High myoglobin level as an independent risk factor for death in elderly patients with critical COVID-19 infection: a retrospective case-control study.

AIM: This study aimed to discover risk factors for death in patients with critical COVID-19 infection in order to identify patients with a higher risk of death at an early stage. METHODS: We retrospectively analyzed the clinical data of patients with critical COVID-19 infection from April 2022 to June 2022. Data were collected from the electronic medical records. Propensity matching scores were used to reduce the effect of confounding factors, such as patient baseline variables. Independent risk factors affecting patient prognosis were assessed using univariate logistic regression and multivariate logistic regression analysis. Restricted cubic spline curves were used to assess the relationship between independent and dependent variables. RESULTS: The data of 132 patients with critical COVID-19 infection were included in the study. Of the 132 patients, 79 survived and 53 died. Among laboratory indicators, patients who died had higher proportions of abnormalities in procalcitonin, aspartate aminotransferase (AST), creatinine, cardiac troponin I, and myoglobin. Univariate and multivariate logistic regression analyses suggested that abnormal AST (OR = 4.98, P = 0.02), creatinine (OR = 7.93, P = 0.021), and myoglobin (OR = 103.08, P = 0.002) were independent risk factors for death. After correction for AST and creatinine, a linear relationship between myoglobin and risk of death in patients was found using restricted cubic splines. CONCLUSION: High myoglobin level is an independent risk factor for death and is therefore a prognostic marker in elderly patients with severe COVID-19 infection.

The 2023 Türkiye-Syria earthquakes: analysis of pediatric victims with crush syndrome and acute kidney Injury.

BACKGROUND: On February 6th, 2023, two consecutive earthquakes struck southeastern Türkiye with magnitudes of 7.7 and 7.6, respectively. This study aimed to analyze the clinical and laboratory findings, as well as management of pediatric victims with Crush Syndrome (CS) and Acute Kidney Injury (AKI). METHODS: The study included pediatric earthquake victims who were presented to Mersin University Hospital. Clinical and laboratory characteristics of the patients were collected retrospectively. RESULTS: Among 649 patients, Crush injury (CI), CS and AKI was observed in 157, 59, and 17 patients, respectively. White blood cell count (12,870 [IQR: 9910-18700] vs. 10,545 [IQR: 8355-14057] /µL, P < 0.001), C-reactive protein (51.27 [IQR: 14.80-88.78] vs. 4.59 [1.04-18.25] mg/L, P < 0.001) and myoglobin levels (443.00 [IQR: 198.5-1759.35] vs. 17 [11.8-30.43] ng/ml) were higher in patients with CS, while their sodium (IQR: 134 [131-137] vs. 136 [134-138] mEq/L, P < 0.001) levels were lower compared to non-CS patients. An increase in myoglobin levels was identified as an independent risk factor for developing CS (OR = 1.017 [1.006-1.027]). Intravenous fluid replacement was administered to the patients with CS at a dose of 4000 cc/m2/day. Hypokalemia was observed in 51.9% of the CS patients on the third day. All patients with AKI showed improvement and no deaths were reported. CONCLUSIONS: Hyponatremia and increase in inflammation markers associated with CS may be observed. An increase in myoglobin levels was identified as a risk factor for CS. Hypokalemia may be seen as a complication of vigorous fluid therapy during hospitalization.

Hemoadsorption therapy for myoglobin removal in rhabdomyolysis: consensus of the hemoadsorption in rhabdomyolysis task force.

