Rhabdomyolysis Research Articles

Evaluation of severe rhabdomyolysis on day 30 mortality in trauma patients admitted to intensive care: a propensity score analysis of the Traumabase registry

BackgroundTraumatic rhabdomyolysis (RM) is common and associated with the development of acute kidney injury and potentially with other organ dysfunctions. Thus, RM may increase the risk of death. The primary objective was to assess the effect of severe RM (Creatine Kinase [CK] > 5000 U/L) on 30-day mortality in trauma patients using a causal inference approach.MethodsIn this multicenter cohort study conducted in France using a national major trauma registry (Traumabase) between January 1, 2012, and July 1, 2023, all patients admitted to a participating major trauma center hospitalized in intensive care unit (ICU) and with CK measurement were included. Confounding variables for both 30-day mortality and exposure were used to establish a propensity score. A doubly robust approach with inverse treatment weighting enabled the calculation of the average treatment effect on the treated (ATT). Analyses were performed in the overall cohort as well as in two subgroups: hemorrhagic shock subgroup (HS) and traumatic brain injury subgroup (TBI). Sensitivity analyses were conducted.ResultsAmong the 8592 patients included, 1544 (18.0%) had severe RM. They were predominantly males (78.6%) with median [IQR] age of 41 [27–58] years and severely injured (ISS 20 [13 – 29]) mainly from blunt trauma (90.8%). In the entire cohort, the ATT, expressed as a risk difference, was 0.073 [-0.054 to 0.200]. Considering the 1311 patients in the HS subgroup, the ATT was 0.039 [0.014 to 0.063]. As in the overall cohort, there was no effect on mortality in the TBI subgroup. Severe RM was associated with greater severity of trauma and more complications (whether related to renal function or not) during the ICU stay. Mortality due to multiorgan failure (39.9% vs 12.4%) or septic shock (2.6% vs 0.8%) was more frequent among patients with severe RM.ConclusionsSevere RM was not associated with 30-day mortality considering the overall cohort. However, it was associated with a 4.0% increase in 30-day mortality among patients with concurrent hemorrhagic shock. Severe RM plays a significant role in ICU morbidity.

Intramuscular heroin-induced severe rhabdomyolysis and acute kidney injury—a case report

Abstract Rhabdomyolysis (RM) is characterised by the breakdown of skeletal muscle tissue, releasing toxic intracellular components into circulation. It presents with dark urine, muscle weakness, myalgia, and elevated creatine phosphokinase levels (CPK). Drug-induced RM is aetiologically significant. This case report describes a 25-year-old male who developed severe RM and Acute Kidney Injury (AKI) after intramuscular (IM) heroin administration as a first time user. IM heroin use can induce higher CPK levels due to direct myocyte toxicity and mechanical trauma. The highly vascularised gluteal muscles with type 1 fibres at the injection site likely exacerbated the severity. Additional factors included lower mitochondrial density in males and alcohol exposure. Despite aggressive fluid resuscitation, renal replacement therapy (RRT) was required, and the patient responded well to haemodialysis. This case highlights AKI as a severe complication of IM heroin use, underscoring the need for further research into drug-induced RM.

One stage anterior sagittal sphincter saving anorectoplasty (ASSSARP) for the repair or rectovestibular fistula: mid and long-term outcome in two tertiary centers

PurposeThis is a retrospective study of one-stage anterior sagittal sphincter saving anorectoplasty (ASSSARP) for repairing rectovestibular fistula (RVF) including operative details and postoperative complications, functional and cosmetic outcome.Patients and methodsRecords of 41 cases of RVF, managed between April 2010 and September 2019 by one-stage ASSSARP, were reviewed. Preoperative preparation, both early and late postoperative care & complications, hospital stay, and functional & cosmetic outcomes were reported.ResultsThe mean age was 6.6 months. Vaginal tear occurred in 5/41 cases, and distal rectal tears in 4/41 cases. Thirteen patients suffered mild superficial wound inflammation; while Skin dehiscence; occurred in five patients. No colostomy or redo was needed. The mean hospital stay was 6.1 days. Mean follow-up was 43.13 months; (Range; 24–100 months). Subclinical anal stricture was detected in six patients. Constipation occurred in 14 cases. Soiling grade I occurred in five patients. Thirty-two patients reached past the age of three years; two of whom showed cough/diarrhea incontinence.ConclusionOne-stage ASSSARP is safe and gives functional and cosmetic results comparable to other techniques. It provides better access during RVF repair. The avoidance of muscle incision protects against muscle breakdown, if infection sets in, and thus against incontinence. It avoids the morbidity, cost and psychological burden of performing a three-stage repair.

