Fatal Statin-Induced Rhabdomyolysis by Possible Interaction with Palbociclib.
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ABSTRACT:
SUBMITTER: Nelson KL
PROVIDER: S-EPMC5511828 | biostudies-other | 2017
REPOSITORIES: biostudies-other
Similar Datasets
Project description:We performed a genome-wide association study in pooled DNA samples from patients with severe statin myopathy and persistent symptoms post-therapy versus pooled DNAs from an age-adjusted statin-tolerant group.
2010-07-09 | GSE17574 | GEO
Project description:We performed a genome-wide association study in pooled DNA samples from patients with severe statin myopathy and persistent symptoms post-therapy versus pooled DNAs from an age-adjusted statin-tolerant group. Affymetrix 100K SNP arrays were used according to the manufacturers instructions with two pools of 19 and 20 statin myopathy patients and two pools of 20 statin-tolerant controls.
2010-07-09 | E-GEOD-17574 | biostudies-arrayexpress
Project description:Rhabdomyolysis is a serious medical condition in which the skeletal muscle tissue gets damaged and breaks down at rapid rates, potentially leading to death if not managed early on. Rhabdomyolysis in adults has several etiologies such as crush injuries, prolonged immobilization, strenuous exercise, hormonal or metabolic causes, infections, and drug-drug interactions. We present a case report of the interaction of two drugs that are used commonly in the general population. We here discuss a case of a 60-year-old female who presented to the hospital with complaints of generalized weakness, muscle aches, and atypical chest pain for a week after her primary care physician started her on sitagliptin while she was already on atorvastatin. After review of literature, this is the second known case of such an interaction causing acute breakdown of skeletal musculature.
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Project description:Acute kidney injury (AKI) represents a syndrome seldom characterized by a single, distinct pathophysiological cause. Rhabdomyolysis-induced acute kidney injury (RIAKI) constitutes roughly 15% of AKI cases, yet its underlying pathophysiology remains poorly understood. Using a murine model of RIAKI induced by muscular glycerol injection, we aimed to analyse transcriptomic alterations by RNAseq.
2024-09-18 | GSE264651 | GEO
Project description:Poor adherence to medication regimens is common, potentially contributing to the occurrence of related disease.The authors sought to assess the risk of fatal stroke associated with nonadherence to statin and/or antihypertensive therapy.We conducted a population-based study using electronic medical and prescription records from Finnish national registers in 1995 to 2007. Of the 58,266 hypercholesterolemia patients age 30+ years without pre-existing stroke or cardiovascular disease, 532 patients died of stroke (cases), and 57,734 remained free of incident stroke (controls) during the mean follow-up of 5.5 years. We captured year-by-year adherence to statin and antihypertensive therapy in both study groups and estimated the excess risk of stroke death associated with nonadherence.In all hypercholesterolemia patients, the adjusted odds ratio for stroke death for nonadherent compared with adherent statin users was 1.35 (95% confidence interval [CI] 1.04 to 1.74) 4 years before and 2.04 (95% CI: 1.72 to 2.43) at the year of stroke death or the end of the follow-up. In hypercholesterolemia patients with hypertension, relative to those who adhered to statins and antihypertensive therapy, the odds ratio at the year of stroke death was 7.43 (95% CI: 5.22 to 10.59) for those nonadherent both to statin and antihypertensive therapy, 1.82 (95% CI: 1.43 to 2.33) for those non-adherent to statin but adherent to antihypertensive therapy, and 1.30 (95% CI: 0.53 to 3.20) for those adherent to statin, but nonadherent to antihypertensive, therapy.Individuals with hypercholesterolemia and hypertension who fail to take their prescribed statin and antihypertensive medication experience a substantially increased risk of fatal stroke. The risk is lower if the patient is adherent to either one of these therapies.
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Project description:Background and purposeRhabdomyolysis is a medical emergency characterized by acute skeletal muscle breakdown with a sudden rise and subsequent fall of serum creatine kinase (CK) levels. Rhabdomyolysis events are provoked by exposure to external triggers, possibly in combination with an increased genetic susceptibility. We aimed to describe comprehensively the external triggers and potentially pathogenic genetic variants possibly implicated in increased rhabdomyolysis susceptibility.MethodsWe performed a retrospective single-center study, including a total of 1302 patients with an acute CK level exceeding 2000 IU/l.ResultsAnoxia was the most frequently reported trigger (40%). A subset of 193 patients were clinically suspected of an underlying genetic disorder (recurrent episodes, a positive family history, very high or persistently increased CK levels). In 72 of these patients, an unequivocal genetic defect was identified. A total of 22 genes with pathogenic variants were identified, including 52 different variants. Of those, 11 genes have been previously associated with rhabdomyolysis (ACADVL, ANO5, CPT2, DMD, DYSF, FKRP, HADHA, PGM1, LPIN1, PYGM, RYR1). Eleven genes are probably implicated in increased susceptibility (including AGL, CAPN3, CNBP, DMPK, MAGT1, ACADM, SCN4A, SGCA, SGCG, SMPD1, TANGO2).ConclusionThese findings suggest that the spectrum of genetic susceptibility for rhabdomyolysis has not yet been completely clarified. With the increasing availability of next-generation sequencing in a diagnostic setting, we expect that in more cases a genetic defect will be identified.
