Increased Creatine Kinase Research Articles

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.

Creatine kinase is associated with glycated haemoglobin in a nondiabetic population. The Tromsø study.

Creatine kinase (CK) has been associated with insulin resistance and identified as a risk marker of cardiovascular disease largely by its relationship with hypertension and increased body mass index. This study determined whether CK is a predictor of glycated haemoglobin (HbA1C) in a nondiabetic general population. Associations between CK and the outcome variable HbA1C (%) were performed by variance and multivariate analyses in 11662 nondiabetic subjects defined as HbA1C (%) <6.5 who participated in the population based Tromsø study (Tromsø 6) in Norway. Abnormal elevated CK was detected in 543/11662 participants (4.66%). Mean HbA1C (%) in the "high CK" group was 5.62 (SD = 0.33) compared to 5.52 (SD = 0.36) in the "normal CK" group, P <0.001. CK increased significantly and linearly with higher levels of HbA1C (%) quartiles in women (P <0.001) and non-linearly in men (P <0.001). In a multivariate analysis, CK was independently associated with HbA1C (%) after adjusting for age, sex, body mass index, blood pressure, glucose, lipids, C-reactive protein, creatinine, alanine transaminase and aspartate aminotransferase. A 1-unit increase in log CK was associated with a 0.17-unit increase in HbA1C (%). These data demonstrate a positive and independent association between CK and glycated haemoglobin in a nondiabetic general population.

Toxic effect of cigarette butts leachates on blood markers of Periophthalmus waltoni species from the Persian Gulf region

Cigarette butts (CBs) are one of the most common, long-lasting, and toxic forms of marine and coastal area debris. Although the significance of CBs and the toxic contents of this waste items are well recognized, but there is still a lack of information about the effects of this waste on the aquatic organisms. Therefore in this study, the in-vivo toxic effects of various CBs leachates (smoked cigarette butts with tobacco [SCBs], smoked CBs without tobacco [SFs], and unsmoked filters [USFs]) on cellular and chemical hematologic markers in fish (Periophthalmus waltoni) were evaluated. In three acute, sub-acute, and sub-chronic exposure measurements, P. waltoni exposed to different CBs leachates showed a significant increase in white blood cells, creatine kinase, lactate dehydrogenase, alkaline phosphatase, alanine transaminase, and aspartate transaminase, as well as a decrease in hemoglobin (Hb) levels. The mean ± SD values of Hb in P. waltoni species exposed to different CBs leachates (control, SCBs, SFs and USFs) in acute (1 day) phase were 7.15 ± 0.34, 6.02 ± 0.29, 6.25 ± 0.25 and 6.89 ± 0.1 g/dl respectively. These values in subacute (28 days) phase were 6.70 ± 0.15, 5.19 ± 0.24, 5.67 ± 0.30 and 6.10 ± 0.24 g/dl and in sub chronic exposure (42 days) phase were 7.20 ± 0.40, 5.16 ± 0.30, 5.88 ± 0.34 and 6.60 ± 0.33 g/dl respectively. Our results showed that CBs leachates act as a stressor, leading to changes in some hematologic markers in P. waltoni species. Because of the continued deposition of CBs waste into global aquatic environments, policies to mitigate this waste in coastal areas are needed to prevent potentially negative effects on fish and other aquatic organisms.

Vernonia amygdalina leaf extract protects against carbon tetrachloride-induced hepatotoxicity and nephrotoxicity: a possible potential in the management of liver and kidney diseases

The rising prevalence of liver and kidney diseases is worrisome and constitutes a major threat to public health. The present study investigates the medicinal potentials of Vernonia amygdalina leaves in the management of liver and kidney diseases. Albino rats were randomly divided into five groups each containing 5 animals. In all groups, except group I (control), animals were exposed to 3 ml/kg bw of CCl4 and then administered further different treatments. Groups III, IV, and V each were treated with 50 mg/kg bw, 100 mg/kg bw of bitter leaf extract, and 100 mg/kg bw of silymarin, respectively. Group II animals were left untreated after exposure to toxicant. Activities of creatine kinase (CK), aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), as well as the level of urea, uric acid, and bilirubin were determined in the serum and tissue homogenates. Lipid profile as well as activities of superoxide dismutase (SOD) and catalase (CAT) were also determined. Exposure to CCl4 resulted in a significant increase in CK, AST, ALP, and ALT levels as well as bilirubin, urea, and uric acid when compared to the control. Lipid profile was disrupted, activities of SOD and CAT were markedly inhibited and the level of GSH was significantly depleted. However, treatment with V. amygdalina reversed the toxic trend in a dose-dependent manner comparable to animals treated with silymarin. In conclusion, V. amygdalina leaf extract restored deranged lipid profile, distorted histoarchitecture as well as liver and kidney function markers. Hence, the plant is a potential candidate for the management of liver and kidney diseases.

