Increased Creatine Kinase Levels Research Articles

Repotrectinib: Redefining the therapeutic landscape for patients with ROS1 fusion-driven non-small cell lung cancer.

The ROS1 proto-oncogene encodes a receptor tyrosine kinase with structural homology to other oncogenic drivers, including ALK and TRKA-B-C. The FDA-approved tyrosine kinase inhibitors (TKIs) crizotinib and entrectinib have demonstrated efficacy in treating ROS1 fusion-positive NSCLC. However, limitations such as poor blood-brain barrier penetration and acquired resistance, particularly the ROS1 G2032R solvent-front mutation, hinder treatment durability. Repotrectinib, a next-generation macrocyclic TKI, was rationally designed to overcome on-target resistance mutations and improve brain distribution through its low molecular weight. In the TRIDENT-1 clinical trial, repotrectinib demonstrated significant efficacy in both TKI-naïve and TKI-pretreated patients with ROS1-rearranged NSCLC, including those with CNS metastases and G2032R resistance mutations. In the TKI-naïve cohort (n = 71), 79% of patients achieved an objective response, with a median progression-free survival (PFS) of 35.7 months, surpassing all previously approved ROS1 TKIs. In patients who had received one prior ROS1 TKI but were chemotherapy-naïve (n = 56), objective responses were observed in 38%, and median PFS was 9.0 months. The safety profile of repotrectinib was consistent with earlier-generation ROS1 TKIs and common adverse events included anemia, neurotoxicity, increased creatine kinase levels, and weight gain. These findings underscore the potential of repotrectinib to address unmet needs in ROS1-rearranged NSCLC, offering durable responses and improved intracranial activity. Future research should prioritize developing next-generation, selective ROS1 inhibitors to reduce Trk-mediated toxicities and improve treatment tolerance.

Comparison of creatine kinase elevation caused by Janus kinase inhibitors and interleukin-6 inhibitors in patients with rheumatoid arthritis: A propensity score-matched study

Objectives: This study aimed to examine whether creatine kinase (CK) elevation occurs with interleukin (IL)-6 inhibitors, as in Janus kinase (JAK) inhibitors, which are reported to increase CK levels in rheumatoid arthritis. Patients and methods: A multicenter database of JAK inhibitor and IL-6 inhibitor treatment was retrospectively searched between January 2016 to December 2022; 142 cases (117 females, 25 males, mean age: 63.8±13.0 years; range, 20 to 85 years), with 71 cases in each group, were extracted by propensity score matching using age, sex, body mass index, and CK at 0 weeks. The outlier rate was compared. Patients’ background characteristics related to elevated CK levels at 24 weeks were investigated by univariate and multivariate analyses. Results: Creatine kinase levels at 4 and 12 weeks were significantly higher with JAK inhibitors than with IL-6 inhibitors (four weeks, 72 vs. 87.5 IU/mL, p=0.016; 12 weeks, 71 vs. 95.5 IU/mL, p=0.028). The outlier rate (Grade 1) with JAK inhibitors increased significantly over time (0 weeks, 4.2%; four weeks, 18.1%; 12 weeks, 21.7%; 24 weeks, 18.3%; p=0.015), whereas that with IL-6 inhibitors increased slightly (0 weeks, 5.6%; four weeks, 9.2%; 12 weeks, 8.6%; 24 weeks, 8.5%; p=0.745), with a significant difference between the groups (p=0.035). No patients discontinued treatment due to myalgia or renal dysfunction. The factors significantly positively related to elevated CK levels at 24 weeks were male sex and creatinine. Those significantly negatively related were Steinbrocker stage and class, modified health assessment questionnaire scores, estimated glomerular filtration rate, and glucocorticoid dose. Conclusion: Mild CK elevations with JAK inhibitors are not a particular clinical problem. CK elevation might be specific to JAK inhibitors.

Effects of Omega-3 Supplementation on the Delayed Onset Muscle Soreness after Cycling High Intensity Interval Training in Overweight or Obese Males.

