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.
Background The majority (approximately 75%) of children with cow’s milk allergy tolerate extensively heated (baked) milk products. Long-term effects of inclusion of dietary baked milk have not been ...reported. Objective We report on the outcomes of children who incorporated baked milk products into their diets. Methods Children evaluated for tolerance to baked milk (muffin) underwent sequential food challenges to baked cheese (pizza) followed by unheated milk. Immunologic parameters were measured at challenge visits. The comparison group was matched to active subjects (by using age, sex, and baseline milk-specific IgE levels) to evaluate the natural history of development of tolerance. Results Over a median of 37 months (range, 8-75 months), 88 children underwent challenges at varying intervals (range, 6-54 months). Among 65 subjects initially tolerant to baked milk, 39 (60%) now tolerate unheated milk, 18 (28%) tolerate baked milk/baked cheese, and 8 (12%) chose to avoid milk strictly. Among the baked milk–reactive subgroup (n = 23), 2 (9%) tolerate unheated milk, and 3 (13%) tolerate baked milk/baked cheese, whereas the majority (78%) avoid milk strictly. Subjects who were initially tolerant to baked milk were 28 times more likely to become unheated milk tolerant compared with baked milk–reactive subjects ( P < .001). Subjects who incorporated dietary baked milk were 16 times more likely than the comparison group to become unheated milk tolerant ( P < .001). Median casein IgG4 levels in the baked milk–tolerant group increased significantly ( P < .001); median milk IgE values did not change significantly. Conclusions Tolerance of baked milk is a marker of transient IgE-mediated cow’s milk allergy, whereas reactivity to baked milk portends a more persistent phenotype. The addition of baked milk to the diet of children tolerating such foods appears to accelerate the development of unheated milk tolerance compared with strict avoidance.
This study represents the most recent epidemiologic trends of head and neck cancer (HNC) in the United States. It provides an important discussion on oropharyngeal cancer and cancers related to the ...human papillomavirus. The objective was to identify trends in HNC (2002 to 2012) within the United States.
This study is a retrospective analysis of the US National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER) submission. Using the November 2014 submission of the SEER database and SEER-18 data files, data from 2002 to 2012 were analyzed to determine the most recent epidemiologic trends. HNCs of all subtypes were analyzed together. Laryngeal cancers were further analyzed separately. Oropharyngeal cancers of the base of tongue and tonsil were analyzed independently to attempt to trend HPV-related cancers.
From 2002 to 2012, there were 149,301 cases of HNC recorded in the SEER database. The HNC rate decreased by 0.22% per year (P = .0549) and the rate of laryngeal cancer decreased by 1.9% per year (P < .0001). The rate of oropharyngeal (HPV-related) cancer increased by 2.5% per year (P < .0001). HNC rates increased significantly in Kentucky and Connecticut and decreased in California (P < .05). HPV-related cancers increased significantly in all states except Georgia, Hawaii, and Michigan (P < .05). Laryngeal cancer rates decreased in California, Georgia, New Jersey, and New Mexico (P < .05).
The overall incidence of HNC is decreasing in the United States. There is an increasing incidence of HPV-related cancers of the oropharynx. Meaningful differences in cancer incidence and rate of change exist between men and women. Furthermore, younger groups have a greater decrease of overall HNC, with an overall increase in HPV-related cancer in patients older than 50 years.
To examine prospectively associations between urinary phthalate metabolite concentrations and body size measures in children.
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.
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).
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 1μM.
► We examine the association between phthalate metabolites and body size in children. ► Overall, no significant associations are reported among children. ► Among overweight children, monoethyl phthalate and body mass index were associated. ► In an overweight children, monoethyl phthalate and waist circumference were associated.
BACKGROUND:High-grade dysplasia is the anal carcinoma precursor. Clinicians ablate high-grade dysplasia with laser, electrocautery, and infrared coagulation to prevent cancer.
OBJECTIVE:The aim of ...this study was to determine the long-term effectiveness of high-grade dysplasia ablation and the incidence of cancer.
DESIGN:This study is a retrospective chart review of patients who were treated for high-grade dysplasia from February 1998 until May 2012.
SETTING:This study was conducted in a surgical practice screening patients for anal cancer and high-grade dysplasia.
PATIENTS:The patients identified were HIV-positive and -negative men who have sex with men.
INTERVENTION:The ablation of high-grade dysplasia was performed.
MAIN OUTCOME MEASURES:The primary outcomes measured were the probability of high-grade dysplasia recurrence postablation and the incidence of cancer.
