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Item does not contain fulltext Treatment with tyrosine kinase inhibitors (TKIs), especially nilotinib, often results in hyperglycemia, which may further increase cardiovascular disease risk in patients with chronic myeloid leukemia (CML). The mechanism underlying the TKI-induced glucose dysregulation is not clear. TKIs are suggested to affect insulin secretion but also insulin sensitivity of peripheral tissue has been proposed to play a role in the pathogenesis of TKI-induced hyperglycemia. Here, we aimed to assess whether skeletal muscle glucose uptake and insulin responses are altered in nondiabetic patients with CML receiving TKI treatment. After a glycogen-depleted exercise bout, an intravenous glucose bolus (0.3 g/kg body weight) was administered to monitor 2-h glucose tolerance and insulin response in 14 patients with CML receiving nilotinib, 14 patients with CML receiving imatinib, and 14 non-CML age- and gender-matched controls. A dynamic [(18)F]-FDG PET scan during a hyperinsulinemic-euglycemic clamp was performed in a subgroup of 12 male patients with CML to assess m. quadriceps glucose uptake. We showed that patients with CML treated with nilotinib have an increased insulin response to intravenous glucose administration after muscle glycogen-depleted exercise. Despite the increased insulin response to glucose administration in patients with CML receiving nilotinib, glucose disappearance rates were significantly slower in nilotinib-treated patients when compared with controls in the first 15 min after glucose administration. Although [(18)F]-FDG uptake in m. quadriceps was not different, patients receiving nilotinib showed a trend toward decreased glucose infusion rates during euglycemic clamping when compared with patients receiving imatinib. Together, these findings indicate disturbed skeletal muscle glucose handling in patients with CML receiving nilotinib therapy.NEW & NOTEWORTHY In this study, we have shown that non-diabetic patients with CML receiving nilotinib therapy show early signs of disturbed skeletal muscle glucose handling, which was not observed in imatinib-treated patients. These observations in nilotinib users may reflect decreased muscle insulin sensitivity, which could serve as a potential target to counteract glycemic dysregulation, and is of clinical importance since these patients have an increased cardiovascular disease risk.

Item does not contain fulltext BACKGROUND: Statin use may exacerbate exercise-induced skeletal muscle injury caused by reduced coenzyme Q10 (CoQ10) levels, which are postulated to produce mitochondrial dysfunction. OBJECTIVES: We determined the effect of prolonged moderate-intensity exercise on markers of muscle injury in statin users with and without statin-associated muscle symptoms. We also examined the association between leukocyte CoQ10 levels and muscle markers, muscle performance, and reported muscle symptoms. METHODS: Symptomatic (n = 35; age 62 ± 7 years) and asymptomatic statin users (n = 34; age 66 ± 7 years) and control subjects (n = 31; age 66 ± 5 years) walked 30, 40, or 50 km/d for 4 consecutive days. Muscle injury markers (lactate dehydrogenase, creatine kinase, myoglobin, cardiac troponin I, and N-terminal pro-brain natriuretic peptide), muscle performance, and reported muscle symptoms were assessed at baseline and after exercise. Leukocyte CoQ10 was measured at baseline. RESULTS: All muscle injury markers were comparable at baseline (P > 0.05) and increased following exercise (P 0.05). Muscle pain scores were higher at baseline in symptomatic statin users (P < 0.001) and increased similarly in all groups following exercise (P < 0.001). Muscle relaxation time increased more in symptomatic statin users than in control subjects following exercise (P = 0.035). CoQ10 levels did not differ among symptomatic (2.3 nmol/U; IQR: 1.8-2.9 nmol/U), asymptomatic statin users (2.1 nmol/U; IQR: 1.8-2.5 nmol/U), and control subjects (2.1 nmol/U; IQR: 1.8-2.3 nmol/U; P = 0.20), and did not relate to muscle injury markers, fatigue resistance, or reported muscle symptoms. CONCLUSIONS: Statin use and the presence of statin-associated muscle symptoms does not exacerbate exercise-induced muscle injury after moderate exercise. Muscle injury markers were not related to leukocyte CoQ10 levels. (Exercise-induced Muscle Damage in Statin Users; NCT05011643).

BACKGROUND The combination of statin therapy and physical activity reduces cardiovascular disease risk in patients with hyperlipidemia more than either treatment alone. However, mitochondrial dysfunction associated with statin treatment could attenuate training adaptations. OBJECTIVES This study determined whether moderate intensity exercise training improved muscle and exercise performance, muscle mitochondrial function, and fiber capillarization in symptomatic and asymptomatic statin users. METHODS Symptomatic (n = 16; age 64 +/- 4 years) and asymptomatic statin users (n = 16; age 64 +/- 4 years) and nonstatin using control subjects (n = 20; age 63 +/- 5 years) completed a 12-week endurance and resistance exercise training program. Maximal exercise performance (peak oxygen consumption), muscle performance and muscle symptoms were determined before and after training. Muscle biopsies were collected to assess citrate synthase activity, adenosine triphosphate (ATP) production capacity, muscle fiber type distribution, fiber size, and capillarization. RESULTS Type I muscle fibers were less prevalent in symptomatic statin users than control subjects at baseline (P = 0.06). Exercise training improved muscle strength (P < 0.001), resistance to fatigue (P = 0.01), and muscle fiber capillarization (P < 0.01), with no differences between groups. Exercise training improved citrate synthase activity in the total group (P < 0.01), with asymptomatic statin users showing less improvement than control subjects (P = 0.02). Peak oxygen consumption, ATP production capacity, fiber size, and muscle symptoms remained unchanged in all groups following training. Quality-of-life scores improved only in symptomatic statin users following exercise training (P < 0.01). CONCLUSIONS A moderate intensity endurance and resistance exercise training program improves muscle performance, capillarization, and mitochondrial content in both asymptomatic and symptomatic statin users without exacerbating muscle complaints. Exercise training may even increase quality of life in symptomatic statin users. (The Effects of Cholesterol-Lowering Medication on Exercise Performance [STATEX]; NL5972/NTR6346) (J Am Coll Cardiol 2021;78:2023-2037) (c) 2021 by the American College of Cardiology Foundation.

