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Based on theoretical considerations, experimental data with cells in vitro, animal studies in vivo, as well as a single case pilot study with one colitis patient, a consolidated hypothesis can be put forward, stating that “oral supplementation with creatine monohydrate (Cr), a pleiotropic cellular energy precursor, is likely to be effective in inducing a favorable response and/or remission in patients with inflammatory bowel diseases (IBD), like ulcerative colitis and/or Crohn’s disease”. A current pilot clinical trial that incorporates the use of oral Cr at a dose of 2 × 7 g per day, over an initial period of 2 months in conjunction with ongoing therapies (NCT02463305) will be informative for the proposed larger, more long-term Cr supplementation study of 2 × 3–5 g of Cr per day for a time of 3–6 months. This strategy should be insightful to the potential for Cr in reducing or alleviating the symptoms of IBD. Supplementation with chemically pure Cr, a natural nutritional supplement, is well tolerated not only by healthy subjects, but also by patients with diverse neuromuscular diseases. If the outcome of such a clinical pilot study with Cr as monotherapy or in conjunction with metformin were positive, oral Cr supplementation could then be used in the future as potentially useful adjuvant therapeutic intervention for patients with IBD, preferably together with standard medication used for treating patients with chronic ulcerative colitis and/or Crohn’s disease.

BackgroundDuchenne muscular dystrophy (DMD/Duchenne) is a progressive X-linked muscular disease with an overall incidence of 1:5,000 live male births. Recent availability in treatment for DMD raised the need of early diagnosis, and DMD became as a selective item of newborn screening (NBS) since Feb. 2021 in our center.Materials and methodsDried blood spots (DBS) muscle-type creatine kinase (CK) isoform was measured with a commercialized kit with age-adjusted cutoffs. Subjects with an elevation of CK in the first screen were requested for a re-screen 2 weeks later. A DBS whole-exome sequencing (WES) panel for dystrophin and other neuromuscular-related genes was applied to confirm the diagnosis for subjects with persistent hyperCKemia.ResultsDuring a 1-year period, 50,572 newborns (male 26,130) received DMD screening at a mean age of 2 days (SD 1 day). Among them, 632 (1.2%) had an elevated CK value. A re-screen at a mean age of 14 days (SD 8 days) revealed 14 subjects with persistent hyperCKemia, and DMD was confirmed in 3 of them. The incidence of DMD in Taiwan was 1:8,710 (95% CI 1 in 2,963 to 1 in 25,610) live birth males. Results of DMD DBS also assisted in Pompe newborn screening.ConclusionsNBS for DMD enables earlier management of the disease. The high re-screening rate could potentially be waived by moving the DBS WES assay to a second-tier test. The long-term benefit and the impact of newborn screening on the prognosis of DMD, however, remain further elucidated.

Background: High-sensitivity cardiac troponin T (hs-cTnT) and creatine kinase (CK)-MB are the most commonly used biomarkers for the diagnosis and prognosis of acute myocardial infarction (AMI). Chronic kidney disease (CKD) often leads to elevated hs-cTnT levels in non-AMI patients. However, studies comparing the prognostic value of both hs-cTnT and CK-MB in patients with AMI and CKD are lacking.Methods: We conducted a retrospective study on AMI patients diagnosed between January 2015 and October 2020. Patients were categorized based on renal function as normal or CKD. Peak hs-cTnT and CK-MB levels during hospitalization were collected, and their diagnostic value was evaluated using receiver operating characteristic (ROC) curves. The impact on in-hospital mortality was analyzed using multivariate logistic regression. The relationship between the hs-cTnT/CK-MB ratio and in-hospital death was examined using a restricted cubic spline (RCS) curve.Results: The study included 5022 AMI patients, of whom 797 (15.9%) had CKD. The AUCs of Hs-cTnT and CK-MB were higher in the CKD group [0.842 (95% CI: 0.789-0.894) and 0.821 (95% CI: 0.760-0.882)] than in the normal renal function group [0.695 (95% CI: 0.604-0.790) and 0.708 (95% CI: 0.624-0.793)]. After full adjustment for all risk factors, hs-cTnT (OR, 2.82; 95% CI, 1.03-9.86; p = 0.038) and CK-MB (OR, 4.91; 95% CI, 1.54-14.68; p = 0.007) above the cutoff values were independent predictors of in-hospital mortality in patients with CKD. However, in patients with normal renal function, only CK-MB above the cutoff (OR, 2.45; 95% CI, 1.02-8.24; p = 0.046) was a predictor of in-hospital mortality, whereas hs-cTnT was not. There was an inverted V-shaped relationship between the hs-cTnT/CK-MB ratio and in-hospital mortality, with an inflection point of 19.61. The ratio within the second quartile (9.63-19.6) was an independent predictor of in-hospital mortality in patients with CKD (OR 5.3, 95% CI 1.66-16.86, p = 0.005).Conclusions: Hs-cTnT independently predicted in-hospital mortality in AMI patients with CKD, whereas its predictive value was not observed in patients with normal renal function. CK-MB was an independent predictor of in-hospital mortality regardless of renal function. Moreover, the hs-cTnT/CK-MB ratio may aid in risk stratification of AMI patients with CKD.

