Correlation of the Ki67 Working Group prognostic risk categories with the Oncotype DX Recurrence Score in early breast cancer.

BACKGROUND: The relationship between Ki67 assessed by immunohistochemistry (IHC) and the Oncotype DX Recurrence Score (RS) is unclear. The objective of this study was to determine the correlation between the 21-gene RS and IHC-measured Ki67 with the prognostic classification groups recommended by the International Ki67 Working Group (IKWG). METHODS: The authors performed a retrospective chart review of women who had hormone receptor (HR)-positive, human epidermal growth factor receptor 2-negative early breast cancer with zero to three positive lymph nodes and both Ki67 and the 21-gene RS performed at their institution from 2013 to 2021. Patients were categorized into low (≤5%), intermediate (6%-29%), and high Ki67 groups (≥30%) according to IKWG recommendations. Overall agreement and risk-stratified agreement between Ki67 and RS were assessed with the proportion of agreement and the κ statistic. RESULTS: The study included 525 patients with HR-positive breast cancer. Among the 49% of patients with intermediate Ki67 values of 6%-29%, the distribution of low (0-10), intermediate (11-25), and high RS (26-100) was 19%, 66%, and 15%, respectively. There was slight agreement (κ = 0.01-0.20) between Ki67 and RS (κ = 0.027) in the overall population, although this was not significant (p = .1985). There was fair agreement (κ = 0.21-0.40) between high Ki67 and RS values (κ = 0.280; p < .0001). A higher progesterone receptor percentage was associated with lower RS values (p > .0001) but not lower Ki67 values. A positive nodal status and a larger tumor size were associated with higher Ki67 values (p = .0059 and p < .0001) but not with RS. CONCLUSIONS: In this group of patients selected to have a 21-gene RS, there was no significant correlation between Ki67 and RS in the overall population, and there was fair agreement between high Ki67 and high RS values. LAY SUMMARY: In patients with early-stage, hormone receptor-positive breast cancer, decisions on adjuvant chemotherapy are based on certain biological features of the cancer and genomic assays such as the Oncotype DX Recurrence Score (RS). The goal of this study was to determine the correlation between Ki67, a marker of proliferation, and the Oncotype DX RS, a 21-gene assay demonstrated to be predictive of an adjuvant chemotherapy benefit in patients with early-stage breast cancer. In 525 patients, the authors did not find a significant correlation between Ki67 and RS.

INTRAVENOUS PAMIDRONATE IS ASSOCIATED WITH REDUCED MORTALITY IN PATIENTS WITH CHRONIC CRITICAL ILLNESS.

OBJECTIVE: Chronic critical illness (CCI), characterized by prolonged mechanical ventilation and tracheostomy, commonly manifests with elevated bone resorption, which has previously been shown to abate after treatment with intravenous (IV) bisphosphonates. Our study assessed the impact of pamidronate administration on clinical outcomes in a CCI cohort. METHODS: A retrospective case series was performed on 148 patients admitted to The Mount Sinai Hospital Respiratory Care Unit (RCU) from 2009-2010. We identified patients with CCI who did (n = 30) or did not (n = 118) receive IV pamidronate (30 to 90 mg). Both groups included patients with normal and abnormal renal function. Pamidronate was administered for elevated urine or serum N-telopeptide, hypercalciuria, or hypercalcemia. RESULTS: RCU and 1-year mortality were significantly lower in the pamidronate group (0 and 20%, respectively) compared to nonreceivers (19 and 56%, respectively) (P = .0077 and P = .0004, respectively). After adjusting for differences in baseline creatinine, estimated glomerular filtration rate, and serum calcium, the association with reduced mortality remained significant at 1 year (P = .0132) and with borderline significance for RCU mortality (P = .0911). Creatinine was significantly lower 7 days following pamidronate administration (P = .0025), with no significant difference at 14 days compared to baseline. Pamidronate receivers showed a greater increase in albumin during the RCU stay (2.49 to 3.23 g/dL), compared to nonreceivers (2.43 to 2.64 g/dL) (P = .0007). Pamidronate administration was associated with a significantly reduced rate of hypoglycemia compared to RCU patients not receiving pamidronate (0.09 versus 0.12; P = .0071). CONCLUSION: Pamidronate use in a CCI population is associated with reduced mortality, lower hypoglycemia rates, improved albumin, and stable renal function. ABBREVIATIONS: BMI = body mass index CCI = chronic critical illness CI = confidence interval CKD = chronic kidney disease CTx = C-telopeptide eGFR = estimated glomerular filtration rate ICU = intensive care unit IV = intravenous NTx = N-telopeptide PMV = prolonged mechanical ventilation RCU = respiratory care unit.

