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Cholesterol-lowering statins are frequently prescribed for primary and secondary prevention of ischaemic vascular events. Whereas most patients tolerate statins without problems, statin-associated myopathy is well documented, as are several risk factors. We present a case report of an 80-90-year-old man with coronary artery disease who rapidly developed severe rhabdomyolysis during treatment with rosuvastatin while in intensive care. He had several concomitant risk factors for statin-induced myopathy including high dosage, old age, renal and hepatic impairment, and a pharmacogenetic SLCO1B1*1 a/*5 variant. Single known risk factors have a low predictive value for statin-induced myopathy and may therefore be underestimated in clinical practice. However, adverse drug reactions frequently involve the joint action of a multitude of environmental and genetic component causes, and statin-induced myopathy should be regarded as a multicausal event. We therefore advocate a proactive multifactorial risk assessment to guide and individualise statin therapy in high-risk patients., Competing Interests: Competing interests: None declared., (© European Association of Hospital Pharmacists 2024. Re-use permitted under CC BY-NC. No commercial re-use. Published by BMJ.)

Purpose: Rhabdomyolysis is a clinical syndrome with the potential to cause cardiac arrhythmias, renal failure, and even death. Currently, there are no studies regarding risk factors for developing post-operative rhabdomyolysis (POR) after spinal fusion surgeries. Our objective was to study risk factors associated with, and to develop a decision-making framework for post-operative rhabdomyolysis after spinal fusion surgery., Methods: We performed a retrospective cohort study of all spinal fusions of three or more levels over 2.25 years by a single surgeon at two centers. POR was defined as a creatine phosphokinase (CPK) greater than 2000 IU/L., Results: 76 surgical procedures on 72 patients were identified. Rate of POR in our cohort was 22% (17/76). Male sex was associated with POR ( p  < 0.05). Previously validated risk factors: younger age, lower ASA score, elevated BMI, higher pre-operative creatinine, increased intraoperative blood loss, specific surgical positions, and length of surgery, were not associated with POR. In a logistic regression model, male gender increases the odds of POR in all patients 5.82-fold ( p  = 0.047). In patients without a second surgery within seven days, a logistic regression model suggests each additional level fused via transpsoas approach, and male gender, increases the risk of POR 1.81-times ( p  = 0.015), and 6.26-times ( p  = 0.047), respectively. In patients with posterior fusions, a logistic regression model suggests increasing the number of lateral levels fused via transpsoas approach in the same surgery, and male gender, increases the risk of POR 1.68-times and 6.34-times, respectively. In these same subgroups, increased thickness of the psoas major in lateral transpsoas fusions increased risk of POR ( p  = 0.023, p  = 0.046, respectively)., Conclusions: In spinal fusions, increasing the number of lateral levels fused via transpsoas approach, and male gender, predispose patients to increased risk of POR in those without a second surgery within seven days, and in those with a simultaneous posterior fusion.

Objectives: The aim of the present study was to clarify the relationships of intraoperative surgical position with the incidence of postoperative rhabdomyolysis and with postoperative renal function to safely perform robot-assisted radical prostatectomy., Methods: The participants in the present study were 276 consecutive patients who underwent robot-assisted radical prostatectomy at our institutions between 2013 and 2020; 130 cases were performed in the opened legs position and 146 cases in the lithotomy position with a steep 23°-25° head-down position. Rhabdomyolysis was defined as creatine kinase values greater than 1000 IU/L. Propensity score matching including age, body mass index, the presence of comorbidities, preoperative creatine kinase, preoperative estimated glomerular filtration rate, and prostate-specific antigen was performed, resulting in a matched cohort of 146 patients (opened legs position group n = 73; lithotomy position group n = 73)., Results: After propensity score matching, creatine kinase values on the first day after surgery were significantly lower in the opened legs position group than in the lithotomy position group (opened legs position group: lithotomy position group = 246.9 ± 114.9 IU/L: 558.2 ± 114.9 IU/L, P = 0.034). There were significantly fewer patients diagnosed with postoperative rhabdomyolysis in the opened legs position group (opened legs position group: lithotomy position group = 0% (0/73): 9.6% (7/73), P < 0.001). In addition, fluid replacement volume was significantly less in the opened legs position group (opened legs position group: lithotomy position group = 5747 ± 180 mL: 6349 ± 0176 mL, P = 0.018)., Conclusions: To prevent rhabdomyolysis after surgery, robot-assisted radical prostatectomy should be performed in the opened legs position., (© 2022 The Japanese Urological Association.)