BackgroundWell-leg compartment syndrome (WLCS) can occur due to compression and lower limb circulation disturbances caused by the surgical position during the procedure. Although rare, with an incidence of 1 in 3500 surgeries performed in the lithotomy position, it can lead to serious complications. Therefore, prevention and early diagnosis are critical. Symptoms of WLCS, such as leg pain, swelling, paresthesia, and serum creatine kinase (CK) levels are useful for diagnosis. This study aimed to investigate the risk factors for postoperative CK elevation in laparoscopic or robot-assisted colorectal cancer surgery performed in the lithotomy-Trendelenburg position.MethodsPostoperative CK levels were measured in 178 patients who underwent laparoscopic or robot-assisted colorectal cancer surgery between February 2022 and March 2023. We compared patient backgrounds, short-term outcomes, and thigh/calf circumferences between patients with CK levels ≥ 250 (n = 62) and those with CK levels < 250 (n = 116). We investigated risk factors for elevated CK levels using both univariate and multivariate analyses.ResultsFour patients with CK levels of 22405 U/L, 4685 U/L, 4050 U/L, and 3824 U/L reported symptoms, which improved with conservative treatment. The following independent prognostic factors were identified by multivariate analysis: male sex (odds ratio [OR], 4.403; 95% CI, 1.960 to 9.892), rectal surgery (OR, 2.779; 95% CI, 1.249 to 6.184), continuous head-down position duration ≥ 180 min (OR, 3.523; 95% CI, 1.552 to 7.997), and preoperative calf circumference ≥ 33 cm (OR, 2.482; 95% CI, 1.154 to 5.339).ConclusionsRisk factors for CK elevation after colorectal cancer surgery in the lithotomy position include male sex, rectal surgery, an extended continuous head-down position without position changes, and a larger preoperative calf circumference. This study highlights the potential importance of intraoperative position changes every 3 h for preventing elevated CK levels, although the preventive effect was not specifically examined.

Insulin resistance is a significant contributor to the development of type 2 diabetes (T2D) and is associated with obesity, physical inactivity, and low maximal oxygen uptake. While intense and prolonged exercise may have negative effects, physical activity can have a positive influence on cellular metabolism and the immune system. Moderate exercise has been shown to reduce oxidative stress and improve antioxidant status, whereas intense exercise can increase oxidative stress in the short term. The impact of exercise on pro‐inflammatory cytokine production is complex and varies depending on intensity and duration. Exercise can also counteract the harmful effects of ageing and inflamm‐ageing. This review aims to examine the molecular pathways altered by exercise in non‐obese individuals at higher risk of developing T2D, including glucose utilization, lipid metabolism, mitochondrial function, inflammation and oxidative stress, with the potential to improve insulin sensitivity. The focus is on understanding the potential benefits of exercise for improving insulin sensitivity and providing insights for future targeted interventions before onset of disease.

Introduction/ObjectivesArticular cartilage and periarticular muscle tissues are strongly affected during knee osteoarthritis (OA). Creatine kinase (CK) is an enzyme expressed in several tissues, but the isoform CK-MM is specific of skeletal muscle, and its serum concentration is used as a biomarker of muscle damage. Genetic variants of the CKM gene have been associated with various pathologies, but to date, there are no reports of association with OA. Due to the rs4884 polymorphism being well represented in the Mexican population, it is used as an ancestry informative marker; thus, the goal of this preliminary report was to evaluate the association of this polymorphism in primary knee OA Mexican patients.MethodEighty-seven patients with primary knee OA were compared with 107 healthy controls. Serum CK-MM was determined using the dot blot system, and genotyping was performed using the OpenArray system. Logistic regression models were used to assess the association between the rs4884 polymorphism and OA susceptibility adjusting by gender, age, and body mass index.ResultsThere were no significant differences in serum CK-MM values between patients and controls. The GG genotype and the G allele had a higher frequency in the control group compared with the OA group (24.3% vs. 12.6%, OR = 0.34, 95% CI = 0.14–0.84, P = 0.019; and 40.2% vs. 28.2%, OR = 0.51, 95% CI = 0.32–0.82, P = 0.005, respectively).ConclusionsOur results suggest a protection role of the rs4884 polymorphism against knee OA development; further studies are required to confirm it.Key Points• CK-MM enzyme catalyzes the conversion of creatine and ATP to create phosphocreatine and ADP; this reaction is reversible.• In tissues that consume ATP rapidly, such as skeletal muscle, the phosphocreatine serves as an important energy reservoir.• During knee OA, peripheral muscle tissues of the joint may be affected.• The rs4884 polymorphism of the CKM gene may participate as a protective factor in the development of OA.

ABSTRACT Isotretinoin can cause toxic myopathy even at low doses with normal CK levels; proximal muscle weakness may be the only sign. EMG is essential for diagnosis, emphasizing the need for clinical vigilance and personalized assessment in patients with unexplained muscle symptoms on isotretinoin.

