Erin Moshier

Morbidity and mortality in common variable immune deficiency over 4 decades

The demographics, immunologic parameters, medical complications, and mortality statistics from 473 subjects with common variable immune deficiency followed over 4 decades in New York were analyzed. Median immunoglobulin levels were IgG, 246 mg/dL; IgA, 8 mg/dL; and IgM, 21 mg/dL; 22.6% had an IgG less than 100 mg/dL. Males were diagnosed earlier (median age, 30 years) than females (median age, 33.5 years; P = .004). Ninety-four percent of patients had a history of infections; 68% also had noninfectious complications: hematologic or organ-specific autoimmunity, 28.6%; chronic lung disease, 28.5%; bronchiectasis, 11.2%; gastrointestinal inflammatory disease, 15.4%; malabsorption, 5.9%; granulomatous disease, 9.7%; liver diseases and hepatitis, 9.1%; lymphoma, 8.2%; or other cancers, 7.0%. Females had higher baseline serum IgM (P = .009) and were more likely to develop lymphoma (P = .04); 19.6% of patients died, a significantly shorter survival than age- and sex-matched population controls (P < .0001). Reduced survival was associated with age at diagnosis, lower baseline IgG, higher IgM, and fewer peripheral B cells. The risk of death was 11 times higher for patients with noninfectious complications (hazard ratio = 10.95; P < .0001). Mortality was associated with lymphoma, any form of hepatitis, functional or structural lung impairment, and gastrointestinal disease with or without malabsorption, but not with bronchiectasis, autoimmunity, other cancers, granulomatous disease, or previous splenectomy.

Dietary baked egg accelerates resolution of egg allergy in children

BACKGROUND Baked egg is tolerated by a majority of egg-allergic children. OBJECTIVE To characterize immunologic changes associated with ingestion of baked egg and evaluate the role that baked egg diets play in the development of tolerance to regular egg. METHODS Egg-allergic subjects who tolerated baked egg challenge incorporated baked egg into their diet. Immunologic parameters were measured at follow-up visits. A comparison group strictly avoiding egg was used to evaluate the natural history of the development of tolerance. RESULTS Of the 79 subjects in the intent-to-treat group followed for a median of 37.8 months, 89% now tolerate baked egg and 53% now tolerate regular egg. Of 23 initially baked egg-reactive subjects, 14 (61%) subsequently tolerated baked egg and 6 (26%) now tolerate regular egg. Within the initially baked egg-reactive group, subjects with persistent reactivity to baked egg had higher median baseline egg white (EW)-specific IgE levels (13.5 kU(A)/L) than those who subsequently tolerated baked egg (4.4 kU(A)/L; P= .04) and regular egg (3.1 kU(A)/L; P= .05). In subjects ingesting baked egg, EW-induced skin prick test wheal diameter and EW-, ovalbumin-, and ovomucoid-specific IgE levels decreased significantly, while ovalbumin- and ovomucoid-specific IgG(4) levels increased significantly. Subjects in the per-protocol group were 14.6 times more likely than subjects in the comparison group (P< .0001) to develop regular egg tolerance, and they developed tolerance earlier (median 50.0 vs 78.7 months; P< .0001). CONCLUSION Initiation of a baked egg diet accelerates the development of regular egg tolerance compared with strict avoidance. Higher serum EW-specific IgE level is associated with persistent baked and regular egg reactivity, while initial baked egg reactivity is not.

