Citations

Abstract INTRODUCTION High-sensitivity cardiac troponin assays have potent prognostic value in stable cardiovascular disease cohorts. Our objective was to assess the prognostic utility of a novel cardiac troponin I (cTnI) high-sensitivity assay, independently and in combination with amino-terminal pro–B-type natriuretic peptide (NT-proBNP), for the future development of heart failure and mortality in the general community. METHODS A well-characterized community-based cohort of 2042 participants underwent clinical assessment and echocardiographic evaluation. Baseline measurements of cTnI with a high-sensitivity assay and NT-proBNP were obtained in 1843 individuals. Participants were followed for new-onset heart failure and mortality with median (25th, 75th percentile) follow-up of 10.7 (7.9, 11.6) and 12.1 (10.4, 13.0) years, respectively. RESULTS When measured with a high-sensitivity assay, cTnI greater than the sex-specific 80th percentile was independently predictive of heart failure [hazard ratio 2.56 (95% confidence interval 1.88–3.50), P < 0.001] and mortality [1.91(1.49–2.46), P < 0.001] beyond conventional risk factors in this community-based cohort, with significant increases in the net reclassification improvement for heart failure. The prognostic utility of cTnI measured with a high-sensitivity assay goes beyond NT-proBNP, yet our data suggest that these 2 assays are complementary and most beneficial when evaluated together in identifying at-risk individuals in the community. CONCLUSIONS Our findings lay the foundation for prospective studies aimed at identification of individuals at high risk by use of a multimarker approach, followed by aggressive prevention strategies to prevent subsequent heart failure.

The cause and treatment of functional movement disorders and nonepileptic spells in children is poorly understood, and an association with migraine has not previously been reported. We retrospectively reviewed children diagnosed with chronic or episodic migraine at our institution from 2006 to 2013 to determine the proportion with nonorganic movement disorders, their phenomenology, provoking factors, and natural history. Thirty-two patients were identified, representing 4.3% of patients with chronic migraine and 0.9% of patients with episodic migraine. Twenty-four of the 32 (75%) had chronic migraine, whereas 8 (25%) had episodic migraine. Nonepileptic spells was the most common phenomenon in both cohorts, followed by tremor and functional gait disorders. Severe migraine attacks preceded these movements in the majority of patients. With appropriate migraine therapy, significant reduction or resolution of these movements was reported. We conclude that nonorganic movement disorders are observed in pediatric migraine, are more prevalent among chronic migraineurs, and can resolve with improved pain control.

Abstract Plasma membrane Ca2+ influx, especially store-operated Ca2+ entry triggered by sarcoplasmic reticulum (SR) Ca2+ release, is a key component of intracellular calcium concentration ([Ca2+]i) regulation in airway smooth muscle (ASM). Agonist-induced Ca2+ oscillations in ASM that involve both influx and SR mechanisms have been previously demonstrated. In nonexcitable cells, [Ca2+]i oscillations involve Ca2+ influx via arachidonic acid (AA) –stimulated channels, which show similarities to store-operated Ca2+ entry, although their molecular identity remains undetermined. Little is known about AA-regulated Ca2+ channels or their regulation in ASM. In enzymatically dissociated human ASM cells loaded with the Ca2+ indicator, fura-2, AA (1–10 μM) triggered [Ca2+]i oscillations that were inhibited by removal of extracellular Ca2+. Other fatty acids, such as the diacylglycerol analog, 1-oleoyl-2-acetyl-SN-glycerol, oleic acid, and palmitic acid (10 μM each), failed to elicit similar [Ca2+]i responses. Preincubation with LaCl3 (1 μM or 1 mM) inhibited AA-induced oscillations. Inhibition of receptor-operated channels (SKF96,365 [10 μM]), lipoxygenase (zileuton [10 μM]), or cyclooxygenase (indomethacin [10 μM]) did not affect oscillation parameters. Inhibition of SR Ca2+ release (ryanodine [10 μM] or inositol 1,4,5-trisphosphate receptor inhibitor, xestospongin C [1 μM]) decreased [Ca2+]i oscillation frequency and amplitude. Small interfering RNA against caveolin-1, stromal interaction molecule 1, or Orai3 (20 nM each) reduced the frequency and amplitude of AA-induced [Ca2+]i oscillations. In ASM cells derived from individuals with asthma, AA increased oscillation amplitude, but not frequency. These results are highly suggestive of a novel AA-mediated Ca2+–regulatory mechanism in human ASM, reminiscent of agonist-induced oscillations. Given the role of AA in ASM intracellular signaling, especially with inflammation, AA-regulated Ca2+ channels could potentially contribute to increased [Ca2+]i in diseases such asthma.