The Protective Effect of Lasia spinosa (Linn.) Dissipates Chemical-Induced Cardiotoxicity in an Animal Model.

Lasia spinosa (L.) Thwaites is a medicinal plant of enormous traditional use with insufficient scientific evidence. This research screened the antioxidative effect of L. spinosa extracts by measuring the total phenolic content, total flavonoid content, DPPH free radical scavenging activity, ABTS scavenging activity, Iron-chelating activity, and Ferric reducing power followed by an evaluation of in vivo cardioprotective effect in doxorubicin-induced Wistar Albino rats. Phytochemical characterization was made by Gas Chromatography-Mass Spectroscopic analysis. L. spinosa showed an excellent antioxidative effect while methanol leaf extract (LSM) was found to be more potent than ethyl acetate leaf extract (LSE) in scavenging the free radicals. Intraperitoneal injection of doxorubicin caused a significant (P < 0.001) increase in lactate dehydrogenase (LDH), creatine kinase (CK-MB), C-reactive protein (CRP), and Cardiac troponin I. Pretreatment with orally administrated (LSM100 and LSM200 mg/kg b.w.) daily for 10days showed a decrease in the cardiac markers, lipid profiles, especially triglycerides (TG), total cholesterol (TC), low-density lipoprotein (LDL), and an increase of high-density lipoprotein (HDL) compared to the disease control group. LSM200 was found to significantly (P < 0.05) decrease the levels of CK-MB and LDH. It also restored TC, TG, and LDL levels compared to the doxorubicin-induced cardiac control group. The protective role of LSM was further confirmed by histopathological examination. This study thus demonstrates that L. spinosa methanol extract could be approached as an alternative supplement for cardiotoxicity, especially in the chemical-induced toxicity of cardiac tissues.

190 FATAL PEMBROLIZUMAB CARDIOTOXICITY REFRACTORY TO CORTICOSTEROID THERAPY: A CASE REPORT OF CLINICALLY SUSPECTED MYOCARDITIS.