9179 Type 2 Diabetes Alters Metabolic Fuel Selection During Intermittent Fasting

Abstract Disclosure: M.O. Conn: None. D.M. Marko: None. J.D. Schertzer: None. Type 2 Diabetes Alters Metabolic Fuel Selection During Intermittent Fasting Diabetes is characterized by elevated blood glucose resulting from defective insulin secretion and/or insulin resistance. Intermittent fasting, a popular weight loss strategy involving periodic reduction of caloric intake, can improve glycemia. Fasting shifts metabolism from carbohydrates to free fatty acids and ketones. However, high blood insulin can inhibit lipolysis and alter metabolic substrate selection in prediabetes, resulting in muscle catabolism to maintain energy homeostasis. Clinical studies have observed a significant decrease in muscle mass in subjects with obesity and diabetes. Our research aims to characterize lean mass versus fat loss after intermittent fasting in a mouse model of obesity and type 2 diabetes (T2D) and investigate the role of muscle alanine catabolism. We hypothesized that intermittent fasting would promote less lipolysis and more muscle alanine catabolism, causing more muscle loss in diabetic mice than controls. We compared male db/db mice manifesting obesity, hyperglycemia, and hyperinsulinemia to age-matched db/+ (control) mice. Our lab established a 5:2 repeated fasting protocol of ad-libitum access to food for 5 days a week and 2 days of fasting on non-consecutive days. Blood glucose was monitored weekly in fed and fasted states to assess glycemic control. While intermittent fasting lowered fasted blood glucose in both groups, no significant body weight or metabolic tissue mass changes were observed. Metabolic cage data demonstrated increased reliance on fat-based substrates for energy in control mice that underwent intermittent fasting during feeding and fasting periods. Diabetic mice did not show significant changes in the fasted state, but intermittent fasting led to increased reliance on carbohydrate oxidation during re-feeding periods, indicating impaired metabolic flexibility. After 10 weeks, the mice were sacrificed, and metabolic tissue histology (adipose, liver, skeletal muscle) will be performed. We will also analyze serum markers (alanine, fatty acids, glycerol, glucose, insulin) and the activity of the metabolic enzyme alanine transaminase (ALT) in the muscle and liver. This experiment will improve our understanding of how lipolysis and protein breakdown in muscle regulate lean mass versus fat mass loss in obesity and T2D, leading to more effective tailoring of fasting to specific populations. Presentation: 6/3/2024