RESULTS:Four hundred fifty-six HIV-positive men who have sex with men (mean age, 45 ± 9 years) and 271 HIV-negative men who have sex with men (mean age, 41 ± 11 years) followed for a median of 2.2 (range, 0.2–13) years underwent high-grade dysplasia ablation by laser, infrared coagulation, and/or electrocautery. Median time to recurrence was 6.8 and 6.9 months for HIV-positive and -negative patients. Kaplan-Meier curves predict a rate of recurrence 1 year after the first ablation for HIV-positive and -negative patients of 53% (95% CI, 49%–58%) and 49% (95% CI, 43%–55%). At 2 and 3 years, the rate of recurrence was 68% (95% CI, 63%–73%) and 77% (95% CI, 7%2–82%) for HIV-positive patients and 57% (95% CI, 51%–64%) and 66% (95% CI, 59%–73%) for HIV-negative patients. The median number of recurrent lesions was ≤2 for HIV-positive patients and ≤1 for HIV-negative patients. Recurrence increased with HIV infection (HR, 1.3; 95% CI, 1.1–1.6) and each additional lesion treated (HR 1.6, 95% CI, 1.1–1.2). Five HIV-positive men who have sex with men developed cancer. The Kaplan-Meier probability of cancer 3 years postablation was 1.97% (95% CI, 0.73%–5.2%).
LIMITATIONS:This is a retrospective study by 1 surgeon who has extensive experience treating anal dysplasia. There was no pathology review, and the type of recurrence cannot be definitively determined because the location could be inaccurate.
CONCLUSIONS:Patients undergoing ablation of intra-anal high-grade dysplasia have high recurrence, but the probability of developing anal cancer is low. HIV infection and increased number of high-grade dysplasias increases the risk of recurrence.
Again, the AUCs for specific IgE levels to casein were greater than the AUCs for specific IgE levels to CM, although the difference was not statistically significant in the first cohort of patients ...(Fig 1, B). ...we found very similar values for the positive and negative decision points (ie, 21.4 and 1.0 kUA/L in the first cohort and 20.2 and 0.7 kUA/L in the second cohort, respectively; see Table E2).\n of patients (%) 23 (23.7) 66 (68.0) 8 (8.3)  38 (29.7) 83 (64.8) 7 (5.5)  Age (y)         Median 7.3 6.5 5.8 .55 8.0 7.5 5.9 .1 Range 3.4-14.9 2.1-17.3 2.6-15.0  4.4-10.9 4.0-11.0 4.1-10.9  Sex, no. (%)         Male 14 (60.9) 43 (65.2) 4 (50) .83 27 (71.1) 59 (71.1) 4 (57.1) .74 Female 9 (39.1) 23 (34.8) 4 (50)  11 (28.9) 24 (28.9) 3 (42.9)  Specific IgE (kUA/L)         CM         Median 11.6 2.5 0.9 .00 11.9 4.0 0.7 .00 Range 0.7-101 0.2-79.1 0.2-6.1  0.8-50.5 0.2-42.3 0.2-4.8  Casein         Median 13.9 1.4 1.5 .00 12.2 2.3 0.4 .00 Range 0.7-101 0.2-79.6 0.5-3.7  0.5-67.0 0.2-30.5 0.2-2.0  β-lactoglobulin         Median 4.6 0.5 0.2 .00 2.0 0.6 0.2 .00 Range 0.2-101 0.2-13.8 0.2-2.3  0.2-15.4 0.2-19.8 0.2-7.8  Specific IgG4 (mgA/L)         Casein         Median 1.5 0.6 1.4 .11 1.2 0.8 0.3 .05 Range 0.0-6.7 0.0-23.8 0.2-31  0.1-10.3 0.0-13.1 0.1-1.9  β-lactoglobulin         Median 0.6 0.4 1.3 .15 0.4 0.4 0.1 .72 Range 0.0-8.4 0.0-31 0.1-31  0.0-2.3 0.0-3.9 0.0-2.4  IgE/IgG4 ratio         Casein         Median 10.6 2.5 1.34 .00 6.0 3.0 1.6 .00 Range 1.9-69.3 0-868 0.1-3.7  0.2-109.8 0.1-63.7 0.1-5.0  β-lactoglobulin         Median 6.3 2.4 0.1 .02 3.9 1.9 3.5 .01 Range 0.11-54.7 0-238 0.1-2.4  0.2-81.1 0.1-80.5 0.1-13.7  Table E1 Study participants' characteristics Diagnostic test First cohort (n = 97) Second cohort (n = 128) Specific IgE to CM Specific IgE to casein Specific IgE to β-lactoglobulin Specific IgE to CM Specific IgE to casein Specific IgE to β-lactoglobulin AUCs 80.8% 84.1% 79.5% 73.7% 77.6% 67.8% Optimal cutoff pointlow * 4.7 4.9 2.4 10.1 10.7 0.5 Sensitivity, specificity 73.9%, 77.0% 78.3%, 82.4% 65.2%, 86.5% 65.8%, 81.1% 60.5%, 87.8% 81.6%, 52.2% PPV, NPV 50.0%, 90.5% 58.1%, 92.4% 60.0%, 88.9% 59.5%, 84.9% 67.7%, 84.0% 41.9%, 87.0% Positive decision pointdagger 28.4 21.4 6.1 25.3 20.2 7.9 Sensitivity, specificity 34.8%, 96.0% 39.1%, 96.0% 43.5%, 96.0% 21.1%, 95.6% 23.7%, 95.6% 10.5%, 95.6% PPV, NPV 72.7%, 82.6% 75.0%, 83.5% 76.9%, 84.5% 66.7%, 74.1% 69.2%, 74.8% 50.0%, 71.7% Negative decision pointdouble dagger 0.8 1.0 ND 1.21 0.7 ND Sensitivity, specificity 95.7%, 23.0% 95.7%, 44.6%  97.4%, 20.0% 97.4%, 21.1%  PPV, NPV 27.9%, 94.4% 34.9%, 97.1%  33.9%, 94.7% 34.3%, 95.0%  Table E2 Characteristics of diagnostic tests for determination of clinical reactivity to baked milk ND, Not determined because the highest sensitivity is less than 95%; NPV, negative predictive value; PPV, positive predictive value.