Background Sports nutritional supplements containing branched-chain amino acids (BCAA) have been widely reported to improve psychological and biological aspects connected to central fatigue and performance in endurance exercise, although the topic is still open to debate. The aim of the present study was to determine whether the intake of a commercially available BCAA-based supplement, taken according to the manufacturer’s recommendations, could affect the rating of perceived exertion (RPE) and performance indexes at the beginning (1d) and end of a 9-week (9w) scheduled high intensity interval training program, with an experimental approach integrating the determination of psychometric, performance, metabolic and blood biochemical parameters. Methods This was a randomized double-blind placebo-controlled study. Thirty-two untrained, healthy young adults (20 males and 12 female) were enrolled. A high-intensity endurance cycling (HIEC) test was used to induce fatigue in the participants: HIEC consisted in ten 90 s sprints interspersed by ten 3 min recovery phases and followed by a final step time to exhaustion was used. In parallel with RPE, haematological values (creatine kinase, alanine, BCAA, tryptophan, ammonia and glucose levels), and performance indexes (maximal oxygen consumption - VO 2max , power associated with lactate thresholds - W LT1 , W LT2 and time to exhaustion - TTE) were assessed. All subject took the supplement (13.2 g of carbohydrates; 3.2 g of BCAA and 1.6 g of L-alanine per dose) or placebo before each test and training session. Dietary habits and training load were monitored during the entire training period. Results The administration of the supplement (SU) at 1d reduced RPE by 9% during the recovery phase, as compared to the placebo (PL); at 9w the RPE scores were reduced by 13 and 21% during the sprint and recovery phase, respectively; at 9w, prolonged supplement intake also improved TTE and TRIMP. SU intake invariably promoted a rapid increase (within 1 h) of BCAA serum blood levels and prevented the post-HIEC tryptophan: BCAA ratio increase found in the PL group, at both 1d and 9w. There was no difference in dietary habits between groups and those habits did not change over time; no difference in glycemia was found between SU and PL. VO 2max , W LT1 and W LT2 values improved over time, but were unaffected by supplement intake. Conclusions On the whole, these results suggest that i) the intake of the BCAA-based commercially available supplement used in this study reduces RPE as a likely consequence of an improvement in the serum tryptophan: BCAA ratio; ii) over time, reduced RPE allows subjects to sustain higher workloads, leading to increased TRIMP and TTE.

The ubiquitin–proteasome system (UPS) is the main cellular proteolytic system responsible for the degradation of normal and abnormal (e.g. oxidised) proteins. Under catabolic conditions characterised by chronic inflammation, the UPS is activated resulting in proteolysis, muscle wasting and impaired muscle function. Milk proteins provide sulphur-containing amino acid and have been proposed to affect muscle inflammation. However, the response of the UPS to aseptic inflammation and protein supplementation is largely unknown. The aim of this study was to investigate how milk protein supplementation affects UPS activity and skeletal muscle function under conditions of aseptic injury induced by intense, eccentric exercise. In a double-blind, cross-over, repeated measures design, eleven men received either placebo (PLA) or milk protein concentrate (PRO, 4×20 g on exercise day and 20 g/d for the following 8 days), following an acute bout of eccentric exercise (twenty sets of fifteen eccentric contractions at 30°/s) on an isokinetic dynamometer. In each trial, muscle biopsies were obtained from the vastus lateralis muscle at baseline, as well as at 2 and 8 d post exercise, whereas blood samples were collected before exercise and at 6 h, 1 d, 2 d and 8 d post exercise. Muscle strength and soreness were assessed before exercise, 6 h post exercise and then daily for 8 consecutive days. PRO preserved chymotrypsin-like activity and attenuated the decrease of strength, facilitating its recovery. PRO also prevented the increase of NF-κB phosphorylation and HSP70 expression throughout recovery. We conclude that milk PRO supplementation following exercise-induced muscle trauma preserves proteasome activity and attenuates strength decline during the pro-inflammatory phase.

Concentrations of serum creatine kinase (CK) and serum lactate are frequently measured to help differentiate between generalized tonic–clonic seizures (GTCS) and syncope. The aim of this prospective cohort study was to systematically compare these two markers. The primary outcome is the measurement of serum lactate and CK in blood samples drawn within 2 h of the event in patients admitted with either a GTCS (n = 49) or a syncope (n = 36). Furthermore, the specificity and sensitivity of serum lactate and CK are determined as diagnostic markers in distinguishing between GTCS and syncope. GTCS patients have significantly higher serum lactate levels compared to syncope patients (p < 0.001). In contrast, CK does not differ between groups at admission. Regarding the first hour after the seizure, we identify a cut-off for serum lactate of 2.45 mmol/l for diagnosing GTCS as the cause of an impairment of consciousness with a sensitivity of 0.94 and a specificity of 0.93 (AUC: 0.97; 95% CI 0.94–1.0). In the second hour after the event, the ROC analysis yields similar results (AUC: 0.94; 95% CI 0.85–1.0). Serum lactate is a sensitive and specific diagnostic marker to discriminate GTCS from syncope and is superior to CK early after admission to the emergency department.