Other search tools

About this data

The publication data currently available has been vetted by Vanderbilt faculty, staff, administrators and trainees. The data itself is retrieved directly from NCBI's PubMed and is automatically updated on a weekly basis to ensure accuracy and completeness.

If you have any questions or comments, please contact us.

Results: 1 to 10 of 78

Publication Record

Connections

Myocarditis in Patients Treated With Immune Checkpoint Inhibitors.
Mahmood SS, Fradley MG, Cohen JV, Nohria A, Reynolds KL, Heinzerling LM, Sullivan RJ, Damrongwatanasuk R, Chen CL, Gupta D, Kirchberger MC, Awadalla M, Hassan MZO, Moslehi JJ, Shah SP, Ganatra S, Thavendiranathan P, Lawrence DP, Groarke JD, Neilan TG
(2018) J Am Coll Cardiol 71: 1755-1764
MeSH Terms: Aged, Antineoplastic Agents, Immunological, Case-Control Studies, Female, Glucocorticoids, Humans, Male, Methylprednisolone, Middle Aged, Myocarditis, Neoplasms, Registries, Troponin T
Show Abstract · Added April 22, 2018
BACKGROUND - Myocarditis is an uncommon, but potentially fatal, toxicity of immune checkpoint inhibitors (ICI). Myocarditis after ICI has not been well characterized.
OBJECTIVES - The authors sought to understand the presentation and clinical course of ICI-associated myocarditis.
METHODS - After observation of sporadic ICI-associated myocarditis cases, the authors created a multicenter registry with 8 sites. From November 2013 to July 2017, there were 35 patients with ICI-associated myocarditis, who were compared to a random sample of 105 ICI-treated patients without myocarditis. Covariates of interest were extracted from medical records including the occurrence of major adverse cardiac events (MACE), defined as the composite of cardiovascular death, cardiogenic shock, cardiac arrest, and hemodynamically significant complete heart block.
RESULTS - The prevalence of myocarditis was 1.14% with a median time of onset of 34 days after starting ICI (interquartile range: 21 to 75 days). Cases were 65 ± 13 years of age, 29% were female, and 54% had no other immune-related side effects. Relative to controls, combination ICI (34% vs. 2%; p < 0.001) and diabetes (34% vs. 13%; p = 0.01) were more common in cases. Over 102 days (interquartile range: 62 to 214 days) of median follow-up, 16 (46%) developed MACE; 38% of MACE occurred with normal ejection fraction. There was a 4-fold increased risk of MACE with troponin T of ≥1.5 ng/ml (hazard ratio: 4.0; 95% confidence interval: 1.5 to 10.9; p = 0.003). Steroids were administered in 89%, and lower steroids doses were associated with higher residual troponin and higher MACE rates.
CONCLUSIONS - Myocarditis after ICI therapy may be more common than appreciated, occurs early after starting treatment, has a malignant course, and responds to higher steroid doses.
Copyright © 2018 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.
0 Communities
1 Members
0 Resources
13 MeSH Terms
Glucocorticoids Reprogram β-Cell Signaling to Preserve Insulin Secretion.
Fine NHF, Doig CL, Elhassan YS, Vierra NC, Marchetti P, Bugliani M, Nano R, Piemonti L, Rutter GA, Jacobson DA, Lavery GG, Hodson DJ
(2018) Diabetes 67: 278-290
MeSH Terms: 11-beta-Hydroxysteroid Dehydrogenase Type 1, Animals, Biomarkers, Calcium Channels, Calcium Signaling, Cell Differentiation, Corticosterone, Cortisone, Cyclic AMP, Glucocorticoids, Glucose, Humans, Hydrocortisone, Insulin, Insulin Secretion, Insulin-Secreting Cells, Kinetics, Mice, Inbred Strains, Mice, Knockout, Tissue Culture Techniques
Show Abstract · Added December 6, 2017
Excessive glucocorticoid exposure has been shown to be deleterious for pancreatic β-cell function and insulin release. However, glucocorticoids at physiological levels are essential for many homeostatic processes, including glycemic control. We show that corticosterone and cortisol and their less active precursors 11-dehydrocorticosterone (11-DHC) and cortisone suppress voltage-dependent Ca channel function and Ca fluxes in rodent as well as in human β-cells. However, insulin secretion, maximal ATP/ADP responses to glucose, and β-cell identity were all unaffected. Further examination revealed the upregulation of parallel amplifying cAMP signals and an increase in the number of membrane-docked insulin secretory granules. Effects of 11-DHC could be prevented by lipotoxicity and were associated with paracrine regulation of glucocorticoid activity because global deletion of 11β-hydroxysteroid dehydrogenase type 1 normalized Ca and cAMP responses. Thus, we have identified an enzymatically amplified feedback loop whereby glucocorticoids boost cAMP to maintain insulin secretion in the face of perturbed ionic signals. Failure of this protective mechanism may contribute to diabetes in states of glucocorticoid excess, such as Cushing syndrome, which are associated with frank dyslipidemia.
