Concept: Creatine kinase
Immune checkpoint inhibitors have improved clinical outcomes associated with numerous cancers, but high-grade, immune-related adverse events can occur, particularly with combination immunotherapy. We report the cases of two patients with melanoma in whom fatal myocarditis developed after treatment with ipilimumab and nivolumab. In both patients, there was development of myositis with rhabdomyolysis, early progressive and refractory cardiac electrical instability, and myocarditis with a robust presence of T-cell and macrophage infiltrates. Selective clonal T-cell populations infiltrating the myocardium were identical to those present in tumors and skeletal muscle. Pharmacovigilance studies show that myocarditis occurred in 0.27% of patients treated with a combination of ipilimumab and nivolumab, which suggests that our patients were having a rare, potentially fatal, T-cell-driven drug reaction. (Funded by Vanderbilt-Ingram Cancer Center Ambassadors and others.).
This study examined the effects of beetroot juice (BTJ) on recovery between two repeated-sprint tests. In an independent groups design, 20 male, team-sports players were randomized to receive either BTJ or a placebo (PLA) (2 × 250 mL) for 3 days after an initial repeated sprint test (20 × 30 m; RST1) and after a second repeated sprint test (RST2), performed 72 h later. Maximal isometric voluntary contractions (MIVC), countermovement jumps (CMJ), reactive strength index (RI), pressure-pain threshold (PPT), creatine kinase (CK), C-reactive protein (hs-CRP), protein carbonyls (PC), lipid hydroperoxides (LOOH) and the ascorbyl free radical (A(•-)) were measured before, after, and at set times between RST1 and RST2. CMJ and RI recovered quicker in BTJ compared to PLA after RST1: at 72 h post, CMJ and RI were 7.6% and 13.8% higher in BTJ vs. PLA, respectively (p < 0.05). PPT was 10.4% higher in BTJ compared to PLA 24 h post RST2 (p = 0.012) but similar at other time points. No group differences were detected for mean and fastest sprint time or fatigue index. MIVC, or the biochemical markers measured (p > 0.05). BTJ reduced the decrement in CMJ and RI following and RST but had no effect on sprint performance or oxidative stress.
Introduction: Catechins, abundant in green tea, exhibit many biological actions for potential clinical applications. Our purpose was to explore the potential benefits of catechin ingestion on recovery of physical performance after downhill running. Methods: ICR mice were used to examine the effects of prior catechin ingestion (0.5% w/w in diet for 3 weeks) on 1) wheelrunning activity, 2) running endurance, 3) muscle force, and 4) muscle oxidative stress and inflammation after downhill running (16 m/min for 5 min; 18 m/min for 5 min; 20 m/min for 10 min; and 22 m/min for 130 min). Results: Voluntary wheel-running activity and the contractile force of the isolated soleus muscle decreased (P<0.05) after downhill running. Notably, catechin ingestion significantly alleviated the running-induced decrease in voluntary wheel-running activity by 35%; the catechin-treated mice maintained endurance running capacity (214 ± 9 min vs. 189 ± 10 min; P<0.05). Further, catechins alleviated (P<0.05) the decrease in tetanic force evident in the soleus muscle after downhill running. Catechins suppressed the running-induced increases in plasma creatine phosphokinase levels by 52%; this was also true of the carbonylated protein content of the soleus muscle by 17% (P<0.05), malondialdehyde levels by 32% in the gastrocnemius muscle, and myeloperoxidase activity of the gastrocnemius by 22% (P<0.05). The levels of tumor necrosis factor-α, interleukin-1β, and monocyte chemoattractant protein-1 in the gastrocnemius muscle were significantly lower (P<0.05) by 33%, 29%, and 35%, respectively, in treated mice; the expression levels of mRNAs encoding these fell in parallel. Conclusion: Our results suggest that long-term intake of catechins, perhaps through their antioxidant properties, attenuate downhill-running-induced muscle damage by suppressing muscle oxidative stress and inflammation, hastening recovery of physical performance in mice.
