Pharmacokinetics of intravenous daptomycin in Japanese pediatric patients: Pharmacokinetic comparisons supporting dosing recommendations in Japanese pediatric patients.

INTRODUCTION: The pharmacokinetics (PK) of daptomycin has not been previously characterized in Japanese pediatric patients with complicated skin and soft tissue infections (cSSTI) or bacteremia. An aim of the study includes evaluation of PK of daptomycin in Japanese pediatric patients and an appropriateness of the age-specific, weight-based dosing regimens in Japanese pediatric patients based on PK comparison with Japanese adult patients. METHODS: The phase 2 trial enrolled Japanese pediatric patients (age 1-17 years) with cSSTI (n = 14) or bacteremia (n = 4) caused by gram-positive cocci in order to evaluate safety, efficacy and PK. The Phase 3 trial in Japanese adult patients (SSTI n = 65, septicemia/right-sided infective endocarditis (RIE) n = 7) was referred to for PK comparison between adult and pediatric. Daptomycin concentrations in plasma were analyzed by reverse-phase high-performance liquid chromatography (HPLC). PK parameters were determined using non-compartmental analysis in Japanese pediatric and Japanese adult patients. The exposures in Japanese pediatric patients were graphically compared with those in Japanese adult patients. The relationship between daptomycin exposures and creatine phosphokinase (CPK) elevation was explored visually. RESULTS: Following administration of the age-specific, weight-based dosing regimens, daptomycin exposures were overlapping across age groups in pediatric patients with cSSTI with similar observations based on clearance. The distribution of individual exposure in Japanese pediatric patients was overlapping with that in Japanese adult patients. No apparent relationship between daptomycin exposures and CPK elevation in Japanese pediatric patients was observed. CONCLUSIONS: The results suggested that the age-specific, weight-based dosing regimens are considered to be appropriate in Japanese pediatric patients.

Trial of Intravenous Immune Globulin in Dermatomyositis.

BACKGROUND: Intravenous immune globulin (IVIG) for the treatment of dermatomyositis has not been extensively evaluated. METHODS: We conducted a randomized, placebo-controlled trial involving patients with active dermatomyositis. The patients were assigned in a 1:1 ratio to receive IVIG at a dose of 2.0 g per kilogram of body weight or placebo every 4 weeks for 16 weeks. The patients who received placebo and those without confirmed clinical deterioration while receiving IVIG could enter an open-label extension phase for another 24 weeks. The primary end point was a response, defined as a Total Improvement Score (TIS) of at least 20 (indicating at least minimal improvement) at week 16 and no confirmed deterioration up to week 16. The TIS is a weighted composite score reflecting the change in a core set of six measures of myositis activity over time; scores range from 0 to 100, with higher scores indicating greater improvement. Key secondary end points included at least moderate improvement (TIS ≥40) and major improvement (TIS ≥60), and change in score on the Cutaneous Dermatomyositis Disease Area and Severity Index. RESULTS: A total of 95 patients underwent randomization: 47 patients were assigned to the IVIG group, and 48 to the placebo group. At 16 weeks, 79% of the patients in the IVIG group (37 of 47) and 44% of those in the placebo group (21 of 48) had a TIS of at least 20 (difference, 35 percentage points; 95% confidence interval, 17 to 53; P<0.001). The results with respect to the secondary end points, including at least moderate improvement and major improvement, were generally in the same direction as the results of the primary end-point analysis, except for the change in creatine kinase level (an individual core measure of the TIS), which did not differ meaningfully between the two groups. Over 40 weeks, 282 treatment-related adverse events occurred in the IVIG group, including headache (in 42% of patients), pyrexia (in 19%), and nausea (in 16%). A total of 9 serious adverse events that were considered to be related to IVIG occurred, including 6 thromboembolic events. CONCLUSIONS: In this 16-week trial involving adults with dermatomyositis, the percentage of patients with a response of at least minimal improvement based on a composite score of disease activity was significantly greater among those who received IVIG than among those who received placebo. IVIG was associated with adverse events, including thromboembolism. (Funded by Octapharma Pharmazeutika; ProDERM ClinicalTrials.gov number, NCT02728752.).