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

BACKGROUND: 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. METHODS: Data were collected using an electronic data-capture platform from 28 international centers. Eligible patients had clinical T-classification 2 (cT2) through cT4aN0M0 urothelial cancer of the bladder and received neoadjuvant GC or methotrexate, vinblastine, doxorubicin, plus cisplatin (MVAC) before undergoing cystectomy. Logistic regression was used to compute propensity scores as the predicted probabilities of patients being assigned to MVAC versus GC given their baseline characteristics. These propensity scores were then included in a new logistic regression model to estimate an adjusted odds ratio comparing the odds of attaining a pathologic complete response (pCR) between patients who received MVAC and those who received GC. RESULTS: In total, 212 patients (146 patients in the GC cohort and 66 patients in the MVAC cohort) met criteria for inclusion in the analysis. The majority of patients in the MVAC cohort (77%) received dose-dense MVAC. The median age of patients was 63 years, they were predominantly men (74%), and they received a median of 3 cycles of neoadjuvant chemotherapy. The pCR rate was 29% in the MVAC cohort and 31% in the GC cohort. There was no significant difference in the pCR rate when adjusted for propensity scores between the 2 regimens (odds ratio, 0.91; 95% confidence interval, 0.48-1.72; P = .77). In an exploratory analysis evaluating survival, the hazard ratio comparing hazard rates for MVAC versus GC adjusted for propensity scores was not statistically significant (hazard ratio, 0.78; 95% confidence interval, 0.40-1.54; P = .48). CONCLUSIONS: Patients who received neoadjuvant GC and MVAC achieved comparable pCR rates in the current analysis, providing evidence to support what has become routine practice.

Randomized controlled double-blind trial of transversus abdominis plane block versus trocar site infiltration in gynecologic laparoscopy.

OBJECTIVE: The objective of the study was to determine whether transversus abdominis plane (TAP) block reduces postoperative pain when compared with trocar site infiltration of bupivacaine in gynecological laparoscopy. STUDY DESIGN: This was a prospective, randomized, double-blinded clinical trial using patients as their own controls. Women undergoing gynecologic laparoscopy using a 4-port symmetrical technique were randomly assigned to right- or left-sided TAP block using 30 mL of 0.25% bupivacaine with epinephrine. Two cohorts of patients were studied. Cohort 1 consisted of anesthesiologist-administered ultrasound-guided TAP block. Cohort 2 consisted of surgeon-administered laparoscopic-guided TAP block. In both cohorts, contralateral port sites were infiltrated with an equal amount of bupivacaine in divided doses. All patients received intraoperative acetaminophen and ketorolac. Postoperative abdominal pain was assessed at 1, 2, 4, 6, 8, 12, 18, 24, and 48 hours on the block and contralateral sides, before and after palpation, using the 10 point visual analog scale. A 2 point difference in the reported pain scores was considered clinically meaningful. RESULTS: Eighty-eight patients were eligible for statistical analysis: 45 and 43 patients in cohorts 1 and 2, respectively. In both cohorts, most patients reported equal pain on the block side and local side. In cohort 1, there was a statistically significant difference in mean reported pain scores at 2 hours and across time favoring the ultrasound-guided block; however, this did not reach clinical significance. There was no statistically significant difference found at all other time points or when pain scores were objectively assessed after palpation of the incisions. When comparing laparoscopic-guided block with local infiltration, there was no statistically significant difference in reported mean pain scores at all time points or after palpation. CONCLUSION: As part of this multimodal analgesic regimen, neither block method provided a significant clinical benefit compared with trocar site bupivacaine infiltration.