8165 A Case Of Rhabdomyolysis-Induced Hypocalcemia And Hypercalcemia

Abstract Disclosure: A. Desai: None. A.L. Izzi: None. B. Flores Chang: None. A. Sajan: None. Introduction: Rhabdomyolysis is a syndrome characterized by muscle breakdown and the release of intracellular muscle contents into circulation. It is associated with electrolyte abnormalities and acute renal failure that can lead to prolonged hospitalization. We report a case of persistent hypercalcemia from recovery of acute renal failure and severe rhabdomyolysis. Case Description: A 47-year-old man with past medical history of polysubstance use initially presented with opiate-induced acute encephalopathy and respiratory failure. He developed severe rhabdomyolysis during the hospital course leading to acute renal failure requiring hemodialysis with hypocalcemia. The initial labs showed corrected calcium 6.2 mg/dL [9.2-11.0], ionized calcium 3.48 mg/dL [4.65-5.28], creatinine kinase level was >72,600 U/L [38-174], BUN 110 mg/dL [8-23], creatinine 7.8 mg/dL [0.6-1.2], and GFR 7 ml/min/BSA. His renal function improved over the next several days in the hospital. The serum creatinine improved to 4 mg/dL, BUN 49 mg/dL and GFR 20 ml/min/BSA respectively after couple of intermittent dialysis sessions. Six days after the last hemodialysis session, patient developed severe hypercalcemia with corrected calcium values ranging from 13.5 to 14.7 mg/dL and ionized calcium 7.41 mg/dL. Labs showed PTH 10 pg/mL [15-65], 1,25-dihydroxyvitamin D <10.0 pg/dL [21-65] and 25-OH Vitamin D levels 15.3 ng/ mL [30-96], which is consistent non-PTH medicated hypercalcemia. The 24-hour urine calcium was 696 mg [0-300 mg/24 hrs, 2900 cc]. PTH-related peptide was not collected. He was treated with intermittent doses of calcitonin and a single dose of pamidronate when the calcium levels were >13 mg/dL. Hypercalcemia resolved in eleven days after initially noted to have hypercalcemia. The corrected calcium improved to 10.1 mg/dL on the day of discharge. Discussion:Severe rhabdomyolysis is associated with acute kidney injury. The initial hypocalcemic phase during rhabdomyolysis is due to entry of calcium into damaged myocytes and deposition of calcium salts in damaged muscle. This is seen in the oliguric phase of acute kidney injury. After the recovery of rhabdomyolysis, the polyuric phase persists during renal recovery. During this time, up to one third of patients may have rebound hypercalcemia due to massive muscle calcium release. As per case reports the hypercalcemia phase lasts from 8 days to 3.5 months. In our case, the patient initially developed hypocalcemia in the oliguric phase of acute kidney injury from rhabdomyolysis. He developed hypercalcemia in the polyuric phase of renal recovery. The hypercalcemia resolved with intravenous hydration, calcitonin and pamidronate. Rhabdomyolysis is a rare cause for both hypocalcemia and hypercalcemia. Our case highlights the biphasic calcium response associated with rhabdomyolysis in the setting of renal impairment and recovery. Presentation: 6/1/2024

Recurrent rhabdomyolysis caused by palmitoyltransferase II (CPT-2) deficiency but complete normal acylcarnitine profile: A patient presentation and review of the literature

Recurrent rhabdomyolysis, marked by skeletal muscle breakdown, can stem from various causes, including genetic disorders. We detail a patient of a 22-year-old male with carnitine palmitoyltransferase II (CPT-2) deficiency manifesting recurrent rhabdomyolysis despite normal acylcarnitine profiles. Whole-genome sequencing identified two CPT2 gene variants: c.338C > T and c.482G > A, confirming the diagnosis. We conducted a case report and a comprehensive literature review encompassing 262 articles related to CPT-2 deficiency available on PubMed. The review detailed 245 cases across various forms, including lethal neonatal, severe infantile hepatocardiomuscular, and myopathic forms. The study highlighted the variability and complexity of CPT-2 deficiency phenotypes, emphasizing correlations between variants and phenotypes as well as gender distribution. Although the CPT-2 deficiency genotype does not entirely predict phenotype severity, it remains informative for most patients, assisting in assessing the severity linked to each genetic variant. The results of our study offer crucial insights into evaluating the severity associated with individual genetic variants. Notably, our patient displayed normal acylcarnitine profiles between illness episodes, indicating possible profile abnormalities only during active disease states.We propose the collection of additional blood samples for acylcarnitine analysis during episodes of rhabdomyolysis without delay in all patients presenting with rhabdomyolysis of unknown cause as a crucial diagnostic strategy. This approach may unveil unexpected underlying diseases, enabling early and accurate diagnoses.

373P Association between the time of diagnosis and muscle breakdown in DMD patients diagnosed under two years of age

373P Association between the time of diagnosis and muscle breakdown in DMD patients diagnosed under two years of age

Statins in the Cause and Prevention of Cancer: Confounding by Indication and Mediation by Rhabdomyolysis and Phosphate Toxicity.