Rhabdomyolysis related to acute recreational drug toxicity-A Euro-DEN study.

BACKGROUND: This study was conducted to retrospectively assess the relationships between: rhabdomyolysis (quantified by creatine kinase (CK) activity) and kidney injury (quantified by serum creatinine concentration), sex, age, body temperature on admission, presence of seizures, and agitation or aggression in patients presenting to the Emergency Department with acute recreational drug toxicity. We also investigated the association with the substances ingested. METHODS: All presentations to the 16 sentinel Euro-DEN centres in 10 European countries with acute recreational drug toxicity during the first year of the Euro-DEN study (October 2013 to September 2014) were considered. Cases that had abnormal CK activity recorded as part of routine clinical care were divided into 3 cohorts depending on peak CK activity. Cases with normal CK activity were included as a control group (4th cohort). RESULTS: Only 1,015 (18.4%) of the 5,529 Euro-DEN presentations had CK activity concentration recorded. Of this group 353 (34.8%) had also creatinine concentration measured. There were 375 (36.9%) with minor rhabdomyolysis, 69 (6.8%) with moderate rhabdomyolysis, and 24 (2.4%) with severe rhabdomyolysis; 547 (53.9%) were included in the control group. There was a positive correlation between CK activity and creatinine concentration (correlation coefficient r = 0.71, p<0.0001). There was no correlation between CK activity and body temperature at the time of presentation to the ED (correlation coefficient r = 0.07, p = 0.03). There was a positive correlation between CK activity and length of stay in the hospital (r = 0.31, p<0.001). There was no association between CK activity and the presence of seizures (p = 0.33) or agitation/aggression (p = 0.45), patients age (p = 0.4) or sex (p = 0.25). The 5 most common agents amongst patients presenting with rhabdomyolysis were: cocaine (n = 107; 22.9% presentations), amphetamine (76; 16.2%), cannabis (74; 15.8%), GHB/GBL (72; 15.4%) and heroin (67; 14.3%). The distribution of rhabdomyolysis in 5 most common drugs was (drug; patients with rhabdomyolysis, patients without rhabdomyolysis): cocaine (107, 122), cannabis (74, 117), GHB/GBL (72, 81), amphetamine (76, 66), heroin (67, 70). CONCLUSIONS: Abnormal values of CK activity occurred in almost half (46.1%) of presentations to the Emergency Department with acute recreational drug toxicity in whom CK activity was measured; however, severe rhabdomyolysis is seen in only a small minority (2.4%). Those with rhabdomyolysis are at significantly higher risk of kidney injury and have a longer length of hospital stay.

Parâmetros sanguíneos de potros da raça Crioula / Blood parameters of crioulo breed horse

Com o propósito de estabelecer valores de hematócrito, proteínas plasmáticas totais, fibrinogênio, creatina quinase , aspartato transferase e lactato em potros da raça Crioula, do nascimento até os dois anos, utilizaram-se amostras sanguíneas de 85 animais, divididos pela estratificação etária: Grupo 1 (G1) Até 15 dias de vida (n=70); grupo 2 (G2), entre 16 dias até um mês (n=67); grupo 3 (G3), entre 1 e 3 meses (n=75); grupo 4 (G4), entre 3 e 6 meses (n=64); grupo 5 (G5), entre 6 e 9 meses (n=59); grupo 6 (G6), entre 9 e 18 meses (n=39); e grupo 7 (G7), entre 18 meses até 2 anos (n=17). Foi realizado estudo estatístico entre os grupos pela análise de variância unidirecional (one-wayANOVA), complementada pelo teste de Tukey. Para comparação das médias entre os sexos utilizou-se o teste t de Student. O hematócrito foi significativamente mais elevado até os 90 dias e nas fêmeas do G7. Para proteínas plasmáticas totais, notou-se aumento significativo nos grupos 3, 4, 6 e 7. Os valores de fibrinogênio foram maiores no G1. A CK apresentou maior concentração no G5 e a AST no G7. A AST assumiu valores semelhantes dos 30 dias até os 2 anos. A concentração de lactato foi mais elevada no G3. Conclui-se que na interpretação dos exames laboratoriais de potros da raça crioula, o gênero não interfere significativamente nos resultados, porém a idade deve ser considerada devido à ocorrência de variações relevantes. Recomenda-se que para interpretação sejam consultadas tabelas específicas para cada análise.