Associations between phthalate metabolite urinary concentrations and body size measures in New York City children

OBJECTIVE To examine prospectively associations between urinary phthalate metabolite concentrations and body size measures in children. METHODS Urinary concentrations of nine phthalate metabolites: monoethyl (MEP); mono-n-butyl (MBP); mono-(3-carboxypropyl) (MCPP); monobenzyl (MBzP); mono-isobutyl (MiBP); mono-(2-ethylhexyl) (MEHP); mono-(2-ethyl-5-oxohexyl) (MEOHP); mono-(2-ethyl-5-carboxypentyl) (MECPP); and mono-(2-ethyl-5-hydroxyhexyl) phthalate (MEHHP) and the molar sum of the low molecular-weight phthalate metabolites (low MWP: MEP, MBP and MiBP) and high molecular-weight phthalate metabolites (high MWP: MECPP, MEHHP, MEOHP, MEHP and MBzP) and of four di-(2-ethylhexyl) phthalate (DEHP) metabolites (ΣDEHP: MEHP, MEHHP, MEOHP, MECPP) and anthropometry, including body mass index and waist circumference were measured among 387 Hispanic and Black, New York City children who were between six and eight years at cohort enrollment (2004-2007). Relationships between baseline metabolite concentrations and body size characteristics obtained one year later were examined using multivariate-adjusted geometric means for each body size characteristic by continuous and categories of phthalate metabolite concentrations. Stratified analyses by body size (age/sex specific) were conducted. RESULTS No significant associations are reported among all girls or boys. Dose response relationships were seen with monoethyl phthalate and the sum of low molecular-weight phthalates and body mass index and waist circumference among overweight children; for increasing monoethyl phthalate concentration quartiles among girls, adjusted mean body mass indexes were as follows: 21.3, 21.7, 23.8, 23.5 and adjusted mean waist circumference (cm) were as follows: 73.4, 73.5, 79.2, 78.8 (p-trend<0.001 for both). CONCLUSION In this prospective analysis we identified positive relationships between urinary concentrations of monoethyl phthalate and the sum of low molecular-weight phthalates and body size measures in overweight children. These are metabolites with concentrations above 1 μM.

Utility of casein-specific IgE levels in predicting reactivity to baked milk

Based on data from a large cohort of milk allergic children, our results show that measurement of casein-specific IgE is a helpful diagnostic indicator for predicting reactivity to baked milk, showing the greatest area under the receiver operating characteristic curve of parameters tested.

Comparative effectiveness of gemcitabine plus cisplatin versus methotrexate, vinblastine, doxorubicin, plus cisplatin as neoadjuvant therapy for muscle‐invasive bladder cancer

Gemcitabine plus cisplatin (GC) has been adopted as a neoadjuvant regimen for muscle‐invasive bladder cancer despite the lack of Level I evidence in this setting.

Pioglitazone modulates vascular inflammation in atherosclerotic rabbits : noninvasive assessment with FDG-PET-CT and dynamic contrast-enhanced MR imaging

OBJECTIVES We sought to determine the antiatherosclerotic properties of pioglitazone using multimethod noninvasive imaging techniques. BACKGROUND Inflammation is an essential component of vulnerable or high-risk atheromas. Pioglitazone, a peroxisome proliferator-activated receptor-gamma agonist, possesses potent anti-inflammatory properties. We aimed to quantify noninvasively the anti-inflammatory effects of pioglitazone on atheroma using (18)F-fluorodeoxyglucose ((18)F-FDG) positron emission tomography (PET)/computed tomography (CT) and dynamic contrast-enhanced (DCE) magnetic resonance imaging (MRI). METHODS Atherosclerotic plaques were induced in the aorta of 15 New Zealand white rabbits by a combination of a hyperlipidemic diet and 2 balloon endothelial denudations. Nine rabbits continued the same diet, whereas 6 rabbits received pioglitazone (10 mg/kg orally) in addition to the diet. Twelve animals underwent (18)F-FDG-PET/CT, and 15 animals underwent DCE-MRI at baseline, 1 month, and 3 months after treatment initiation. Concomitantly, serum metabolic parameters were monitored. After imaging was completed, aortic histologic analysis and correlation analysis were performed. RESULTS The (18)F-FDG-PET/CT imaging detected an increase in average standardized uptake value in the control group (p < 0.01), indicating progressive inflammation, whereas stable standardized uptake values were observed in the treatment group, indicating no progression. The DCE-MRI analysis detected a significant decrease in the area under the curve for the pioglitazone group (p < 0.01). Immunohistologic examination of the aortas demonstrated a significant decrease in macrophage and oxidized phospholipid immunoreactivity in the pioglitazone group (p = 0.04 and p = 0.01, respectively) with respect to control animals, underlining the imaging results. Serum metabolic parameters showed no difference between groups. Strong positive correlations between standardized uptake value and macrophage density and between area under the curve and neovessels were detected (r(2) = 0.86 and p < 0.0001, and r(2) = 0.66 and p = 0.004, respectively). CONCLUSIONS Both (18)F-FDG-PET/CT and DCE-MRI demonstrate noninvasively the anti-inflammatory effects of pioglitazone on atheroma. Both imaging methods seem suited to monitor inflammation in atherosclerosis.