It is well established that exercise-induced muscle damage (EIMD) has a detrimental effect on endurance exercise performed in the days that follow. However, it is unknown whether such effects remain after a repeated bout of EIMD. Therefore, the purpose of this study was to examine the effects of repeated bouts of muscle-damaging exercise on sub-maximal running exercise. Nine male participants completed baseline measurements associated with a sub-maximal running bout at lactate turn point. These measurements were repeated 24-48 h after EIMD, comprising 100 squats (10 sets of 10 at 80 % body mass). Two weeks later, when symptoms from the first bout of EIMD had dissipated, all procedures performed at baseline were repeated. Results revealed significant increases in muscle soreness and creatine kinase activity and decreases in peak knee extensor torque and vertical jump performance at 24-48 h after the initial bout of EIMD. However, after the repeated bout, symptoms of EIMD were reduced from baseline at 24-48 h. Significant increases in oxygen uptake [Formula: see text], minute ventilation [Formula: see text], blood lactate ([BLa]), rating of perceived exertion (RPE), stride frequency and decreases in stride length were observed during sub-maximal running at 24-48 h following the initial bout of EIMD. However, following the repeated bout of EIMD, [Formula: see text] [BLa], RPE and stride pattern responses during sub-maximal running remained unchanged from baseline at all time points. These findings confirm that a single resistance session protects skeletal muscle against the detrimental effects of EIMD on sub-maximal running endurance exercise.
Creatinine phosphokinase (CPK) and lactate dehydrogenase (LDH) are important biological markers of various myocardial disorders and exercise-induced muscle damage. Lycopene, on the other side, is a natural anti-oxidant with protective action against cardiovascular risk. Fifteen anaerobically trained athletes with elevated LDH and CPK baseline levels were enrolled in this study after undergoing thorough biochemical and cardiovascular evaluation with echocardiocraphy. In nine athletes tomato juice, a lycopene plain juice, was administered during and after exercise, replacing the carbohydrate supplementation beverages commonly used during training for over a two-month period. Tomato juice administration significantly reduced LDH and CPK levels, which returned back to almost normal levels. At the same time homocysteine and C-reactive protein were also attenuated. No changes were observed in the control group, where the usual carbohydrate supplementation had been followed.
Sporadic inclusion body myositis (IBM) is the most common idiopathic inflammatory myopathy (IIM) after age 50 years. It presents with chronic insidious proximal leg and distal arm asymmetric muscle weakness. Despite similarities with polymyositis (PM), it is likely that IBM is primarily a degenerative disorder rather than inflammatory muscle disease. IBM is associated with a modest degree of creatine kinase (CK) elevation and an electromyogram (EMG) demonstrates a chronic irritative myopathy. Muscle histopathology demonstrates endomysial inflammatory exudates surrounding and invading non-necrotic muscle fibers often times accompanied by rimmed vacuoles. We review IBM with emphasis on recent developments in the field and discuss ongoing clinical trials.
Recently, there have been important advances in the understanding of the pathophysiologic features, assessment, and management of patients with a newly diagnosed idiopathic inflammatory myopathy (IIM). Myositis-specific autoantibodies have been identified to define patient subgroups and offer prognostic implications. Similarly, proinflammatory cytokines, such as interleukin 6 and type 1 interferon-dependent genes, may serve as potential biomarkers of disease activity in adult and juvenile patients with dermatomyositis (DM). Moreover, magnetic resonance imaging has become an important modality for the assessment of muscle inflammation in adult IIM and juvenile DM. Immune-mediated necrotizing myopathies also are being recognized as a subset of IIM triggered by medications such as statins. However, confusion exists regarding effective management strategies for patients with IIM because of the lack of large-scale, randomized, controlled studies. This review focuses primarily on our current management and treatment algorithms for IIM including the care of pediatric patients with juvenile DM. For this review, we conducted a search of PubMed and MEDLINE for articles published from January 1, 1970, to December 1, 2011, using the following search terms: idiopathic inflammatory myopathies, dermatomyositis, polymyositis, juvenile dermatomyositis, sporadic inclusion body myositis, inclusion body myositis, inflammatory myositis, myositis, myopathies, pathogenesis, therapy, and treatment. Studies published in English were selected for inclusion in our review as well as additional articles identified from bibliographies.