Plasma levels of hematocrit, total plasma protein, fibrinogen, creatine phosphokinase, aspartate transferase, and lactate were analyzed in blood samples of 85 Crioula breed foals, from birth to two years of age. The animals were divided into age groups: G1 (up to 15 days of age; n=70), G2 (from 16 days to one month of age; n=67), G3 (between one and three months of age; n=75), G4 (between three and six months of age; n=64), G5 (between six and nine months of age; n=59), G6 (between nine and 18 months of age; n=39), and G7 (between 18 months and two years of age; n=17). These groups were statistically analyzed by one-way variance analysis (ANOVA) and Tukey’s test. Male and female means were compared by Student’s t-test. Hematocrit levels were significantly higher up to 90 days of age and in G7 females. Total plasma proteins increased significantly in groups 3, 4, 6, and 7. The highest fibrinogen levels were found in G1. Yet for creatine phosphokinase, the highest concentrations were detected in G5, whereas those of aspartate aminotransferase in G7. The levels of this enzyme remained similar from 30 days to two years of age. Lactate concentrations were higher in G3. We concluded that the sex of the animal had no significant effect on laboratory test interpretations. By contrast, the age of the animal should be considered since relevant variations were observed with time. Nevertheless, specific tables for each analysis should be consulted for interpretation of results.

Blood parameters of crioulo breed horse / Parâmetros sanguíneos de potros da raça Crioula

Plasma levels of hematocrit, total plasma protein, fibrinogen, creatine phosphokinase, aspartate transferase, and lactate were analyzed in blood samples of 85 Crioula breed foals, from birth to two years of age. The animals were divided into age groups: G1 (up to 15 days of age; n=70), G2 (from 16 days to one month of age; n=67), G3 (between one and three months of age; n=75), G4 (between three and six months of age; n=64), G5 (between six and nine months of age; n=59), G6 (between nine and 18 months of age; n=39), and G7 (between 18 months and two years of age; n=17). These groups were statistically analyzed by one-way variance analysis (ANOVA) and Tukey's test. Male and female means were compared by Student's t-test. Hematocrit levels were significantly higher up to 90 days of age and in G7 females. Total plasma proteins increased significantly in groups 3, 4, 6, and 7. The highest fibrinogen levels were found in G1. Yet for creatine phosphokinase, the highest concentrations were detected in G5, whereas those of aspartate aminotransferase in G7. The levels of this enzyme remained similar from 30 days to two years of age. Lactate concentrations were higher in G3. We concluded that the sex of the animal had no significant effect on laboratory test interpretations. By contrast, the age of the animal should be considered since relevant variations were observed with time. Nevertheless, specific tables for each analysis should be consulted for interpretation of results.

Com o propósito de estabelecer valores de hematócrito, proteínas plasmáticas totais, fibrinogênio, creatina quinase , aspartato transferase e lactato em potros da raça Crioula, do nascimento até os dois anos, utilizaram-se amostras sanguíneas de 85 animais, divididos pela estratificação etária: Grupo 1 (G1) Até 15 dias de vida (n=70); grupo 2 (G2), entre 16 dias até um mês (n=67); grupo 3 (G3), entre 1 e 3 meses (n=75); grupo 4 (G4), entre 3 e 6 meses (n=64); grupo 5 (G5), entre 6 e 9 meses (n=59); grupo 6 (G6), entre 9 e 18 meses (n=39); e grupo 7 (G7), entre 18 meses até 2 anos (n=17). Foi realizado estudo estatístico entre os grupos pela análise de variância unidirecional (one-wayANOVA), complementada pelo teste de Tukey. Para comparação das médias entre os sexos utilizou-se o teste t de Student. O hematócrito foi significativamente mais elevado até os 90 dias e nas fêmeas do G7. Para proteínas plasmáticas totais, notou-se aumento significativo nos grupos 3, 4, 6 e 7. Os valores de fibrinogênio foram maiores no G1. A CK apresentou maior concentração no G5 e a AST no G7. A AST assumiu valores semelhantes dos 30 dias até os 2 anos. A concentração de lactato foi mais elevada no G3. Conclui-se que na interpretação dos exames laboratoriais de potros da raça crioula, o gênero não interfere significativamente nos resultados, porém a idade deve ser considerada devido à ocorrência de variações relevantes. Recomenda-se que para interpretação sejam consultadas tabelas específicas para cada análise.