Randomized controlled trial of insulin detemir versus NPH for the treatment of pregnant women with diabetes.

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.

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.

Long-term outcome of ablation of anal high-grade squamous intraepithelial lesions: recurrence and incidence of cancer.

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.

Association of glycemic control parameters with clinical outcomes in chronic critical illness.

OBJECTIVE: Chronic critical illness (CCI) is a term used to designate patients requiring prolonged mechanical ventilation and tracheostomy with associated poor outcomes. The present study assessed the impact of glycemic parameters on outcomes in a CCI population. METHODS: A retrospective case series was performed including 148 patients in The Mount Sinai Hospital Respiratory Care Unit (2009-2010). Utilizing a semi-parametric mixture model, trajectories for the daily mean blood glucose (BG), BG range, and hypoglycemia rate over time identified low- (n = 87) and high-risk (n = 61) hyperglycemia groups and low- (n = 90) and high-risk (n = 58) hypoglycemia groups. The cohort was also classified into diabetes (DM, n = 48), stress hyperglycemia (SH, n = 85), and normal glucose (n = 15) groups. RESULTS: Hospital- (28% vs. 13%, P = .0199) and 1-year mortality (66% vs. 46%, P = .0185) rates were significantly greater in the high- versus low-risk hyperglycemia groups, respectively. The hypoglycemia rate (<70 mg/dL) was lower among ventilator-liberated patients compared to those who failed to liberate (0.092 vs. 0.130, P<.0001). In the SH group, both hospital mortality (high-risk hyperglycemia 48% and low-risk hyperglycemia 15%, P = .0013) and 1-year mortality (high-risk 74% and low-risk 50%, P = .0482) remained significantly different, while no significant difference in the diabetes group was observed. There were lower hypoglycemia rates with SH compared to diabetes (<70 mg/dL: 0.086 vs. 0.182, P<.0001; <40 mg/dL: 0.012 vs. 0.022, P = .0118, respectively). CONCLUSION: Tighter glycemic control was associated with improved outcomes in CCI patients with SH but not in CCI patients with diabetes. Confirmation of these findings may lead to stratified glycemic control protocols in CCI patients based on the presence or absence of diabetes.

Misperceptions about the risks of abortion in women presenting for abortion.

OBJECTIVE: Misinformation about the risks and sequelae of abortion is widespread. The purpose of this study was to examine whether women having an abortion who believe that there should be restrictions to abortion (i.e., that some other women should not be allowed to have an abortion) also believe this misinformation about the health risks associated with abortion. METHODS: We carried out a cross-sectional survey of women presenting consecutively for an abortion at an urban abortion clinic in Vancouver, British Columbia, between February and September 2012. RESULTS: Of 1008 women presenting for abortion, 978 completed questionnaires (97% response rate), and 333 of these (34%) favoured abortion restrictions. More women who favoured restrictions believed that the health risk of an abortion was the same as or greater than the health risk of childbirth (84.2% vs. 65.6%, P < 0.001), that abortion caused mental health problems (39.1% vs. 28.3%, P < 0.001), and that abortion caused infertility (41.7% vs. 21.9%, P < 0.001). Using multivariate logistic regression analyses, believing that abortion should not be restricted was found to be a significantly correlated with correct answers about health risks, mental health problems, and infertility. CONCLUSION: Misinformed beliefs about the risks of abortion are common among women having an abortion. Women presenting for abortion who favoured restrictions to abortion have more misperceptions about abortion risks than women who favour no restrictions.