Abstract We report the case of an 80 years old, fit, mildly hypertensive man receiving adjuvant immunotherapy with Pembrolizumab for stage IIIC (pT4a pN1b) cutaneous nodular melanoma, for which he had also undergone radical surgery. His preoperative ECG was unremarkable. Few days after his first Pembrolizumab dose, he started complaining of gradually worsening muscle aches and weakness and double vision, as well as of brief episodes of otherwise asymptomatic palpitations, so that he finally showed up at the Emergency Department (day 1). Clinical examination revealed mild hypertension, low-grade temperature, subtotal bilateral ophthalmoplegia, fatigable left palpebral ptosis, dysarthria, dysphagia, and neck and limb hyposthenia. Laboratory analyses indicated an inflammatory state with mild neutrophilia and elevated C reactive protein, associated to an increase in serum creatinine, creatine kinase and transaminases. Chest x-ray and brain CT demonstrated no alterations. The ECG showed sinus rhythm at 90 bpm and a previously unknown right bundle branch block (RBBB). The patient was admitted to the Internal Medicine ward in the suspect of Pembrolizumab toxicity leading to myositis and myasthenia and to hepatorenal dysfunction, and Methylprednisolone 1 mg/kg/day was administered intravenously ex adiuvantibus, together with Pyridostigmine and low flow oxygen. The next morning (day 2), dyspnea and palpitations ensued, atrial fibrillation at 130 bpm with RBBB was recorded, while the echocardiogram showed normal biventricular dimensions and systodiastolic function, mild aortic and mitral regurgitations, and the absence of pericardial effusion or inferior vena cava congestion. A single, oral, 60 mg dose of Diltiazem was administered, but suspended few hours later upon evidence of atrioventricular block (AVB) 2:1 (HR 40 bpm) quickly escalating to 3:1 (HR 40 bpm) and, later on, of atrial fibrillation with slow ventricular rate (HR 36 bpm). Given a CHA2DS2-VASc score equal to 3, anticoagulation was started. The patient was then moved to the intensive care unit for bradycardia and worsening tachydyspnea. Respiratory function as well as clinical and laboratory parameters of neuromuscular, renal and hepatic impairment began improving (day 3). However, rhythm monitoring showed progression of conduction anomalies with the appearance of sino-atrial block, left bundle branch block and alternance between Mobitz I AVB, AVB 2:1 and complete AVB. High-sensitivity cardiac troponin I remained stably highly elevated, around 25000 ng/L. Control echocardiography showed the onset of mild left ventricular systolic dysfunction with a mild pericardial effusion. A cardiac magnetic resonance was planned to corroborate the hypothesis of Pembrolizumab-induced myocarditis. However, on day 5 respiratory and hemodynamic worsening occurred, up to cardiocirculatory arrest due to an electrical storm of ventricular tachycardia and fibrillation, despite in-range electrolytes, with emergency echocardiogram revealing also a dysfunctioning right ventricle. Despite prolonged resuscitation attempts, including high-dose corticosteroid, death ensued. Widely used in cancer treatment, immune checkpoint inhibitors (ICI) bear the potential for immune-related adverse events, including cardiovascular ones: brady- and tachy- arrhythmias, acute myocardial infarction, pericarditis, myocarditis, pulmonary embolism, and vasculitis; in particular, ICI-related myocarditis, reportedly highly arrhythmogenic, often occurs together with myositis and myasthenia (“triple M rule”); despite immunosuppression, mortality still remains high.

Rhabdomyolysis in a male adolescent associated with monotherapy of fluvoxamine

Rhabdomyolysis is a syndrome resulting from striated muscular breakdown, which may occur due to drug therapy with agents such as selective serotonin reuptake inhibitors (SSRIs). Although studies have shown that...

Lifetime prevalence and correlates of syncope in five ancestry groups. The HELIUS study.

To explore the lifetime prevalence and correlates of syncope in the general population. Through stratified random sampling, we included 14,937 White-European, Asian, Turkish, Moroccan, and West-African ancestry adults (18-70 y) in the cross-sectional Healthy Life in an Urban Setting (HELIUS) population study. We assessed syncope history by ancestry, and the potential correlates body mass index (BMI), systolic/diastolic blood pressure (SBP/DBP), resting plasma activity of creatine kinase (CK), the ATP-generating enzyme that facilitates cardiovascular contractility and sodium retention, and in a subgroup, supine cardiac contractility (dP/dt), cardiac output (CO) and systemic vascular resistance (SVR). Mean age of the participants (39% men) was 43.3 y (SD12.9). Lifetime prevalence of syncope in women/men was respectively (%), White-European 42/24; Asian 34/19; Moroccan 32/16; Turkish 30/17; and West-African 20/14. Mean age at first syncope was 24 y (SD13). Participants with syncope history had lower SBP, DBP, BMI, CK, and modestly lower dP/dt and CO, but not SVR. In multivariable regression analysis, male sex (OR 0.52 [0.48 to 0.57]), West-African ancestry (0.59 [0.54 to 0.65]), and CK (0.56 [0.46 to 0.69]/log CK increase) were negatively associated with syncope. This study indicates that West-African ancestry, male sex, and high activity of the pressor enzyme CK are associated with lower syncope prevalence. These findings may inform further studies on the hemodynamics of syncope.

Anti-programmed death-1 inhibitor nivolumab-induced immune-related adverse events: hepatitis, renal insufficiency, myositis, vitiligo, and hypothyroidism: a case-based review.