Circulating markers of oxidative stress are associated with a muscle injury in patients with muscular dystrophy Duchenne.

BACKGROUND: A small number of studies have confirmed the presence of oxidative damage in patients with Duchenne muscular dystrophy (DMD). Nevertheless, it is unknown if there a relationship of circulating markers of oxidative stress with a muscle injury. OBJECTIVE: We evaluated if oxidative damage and anti-oxidant markers are associated with muscle damage in DMD. METHODS: This cross-sectional study included 24 patients with DMD classified in ambulatory and non-ambulatory. Markers of muscle damage (creatine kinase [CK]), oxidative damage (malondialdehyde [MDA], and 8-isoprostane), anti-oxidant function (Thiol and mRNA of NRF2 and NF-κB) and nitric oxide (NO) were quantified in circulation. RESULTS: Total NO, MDA, and 8-isoprostane concentrations were significantly (p < 0.05) higher, and thiol concentration was lower in non-ambulatory than ambulatory patients. A significant correlation (p < 0.05) between muscle injury (evaluated by Vignos scale) with CK (r = -0.382), NO (r = 0.444), MDA (r = 0.503), 8-isoprostanes (r = 0.435) and thiol (r = -0.430) was observed. CONCLUSION: These findings suggest that non-ambulatory have high oxidative damage and low anti-oxidant function than ambulatory patients with DMD. Total nitric oxide and oxidative damage plasma markers increase, but the anti-oxidant marker thiol decreases with a muscle injury in boys with DMD. The findings of this study suggest that these markers could be considered as goods indicators of oxidative damage in longitudinal studies to evaluate the muscle injury during DMD progression. Additionally, these findings add new information about the pathophysiology of DMD.

Genetic spectrum of Charcot-Marie-Tooth disease associated with myelin protein zero gene variants in Japan.

We aimed to reveal the genetic features associated with MPZ variants in Japan. From April 2007 to August 2017, 64 patients with 23 reported MPZ variants and 21 patients with 17 novel MPZ variants were investigated retrospectively. Variation in MPZ variants and the pathogenicity of novel variants was examined according to the American College of Medical Genetics standards and guidelines. Age of onset, cranial nerve involvement, serum creatine kinase (CK), and cerebrospinal fluid (CSF) protein were also analyzed. We identified 64 CMT patients with reported MPZ variants. The common variants observed in Japan were different from those observed in other countries. We identified 11 novel pathogenic variants from 13 patients. Six novel MPZ variants in eight patients were classified as likely benign or uncertain significance. Cranial nerve involvement was confirmed in 20 patients. Of 30 patients in whom serum CK levels were evaluated, eight had elevated levels. Most of the patients had age of onset >20 years. In another subset of 30 patients, 18 had elevated CSF protein levels; four of these patients had spinal diseases and two had enlarged nerve root or cauda equina. Our results suggest genetic diversity across patients with MPZ variants.

Resveratrol improves motor function in patients with muscular dystrophies: an open-label, single-arm, phase IIa study.

Muscular dystrophies (MDs) are inherited disorders characterized by progressive muscle weakness. Previously, we have shown that resveratrol (3,5,4'-trihydroxy-trans-stilbene), an antioxidant and an activator of the protein deacetylase SIRT1, decreases muscular and cardiac oxidative damage and improves pathophysiological conditions in animal MD models. To determine whether resveratrol provides therapeutic benefits to patients with MDs, an open-label, single-arm, phase IIa trial of resveratrol was conducted in 11 patients with Duchenne, Becker or Fukuyama MD. The daily dose of resveratrol was 500 mg/day, which was increased every 8 weeks to 1000 and then 1500 mg/day. Primary outcomes were motor function, evaluated by a motor function measure (MFM) scale, muscular strength, monitored with quantitative muscle testing (QMT), and serum creatine kinase (CK) levels. Adverse effects and tolerability were evaluated as secondary outcomes. Despite the advanced medical conditions of the patients, the mean MFM scores increased significantly from 34.6 to 38.4 after 24 weeks of medication. A twofold increase was found in the mean QMT scores of scapula elevation and shoulder abduction. Mean CK levels decreased considerably by 34%. Diarrhoea and abdominal pain was noted in six and three patients, respectively. Resveratrol may provide some benefit to MD patients.