People with overweight or obesity preferred high-intensity interval training (HIIT) due to the time-efficiency and pleasure. However, HIIT leads to delayed onset muscle soreness (DOMS). The present study aimed to investigate the effects of omega-3 supplementation on DOMS, muscle damage, and acute inflammatory markers induced by cycling HIIT in untrained males with overweight or obesity. A randomized, double-blinded study was used in the present study. Twenty-four males with a sedentary lifestyle were randomly assigned to either receive omega-3 (O3) (4 g fish oil) or placebo (Con). Subjects consumed the capsules for 4 weeks and performed cycling HIIT at the 4th week. After 4 weeks-intervention, the omega-3 index of O3 group increased by 52.51% compared to the baseline. All subjects performed HIIT at 4th week. The plasma creatine kinase (CK) level of Con group increased throughout 48h after HIIT. While the CK level of O3 group increased only immediately and 24h after HIIT and decreased at 48h after HIIT. The white blood cell count (WBC) of Con group increased immediately after the HIIT, while O3 group did not show such increase. There was no change of CRP in both groups. O3 group had a higher reduction of calf pain score compared to Con group. O3 group also showed a recovery of leg strength faster than Con group. Omega-3 supplementation for 4 weeks lower increased CK level, reduced calf pain score, and recovery leg strength, DOMS markers after cycling HIIT.

Clinical features and recovery pattern of secondary hypokalaemic paralysis.

Information regarding frequency, details of neurological signs and recovery patterns of patients with secondary hypokalaemic paralysis (HP) is limited. This study aimed to analyse the frequency, aetiology, clinical features and recovery patterns of patients with secondary HP. The clinical and laboratory records of 18 consecutive patients with secondary HP aged ≥ 18years admitted to our hospital between April 2011 and March 2022 were reviewed. Patients with inherited hypokalaemic periodic paralysis were excluded. Of the 18 patients, 16 had a common aetiology: chronic alcoholism, diarrhoea or an imbalanced diet. Initial symptoms, such as fatigue, were often atypical. Three patients had prominent asymmetric limb weakness and four had predominant upper limb weakness. On admission, the mean serum potassium and creatine kinase (CK) levels of the patients were 1.90mmol/L and 4488U/mL, respectively. Ten patients (56%) had decreased potassium levels after admission, despite potassium replacement treatment (rebound hypokalaemia). Twelve patients presented with increased CK levels even after 2-5days (delayed hyperCKaemia). Low serum magnesium levels significantly correlated with rebound hypokalaemia. Secondary HP can be caused by a variety of conditions, but mainly occurs due to lifestyle conditions/disorders. Secondary HP often presents with atypical symptoms, and the initial symptoms can be non-specific. Rebound hypokalaemia and delayed hyperCKaemia are common in secondary HP, despite potassium replacement. As such, careful serial monitoring is needed for patients with secondary HP.

BRAF–MEK Inhibition in Newly Diagnosed Papillary Craniopharyngiomas

BackgroundCraniopharyngiomas, primary brain tumors of the pituitary–hypothalamic axis, can cause clinically significant sequelae. Treatment with the use of surgery, radiation, or both is often associated with substantial morbidity related to vision loss, neuroendocrine dysfunction, and memory loss. Genotyping has shown that more than 90% of papillary craniopharyngiomas carry BRAF V600E mutations, but data are lacking with regard to the safety and efficacy of BRAF–MEK inhibition in patients with papillary craniopharyngiomas who have not undergone previous radiation therapy.MethodsEligible patients who had papillary craniopharyngiomas that tested positive for BRAF mutations, had not undergone radiation therapy previously, and had measurable disease received the BRAF–MEK inhibitor combination vemurafenib–cobimetinib in 28-day cycles. The primary end point of this single-group, phase 2 study was objective response at 4 months as determined with the use of centrally determined volumetric data.ResultsOf the 16 patients in the study, 15 (94%; 95% confidence interval [CI], 70 to 100) had a durable objective partial response or better to therapy. The median reduction in the volume of the tumor was 91% (range, 68 to 99). The median follow-up was 22 months (95% CI, 19 to 30) and the median number of treatment cycles was 8. Progression-free survival was 87% (95% CI, 57 to 98) at 12 months and 58% (95% CI, 10 to 89) at 24 months. Three patients had disease progression during follow-up after therapy had been discontinued; none have died. The sole patient who did not have a response stopped treatment after 8 days owing to toxic effects. Grade 3 adverse events that were at least possibly related to treatment occurred in 12 patients, including rash in 6 patients. In 2 patients, grade 4 adverse events (hyperglycemia in 1 patient and increased creatine kinase levels in 1 patient) were reported; 3 patients discontinued treatment owing to adverse events.ConclusionsIn this small, single-group study involving patients with papillary craniopharyngiomas, 15 of 16 patients had a partial response or better to the BRAF–MEK inhibitor combination vemurafenib–cobimetinib. (Funded by the National Cancer Institute and others; ClinicalTrials.gov number, NCT03224767.)