Item does not contain fulltext Drugs are prescribed to manage or prevent symptoms and diseases, but may sometimes cause unexpected toxicity to muscles. The symptomatology and clinical manifestations of the myotoxic reaction can vary significantly between drugs and between patients on the same drug. This poses a challenge on how to recognize and prevent the occurrence of drug-induced muscle toxicity. The key to appropriate management of myotoxicity is prompt recognition that symptoms of patients may be drug related and to be aware that inter-individual differences in susceptibility to drug-induced toxicity exist. The most prevalent and well-documented drug class with unintended myotoxicity are the statins, but even today new classes of drugs with unintended myotoxicity are being discovered. This review will start off by explaining the principles of drug-induced myotoxicity and the different terminologies used to distinguish between grades of toxicity. The main part of the review will focus on the most important pathogenic mechanisms by which drugs can cause muscle toxicity, which will be exemplified by drugs with high risk of muscle toxicity. This will be done by providing information on key clinical and laboratory aspects, muscle electromyography patterns and biopsy results, and pathological mechanism and management for a specific drug from each pathogenic classification. In addition, rather new classes of drugs with unintended myotoxicity will be highlighted. Furthermore, we will explain why it is so difficult to diagnose drug-induced myotoxicity, and which tests can be used as a diagnostic aid. Lastly, a brief description will be given of how to manage and treat drug-induced myotoxicity.

Contains fulltext : 208380.pdf (Publisher’s version ) (Open Access)

Key Points Patients with transposition of the great arteries (TGA) and systemic right ventricles have premature congestive heart failure; there is also a growing concern that athletes who perform extraordinary endurance exercise may injure the right ventricle. Therefore we felt it essential to determine whether exercise training might injure a systemic right ventricle which is loaded with every heartbeat. Previous studies have shown that short term exercise training is feasible in TGA patients, but its effect on ventricular function is unclear. We demonstrate that systemic right ventricular function is preserved (and may be improved) in TGA patients with exercise training programmes that are typical of recreational and sports participation, with no evidence of injury on biomarker assessment. Stroke volume reserve during exercise correlates with exercise training response in our TGA patients, identifying this as a marker of a systemic right ventricle (SRV) that may most tolerate (and possibly even be improved by) exercise training. Abstract We aimed to assess the haemodynamic effects of exercise training in transposition of the great arteries (TGA) patients with systemic right ventricles (SRVs). TGA patients have limited exercise tolerance and early mortality due to systemic (right) ventricular failure. Whether exercise training enhances or injures the SRV is unclear. Fourteen asymptomatic patients (34 ± 10 years) with TGA and SRV were enrolled in a 12 week exercise training programme (moderate and high-intensity workouts). Controls were matched on age, gender, BMI and physical activity. Exercise testing pre- and post- training included: (a) submaximal and peak; (b) prolonged (60 min) submaximal endurance and (c) high-intensity intervals. Oxygen uptake (VO2; Douglas bag technique), cardiac output (Qc, foreign-gas rebreathing), ventricular function (echocardiography and cardiac MRI) and serum biomarkers were assessed. TGA patients had lower peak VO2, Qc, and stroke volume (SV), a blunted Qc/VO2 slope, and diminished SV response to exercise (SV increase from rest: TGA = 15.2%, controls = 68.9%, P

Contains fulltext : 187814.pdf (Publisher’s version ) (Closed access) OBJECTIVE: Blisters are common foot injuries during and after prolonged walking. However, the best treatment remains unclear. The aim of the study was to compare the effect of 2 different friction blister treatment regimens, wide area fixation dressing versus adhesive tape. DESIGN: A prospective observational cohort study. SETTING: The 2015 Nijmegen Four Days Marches in the Netherlands. PARTICIPANTS: A total of 2907 participants (45 +/- 16 years, 52% men) were included and received 4131 blister treatments. INTERVENTIONS: Blisters were treated with either a wide area fixation dressing or adhesive tape. MAIN OUTCOME MEASURES: Time of treatment application was our primary outcome. In addition, effectiveness and satisfaction were evaluated in a subgroup (n = 254). During a 1-month follow-up period, blister healing, infection and the need for additional medical treatment were assessed in the subgroup. RESULTS: Time of treatment application was lower (41.5 minutes; SD = 21.6 minutes) in the wide area fixation dressing group compared with the adhesive tape group (43.4 minutes; SD = 25.5 minutes; P = 0.02). Furthermore, the wide area fixation dressing group demonstrated a significantly higher drop-out rate (11.7% vs 4.0%, P = 0.048), delayed blister healing (51.9% vs 35.3%, P = 0.02), and a trend toward lower satisfaction (P = 0.054) when compared with the adhesive tape group. CONCLUSIONS: Wide area fixation dressing decreased time of treatment application by 2 minutes (4.5%) when compared with adhesive tape. However, because of lower effectiveness and a trend toward lower satisfaction, we do not recommend the use of wide area fixation dressing over adhesive tape in routine first-aid treatment for friction blisters. 01 januari 2018