Efficacy of the opened legs position for protecting against postoperative rhabdomyolysis after robot-assisted radical prostatectomy: A propensity score-matched analysis of perioperative outcomes.

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.

Timing is everything: Impact of combined long bone fracture and major arterial injury on outcomes.

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.

Risk factors and future directions for preventing and diagnosing exertional rhabdomyolysis.

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.

Guidelines for the acute care of severe limb trauma patients

To provide healthcare professionals with comprehensive multidisciplinary expert recommendations for the acute care of severe limb trauma patients, both during the prehospital phase and after admission to a Trauma Centre. A consensus committee of 21 experts was formed. A formal conflict-of-interest (COI) policy was developed at the onset of the process and enforced throughout. The entire guidelines process was conducted independently of any industrial funding (i.e., pharmaceutical, medical devices). The authors were advised to follow the rules of the Grading of Recommendations Assessment, Development and Evaluation (GRADE®) system to guide assessment of the quality of evidence. The potential drawbacks of making strong recommendations in the presence of low-quality evidence were emphasised. Few recommendations remained non-graded. The committee addressed eleven questions relevant to the patient suffering severe limb trauma: 1) What are the key findings derived from medical history and clinical examination which lead to the patient's prompt referral to a Level 1 or Level 2 Trauma Centre? 2) What are the medical devices that must be implemented in the prehospital setting to reduce blood loss? 3) Which are the clinical findings prompting the performance of injected X-ray examinations? 4) What are the ideal timing and modalities for performing fracture fixation? 5) What are the clinical and operative findings which steer the surgical approach in case of vascular compromise and/or major musculoskeletal attrition? 6) How to best prevent infection? 7) How to best prevent thromboembolic complications? 8) What is the best strategy to precociously detect and treat limb compartment syndrome? 9) How to best and precociously detect post-traumatic rhabdomyolysis and prevent rhabdomyolysis-induced acute kidney injury? 10) What is the best strategy to reduce the incidence of fat emboli syndrome and post-traumatic systemic inflammatory response? 11) What is the best therapeutic strategy to treat acute trauma-induced pain? Every question was formulated in a PICO (Patient Intervention Comparison Outcome) format and the evidence profiles were produced. The literature review and recommendations were made according to the GRADE® methodology. The experts' synthesis work and the application of the GRADE method resulted in 19 recommendations. Among the formalised recommendations, 4 had a high level of evidence (GRADE 1+/-) and 12 had a low level of evidence (GRADE 2+/-). For 3 recommendations, the GRADE method could not be applied, resulting in an expert advice. After two rounds of scoring and one amendment, strong agreement was reached on all the recommendations. There was significant agreement among experts on strong recommendations to improve practices for severe limb trauma patients.

[Rhabdomyolysis: early management]. / Rhabdomyolyse: prise en charge médicale initiale.

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.

La rhabdomyolyse, définie comme étant les conséquences de la destruction du muscle strié, se caractérise par l'association de myalgies, d'un myo-œdème éventuellement douloureux et d'une faiblesse musculaire. Parmi les étiologies fréquentes, on peut citer l'effort, les causes toxiques (alcool et médicament) et traumatiques. Elle résulte d'un épuisement de l'adénosine triphosphate du myocyte, menant à une augmentation du calcium intracellulaire et à sa destruction. Le diagnostic repose sur le dosage de la créatine kinase (CK). Le spectre de la rhabdomyolyse englobe une élévation asymptomatique des CK, mais aussi des complications redoutables telles qu'une insuffisance rénale aiguë sévère ou des troubles électrolytiques pouvant mettre en jeu le pronostic vital. Le traitement est centré sur la prévention et la prise en charge de ces complications.

Reduced doses of dabrafenib and trametinib combination therapy for BRAF V600E-mutant non-small cell lung cancer prevent rhabdomyolysis and maintain tumor shrinkage: a case report.

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.

Recurrent Dystonic Crisis and Rhabdomyolysis Treated with Dantrolene in Two Patients with Aromatic L-Amino Acid Decarboxylase Deficiency.

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.

Exertion-Related Illness: The Critical Roles of Leadership and Followership.

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.

Exercise-Induced Muscle Damage and Cardiac Stress During a Marathon Could be Associated with Dietary Intake During the Week Before the Race.

: 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 (ß) = 0.643; p < 0.01) and myoglobin (ß = 0.698; p < 0.001). Vegetables were negatively associated the concentration of post-race CK (ß = -0.482; p = 0.002). Butter and fatty meat were positively associated with NT-proBNP (ß = 0.796; p < 0.001) and TNI (ß = 0.396; p < 0.001) post-marathon values. However, fish intake was negatively associated with CK (ß = -0.272; p = 0.042), TNI (ß = -0.593; p < 0.001) and TNT (ß = -0.640; p = 0.002) post-marathon concentration. Olive oil was negatively associated with TNI (ß = -0.536; p < 0.001) and TNT (ß = -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.

Nephroprotective Role of Selenium Nanoparticles Against Glycerol-Induced Acute Kidney Injury in Rats.

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-1ß, 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.

[Viral myositis, a pediatric case report]. / Miositis viral, reporte de un caso pediátrico.

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.

La miositis viral aguda es una complicación posterior a una infección viral causada, principalmente, por virus influenza A y B. Se caracteriza por ser un proceso inflamatorio transitorio, súbito, autolimitado y benigno. Generalmente, afecta a niños preescolares y escolares, que presentan dolor bilateral y sensibilidad en los grupos musculares de los miembros inferiores sin alteración en el examen neurológico. Puede generar alteración de la marcha o de la bipedestación. Su principal complicación es la rabdomiólisis, por lo que se debe hacer un seguimiento clínico y de los valores de la creatinfosfoquinasa. Se presenta el caso de un niño en edad escolar con diagnóstico de miositis viral aguda. Debido a que es poco frecuente y su incidencia en Latinoamérica es desconocida, se considera importante el reporte del caso y la revisión del tema, ya que su curso es benigno, de fácil manejo, y su conocimiento evita estudios y hospitalizaciones innecesarias.

5-Aminolevulinic acid exerts renoprotective effect via Nrf2 activation in murine rhabdomyolysis-induced acute kidney injury.

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.

Drug-Induced Rhabdomyolysis Atlas (DIRA) for idiosyncratic adverse drug reaction management.

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.

N-(2-hydroxyphenyl)acetamide and its gold nanoparticle conjugation prevent glycerol-induced acute kidney injury by attenuating inflammation and oxidative injury in mice.

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.

Predicted Risk for Exacerbation of Exercise-Associated Hyponatremia from Indiscriminate Postrace Intravenous Hydration of Ultramarathon Runners.

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.