Can coenzyme Q10 alleviate the toxic effect of fenofibrate on skeletal muscle?

Fenofibrate (FEN) is an antilipidemic drug that increases the activity of the lipoprotein lipase enzyme, thus enhancing lipolysis; however, it may cause myopathy and rhabdomyolysis in humans. Coenzyme Q10 (CoQ10) is an endogenously synthesized compound that is found in most living cells and plays an important role in cellular metabolism. It acts as the electron carrier in the mitochondrial respiratory chain. This study aimed to elucidate FEN-induced skeletal muscle changes in rats and to evaluate CoQ10 efficacy in preventing or alleviating these changes. Forty adult male rats were divided equally into four groups: the negative control group that received saline, the positive control group that received CoQ10, the FEN-treated group that received FEN, and the FEN + CoQ10 group that received both FEN followed by CoQ10 daily for 4 weeks. Animals were sacrificed and blood samples were collected to assess creatine kinase (CK). Soleus muscle samples were taken and processed for light and electron microscopic studies. This study showed that FEN increased CK levels and induced inflammatory cellular infiltration and disorganization of muscular architecture with lost striations. FEN increased the percentage of degenerated collagen fibers and immune expression of caspase-3. Ultrastructurally, FEN caused degeneration of myofibrils with distorted cell organelles. Treatment with CoQ10 could markedly ameliorate these FEN-induced structural changes and mostly regain the normal architecture of muscle fibers due to its antifibrotic and antiapoptotic effects. In conclusion, treatment with CoQ10 improved muscular structure by suppressing oxidative stress, attenuating inflammation, and inhibiting apoptosis.

Metabolic adverse effects of antipsychotics: the state of the problem and management options

Antipsychotic drugs are widely used for many psychiatric disorders, such as schizophrenia, bipolar affective disorder, delusions and hallucinations due to neurological disorders, depression with severe psychotic symptoms. Metabolic disorders including weight gain, dyslipidemia and hyperglycemia are one of the most common side effects of antipsychotic therapy. Psychiatric patients have higher risk of cardiovascular disease, so that the development of metabolic side effects is an important clinical problem that should be solved. Antipsychotic-induced weight gain may cause distress that leads to antipsychotics withdraw and repeated hospitalizations. Lifestyle changes, correction of the antipsychotic treatment, additional medications and their combination are the possible solutions of antipsychotic metabolic side effects. Lifestyle modification is a first-line therapy that should complement other options, when it feasible. At the same time, it can be extremely difficult for patients receiving antipsychotic to adhere dietary and physical activity recommendations. Replacing an antipsychotic with a milder drug is not always possible and may not be enough effective. Metformin seems to be the most well-studied, safe and effective agent that is prescribed to deal with antipsychotic-induced weight gain and associated metabolic disorders. Glucagon-like peptide type 1 receptor agonists and thiazolidinediones are mentioned as alternative medications, but clinical data on their efficacy and safety in this patient group are extremely limited. Dyslipidemia can develop as an independent antipsychotic side effect even without an increase in body weight. The most effective treatment, as in the general population, is statin therapy. However, the joint appointment of statins and antipsychotic significantly increases the risk of adverse reactions, such as myalgia, myopathy, increased creatine kinase levels, due to the competition of drugs for the cytochrome system. It is still unknown what scales should be used for cardiovascular risk stratification in patients taking antipsychotic and whether it is possible to use metformin to prevent antipsychotic-induced weight gain, and if so, how to select patients for whom such therapy can be indicated. Finally, more clinical trials are needed to evaluate the efficacy and safety of other classes of hypoglycemic and lipid-lowering drugs in patients on antipsychotics.

