Abnormal liver function tests associated with severe rhabdomyolysis

Rhabdomyolysis is a syndrome of skeletal muscle injury with release of cellular constituents such as potassium,phosphate,urate and intracellular proteins such as myoglobin into the circulation,which may cause complications including acute kidney injury,electrolyte disturbance and cardiac instability.Abnormal liver function tests are frequently observed in cases of severe rhabdomyolysis.Typically,there is an increase in serum aminotransferases,namely aspartate aminotransferase and alanine aminotransferase.This raises the question of liver injury and often triggers a pathway of investigation which may lead to a liver biopsy.However,muscle can also be a source of the increased aminotransferase activity.This review discusses the dilemma of finding abnormal liver function tests in the setting of muscle injury and the potential implications of such an association.It delves into some of the clinical and experimental evidence for correlating muscle injury to raised aminotransferases,and discusses pathophysiological mechanisms such as oxidative stress which may cause actual liver injury.Serum aminotransferases lack tissue specificity to allow clinicians to distinguish primary liver injury from muscle injury.This review also explores potential approaches to improve the accuracy of our diagnostic tools,so that excessive or unnecessary liver investigations can be avoided.     

Premature Ticagrelor Discontinuation in Secondary Prevention of Atherosclerotic CVD: JACC Review Topic of the Week

Ticagrelor is a cornerstone of modern antithrombotic therapy alongside aspirin in patients with acute coronary syndrome and after percutaneous coronary intervention. Adverse effects such as bleeding and dyspnea have been associated with premature ticagrelor discontinuation, which may limit any potential advantage of ticagrelor over clopidogrel. The randomized trials of ticagrelor captured adverse events, offering the opportunity to more precisely quantify these effects across studies. Therefore, a meta-analysis of 4 randomized clinical trials of ticagrelor conducted between January 2007 and June 2017 was performed to quantify the incidence and causes of premature ticagrelor discontinuation. Among 66,870 patients followed for a median 18 months, premature ticagrelor discontinuation was seen in 25%; bleeding was the most common cause of discontinuation followed by dyspnea. Versus the comparators, the relative risk of dyspnea-related discontinuation during follow-up was 6.4-fold higher, the relative risk of bleeding was 3.2-fold higher, and the relative risk of discontinuation due to any adverse event was 59% higher for patients receiving ticagrelor. Understanding these potential barriers to adherence to ticagrelor is crucial for informed patient-physician decision making and can inform future efforts to improve ticagrelor adherence. This review discusses the incidence, causes, and biological mechanisms of ticagrelor-related adverse effects and offers strategies to improve adherence to ticagrelor.     

Intrathecal Ziconotide in the Treatment of Chronic Nonmalignant Pain: A Randomized,Double‐Blind,Placebo‐Controlled Clinical Trial

Objective. The safety and efficacy of intrathecal (IT) ziconotide was studied in a randomized, double‐blind, placebo‐controlled trial. Materials and Methods. Patients (169 ziconotide, 86 placebo) with severe chronic nonmalignant pain unresponsive to conventional therapy and a visual analog scale of pain intensity (VASPI score) ≥ 50 mm were treated over a 6‐day period in an inpatient hospital setting. Initial starting dose was 0.4 µg/hour and was titrated to analgesia or intolerance (maximum dose 7.0 µg/hour). The starting and maximum doses were reduced to 0.1 µg/hour and 2.4 µg/hour, respectively, due to adverse events (AEs). Results. The mean percent reduction in VASPI score from baseline was 31.2% and 6.0% for ziconotide‐ and placebo‐treated patients, respectively (p ≤ 0.001). During the initial titration phase, a significantly greater percentage of patients in the ziconotide group compared to the placebo group reported AEs, including abnormal gait, amblyopia, dizziness, nausea, nystagmus, pain, urinary retention, and vomiting. Conclusion. Ziconotide provided significant analgesia in patients for whom conventional therapy failed. However, there was a considerable incidence of ziconotide‐associated AEs due to the rapid titration and high doses administered.     

