Increased Creatine Phosphokinase Levels Research Articles

Serological Biomarkers in Individuals with Interstitial Lung Disease after SARS-CoV-2 Infection and Association with Post-COVID-19 Symptoms.

Patients with interstitial lung disease (ILD) represent a vulnerable population against an acute SARS-CoV-2 infection. It has been observed that up to 80% of patients with ILD can develop post-COVID-19 symptomatology one year after. This secondary analysis aimed to, 1, compare serological biomarkers before and after surpassing a SARS-CoV-2 infection in individuals with interstitial lung disease (ILD) and, 2, to compare serological biomarkers between ILD patients who develop and those who do not develop post-COVID-19 symptoms. Seventy-six patients with ILD (40.4% women, age: 69, SD: 10.5 years) who survived a SARS-CoV-2 infection participated. High-resolution computerized tomography (CT) of the lungs, two pulmonary function tests (forced vital capacity (FVC) and diffusion value of carbon monoxide (DLCO)) and fourteen serological biomarkers were collected before and after SARS-CoV-2 infection. Participants were asked for the presence of post-COVID-19 symptomatology a mean of twelve (SD: eight) months after infection. Sixty patients (79%) showed post-COVID-19 symptoms (mean: 3.5, SD 1.1), with fatigue (68.4%), dyspnea (31.5%), and concentration loss (27.6%) being the most prevalent. Creatine phosphokinase (CPK) was the only biomarker showing differences in our study. In fact, CPK levels were higher after the acute SARS-CoV-2 infection (mean difference: 41.0, 95%CI 10.1 to 71.8, p = 0.03) when compared to before the infection. Thus, CPK levels were also higher in ILD patients with post-COVID-19 fatigue (mean difference: 69.7, 95%CI 12.7 to 126.7, p = 0.015) or with post-COVID-19 dyspnea (mean difference: 34.8, 95%CI 5.2 to 64.4, p = 0.025) than those patients without these post-COVID-19 symptoms. No significant changes in CT or functional pulmonary tests were observed after COVID-19 in patients with ILD. In conclusion, patients with ILD exhibited an increase in CPK levels after SARS-CoV-2 infection, albeit no changes in other serological biomarkers were identified. Similarly, the presence of post-COVID-19 fatigue or dyspnea was also associated with higher CPK levels in ILD patients. Studies investigating long COVID mechanisms in vulnerable populations such as ILD are needed.

ПОВЫШЕНИЕ КРЕАТИНФОСФОКИНАЗЫ КАК ДИАГНОСТИЧЕСКАЯ ПРОБЛЕМА У МУЛЬТИМОРБИДНОГО ПАЦИЕНТА С COVID-19 (КЛИНИЧЕСКОЕ НАБЛЮДЕНИЕ)

Background. Creatine phosphokinase is an enzyme that is often associated with muscle and myocardial disorders. However, other causes of elevated level of this enzyme are possible, such as stroke, hypothyroidism, paraneoplastic syndrome, as well as various pharmacological effects, including taking statins and the development of statin-associated muscle symptoms, the consequences of a previous coronavirus infection COVID-19. The aim of the work. To determine the cause of increased creatine phosphokinase in a patient after coronavirus infection associated with concomitant diseases; to carry out differential diagnosis of an increase in this enzyme. Results. We carried out an analysis of the patient’s medical history with a significantly increased creatine phosphokinase and subsequent differential diagnosis in order to identify the main causes of this change. The study was performed based on the assessment of general medical condition of the patient, as well as of the results of complete and bio-chemical blood counts (including the level of creatine phosphokinase and lactate dehydrogenase). Instrumental studies such as electroneuromyography, electrocardiography, echocardiography and ultrasound scanning were also carried out. The patient was diagnosed with ischemic cardiovascular disease and hypothyroidism. However, the increased creatine phosphokinase was not associated with statin use, since it was discontinued during observation, and the enzyme level increased over time. Other causes of increased creatine phosphokinase were also excluded, and the results indicate that the increase in this enzyme is likely caused by a previous coronavirus infection with concomitant diseases. Conclusion. The present study highlights the importance of a comprehensive approach to the differential diagnosis and treatment of increased creatine phosphokinase levels in patients with comorbid pathology, as this may be a con-sequence of various factors, including infections, concomitant diseases and pharmacological intervention.