Statins are drugs used in cardiovascular pharmacotherapy to decrease hypercholesterolemia and lower the risk of atherosclerosis. Statins also increase the risk of rhabdomyolysis, which is often minimized in comparison with large relative risk reductions of cardiovascular disease reported in clinical trials. By contrast, absolute risk reductions of cardiovascular disease are often clinically insignificant and unreported in statin clinical trials. Additionally, cytotoxic effects of statins inhibit cancer cell proliferation and reduce cancer risk, but other studies found that statins are carcinogenic. Due to an inverse association between incidence of cancer and atherosclerosis, the indication to prescribe statins likely biases the association of statins with cancer prevention. Dietary patterns associated with atherosclerosis and cancer contain inverse amounts of cholesterol and phosphate, an essential mineral that stimulates tumorigenesis. Accordingly, lower cancer risk is associated with high dietary cholesterol intake and increased risk of atherosclerosis. Furthermore, serum is exposed to excessive inorganic phosphate that could increase cancer risk as rhabdomyolysis induced by statins releases phosphate from skeletal muscle breakdown. Increased risk of comorbid conditions associated with statins may share the mediating factor of phosphate toxicity. More research is warranted on statins in the cause and prevention of cancer.

Muscle protein catabolism and splanchnic arginine consumption drive arginine dysregulation during Pseudomonas Aeruginosa induced early acute sepsis in swine.

Human sepsis is characterized by increased protein breakdown and changes in arginine and citrulline metabolism. However, it is unclear whether this is caused by changes in transorgan metabolism. We therefore studied in a Pseudomonas aeruginosa induced pig sepsis model the changes in protein and arginine related metabolism on whole body (Wb) and transorgan level. We studied 22 conscious pigs for 18 hours during sepsis, induced by infusing live bacteria (Pseudomonas aeruginosa) or after placebo infusion (control). We used stable isotope tracers to measure Wb and skeletal muscle protein synthesis and breakdown, as well as Wb, splanchnic, skeletal muscle, hepatic and portal drained viscera (PDV) arginine and citrulline disposal and production rates. During sepsis, arginine Wb production (p=0.0146), skeletal muscle release (p=0.0035) and liver arginine uptake were elevated (p=0.0031). Wb de novo arginine synthesis, citrulline production, and transorgan PDV release of citrulline, glutamine and arginine did not differ between sepsis and controls. However, Wb (p<0.0001) and muscle (p<0.001) protein breakdown were increased, suggesting that the enhanced arginine production is predominantly derived from muscle breakdown in sepsis. In conclusion, live-bacterium sepsis increases muscle arginine release and liver uptake, mirroring previous pig endotoxemia studies. In contrast to observations in humans, acute live-bacterium sepsis in pigs does not change citrulline production or arterial arginine concentration. We therefore conclude that the arginine dysregulation observed in human sepsis is possibly initiated by enhanced protein catabolism and splanchnic arginine catabolism, while decreased arterial arginine concentration and citrulline metabolism may require more time to fully manifest in patients.

Interpretable machine learning model for early prediction of acute kidney injury in patients with rhabdomyolysis

Abstract Background Rhabdomyolysis (RM) is a complex set of clinical syndromes. RM-induced acute kidney injury (AKI) is a common illness in war and military operations. This study aimed to develop an interpretable and generalizable model for early AKI prediction in patients with RM. Methods Retrospective analyses were performed on 2 electronic medical record databases: the eICU Collaborative Research Database and the Medical Information Mart for Intensive Care III database. Data were extracted from the first 24 hours after patient admission. Data from the two datasets were merged for further analysis. The extreme gradient boosting (XGBoost) model with the Shapley additive explanation method (SHAP) was used to conduct early and interpretable predictions of AKI. Results The analysis included 938 eligible patients with RM. The XGBoost model exhibited superior performance (area under the receiver operating characteristic curve [AUC] = 0.767) compared to the other models (logistic regression, AUC = 0.711; support vector machine, AUC = 0.693; random forest, AUC = 0.728; and naive Bayesian, AUC = 0.700). Conclusion Although the XGBoost model performance could be improved from an absolute perspective, it provides better predictive performance than other models for estimating the AKI in patients with RM based on patient characteristics in the first 24 hours after admission to an intensive care unit. Furthermore, including SHAP to elucidate AKI-related factors enables individualized patient treatment, potentially leading to improved prognoses for patients with RM.