Acute kidney injury in severely injured patients admitted to the intensive care unit.

BACKGROUND: Our objective was to identify possible associations between clinical and laboratory variables and the risk of developing acute kidney injury (AKI) in severely injured patients admitted to the intensive care unit (ICU) for whom creatine kinase (CK) levels were available. METHODS: For this retrospective observational study, we analyzed adult trauma patients admitted to the ICU from 2011 to 2015 at Fundación Valle del Lili (FVL) University Hospital. Our primary outcome was the incidence of AKI. Multivariate regression analysis was used to assess risk factors for this outcome. RESULTS: A total of 315 patients were included. The trauma mechanisms were blunt (n = 130), penetrating (n = 66) and blast (n = 44) trauma. The median (interquartile range, IQR) of injury severity score (ISS) was 21 (16-29). AKI developed in 75 patients (23.8%). Multivariate regression analysis revealed that the thoracic abbreviated injury scale (AIS) value (median (IQR) in the AKI group: 3 (0-4)), Acute Physiology and Chronic Health Evaluation (APACHE II) score (median (IQR) in the AKI group: 18 (10-27)), CK greater than 5000 U/L, lactic acid concentration at admission, and dobutamine administration were independently associated with AKI. CONCLUSION: We found that age, APACHE II score, thoracic trauma, lactic acidosis, and dobutamine administration were independently associated with AKI. Trauma surgeons need to be aware of the increased odds of AKI if one of these factors is identified during the evaluation and treatment of injured patients.

Characteristics and Outcomes of Patients Infected with SARS-CoV-2 in Israel: Correlation between Laboratory Findings on Admission to Emergency Department and Subsequent Respiratory Failure.

BACKGROUND: There is limited clinical information on coronavirus disease-19 (COVID-19) patients in Israel. OBJECTIVES: To describe the characteristics, outcomes, and potential associations of hospitalized COVID-19 patients in Israel. METHODS: We conducted a single-center, retrospective study of 58 consecutive laboratory-confirmed COVID-19 patients admitted to Laniado Hospital, Israel, between 14 March 2020 and 14 May 2020. Demographic, clinical, and laboratory data on admission were collected and analyzed, and the association to subsequent respiratory failure was assessed. RESULTS: Mean age of patients was 70.7 ± 16.9 years (53% males, 47% females.); 74% had at least one co-morbidity. Most patients were of Jewish Ashkenazi descent. During hospitalization 15 patients (mean age 78.18 ± 10.35 years); 80% male, 73% Sephardi descent developed respiratory failure rates of 60% occurring on average 10.6 days following intubation. Laboratory tests at admission displayed a significant increase in C-reactive protein (CRP) and creatine kinase (CK) and a decrease in absolute lymphocyte count (ALC) in patients who eventually developed respiratory failure (163.97 mg/L, 340.87 IU/L, 0.886 K/µl vs. 50.01 mg/L and 123.56 IU/L, 1.28 K/µl, respectively). Multivariate logistic analysis revealed an integrated parameter of CRP, CK, and ALC highly correlated with respiratory failure. Receiver operating characteristic curve revealed the area under the curve of CRP, CK, and ALC and the integrated parameter to be 0.910, 0.784, and 0.754, respectively. CRP was the strongest predictor to correlate with respiratory failure. CONCLUSIONS: CRP, CK, and ALC levels on admission could possibly be used to detect high-risk patients prone to develop respiratory failure.