The Effect Of Acute Jamu Kunyit Asam After Strenuous Physical Exercise On Creatine Kinase Levels

Strenuous physical exercise can trigger muscle damage causing an increase in creatine kinase levels. One of the strategies to prevent muscle damage is to consume antioxidants and anti-inflammatory. Jamu Kunyit Asam is known to have antioxidant and anti-inflammatory activity. The aim of this study was to determine the effect of acutely giving Jamu Kunyit Asam on creatine kinase levels after strenuous physical exercise. The research sample used 20 trained males. The sample was divided into two groups (Experiment = 10; Placebo = 10). The pre-test was done by checking creatine kinase levels before engaging in strenuous physical exercise. After doing strenuous physical exercise by running on a treadmill with an intensity of 90-100% for 30 minutes, the experimental group was given 250 ml of Jamu Kunyit Asam every day for 3 days, while the control group was given a placebo drink. Creatine kinase levels were measured immediately, 24 hours, 48 hours, and 72 hours after strenuous physical exercise. The results showed that CK levels decreased significantly 24 hours, 48 hours and 72 hours after strenuous physical exercise in the Jamu Kunyit Asam group compared to the placebo group (p<0.05). The conclusion of this study is that giving Jamu Kunyit Asam acutely after doing strenuous physical exercise can reduce creatine kinase levels in trained male athletes. Acute Jamu Kunyit Asam supplementation in this study can help reduce muscle damage due to strenuous physical exercise through nutritional interventions.

A survey of clinical and laboratory characteristics of the dengue fever epidemic from 2017 to 2019 in Zhejiang, China.

To explore the epidemic, clinical, and laboratory characteristics of dengue patients in Zhejiang and the possible mechanism. Epidemic, clinical and laboratory data of 231 dengue patients admitted to the Second Affiliated Hospital of Zhejiang Traditional Chinese Medicine University between August 2017 and December 2019 were collected. GSE43777 dataset was downloaded from the Gene Expression Omnibus database and was used for the immune cell infiltration analysis, logistic regression analysis, and nomogram construction. Gene set enrichment analysis (GSEA) was performed to explore the possible regulatory pathways in dengue infection. Further, the receiver operating characteristic curve analysis and decision curve analysis were conducted to evaluate the value of related immune cells in predicting dengue severity. Among the 231 patients, the gender ratio was 1:1.1 (male/female). The patients in the <60 years age group, 60 to 80 years age group, and >80 years age group were 47.2%, 45.5%, and 7.3%, respectively. The major symptoms were fever (100%), weak (98.3%), anorexia (76.6%), muscle and joint pain (62.3%), and nausea (46.8%). In dengue patients, 98.7% of serum samples had decreased platelet levels, 96.5% of them had decreased white blood cell (WBC) levels, 97.8% had elevated aspartate aminotransferase levels, 82.3% had elevated lactate dehydrogenase levels, 49.4% had increased creatinine levels, and 35.5% had increased creatine kinase levels. Pneumonia, pleural effusion, and bilateral pleural reaction were observed in 16.5%, 8.2%, and 4.8%, respectively of dengue patients. Gallbladder wall roughness and splenomegaly accounted for 6.1% and 4.3% of all cases. Moreover, the levels of T cell, B cell, and dendritic cells were significantly higher in the convalescent group and they were involved in immune- and metabolism-related pathways. Of note, low levels of these 3 immune cells correlated with high dengue infection risk, while only dendritic cells exhibited satisfactory performance in predicting dengue severity. Dengue fever patients often onset with fever, accompanied by mild abnormalities of the blood system and other organ functions. Moreover, T cells, B cells, and dendritic cells might be involved in dengue infection and development.

Acute rhabdomyolysis due to levetiracetam in a two-year-old girl

Levetiracetam is one of the safest drugs which is used for the treatment of focal and generalized seizures during childhood. Until now, few patients have been reported with the diagnosis of acute rhabdomyolysis due to levetiracetam and our case is the youngest patient in the literature. Two-year old girl followed with atypical Rett syndrome (CDKL 5 deficiency) was admitted to our hospital with pneumonia and respiratory insufficiency. She was receiving intravenous antibiotics and levetiracetam therapy. During follow-up, the increase of creatine kinase levels continued, intravenous hydration and alkalinization was added on therapy. As we could not find any etiology explaining the raising creatine kinase levels in our patient, levetiracetam was thought to be the cause of rhabdomyolysis and withdrawn. After discontinuation of levetiracetam, creatine kinase levels began to decline within 24 h and returned to normal levels in one week. Levetiracetam-induced rhabdomyolysis is quite rare but is a life-threatening condition and should be kept in mind especially during childhood. The creatine kinase levels and renal function tests of all patients should be followed in the first week of levetiracetam therapy. Early diagnosis and supportive therapy is very important in order to prevent acute kidney injury. CDKL 5 deficiency can be a protective factor which might prevent acute kidney injury in our patient but more research is needed about this topic.

Longitudinal Changes of Serum Creatine Kinase and Acute Kidney Injury among Patients with Severe COVID-19.