A study of serum creatine phosphokinase and severity of organophosphorus poisoning

Organophosphorus (OP) poisoning is an important global health problem especially in developing countries. Estimation of erythrocyte cholinesterase (EChE) and plasma cholinesterase (BChE) as an evidence of OP poisoning is costly, not regularly performed and shows wide inter-individual variability. To study the feasibility of using serum creatine phosphokinase (CPK) as a predictor for severity of OP poisoning. Thirty four patients were included in this study who were admitted to tertiary care centre with history of OP poisoning less than 24hrs. The clinical severity of patients categorized according to Peradeniya organophosphorus poisoning (POP) scale. In our study 53.0% were male, 47.0% were female. Incidence of OP poisoning was more common among age group 21-30 years. Farmers (38.2%) were more common among occupation. Monocrotophos (46.0%) was commonly used compound for poisoning. 38.2% patients were severe. There was significant reduction in plasma cholinesterase and significant increase in CPK levels. There was a highly significant correlation between initial serum CPK levels and severity of acute OP poisoning. This study recommends CPK as an alternative biomarker for acute OP poisoning.

Spinal Muscular Atrophy 5q under the Mask of Myopathy: 10 Clinical Cases

Background. Spinal muscular atrophy 5q (5q SMA) is the most frequent autosomal recessive hereditary neuromuscular disease. Molecular genetic testing is used for SMA diagnosis, and it can confirm only 5q SMA. The clinical findings and results of paraclinical studies may overlap with hereditary primary-muscular diseases making the diagnosis difficult and delaying the administration of pathogenetic treatment for 5q SMA.Clinical case description. Clinical description of 10 patients with 5q SMA aged from 3 months to 25 years with different severity of proximal tetraparesis, skeletal muscular atrophy and tendon reflexes depression is given. 3 patients under 2 years of age with myogenic pattern at needle electromyography (nEMG) in lateral vastus muscle and 7 patients over 2 years of age with increased levels of creatine phosphokinase (CPK) in blood serum were mistakenly diagnosed for inherited primary-muscular diseases for the period from 1 month to 12 years. After the genetic counselling based on the disease course and clinical findings we suspected and later confirmed 5q SMA.Conclusion. In case of flaccid proximal tetraparesis associated with myogenic pattern at nEMG in young children or with increased CPK levels at late manifestation it is crucial to perform differential diagnosis of 5q SMA since there are options of pathogenetic therapy.

Statin-induced rhabdomyolysis in a 60-year-old woman with decompensated type 2 diabetes: a case report

Rhabdomyolysis is a very rare and most severe form of statin-induced muscle adverse event characterized by muscle pain, muscle necrosis with myoglobinemia and/or myoglobinuria with a very high risk of acute kidney injury and death. The article presents a case report of developing rhabdomyolysis in a middleaged female patient with hypertension, decompensated type 2 diabetes and albuminuria. A 60-year-old woman was admitted to the hospital for emergency indications with complaints of severe muscle weakness that began in the neck, which spread over several days to the upper and lower extremities, with a symptoms progression up to paresis. According to the appointment of a primary care physician, three months before hospitalization, the patient was switched from therapy with European generic brand-name rosuvastatin 20 mg to the Russian generic unbranded atorvastatin in the same dose (20 mg), which is not comparable in lipid-lowering effect. In a laboratory study, an increase in creatine phosphokinase level by 348 times (50462 U/L) of upper normal limit in combination with severe hypokalemia 1б7 mmol/L in the absence of renal dysfunction was recorded. Cancellation of statin, metformin and empagliflozin, intensive infusion therapy and treating electrolyte imbalance made it possible to prevent the development of acute renal damage, life-threatening arrhythmias and completely stop muscle complaints within a few days. The patient was discharged from the hospital on the 23rd day with reference clinical and laboratory values, including creatine phosphokinase.This case emphasizes the importance of maintaining clinical suspicion regarding rhabdomyolysis in patients receiving statin therapy in the presence of risk factors (in this case, female sex, hyperglycemia, chronic kidney disease, concomitant therapy), as well as the relevance of timely diagnosis and treatment of this condition.