BACKGROUND: Rhabdomyolysis describes a syndrome characterized by muscle necrosis and the subsequent release of creatine kinase and myoglobin into the circulation. Myoglobin elimination with extracorporeal hemoadsorption has been shown to effectively remove myoglobin from the circulation. Our aim was to provide best practice consensus statements developed by the Hemoadsorption in Rhabdomyolysis Task Force (HRTF) regarding the use of hemadsorption for myoglobin elimination. METHODS: A systematic literature search was performed until 11th of January 2023, after which the Rhabdomyolysis RTF was assembled comprising international experts from 6 European countries. Online conferences were held between 18th April - 4th September 2023, during which 37 consensus questions were formulated and using the Delphi process, HRTF members voted online on an anonymised platform. In cases of 75 to 90% agreement a second round of voting was performed. RESULTS: Using the Delphi process on the 37 questions, strong consensus (> 90% agreement) was achieved in 12, consensus (75 to 90% agreement) in 10, majority (50 to 74%) agreement in 13 and no consensus (< 50% agreement) in 2 cases. The HRTF formulated the following recommendations: (1) Myoglobin contributes to the development of acute kidney injury; (2) Patients with myoglobin levels of > 10,000 ng/ml should be considered for extracorporeal myoglobin removal by hemoadsorption; (3) Hemoadsorption should ideally be started within 24 h of admission; (4) If myoglobin cannot be measured then hemoadsorption may be indicated based on clinical picture and creatinine kinase levels; (5) Cartridges should be replaced every 8-12 h until myoglobin levels < 10,000 ng/ml; (6) In patients with acute kidney injury, hemoadsorption can be discontinued before dialysis is terminated and should be maintained until the myoglobin concentration values are consistently < 5000 ng/ml. CONCLUSIONS: The current consensus of the HRTF support that adjuvant hemoadsorption therapy in severe rhabdomyolysis is both feasible and safe and may be an effective method to reduce elevated circulating levels of myoglobin.

Temporal tracking of cysteine 34 oxidation of plasma albumin as a biomarker of muscle damage following a bout of eccentric exercise.

PURPOSE: Exercise-induced muscle damage (EIMD) results in the generation of reactive oxygen species (ROS), but little is known about the temporal profile of change in ROS post-EIMD and how ROS levels relate to the onset of and recovery from EIMD. Our primary aim was to examine the effect of EIMD on the pattern of change in the blood level of thiol-oxidised albumin, a marker of oxidative stress. METHODS: Seven male participants were subjected on separate days to eccentric muscle contraction to cause EIMD or a no-exercise condition. After each session, the participants collected daily dried blood spots to measure thiol-oxidised albumin and returned to the laboratory every 2 days for the assessment of indirect markers of EIMD, namely maximal voluntary contraction (MVC), delayed onset muscle soreness (DOMS), creatine kinase (CK), and myoglobin. RESULTS: Eccentric exercise resulted in a significant decrease in MVC and increase in DOMS, CK, myoglobin, and thiol-oxidised albumin with the latter reaching above baseline level within 24-48 h post-exercise. All the markers of EIMD returned to baseline level within 6 days post-exercise, but not the level of thiol-oxidised albumin which remained elevated for 10 days after exercise. There was a moderate correlation between changes in thiol-oxidised albumin and DOMS, but no significant relationship between any other markers of muscle damage. CONCLUSION: The levels of thiol-oxidised albumin increase in response to EIMD and remain elevated for several days post-exercise. The temporal pattern of change in the level of thiol-oxidised albumin suggests that this may be a useful biomarker of muscle repair post-EIMD.

Correlation Between Early Serum Myoglobin Levels and the Incidence and Prognosis of Intensive Care Unit-Acquired Weakness (ICU-AW) in Septic Shock Patients: A Comparative Study.

Intensive Care Unit-acquired weakness (ICU-AW) is a common complication that significantly impedes patient recovery. In the study, we investigated the correlation between early serum myoglobin levels in patients with septic shock due to pneumonia, and the incidence of ICU-AW, duration of mechanical ventilation, and prognosis. Patients were classified based on the development of ICU-AW within the first 10 days of ICU admission. We measured serum myoglobin levels upon ICU entry, and analyzed demographic data, APACHE II scores, use of mechanical ventilation, and clinical outcomes, including mortality and duration of mechanical ventilation. The results indicated significantly elevated serum myoglobin levels in the ICU-AW group, correlated with prolonged mechanical ventilation and increased mortality. ROC analysis revealed myoglobin as a promising biomarker for predicting ICU-AW, with an area under the curve of 0.843 (95% CI: 0.819~0.867), demonstrating a sensitivity of 76.00% and specificity of 82.30%. These findings underscored serum myoglobin as a predictive biomarker for early ICU-AW in septic shock patients, highlighting its potential to guide clinical decision-making.