Background Acute kidney injury (AKI) is a common complication of COVID-19. Several etiologies have been identified, including pigment deposition likely associated with myopathic damage. Nevertheless, the relationship between longitudinal creatine-kinase trends and renal outcomes is uncertain. Aim To correlate longitudinal changes in serum creatine-kinase levels with hospital-acquired AKI (beyond 48 h of hospital admission) in severe COVID-19 patients. Methods This is a retrospective cohort study, and creatine-kinase levels were assessed over time in 1551 hospitalized patients with normal renal function at the time of hospital admission. Results In subjects who developed hospital-acquired AKI (n = 126, 8.1%), the serum creatine-kinase concentration before AKI onset was not different when compared to patients without AKI (slope of log creatine-kinase/day = −0.09 [95% CI −0.17 to +0.19] vs. +0.03 [95% CI −0.1 to +0.1]). After AKI diagnosis, serum creatine-kinase levels showed a significantly ascendent slope (slope of log creatine-kinase/day after AKI diagnosis = +0.14; 95% CI + 0.05 to +0.3). The AKI evolution was the main factor associated with the creatine-kinase trend. Subjects with persistent AKI (n = 40, 32%) had rising creatine-kinase levels during hospitalization (slope of log creatine-kinase/day = +0.30 95% CI + 0.19 to +0.51). A rising creatine-kinase trend (n = 114, 8%) was associated with a 1.89-fold higher risk of in-hospital death (95% CI 1.14 to 3.16). Nevertheless, this association disappeared after adjusting AKI evolution and LDH baseline levels. Conclusion In severe COVID-19 patients, a slight increase in creatine-kinase levels was observed after AKI occurrence but not before. Our results show that, at least for the appearance of hospital-acquired AKI, the CK rise does not meet the temporality criterion of causality regarding the occurrence of AKI. Rising creatine-kinase trends were associated with a higher risk of mortality, but this association was modified by AKI evolution and inflammation. There is a limited efficiency for AKI prognosis in the serial follow-up of CK levels in severe COVID-19 patients with normal renal function.

Clinical and electrophysiological characteristics of respiratory onset amyotrophic lateral sclerosis: a single-centre study.

We compared the clinical characteristics of patients with respiratory, bulbar and limb onset amyotrophic lateral sclerosis (ALS) who visited a single tertiary centre for 8years. Total of 115 ALS patients with respiratory, bulbar and limb onset ALS, including sex, body mass index (BMI), presence of lung disease, age at diagnosis, disease duration after initial symptoms, ALS Functional Rating Scale (ALSFRS-R) and progression rate (Delta-FS), pulmonary function, amplitude and distal latency (DL) of the phrenic nerves and blood creatine kinase (CK) and uric acid levels were collected. The prevalence of respiratory, bulbar and limb onset ALS were 5.2%, 28.7% and 66.1%, respectively. The mean age at diagnosis and ALSFRS-R were 67.8 ± 5.5, 63.8 ± 10.1 and 59.2 ± 11.7 in the descending order. The mean amplitude (0.18 ± 0.10mV) and DL (9.5 ± 1.7ms) of the phrenic nerves were significantly decreased and prolonged in respiratory onset ALS compared with other types of ALS patients. Patients with respiratory onset ALS had normal creatine kinase (CK) levels, whereas patients with other types of ALS had increased CK levels. Although rare, respiratory onset ALS may occur and should be considered during the initial differential diagnosis. In this study, patients with respiratory onset ALS were characterised by male predominance, with a higher baseline ALSFRS-R, lower BMI and phrenic nerve study well discriminated respiratory onset ALS from bulbar or limb onset ALS patients.

An ultra-rare cause of severe hypotonia mimicking Pompe disease in an infant: RRM2B related mitochon- drial DNA depletion syndrome with a novel mutation

Ribonucleotide-diphosphate reductase subunit M2B(RRM2B)-related mitochondrial disease is one of the ultra-rare mitochondrial depletion syndromes. A-2-months of age girl who had severe hypotonia with absent reflexes, failure to thrive, and developmental delay was hospitalized under our care. The initial diagnosis was Pompe disease with absent reflexes and increased creatine kinase level. Enzyme analysis for Pompe disease was normal and next-generation sequence panel analysis of 450 genes related to metabolic disorders revealed a novel mutation in the RRM2B gene. The patient died at the age of 2.5 months. Up to date, there have been reports of 31 patients with infantile forms of RRM2B. This patient presented with little features to suggest a mitochondrial disorder. In conclusion, RRM2B mutations should be included in the differential diagnosis of the Pompe disease in infants with severe hypotonia. This case report also expands the mutation spectrum of rare infantile form of the RRM2B mutations.