Responses of CDKs and p53 in Delayed Ischemic Neuronal Death

Stroke is a debilitating disease that affects millions each year.While in many cases cerebral ischemic in jury can be limited by effectivw resuscitation or thrombolytic treatment,the injured neurons wither in a process known as delayed neuronal death(DND).Mounting evidence indicates that DND is not simply necrosis played out in slow motion but apoptosis is triggered.Of particular interest are two groups of signal proteins that participate in apoptosis-cyclin dependent kinases(CDKs) and p53-among a myriad of signaling events after an ischemic insult.Recent investigations have shown that CDKs,a family of enzymes initially known for their role in cell cycle regulation,are activated in injured neurons in DND.As for p53,new reports suggest that its up-regulation may represent a failed attempt to rescue in jured neurons,although its up-regulation was previously considered an indication of apoptosis.These observations thus rekindle an old quest to identify new neuroprotective targets to minimize the stroke damage.In this review,the author will examine the evidence that indicates the participation of CDKs and p53 in DND and then introduce pre-clinical data to explore CDK inhibition as a potential neuroprotective target.Finally,using CDK inhibition as an example,this paper will discuss the pertinent criteria for a viable neuroprotective strategy for ischemic in jury.     

Coping, pain severity, interference, and disability: the potential mediating and moderating roles of race and education.

Researchers have demonstrated that certain types of pain coping are correlated with less pain severity and disability and that there are differences between Caucasians and African-American pain patients in their use of specific coping strategies. However, the extent to which racial group differences exist in the associations between pain coping strategies and pain severity, interference, and disability is unclear. Furthermore, the role of education in these associations is uncertain. We recruited a diverse community sample of individuals with chronic pain and their spouses to examine this issue (N = 105). Participants completed the Coping Strategies Questionnaire, Multidimensional Pain Inventory, and Sickness Impact Profile. Results showed that African-American participants reported significantly more pain severity, interference, and disability and reported using diverting attention and prayer and hoping pain-coping strategies significantly more often than Caucasian participants; however, only the racial group difference in prayer and hoping remained when controlling for education. We also examined whether race and education interacted with coping strategies in relating to pain and disability. Significant three-way interactions were found for physical and psychosocial disability, suggesting that educational level should be included in analyses exploring racial group differences. The results suggest the need for pain treatments that take into account the educational and cultural context of pain. PERSPECTIVE: This article demonstrates that demographic variables such as race and education should be considered together when evaluating the effectiveness of coping with pain. The findings have the potential to enhance research and clinical practice with diverse groups.     

Value of MR imaging in the evaluation of chronic infiltrative lung diseases: comparison with CT.

The value of MR imaging was compared with that of high-resolution CT in assessing chronic infiltrative lung disease in 25 patients. The cases included nine patients with usual interstitial pneumonia, six with sarcoidosis, four with hypersensitivity pneumonitis, and six with miscellaneous conditions. The diagnosis was proved by biopsy (n = 17) or by means of clinical, laboratory, and radiologic criteria (n = 8). All patients had 1.5-T MR imaging and CT of the chest. Cardiac-gated T1-, proton density-, and T2-weighted spin-echo sequences were obtained. Initially, the MR images were assessed independently; later they were compared directly with the corresponding CT scans. In six patients, MR images and CT scans were obtained before open lung biopsy, and the images and scans were assessed prospectively. CT was superior to MR imaging in the anatomic assessment of the lung parenchyma and in showing fibrosis. However, areas of air-space opacification (ground-glass opacities) were seen as well on MR as on high-resolution CT. In the six patients who had open lung biopsy, areas of air-space opacification seen on MR and on CT corresponded to areas of active alveolitis or air-space infiltrates pathologically. Follow-up in six patients showed equal degrees of change in the air-space opacification over time on MR and CT. We conclude that, although MR imaging is inferior to high-resolution CT in the assessment of chronic infiltrative lung diseases, it may play a role in the assessment and follow-up of patients with air-space opacification.     

Terrorist bombing

Bombings and explosion incidents directed against innocent civilians are the primary instrument of global terror. In the present review we highlight the major observations and lessons learned from these events. Five mechanisms of blast injury are outlined and the different type of injury that they cause is described. Indeed, the consequences of terror bombings differ from those of non-terrorism trauma in severity and complexity of injury, and constitute a new class of casualties that differ from those of conventional trauma. The clinical implications of terror bombing, in treatment dilemmas in the multidimensional injury, ancillary evaluation and handling of terror bombing mass casualty event are highlighted. All this leads to the conclusion that thorough medical preparedness to cope with this new epidemic is required, and that understanding of detonation and blast dynamics and how they correlate with the injury patterns is pivotal for revision of current mass casualty protocols.