Background: Timing of extremity fracture fixation in patients with an associated major vascular injury remains controversial. Some favor temporary fracture fixation before definitive vascular repair to limit potential graft complications. Others advocate immediate revascularization to minimize ischemic time. The purpose of this study was to evaluate the timing of fracture fixation on outcomes in patients with concomitant long bone fracture and major arterial injury., Methods: Patients with a combined long bone fracture and major arterial injury in the same extremity requiring operative repair over 11 years were identified and stratified by timing of fracture fixation. Vascular-related morbidity (rhabdomyolysis, acute kidney injury, graft failure, extremity amputation) and mortality were compared between patients who underwent fracture fixation prerevascularization (PRE) or postrevascularization (POST)., Results: One hundred four patients were identified: 19 PRE and 85 POST. Both groups were similar with respect to age, sex, Injury Severity Score, admission base excess, 24-hour packed red blood cells, and concomitant venous injury. The PRE group had fewer penetrating injuries (32% vs. 60%, p = 0.024) and a longer time to revascularization (9.5 vs. 5.8 hours, p = 0.0002). Although there was no difference in mortality (0% vs. 2%, p > 0.99), there were more vascular-related complications in the PRE group (58% vs. 32%, p = 0.03): specifically, rhabdomyolysis (42% vs. 19%, p = 0.029), graft failure (26% vs. 8%, p = 0.026), and extremity amputation (37% vs. 13%, p = 0.013). Multivariable logistic regression identified fracture fixation PRE as the only independent predictor of graft failure (odds ratio, 3.98; 95% confidence interval, 1.11-14.33; p = 0.03) and extremity amputation (odds ratio, 3.924; 95% confidence interval, 1.272-12.111; p = 0.017)., Conclusion: Fracture fixation before revascularization contributes to increased vascular-related morbidity and was consistently identified as the only modifiable risk factor for both graft failure and extremity amputation in patients with a combined long bone fracture and major arterial injury. For these patients, delaying temporary or definitive fracture fixation until POST should be the preferred approach., Level of Evidence: Prognostic study, Level IV., (Copyright © 2021 American Association for the Surgery of Trauma.)

Exertional rhabdomyolysis may occur when an individual is subjected to strenuous physical exercise. It is occasionally associated with myoglobinuria (i.e. "cola-colored" urine) alongside muscle pain and weakness. The pathophysiology of exertional rhabdomyolysis involves striated muscle damage and the release of cellular components into extracellular fluid and bloodstream. This can cause acute renal failure, electrolyte abnormalities, arrhythmias and potentially death. Exertional rhabdomyolysis is observed in high-performance athletes who are subjected to intense, repetitive and/or prolonged exercise but is also observed in untrained individuals and highly trained or elite groups of military personnel. Several risk factors have been reported to increase the likelihood of the condition in athletes, including: viral infection, drug and alcohol abuse, exercise in intensely hot and humid environments, genetic polymorphisms (e.g. sickle cell trait and McArdle disease) and epigenetic modifications. This article reviews several of these risk factors and proposes screening protocols to identify individual susceptibility to exertional rhabdomyolysis as well as the relevance of proteomics for the evaluation of potential biomarkers of muscle damage., Competing Interests: Declarations of Competing Interest All authors declare no potential conflict of interest related to this manuscript., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Rhabdomyolysis is defined by myalgia, potentially painful myoedema and muscular weakness due to death of muscular fiber in the striated muscle. Frequent etiologies include physical effort, intoxication (alcohol, drugs and medication) and physical trauma. Depletion of myocyte' s adenosine triphosate (ATP) leads to an increase in intracellular calcium and myocyte death. Diagnosis relies on creatine kinase (CK) levels. The clinical spectrum of rhabdomyolysis includes an asymptomatic increased amount of CK as well as severe, life threatening complications such as acute renal failure and electrolyte disorders. Treatment is based on prevention and addressing complications., Competing Interests: Les auteurs n’ont déclaré aucun conflit d’intérêts en relation avec cet article.

Aromatic L-amino acid decarboxylase (AADC) deficiency is a rare, autosomal recessive inborn error of metabolism in which several neurotransmitters including serotonin, dopamine, norepinephrine and epinephrine are deficient. Symptoms typically appear in the first year of life and include oculogyric crises and dystonia, hypotonia, and global developmental delay. Dystonia is of particular concern as a dystonic storm can ensue leading to rhabdomyolysis. Rhabdomyolysis can become life-threating and therefore its recognition and prompt management is of significant importance. Here we present two cases of patients with AADC deficiency and a history of dystonic crisis causing rhabdomyolysis. We hypothesize that in addition to the hypodopaminergic, a hypercholinergic state is contributing to the pathophysiology of dystonia in AADC deficiency, as well as to the associated rhabdomyolysis. We were able to prevent rhabdomyolysis in both patients with using Dantrolene and we suggest using a trial of this medication in cases of sustained dystonic crisis in AADC deficiency patients., Competing Interests: None declared, (Georg Thieme Verlag KG Stuttgart · New York.)

Acute kidney injury (AKI) is a clinical syndrome associated with the incidence of rhabdomyolysis (RM). The current study was carried out to evaluate whether selenium nanoparticles (SeNPs) can protect against the glycerol-induced AKI model. Rats were distributed into four equal groups (n = 7): the control group (G1), SeNPs group (G2), AKI group (G3), and SeNPs+AKI group (G4). Rats in G1 were intramuscularly injected with physiological saline (0.9% NaCl). Rats in G2 were gavaged with SeNPs (0.1 mg/kg) for 14 days. Rats in G3 were intramuscularly injected with 50% glycerol (10 ml/kg). Rats in G4 were administered with SeNPs for 14 days and then injected with glycerol, as in G3. Glycerol-injected rats showed a significant increase in the kidney relative weight, as well as in the serum urea, creatinine, Kim-1, and renal malondialdehyde, nitric oxide, TNF-α, IL-1β, cytochrome c, Bax, and caspase-3 levels. In addition, a significant decrease in glutathione, glutathione peroxidase, glutathione reductase, superoxide dismutase, and catalase was recorded in the renal tissue. Selenium nanoparticles reduced the biochemical, molecular, and histological changes produced by glycerol. Overall, our results suggest that selenium nanoparticles could be used to protect against AKI development via antioxidant, anti-inflammatory, and anti-apoptotic activities.