Fluorescence turn-off detection of myoglobin as a cardiac biomarker using water-stable L-glutamic acid functionalized cesium lead bromide perovskite quantum dots.

Water dispersible L-glutamic acid (Glu) functionalized cesium lead bromide perovskite quantum dots (CsPbBr3 PQDs), namely CsPbBr3@Glu PQDs were synthesized and used for the fluorescence "turn-off" detection of myoglobin (Myo). The as-prepared CsPbBr3@Glu PQDs exhibited an exceptional photoluminescence quantum yield of 25% and displayed emission peak at 520 nm when excited at 380 nm. Interestingly, the fluorescence "turn-off" analytical approach was designed to detect Myo using CsPbBr3@Glu PQDs as a simple optical probe. The developed probe exhibited a wide linear range (0.1-25 µM) and a detection limit of 42.42 nM for Myo sensing. The CsPbBr3@Glu PQDs-based optical probe provides high ability to determine Myo in serum and plasma samples.

An Unusual Case of Myoglobin Cast Nephropathy in a Patient with Bartter Syndrome: A Rare Entity.

A 5-year-old male child with complaints of failure to thrive (since 4 months of age) and developmental delay presented to the nephrology department with complaints of weakness in all four limbs for 5 days. On examination, he was hypotensive, dehydrated, and had reduced tone in all four limbs. Biochemistry revealed acute kidney injury (AKI), hyponatremia, hypocalcemia, and hypokalemia. Renal needle biopsy (in view of unexplained AKI) revealed ropy, granular pigment casts with marked tubular injury. Myoglobin stain was positive. The positive genetic analysis of the patient (CLCNKB gene) confirmed the clinical diagnosis of Bartter syndrome (BS). The child was managed with aggressive intravenous hydration with potassium and calcium supplementation, and AKI recovered.

IS IT MEANINGFUL FOR SERUM MYOGLOBIN IN PATIENTS WITH COVID-19 DECREASED?

More than 3 years since cases were first reported, the COVID-19 pandemic remains an acute global emergency. As of April 12, the number of confirmed deaths worldwide was 6,897,025. Since January 8, 2023, based on the evaluation of the virus mutation, prevention, and control situation, according to the Infectious Diseases Prevention and Control Law, COVID-19 disease has been under Category B management in China. The number of COVID-19 cases in Chinese hospitals nationwide peaked (1.625 million) on January 5, 2023, and then decreased continually to 248,000 on January 23, 2023, with an 84.8% reduction from the peak. During the national COVID-19 pandemic in January 2023, we found that serum myoglobin reduced below the reference interval in 956 patients with COVID-19 who presented to the emergency department of our hospital from January 1 to January 31, 2023. So far, no articles specifically reporting the decrease of serum myoglobin in patients with COVID-19 have been retrieved. These 956 patients with low serum myoglobin were identified from 1142 COVID-19 patients who came to the emergency department of our hospital with symptoms of palpitations or chest tightness or chest pain. All 956 patients visited the hospital more than 2 weeks after the first symptoms appeared. The patient's initial symptoms were fever or cough but resolved before they arrived in the emergency department. There were 358 males and 598 females, aged from 14 to 90 years. Electrocardiogram showed no myocardial damage. Chest CT showed no signs of acute pulmonary infection. Cardiac enzymes and blood cell analysis were performed. The reference interval of serum myoglobin in our hospital is 28.0-72.0 ng/ml in males and 25.0-58.0 ng/ml in females. Patient data were obtained from a review of the electronic medical record system. What is the significance of serum myoglobin falling below the reference interval in patients with COVID-19? So far, no reports have been found in the literature. It may have the following implications: 1. Of cardiac biomarkers, an increase in myoglobin could efficiently predict COVID-19 severity in its early stages. Perhaps a decrease in myoglobin also predicts that COVID-19 patients will not have severe myocardial damage later in the disease. 2. Individuals differ widely in the clinical consequences of SARS-CoV-2 infection, from asymptomatic illness to death. Cong Chen et al. have indirectly demonstrated that SARS-CoV-2 can infect human cardiomyocytes. Most markers in the cardiac enzymes and blood cell analysis of 956 patients did not increase, indicating that the SARS-CoV-2 may not cause myocardial damage in these patients, but cardiac nerve function damage in the later stage of the disease, and then cause palpitations and other symptoms, but not serious cardiovascular disease. 3. It is possible that the virus resides somewhere in the body, such as the nerves of the heart, to cause lasting effects. 4. It may help in the research of drugs to treat COVID-19. The serum myoglobin of 956 patients was significantly decreased without myocardial damage, so we speculated that the symptoms of patients such as heart palpitations were caused by the damage of heart nerves caused by SARS-CoV-2. We further speculated that cardiac nerves were potential drug targets for the treatment of COVID-19. Echocardiography was not performed in 956 patients due to emergency department conditions and time constraints. These 956 patients were not hospitalized or followed up because they did not have myocardial injury or acute pneumonia. The emergency department also did not have adequate laboratory conditions for follow-up studies. We hope that the qualified researchers all over the world will continue to study this.