Efficacy and safety of atorvastatin and rosuvastatin in ischemic heart disease patients: A prospective study

Purpose: To compare the safety and efficacy of two commonly used statins namely; atorvastatin and rosuvastatin, and determine the efficiency of CoQ10 in the reversal of statin-induced myopathy.
 Methods: An investigational study design was adopted using randomized trials involving patients suffering from ischemic heart disease and receiving either atorvastatin or rosuvastatin. The study was conducted at Punjab Institute of Cardiology, Lahore, Pakistan during the period, November 2016 - February 2017. A total number of 95 male and female patients, between the ages of 40 and 80 years, were selected. Their blood samples were analyzed for lipid profile, total cholesterol, serum high-density lipoprotein-cholesterol (HDL-C), serum triglycerides, low-density lipoproteins-cholesterol (LDL-C) and total cholesterol/HDL-C ratio.
 Results: Gender and dose showed significant correlation with creatine phosphokinase (CPK) levels, (p = 0.001) and (p > 0.001), respectively. The patients using rosuvastatin 20 mg had a higher risk of developing myopathy than those treated with atorvastatin 40 mg (p = 0.023), while atorvastatin 20 mg patients were more prone to induce myopathy than 10 mg (p = 0.001) recipients. Atorvastatin 20 mg produced higher CPK levels than rosuvastatin 10 mg (p = 0.002). A substantial increase in CPK levels was found with rosuvastatin 20 mg and atorvastatin 20 mg usage (p > 0.001). It was observed that rosuvastatin 20 mg significantly increased the risk of myopathy compared to atorvastatin 10 mg (p > 0.001). However, rosuvastatin 20 mg/day considerably reduced the blood cholesterol as compared to atorvastatin 10mg/day (p = 0.001). CPK levels reduced significantly following treatment with CoQ10 (p = 0.022).
 Conclusion: Rosuvastatin users are more prone to the risk of myopathy, myalgic symptoms and rise in CPK levels than atorvastatin users, and these effects are dose related. CoQ10 is effective in lowering CPK levels and reversing myalgia.

PERBANDINGAN KADAR ENZIM KREATININ FOSFOKINASE DAN NYERI OTOT SEBELUM DAN SESUDAH LATIHAN BERENANG SELAMA EMPAT MINGGU PADA PERENANG UNIT KEGIATAN MAHASISWA KLUB RENANG

A research has been done to compare the differences on the enzyme creatine phosphokinase (CPK) level and muscle soreness before and after 4-weeks swim practices on swimmers of College swimming club. Eighteen healthy male swimmers (mean ± SD; age: 19,94 ± 1,86 years; weight: 65,28 ± 6,14 kg; height: 1,72 ± 0,43 m) participated in this study. All subjects performed their 4-weeks swim practices which consist of 2x120 hours per week with 500 meters average daily swim distance and weight training. Blood was collected before and after the practices and CPK were analyzed. Questionnaires concerning muscle soreness were filled put before each blood draw. Results were analyzed using normality test and Wilcoxon signed rank test (p<0.05). There was significant increase in CPK level during 4-weeks swim practices by 59.41% (p=0.044). Whereas for muscle soreness (overall and specifically in arms and thighs), there was no significant differences between before and after the 4-weeks swim practices. As a conclusion, participation in 4-weeks swim practices resulted in significant serum CPK enzyme elevation, but there was lack of significance in muscle soreness differences on swimmers of College swimming club.