Exertional Rhabdomyolysis and Ultra-Trail Races: A Systematic Review Highlighting the Significant Impact of Eccentric Load

Exertional rhabdomyolysis (ER) is a condition where muscle breakdown occurs after intense and unaccustomed exercise in healthy individuals. It is characterized by muscle pain, weakness, and myoglobinuria, potentially leading to acute kidney injury and worsening the patients’ prognosis. Ultra-trail races (UT) necessitate high energy and extreme muscular exertion, which can result in significant muscle breakdown, leading to ER and elevated biomarkers such as creatine kinase (CK) and lactate dehydrogenase (LDH). These races involve longer durations and both uphill and downhill elevations, with the latter causing more muscle damage. This systematic review aims to analyse the effect of downhill elevation (at least 1000 m) in UT on muscle and liver damage biomarkers. We conducted a systematic review of four electronic databases (Pubmed, Web of Science, Scopus, and Sportdiscus) based on PRISMA guidelines for systematic reviews. We included a total of 15 articles out of 6670 published between January 2005 and March 2024. The total population sample included 348 subjects, comprising 294 men (84.48%) and 54 women (15.52%) with a mean age of 39.82 ± 6.89 years. Only one subject (0.28%) was diagnosed with ER. The median increase in CK post vs. pre was 5370.63 ± 7289.71%, LDH post vs. pre was 311.20 ± 164.4%, and liver damage biomarkers aspartate transaminase (AST) and alanine aminotransferase (ALT) obtained mean increases of 1009.94 ± 743.97% and 207.02 ± 92.84%, respectively. No liver injury cases were reported. These findings suggest that ER is often misdiagnosed in UT and may result in acute kidney injury under certain circumstances. Therefore, it is crucial to define and prepare the characteristics required for ultra runners to safely participate in these extreme races.

Cellular mechanisms of acute rhabdomyolysis in inherited metabolic diseases.

Acute rhabdomyolysis (RM) constitutes a life-threatening emergency resulting from the (acute) breakdown of skeletal myofibers, characterized by a plasma creatine kinase (CK) level exceeding 1000 IU/L in response to a precipitating factor. Genetic predisposition, particularly inherited metabolic diseases, often underlie RM, contributing to recurrent episodes. Both sporadic and congenital forms of RM share common triggers. Considering the skeletal muscle's urgent need to rapidly adjust to environmental cues, sustaining sufficient energy levels and functional autophagy and mitophagy processes are vital for its preservation and response to stressors. Crucially, the composition of membrane lipids, along with lipid and calcium transport, and the availability of adenosine triphosphate (ATP), influence membrane biophysical properties, membrane curvature in skeletal muscle, calcium channel signaling regulation, and determine the characteristics of autophagic organelles. Consequently, a genetic defect involving ATP depletion, aberrant calcium release, abnormal lipid metabolism and/or lipid or calcium transport, and/or impaired anterograde trafficking may disrupt autophagy resulting in RM. The complex composition of lipid membranes also alters Toll-like receptor signaling and viral replication. In response, infections, recognized triggers of RM, stimulate increased levels of inflammatory cytokines, affecting skeletal muscle integrity, energy metabolism, and cellular trafficking, while elevated temperatures can reduce the activity of thermolabile enzymes. Overall, several mechanisms can account for RMs and may be associated in the same disease-causing RM.

Effect of C60 Fullerene on Muscle Injury-Induced Rhabdomyolysis and Associated Acute Renal Failure.

Rhabdomyolysis, as an acute stage of myopathy, causes kidney damage. It is known that this pathology is caused by the accumulation of muscle breakdown products and is associated with oxidative stress. Therefore, the present study evaluated the effect of intraperitoneal administration (dose 1 mg/kg) of water-soluble C60 fullerenes, as powerful antioxidants, on the development of rat kidney damage due to rhabdomyolysis caused by mechanical trauma of the muscle soleus of different severity (crush syndrome lasting 1 min under a pressure of 2.5, 3.5, and 4.5 kg/cm2, respectively). Using tensometry, biochemical and histopathological analyses, the biomechanical parameters of muscle soleus contraction (contraction force and integrated muscle power), biochemical indicators of rat blood (concentrations of creatinine, creatine phosphokinase, urea and hydrogen peroxide, catalase and superoxide dismutase activity), glomerular filtration rate and fractional sodium excretion value, as well as pathohistological and morphometric features of muscle and kidney damages in rats on days 1, 3, 6 and 9 after the initiation of the injury were studied. Positive changes in biomechanical and biochemical parameters were found during the experiment by about 27-30 ± 2%, as well as a decrease in pathohistological and morphometric features of muscle and kidney damages in rats treated with water-soluble C60 fullerenes. These findings indicate the potential application of water-soluble C60 fullerenes in the treatment of pathological conditions of the muscular system caused by rhabdomyolysis and the associated oxidative stress.