One-step hydrothermal synthesis of WS2 quantum dots as fluorescent sensor for sensitive and selective recognition of hemoglobin and cardiac biomarker myoglobin.

Transition metal dichalcogenide (TMD) dots exhibit excellent photoluminescence performance due to the quantum confinement effect and edge effect, and are extensively applied in electronic and optical devices, sensors, catalysis, and bioimaging. In this work, WS2 quantum dots (WS2 QDs) were prepared under a simple one-step hydrothermal method by optimizing the reaction conditions, and a quantum yield of 11.23% was achieved. The as-prepared WS2 QDs possess good photo-bleaching resistance, salt tolerance, and pH stability. The fluorescence investigations showed that the WS2 QDs acted as a highly efficient fluorescent sensor to detect hemoglobin (Hb) and cardiac biomarker myoglobin (Myo). The linear range was 1-600 µg/mL for Hb and 0.01-120 µg/mL for Myo, with detection limits as low as 260 and 7.6 ng/mL, respectively. Importantly, the WS2 QDs were used to determine the Hb/Myo content in human blood/serum samples, with satisfactory results, indicating that this technique holds promise for application in clinical diagnosis associated with Hb/Myo levels. To the best of our knowledge, this is the first example of TMD QDs without any modification as a fluorescent sensor for detecting Hb and Myo simultaneously.

Cilastatin Ameliorates Rhabdomyolysis-induced AKI in Mice.

BACKGROUND: Rhabdomyolysis, the destruction of skeletal muscle, is a significant cause of AKI and death in the context of natural disaster and armed conflict. Rhabdomyolysis may also initiate CKD. Development of specific pharmacologic therapy is desirable because supportive care is nearly impossible in austere environments. Myoglobin, the principal cause of rhabdomyolysis-related AKI, undergoes megalin-mediated endocytosis in proximal tubule cells, a process that specifically injures these cells. METHODS: To investigate whether megalin is protective in a mouse model of rhabdomyolysis-induced AKI, we used male C57BL/6 mice and mice (14-32 weeks old) with proximal tubule-specific deletion of megalin. We used a well-characterized rhabdomyolysis model, injection of 50% glycerol in normal saline preceded by water deprivation. RESULTS: Inducible proximal tubule-specific deletion of megalin was highly protective in this mouse model of rhabdomyolysis-induced AKI. The megalin knockout mice demonstrated preserved GFR, reduced proximal tubule injury (as indicated by kidney injury molecule-1), and reduced renal apoptosis 24 hours after injury. These effects were accompanied by increased urinary myoglobin clearance. Unlike littermate controls, the megalin-deficient mice also did not develop progressive GFR decline and persistent new proteinuria. Administration of the pharmacologic megalin inhibitor cilastatin to wild-type mice recapitulated the renoprotective effects of megalin deletion. This cilastatin-mediated renoprotective effect was dependent on megalin. Cilastatin administration caused selective proteinuria and inhibition of tubular myoglobin uptake similar to that caused by megalin deletion. CONCLUSIONS: We conclude that megalin plays a critical role in rhabdomyolysis-induced AKI, and megalin interference and inhibition ameliorate rhabdomyolysis-induced AKI. Further investigation of megalin inhibition may inform translational investigation of a novel potential therapy.