An Analytical Study about Serum Creatine Phosphokinase as Predictor and Marker of Severity in Organophosphorus Poisoning

Introduction: Organophosphorus (OP) toxicity is an important global health problem, especially in many developing countries because of their widespread use and easy accessibility. The objectives of our study were to measure serial serum creatine phosphokinase (CPK) levels, to correlate CPK levels with severity of poisoning, and to record the total dose of atropine required. Methods: This was a retrospective and analytical study. One hundred patients of either sex, having age >14 years, presented within 12 h of ingestion or inhalation of OP. It was observed that confirmation of OP poisoning was done by seeing the packet/container with clinical presentation. Clinical severity was categorized according to Peradeniya organophosphorus poisoning (POP) scale. Results: The severity of the poisoning increased in respect to POP score, the serum CPK levels, and total dose of atropine required for treatment also increased. The difference in serial CPK levels in patients without intermediate syndrome (IMS) and with IMS, it was observed that the difference in CPK between these patients was highly significant at baseline and 48 h. There was an increase in CPK levels at admission and 48 h, but reduced by 96 h. A weak positive correlation was observed between POP score and CPK levels, as well as CPK, and atropine dose. A negative correlation was observed between butyrylcholinesterase and CPK levels. Conclusion: In our opinion, these observations suggest that there is a direct relation between serum CPK levels and IMS. Hence, it is necessary for estimating CPK levels, especially after 48 h, in moderate-to-severe poisoning patients so that IMS can be recognized at the earliest and patients can be referred to higher centers for immediate management of respiratory failure, reducing morbidity and mortality.

PERBANDINGAN KADAR ENZIM KREATININ FOSFOKINASE DAN NYERI OTOT SEBELUM DAN SESUDAH LATIHAN BERENANG SELAMA EMPAT MINGGU PADA PERENANG UNIT KEGIATAN MAHASISWA KLUB RENANG

A research has been done to compare the differences on the enzyme creatine phosphokinase (CPK) level and muscle soreness before and after 4-weeks swim practices on swimmers of College swimming club. Eighteen healthy male swimmers (mean ± SD; age: 19,94 ± 1,86 years; weight: 65,28 ± 6,14 kg; height: 1,72 ± 0,43 m) participated in this study. All subjects performed their 4-weeks swim practices which consist of 2x120 hours per week with 500 meters average daily swim distance and weight training. Blood was collected before and after the practices and CPK were analyzed. Questionnaires concerning muscle soreness were filled put before each blood draw. Results were analyzed using normality test and Wilcoxon signed rank test (p<0.05). There was significant increase in CPK level during 4-weeks swim practices by 59.41% (p=0.044). Whereas for muscle soreness (overall and specifically in arms and thighs), there was no significant differences between before and after the 4-weeks swim practices. As a conclusion, participation in 4-weeks swim practices resulted in significant serum CPK enzyme elevation, but there was lack of significance in muscle soreness differences on swimmers of College swimming club.

Multicentre, retrospective study of the efficacy and safety of nivolumab for recurrent and metastatic salivary gland carcinoma

Although immune-checkpoint inhibitors (ICIs) are effective against various cancers, little is known regarding their role in salivary gland carcinoma (SGC) treatment. Therefore, we evaluated the efficacy and safety of nivolumab monotherapy in patients with recurrent and/or metastatic SGC. In this multicentre retrospective study, nivolumab (240 mg) was administered every 2 weeks. The overall response rate (ORR), progression-free survival (PFS), overall survival (OS), and safety were examined; the correlation between treatment outcomes and clinicopathological factors was analysed. Twenty-four patients were enrolled; the most common histopathology was salivary duct carcinoma. Eleven tumours were PD-L1-positive; no tumour was microsatellite instability-high. The ORR was 4.2%, and the median PFS and OS were 1.6 and 10.7 months, respectively. One patient continued nivolumab for 28 months without disease progression. One patient showed grade 4 increase in creatine phosphokinase levels and grade 3 myositis. Biomarker analysis revealed significantly increased OS in patients with performance status of 0; modified Glasgow prognostic score of 0; low neutrophil-to-lymphocyte ratio, lactate dehydrogenase, and C-reactive protein; and high lymphocyte-to-monocyte ratio and in patients who received systemic therapy following nivolumab. Although nivolumab’s efficacy against SGC was limited, some patients achieved long-term disease control. Further studies are warranted on ICI use for SGC.