Nivolumab (NIVO) is a monoclonal antibody used to treat renal cell cancer. It is an anti-programmed death-1 (anti-PD-1) inhibitor, enhancing the tumor-targeted immune response of T lymphocytes, resulting in immune-mediated adverse events (AEs). We present five immunologicalAEs in a single patient treated with NIVO. A 68-year-old male patient with metastatic renal cell carcinoma and right-sided nephrectomy received NIVO after pazopanib and sunitinib treatment. Two and a half months after starting NIVO, hepatocellular enzymes and creatinine were elevated. Concomitantly, the patient noticed hypopigmentation of the hand skin and a change in voice and speech. Due to hepatitis, he has been treated with dexamethasone 16mg daily for 22days, after which hypothyroidism and increased creatine kinase were found without muscle pain and functional impairment. Dexamethasone was continued, and a rapid decline in all parameters except thyroid-stimulating hormone (TSH) and vitiligo was observed. Myositis was initially considered a part of hypothyroidism and elevated renal parameters due to hypohydration. The rapid regression on glucocorticoid treatment and a longer time for creatinine normalization than expected with hydration were noticed. Nivolumab likely induced those side effects as assessed by Naranjo Adverse Drug Reaction Probability Scale. The literature review shows that theconsequences of PD-1 inhibition are not uniform. Side effects of checkpoint inhibitors should be monitored carefully in the early and later treatment schedules evaluating subclinical manifestations like myositis and worsening of kidney parameters. Early administered higher doses of glucocorticoids can stop drug toxicity and reverse-induced tissue damage.

Coxsackievirus A6 was the most common enterovirus serotype causing hand, foot, and mouth disease in Shiyan City, central China.

Hand, foot, and mouth disease (HFMD) has become one of the most common infectious diseases in China. Before 2016, the primary causal serotypes were enterovirus A71 (EV-A71) and coxsackievirus A16 (CV-A16). Following the introduction of EV-A71 vaccines in China since 2016, the situation could change. CV-A6 has recently replaced EV-A71 and CV-A16 in some areas of China. However, the epidemiological characteristics of central China remain unknown. To investigate the clinical symptoms and pathogen spectrum of HFMD in Shiyan City, central China, in recent years. The epidemiological, clinical, and laboratory data from HFMD cases reported to the Shiyan Center for Disease Control and Prevention between January 2016 and December 2020 were analyzed. 196 throat swab specimens were collected from hospitalized HFMD patients between January 2018 and December 2020. To detect and genotype enteroviruses, real-time reverse transcription-polymerase chain reaction and sequencing of the 5'-untranslated region were used. In Shiyan, 168 laboratory-confirmed HFMD cases were studied using a logistic regression model to determine the effect of predominant enterovirus serotypes. Based on the logistic regression model, the least absolute shrinkage and selection operator model was used to analyze the correlation between CV-A6 infection and various clinical characteristics in HFMD patients in Shiyan. From 2016 to 2020, 35840 HFMD cases were reported in Shiyan. The number of cases decreased by 48.4% from 2016 to 2017. Approximately 1.58-fold increases were found in 2018 and 2019 when compared to the previous year, respectively. In 2020, a decrease of about 85.5% was reported when compared to 2019. The most common serotypes shifted from EV-A71 and CV-A16 (about 60%-80% in 2016 and 2018) to others (more than 80.0% in 2017, 2019, and 2020). EV-A71 lost its dominance in 2017 in Shiyan. Among 196 confirmed HFMD cases, 85.7% tested positive for enterovirus, with CV-A6 being the most common serotype (121/168, 72.0%). The positive rates for CV-A16 and CV-A10 were 4.8% and 3.0%, respectively. There was no EV-A71 discovered. Infection with CV-A6 was linked to fever, myocardial damage, increased creatine kinase MB isoenzyme, and lactate dehydrogenase levels. CV-A6 was the most common enterovirus serotype in Shiyan City, replacing EV-A71 and CV-A16 as the HFMD pathogen. Developing vaccines against CV-A6 or multiple pathogens, as well as rising CV-A6 surveillance, will help prevent HFMD in central China.