Background: A BRAF V600E mutation is found as driver oncogene in patients with non-small cell lung cancer. Although combined treatment with dabrafenib and trametinib is highly effective, the efficacy of reduced doses of the drugs in combination therapy has not yet been reported., Case Presentation: A Japanese man in his mid-sixties was diagnosed with unresectable lung adenocarcinoma and was unresponsive to cytotoxic chemotherapy and immune checkpoint inhibitors. The BRAF V600E mutation was detected by next generation sequencing, and the patient was subjected to treatment with dabrafenib and trametinib in combination. Although the treatment reduced the tumor size, he experienced myalgia and muscle weakness with elevated serum creatine kinase and was diagnosed with rhabdomyolysis induced by dabrafenib and trametinib. After the patient recovered from rhabdomyolysis, the treatment doses of dabrafenib and trametinib were reduced, which prevented further rhabdomyolysis and maintained tumor shrinkage., Conclusion: The reduction of the doses of dabrafenib and trametinib was effective in the treatment of BRAF V600E-mutant NSCLC, and also prevented the incidence of rhabdomyolysis.

: Adequate food intake is important prior to endurance running competitions to facilitate adequate exercise intensity. However, no investigations have examined whether dietary intake could prevent exercise-induced muscle damage (EIMD) and cardiac stress (EICS). Thus, this study's objective was to determine the associations between EIMD, EICS and endurance athlete diets one week before a marathon race. Sixty-nine male runners participated in this study. Food intake during the week prior to the race was collected through a seven-day weighed food record. Dietary intake on race day was also recorded. At the end of the marathon, blood samples were drawn to determine serum creatine kinase (CK) and myoglobin, and muscle-brain isoform creatine kinase (CK-MB), prohormone of brain natriuretic peptide (NT-proBNP), cardiac troponin I (TNI), and cardiac troponin T (TNT) concentration as markers of EIMD and EICS, respectively. To determine the association between these variables, a stepwise regression analysis was carried out. The dependent variable was defined as EIMD or EICS and the independent variables were defined as the number of servings within each different food group. Results showed that the intake of meat during the previous week was positively associated with post-race CK (Standardized Coefficients (β) = 0.643; p < 0.01) and myoglobin (β = 0.698; p < 0.001). Vegetables were negatively associated the concentration of post-race CK (β = -0.482; p = 0.002). Butter and fatty meat were positively associated with NT-proBNP (β = 0.796; p < 0.001) and TNI (β = 0.396; p < 0.001) post-marathon values. However, fish intake was negatively associated with CK (β = -0.272; p = 0.042), TNI (β = -0.593; p < 0.001) and TNT (β = -0.640; p = 0.002) post-marathon concentration. Olive oil was negatively associated with TNI (β = -0.536; p < 0.001) and TNT (β = -0.415; p = 0.021) values. In conclusion, the consumption of meat, butter, and fatty meat might be associated with higher levels of EIMD and EICS. On the other hand, fish, vegetables, and olive oil might have a protective role against EIMD and EICS. The selection of an adequate diet before a marathon might help to reduce some of the acute burdens associated with marathon races., Competing Interests: The authors declare no conflict of interest.

Exertion-related illness (ERI), despite aggressive efforts with both prevention and emergency action planning, continues to be a considerable threat to both athletes and warfighters. Numerous case reports and series have served to elucidate risk factors, which have in turn become the focus of prevention strategies. While this approach has assisted in mitigating athlete risk, recent institutional guidance has identified the need for greater protection of athletes by accountability of training programs and the recognition of periods of distinct athlete vulnerability. These recommendations, in addition to observations from lessons learned from the aforementioned cluster reports of ERI, have a strong call-out for the role of leadership as both a culprit for injury and a potential mechanism for prevention. This commentary introduces a leader-follower framework and explores this model in the evolution of ERI and offers recommendations as to how we move forward toward making progress in prevention.

Acute viral myositis is a complication after a viral infection mainly caused by Influenza A and B viruses. It is characterized as a transitory, sudden, self-limiting and benign inflammatory process. It usually affects preschool and school children presenting bilateral pain and sensitivity in the muscle groups of the lower limbs without alteration in the neurological examination. It can affect the gait or standing. The main complication is rhabdomyolysis, which is why clinical followup and values of creatine phosphokinase must be done. We present the case of a school-age child diagnosed with acute viral myositis. Because it is not a frequent entity and its incidence in Latin America is unknown, we consider important to report the case and review the topic, as its clinical course is benign, easily treated, and its knowledge can avoid unnecessary studies and hospitalizations., Competing Interests: The authors report no conflicts of interest in this work., (Sociedad Argentina de Pediatría.)

Background: Asymptomatic or mildly symptomatic exercise-associated hyponatremia (EAH) can be exacerbated by aggressive hydration., Objective: This work predicts the percentage of athletes at risk for exacerbation of EAH from indiscriminate hydration after an ultramarathon., Methods: Postrace serum sodium, creatinine, creatine kinase (CK), and urea nitrogen concentrations were determined for 161-km ultramarathon participants. Body mass was measured prior to and immediately after the race. Incidents when serum CK was > 20,000 U/L or creatinine ≥ 1.5 times estimated baseline were considered to be "at risk for receiving I.V. hydration" if presenting to a hospital. Those with EAH without body mass loss during the race were considered "overhydrated" and "at risk for EAH exacerbation.", Results: Among 627 finishers, 16 (2.6%) were at risk for EAH exacerbation. Considering 421 observations at risk for receiving I.V. hydration, 16 (47.1%) of the 34 observations with EAH were at risk for EAH exacerbation. Among those at risk for receiving I.V. hydration and with EAH, serum urea nitrogen and creatine concentration as a multiple of estimated baseline were lower (p < 0.05) for those at risk for EAH exacerbation, compared with those without overhydration, but there were no clinically useful laboratory findings to distinguish these two groups due to considerable overlap of values., Conclusions: Whether in the field or hospital setting, I.V. hydration of an athlete after an ultramarathon carries a notable risk for exacerbating EAH, so clinicians should use caution when hydrating athletes after endurance events., (Published by Elsevier Inc.)