© 2017 by the American Diabetes Association.
0 Communities
1 Members
0 Resources
20 MeSH Terms
Loss of αB-crystallin function in zebrafish reveals critical roles in the development of the lens and stress resistance of the heart.
Mishra S, Wu SY, Fuller AW, Wang Z, Rose KL, Schey KL, Mchaourab HS
(2018) J Biol Chem 293: 740-753
MeSH Terms: Animals, Cardiomyopathies, Edema, Glucocorticoids, Image Processing, Computer-Assisted, Lens, Crystalline, Molecular Chaperones, Mutation, Myocardium, Pericardium, Phenotype, Receptors, Glucocorticoid, Signal Transduction, Stress, Physiological, Transgenes, Zebrafish, alpha-Crystallin A Chain, alpha-Crystallin B Chain
Show Abstract · Added April 3, 2018
Genetic mutations in the human small heat shock protein αB-crystallin have been implicated in autosomal cataracts and skeletal myopathies, including heart muscle diseases (cardiomyopathy). Although these mutations lead to modulation of their chaperone activity , the functions of αB-crystallin in the maintenance of both lens transparency and muscle integrity remain unclear. This lack of information has hindered a mechanistic understanding of these diseases. To better define the functional roles of αB-crystallin, we generated loss-of-function zebrafish mutant lines by utilizing the CRISPR/Cas9 system to specifically disrupt the two αB-crystallin genes, α and α We observed lens abnormalities in the mutant lines of both genes, and the penetrance of the lens phenotype was higher in α than α mutants. This finding is in contrast with the lack of a phenotype previously reported in αB-crystallin knock-out mice and suggests that the elevated chaperone activity of the two zebrafish orthologs is critical for lens development. Besides its key role in the lens, we uncovered another critical role for αB-crystallin in providing stress tolerance to the heart. The αB-crystallin mutants exhibited hypersusceptibility to develop pericardial edema when challenged by crowding stress or exposed to elevated cortisol stress, both of which activate glucocorticoid receptor signaling. Our work illuminates the involvement of αB-crystallin in stress tolerance of the heart presumably through the proteostasis network and reinforces the critical role of the chaperone activity of αB-crystallin in the maintenance of lens transparency.
© 2018 by The American Society for Biochemistry and Molecular Biology, Inc.
0 Communities
1 Members
0 Resources
18 MeSH Terms
Seasonal patterns of Asthma medication fills among diverse populations of the United States.
Turi KN, Gebretsadik T, Lee RL, Hartert TV, Evans AM, Stone C, Sicignano NM, Wu AC, Iribarren C, Butler MG, Mitchel E, Morrow J, Larkin EK, Wu P
(2018) J Asthma 55: 764-770
MeSH Terms: Administration, Inhalation, Administration, Oral, Adolescent, Adrenergic beta-Agonists, Adult, Anti-Asthmatic Agents, Asthma, Child, Child, Preschool, Drug Prescriptions, Drug Therapy, Combination, Female, Glucocorticoids, Humans, Male, Medication Adherence, Middle Aged, Retrospective Studies, Seasons, United States, Young Adult
Show Abstract · Added March 14, 2018
OBJECTIVE - Nonadherence to controller and overuse of reliever asthma medications are associated with exacerbations. We aimed to determine patterns of seasonal asthma medication use and to identify time period(s) during which interventions to improve medication adherence could reduce asthma morbidity.
