Clinical and Neuroimaging Correlates of Post-Transplant Delirium.

Delirium is common among adults undergoing hematopoietic stem cell transplantation (HCT), although the clinical and neuroimaging correlates of post-HCT delirium have not been adequately delineated. We therefore examined the frequency of delirium and neuroimaging correlates of post-transplant delirium in a retrospective cohort of 115 adults undergoing neuroimaging after allogeneic HCT. Delirium was established using previously validated methods for retrospective identification of chart-assessed postprocedural delirium. Chart reviews were independently conducted by a multidisciplinary team with expertise in HCT, psychiatry, and psychology on consecutive allogeneic HCT patients who underwent neuroimaging assessments and transplantation at a single center between January 2009 and December 2016. Neuroimaging markers of white matter damage and brain volume loss were also recorded. In total, 115 patients were included, ranging in age from 20 to 74 years (mean [SD] age, 49 [13]). Fifty-three patients (46%) developed post-HCT delirium. In an adjusted model, delirium incidence was associated with older age (odds ratio [OR], 1.92 [1.28, 2.87] per decade, P = .002), greater severity of white matter hyperintensities (OR, 1.95 [1.06, 3.57], P = .031), and conditioning intensity (OR, 6.37 [2.20, 18.45], P < .001) but was unrelated to cortical atrophy (P = .777). Delirium was associated with fewer hospital-free days (P = .023) but was not associated with overall survival (hazard ratio, 0.95 [0.56, 1.61], P = .844). Greater incidence of delirium following HCT was associated with greater age, microvascular burden, and conditioning intensity. Pre-HCT consideration of microvascular burden and other neuroimaging biomarkers of risk may be warranted.

Neurological Sequelae and Clinical Outcomes After Lung Transplantation.

BACKGROUND: Neurological complications are common after lung transplantation. However, no large cohort studies have examined the incidence, predictors, and clinical significance of neurological events sustained by lung transplant recipients. METHODS: We conducted a retrospective cohort analysis of a consecutive series of lung transplant recipients, transplanted at Duke University Medical Center between May 2014 and February 2017 (n = 276). Early neurological complications (ie, occurring during the first week after transplant) were documented by transplant mental health specialists and included delirium, ischemic injury, and posterior reversible encephalopathy syndrome. Analyses accounted for age, native disease, sex, type of transplant, lung allocation score, and primary graft dysfunction. The objectives of the study were to characterize the prevalence and predictors of early neurological sequelae (NSE), occurring during the first week posttransplant, and the association between NSE and subsequent clinical outcomes, including length of stay and mortality. RESULTS: Neurological sequelae were common, occurring in 123 (45%) patients. Fifty-seven patients died over a follow-up interval of 2.1 years. The most common NSE were postoperative delirium (n = 110 [40%]) and posterior reversible encephalopathy syndrome (n = 12 [4%]), followed by stroke/transient ischemic attack and neurotoxicity. Higher lung allocation score was the strongest predictor of delirium. The presence of a NSE was associated with longer length of hospital stay (32 days vs 17 days, P < 0.001) and greater mortality (hazard ratio, 1.90; 95% confidence interval, 1.09-3.32], P = 0.024), with the greatest mortality risk occurring approximately 2 years after transplantation. CONCLUSIONS: Neurological events are relatively common after lung transplantation and associated with adverse clinical outcomes.

Association of atrial fibrillation risk alleles and response to acute rate control therapy.

OBJECTIVES: Given the sparse evidence for selection of first-line therapy for acute atrial fibrillation (AF) based on clinical factors alone, incorporation of genotype data may improve the effectiveness of treatment algorithms and advance the understanding of interpatient heterogeneity. We tested whether candidate nucleotide polymorphisms (SNPs) related to AF physiologic responses are associated with ventricular rate control after intravenous diltiazem in the emergency department (ED). METHODS: We conducted an analysis within a prospective observational cohort of ED patients with acute symptomatic AF, ventricular rate >110 beats per minute within the first 2 hours, initially treated with intravenous diltiazem, and who had DNA available for analysis. We evaluated 24 candidate SNPs that were grouped into 3 categories based on their phenotype response (atrioventricular nodal [AVN] conduction, resting heart rate, disease susceptibility) and calculated 3 genetic scores for each patient. Our primary outcome was maximum heart rate reduction within 4 hours of diltiazem administration. Multivariable regression was used to identify associations with the outcome while adjusting for age, sex, baseline heart rate, and diltiazem dose. RESULTS: Of the 142 patients, 127 had complete data for the primary outcome. None of the genetic scores for AVN conduction, resting heart rate, or AF susceptibility showed a significant association with maximal heart rate response. CONCLUSION: Using a candidate SNP approach, screening for genetic variants associated with AVN conduction, resting heart rate, or AF susceptibility failed to provide significant data for predicting successful rate control response to intravenous diltiazem for treating acute AF in the ED.