- Journal of medical toxicology : official journal of the American College of Medical Toxicology
- Published over 3 years ago
Synthetic cathinones have emerged as popular drugs of abuse and produce sympathomimetic toxicity. It is unknown if rhabdomyolysis occurs more frequently following the use of synthetic cathinones compared to other stimulants. This retrospective study sought to determine the prevalence of rhabdomyolysis in patients with sympathomimetic toxicity and compare rates among patients using specific agents. Patients greater than 14 years of age with sympathomimetic toxicity and detection of a stimulant agent in urine via gas chromatography-mass spectroscopy (GC-MS) were included. Patients were excluded if clinical sympathomimetic toxicity was not present, a serum creatine kinase (CK) was not measured, or urine GC-MS was not performed. Rhabdomyolysis and severe rhabdomyolysis were defined as CK > 1000 and 10,000 IU/L, respectively. Prevalence of rhabdomyolysis and severe rhabdomyolysis were reported. Logistic regression was performed to determine the relative effect in single-agent exposures of a synthetic cathinone compared to other sympathomimetics on rhabdomyolysis. A secondary outcome, a composite endpoint defined as need for mechanical ventilation, renal replacement therapy, development of compartment syndrome, or death, was also analyzed. One hundred two subjects met inclusion criteria; median age (IQR) was 32 (25-42) years with a range of 14-65 years; 74 % were male. Rhabdomyolysis occurred in 42 % (43/102) of subjects. Patients whose sympathomimetic toxicity could be ascribed to a single agent were considered for further statistical analysis and placed into four groups: methamphetamine (n = 55), synthetic cathinone (n = 19), cocaine (n = 9), and other sympathomimetic (n = 6). In 89 subjects with single stimulant exposure, the prevalence of rhabdomyolysis was as follows: synthetic cathinone, 12/19 (63 %); methamphetamine, 22/55 (40 %); cocaine, 3/9 (33 %); and other single agent, 0/6 (0 %). The occurrence of severe rhabdomyolysis (CK > 10,000 IU/L) for each of the four groups was synthetic cathinone with 5/19 (26 %), methamphetamine with 2/55 (3.6 %), cocaine with 1/9 (11 %), and other with 0/6 (0 %). Median maximal CK (range) by groups was as follows: synthetic cathinone, 2638 (62-350,000+) IU/L; methamphetamine, 665 (61-50,233) IU/L; cocaine, 276 (87-25,614) IU/L; and other, 142 (51-816) IU/L. A statistically significant difference (p = 0.004) was found when comparing maximal CK among the four groups. Exposure to a synthetic cathinone compared with other sympathomimetics was associated with increased risk of developing rhabdomyolysis and severe rhabdomyolysis with odds ratios of 3.09 and 7.98, respectively. In this cohort of patients with sympathomimetic toxicity, 42 % developed rhabdomyolysis. Synthetic cathinones were associated with an increased risk of rhabdomyolysis and severe rhabdomyolysis compared with other stimulants.
Exertional rhabdomyolysis can occur in individuals performing various types of exercise but it is unclear why some individuals develop this condition while others do not. Previous investigations have determined the role of several single nucleotide polymorphisms (SNPs) to explain inter-individual variability of serum creatine kinase (CK) concentrations after exertional muscle damage. However, there has been no research about the interrelationship among these SNPs. The purpose of this investigation was to analyze seven SNPs that are candidates for explaining individual variations of CK response after a marathon competition (ACE = 287bp Ins/Del, ACTN3 = p.R577X, CKMM = NcoI, IGF2 = C13790G, IL6 = 174G>C, MLCK = C37885A, TNFα = 308G>A).
Statin-associated muscle symptoms (SAMS) are one of the principal reasons for statin non-adherence and/or discontinuation, contributing to adverse cardiovascular outcomes. This European Atherosclerosis Society (EAS) Consensus Panel overviews current understanding of the pathophysiology of statin-associated myopathy, and provides guidance for diagnosis and management of SAMS. Statin-associated myopathy, with significant elevation of serum creatine kinase (CK), is a rare but serious side effect of statins, affecting 1 per 1000 to 1 per 10 000 people on standard statin doses. Statin-associated muscle symptoms cover a broader range of clinical presentations, usually with normal or minimally elevated CK levels, with a prevalence of 7-29% in registries and observational studies. Preclinical studies show that statins decrease mitochondrial function, attenuate energy production, and alter muscle protein degradation, thereby providing a potential link between statins and muscle symptoms; controlled mechanistic and genetic studies in humans are necessary to further understanding. The Panel proposes to identify SAMS by symptoms typical of statin myalgia (i.e. muscle pain or aching) and their temporal association with discontinuation and response to repetitive statin re-challenge. In people with SAMS, the Panel recommends the use of a maximally tolerated statin dose combined with non-statin lipid-lowering therapies to attain recommended low-density lipoprotein cholesterol targets. The Panel recommends a structured work-up to identify individuals with clinically relevant SAMS generally to at least three different statins, so that they can be offered therapeutic regimens to satisfactorily address their cardiovascular risk. Further research into the underlying pathophysiological mechanisms may offer future therapeutic potential.