The Effects of Hypertension and Body Mass Index on Cognition in Schizophrenia

OBJECTIVE In recent years there has been a greater appreciation of the elevated prevalence of cardiovascular risk factors in the schizophrenia population and the liability some treatments have for their development. These vascular risk factors are in turn important risk factors in the development of dementia and more subtle cognitive impairments. However, their impact on the cognitive functions of patients with schizophrenia remains underexplored. The authors investigated whether vascular risk factors influence the cognitive impairments of schizophrenia and whether their effects on cognition in schizophrenia are different from those observed in nonpsychiatric comparison subjects. METHOD The authors compared 100 patients with schizophrenia and 53 comparison subjects on cognitive test performance in 2×2 matrices composed of individual vascular risk factors and group (schizophrenia patients and comparison subjects). RESULTS Hypertension exerted a significant negative effect on immediate delayed and recognition memory in both groups. Patients with schizophrenia and hypertension were adversely affected in recognition memory, whereas comparison subjects were not. A body mass index above 25 was associated with negative effects on delayed memory in both groups, although the association fell short of statistical significance. CONCLUSIONS Given that patients with schizophrenia have a higher prevalence of vascular risk factors than the general population and are undertreated for them, treatment of these risk factors may significantly improve cognitive outcome in schizophrenia.

Effectiveness of Adjuvant Chemotherapy for Locally Advanced Bladder Cancer

PURPOSE Given that randomized trials exploring adjuvant chemotherapy for bladder cancer have been underpowered and/or terminated prematurely, yielding inconsistent results and creating an evidence gap, we sought to compare the effectiveness of cystectomy versus cystectomy plus adjuvant chemotherapy in real-world patients. PATIENTS AND METHODS We conducted an observational study to compare the effectiveness of adjuvant chemotherapy versus observation postcystectomy in patients with pathologic T3-4 and/or pathologic node-positive bladder cancer using the National Cancer Data Base. We compared overall survival using propensity score (-adjusted, -stratified, -weighted, and -matched) analyses based on patient-, facility-, and tumor-level characteristics. A sensitivity analysis was performed to examine the impact of performance status. RESULTS A total of 5,653 patients met study inclusion criteria; 23% received adjuvant chemotherapy postcystectomy. Chemotherapy-treated patients were younger and more likely to have private insurance, live in areas with a higher median income and higher percentage of high school-educated residents, and have lymph node involvement and positive surgical margins (P < .05 for all comparisons). Stratified analyses adjusted for propensity score demonstrated an improvement in overall survival with adjuvant chemotherapy (hazard ratio, 0.70; 95% CI, 0.64 to 0.76), and similar results were achieved with propensity score matching and weighting. The association between adjuvant chemotherapy and improved survival was consistent in subset analyses and was robust to the effects of poor performance status. CONCLUSION In this observational study, adjuvant chemotherapy was associated with improved survival in patients with locally advanced bladder cancer. Although neoadjuvant chemotherapy remains the preferred approach based on level I evidence, these data lend further support for the use of adjuvant chemotherapy in patients with locally advanced bladder cancer postcystectomy who did not receive chemotherapy preoperatively.