The Problem of Drug Interactions Between Rosuvastatin and Ticagrelor in the Aspect of the Risk of Rhabdomyolysis: Discussion of the Problem and Description of the Clinical Case

Background. Combination therapy with two antiplatelet agents (ticagrelor or clopidogrel plus acetylsalicylic acid) and a high dose statin is recommended in accordance with clinical guidelines for patients undergoing acute coronary syndrome and coronary intervention. Combined therapeutic regimens have drug-drug interaction potential. Rhabdomyolysis is a known side effect of statin therapy, and there is evidence that co-therapy with ticagrelor increases the risk of this complication.Case description. A 72-year-old female patient was hospitalized with typical signs of rhabdomyolysis: muscle pain, oliguria, weakness, significant increases in creatine kinase (CK), myoglobin and creatinine. One month before that, she was urgently hospitalized with acute recurrent ST-elevation myocardial infarction and underwent endovascular intervention on a critical stenosis of the left anterior descending artery with stent implantation. After that, rosuvastatin 40 mg per day and ticagrelor 90mg 2 times a day were added to her therapy. During the current hospitalization, rosuvastatin, ACE inhibitors and spirolactone were canceled, infusion therapy was carried out, which led to a rapid regression of symptoms, restoration of adequate diuresis, and normalization of CK, myoglobin and creatinine levels. Conclusions. The combined use of ticagrelor with rosuvastatin (especially at a high dose) increases the risk of rhabdomyolysis in elderly patients. Patients taking ticagrelor may require changes in statin therapy, dose adjustments, and possible drug changes to avoid pharmacological interactions and an increased risk of side effects.

Sodium and quantitative hydrogen parameter changes in muscle tissue after eccentric exercise and in delayed-onset muscle soreness assessed with magnetic resonance imaging.

The objective of the current study was to assess sodium (23 Na) and quantitative proton (1 H) parameter changes in muscle tissue with magnetic resonance imaging (MRI) after eccentric exercise and in delayed-onset muscle soreness (DOMS). Fourteen participants (mean age: 25 ± 4 years) underwent 23 Na/1 H MRI of the calf muscle on a 3-T MRI system before exercise (t0), directly after eccentric exercise (t1), and 48 h postintervention (t2). In addition to tissue sodium concentration (TSC), intracellular-weighted sodium (ICwS) signal was acquired using a three-dimensional density-adapted radial projection readout with an additional inversion recovery preparation module. Phantoms containing saline solution served as references to quantify sodium concentrations. The 1 H MRI protocol consisted of a T1 -weighted turbo spin echo sequence, a T2 -weighted turbo inversion recovery, as well as water T2 mapping and water T1 mapping. Additionally, blood serum creatine kinase (CK) levels were assessed at baseline and 48 h after exercise. The TSC and ICwS of exercised muscles increased significantly from t0 to t1 and decreased significantly from t1 to t2. In the soleus muscle (SM), ICwS decreased below baseline values at t2. In the tibialis anterior muscle (TA), TSC and ICwS remained at baseline levels at each measurement point. However, high-CK participants (i.e., participants with a more than 10-fold CK increase, n = 3) displayed different behavior, with 2- to 4-fold increases in TSC values in the medial gastrocnemius muscle (MGM) at t2. 1 H water T1 relaxation times increased significantly after 48 h in the MGM and SM. 1 H water T2 relaxation times and muscle volume increased in the MGM at t2. Sodium MRI parameters and water relaxation times peaked at different points. Whereas water relaxation times were highest at t2, sodium MRI parameters had already returned to baseline values (or even below baseline values, for low-CK participants) by this point. The observed changes in ion concentrations and water relaxation time parameters could enable a better understanding of the physiological processes during DOMS and muscle regeneration. In the future, this might help to optimize training and to reduce associated sports injuries.