Drug-induced rhabdomyolysis (DIR) is an idiosyncratic and fatal adverse drug reaction (ADR) characterized in severe muscle injuries accompanied by multiple-organ failure. Limited knowledge regarding the pathophysiology of rhabdomyolysis is the main obstacle to developing early biomarkers and prevention strategies. Given the lack of a centralized data resource to curate, organize, and standardize widespread DIR information, here we present a Drug-Induced Rhabdomyolysis Atlas (DIRA) that provides DIR-related information, including: a classification scheme for DIR based on drug labeling information; postmarketing surveillance data of DIR; and DIR drug property information. To elucidate the utility of DIRA, we used precision dosing, concomitant use of DIR drugs, and predictive modeling development to exemplify strategies for idiosyncratic ADR (IADR) management., (Published by Elsevier Ltd.)

The protective activity of N-(2-hydroxyphenyl)acetamide (NA-2) and NA-2-coated gold nanoparticles (NA-2-AuNPs) in glycerol-treated model of acute kidney injury (AKI) in mice was investigated. NA-2 (50 mg/kg) and NA-2-AuNPs (30 mg/kg) were given to the animals for four days followed by 24-h water deprivation and injection of 50% glycerol (10 ml/kg im). The animals were sacrificed on the next day. Blood and kidneys were collected for biochemical investigations (urea and creatinine), histological studies (hematoxylin and eosin; and periodic acid-Schiff staining), immunohistochemistry (actin and cyclooxygenase-2, Cox-2), and real-time RT-PCR (inducible nitric oxide synthase, iNOS; nuclear factor-κB p50, NFκB; hemeoxygenase-1, HO-1; and kidney injury molecule-1, Kim-1). NA-2 protected renal tubular necrosis and inflammation, though the result of NA-2-AuNPs was better than compound alone and it also exhibited the activity at far less dose. The test compound and its gold nano-formulation decreased the levels of serum urea and creatinine level in the treated animals. Both NA-2 and NA-2-AuNPs also conserved actin cytoskeleton, and lowered COX-2 protein expression. Moreover, the mRNA expressions of iNOS and NFkB p50 were down-regulated, and HO-1 and Kim-1 genes were up-regulated. We conclude that NA-2 and NA-2-AuNPs ameliorates kidney inflammation and injury in glycerol-induced AKI animal model via anti-oxidant and anti-inflammatory mechanisms which make it a suitable candidate for further studies. We believe that these findings will contribute in the understanding of the mechanism of action of paracetamol-like drugs and can be considered for clinical research for the prevention of AKI.

Aim: Acute kidney injury (AKI) is associated with chronic kidney disease, as well as high mortality, but effective treatments for AKI are still lacking. A recent study reported the prevention of renal injury, such as ischemia-reperfusion injury, by 5-aminolevulinic acid (ALA), which induces an antioxidant effect. The current study aimed to investigate the effect of ALA in a rhabdomyolysis-induced mouse model of AKI created by intramuscular injection of 50% glycerol., Methods: Rhabdomyolysis-induced AKI was induced by an intramuscular injection of glycerol (5 mL/kg body weight) into mice. Administration of ALA (30 mg/kg, by gavage) was started from 48 h before or 24 h after glycerol injection. The mice were sacrificed at 72 h after glycerol injection. The roles of nuclear factor erythroid 2-related factor 2 (Nrf2) and heme oxygenase-1 (HO-1), which is one of the Nrf2-related antioxidants, were further investigated through in vivo and in vitro methods., Results: 5-aminolevulinic acid markedly reduced renal dysfunction and tubular damage in mice with rhabdomyolysis-induced AKI. ALA administration decreased oxidative stress, macrophage infiltration, and inflammatory cytokines and apoptosis. The expression of Nrf2 was upregulated by ALA administration. However, administration of Zinc protoporphyrin-9 (ZnPPIX) to inhibit HO-1 activity did not abolish these improvements by ALA. The expression of Nrf2-associated antioxidant factors other than HO-1 was also increased., Conclusion: These findings indicate that ALA exerts its antioxidant activity via Nrf2-associated antioxidant factors to provide a renoprotective effect against rhabdomyolysis-induced AKI., (© 2017 Asian Pacific Society of Nephrology.)

A 36-year-old African American with a medical history of nonanesthesia-related malignant hyperthermia (MH) who was taking chronic oral dantrolene therapy presented with right upper quadrant pain for a laparoscopic cholecystectomy. A multidisciplinary perioperative plan was implemented with the goal of avoiding triggering an MH episode or rhabdomyolysis. He developed a postoperative left brachial vein thrombus of unclear etiology, possibly related to dantrolene administration or his underlying susceptibility to MH.