Dissociation between exercise intensity thresholds: mechanistic insights from supine exercise.

This study tested the hypothesis that the respiratory compensation point (RCP) and breakpoint in deoxygenated [heme] [deoxy[heme]BP, assessed via near-infrared spectroscopy (NIRS)] during ramp incremental exercise would occur at the same metabolic rate in the upright (U) and supine (S) body positions. Eleven healthy men completed ramp incremental exercise tests in U and S. Gas exchange was measured breath-by-breath and time-resolved-NIRS was used to measure deoxy[heme] in the vastus lateralis (VL) and rectus femoris (RF). RCP (S: 2.56 ± 0.39, U: 2.86 ± 0.40 L·min-1, P = 0.02) differed from deoxy[heme]BP in the VL in U (3.10 ± 0.44 L·min-1, P = 0.002), but was not different in S in the VL (2.70 ± 0.50 L·min-1, P = 0.15). RCP was not different from the deoxy[heme]BP in the RF for either position (S: 2.34 ± 0.48 L·min-1, U: 2.76 ± 0.53 L·min-1, P > 0.05). However, the deoxy[heme]BP differed between muscles in both positions (P < 0.05), and changes in deoxy[heme]BP did not relate to ΔRCP between positions (VL: r = 0.55, P = 0.080, RF: r = 0.26, P = 0.44). The deoxy[heme]BP was consistently preceded by a breakpoint in total[heme], and was, in turn, itself preceded by a breakpoint in muscle surface electromyography (EMG). RCP and the deoxy[heme]BP can be dissociated across muscles and different body positions and, therefore, do not represent the same underlying physiological phenomenon. The deoxy[heme]BP may, however, be mechanistically related to breakpoints in total[heme] and muscle activity.

Simulated microgravity disturbs iron metabolism and distribution in humans: Lessons from dry immersion, an innovative ground-based human model.

The objective of the present study was to determine the effects of dry immersion, an innovative ground-based human model of simulated microgravity and extreme physical inactivity, on iron homeostasis and distribution. Twenty young healthy men were recruited and submitted to 5 days of dry immersion (DI). Fasting blood samples and MRI were performed before and after DI exposure to assess iron status, as well as hematological responses. DI increased spleen iron concentrations (SIC), whereas hepatic iron store (HIC) was not affected. Spleen iron sequestration could be due to the concomitant increase in serum hepcidin levels (P < .001). Increased serum unconjugated bilirubin, as well as the rise of serum myoglobin levels support that DI may promote hemolysis and myolysis. These phenomena could contribute to the concomitant increase of serum iron and transferrin saturation levels (P < .001). As HIC remained unchanged, increased serum hepcidin levels could be due both to higher transferrin saturation level, and to low-grade pro-inflammatory as suggested by the significant rise of serum ferritin and haptoglobin levels after DI (P = .003 and P = .003, respectively). These observations highlight the need for better assessment of iron metabolism in bedridden patients, and an optimization of the diet currently proposed to astronauts.

Efficacy and safety of the Clearum dialyzer.

The Clearum dialyzer, built by Medtronic, became commercially available in several European countries in 2020, but there are still no reports of in vivo data. The aim of this study was to evaluate the efficacy and risk of hypoalbuminemia of this dialyzer compared with previously evaluated hemodialysis (HD), expanded hemodialysis (HDx), and postdilution hemodiafiltration (HDF) treatments. A prospective study was carried out in 15 patients. Each patient underwent seven dialysis sessions: FX80 Cordiax in HD, Clearum HS17 in HD, Phylther 17-SD in HDx, Theranova 400 in HDx, Phylther 17-G in postdilution HDF, Clearum HS17 in postdilution HDF, and FX80 Cordiax in postdilution HDF. The reduction ratios of urea, creatinine, ß2 -microglobulin, myoglobin, prolactin, α1 -microglobulin, α1 -acid glycoprotein, and albumin were compared intraindividually. Dialysate albumin loss was also measured. Comparison of dialysis techniques revealed no differences between small molecules, but HDx and HDF were significantly higher than HD with medium and large molecular weights. The Clearum dialyzer in HDF obtained similar results to FX80 Cordiax in HDF, was slightly superior to Phylther 17-G in HDF, and was statistically superior to both dialyzers in HDx. Albumin losses with the Clearum dialyzer were among the lowest, both in HD and HDF treatments. The highest global removal score (GRS) values were obtained with the helixone and Clearum dialyzers in HDF, with similar results both in HD and HDF. In addition, the GRS values with HDx treatments were statistically significantly higher than those with HD. The new Clearum dialyzer has excellent behavior and tolerance in HD and HDF. Its adequate permeability has been proven with its maximal performance in HDF, which could represent an upgrade versus its predecessor polyphenylene dialyzers.