Objectif : La désinformation au sujet des risques et des séquelles de l'avortement est généralisée. Cette étude avait pour objectif de tenter de déterminer si les femmes subissant un avortement qui estiment que des restrictions devraient être imposées en matière d'avortement (c.-à-d. qui estiment que certaines autres femmes ne devraient pas avoir le droit de subir un avortement) sont susceptibles de croire cette désinformation au sujet des risques pour la santé qui sont associés à l'avortement. Méthodes : Nous avons mené un sondage transversal auprès des femmes s'étant consécutivement présentées à une clinique urbaine d'avortement de Vancouver, en Colombie-Britannique, entre février et septembre 2012, en vue d'y obtenir un avortement. Résultats : Des 1 008 femmes s'étant présentées à cette clinique en vue d'y obtenir un avortement, 978 ont rempli le questionnaire (taux de réponse de 97 %) et 333 d'entre elles (34 %) favorisaient l'imposition de restrictions en matière d'avortement. Un nombre supérieur de femmes favorisant l'imposition de restrictions estimaient que les risques pour la santé associés à l'avortement étaient égaux ou supérieurs aux risques pour la santé associés à l'accouchement (84,2 % vs 65,6 %, P < 0,001), que l'avortement causait des problèmes de santé mentale (39,1 % vs 28,3 %, P < 0,001) et que l'avortement causait l'infertilité (41,7 % vs 21,9%, P < 0,001). En utilisant des analyses de régression logistique multivariées, nous avons constaté que le fait d'estimer que l'avortement ne devrait pas faire l'objet de restrictions était en corrélation significative avec l'offre de réponses exactes au sujet des risques pour la santé, des problèmes de santé mentale et de l'infertilité. Conclusion : Les opinions erronées au sujet des risques de l'avortement sont courantes chez les femmes qui subissent un avortement. Les femmes cherchant à obtenir un avortement qui favorisent l'imposition de restrictions à l'avortement sont plus susceptibles d'avoir des perceptions erronées, au sujet des risques de l'avortement, que les femmes qui ne favorisent pas l'imposition de telles restrictions.

Trends and variations in utilization of nephron-sparing procedures for stage I kidney cancer in the United States.

PURPOSE: The incidental detection of early-stage kidney tumors is increasing in the United States. Nephron-sparing approaches (NS) to managing these tumors are equivalent to radical nephrectomy (RN) in oncologic outcomes and have a decreased impact on renal function. Our objective was to evaluate trends in the use of NS over the past decade and the socioeconomic factors associated with its use. METHODS: The National Cancer Database was queried to identify patients with stage I kidney cancer between 2000 and 2008. Patients were classified by the type of surgery as NS (local destruction and local excision) or RN. Patients were further categorized by age, race, insurance status, and income. Log-binomial regression was used to estimate prevalence ratios (PR) for the proportion of NS to RN according to demographic and socioeconomic characteristics. RESULTS: From 2000 to 2008, there were 142,194 cases of kidney cancer reported to the NCDB. In these cases, 43,034 (30.3 %) patients had NS, and 86,431 (60.78 %) patients had RN. The prevalence of NS increased 10 % per year (PR = 1.10, p < 0.0001)-from 20.0 % in 2000 to 45.1 % in 2008. Older age, lower income, Black race, Hispanic ethnicity, and lack of health insurance were associated with a decreased prevalence of NS. CONCLUSIONS: NS as a treatment for stage I kidney cancer has increased steadily since 2000. Age, racial, and socioeconomic differences may exist in the utilization of NS. Additional analyses, with patient level data, are required to address the independent significance of these variables in an effort to develop strategies to mitigate these potential disparities.

Cytoreductive nephrectomy for metastatic renal cell carcinoma in the era of targeted therapy in the United States: a SEER analysis.