METHODS - We conducted a retrospective cohort study of asthmatics 4-50 years of age and enrolled in three diverse health insurance plans. Seasonal patterns of medications were reported by monthly prescription fill rates per 1000 individuals with asthma from 1998 to 2013, and stratified by healthcare plan, sex, and age.
RESULTS - There was a distinct and consistent seasonal fill pattern for all asthma medications. The lowest fill rate was observed in the month of July. Fills increased in the autumn and remained high throughout the winter and spring. Compared with the month of May with high medication fills, July represented a relative decrease of fills ranging from 13% (rate ratio, RR: 0.87, 95% confidence interval, 95%CI: 0.72-1.04) for the combination of inhaled corticosteroids (ICS) + long acting beta agonists (LABA) to 45% (RR: 0.55, 95%CI: 0.49-0.61) for oral corticosteroids. Such a seasonal pattern was observed each year across the 16-year study period, among healthcare plans, sexes, and ages. LABA containing control medication (ICS+LABA and LABA) fill rates were more prevalent in older asthmatics, while leukotriene receptor antagonists were more prevalent in the younger population.
CONCLUSIONS - A seasonal pattern of asthma medication fill rates likely represents a reactive response to a loss of disease control and increased symptoms. Adherence to and consistent use of asthma medications among individuals who use medications in reaction to seasonal exacerbations might be a key component in reducing the risk of asthma exacerbations.
0 Communities
1 Members
0 Resources
21 MeSH Terms
Fulminant Myocarditis with Combination Immune Checkpoint Blockade.
Johnson DB, Balko JM, Compton ML, Chalkias S, Gorham J, Xu Y, Hicks M, Puzanov I, Alexander MR, Bloomer TL, Becker JR, Slosky DA, Phillips EJ, Pilkinton MA, Craig-Owens L, Kola N, Plautz G, Reshef DS, Deutsch JS, Deering RP, Olenchock BA, Lichtman AH, Roden DM, Seidman CE, Koralnik IJ, Seidman JG, Hoffman RD, Taube JM, Diaz LA, Anders RA, Sosman JA, Moslehi JJ
(2016) N Engl J Med 375: 1749-1755
MeSH Terms: Aged, Antibodies, Monoclonal, Arrhythmias, Cardiac, Electrocardiography, Fatal Outcome, Female, Glucocorticoids, Heart Block, Humans, Immunotherapy, Ipilimumab, Male, Melanoma, Middle Aged, Myocarditis, Myocardium, Myositis, Nivolumab
Show Abstract · Added March 26, 2017
Immune checkpoint inhibitors have improved clinical outcomes associated with numerous cancers, but high-grade, immune-related adverse events can occur, particularly with combination immunotherapy. We report the cases of two patients with melanoma in whom fatal myocarditis developed after treatment with ipilimumab and nivolumab. In both patients, there was development of myositis with rhabdomyolysis, early progressive and refractory cardiac electrical instability, and myocarditis with a robust presence of T-cell and macrophage infiltrates. Selective clonal T-cell populations infiltrating the myocardium were identical to those present in tumors and skeletal muscle. Pharmacovigilance studies show that myocarditis occurred in 0.27% of patients treated with a combination of ipilimumab and nivolumab, which suggests that our patients were having a rare, potentially fatal, T-cell-driven drug reaction. (Funded by Vanderbilt-Ingram Cancer Center Ambassadors and others.).
0 Communities
5 Members
0 Resources
18 MeSH Terms
Moderating effects of immunosuppressive medications and risk factors for post-operative joint infection following total joint arthroplasty in patients with rheumatoid arthritis or osteoarthritis.