Exertional rhabdomyolysis: an analysis of 321 hospitalised US military service members and its relationship with heat illness

IntroductionExertional rhabdomyolysis is a syndrome of muscle breakdown following exercise. This study describes laboratory and demographic trends of service members hospitalised for exertional rhabdomyolysis and examines the relationships with heat...

Dietary protein re-alimentation following restriction improves protein deposition via changing amino acid metabolism and transcriptional profiling of muscle tissue in growing beef bulls

This study aimed to develop a compensatory growth model using growing beef cattle by changing dietary protein and to investigate the underlying mechanisms of compensatory protein deposition in muscle tissue. Twelve Charolais bulls were randomly assigned to one of two groups with two periods: 1) a control group (CON) fed a 13% crude protein (CP) diet for 6 weeks; 2) a treatment group (REC) fed a 7% CP diet for 4 weeks (restriction period) and fed a 13% CP diet in the following 2 weeks (re-alimentation period). Growth performance, digestibility, nitrogen balance, targeted metabolomics of amino acids (AA) in plasma, and transcriptional profiling in muscle tissue were analyzed. Protein restriction decreased average daily gain (ADG; P < 0.05), while protein re-alimentation increased ADG relative to the CON (P < 0.05). Compared to the CON, REC reduced retained N (P < 0.05), and protein re-alimentation increased retained N and N utilization efficiency (P < 0.05), due to reduced urinary urea, hippuric acid, and creatinine excretions (P < 0.05). Ruminal NH3-N in the REC was lower than that in the CON in the protein re-alimentation period (P < 0.05). However, there was no difference in microbial protein and plasma urea nitrogen concentrations. Dietary protein restriction decreased plasma valine and aspartic acid concentrations relative to the CON (P < 0.05), and increased proline and 3-methyl-L-histidine concentrations (P < 0.05). After dietary protein re-alimentation, REC increased plasma citrulline concentrations (P < 0.05). The transcriptional profiling revealed that REC upregulated the AA transporter SLC3A1, and protein re-alimentation downregulated SLC7A8 in the muscle cell membrane. Within the muscle cell, upregulated cytosolic arginine sensor for mTORC1 subunit 2 (CASTOR2) inhibited protein synthesis by inhibiting the mammalian target of rapamycin complex 1 phosphorylation in the protein restriction period, while DNA-damage-inducible transcript 4 (DDIT4) activated the mTOR signaling pathway and promoted protein synthesis in the protein re-alimentation period. In summary, the targeted metabolomics and transcriptomics analyses demonstrated that protein re-alimentation following restriction can promote protein synthesis and reduce muscle breakdown by regulating AA metabolism and functional transcripts related to AA transporters and the mTOR signaling pathway.

РАННЯЯ ДИАГНОСТИКА МИОДИСТРОФИИ ДЮШЕННА: АКТУАЛЬНОСТЬ, ПРОБЛЕМЫ, ВОЗМОЖНОСТИ И ПЕРСПЕКТИВЫ

Duchenne muscular dystrophy (DMD) is an orphan neuromuscular progressive genetic disease that causes muscle breakdown and subsequent loss. Provided early diagnosis, complex standard and pathogenetic therapy significantly changes the trajectory of the disease, making it more benign. Diagnosis of DMD is a two-pillar system with creatine kinase (CK) level measured at the first stage followed by molecular genetic study in case the enzyme threshold values. The quality of genetic diagnostics in Russia has reached the best worldwide standards recently though identifying children with elevated CK levels is yet difficult. The number of diagnosed DMD patients in Russia is significantly lower than the statistically estimated global amount. The average age for diagnosis is not decreasing either. Thus, the median age for DMD and Becker muscular dystrophy (BMD) molecular diagnosis is 7 years and 8 months old. The number of identified children below the age of 2 y/o in Russia has remained consistently low over the past three years. According to the results of a familial cases survey, the correct primary diagnosis of DMD was established in less than half of all cases, 47.1%. The most common incorrect diagnoses were as follows: asymptotic hepatitis (25.1%), perinatal damage to the central nervous system (6.4%), cerebral palsy (2.7%), autism spectrum disorder (ASD) (2.7%) and flat feet, hallux valgus etc. (16% in total). The median duration between the initial DMD manifestation and molecular diagnosis is 3 years and 8 months as yet whilst the age-specific guidelines suggest prescribing standard and pathogenetic therapy during the 2 to 5 y/o period of life. Therefore, the Russia’s average age of DMD diagnosis above 7 y/o lies far beyond the optimal age for initiating of the DMD therapy with the purpose of gaining its maximum possible clinical benefit. The accumulated international and Russian experience demonstrates the possibility for improving of the primary DMD and BMD diagnosis in early preschool age and therefore requires its nationwide introduction.