This article reviews advancements in the genetics of malignant hyperthermia, new technologies and approaches for its diagnosis, and the existing limitations of genetic testing for malignant hyperthermia. It also reviews the various RYR1-related disorders and phenotypes, such as myopathies, exertional rhabdomyolysis, and bleeding disorders, and examines the connection between these disorders and malignant hyperthermia.

Background: Ecstasy (Ec) use produces hyperthermia, excessive sweating, intense thirst, an inappropriate antidiuretic hormone secretion (SIADH) and a multisystemic toxicity due to oxidative stress (OS). Intense thirst induces high intake of pure water, which associated with SIADH, usually develops into acute hyponatremia (Hn). As Hn is induced rapidly, experiments to check if Ec acted directly on the Inner Medullary Collecting Ducts (IMCD) of rats were conducted. Rhabdomyolysis and OS were also studied because Ec is known to induce Reactive Oxygen Species (ROS) and tissue damage. To decrease OS, the antioxidant inhibitors N-acetylcysteine (NAC) and Allopurinol (Allo) were used., Methods: Rats were maintained on a lithium (Li) diet to block the Vasopressin action before Ec innoculation. AQP2 (Aquaporin 2), ENaC (Epitheliun Sodium Channel) and NKCC2 (Sodium, Potassium, 2 Chloride) expression were determined by Western Blot in isolated IMCDs. The TBARS (thiobarbituric acid reactive substances) and GSH (reduced form of Glutathione) were determined in the Ec group (6 rats injected with Ec-10mg/kg), in Ec+NAC groups (NAC 100mg/Kg/bw i.p.) and in Allo+Ec groups (Allo 50mg/Kg/i.p.)., Results: Enhanced AQP2 expression revealed that Ec increased water transporter expression, decreased by Li diet, but the expression of the tubular transporters did not change. The Ec, Ec+NAC and Allo+Ec results showed that Ec increased TBARS and decreased GSH, showing evidence of ROS occurrence, which was protected by NAC and Allo. Rhabdomyolysis was only protected by Allo., Conclusion: Results showed that Ec induced an increase in AQP2 expression, evidencing another mechanism that might contribute to cause rapid hyponatremia. In addition, they showed that NAC and Allo protected against OS, but only Allo decreased rhabdomyolysis and hyperthermia.

Purpose of Review: The aim of this review is to examine data relating to perioperative management of the patient with neuromuscular disorders RECENT FINDINGS: Patients with pre-existing neuromuscular disorders are at risk for a number of postoperative complications that are related to anesthetic drugs that are administered intraoperatively. Careful preoperative assessment is necessary to reduce morbidity and mortality. In particular, the risk of postoperative respiratory failure and need for long-term ventilation should be reviewed with patients. The use of succinylcholine should be avoided in muscular dystrophies, motor neuron diseases, and intrinsic muscle disease due to a risk of malignant hyperthermia, hyperkalemia, rhabdomyolysis, and cardiac arrest. The use of quantitative neuromuscular monitoring should be strongly considered whenever nondepolarizing neuromuscular blocking agents are administered. A number of case series and reports have been recently published demonstrating that sugammadex can be safely used in patients with neuromuscular disease; the risk of residual neuromuscular is nearly eliminated when this agent is administered intraoperatively., Summary: Careful assessment and management of patients with underlying neuromuscular diseases is required to reduce postoperative complications. This article reviews the anesthetic implications of patients undergoing surgery with neuromuscular disorder.

Background: Rhabdomyolysis results from damage to skeletal muscle. Improper resistance training may result in rhabdomyolysis, which can cause acute kidney injury, serious metabolic abnormalities, compartmental syndrome and even death. Proper counselling for athletes may prevent this condition., Objective: We present two patients with unilateral swelling after resistance exercise. The workup revealed rhabdomyolysis. We highlight the importance of counselling to prevent rhabdomyolysis secondary to resistance exercise., Discussion: Trainers and primary care physicians need to be educated about the main features of rhabdomyolysis and urgently refer trainees suspected of having this condition. Treatment consists mainly of hydration and correction of metabolic abnormalities. Primary care physicians need to counsel patients on ways to prevent rhabdomyolysis. Trainers and primary care physicians should instruct novice trainees who are performing resistance exercise to start low and gradually increase the load. Training with loads of 60-70% of one repetition maximum for 8-12 repetitions and use of one to three sets per exercise is recommended.