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Project description:Rhabdomyolysis is one of the main causes of community-acquired acute kidney injury (AKI). Although inflammation is involved in the pathogenesis of rhabdomyolysis-induced AKI (RIAKI), little is known about the mechanism that triggers inflammation during RIAKI. Recent evidence has indicated that sterile inflammation triggered by tissue injury can be mediated through multiprotein complexes called the inflammasomes. Therefore, we investigated the role of NLRP3 inflammasomes in the pathogenesis of RIAKI using a glycerol-induced murine rhabdomyolysis model. Inflammasome-related molecules were upregulated in the kidney of RIAKI. Renal tubular injury and dysfunction preceded leukocyte infiltration into the kidney during the early phase of RIAKI, and they were markedly attenuated in mice deficient in NLRP3, ASC, caspase-1, and interleukin (IL)-1? compared with those in wild-type mice. No difference in leukocyte infiltration was observed between wild-type and NLRP3-deficient mice. Furthermore, NLRP3 deficiency strikingly suppressed the expression of renal injury markers and inflammatory cytokines and apoptosis of renal tubular cells. These results demonstrated that NLRP3 inflammasomes contribute to inflammation, apoptosis, and tissue injury during the early phase of RIAKI and provide new insights into the mechanism underlying the pathogenesis of RIAKI.
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Project description:Statins, a class of lipid-lowering medications, have been a keystone treatment in cardiovascular health. However, adverse effects associated with statin use impact patient adherence, leading to statin discontinuation. Statin-induced myotoxicity (SIM) is one of the most common adverse effects, prevalent across all ages, genders, and ethnicities. Although certain demographic cohorts carry a higher risk, the impaired quality of life attributed to SIM is significant. The pathogenesis of SIM remains to be fully elucidated, but it is clear that SIM is multifactorial. These factors include drug-drug interactions, renal or liver dysfunction, and genetics. Genetic-inferred risk for SIM was first reported by a landmark genome-wide association study, which reported a higher risk of SIM with a polymorphism in the SLCO1B1 gene. Since then, research associating genetic factors with SIM has expanded widely and has become one of the foci in the field of pharmacogenomics. This review provides an update on the genetic risk factors associated with SIM.
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Project description:Exercise-induced rhabdomyolysis (exRML), a pathophysiological condition of skeletal muscle cell damage that may cause acute renal failure and in some cases death. Increased Ca2+ level in cells along with functional degradation of cell signaling system and cell matrix have been suggested as the major pathological mechanisms associated with exRML. The onset of exRML may be exhibited in athletes as well as in general population. Previous studies have reported that possible causes of exRML were associated with excessive eccentric contractions in high temperature, abnormal electrolytes balance, and nutritional deficiencies possible genetic defects. However, the underlying mechanisms of exRML have not been clearly established among health professionals or sports medicine personnel. Therefore, we reviewed the possible mechanisms and correlated prevention of exRML, while providing useful and practical information for the athlete and general exercising population.
| S-EPMC6188610 | biostudies-other
Project description:The overarching goal of this study was to simultaneously model the dynamic relationships among statin exposure, statin discontinuation, and potentially statin-related myopathic outcomes. We extracted data from the Indiana Network of Patient Care for 134,815 patients who received statin therapy between January 4, 2004, and December 31, 2008. All individuals began statin treatment, some discontinued statin use, and some experienced myopathy and/or rhabdomyolysis while taking the drug or after discontinuation. We developed a militate model to characterize 12 transition probabilities among six different states defined by use or discontinuation of statin and its associated myopathy or rhabdomyolysis. We found that discontinuation of statin therapy was common and frequently early, with 44.4% of patients discontinuing therapy after 1 month, and discontinuation is a strong indicator for statin-induced myopathy (risk ratio, 10.8; p < 0.05). Women more likely than men (p < 0.05) and patients aged 65 years and older had a higher risk than those aged younger than 65 years to discontinue statin use or experience myopathy. In conclusion, we introduce an innovative multistate model that allows clear depiction of the relationship between statin discontinuation and statin-induced myopathy. For the first time, we have successfully demonstrated and quantified the relative risk of myopathy between patients who continued and discontinued statin therapy. Age and sex were two strong risk factors for both statin discontinuation and incident myopathy.
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