Clinical Characteristics of Novel Coronavirus Disease in the Pediatric Population

Objectives: To assess the clinical characteristics of COVID-19 Virus disease in the pediatric population in Pakistan.&#x0D; Study Design: Cross-sectional study.&#x0D; Place and Duration of Study: Pak Emirates Military Hospital, Rawalpindi Pakistan, from Mar 2020 to Jan 2021.&#x0D; Methodology: All children presenting to the department with symptoms consistent with COVID-19 disease were tested for the virus. Patients who tested positive on the PCR were included in the study. Patients with non-consistent symptoms of COVID-19 and those who tested negative on the PCR were excluded from the study. All clinical data, including the age of the child, the onset of symptoms, the gap between the onset of symptoms and presentation as well as clinical symptoms, were documented on a predefined proforma.&#x0D; Results: A total of 106 patients were enrolled on the study. The mean age of patients was 5.6±2.5 years. The most frequent symptoms were fever (63, 59.6%) and cough (49, 46.2%). There were 3(2.9%) cases with severe or critical illness. The most frequent abnormal laboratory findings were leukopenia (29, 27.4%) and increased creatine kinase (38, 36.0%). Ground-glass opacities were observed in the HRCT chest of 17(65.3%) cases, out of 26 children diagnosed with pneumonia. The majority (70, 66%), had a positive exposure history. 88(83%) cases did not abide by the precautionary measures against the COVID-19 disease.&#x0D; Conclusions: The current study indicates that children usually present with mild symptoms but can present as severe diseases, as observed in this study.

Effects of Crude Rice Bran Oil and a Flaxseed Oil Blend in Young Horses Engaged in a Training Program.

Rice bran oil and flaxseed oil contain omega-3 fatty acids with the potential to reduce post-exercise inflammation and muscle damage. This study measures plasma interleukin-1β and creatine kinase and fatty acid profiles in lightly worked, young horses (Equus caballus) undergoing an exercise test after 60 days (d) of oil consumption, where the oil replaced 25% of concentrate calories. Treatments consisted of CON (no oil), FLAX (flaxseed oil blend), and RICE (crude rice bran oil). Blood was collected pre-exercise, and again at 1 min, 30 min, 24 h, 48 h, and 72 h post-IET. Data were analyzed by repeated measures ANOVA. Plasma creatine kinase activity was not different in CON during the study, greater (p &lt; 0.05) in RICE from pre-exercise to 30 min post-exercise across all exercise tests, and lesser (p &lt; 0.05) in FLAX at 30 min post-exercise on d 30 compared to d 0. Plasma interleukin-1β was greater (p &lt; 0.01) in CON on d 60, but no differences were observed in FLAX and RICE throughout the study. Plasma alpha-linolenic and linoleic acids were greatest (p &lt; 0.05) in FLAX after 30 d of inclusion, while CON horses had greater (p &lt; 0.05) EPA across all exercise tests and DHA after 60 d. These results indicate that 60 d of inclusion of crude rice bran oil or a flaxseed oil blend may benefit lightly worked, young horses by reducing training-program-related increases in interleukin-1β, while a flaxseed oil blend may reduce exercise-induced increases in creatine kinase. Additionally, the flaxseed oil blend has the potential to increase plasma omega-3 and omega-6 fatty acids. Replacing 25% of concentrate calories with flaxseed or rice bran oil has potential benefits for young horses in training.

Severity and Mortality Predictors of COVID-19 Patients with Thrombotic Events-Evidence from the "COVID-One" Hospital in Albania.

COVID-19 vaccination leads to lower infection, morbidity, and mortality rates. However, COVID-19 infection leads to the development of coagulopathy-related manifestations in the form of both venous and arterial thromboembolism. This study aimed to assess the severity and mortality predictors of COVID-19 patients with thrombotic events in hospitalized patients in Albania. This is a retrospective study conducted in the “Mother Tereza” University Hospital of Tirana. Data were retrieved from the electronic databases of the hospital and only COVID-19 cases admitted to the infectious department during August−December 2020 were selected. Patients who, at admission, had a C-reactive protein (CRP) (mg/L) more than double and a D-dimer (ng/mL) more than triple according to international standards were included in the study. We performed univariate and multivariable logistic regression analysis, calculating unadjusted and adjusted odds ratios (ORs). A p-value < 0.05 was considered statistically significant. The study population included 60 hospitalized persons with a mean age of 64.4 years. Increased lactate dehydrogenase (LDH) (OR = 2.93; 95% CI = 0.82−10.42, p-value = 0.1) and increased creatine kinase (CK) (OR = 2.17; 95% CI = 0.63−7.46, p-value = 0.22) were related with increased probability of death. Moreover, a decreased number of lymphocytes was associated with increased mortality but with no statistical significance (OR = 0.40; 95% CI = 0.11−1.40, p-value = 0.15). The survival rate was higher for patients without comorbidities (p = 0.045). These results could serve as a baseline and as a reference for healthcare personnel who provides services to hospitalized patients with COVID-19. Further studies should take into consideration the vaccination of the population as well as including more hospitals and patients.