Salt E, Wiggins AT, Rayens MK, Morris BJ, Mannino D, Hoellein A, Donegan RP, Crofford LJ
(2017) Semin Arthritis Rheum 46: 423-429
MeSH Terms: Aged, Allopurinol, Arthritis, Rheumatoid, Arthroplasty, Replacement, Arthroplasty, Replacement, Hip, Arthroplasty, Replacement, Knee, Arthroplasty, Replacement, Shoulder, Case-Control Studies, Comorbidity, Diabetes Mellitus, Female, Glucocorticoids, Gout, Gout Suppressants, HIV Infections, Humans, Immunologic Deficiency Syndromes, Immunosuppressive Agents, Logistic Models, Lupus Erythematosus, Systemic, Male, Middle Aged, Multivariate Analysis, Neoplasms, Obesity, Osteoarthritis, Osteoarthritis, Hip, Osteoarthritis, Knee, Prednisone, Prosthesis-Related Infections, Retrospective Studies, Risk Factors, Sex Factors, Shoulder Joint, Surgical Wound Infection
Show Abstract · Added March 25, 2020
OBJECTIVE - Inconclusive findings about infection risks, importantly the use of immunosuppressive medications in patients who have undergone large-joint total joint arthroplasty, challenge efforts to provide evidence-based perioperative total joint arthroplasty recommendations to improve surgical outcomes. Thus, the aim of this study was to describe risk factors for developing a post-operative infection in patients undergoing TJA of a large joint (total hip arthroplasty, total knee arthroplasty, or total shoulder arthroplasty) by identifying clinical and demographic factors, including the use of high-risk medications (i.e., prednisone and immunosuppressive medications) and diagnoses [i.e., rheumatoid arthritis (RA), osteoarthritis (OA), gout, obesity, and diabetes mellitus] that are linked to infection status, controlling for length of follow-up.
METHODS - A retrospective, case-control study (N = 2212) using de-identified patient health claims information from a commercially insured, U.S. dataset representing 15 million patients annually (from January 1, 2007 to December 31, 2009) was conducted. Descriptive statistics, t-test, chi-square test, Fisher's exact test, and multivariate logistic regression were used.
RESULTS - Male gender (OR = 1.42, p < 0.001), diagnosis of RA (OR = 1.47, p = 0.031), diabetes mellitus (OR = 1.38, p = 0.001), obesity (OR = 1.66, p < 0.001) or gout (OR = 1.95, p = 0.001), and a prescription for prednisone (OR = 1.59, p < 0.001) predicted a post-operative infection following total joint arthroplasty. Persons with post-operative joint infections were significantly more likely to be prescribed allopurinol (p = 0.002) and colchicine (p = 0.006); no significant difference was found for the use of specific disease-modifying anti-rheumatic drugs and TNF-α inhibitors.
CONCLUSION - High-risk, post-operative joint infection groups were identified allowing for precautionary clinical measures to be taken.
Copyright © 2017 Elsevier Inc. All rights reserved.
0 Communities
1 Members
0 Resources
MeSH Terms
Sustained glucocorticoid exposure recruits cortico-limbic CRH signaling to modulate endocannabinoid function.
Gray JM, Wilson CD, Lee TT, Pittman QJ, Deussing JM, Hillard CJ, McEwen BS, Schulkin J, Karatsoreos IN, Patel S, Hill MN
(2016) Psychoneuroendocrinology 66: 151-8
MeSH Terms: Amygdala, Animals, Corticotropin-Releasing Hormone, Endocannabinoids, Glucocorticoids, Limbic System, Male, Mice, Mice, Inbred C57BL, Mice, Transgenic, Prefrontal Cortex, Rats, Rats, Sprague-Dawley, Restraint, Physical, Signal Transduction, Stress, Psychological
Show Abstract · Added March 14, 2018
Sustained exposure to stress or corticosteroids is known to cause changes in brain endocannabinoid (eCB) signaling, such that tissue contents of the eCBs N-arachidonylethanolamine (AEA) are generally reduced while 2-arachidonoylglycerol (2-AG) levels increase. These changes in eCB signaling are important for many of the aspects of chronic stress, such as anxiety, reward sensitivity and stress adaptation, yet the mechanisms mediating these changes are not fully understood. We have recently found that the stress-related neuropeptide corticotropin-releasing hormone (CRH), acting through the CRH type 1 receptor (CRHR1), can reduce AEA content by increasing its hydrolysis by the enzyme fatty acid amide hydrolase (FAAH) as well as increase 2-AG contents. As extra-hypothalamic CRH is upregulated by chronic corticosteroid or stress exposure, we hypothesized that increased CRH signaling through CRHR1 contributes to the effects of chronic corticosteroid exposure on the eCB system within the amygdala and prefrontal cortex. Male rats were exposed to 7 days of systemic corticosterone capsules, with or without concurrent exposure to a CRHR1 antagonist, after which we examined eCB content. Consistent with previous studies in the amygdala, sustained corticosterone exposure increases CRH mRNA in the prefrontal cortex. As was shown previously, FAAH activity was increased and AEA contents were reduced within the amygdala and prefrontal cortex following chronic corticosterone exposure. Chronic corticosterone exposure also elevated 2-AG content in the prefrontal cortex but not the amygdala. These corticosteroid-driven changes were all blocked by systemic CRHR1 antagonism. Consistent with these data indicating sustained increases in CRH signaling can mediate the effects of chronic elevations in corticosteroids, CRH overexpressing mice also exhibited increased FAAH-mediated AEA hydrolysis in the amygdala and prefrontal cortex compared to wild type. CRH overexpression increased 2-AG content in the amygdala, but not the prefrontal cortex. These data indicate that chronic elevations in CRH signaling, as is seen following exposure to chronic elevations in corticosterone or stress, drive persistent changes in eCB function. As reductions in AEA signaling mediate the effects of CRH and chronic stress on anxiety, these data provide a mechanism linking these processes.