Efficacy and Safety of Selumetinib in Pediatric Patients With Neurofibromatosis Type 1: A Systematic Review and Meta-analysis.

Although the recent approval of selumetinib is expected to transform the management of children with neurofibromatosis type 1 (NF1), particularly those with symptomatic and inoperable plexiform neurofibromas, no systematic review has summarized its efficacy and safety based on the latest studies. This study was conducted to systematically evaluate the efficacy and safety of selumetinib in children with NF1. Original articles reporting the efficacy and safety of selumetinib in patients with NF1 were identified in PubMed and EMBASE up to January 28, 2021. The pooled objective response rates (ORRs) and disease control rates (DCRs) were calculated using the DerSimonian-Laird method based on random-effects modeling. The pooled proportion of adverse events (AEs) was also calculated. The quality of the evidence was assessed using the Grading of Recommendations, Assessment, Development and Evaluation system. Five studies involving 126 patients were included in our analysis. The studies had a very low to moderate quality of the evidence. The pooled ORR was 73.8% (95% CI 57.3%-85.5%) and the DCR was 92.5% (95% CI 66.5%-98.7%). The 2 most common AEs were diarrhea, which had a pooled rate of 63.8% (95% CI 52.9%-73.4%), and an increase in creatine kinase levels, which had a pooled rate of 63.3% (95% CI 35.6%-84.3%). Our results indicate that selumetinib is an effective and safe treatment for pediatric patients with symptomatic, inoperable plexiform neurofibromas. Further larger-scale randomized controlled studies are needed to confirm the long-term outcome of patients treated with this drug.

Efficacy and safety of glucocorticoids in the treatment of progressive muscular dystrophy in children: a systematic review and meta-analysis.

BackgroundHormonal drug therapy has been widely used in clinical practice for the treatment of progressive muscular dystrophy (PMD). Glucocorticoids, as a common drug in the clinical treatment of PMD, have been reported in several clinical studies.MethodsChinese and English databases were respectively searched using “randomized controlled trials”, “Duchenne-type myotonic dystrophy”, “glucocorticoids”, Prednisone”, “Prednisolone”, and “Methylprednisolone”, and “Defibrotide” were used as search terms. The meta-analysis was performed using the RevMan 5.3 and Stata 13 software provided by the Cochrane system.Resultsthis study included five randomized controlled trials, all of which described the correct randomization method. There were four detailed descriptions of hidden distribution schemes. There were four literatures using blind method. Heterogeneity analysis showed that there was some heterogeneity between the results of the mean prognostic muscle strength, walking time of 9 meters, and 4 flights of stairs climbing between the glucocorticoid-treated group (the experimental group) and the placebo group (the control group). There were no significant differences between the experimental group and the control group in average muscle strength level, walking time of 9 meters and climbing time of 4 flights of stairs (MD =1.77; 95% CI: −0.95 to 4.48; P=0.20>0.05), (MD =−12.27; 95% CI: −35.94 to 11.40; P=0.31>0.01), (MD =−3.09; 95% CI: −11.16 to 4.99; P=0.45>0.05). In addition, glucocorticoid treatment significantly increased creatine kinase level in patients with PMD (MD =−0.28, 95% CI: −0.57 to 0.00; P=0.05). In terms of the incidence of adverse reactions, glucocorticoid treatment significantly increased the prognostic probability of acne, rapid hair growth, and emotional irritability in PMD patients (OR =2.40; 95% CI: 1.09 to 5.27; P=0.03<0.05), (OR =3.05; 95% CI: 1.55 to 5.99; P=0.001<0.05), (OR =4.04; 95% CI: 1.82 to 10.63; P=0.001<0.05). There was no significant difference in the incidence of prognostic depression between the experimental group and the control group (OR =5.11; 95% CI: 0.80 to 32.79; P=0.09>0.05).DiscussionThe results suggest that glucocorticoids have a significant effect on PMD patients, but to a certain extent they increase the incidence of adverse reactions in patients after treatment. However, due to the lack of complete clinical data in some ongoing studies, our conclusions may not be fully representative.