PURPOSE: Two randomized trials published in 2001 provided level 1 evidence for the use of cytoreductive nephrectomy (CyNx) for the treatment of metastatic renal cell carcinoma (mRCC). However, the regulatory approval of vascular endothelial growth factor tyrosine kinase inhibitors (VEGFR-TKI) in 2005 has left an "evidence void" regarding the use of CyNx. We evaluated the patterns in the use of CyNx in the cytokine and VEGFR-TKI eras, and the patient characteristics associated with the use of CyNx. METHODS: The Surveillance, Epidemiology, and End Results registry was used to identify patients with histologically or cytologically confirmed stage IV RCC between 2001 and 2008. Patients were classified as treated during the cytokine (2001-2005) or VEGFR-TKI (2006-2008) eras. A multivariate logistic regression analysis was performed to calculate the odds of undergoing CyNx according to treatment era and socioeconomic characteristics. RESULTS: Overall, 1,112 of 2,448 patients (45%) underwent CyNx. CyNx use remained stable between 2001 and 2005 (50%), but decreased to 38% in 2008. Logistic regression analysis revealed that older age (OR 0.82, 95% CI: 0.68, 0.99), black race (OR 0.64, 95% CI: 0.46, 0.91), Hispanic ethnicity (OR 0.71, 95% CI: 0.54, 0.93), and treatment in the VEGFR-TKI era (OR 0.82, 95% CI: 0.68, 0.99) were independently associated with decreased use of CyNx. CONCLUSIONS: Use of CyNx in the United States has declined in the VEGFR-TKI era. Older patients and minorities are less likely to receive CyNx. Results of ongoing phase III trials are needed to refine the role of this treatment modality.

Preimplantation genetic screening (PGS) with Comparative genomic hybridization (CGH) following day 3 single cell blastomere biopsy markedly improves IVF outcomes while lowering multiple pregnancies and miscarriages.

PURPOSE: To determine benefits of cleavage-stage preimplantation genetic screening (PGS) by array comparative genomic hybridization (CGH). METHODS: A retrospective case-control study was performed at a tertiary care university-affiliated medical center. Implantation rate was looked at as a primary outcome. Secondary outcomes included clinical and ongoing pregnancy rates, as well as multiple pregnancy and miscarriage rates. Thirty five patients underwent 39 fresh cycles with PGS by aCGH and 311 similar patients underwent 394 invitro fertilization cycles. RESULT(S): The implantation rate in the CGH group doubled when compared to the control group (52.63 % vs. 19.15 %, p = < 0.001), clinical pregnancy rate was higher (69.23 % vs. 43.91 %, p = 0.0002), ongoing pregnancy rate almost doubled (61.54 % vs. 32.49 %, p = < 0.0001), multiple pregnancy rate decreased (8.33 % vs. 34.38 %, p = 0.0082) and miscarriage rate trended lower (11.11 % vs. 26.01 %, p = 0.13). CONCLUSION: Cleavage stage PGS with CGH is a feasible and safe option for aneuploidy screening that shows excellent outcomes when used in fresh cycles. This is the first report of cleavage stage PGS by CGH showing improved ongoing pregnancy rates.

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.

Prevalence and characteristics of patients with metastatic cancer who receive no anticancer therapy.