Frequent blood flow restricted training not to failure and to failure induces similar gains in myonuclei and muscle mass.

The purpose of the present study was to compare the effects of short-term high-frequency failure vs non-failure blood flow-restricted resistance exercise (BFRRE) on changes in satellite cells (SCs), myonuclei, muscle size, and strength. Seventeen untrained men performed four sets of BFRRE to failure (Failure) with one leg and not to failure (Non-failure; 30-15-15-15 repetitions) with the other leg using knee-extensions at 20% of one repetition maximum (1RM). Fourteen sessions were distributed over two 5-day blocks, separated by a 10-day rest period. Muscle samples obtained before, at mid-training, and 10-day post-intervention (Post10) were analyzed for muscle fiber area (MFA), myonuclei, and SC. Muscle size and echo intensity of m.rectus femoris (RF) and m.vastus lateralis (VL) were measured by ultrasonography, and knee extension strength with 1RM and maximal isometric contraction (MVC) up until Post24. Both protocols increased myonuclear numbers in type-1 (12%-17%) and type-2 fibers (20%-23%), and SC in type-1 (92%-134%) and type-2 fibers (23%-48%) at Post10 (p < 0.05). RF and VL size increased by 5%-10% in both legs at Post10 to Post24, whereas the MFA of type-1 fibers in Failure was decreased at Post10 (-10 ± 16%; p = 0.02). Echo intensity increased by ~20% in both legs during Block1 (p < 0.001) and was ~8 to 11% below baseline at Post24 (p = 0.001-0.002). MVC and 1RM decreased by 5%-10% after Block1, but increased in both legs by 6%-11% at Post24 (p < 0.05). In conclusion, both short-term high-frequency failure and non-failure BFRRE induced increases in SCs, in myonuclei content, muscle size, and strength, concomitant with decreased echo intensity. Intriguingly, the responses were delayed and peaked 10-24 days after the training intervention. Our findings may shed light on the mechanisms involved in resistance exercise-induced overreaching and supercompensation.

Circulating microRNAs after a 24-h ultramarathon run in relation to muscle damage markers in elite athletes.

Ultra-endurance sports are growing in popularity but can be associated with adverse health effects, such as exercise-induced muscle damage (EIMD), which can lead to exertional rhabdomyolysis. Circulating microRNAs (miRNAs) may be useful to approach the degree of EIMD. We aimed to (1) investigate the relevance of circulating miRNAs as biomarkers of muscle damage and (2) examine the acute response of skeletal/cardiac muscle and kidney biomarkers to a 24-h run in elite athletes. Eleven elite athletes participated in the 24-h run World Championships. Counter-movement jump (CMJ), creatine kinase (CK), myoglobin (Mb), creatinine (Cr), high-sensitive cardiac troponin T (hs-cTnT), and muscle-specific miRNA (myomiR) levels were measured before, immediately after, and 24 and 48h after the race. CMJ height was reduced immediately after the race (-84.0 ± 25.2%, p < 0.001) and remained low at 24 h (-43.6 ± 20.4%, p = 0.002). We observed high CK activity (53 239 ± 63 608 U/L, p < 0.001) immediately after the race, and it remained elevated 24h after (p < 0.01). Circulating myomiR levels (miR-1-3p, miR-133a-3p, miR-133b, miR-208a-3p, miR-208b-3p, and miR-499a-5p) were elevated immediately after the 24-h run (fold changes: 18-124,723, p<0.001) and significantly (p < 0.05) correlated or tended to significantly (p < 0.07) correlate with the reduction in CMJ height at 24 h. We found no significant correlation between CMJ height loss at 24 h and CK (p = 0.23) or Mb (p = 0.41) values. All elite ultramarathon runners included in our study were diagnosed with exertional rhabdomyolysis after the 24-h ultramarathon race. MyomiR levels may be useful to approach the degree of muscle damage.