Background: Acute kidney injury (AKI) is the most severe complication of rhabdomyolysis. Allopurinol (Allo), a xanthine oxidase inhibitor, has been in the spotlight in the last decade due to new therapeutic applications related to its potent antioxidant effect. The aim of this study was to evaluate the efficacy of Allo in the prevention and treatment of rhabdomyolysis-associated AKI., Methods: Male Wistar rats were divided into five groups: saline control group; prophylactic Allo (300mg/L of drinking water, 7 days); glycerol (50%, 5ml/kg, IM); prophylactic Allo + glycerol; and therapeutic Allo (50mg/Kg, IV, 30min after glycerol injection) + glycerol., Results: Glycerol-injected rats showed markedly reduced glomerular filtration rate associated with renal vasoconstriction, renal tubular damage, increased oxidative stress, apoptosis and inflammation. Allo ameliorated all these alterations. We found 8-isoprostane-PGF 2a (F2-IsoP) as a main factor involved in the oxidative stress-mediated renal vasoconstriction following rhabdomyolysis. Allo reduced F2-IsoP renal expression and restored renal blood flow. Allo also reduced oxidative stress in the damaged muscle, attenuated muscle lesion/inflammation and accelerated muscular recovery. Moreover, we showed new insights into the pathogenesis of rhabdomyolysis-associated AKI, whereas Allo treatment reduced renal inflammation by decreasing renal tissue uric acid levels and consequently inhibiting the inflammasome cascade., Conclusions: Allo treatment attenuates renal dysfunction in a model of rhabdomyolysis-associated AKI by reducing oxidative stress (systemic, renal and muscular), apoptosis and inflammation. This may represent a new therapeutic approach for rhabdomyolysis-associated AKI - a new use for an old and widely available medication., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Exertional rhabdomyolysis (ER) is a medical condition whereby damage to skeletal muscle is induced by excessive physical activity in otherwise healthy individuals. The individual performs so much activity that he/ she presumably depletes local muscle energy stores and muscle cells are unable to maintain cellular integrity, resulting in cell damage and the release of cellular contents, with resultant secondary complications. In the military services, the incidence of ER appeared to increase in the period 2004 to 2015. Risk factors for ER include male sex, younger age, a prior heat injury, lower educational level, lower chronic physical activity, and activity in the warmer months of the year. Acute kidney injury is the most serious potential complication of ER and is thought to be due to a disproportionate amount of free myoglobin that causes renal vasoconstriction, nephrotoxic effects, and renal tubular obstructions. Patients typically present with a history of heavy and unaccustomed exercise with muscle pain, swelling, weakness, and decreased range of motion, largely localized to the muscle groups that were involved in the activity. Diagnostic criteria include the requisite clinical presentation with a serum creatine kinase level at least level 5 times higher than the upper limit of normal and/ or a urine dipstick positive for blood (due to the presence of myoglobin) but lacking red blood cells under microscopic urinalysis. Core treatment is largely supportive with aggressive fluid hydration. Although the great majority of individuals return to activity without consequence, patients should initially be stratified into high and low risk for recurrence, and those at high risk provided additional evaluation. Risk of ER in normal healthy individuals can be reduced by emphasizing graded, individual preconditioning before beginning a more strenuous exercise regimen after recommended work/rest and hydration schedules in hot weather, and discussing supplements and medications with knowledgeable medical personnel., (2016.)

The 2013 American College of Cardiology/American Heart Association guidelines on cholesterol management have placed greater emphasis on high-intensity statin dosing for those with known cardiovascular disease or diabetes mellitus. Differences in risk of hepatotoxicity, new onset diabetes and rhabdomyolysis specifically between the high-intensity statins and the most common moderate-intensity statin, simvastatin, were not found to a significant degree in this review. Rather, baseline characteristics and drug-drug interactions (DDIs) appear to be more important regarding the risk of these adverse effects. Pharmacogenetic differences in statin metabolism may explain individual susceptibility, however genetic testing is not felt to be cost effective at this time. More importantly, statin choice should consider concomitant use of the many prevalent CYP3A4 inhibitors or inducers, and when present, rosuvastatin selection is recommended to reduce DDIs and risk of statin-induced adverse effects., (Copyright © 2016 Elsevier Inc. All rights reserved.)

A patient undergoing cyclosporine therapy presented with muscle weakness. This was preceded by diarrhea and treated with ciprofloxacin. Rhabdomyolysis was diagnosed clinically and biochemically. This was presumably drug-induced triggered by a combined therapy with cyclosporine, amlodipine, simvastatin and ciprofloxacin. The case presented demonstrates that during therapy with several substances which inhibit the degradation of simvastatin, the additional administration of ciprofloxacin should be considered with extreme caution.

Importance: Muscle-related statin intolerance is reported by 5% to 20% of patients., Objective: To identify patients with muscle symptoms confirmed by statin rechallenge and compare lipid-lowering efficacy for 2 nonstatin therapies, ezetimibe and evolocumab., Design, Setting, and Participants: Two-stage randomized clinical trial including 511 adult patients with uncontrolled low-density lipoprotein cholesterol (LDL-C) levels and history of intolerance to 2 or more statins enrolled in 2013 and 2014 globally. Phase A used a 24-week crossover procedure with atorvastatin or placebo to identify patients having symptoms only with atorvastatin but not placebo. In phase B, after a 2-week washout, patients were randomized to ezetimibe or evolocumab for 24 weeks., Interventions: Phase A: atorvastatin (20 mg) vs placebo. Phase B: randomization 2:1 to subcutaneous evolocumab (420 mg monthly) or oral ezetimibe (10 mg daily)., Main Outcome and Measures: Coprimary end points were the mean percent change in LDL-C level from baseline to the mean of weeks 22 and 24 levels and from baseline to week 24 levels., Results: Of the 491 patients who entered phase A (mean age, 60.7 [SD, 10.2] years; 246 women [50.1%]; 170 with coronary heart disease [34.6%]; entry mean LDL-C level, 212.3 [SD, 67.9] mg/dL), muscle symptoms occurred in 209 of 491 (42.6%) while taking atorvastatin but not while taking placebo. Of these, 199 entered phase B, along with 19 who proceeded directly to phase B for elevated creatine kinase (N = 218, with 73 randomized to ezetimibe and 145 to evolocumab; entry mean LDL-C level, 219.9 [SD, 72] mg/dL). For the mean of weeks 22 and 24, LDL-C level with ezetimibe was 183.0 mg/dL; mean percent LDL-C change, -16.7% (95% CI, -20.5% to -12.9%), absolute change, -31.0 mg/dL and with evolocumab was 103.6 mg/dL; mean percent change, -54.5% (95% CI, -57.2% to -51.8%); absolute change, -106.8 mg/dL (P < .001). LDL-C level at week 24 with ezetimibe was 181.5 mg/dL; mean percent change, -16.7% (95% CI, -20.8% to -12.5%); absolute change, -31.2 mg/dL and with evolocumab was 104.1 mg/dL; mean percent change, -52.8% (95% CI, -55.8% to -49.8%); absolute change, -102.9 mg/dL (P < .001). For the mean of weeks 22 and 24, between-group difference in LDL-C was -37.8%; absolute difference, -75.8 mg/dL. For week 24, between-group difference in LDL-C was -36.1%; absolute difference, -71.7 mg/dL. Muscle symptoms were reported in 28.8% of ezetimibe-treated patients and 20.7% of evolocumab-treated patients (log-rank P = .17). Active study drug was stopped for muscle symptoms in 5 of 73 ezetimibe-treated patients (6.8%) and 1 of 145 evolocumab-treated patients (0.7%)., Conclusions and Relevance: Among patients with statin intolerance related to muscle-related adverse effects, the use of evolocumab compared with ezetimibe resulted in a significantly greater reduction in LDL-C levels after 24 weeks. Further studies are needed to assess long-term efficacy and safety., Trial Registration: clinicaltrials.gov Identifier: NCT01984424.