Intermediate-Term Efficacy and Tolerance of Statins in Children

To evaluate the intermediate-term efficacy and tolerance of statins in children and adolescents with familial hypercholesterolemia. A total of 131 children or adolescents treated with statins for familial hypercholesterolemia were prospectively included. The efficacy of treatment was established by the percentage of children who achieved low density lipoprotein-cholesterol (LDL-C) levels <160mg/dL during treatment. Treatment tolerance was evaluated by the occurrence of clinical or laboratory side effects, regularity of increases in height and weight, and pubertal development. The median duration of treatment with statins was 4years. A median decrease of 32% in LDL-C levels was observed (P<.0001). The therapeutic target (LDL-C <160mg/dL) was achieved in 67% of cases. Increases in height and weight and sexual maturation were not affected by the treatment. Minor side effects were reported for 24 (18.4%) patients including 3 cases of a clinically asymptomatic increase in creatine phosphokinase (CPK) levels, 2 cases of an increase in CPK levels with muscular symptoms, 14 cases of myalgia without an increase in CPK levels, 3 cases of abdominal pain, 1 case of dysuria, and 1 case of diffuse pain. None of these side effects led to the discontinuation of statin therapy, although a change of statin was required in 7 cases. This new statin was tolerated in all cases. No patients had abnormal liver function during treatment. The results of this large cohort confirm the intermediate-term safety and efficacy of statin therapy in children with familial hypercholesterolemia.

Brigatinib: Novel ALK Inhibitor for Non-Small-Cell Lung Cancer.

We review here the pharmacology, pharmacokinetics, efficacy, safety, dosage and administration, potential drug-drug interactions and place in therapy of brigatinib for abnormal anaplastic lymphoma kinase (ALK) specific non-small-cell lung cancer (NSCLC). A literature search using PubMed was conducted using the terms brigatinib and ALK positive NSCLC from January 2013 to November 2018. All English-language articles evaluating brigatinib were analyzed for this review. Brigatinib was granted approval for the treatment of patients with metastatic ALK+ NSCLC who have progressed on or are intolerant to crizotinib. It is administered at a dose of 90 mg orally once daily for the first 7 days then, if tolerated, increased to a dose of 180 mg orally once daily. Common adverse effects include nausea, fatigue, diarrhea, increased creatine phosphokinase levels, headache, dyspnea, and hypertension. Serious treatment-emergent adverse effects were pulmonary related. Relevance to Patient Care and Clinical Practice: This article discusses the clinical trials that led to the accelerated approval of brigatinib for its ability to overcome crizotinib-resistant mutations and for its increased central nervous system penetration properties. Brigatinib was granted accelerated approval for the treatment of patients with metastatic ALK+ NSCLC who have progressed on or are intolerant to crizotinib. In a subset of NSCLC patients, brigatinib increases survival for approximately 1 year; however, side effects were detected.

Minimally invasive surgery for resection of ossification of the ligamentum flavum in the thoracic spine.

IntroductionThoracic ossification of the ligamentum flavum (TOLF) is a common cause of progressive thoracic myelopathy. Surgical decompression is commonly used to treat TOLF.AimTo evaluate the clinical outcomes of microsurgical decompression of TOLF via a paraspinal approach, using a percutaneous tubular retractor system.Material and methodsFirst, three-dimensional (3D) image reconstruction and printed models were made from thin computed tomography scans for each patient. Then, 3D computer-assisted virtual surgery was performed using the 3D reconstruction to calculate the precise location and sizes of the bone window and the angle of insertion of the percutaneous tubular retractor system. In total, 13 patients underwent the surgery through the percutaneous micro channel unilateral vertebral approach under electrophysiological monitoring. Five days after the surgery, increased creatine phosphokinase levels returned to preoperative levels. The Japanese Orthopedic Association (JOA) score was improved and computed tomography reconstruction and magnetic resonance imaging of the thoracic spine showed that decompression was achieved without injuries to the spinal cord or nerve root. The stability of the spine was not affected, nor were any deformities of the spine detected. Finally, nerve functional recovery was achieved with minimal injury to the paraspinal muscle, articulum, spinous process and ligament.ResultsThe mean operative time was 98.23 ±19.10 min, and mean blood loss was 19.77 ±5.97 ml. At a mean follow-up of 13.3 months (median: 12 months), the mean JOA score was 7.54 ±1.13 at the final follow-up, yielding a mean RR of 49.10 ±15.71%. Using The recovery rate, 7 (53.85%) patients had good outcomes, 5 (38.46%) patients had a fair outcome, and 1 (7.69%) patient had poor outcomes, indicating significant improvement by the final follow-up examination (p < 0.05).ConclusionsThe 3D printed patient model-based microsurgical resection of TOLF via the paraspinal approach can achieve decompression of the spinal canal with minimal complications, faster recovery and improved stability of the vertebral body.