Key Points Tac/Sir prophylaxis provides equivalent GVHD-free survival when compared with Tac/Mtx in MRD transplantation. Tac/Sir is associated with more rapid engraftment and reduced oropharyngeal mucositis after MRD transplantation.

Herbal supplements are commonly used by patients for various problems. It is a well-known fact that most patients do not tell their physicians about the use of herbal supplements unless they are specifically asked. As a result, sometimes important information regarding drug side effects is missed in history taking. During our literature search, we found several retrospective studies and other meta-analyses that claim a lacking or weak link between black cohosh use and hepatotoxicity. We present a case of a 44-year-old female who developed subacute liver injury demonstrated on a CT scan and liver biopsy within a month of using the drug to resolve her hot flashes and discuss a possible temporal and causal association between black cohosh use and liver disease. Since the patient was not taking any other drugs, we concluded that the acute liver injury was caused by the use of black cohosh. We agree with the United States Pharmacopeia recommendations that a cautionary warning about hepatotoxicity should be labeled on the drug package.

Background: Mesalamine and thiopurines (6-mercaptopurine and azathioprine) have been shown to increase the risk of developing acute pancreatitis in inflammatory bowel disease (IBD) patients. Tumor necrosis factor-α (TNF-α) inhibitors have been shown to protect against pancreatitis in animal models. Objective: To determine the risk of pancreatitis when comparing thiopurine monotherapy, mesalamine monotherapy, and thiopurine and mesalamine dual therapy to identical treatments but with the addition of a TNF-α inhibitor. Methods: Using a case-control design, the Food and Drug Administration Adverse Event Reporting System was queried for cases of pancreatitis and control reactions in IBD patients on a thiopurine or mesalamine. The proportional reporting ratio method was used to compare the different therapy regimens with the same regimen combined with a TNF-α inhibitor. Results: In all, 549 cases and controls were identified. When comparing thiopurine monotherapy with thiopurines combined with a TNF-α inhibitor, the odds of pancreatitis were lower in those on combination therapy (odds ratio [OR] = 0.04; 95% CI = 0.01-0.12). A similar trend was seen when comparing mesalamine monotherapy to mesalamine combined with a TNF-α inhibitor (OR = 0.08; 95% CI = 0.04-0.14) and when comparing those on both a thiopurine and mesalamine with those on all 3 therapies (OR = 0.04; 95% CI = 0.01-0.16). Conclusions: Combination therapy with TNF-α inhibitors appears to be associated with a lower risk of pancreatitis in IBD patients on mesalamine, thiopurines, or a combination of both. Physicians should consider using TNF-α inhibitors in those with the greatest risk of pancreatitis, although prospective studies are needed.

It is with great pride that we present this Neurosurgical Focus video supplement on endovascular neurosurgery. We were privileged to view a multitude of outstanding quality videos demonstrating the current state-of-the-art in endovascular neurosurgery. Careful and critical review was required to narrow down the videos to a workable volume for this supplement, though there were many more that we would have liked to have included. This issue consists of several videos that represent modern neuroendovascular techniques for the treatment of cerebrovascular disease. The videos demonstrate the cutting-edge as well as standard endovascular therapies, which will be valuable to both the novice and the expert endovascular neurosurgeons. We are greatly honored to be involved with this project, and are very proud of its content and expert authors. We confidently believe you will enjoy the video content of this supplement.