Serum creatine kinase (CK), manual muscle testing of 8 muscle groups (MMT8), Inclusion Body Myositis-Functional Rating Scale (IBM-FRS) were measured. This study was approved by the ethics committee of the Nara Medical University School of Medicine. Results: All subjects were females and their ages at the examination were 54 years old (P1), 44(P2) and 69(P3). P1 and P2 had already initiated oral steroid therapy. Although all three patients had no high serum CK level nor decline in IBM-FRS, nEMG revealed that abnormally short durations of the motor unit potential (MUP) patterns in the deltoid and biceps. P3 presented the same MUP pattern in vastus lateralis. MRI revealed inflammatory changes in P2 at left triceps and P3 at anterolateral femurs and posterolateral lower legs. Conclusion: nEMG is usually performed when patients exhibit muscle weakness, but this examination tool can be applicated to detect muscle damage in patients with anti-ARS antibody-associated ILD, prior to muscle weakness, myalgia, and declines in ADLs.

Preliminary exploration of detoxification mechanism of processing methods on cardiotoxicity induced by radix Tripterygium wilfordii in mice via Nrf2/HO-1 pathway

This study aims to investigate the detoxification effects of different processing methods on the cardiotoxicity induced by radix Tripterygium wilfordii, and preliminarily explore the detoxification mechanism via the nuclear factor E2-related factor 2(Nrf2)/heme oxygenase 1(HO-1) pathway. The raw and processed products [stir-fried product, product stir-fried with Lysimachiae Herba(JQC), product stir-fried with Phaseoli Radiati Semen(LD), product stir-fried with Paeoniae Radix Alba(BS), product stir-fried with Glycyrrhizae Radix et Rhizoma(GC), and product stir-fried with vinegar(CZ)] of radix T. wilfordii were administrated to mice by gavage at a dose of 2 g·kg~(-1)(based on crude drugs) for 28 days. Twenty-four hours after the last administration, we measured the serum biochemical indexes of mice to evaluate the detoxification effect. Furthermore, we determined the expression of key proteins of Nrf2/HO-1 pathway in mouse heart tissue by Western blot and some oxidation/antioxidation-related indexes by corresponding kits to explore the detoxification mechanism. The administration of the raw product elevated the levels of serum creatine kinase, lactate dehydrogenase, and malondialdehyde, a product of cardiac lipid peroxidation(P&lt;0.01), down-regulated the protein levels of Nrf2 and HO-1(P&lt;0.01), and reduced the levels of total superoxide dismutase, glutathione, glutathione peroxidase, and glutathione S-transferase(P&lt;0.01). However, after the administration of the products stir-fried with JQC, LD, BS, GC, and CZ, the abnormalities of the above indexes induced by the raw product were recovered(P&lt;0.05 or P&lt;0.01). In particular, the product stir-fried with JQC showed the best performance. Taken all together, the cardiotoxicity induced by radix T. wilfordii could be attenuated by stir-frying with JQC, LD, BS, GC, and CZ, and the stir-frying with JQC showed the best detoxification effect. The mechanism might be associated with the cardiac antioxidant defense and oxidative damage mitigation mediated by the up-regulated Nrf2.

ROS and iron homeostasis dependent ferroptosis play a vital role in 5-Fluorouracil induced cardiotoxicity in vitro and in vivo

5-Fluorouracil (5-FU) was a key chemotherapeutic agent in the treatment of different solid tumors. However, cardiotoxicity was included among the therapeutic strategies of 5-FU. The molecular mechanism of cardiotoxicity induced by 5-FU remains unclear. The aim of the study was to investigate whether ferroptosis was involved in 5-FU-induced cardiotoxicity in vivo and in vitro. The in vivo cardiotoxicity model was induced by intraperitoneal injection of 5-FU at the dose of 15, 30, 60 mg/kg for 7 days. Body weight, general condition and plasma enzyme activities of the mice were observed to evaluate heart function. In addition, HE staining, MASSON staining and TEM technology was used. Western-blot analysis were performed to evaluate the protein level of iron transport, iron storage and reactive oxygen species (ROS) of ferroptosis. In H9c2 cardiomyocyte cells, cell viability, generation of ROS, mitochondrial activity and cellular Fe2+ levels were measured. The in vivo results showed that 5-FU significantly impaired cardiac function and structure. The serum creatine kinase (CK) and lactate dehydrogenase (LDH) levels were significantly increased in 5-FU group. HE and MASSON staining showed that 5-FU caused structural injuries. In addition, 5-FU increased the level of ferroptosis markers involving malonaldehyde (MDA) and Fe2+ content. Ferrostatin-1 (Fer-1) was an aromatic amine that specifically binds with lipid ROS and protects cells against lipid peroxidation. Furthermore, 5-FU markedly induced ferroptosis in H9c2 cardiomyocyte cells, which mainly embodied as declined cell vitality, accumulated iron, elevated lipid peroxides. Conversely, inhibition of ferroptosis by Fer-1 completely abolished 5-FU-induced effects. Both in vivo and in vitro experiments indicated that 5-FU increased the expression of ferroptosis, mainly by reducing the expression of glutathione peroxidase 4 (GPX4) and ferritin heavy chain 1 (FTH1), but enhancing the expression of transferrin receptor 1 (TfR1). In conclusion, the present study suggested that ROS and iron homeostasis dependent ferroptosis played a vital role in 5-FU induced cardiotoxicity.