Effects of Hemorrhagic Shock and Rhabdomyolysis on Renal Microcirculation, Oxygenation, and Function in a Female Swine Model.

Hemorrhagic shock (HS) and rhabdomyolysis (RM) are two important risk factors for acute kidney injury after severe trauma; however, the effects of the combination of RM and HS on kidney function are unknown. The purpose of this study was to determine the impact of RM and HS on renal function, oxygenation, perfusion, and morphology in a pig model. Forty-seven female pigs were divided into five groups: sham, RM, HS, HS and moderate RM (RM4/HS), and HS and severe RM (RM8/HS). Rhabdomyolysis was induced by intramuscular injection of glycerol 50% with a moderate dose (4 ml/kg for the RM4/HS group) or a high dose (8 ml/kg for the RM and RM8/HS groups). Among animals with HS, after 90 min of hemorrhage, animals were resuscitated with fluid followed by transfusion of the withdrawn blood. Animals were followed for 48 h. Macro- and microcirculatory parameters measurements were performed. RM alone induced a decrease in creatinine clearance at 48 h (19 [0 to 41] vs. 102 [56 to 116] ml/min for RM and sham, respectively; P = 0.0006) without alteration in renal perfusion and oxygenation. Hemorrhagic shock alone impaired temporarily renal microcirculation, function, and oxygenation that were restored with fluid resuscitation. The RM4/HS and RM8/HS groups induced greater impairment of renal microcirculation and function than HS alone at the end of blood spoliation that was not improved by fluid resuscitation. Mortality was increased in the RM8/HS and RM4/HS groups in the first 48 h (73% vs. 56% vs. 9% for the RM8/HS, RM4/HS, and HS groups, respectively). The combination of HS and RM induced an early deleterious effect on renal microcirculation, function, and oxygenation with decreased response to resuscitation and transfusion compared with HS or RM alone.

Beclin-mediated Autophagy Drives Dorsal Longitudinal Flight Muscle Histolysis in the Variable Field Cricket, Gryllus lineaticeps.

Flight muscle histolysis is a widespread strategy used by insects to break down functional flight muscle and modulate the energetic costs associated with flight muscle use and maintenance. The variable field cricket, Gryllus lineaticeps, undergoes histolysis during their transition between dispersal flight and reproduction. Despite the importance of histolysis on insect reproduction and fitness, the molecular mechanisms driving this flight muscle breakdown are not well understood. Here, we show that beclin-mediated autophagy, a conserved lysosomal-dependent degradation process, drives breakdown of dorsal longitudinal flight muscle in female flight-capable G. lineaticeps. We found that female G. lineaticeps activate autophagy in their dorsal longitudinal flight muscle (DLM), but to a greater extent than the neighboring dorsoventral flight muscle (DVM) during histolysis. RNA interference knockdown of beclin, a gene that encodes a critical autophagy initiation protein, delayed DLM histolysis, but did not affect DVM histolysis. This suggests that crickets selectively activate autophagy to break down the DLMs, while maintaining DVM function for other fitness-relevant activities such as walking. Overall, we confirmed that autophagy is a critical pathway used to remodel flight muscle cells during flight muscle histolysis, providing novel insights into the mechanisms underlying a major life history transition between dispersal and reproduction.