Spontaneous poisoning by Prosopis juliflora (Leguminosae) in sheep

ABSTRACT: The aim of this paper is to describe the first report of spontaneous poisoning by Prosopis juliflora in sheep. From flock of 500 sheep at risk, four adult male sheep were affected. One died spontaneously and three other were examined, euthanized and necropsied. Neurologic examination focused particularly on motor and sensory-cranial nerve function, complete blood counts, serum biochemistry and urinalysis were done. The evolution of the disease was chronic and to present signs of poisoning, sheep had to ingest a diet containing at least 80% of P. juliflora pods during 21 months. The biochemistry revealed a substantial increase in creatine phosphokinase levels. Clinical signs included drooling of saliva, dropped jaw, tongue protrusion and loss of food from the mouth. Gross and histological lesions were similar to those previously reported in cattle and goats. Sheep are more resistant to poisoning by P. juliflora considering that it took 21 months of pod consumption to show clinical signs. There is no specific treatment for P. juliflora poisoning in ruminants.

Fetal Nerve Cell Transplantation in Early Post-Resuscitation Period in Rats.

IntroductionFetal cell transplantation is a promising biomedical approach for disease treatment; however, the use of fetal cell therapy is still experimental. This research was deemed a necessity to provide evidence-based research for the application of cell transplantation as a treatment method. The aim of this study was to evaluate the effect of fetal nerve cell transplantation in rat survivors (and non-survivors) after clinical death by mechanical asphyxia.Methods68 white laboratory rats were divided into two groups of identical age and sex: a control group of 12-month adult male rats (n = 26) and an experimental group (n = 42). Rats were fixed under ether anesthesia. We then blocked the oral and nasal regions with cotton wool soaked in saline solution. A four-minute clinical death though acute mechanical asphyxia was simulated by applying the method of N. Shim. After the 4-minute clinical death, we resuscitated the rats using external cardiac massage and artifical respiration. Suspension of the fetal nerve cells was injected intraperitoneally at 1mm3 per 25g at the time of cardiac activity restoration. Lactate dehydrogenase (LDH) and creatine phosphokinase (CPK) levels were examined in the homogenate cerebral cortex of reanimated animals. We recorded the survival rate during the post-resuscitation period and analyzed the integrative brain functions using anxiety-phobic status and latent inhibition.ResultsAfter fetal nerve cell transplantation, the enzymatic reactions in the experimental group became normal with a significant decrease in LDH and an increase in CPK levels compared to the control group. In the control group, 10 rats died and 16 lived (62% survival rate), while 7 rats died and 35 lived (83% survival rate) in the experimental group during the first 7 days. Rats that did not receive the treatment tended to die sooner than those in the experimental group. As a result of transplantation, the anxiety level in the experimental group was less than in the control group. Moreover, cell therapy improved the reflexes in the experimental animals.ConclusionsThe study revealed the positive neuroprotective effect of the fetal nerve cells on the recovery in the early post-resuscitation period. This was confirmed by the normalization of enzymatic reactions, improvement reflective activity, and increase in the survival rate of the resuscitated animals in the group treated with fetal nerve cell transplantation. These findings warrant future research on the mechanisms associated with reflex improvement.