MRI of Potassium and Sodium Enables Comprehensive Analysis of Ion Perturbations in Skeletal Muscle Tissue After Eccentric Exercise.

The aims were to investigate if potassium ( 39 K) magnetic resonance imaging (MRI) can be used to analyze changes in the apparent tissue potassium concentration (aTPC) in calf muscle tissue after eccentric exercise and in delayed-onset muscle soreness, and to compare these to corresponding changes in the apparent tissue sodium concentration (aTSC) measured with sodium ( 23 Na) MRI. Fourteen healthy subjects (7 female, 7 male; 25.0 ± 2.8 years) underwent 39 K and 23 Na MRI at a 7 T MR system, as well as 1 H MRI at a 3 T MR system. Magnetic resonance imaging data and blood samples were collected at baseline (t0), directly after performing eccentric exercise (t1) and 48 hours after exercise (t2). Self-reported muscle soreness was evaluated using a 10-cm visual analog scale for pain (0, no pain; 10, worst pain) at t0, t1, and t2. Quantification of aTPC/aTSC was performed after correcting the measured 39 K/ 23 Na signal intensities for partial volume and relaxation effects using 5 external reference phantoms. Edema volume and 1 H T 2 relaxation times were determined based on the 1 H MRI data. Participants were divided according to their increase in creatine kinase (CK) level into high (CK t2 ≥ 10·CK t0 ) and low CK (CK t2 < 10·CK t0 ) subjects. Blood serum CK and edema volume were significantly increased 48 hours after exercise compared with baseline ( P < 0.001). Six participants showed a high increase in blood serum CK level at t2 relative to baseline, whereas 8 participants had only a low to moderate increase in blood serum CK. All participants reported increased muscle soreness both at rest and when climbing stairs at t1 (0.4 ± 0.7; 1.4 ± 1.2) and t2 (1.6 ± 1.4; 4.8 ± 1.9) compared with baseline (0 ± 0; 0 ± 0). Moreover, aTSC was increased at t1 in exercised muscles of all participants (increase by 57% ± 24% in high CK, 73% ± 33% in low CK subjects). Forty-eight hours after training, subjects with high increase in blood serum CK still showed highly increased aTSC (increase by 79% ± 57% compared with t0). In contrast, aTPC at t2 was elevated in exercised muscles of low CK subjects (increase by 19% ± 11% compared with t0), in which aTSC had returned to baseline or below. Overall, aTSC and aTPC showed inverse evolution, with changes in aTSC being approximately twice as high as in aTPC. Our results showed that 39 K MRI is able to detect changes in muscular potassium concentrations caused by eccentric exercise. In combination with 23 Na MRI, this enables a more holistic analysis of tissue ion concentration changes.

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.

Belt Electrode-Skeletal Muscle Electrical Stimulation in Older Hemodialysis Patients with Reduced Physical Activity: A Randomized Controlled Pilot Study.

Background: Although patients receiving hemodialysis are more likely to develop metabolic disorders and muscle weakness at an earlier stage than healthy individuals, many older dialysis patients have difficulty establishing exercise habits to prevent these problems. Therefore, we evaluated the use of belt electrode-skeletal muscle electrical stimulation (B-SES), which can stimulate a wider area than conventional electrical muscle stimulation (EMS), to examine its application and safety in older hemodialysis patients as a means to improve lower extremity function without voluntary effort. Methods: This study was a randomized controlled trial (RCT) involving 20 older dialysis patients (>65 years old) with reduced physical activity. The control group received 12 weeks of routine care only and the intervention group received 12 weeks of B-SES during hemodialysis in addition to routine care. The primary endpoint was the 6 min walk test (6MWT) distance, while the Short Physical Performance Battery (SPPB), body composition, Functional Independence Measure (FIM), biochemistry test, and blood pressure/pulse measurements were used as secondary endpoints. Results: As a result of the 12-week B-SES intervention, no increase in creatine kinase or C-reactive protein levels was observed after the intervention in either group, and no adverse events attributed to the B-SES intervention were observed in the intervention group. Furthermore, the intervention group showed a significant improvement in the 6MWT and SPPB scores after the intervention. Conclusions: The results of this study suggest that a 12-week B-SES intervention during hemodialysis sessions safely improves 6MWT distance and SPPB scores in older patients with a reduced level of physical activity.