126 A nutritional solution based on calcidiol (25-OH-D3, HyD) and triterpenoid affects muscle protein synthesis pathways in grower-finisher pigs

Abstract To boost profitability in pig production, it is important to achieve increased lean growth rates and maximize efficiency, especially in grower-finisher pigs where feed intakes are high. Molecular research, especially the study of gene expression, is a proven tool for understanding the precise mechanisms behind muscle tissue growth, including a recent focus on pathways such as the mammalian target of rapamycin (mTOR). In the current work, gene expression analyses were used to study the mode of action of the combination of calcidiol (25-OH-D3, HyD) and triterpenoid, which has shown significant growth and efficiency improvements in grower-finisher pigs (McCormack et al., 2024). Three experimental diets were evaluated for 7 wk; Positive control: 0.7% total Ca, 0.36% total P, vit D3 at 1500IU/kg feed (PC), negative control: PC diet + 30% reduced Ca and 10% reduced P (NC), and NC diet with 1,500IU D3 in calcidiol form (25-OH-D3, HyD) and triterpenoid (NC+). At 19 wk of age, 16 animals per treatment were sacrificed and tissue samples were taken from the longissimus muscle and preserved in RNA later solution. The RNA was extracted, quality control checked, and mRNA sequenced using the Illumina platform with 150 base pair paired-end sequencing and 30M read depth. The sequenced data were aligned to the Sus scrofa reference genome (Sscrofa11.1) using Kallisto. Data were normalized and analyzed for differentially expressed genes (DEGs) between treatments using DeSeq2. Genes were assigned to biological pathways using Biofractal’s customisation of the Reactome pathway database. For statistical analysis, RNA integrity number and treatment were included in the model. In the PC compared with the NC, there were 71 DEGs using a false discovery rate (FDR) of &amp;lt; 0.10. Altered pathways included the inhibition of cellular stress pathways and increased cell turnover in the muscle of PC compared with NC pigs. In the NC+ compared with the NC, there were 155 DEGs (FDR &amp;lt; 0.10). The most significantly upregulated gene in the NC+ treatment was adenylate cyclase (FDR &amp;lt; 0.001), an upstream regulator of several pathways related to energy metabolism and muscle protein synthesis. This mechanism was confirmed in the pathway analysis, which found that the NC+ treatment activated PKA-mediated phosphorylation of CREB, a pathway that inhibits muscle atrophy. Furthermore, the NC+ treatment activated several pathways related to muscle growth, including the mammalian target of rapamycin complex 1 (mTORC1). In this study the addition of calcidiol (25-OH-D3, HyD) and triterpenoid to the diet was found to specifically affect molecular pathways in the muscle of grower-finisher pigs involved in both the inhibition of muscle breakdown as well as activating muscle growth.

An Observational Study of Nutritional Assessment, Prescription, Practices, and Its Outcome among Critically Ill Patients Admitted to an Intensive Care Unit.

Optimal feeding strategy for critically ill patients of intensive care unit (ICU) is often a matter of debate as patients admitted to ICU are highly catabolic and reduction in muscle mass is very common. We aimed at early achievement of nutritional goals in preventing skeletal muscle breakdown and improving clinical outcomes among critically ill patients with high risk of malnutrition. Nutrition risk in the critically ill (mNUTRIC) Score was used to identify the risk of malnutrition within 24 hours of admission. Quadriceps muscle mass index was measured within 24 hours of admission to ICU and repeated on 7th day. Enteral feeding was monitored by the nutrition expert as part of routine patient care and clinical outcomes were monitored. A total of 287 patients admitted in ICU were screened for malnutrition and 60 (20.9%) of them had high score (>5). There was no statistically significant reduction in the quadriceps muscle mass index (p < 0.05) (t = 0.601) measured within 24 hours of admission and on the 7th day of ICU stay, signifying that the nutritional prescription and monitoring may be useful in preserving the muscle mass. This study did not find statistically significant association between the high mNUTRIC score on admission and the clinical outcomes, such as 28 days mortality, incidence of pressure ulcers, length of ICU stay, and hospital-acquired infection (p > 0.05). Early initiation and maintenance of enteral nutrition is essential for meeting target calories and protein requirements. It may help to preserve muscle mass in critically ill patients who are otherwise at high risk of malnutrition. Sharon T, Nayak SG, Shanbhag V, Hebbar S. An Observational Study of Nutritional Assessment, Prescription, Practices, and Its Outcome among Critically Ill Patients Admitted to an Intensive Care Unit. Indian J Crit Care Med 2024;28(4):364-368.