Evaluating the HATCH score for predicting progression to sustained atrial fibrillation in ED patients with new atrial fibrillation.

OBJECTIVES: Atrial fibrillation (AF) is often first detected in the emergency department (ED). Not all AF patients progress to sustained AF (ie, episodes lasting >7 days), which is associated with increased morbidity. The HATCH score stratifies patients with paroxysmal AF according to their risk for progression to sustained AF within 1 year. The HATCH score has previously never been tested in ED patients. We evaluated the accuracy of the HATCH score to predict progression to sustained AF within 1 year of initial AF diagnosis in the ED. METHODS: We conducted a retrospective cohort study of 253 ED patients with new onset AF and known rhythm status for 1 year following the initial AF detection. The exposure variable was the HATCH score at initial ED evaluation. The primary outcome was rhythm status at 1 year following initial AF diagnosis. We constructed a receiver operating characteristic curve and calculated the area under the curve to estimate the HATCH score's accuracy of predicting progression to sustained AF. RESULTS: Overall, 61 (24%) of 253 of patients progressed to sustained AF within 1 year of initial detection, and the HATCH score receiver operating characteristic area under the curve was 0.62 (95% confidence interval, 0.54-0.70). CONCLUSIONS: Among ED patients with new onset AF, the HATCH score was a modest predictor of progression to sustained AF. Because only 2 patients had a HATCH greater than 5, this previously recommended cut-point was not useful in identifying high-risk patients in this cohort. Refinement of this decision aid is needed to improve its prognostic accuracy in the ED population.

Selectivity in biomineralization of barium and strontium.

The desmid green alga Closterium moniliferum belongs to a small number of organisms that form barite (BaSO(4)) or celestite (SrSO(4)) biominerals. The ability to sequester Sr in the presence of an excess of Ca is of considerable interest for the remediation of (90)Sr from the environment and nuclear waste. While most cells dynamically regulate the concentration of the second messenger Ca(2+) in the cytosol and various organelles, transport proteins rarely discriminate strongly between Ca, Sr, and Ba. Herein, we investigate how these ions are trafficked in C. moniliferum and how precipitation of (Ba,Sr)SO(4) crystals occurs in the terminal vacuoles. Towards this goal, we simultaneously visualize intracellular dynamics of multiple elements using X-ray fluorescence microscopy (XFM) of cryo-fixed/freeze-dried samples. We correlate the resulting elemental maps with ultrastructural information gleaned from freeze-fracture cryo-SEM of frozen-hydrated cells and use micro X-ray absorption near edge structure (micro-XANES) to determine sulfur speciation. We find that the kinetics of Sr uptake and efflux depend on external Ca concentrations, and Sr, Ba, and Ca show similar intracellular localization. A highly ion-selective cross-membrane transport step is not evident. Based on elevated levels of sulfate detected in the terminal vacuoles, we propose a "sulfate trap" model, where the presence of dissolved barium leads to preferential precipitation of (Ba,Sr)SO(4) due to its low solubility relative to SrSO(4) and CaSO(4). Engineering the sulfate concentration in the vacuole may thus be the most direct way to increase the Sr sequestered per cell, an important consideration in using desmids for phytoremediation of (90)Sr.

Nanoceria exhibit redox state-dependent catalase mimetic activity.

In this study we have found that cerium oxide nanoparticles exhibit catalase mimetic activity. Surprisingly, the catalase mimetic activity correlates with a reduced level of cerium in the +3 state, in contrast to the relationship between surface charge and superoxide scavenging properties.

ACE I/D polymorphism associated with abnormal atrial and atrioventricular conduction in lone atrial fibrillation and structural heart disease: implications for electrical remodeling.