Malignant hyperthermia when dantrolene is not readily available.

BACKGROUND: Malignant hyperthermia is a rare but life-threatening pharmacogenetic muscle disorder characterized by abnormal hypermetabolic reactions and commonly triggered in susceptible individuals by volatile anesthetics or succinylcholine, or both. Unfortunately, the specific medicine dantrolene is not readily available in many countries including China. The aim of this study was to find the characteristics of malignant hyperthermia under the situation that dantrolene is not readily available. METHODS: The cases of malignant hyperthermia reported on the most commonly used databases in China from 1985 to 2020 were analyzed. The inclusion criteria were the MH episodes only related to anesthesia. The exclusion criteria were dubious MH episodes only caused by Ketamine administration or MH episodes irrelevant to anesthesia. Independent samples t-test and Pearson's chi-squared test were applied to assess the difference between the survived and death cases. RESULTS: Ninety-two cases of malignant hyperthermia reported on the most commonly used databases in China from 1985 to 2020 were analyzed. Median (IQR [range]) age was 18.5 (11.8-37.0 [0-70.0]) years. Compared with the survived cases, the death cases had higher maximum end-tidal partial pressure of CO2 (P = 0.033), the maximum arterial partial pressure of CO2 (P = 0.006), temperature first measured when the patient was first discovered abnormal (P = 0.012), and maximum temperature (P < 0.001). Besides, the death cases had less minimum pH (P < 0.001) and higher potassium (P < 0.001) and were more likely to have coagulation disorders (p = 0.018). Concerning treatment, cases used furosemide (P = 0.024), mannitol (P = 0.029), blood purification treatment (P = 0.017) had the advantage on the outcome. Creatine phosphokinase, myoglobin, and MB isoenzyme of creatine phosphokinase differed greatly among cases during the first week. 43 (46.7%) cases had congenital diseases. 12 (13.0%) cases were reported with abnormal laboratory test results or abnormal signs that are possibly relevant before anesthesia. CONCLUSIONS: In countries that dantrolene is not readily available, early warning, diagnosis, and prompt effective therapies are crucial for MH patients to survive.

Changes in Urinary Titin Fragment in Response to Different Types of Dynamic Eccentric Exercises.

The urinary level of the titin fragment has been considered a non-invasive and sensitive biomarker for muscle damage in clinical cases. However, there is little evidence regarding changes in the urinary titin fragment in response to exercise-induced muscle damage. In this study, we aimed to investigate whether the urinary titin fragment reflects the magnitude of muscle damage induced by two lower-limb eccentric exercises. In this study, healthy young male subjects performed drop jump (n=9) and eccentric ergometer exercise (n=9). Blood and urine samples were collected at various time points before and after the exercises. Although perceived muscle soreness assessed by sit-to-stand tasks was increased at 24 h and 48 h after both drop jump and the eccentric ergometer exercise groups, the pressure pain threshold was not changed. Changes of the urinary titin fragment, plasma myomesin 3 fragments, creatine kinase (CK), and myoglobin (Mb) after the eccentric exercises were increased but not statistically significant. Meanwhile, we found that the changes in the urinary titin fragment levels in response to both drop jump and the eccentric ergometer exercise were correlated with those of plasma CK and Mb levels. These results provide evidence that the urinary titin fragment level is a non-invasive biomarker reflecting the magnitude of eccentric exercise-induced muscle damage.

Myoglobin: a new biomarker for spinal and bulbar muscular atrophy?