The elderly population is increasing worldwide and shows an increasing prevalence of frailty. Frailty is recognized as an important factor for inappropriate drug prescribing in elderly patients. Appropriate drug prescription, either in terms of drug choice or in terms of drug dosage, is of paramount importance among the frail elderly patients, this requiring the need of a difficult balance between efficacy, safety and tolerability. Bacterial infections are quite frequent among the elderly, and use of antimicrobials may be associated with severe adverse events in this population, especially when in presence of co-medications and/or of co-morbidities. The aim of this paper is to argue about the most recent published evidences on how to prevent major adverse events whenever antimicrobials should be co-prescribed in frail elderly patients., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Introduction: Lipin 1 gene (LPIN1) mutations lead to cellular energy deficiency and cause up to 50% of the rhabdomyolysis episodes seen in pediatric patients. These episodes are associated with poor prognosis, as treatment options have been limited. We propose a novel therapeutic strategy based on prevention and early treatment of catabolism., Methods: Five patients were diagnosed with LPIN1 mutations. They were instructed to maintain high caloric intake in situations possibly leading to catabolism such as viral infections or excessive physical activity. When an episode of rhabdomyolysis occurred, patients were treated with intravenous high-concentration glucose at first symptoms., Results: The therapeutic strategies described limited the number of rhabdomyolyis episodes, and the duration of episodes was reduced from 7-10 days, as reported in the literature, to 5 days., Conclusion: In this small series, patients with LPIN1 mutations appear to have benefited from prevention and early treatment of catabolism., (© 2015 Wiley Periodicals, Inc.)

Psychogenic polydipsia leading to severe hyponatremia is well documented in the literature. This electrolyte disorder can result in encephalopathy, cerebral edema and epileptic seizures. Another rare effect is rhabdomyolysis with all its well known complications (e.g. renal failure, hyperkalemia and cardiac arrhythmia) and even resulting in compartment syndrome due to severe muscle edema. We present the case of a patient with severe hyponatremia caused by psychogenic polydipsia leading to rhabdomyolysis and compartment syndrome.

Objectives: In cardiac muscle, ischemia reperfusion (IR) injury is attenuated by mitochondrial function, which may be upregulated by focal adhesion kinase (FAK). The aim of this study was to determine whether increased FAK levels reduced rhabdomyolysis in skeletal muscle too., Material and Methods: In a translational in vivo experiment, rat lower limbs were subjected to 4 hours of ischemia followed by 24 or 72 hours of reperfusion. FAK expression was stimulated 7 days before (via somatic transfection with pCMV-driven FAK expression plasmid) and outcomes were measured against non-transfected and empty transfected controls. Slow oxidative (i.e., mitochondria-rich) and fast glycolytic (i.e., mitochondria-poor) type muscles were analyzed separately regarding rhabdomyolysis, apoptosis, and inflammation. Severity of IR injury was assessed using paired non-ischemic controls., Results: After 24 hours of reperfusion, marked rhabdomyolysis was found in non-transfected and empty plasmid-transfected fast-type glycolytic muscle, tibialis anterior. Prior transfection enhanced FAK concentration significantly (p = 0.01). Concomitantly, levels of BAX, promoting mitochondrial transition pores, were reduced sixfold (p = 0.02) together with a blunted inflammation (p = 0.01) and reduced rhabdomyolysis (p = 0.003). Slow oxidative muscle, m. soleus, reacted differently: although apoptosis was detectable after IR, rhabdomyolysis did not appear before 72 hours of reperfusion; and FAK levels were not enhanced in ischemic muscle despite transfection (p = 0.66)., Conclusions: IR-induced skeletal muscle rhabdomyolysis is a fiber type-specific phenomenon that appears to be modulated by mitochondria reserves. Stimulation of FAK may exploit these reserves constituting a potential therapeutic approach to reduce tissue loss following acute limb IR in fast-type muscle., (Copyright © 2014 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Although statins remain the cornerstone of lipid-lowering therapy for reducing the burden of atherosclerotic vascular disease, their administration has been associated with muscle-related adverse effects, including myalgia and rhabdomyolysis. Such adverse events are probably due to reduced antioxidant defenses associated with fewer intermediate metabolites in the cholesterol synthesis pathway. We hypothesize that the concomitant inhibition of xanthine oxidase via coadministration of allopurinol with statins could diminish reactive oxygen species (ROS)-related muscle damage, which would have in turn have positive effects on both the incidence of muscle-related adverse events and cardiovascular outcomes. Accordingly, inhibition of xanthine oxidase has been previously shown to be effective for reducing biomarkers of muscle damage following exercise in professional athletes. Because of the widespread statin utilization and increasing trends in their therapeutic use in atherosclerotic vascular diseases, the proposed strategy could have important clinical implications for reducing statin-induced myalgia and rhabdomyolysis., (Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.)