Respuesta de creatina quinasa a un ejercicio anaerobio supramáximo en genotipos de ACTN3 / Response of Creatine Kinase to an Anaerobic Supramaximal Exercise in ACTN3 Genotypes

El objetivo del presente estudio fue investigar las diferencias en la actividad de la enzima Creatina Quinasa (CK) en pre y post ejercicio anaerobio supramáximo (EASM) en portadores de los genotipos del gen de la alfa-actinina-3 (ACTN3). Se reclutaron 39 hombres sanos físicamente activos (18-35 años) y se sometieron a un EASM de 30 s (Wingate). El gen ACTN3 se determinó a partir del ADN de glóbulos blancos en sangre periférica y se evaluó la actividad de la CK en muestras sanguíneas en condiciones basales, a las 24 y 48 h post EASM. Los portadores del genotipo XX vs RR presentaron 1,4 veces menor actividad de CK en condiciones basales (p < 0,05) y una mayor actividad de CK a las 24 h post ejercicio (p < 0,05). Una serie de EASM fue capaz de causar un incremento significativo de la actividad de CK a las 24 h en los portadores del genotipo XX

The aim of the present study was to investigate the differences in the activity of the enzyme Creatine Kinase (CK) in pre and post anaerobic supramaximal exercise (ASME) on carriers of the genotypes of the alpha-actinin-3 gene (ACTN3). 39 healthy physically active men (18-35 years) were enrolled and underwent an ASME of 30 s (Wingate). The ACTN3 gene was determined from the DNA of white blood cells in peripheral blood and the CK activity was evaluated in blood samples in basal conditions, at 24 and 48 h after of ASME. The carriers of genotype XX vs RR had 1.4 times lower CK activity in basal conditions (p < 0.05) and higher CK activity at 24 h after exercise (p < 0.05). A series of ASME was capable of causing a significant increase in CK activity at 24 h in the XX genotype carriers

Actualización en distrofia miotónica tipo 1 del adulto / Adult myotonic dystrophy type 1: an update

La distrofia muscular miotónica tipo 1 (DM1) o enfermedad de Steinert (CIE-9-C: 359.21; CIE-10-ES: G71.11, ORPHA: 273) es una miopatía autosómica dominante de baja prevalencia (<5/10.000) con penetrancia casi completa y daño multiorgánico (neurológico, cardiológico, respiratorio, endocrinológico y digestivo). Es una de las enfermedades humanas con mayor variabilidad clínica. Los síntomas más incapacitantes o molestos para estos enfermos (limitación de la movilidad, cansancio crónico, somnolencia diurna o trastornos digestivos) y sus familias (apatía y falta de iniciativa) no son necesariamente los de peor pronóstico. Las complicaciones respiratorias y los trastornos cardíacos reducen la esperanza de vida de los afectados. No existe tratamiento que modifique su evolución. La función del médico de atención primaria es decisiva en el seguimiento de la DM1, ya sea coordinando a las diferentes especialidades implicadas en el mismo o detectando las complicaciones tratables, en las cuales se centra el presente trabajo

Myotonic dystrophy type 1 (DM1) or Steinert's disease (CIE-9-C: 359.21; CIE-10-ES: G71.11, ORPHA: 273) is a rare autosomal dominant inherited myopathy with almost complete penetrance and multisystemic consequences (neurological, cardiological, respiratory, endocrinological, and gastrointestinal). It is one of the clinical most variable diseases. The most bothersome symptoms for the patients (mobility problems, fatigue, hypersomnia, or gastrointestinal symptoms) and their families (apathy, lack of initiative) are not necessarily the most dangerous. Respiratory problems and cardiac arrhythmias shorten life expectancy. There is no specific treatment. The role of the Primary Care physician is crucial in the follow-up of DM1, either by coordinating the different professionals or detecting treatable complications. This work addresses the latter

Extremely High Creatine Kinase Activity in Rhabdomyolysis without Acute Kidney Injury.