Clinico-hematological, patho-anatomical and molecular based investigation of blackleg disease in Cholistani cattle

Clostridium chauvoei, causing myonecrosis in livestock animals, lives in the feces, surface water and soil. The blackleg due to C. chauvoei is very common in dairy animals. Still, no report is available about the pathophysiology of disease in Cholistani cattle kept under tropical and desert conditions of Cholistan, Pakistan. Therefore, in this study, we report for the first time the pathophysiology of a visceral form of blackleg infection in indigenous cholistani cattle breed reared in desert conditions of Cholistan. Clinically morbid animals exhibited different signs of infection including fever, crepitation sounds, gaseous swelling and edematous lesions. Blood was collected for hematological and serum biochemical investigation. Hematological examination indicated a significant increased erythrocyte sedimentation rate, lower red blood cells, hematocrit, and total white blood cell count. Results on serum biochemistry showed significantly (p<0.02) increased creatine kinase levels, creatinine, urea, alanine aminotransferase, aspartate aminotransferase, alkaline phosphates, creatinine phosphokinase and lactate dehydrogenase in infected cattle. At necropsy level, light pink color fluid under swelling areas of skin, gas bubbles, dark to black in color of affected muscles and crepitation sounds at palpation were observed. Necropsy showed marked myocarditis, petechial hemorrhages, consolidation and severe pulmonary edema. Spleen showed petechial hemorrhages and congestion. Histological analysis of muscular tissues indicated severe inflammatory reaction comprising of cellular infiltration, marked edema, necrosis and disruption of myofibrils. PCR confirmed the presence of C. chauvoei in muscles, heart and exudates of the lungs. This is the first report on molecular detection of Clostridium chauvoei from a visceral form of Blackleg disease in cholistani breed of cattle naturally infected in the Cholistan desert of Punjab, Pakistan.

The Effect of Acute Beetroot Juice Supplementation After Strenuous Physical Activity on Creatine Kinase Levels

Strenuous physical activity can cause muscle damage which is marked by an increase in creatine kinase levels. One of the strategies to prevent muscle damage is to consume antioxidants and anti-inflammatory. Beetroot (Beta vulgaris L.) is known to have antioxidant and anti-inflammatory activity. The aim of this study was to determine the effect of acutely giving beetroot juice on creatine kinase levels after strenuous physical activity. The research sample used 20 trained males. The sample was divided into two groups (Experiment = 10; Placebo = 10). The pre-test was done by checking creatine kinase levels before engaging in strenuous physical activity. After doing strenuous physical activity by running on a treadmill with an intensity of 90-100% for 30 minutes, the experimental group was given 300 ml of beetroot juice (BRJ) every day for 3 days, while the control group was given a placebo drink. Creatine kinase levels were measured immediately, 24 hours, 48 hours, and 72 hours after strenuous physical activity. The results showed that CK levels decreased significantly 24 hours, 48 hours and 72 hours after strenuous physical activity in the BRJ group compared to the placebo group (p <0.05) The conclusion of this study is that giving BRJ acutely after doing strenuous physical activity can reduce creatine kinase levels in trained male athletes. Acute JBR supplementation in this study can help reduce muscle damage due to strenuous physical exercise through nutritional interventions

Modeling of Changes in Creatine Kinase after HMG-CoA Reductase Inhibitor Prescription

Background: Statin-associated muscle symptoms are one of the side effects that physicians should consider when prescribing statins. In this study, creatine kinase (CK) levels were measured following statin prescription, and various factors affecting the CK levels were determined using machine learning.Methods: Changes in the CK were observed every 3 months for a 12-month period in patients who received statins for the first time at Seoul St. Mary's Hospital. For each visit, we developed four basic models based on changes in the CK levels. Extreme gradient boosting, a scalable end-to-end tree boosting algorithm, which employs a decision-tree-based ensemble machine learning algorithm, was used for the prediction of changes in the CK.Results: A total of 23,860 patients were included. Among them, 19 patients (0.08%) had increased CK levels of 2,000 IU·L&lt;sup&gt;−1&lt;/sup&gt; or more 3 months after statin prescription, and 65 patients (0.27%) exhibited CK levels of over 2,000 IU·L&lt;sup&gt;−1&lt;/sup&gt; at least once during the 12-month study period. The area under the receiver operator characteristic of each model for each visit was 0.709–0.769, and the accuracy was 0.700–0.803. In each of the models, the variables that had the strongest influence on changes in the CK were sex and previous CK value.Conclusions: Through machine learning, factors influencing changes in the CK were identified. These results will provide the basis for future research, through which the optimal parameters of the CK prediction model can be found and the model can be used in clinical applications.