Introduction: Drugs like statins may induce rhabdomyolysis. Simvastatin and lovastatin have a high hepatic metabolism and their potential toxicity could be increased by interactions with other drugs that reduce their metabolism., Patients and Methods: A case-report is presented of an HIV-infected patient treated with antiretroviral drugs who developed a rhabdomyolysis-induced renal failure and liver toxicity when simvastatin was substituted for atorvastatin. A literature review is also presented., Results: The patient required hospital admission and showed a favorable response after hydration and urine alkalinization. There were 4 additional cases published of which there was one death., Conclusions: Drug-drug interactions can increase the risk of statin induced rhabdomyolysis. In order to evaluate them properly, physicians at all levels of clinical care should be aware of all drugs prescribed to their patients and the contraindicated combinations., (Copyright © 2014 Elsevier España, S.L.U. y Sociedad Española de Enfermedades Infecciosas y Microbiología Clínica. All rights reserved.)

Genetic muscular disorders are known risk factors for rhabdomyolysis, which may result in acute kidney injury. Recurrent episodes of acute kidney injury can lead to chronic kidney disease and eventually end-stage renal failure. We describe a patient with chronic kidney disease that developed in the setting of recurrent rhabdomyolysis, resulting in the requirement for renal transplantation. After transplantation, the maintenance of tacrolimus trough concentrations above what is typically prescribed for standard renal transplant recipients appeared to confer protection from further episodes of rhabdomyolysis. This is consistent with previous case series that demonstrated a therapeutic benefit of the calcineurin inhibitor cyclosporine in collagen VI myopathies in the nontransplant population. This case report suggests the potential application of higher tacrolimus targets in patients who have undergone renal transplantation in the setting of recurrent rhabdomyolysis leading to end-stage renal failure.

This review includes a variety of extremely rare and unusual hymenoptera sting (HS) circumstances with regard to sting localization, geographic region, massivity of multiple stings, and particularly related to clinical symptoms. Such reactions occur in a temporal relationship to HS (s), differ from typical allergic symptomatology, and sometimes need follow-up during many months. With respect to pathogenesis, the major mechanisms involved are toxic, autoimmune, and other delayed immunological ones. While delayed inflammatory symptoms of the nervous system are considered as delayed hypersensitization or autoimmune entities, generalized rhabdomyolysis and consecutive acute kidney injury is considered a toxic reaction, mostly induced by massive envenomation to wasps or "Africanized" bees. Hemorrhagic episodes of targeted organ (s) could be additional potential risk for acute kidney injury, while the bee venom-induced hemorrhage is proposed to be a nonimmune-mediated anaphylactic symptom. The hemodynamic involvement of vital organs and systems with hypoxia and hypovolemia together with simultaneous immunoglobulin E (IgE) sensitization are considered potential indications for venom immunotherapy. In contrast, patients who have experienced various complications with unknown or nonallergic mechanisms should be informed about the importance of epinephrine's use and additional measures on future sting avoidance. In conclusion, although unusual reactions are extremely rare, it is important to keep them in mind.

We report the anesthetic management with total intravenous anesthesia of a 61-year-old male diagnosed with limb-girdle muscular dystrophy admitted for replacement of ascending aorta due to an aortic aneurysm. Limb-girdle muscular dystrophy belongs to a genetically heterogeneous group of muscular dystrophies involving shoulder and hip girdles. Although the risk of malignant hyperthermia does not seem to be increased in these patients compared with the general population, the exposure to inhaled anesthetics and succinylcholine should probably be avoided because these patients have a predisposition to hyperkalemia and rhabdomyolysis. We chose to use total intravenous anesthesia with propofol, remifentanil and muscle relaxants to reduce oxygen consumption, and later to reduce the doses of propofol and remifentanil. The combination of a carefully planned anesthetic strategy, anesthetic depth, and neuromuscular blockade monitoring is explained., (Copyright © 2013 Sociedad Española de Anestesiología, Reanimación y Terapéutica del Dolor. Published by Elsevier España. All rights reserved.)

Positioning injuries in the perioperative period are one of the inherent risks of surgery, but particularly in robot-assisted urologic surgery, and can result in often unrecognized morbidity. Injuries such as upper or lower extremity peripheral neuropathies occur via neural mechanisms and injuries such as compartment syndrome, rhabdomyolysis, ischemic optic neuropathy, and acute arterial occlusion occur via vascular mechanisms. The risk of injury may be exacerbated by operative and patient-related risk factors. Patient-related risk factors include ASA class and BMI, while surgery-related risk factors include physical orientation of the patient and operative length. These injuries can be prevented or reduced by joint effort of the surgeon, anesthesiologist, and operating room staff.