Atorvastatin Metabolite Pattern in Skeletal Muscle and Blood from Patients with Coronary Heart Disease and Statin-Associated Muscle Symptoms.

Self-perceived statin-associated muscle symptoms (SAMS) are prevalent, but only a minority is drug-dependent. Diagnostic biomarkers are not yet identified. The local statin exposure in skeletal muscle tissue may correlate to the adverse effects. We aimed to determine whether atorvastatin metabolites in blood reflect the corresponding metabolite levels in skeletal muscle, and whether genetic variants of statin transporters modulate this relationship. We also addressed atorvastatin metabolites as potential objective biomarkers of SAMS. Muscle symptoms were examined in patients with coronary disease and self-perceived SAMS during 7 weeks of double-blinded treatment with atorvastatin 40 mg/day and placebo in randomized order. A subset of 12 patients individually identified with more muscle symptoms on atorvastatin than placebo (confirmed SAMS) and 15 patients with no difference in muscle symptom intensity (non-SAMS) attended the present follow-up study. All received 7 weeks of treatment with atorvastatin 40 mg/day followed by 8 weeks without statins. Biopsies from the quadriceps muscle and blood plasma were collected after each treatment period. Strong correlations (rho > 0.7) between muscle and blood plasma concentrations were found for most atorvastatin metabolites. The impact of the SLCO1B1 c.521T>C (rs4149056) gene variant on atorvastatin's systemic pharmacokinetics was translated into muscle tissue. The SLCO2B1 c.395G>A (rs12422149) variant did not modulate the accumulation of atorvastatin metabolites in muscle tissue. Atorvastatin pharmacokinetics in patients with confirmed SAMS were not different from patients with non-SAMS. In conclusion, atorvastatin metabolite levels in skeletal muscle and plasma are strongly correlated, implying that plasma measurements are suitable proxies of atorvastatin exposure in muscle tissue. The relationship between atorvastatin metabolites in plasma and SAMS deserves further investigation.

Strangulated intercostal liver herniation subsequent to blunt trauma. First report with review of the world literature.

Traumatic transdiaphragmatic intercostal hernia, defined as an acquired herniation of abdominal contents through disrupted intercostal muscles, is a rarely reported entity. We present the first reported case of a traumatic transdiaphragmatic intercostal hernia complicated by strangulation of the herniated visceral contents.Following blunt trauma, a 61-year old man developed a traumatic transdiaphragmatic intercostal hernia complicated by strangulation of liver segment VI. Due to pre-existing respiratory problems and the presence of multiple other injuries (grade III kidney laceration and lung contusion) the hernia was managed non-operatively for the first 2 weeks.The strangulated liver segment eventually underwent ischemic necrosis. Six weeks later the resulting subcutaneous abscess required surgical drainage. Nine months post injury the large symptomatic intercostal hernia was treated with laparoscopic mesh repair. Twelve months after the initial trauma, a small recurrence of the hernia required laparoscopic re-fixation of the mesh.This paper outlines important steps in managing a rare post traumatic entity. Early liver reduction and hernia repair would have been ideal. The adopted conservative approach caused liver necrosis and required staged procedures to achieve a good outcome.