BACKGROUND Elevation of creatine kinase (CK) activity has been shown to be predictive of acute kidney injury (AKI) in rhabdomyolysis. Patients with extremely high CK activity with preserved renal function are uncommon. This report describes a case of non-traumatic rhabdomyolysis, with a markedly elevated CK activity, without associated AKI. CASE REPORT A 22-year-old male presented with severe generalized myalgias and darkened urine for 1 week prior to his admission. The patient presented to the Emergency Department with initial CK activity of >40 000 U/L and a serum creatinine level of 0.77 mg/dL. Urinalysis was positive for myoglobinuria. Serum cystatin C confirmed an estimated glomerular filtration rate of 144 mL/min/1.73 m². Several causes of rhabdomyolysis, including viral infections, Lyme disease, viral hepatitis, hypothyroidism, and cocaine abuse were investigated; however, all were negative. He was given a bolus of 2 liters of normal saline and continued on intravenous normal saline at 250 mL/hour throughout his hospital stay. Urine output remained adequate. We were able to quantify his serum CK activity by dilution method, which revealed a serum CK activity of >150 000 U/L. His CK levels consistently trended down with treatment. CONCLUSIONS An extremely high CK activity in rhabdomyolysis may lead to AKI. However, preserved kidney function is possible. Young age, no concurrent cocaine use, and adequate oral fluid hydration may prevent AKI in rhabdomyolysis. Physicians need to remain vigilant for cases of rhabdomyolysis that have not yet caused renal compromise.

Blood collection from dairy calves at exsanguination post-slaughter yields similar biochemical and packed cell volume measurements compared with in vivo collection during lairage.

Blood collection at exsanguination is a method of collecting samples at abattoirs which itself has no effect on animal welfare, compared with collection prior to stunning. However, there is the potential for artefact to affect measurements. It was hypothesised that, for most blood analytes measured, the differences between lairage and exsanguination measurements would be minimal, except for creatine kinase, which was expected be higher in exsanguination samples. Fifty-nine male dairy calves approximately 5-10 days old were sampled prior to slaughter, and again during exsanguination after stunning. Each sample was analysed for packed cell volume, serum urea, beta-hydroxybutyrate, gamma-glutamyl transferase, total protein, glucose and creatine kinase concentrations. Exsanguination and lairage blood results were compared using a paired t-test. There were no significant differences between the measurements taken at exsanguination compared with lairage for packed cell volume, urea and beta-hydroxybutyrate. Glucose concentrations were higher in exsanguination samples, and total protein concentrations were lower, but for both of these analytes the differences were clinically small. Gamma-glutamyl transferase activity was lower in exsanguination samples compared with lairage samples. Creatine kinase activity was higher in exsanguination samples. It was concluded that collecting blood at exsanguination is a valid method for collecting samples for measurement of packed cell volume, urea, and beta-hydroxybutyrate in calves. Glucose and total protein can also yield useful measurements in these samples, though care needs to be taken with interpretation given the minor differences between exsanguination and lairage measurements. Exsanguination samples may be unsuitable for creatine kinase and gamma-glutamyl transferase measurement.

Comparative efficacy of active recovery and cold water immersion as post-match recovery interventions in elite youth soccer.

The current study compared cold-water immersion (CWI) and active recovery (AR) to static stretching (SS) on muscle recovery post-competitive soccer matches in elite youth players (n = 15). In a controlled crossover design, participants played a total of nine competitive soccer games, comprising three 80 minute games for each intervention (SS, CWI and AR). Muscle oedema, creatine kinase (CK), countermovement jump performance (CMJA) and perceived muscle soreness (PMS) were assessed pre-, immediately post-, and 48 hours post-match and compared across time-intervals and between interventions. Following SS, all markers of muscle damage remained significantly elevated (P < 0.05) compared to baseline at 48 hours post-match. Following AR and CWI, CMJA returned to baseline at 48 hours post-match, whilst CK returned to baseline following CWI at 48 hours post-match only. Analysis between recovery interventions revealed a significant improvement in PMS (P < 0.05) at 48 hours post-match when comparing AR and CWI to SS, with no significant differences between AR and CWI observed (P > 0.05). Analysis of %change for CK and CMJA revealed significant improvements for AR and CWI compared to SS. The present study indicated both AR and CWI are beneficial recovery interventions for elite young soccer players following competitive soccer matches, of which were superior to SS.

Periprocedural elevated myocardial biomarkers and clinical outcomes following elective percutaneous coronary intervention: a comprehensive dose-response meta-analysis of 44,972 patients from 24 prospective studies.