BACKGROUND: The angiotensin-converting enzyme (ACE) gene contains a common polymorphism based on the insertion (I) or deletion (D) of a 287-bp intronic DNA fragment. The D allele is associated with higher ACE activity and thus higher angiotensin II levels. Angiotensin II stimulates cardiac fibrosis and conduction heterogeneity. OBJECTIVE: The purpose of this study was to determine whether the ACE I/D polymorphism modulates cardiac electrophysiology. METHODS: Three different cohorts of patients were studied: 69 patients with paroxysmal lone atrial fibrillation (AF), 151 patients with structural heart disease and no history of AF, and 161 healthy subjects without cardiovascular disease or AF. Patients taking drugs that affect cardiac conduction were excluded from the study. ECG parameters during sinus rhythm were compared among the ACE I/D genotypes. RESULTS: The ACE I/D polymorphism was associated with the PR interval and heart block in the lone AF cohort. In multivariable linear regression models, the D allele was associated with longer PR interval in the lone AF and heart disease cohorts (12.0-ms and 7.1-ms increase per D allele, respectively). P-wave duration showed a similar trend, with increase in PR interval across ACE I/D genotypes in the lone AF and heart disease cohorts. CONCLUSION: The ACE D allele is associated with electrical remodeling in patients with lone AF and in those with heart disease, but not in control subjects. ACE activity may play a role in cardiac remodeling after the development of AF and heart disease.

The prevalence of anemia in patients with chronic kidney disease.

OBJECTIVE: Anemia is a complication of chronic kidney disease and may contribute to adverse clinical outcomes. Early identification and treatment of anemia may improve cardiovascular morbidity and mortality. No large-scale population data are available specifically for patients with chronic kidney disease regarding prevalence of anemia, subpopulations at risk, and relationships between anemia and kidney function. This study was undertaken to address these questions in patients with chronic kidney disease, and investigate the relationship between anemia and glomerular filtration rate. RESEARCH DESIGN AND METHODS: Large-scale, cross-sectional, US multicenter survey; 5222 patients (mean age, 68.2 years; 46.6% male); 237 physician practices. Eligible patients: > or = 18 years of age; serum creatinine: 1.5 mg/dL-6.0 mg/dL (females), 2.0 mg/dL-6.0 mg/dL (males). MAIN OUTCOME MEASURES: Primary study end point: prevalence and severity of anemia (hemoglobin < or = 12 g/dL). Data further stratified by hemoglobin (< or = 12 g/dL, < or = 10 g/dL). RESULTS: Primary etiologies of chronic kidney disease (5222 evaluable patients): diabetes (49.5%); hypertension (33.0%). Glomerular filtration rate: < 60 mL/min/1.73 m2 for 97.7% of evaluable patients. Mean +/- SD serum creatinine level: 2.2 mg/dL +/- 0.9 mg/dL; 2.5 mg/dL +/- 1.0 mg/dL for males, 2.0 mg/dL +/- 0.8 mg/dL for females. Mean +/- SD hemoglobin: 12.2 g/dL +/- 1.6 g/dL (47.7% had hemoglobin < or = 12 g/dL; 8.9% had hemoglobin < or = 10 g/dL). Prevalence of anemia was strongly associated with declining glomerular filtration rate. Percentage of patients with hemoglobin < or = 12 g/dL increased from 26.7% to 75.5% when glomerular filtration rate decreased from > or = 60 mL/min/1.73 m2 to < 15 mL/min/1.73 m2. Prevalence of hemoglobin < or = 10 g/dL increased substantially from 5.2% to 27.2% when glomerular filtration rate diminished from > or = 60 mL/min/1.73 m2 to < 15 mL/min/1.73 m2. After controlling for other patient characteristics associated with increased prevalence of anemia, the prevalence odds ratio for hemoglobin < or = 10 g/dL was 0.54 (0.49-0.60) and for hemoglobin < or = 12 g/dL was 0.68 (0.65-0.72), with each 10-mL/min/1.73 m2 increase in glomerular filtration rate. Predictors of anemia: diabetes, female sex, and race/ethnicity. CONCLUSIONS: Anemia was present in 47.7% of 5222 predialysis patients with chronic kidney disease. Prevalence of anemia increased as kidney function decreased. Certain subgroups are at increased risk for anemia.