Creatine Phosphokinase and Visual Analogue Scale as Indicators for Muscle Injury in Untrained Bodybuilders

Background : Skeletal muscle is a vital tissue in the human body to enable breathing, walking and performing several sports activities. However, this muscle is persistently injured throughout every sports session. Some exercises demand a muscle injury occurrence in order to build a stronger muscle through an adaptation process namely bodybuilding exercise. Importantly, every muscle injury should occur within a physiological range which can be identified by several biomarkers as well as pain scale. The aim of this study was to identify changes on the level of Creatine phosphokinase (CPK) and Visual analogue scale (VAS) between pre and post training sessions and the correlation between these two indicators. Methods : This was an observational analytical cross sectional comparison study which was conducted in October 2012 and the subjects were adult untrained bodybuilders at the Jatinangor fitness center. The data was obtained by measuring serum CPK and marked VAS. The data were analyzed by t-test, Wilcoxon’s test and Spearman’s correlation. Results : Both CPK and VAS increased significantly by 296 U/L and 19.9 mm respectively. There was a strong positive significant correlation between VAS and CPK (p=0.01, r = 0.711). Conclusion : The healthy untrained bodybuilders chosen in this study experienced a mild (&lt;2000 U/L) muscle injury throughout the training sessions with general increased CPK levels and VAS measurement. [AMJ.2015;2(1):147–52]

Tolerability of High Doses of Daptomycin in the Treatment of Prosthetic Vascular Graft Infection: A Retrospective Study.

IntroductionIn treatment of prosthetic vascular graft infection (PVGI), appropriate antimicrobial treatment is crucial for controlling the septic process and preventing re-infection of the new graft. Glycopeptides are the mainstay of treatment for device-related infections by methicillin-resistant Staphylococcus aureus strains, but with some limitations, especially concerning vancomycin-intermediate and glycopeptide-intermediate S. aureus. We report our experience using a high dose of daptomycin (DAP) for treatment of PVGI.MethodsWe reviewed medical reports of 26 patients treated with high doses of DAP (>8 mg/kg) and beta-lactams/aminosides for PVGI, defined as positive bacterial culture of intraoperative specimens or blood samples and/or clinical, biological, and radiological signs of infection. Clinical success was defined by resolution of all clinical signs at the end of follow-up, without the need for additional antibiotic therapy, and/or negative culture in case of new surgery.ResultsCultures of intraoperative samples were positive in 21 patients (80.8%). Blood and intraoperative cultures were concomitantly positive in 10 patients. The main microorganism identified in microbiological samples was S. aureus (n = 18). Surgery was performed in 23 patients (88.4%). The mean duration of the DAP regimen was 12.3 ± 11.9 days. DAP was discontinued in 26 patients [need to switch to microbiological results (n = 19), bacterial pneumonia (n = 2), and increased creatine phosphokinase levels (n = 4)]. One patient had myalgia, while 9 received concomitant statins.ConclusionHigh-dose DAP therapy shows a satisfactory toxicity profile even in severely ill patients with multiple comorbidities, and may favorably compete with vancomycin, especially concerning the risk of induced nephrotoxicity.Electronic supplementary materialThe online version of this article (doi:10.1007/s40121-014-0035-9) contains supplementary material, which is available to authorized users.