AIMS: The optimal cut-off value of isolated cardiac biomarker elevation for defining prognostically important percutaneous coronary intervention (PCI)-related myocardial injury is not known. We performed a meta-analysis to evaluate the dose-response relationship between isolated cardiac biomarker elevations and the risk of all-cause mortality following elective PCI. METHODS AND RESULTS: Twenty-four prospective studies (44,972 patients) were included. Patients with an isolated elevation of cardiac biomarkers had an increased risk of all-cause mortality when compared to those with no elevations (cardiac troponin I: odds ratio [OR] 1.42, 95% confidence interval [CI]: 1.19-1.69; creatine kinase-MB isoenzyme [CK-MB]: OR 1.43, 95% CI: 1.19-1.70). For the dose-response analysis, elevations of cardiac troponin I >3x or CK-MB >1x the 99th percentile upper reference limit (URL) were associated with increased mortality (cardiac troponin I: OR 1.51, 95% CI: 1.05-2.17; CK-MB: OR 1.25, 95% CI: 1.05-1.48). The pooled OR of mortality for each 3xURL increment of cardiac troponin I or CK-MB was 1.33 (95% CI: 1.15-1.53) and 1.38 (95% CI: 1.30-1.47). CONCLUSIONS: We found that a positive dose-response relationship between isolated cardiac troponin I and CK-MB with all-cause mortality and elevated cardiac troponin I >3x or CK-MB >1x the 99th percentile URL was associated with an increased risk of mortality.

Biochemical findings in sudden unexpected death in epilepsy: Hospital based case-control study.

PURPOSE: A review study on the biochemistry of epilepsy showed that in epileptic patients, serum glucose and cholesterol concentrations are low, sodium is unaffected, potassium increases, glucose is high and mild hypocalcemia. We have conducted a biochemical study on sudden unexpected death in epilepsy (SUDEP) cases in an attempt to establish the characteristic biochemical values to diagnose these deaths. METHODS: This was a hospital based case-control study done at All India Institute of Medical Sciences, New Delhi for one year. Twenty SUDEP cases and 20 age- and sex-matched controls were included in the study. Femoral blood, cerebrospinal fluid, vitreous humor, and pericardial fluid were biochemically analyzed for sodium, potassium, calcium, glucose, N-acetyl- cysteine activated creatine kinase (CK-NAC) and isoenzyme CK-MB. RESULT: Serum sodium, CK-MB and CK-NAC level was found significantly increased and potassium level was found decreased in SUDEP cases in comparison to non-epileptic deaths. Likewise, in CSF, sodium and CK-NAC was found increased and potassium level was found decreased in SUDEP cases. In vitreous humor, sodium and CK-MB level was found increased and potassium level was found decreased in SUDEP cases in comparison to non-epileptic deaths. In pericardial fluid, sodium, CK-NAC and CK-MB level was found increased and potassium level was found decreased in SUDEP cases in comparison to non-epileptic deaths. CONCLUSION: It concludes that high sodium level and low potassium level could be associated with SUDEP. However, this is a small size study, a larger study is needed to verify the findings. Furthermore, it is difficult to conclude whether these findings are exclusive to SUDEP.

Elevated Liver Enzymes as a Manifestation of Haff Disease.

BACKGROUND: Haff disease is a rare syndrome of rhabdomyolysis thought to be caused by a heat-stable toxin associated with the consumption of seafood from fresh or brackish water. CASE REPORT: We present the case of a patient with Haff disease who presented to the emergency department with nausea/vomiting, diarrhea, and myalgias after a seafood buffet. Initially, he was treated with i.v. fluids and antiemetics for presumed gastroenteritis, but his symptoms did not improve. He was found to have elevated aspartate aminotransferase and alanine aminotransferase, normal point-of-care ultrasound, urinalysis with large blood and no red blood cells, and an elevated creatine phosphokinase (CPK). He was admitted to the hospital to receive ongoing fluid resuscitation for rhabdomyolysis presumed to be from fish. Liver enzymes and CPK downtrended, and patient was discharged on hospital day 3. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: Undiagnosed Haff disease has important clinical implications, including multi-organ failure and death. Always maintain a high level of suspicion for Haff disease in patients with symptoms suggestive of gastroenteritis, but complicated by minor liver function test elevations and dipstick positivity for heme, without significant numbers of red blood cells per high-power field, in the setting of recent seafood ingestion.