Perioperative rosuvastatin therapy increases creatine kinase and the risk of acute kidney injury in patients undergoing cardiac surgery

Abstract Introduction In patients undergoing cardiac surgery, perioperative statin therapy does not prevent atrial fibrillation or myocardial injury, but results in increased creatinine levels after surgery. Here we investigated the incidence of acute kidney injury (AKI) in 1922 patients scheduled for elective cardiac surgery who were randomized to perioperative rosuvastatin (20 mg once daily) or placebo in the Statin Therapy In Cardiac Surgery (STICS) trial. Methods AKI post-surgery was defined according to international guidelines using plasma creatinine. Biomarkers related to kidney function, muscle injury and inflammation were investigated, including cystatin C, total creatine kinase (CK), troponin I, growth differentiation factor 15 (GDF-15), interleukin-6 (IL-6), procalcitonin, and placental growth factor (PGF). Results At 48 hours post-surgery, AKI was significantly more common in patients allocated to rosuvastatin compared to placebo when defined by creatinine (24.7% vs 19.3%; OR 1.37 [95% CI 1.10–1.70]; p=0.005; Figure 1A) or by cystatin C (9.2% vs 5.1%; OR 1.86 [95% CI 1.29–2.67]; p&amp;lt;0.001; Figure 1B). Elevations in CK to &amp;gt;10x and &amp;gt;40x baseline level were also more frequent in rosuvastatin-allocated patients compared to placebo (30.9% vs 26.5%, p=0.02, and 2.1% vs 0.7%, p=0.02, respectively; Figure 1C). Post-operative concentrations of troponin I, GDF-15, IL-6, procalcitonin, and PGF were similar between the groups (Table 1). Conclusions Perioperative rosuvastatin initiation increased the absolute risk of AKI after cardiac surgery by 4–5%. Rosuvastatin also led to greater elevations in post-operative creatine kinase, but did not affect other biomarkers of tissue injury, inflammation, and myocardial injury. Further research is needed to delineate the underlying mechanism of AKI with perioperative rosuvastatin. Funding Acknowledgement Type of funding sources: Foundation. Main funding source(s): British Heart Foundation

Case report: One child with an autism spectrum disorder who had chronically elevated serum levels of CK and CK-MB

Some patients with autism spectrum disorder (ASD) exhibit elevated serum creatine kinase levels, which are believed to be associated with mitochondrial dysfunction. Although a few articles have reported this situation in the past and the increase mostly ranges from 100 to 300 U/L, there is a paucity of previous study focusing on the serum creatine kinase MB isoenzyme. This article discusses a 5-year-old girl with ASD, whose serum creatine kinase and creatine kinase MB isoenzyme have been rising for nearly 2 years, fluctuating at 584–993 and 111–625 U/L respectively. Except for behavioral and language symptoms associated with ASD, the child appears normal in other aspects. The child's laboratory tests showed no abnormality, except that the serum levels of lactic acid was slightly higher than normal (1.89 mmol/L, normal 1.33–1.78 mmol/L). The child was prescribed with a traditional Chinese medicine during the process and the serum creatine kinase MB isoenzyme level decreased dramatically to 111 U/L after the treatment. This study firstly recorded the serum creatine kinase levels and the MB isoenzyme in patients with autism spectrum disorder for nearly 2 years, indicating that patients with ASD may experience long-term increases in serum creatine kinase and creatine kinase MB isoenzyme, and that the traditional Chinese medicine decoction Xinfukang can temporarily reduce the serum creatine kinase MB isoenzyme level in patients. Nevertheless, the effect is not sustained. Therefore, it is of great importance to conduct long-term longitudinal studies so as to elucidate the potential mechanism responsible for long-term elevation of serum creatine kinase level.