Atorvastatin Safety in Kawasaki Disease Patients With Coronary Artery Aneurysms

Statins (HMG-CoA reductase inhibitors) may decrease inflammation in postacute Kawasaki disease (KD) complicated by coronary artery aneurysm (CAA) and promote vascular remodeling. There are limited data on their safety in young children. Twenty patients with CAAs after KD (median CAA z-score=+25) were treated with 5/10mg atorvastatin daily for a median of 2.5years (range 0.5-6.8) starting at a median of 2.3years (range 0.3-8.9) after acute KD (median age 9.3years [range 0.7-14.3]). Compliance with treatment was excellent: only one patient reported minor side effects (joint pain, no change in medication). Average total cholesterol before atorvastatin was 3.73±0.84mmol/L and after atorvastatin was 3.21±0.46mmol/L (relative decrease -14%, p=0.02); low-density lipoprotein cholesterol was 1.99±0.76mmol/L before and only 1.49±0.27mmol/L after (relative decrease -20%, p=0.04); high-density lipoprotein was 1.39±0.36mmol/L before and 1.30±0.27mmol/L after (relative decrease -4%, p=0.35); and triglycerides were 0.71±0.28mmol/L before and 0.71±0.18mmol/L after (relative decrease -5%, p=0.38). Nine of 20 patients (45%) experienced at least 1 episode of hypocholesterolemia (total cholesterol <3.1mmol/L), and 2 patients required atorvastatin dose lowering. Transient mild increase of liver enzymes (aspartate aminotransferase/alanine aminotransferase 45-60U/L) were seen in 7 of 20 (35%) patients with no patients experiencing more severe increases. Only one patient experienced increased creatine phosphokinase levels (>500U/L). Serial measurements of age- and sex-specific percentiles of weight (estimated change: 1.4 [2.7]% per year, p=0.60), height (estimated change: -3.2 [3.2]% per year, p=0.32), and body mass index (estimated change: 1.0 [2.9]% per year, p=0.73) showed no association between anthropomorphic growth and atorvastatin treatment. Atorvastatin use in very young children with KD is safe but should be closely monitored.

Gender Effects on Statin-Associated Muscular Adverse Events: An Analysis of the FDA AERS Database

Objective: The reports submitted to the US Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS) from 1997 to 2011 were reviewed to assess the gender effects on muscular adverse events induced by the administration of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors (statins). Methods: After the deletion of duplicated submissions and the revision of arbitrary drug names, the reports involving pravastatin, simvastatin, atorvastatin, rosuvastatin, and cerivastatin were analyzed. Data mining algorithms were applied for the quantitative detection of signals, where a signal means a drug-associated adverse event, including the proportional reporting ratio, the reporting odds ratio, the information component, and the empirical Bayes geometric mean. Myopathy, myalgia, myositis, rhabdomyolysis, and an increase in creatine phosphokinase level were focused on as the muscular adverse events. Results: The total number of reports was 3,472,494. The signal scores suggested that all 5 statins were associated with 5 muscular adverse events in both male and female patients. The scores varied among statins, but were more noteworthy for cerivastatin. Conclusion: The data strongly suggested the necessity of well-organized clinical studies on statin-associated muscular adverse events.

Statin-Associated Muscular and Renal Adverse Events: Data Mining of the Public Version of the FDA Adverse Event Reporting System

ObjectiveAdverse event reports (AERs) submitted to the US Food and Drug Administration (FDA) were reviewed to assess the muscular and renal adverse events induced by the administration of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors (statins) and to attempt to determine the rank-order of the association.MethodsAfter a revision of arbitrary drug names and the deletion of duplicated submissions, AERs involving pravastatin, simvastatin, atorvastatin, or rosuvastatin were analyzed. Authorized pharmacovigilance tools were used for quantitative detection of signals, i.e., drug-associated adverse events, including the proportional reporting ratio, the reporting odds ratio, the information component given by a Bayesian confidence propagation neural network, and the empirical Bayes geometric mean. Myalgia, rhabdomyolysis and an increase in creatine phosphokinase level were focused on as the muscular adverse events, and acute renal failure, non-acute renal failure, and an increase in blood creatinine level as the renal adverse events.ResultsBased on 1,644,220 AERs from 2004 to 2009, signals were detected for 4 statins with respect to myalgia, rhabdomyolysis, and an increase in creatine phosphokinase level, but these signals were stronger for rosuvastatin than pravastatin and atorvastatin. Signals were also detected for acute renal failure, though in the case of atorvastatin, the association was marginal, and furthermore, a signal was not detected for non-acute renal failure or for an increase in blood creatinine level.ConclusionsData mining of the FDA's adverse event reporting system, AERS, is useful for examining statin-associated muscular and renal adverse events. The data strongly suggest the necessity of well-organized clinical studies with respect to statin-associated adverse events.