Regression of Inflammation in Atherosclerosis by the LXR Agonist R211945 A Noninvasive Assessment and Comparison With Atorvastatin

OBJECTIVES The aim of this study was to noninvasively detect the anti-inflammatory properties of the novel liver X receptor agonist R211945. BACKGROUND R211945 induces reversal cholesterol transport and modulates inflammation in atherosclerotic plaques. We aimed to characterize with (18)F-fluorodeoxyglucose (FDG)-positron emission tomography (PET)/computed tomography (CT) and dynamic contrast-enhanced cardiac magnetic resonance (DCE-CMR) inflammation and neovascularization, respectively, in atherosclerotic plaques with R211945 treatment compared with atorvastatin treatment and a control. METHODS Twenty-one atherosclerotic New Zealand white rabbits were divided into 3 groups (control, R211945 [3 mg/kg orally], and atorvastatin [3 mg/kg orally] groups). All groups underwent (18)F-FDG-PET/CT and DCE-CMR at baseline and at 1 and 3 months after treatment initiation. Concomitantly, serum metabolic parameters and histology were assessed. For statistical analysis, continuous DCE-CMR and PET/CT outcomes were modeled as linear functions of time by using a linear mixed model, whereas the histological data, animal characteristics data, and nonlinear regression imaging data were analyzed with a 2-tailed Student t test. RESULTS (18)F-FDG-PET/CT detected a decrease in mean and maximum standard uptake values (SUV) over time in the R211945 group (both p = 0.001), indicating inflammation regression. The atorvastatin group displayed no significant change (p = 0.371 and p = 0.600, respectively), indicating no progression or regression. The control group demonstrated an increase in SUV (p = 0.01 and p = 0.04, respectively), indicating progression. There was a significant interaction between time and group for mean and maximum SUV (p = 0.0003 and p = 0.0016, respectively) . DCE-CMR detected a trend toward difference (p = 0.06) in the area under the curve in the atorvastatin group, suggesting a decrease in neovascularization. There was no significant interaction between time and group (p = 0.6350 and p = 0.8011, respectively). Macrophage and apolipoprotein B immunoreactivity decreased in the R211945 and atorvastatin groups (p < 0.0001 and p = 0.0004, respectively), and R211945 decreased oxidized phospholipid immunoreactivity (p = 0.02). CONCLUSIONS Noninvasive imaging with (18)F-FDG-PET/CT and DCE-CMR and histological analysis demonstrated significant anti-inflammatory effects of the LXR agonist R211945 compared with atorvastatin. The results suggest a possible role for LXR agonists in the treatment of atherosclerosis.

Contemporary outcomes with the latest 1000 cases of multifetal pregnancy reduction (MPR).

OBJECTIVE This study was undertaken to report on the outcome of multifetal pregnancy reduction in the most up-to-date largest single center experience with this procedure, and compare the outcome to the first 1000 cases performed at the same institution. STUDY DESIGN 1000 consecutive cases of multifetal pregnancy reduction performed at the Mount Sinai Medical Center between the years 1999-2006 were identified. Pregnancy outcomes were retrieved from a large database as well as chart review. Differences in means and proportions were evaluated by analysis of variance, chi-square, Cochran-Armitage test for trend or 2-tailed Fisher exact test as appropriate. RESULTS Outcomes were available on 841 cases, for a follow-up rate of 84.1%; 95.2% of patients delivered after 24 weeks, for a complete loss rate of 4.7%. There was a significant trend toward decreasing loss rates with decreasing starting numbers. Mean gestational age at delivery was later, and birthweights greater, for reduction to singletons vs twins. CONCLUSION Loss rates after multifetal pregnancy reduction have remained stable at 4.7%. The lowest loss rate occurred in the patients reducing from twins to a singleton (2.1%). Reduction to a singleton was also associated with higher birthweights and lower rates of preterm deliveries.