OBJECTIVES: There is a primary muscular affection in spinal and bulbar muscular atrophy (SBMA). Myoglobin (Myo) is mainly distributed in the myocardium and skeletal muscle. The purpose of the study was to explore the significance of serum Myo detection in the diagnosis and clinical evaluation of SBMA. MATERIALS AND METHODS: In this study, serum creatine kinase (CK), Myo, and Troponin T (cTNT) levels were assessed in 80 patients with SBMA and were compared with those of 60 patients with amyotrophic lateral sclerosis (ALS). All measurement data were analyzed using the t-test and enumeration data using the χ2-test. RESULTS: The rate of abnormal Myo levels in the SBMA group was 100%, however, none of the patients with ALS had an abnormal Myo level. There was no overlap between the two groups. The Myo levels in patients with SBMA were correlated with the course of the disease. Further, their CK level was significantly elevated compared with that in patients with ALS, however, there was an overlap between the two groups. The serum cTNT level in patients with SBMA was not significantly different from that in patients with ALS. CONCLUSION: Myo, as a simple, inexpensive, and readily available biochemical indicator, is likely to be used for the differentiation between SBMA and ALS, and used as a new biomarker for the clinical evaluation of SBMA.

Electrical weapons and rhabdomyolysis.

It has been suggested that an application of a conducted electrical weapon (CEW) might cause muscle injury such as rhabdomyolysis and an acute inflammatory response. We explored this hypothesis by testing the effects of electrical weapons on circulating markers of inflammation and muscle damage. In a prospective study, 29 volunteers received a full-trunk 5-s TASER® X26(E) CEW exposure. Venous blood samples were taken before, 5 min after, and at 24 h following the discharge. We tested for changes in serum levels of C-reactive protein (CRP), alkaline phosphatase (ALP), myoglobin, albumin, globulin, albumin/globulin ratio, aspartate and alanine aminotransferase, creatine kinase, total protein, bilirubin, and lactic acid dehydrogenase. Uncorrected CRP and myoglobin levels were lower in the immediate post exposure period (CRP levels 1.44 ± 1.39 v 1.43 ± 1.32 mg/L; p = 0.046 and myoglobin 36.8 ± 11.9 v 36.1 ± 13.9 µg/L; p = 0.0019) but these changes were not significant after correction for multiple comparisons. There were no changes in other biomarkers. At 24 h, CRP levels had decreased by 30% to 1.01 ± 0.80 mg/L (p = 0.001 from baseline). ALP was unchanged immediately after the CEW application but was reduced by 5% from baseline (66.2 ± 16.1 to 62.7 ± 16.1 IU/L; p = 0.0003) at 24 h. No other biomarkers were different from baseline at 24 h. A full-trunk electrical weapon exposure did not lead to clinically significant changes in the acute phase protein levels or changes in measures of muscle cellular injury. We found no biomarker evidence of rhabdomyolysis.

A metabolomics study: Reveals the protective effect and mechanism of Terminalia chebula Retz on the cardiotoxicity induced by radix Aconiti kusnezoffii Reichb.

To reveal the protective effect of Terminalia chebula Retz (TCR) on cardiotoxicity induced by radix of Aconitum kusnezoffii Reichb (AKR). Control, AKR, AKR-TCR 1:3, AKR-TCR 1:1, AKR-TCR 3:1 and TCR-prepared AKR groups were set up. After treatment, the heart tissues were observed by H&E staining and transmission electron microscope. Serum myoglobin (MB) and troponin (cTn) were detected by ELISA. UPLC-Q Exactive/MS analysis was performed to detect the metabolic difference among the groups. ELISA results showed that the MB and cTn values of AKR group were significantly higher than Control group (P<0.05), while those of the other groups were lower than AKR group. TCR-prepared AKR group had similar MB and cTn contents to the Control group. Histopathological examination also indicated better detoxifying effects in the TCR-prepared AKR and AKR-TCR 1:1 group. The serum metabolomics analysis showed obvious distinction between the AKR and Control groups, while AKR-TCR combination reversed the metabolomics changes induced by AKR. Through multivariate statistical analysis, 9 metabolic markers related to energy, nucleic acid and amino acid metabolism were identified. Conclusively, AKR-induced cardiotoxicity may be related to energy, nucleic acid and amino acid metabolism, and TCR can reduce the cardiotoxicity by regulating the relative metabolism pathways.