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.
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.
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.
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.
Objective To test the hypothesis that the blastulation rate is higher in euploid embryos than in aneuploid embryos as assessed by cleavage-stage biopsy with array-comprehensive genomic hybridization ...(aCGH). Design Retrospective cohort study. Setting University-affiliated institution. Patient(s) Forty-one patients with 48 in vitro fertilization (IVF) cycles and 385 embryos that underwent cleavage-stage preimplantation genetic screening (PGS) with aCGH at the Continuum Reproductive Center between January 2010 and September 2013. Intervention(s) None. Main Outcome Measure(s) Probability of blastocyst and/or fully expanded or hatching blastocyst (FEHB) progression depending on number of chromosomal abnormalities. Result(s) Euploid embryos are twice as likely to progress to blastocyst and three times as likely to progress to FEHB than aneuploid embryos: 76% versus 37% and 56% versus 18%, respectively. For every additional chromosomal abnormality, the likelihood of progressing to the blastocyst stage decreases by 22% and the likelihood of progressing to FEHB decreases by 33%. Conclusion(s) Euploid embryos are far more likely than aneuploid embryos to progress to the blastocyst and FEHB stages. There is a linear decrease in probability of blastulation with the increasing number of chromosomal abnormalities.
Objective We sought to determine if insulin detemir (IDet) is noninferior to insulin neutral protamine Hagedorn (NPH) for the treatment of gestational diabetes mellitus (GDM) and type 2 diabetes ...mellitus (T2DM) in pregnancy. Study Design We conducted a randomized, controlled noninferiority trial of women with GDM and T2DM who entered our Diabetes in Pregnancy Program from March 2013 through October 2014. Exclusion criteria were type 1 diabetes, age <18 years, and insulin allergy. Women who failed to achieve good glycemic control (GC) (mean blood glucose BG <100 mg/dL) on diet and/or hypoglycemic agents were randomized to receive either IDet or NPH, with short-acting insulin aspart added as needed. Patients were instructed to test BG 4 times a day (fasting and 2-hour postprandial). Targets of GC were fasting BG <90 mg/dL and postprandial BG <120 mg/dL, and insulin was adjusted as needed to achieve the targets. The primary outcome was overall mean BG during insulin treatment; secondary outcomes included overall mean postprandial and fasting BG, median number of weeks to achieve GC, percent of patients with overall GC, maternal weight gain, perinatal/neonatal outcomes, and number of hypoglycemic events. Power analysis (90% power) determined that 88 patients would need to be randomized, assuming a maximal acceptable difference in overall mean BG of 7 mg/dL (SD ± 10 mg/dL). A per protocol analysis was performed. Results In all, 105 women were randomized. Eighteen women were excluded leaving 87 participants for analysis (45 NPH, 42 IDet). Maternal characteristics were similar in both groups. The difference in the mean BG of the groups was 2.1 mg/dL with a 1-sided upper 95% confidence limit of 5.5 mg/dL (less than the maximal acceptable difference of 7 mg/dL; P = .2937). There was no significant difference in the primary outcome when an intent-to-treat analysis was performed or when the T2DM patients were excluded. The time to achieve GC was similar in both groups. There were no differences in perinatal outcomes and maternal weight gain among the groups. There were more hypoglycemic events per patient in the NPH group. Conclusion IDet is noninferior to insulin NPH for the treatment of GDM and T2DM in pregnancy.
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