The etiology of rhabdomyolysis: an interaction between genetic susceptibility and external triggers.

Background and purposeRhabdomyolysis is a medical emergency characterized by acute skeletal muscle breakdown with a sudden rise and subsequent fall of serum creatine kinase (CK) levels. Rhabdomyolysis events are provoked by exposure to external triggers, possibly in combination with an increased genetic susceptibility. We aimed to describe comprehensively the external triggers and potentially pathogenic genetic variants possibly implicated in increased rhabdomyolysis susceptibility.MethodsWe performed a retrospective single‐center study, including a total of 1302 patients with an acute CK level exceeding 2000 IU/l.ResultsAnoxia was the most frequently reported trigger (40%). A subset of 193 patients were clinically suspected of an underlying genetic disorder (recurrent episodes, a positive family history, very high or persistently increased CK levels). In 72 of these patients, an unequivocal genetic defect was identified. A total of 22 genes with pathogenic variants were identified, including 52 different variants. Of those, 11 genes have been previously associated with rhabdomyolysis (ACADVL, ANO5, CPT2, DMD, DYSF, FKRP, HADHA, PGM1, LPIN1, PYGM, RYR1). Eleven genes are probably implicated in increased susceptibility (including AGL, CAPN3, CNBP, DMPK, MAGT1, ACADM, SCN4A, SGCA, SGCG, SMPD1, TANGO2).ConclusionThese findings suggest that the spectrum of genetic susceptibility for rhabdomyolysis has not yet been completely clarified. With the increasing availability of next‐generation sequencing in a diagnostic setting, we expect that in more cases a genetic defect will be identified.

Ultra-Endurance Associated With Moderate Exercise in Rats Induces Cerebellar Oxidative Stress and Impairs Reactive GFAP Isoform Profile.

Ultra-endurance (UE) race has been associated with brain metabolic changes, but it is still unknown which regions are vulnerable. This study investigated whether high-volume training in rodents, even under moderate intensity, can induce cerebellar oxidative and inflammatory status. Forty-five adult rats were divided into six groups according to a training period, followed or not by an exhaustion test (ET) that simulated UE: control (C), control + ET (C-ET), moderate-volume (MV) training and MV-ET, high-volume training (HV) and HV-ET. The training period was 30 (MV) and 90 (HV) min/day, 5 times/week for 3 months as a continuous running on a treadmill at a maximum velocity of 12 m/min. After 24 h, the ET was performed at 50% maximum velocities up to the animals refused to run, and then serum lactate levels were evaluated. Serum and cerebellar homogenates were obtained 24 h after ET. Serum creatine kinase (CK), lactate dehydrogenase (LDH), and corticosterone levels were assessed. Lipid peroxidation (LP), nitric oxide (NO), Interleukin 1β (IL-1β), and GFAP proteins, reduced and oxidized glutathione (GSH and GSSG) levels, superoxide dismutase (SOD) and catalase (CAT) activities were quantified in the cerebellum. Serum lactate concentrations were lower in MV-ET (∼20%) and HV-ET (∼40%) compared to the C-ET group. CK and corticosterone levels were increased more than ∼ twofold by HV training compared to control. ET increased CK levels in MV-ET vs. MV group (P = 0.026). HV induced higher LP levels (∼40%), but an additive effect of ET was only seen in the MV-ET group (P = 0.02). SOD activity was higher in all trained groups vs. C and C-ET (P < 0.05). CAT activity, however, was intensified only in the MV group (P < 0.02). The 50 kDa GFAP levels were enhanced in C-ET and MV-ET vs. respective controls, while 42 kDa (∼40%) and 39 kDa (∼26%) isoform levels were reduced. In the HV-ET group, the 50 KDa isoform amount was reduced ∼40–60% compared to the other groups and the 39 KDa isoform, increased sevenfold. LDH levels, GSH/GSSG ratio, and NO production were not modified. ET elevated IL-1β levels in the CT and MV groups. Data shows that cerebellar resilience to oxidative damage may be maintained under moderate-volume training, but it is reduced by UE running. High-volume training per se provoked systemic metabolic changes, cerebellar lipid peroxidation, and unbalanced enzymatic antioxidant resource. UE after high-volume training modified the GFAP isoform profile suggesting impaired astrocyte reactivity in the cerebellum.