Copyright © 2016 Elsevier Ltd. All rights reserved.
0 Communities
1 Members
0 Resources
16 MeSH Terms
Genetics of glucocorticoid-associated osteonecrosis in children with acute lymphoblastic leukemia.
Karol SE, Yang W, Van Driest SL, Chang TY, Kaste S, Bowton E, Basford M, Bastarache L, Roden DM, Denny JC, Larsen E, Winick N, Carroll WL, Cheng C, Pei D, Fernandez CA, Liu C, Smith C, Loh ML, Raetz EA, Hunger SP, Scheet P, Jeha S, Pui CH, Evans WE, Devidas M, Mattano LA, Relling MV
(2015) Blood 126: 1770-6
MeSH Terms: Biomarkers, Child, Cohort Studies, Dexamethasone, Female, Follow-Up Studies, Genetic Predisposition to Disease, Genome-Wide Association Study, Glucocorticoids, Humans, Male, Meta-Analysis as Topic, Neoplasm Staging, Osteonecrosis, Polymorphism, Single Nucleotide, Precursor Cell Lymphoblastic Leukemia-Lymphoma, Prognosis, Receptors, N-Methyl-D-Aspartate, Risk Factors
Show Abstract · Added April 11, 2017
Glucocorticoids are important therapy for acute lymphoblastic leukemia (ALL) and their major adverse effect is osteonecrosis. Our goal was to identify genetic and nongenetic risk factors for osteonecrosis. We performed a genome-wide association study of single nucleotide polymorphisms (SNPs) in a discovery cohort comprising 2285 children with ALL, treated on the Children's Oncology Group AALL0232 protocol (NCT00075725), adjusting for covariates. The minor allele at SNP rs10989692 (near the glutamate receptor GRIN3A locus) was associated with osteonecrosis (hazard ratio = 2.03; P = 3.59 × 10(-7)). The association was supported by 2 replication cohorts, including 361 children with ALL on St. Jude's Total XV protocol (NCT00137111) and 309 non-ALL patients from Vanderbilt University's BioVU repository treated with glucocorticoids (odds ratio [OR] = 1.87 and 2.26; P = .063 and .0074, respectively). In a meta-analysis, rs10989692 was also highest ranked (P = 2.68 × 10(-8)), and the glutamate pathway was the top ranked pathway (P = 9.8 × 10(-4)). Osteonecrosis-associated glutamate receptor variants were also associated with other vascular phenotypes including cerebral ischemia (OR = 1.64; P = 2.5 × 10(-3)), and arterial embolism and thrombosis (OR = 1.88; P = 4.2 × 10(-3)). In conclusion, osteonecrosis was associated with inherited variations near glutamate receptor genes. Further understanding this association may allow interventions to decrease osteonecrosis. These trials are registered at www.clinicaltrials.gov as #NCT00075725 and #NCT00137111.
© 2015 by The American Society of Hematology.
0 Communities
3 Members
0 Resources
19 MeSH Terms
Effect of glucocorticoids on expression of cutaneous antimicrobial peptides in northern leopard frogs (Lithobates pipiens).
Tatiersky L, Rollins-Smith LA, Lu R, Jardine C, Barker IK, Clark ME, Caswell JL
(2015) BMC Vet Res 11: 191
MeSH Terms: Amphibian Proteins, Animals, Antimicrobial Cationic Peptides, Gene Expression Regulation, Glucocorticoids, Methylprednisolone, Rana pipiens, Skin
Show Abstract · Added April 18, 2017
BACKGROUND - Many species of frogs secrete cutaneous antimicrobial peptides that are capable of killing Batrachochytrium dendrobatidis. Some of these species are nonetheless susceptible to chytridiomycosis, suggesting that host factors causing dysregulation of this innate immune response may be important in pathogenesis. Since stresses, such as from environmental perturbations, are a potential cause of such dysregulation, this study investigated the effect of glucocorticoid on cutaneous gene expression of these antimicrobial peptides.
RESULTS - Northern leopard frogs (Lithobates pipiens) were injected with either the corticosteroid methylprednisolone or saline every 48 h. Norepinephrine-elicited cutaneous secretions were collected every 8 days for 40 days. Gene expression of antimicrobial peptides (brevinin-1P and ranatuerin-2P) in the cutaneous secretions was measured relative to the reference genes EF1-α and RPL8 using quantitative RT-PCR. Corticosteroid treatment was associated with a significant increase in brevinin-1P gene expression, which was most notable at 24-40 days of corticosteroid administration. Ranatuerin-2P expression followed a similar but non-significant trend.
CONCLUSION - This treatment protocol, including corticosteroid-administration and frequent norepinephrine-induced secretion, increased AMP gene expression in the skin of L. pipiens under these experimental conditions. The findings do not support the hypothesis that environmental stress predisposes frogs to chytridiomycosis by causing glucocorticoid-induced suppression of antimicrobial peptide defences.
0 Communities
1 Members
0 Resources
8 MeSH Terms
Randomized controlled trial comparing esophageal dilation to no dilation among adults with esophageal eosinophilia and dysphagia.
Kavitt RT, Ates F, Slaughter JC, Higginbotham T, Shepherd BD, Sumner EL, Vaezi MF
(2016) Dis Esophagus 29: 983-991
MeSH Terms: Adult, Deglutition Disorders, Dexlansoprazole, Dilatation, Eosinophilic Esophagitis, Esophageal Stenosis, Esophagoplasty, Esophagoscopy, Esophagus, Female, Fluticasone, Glucocorticoids, Humans, Male, Proton Pump Inhibitors, Single-Blind Method, Treatment Outcome, Young Adult
Show Abstract · Added September 28, 2015
The role of esophageal dilation in patients with esophageal eosinophilia with dysphagia remains unknown. The practice of dilation is currently based on center preferences and expert opinion. The aim of this study is to determine if, and to what extent, dysphagia improves in response to initial esophageal dilation followed by standard medical therapies. We conducted a randomized, blinded, controlled trial evaluating adult patients with dysphagia and newly diagnosed esophageal eosinophilia from 2008 to 2013. Patients were randomized to dilation or no dilation at time of endoscopy and blinded to dilation status. Endoscopic features were graded as major and minor. Subsequent to randomization and endoscopy, all patients received fluticasone and dexlansoprazole for 2 months. The primary study outcome was reduction in overall dysphagia score, assessed at 30 and 60 days post-intervention. Patients with severe strictures (less than 7-mm esophageal diameter) were excluded from the study. Thirty-one patients were randomized and completed the protocol: 17 randomized to dilation and 14 to no dilation. Both groups were similar with regard to gender, age, eosinophil density, endoscopic score, and baseline dysphagia score. The population exhibited moderate to severe dysphagia and moderate esophageal stricturing at baseline. Overall, there was a significant (P < 0.001) but similar reduction in mean dysphagia score at 30 and 60 days post-randomization compared with baseline in both groups. No significant difference in dysphagia scores between treatment groups after 30 (P = 0.93) or 60 (P = 0.21) days post-intervention was observed. Esophageal dilation did not result in additional improvement in dysphagia score compared with treatment with proton pump inhibitor and fluticasone alone. In patients with symptomatic esophageal eosinophilia without severe stricture, dilation does not appear to be a necessary initial treatment strategy.
© 2015 International Society for Diseases of the Esophagus.
0 Communities
1 Members
0 Resources
18 MeSH Terms