BACKGROUND: A subset of patients who present with metastatic solid tumors never receive anticancer therapy. Reasons may include poor functional status, comorbidities, and patient preference. To the authors' knowledge, the prevalence and characteristics of this population have not previously been described. METHODS: The National Cancer Data Base was queried for patients diagnosed with metastatic (stage IV according to the American Joint Committee on Cancer) solid tumors (including those of the breast, cervix, colon, and kidney; small cell and nonsmall cell lung cancer [NSCLC]; and tumors of the prostate, rectum, and uterus) who received neither radiotherapy nor systemic therapy. Log-binomial regression analysis was used to estimate prevalence ratios (PRs) for the percentage of untreated to treated patients with stage IV cancer. RESULTS: Between 2000 and 2008, 773,233 patients with stage IV cancer were identified, 159,284 of whom (20.6%; 95% confidence interval, 20.5%-20.7%) received no anticancer therapy. Patients with NSCLC accounted for 55% of the untreated population. Patients with cancers of the kidney and lung had the highest rates of no treatment at 25.5% and 24.0%, respectively, whereas patients with prostate cancer had the lowest rate of no treatment at 11.1%. Across all cancer types, older age (PR range, 1.37-1.49; all P < .001), black race (PR range, 1.05-1.32; all P < .001), lack of medical insurance (PR range, 1.47-2.46; all P < .001), and lower income (except for cancer of the uterus; PR range, 0.91-0.98 for every $10,000-increase in income [all P < .001]) were associated with a lack of treatment. CONCLUSIONS: Approximately 20% of patients who present with stage IV solid tumors do not receive anticancer therapy. Although there are likely multiple reasons for this lack of treatment, including appropriate indications, these findings have potential implications with regard to health care policy and access to care.

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.

Dietary baked milk accelerates the resolution of cow's milk allergy in children.

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 IgG(4) 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.

Filanesib plus bortezomib and dexamethasone in relapsed/refractory t(11;14) and 1q21 gain multiple myeloma.

Filanesib is a first-in-class kinesin spindle protein inhibitor which demonstrated safety and encouraging activity in combination with bortezomib and dexamethasone in relapsed/refractory multiple myeloma in a preliminary analysis of dose-escalation phase results. This multicenter study included first a dose-escalation phase to determine maximum tolerated dose of two schedules of filanesib, bortezomib, and dexamethasone and a subsequent dose-expansion phase using the maximum tolerated doses. In the dose-expansion phase, 28 patients were evaluable for safety and efficacy. The most common grade ≥3 adverse events were neutropenia (21%) and anemia (18%), which were noncumulative and reversible, and hypertension (18%). The overall response rate was 43% with median duration of response not yet reached (range, 2.8-23.7+ months) with median follow-up of 6.3 months. A post hoc analysis incorporated 29 dose-escalation phase patients who received therapeutic filanesib doses, with an overall response rate of 39% and median duration of response of 18.0 months among the 57 total patients with median progression-free survival of 8.5 months. Notably, the PFS of high risk patients was comparable at 8.5 months, driven by the patients with 1q21 gain, characterized by increased MCL-1 expression, with a PFS of 9.1 months versus 3.5 months for the remainder of high risk patients. Patients with t(11;14) also had an encouraging PFS of 15.0 months. The combination of filanesib, bortezomib, and dexamethasone continues to show safety and encouraging activity in relapsed/refractory multiple myeloma, particularly in those patients with 1q21 gain and t(11;14).

Gender and respiratory findings in workers occupationally exposed to organic aerosols: a meta analysis of 12 cross-sectional studies.

BACKGROUND: Gender related differences in respiratory disease have been documented. The aim of this study was to investigate gender related differences in respiratory findings by occupation. We analyzed data from 12 of our previously published studies. METHODS: Three thousand and eleven (3011) workers employed in "organic dust" industries (1379 female and 1632 male) were studied. A control group of 806 workers not exposed to any kind of dust were also investigated (male = 419, female = 387). Acute and chronic respiratory symptoms and lung function were measured. The weighted average method and the Mantel-Haentszel method were used to calculate the odds ratios of symptoms. Hedge's unbiased estimations were used to measure lung function differences between men and women. RESULTS: There were high prevalences of acute and chronic respiratory symptoms in all the "dusty" studied groups compared to controls. Significantly less chronic cough, chronic phlegm as well as chronic bronchitis were found among women than among men after the adjustments for smoking, age and duration of employment. Upper respiratory tract symptoms by contrast were more frequent in women than in men in these groups. Significant gender related lung function differences occurred in the textile industry but not in the food processing industry or among farmers. CONCLUSION: The results of this study suggest that in industries processing organic compounds there are gender differences in respiratory symptoms and lung function in exposed workers. Whether these findings represent true physiologic gender differences, gender specific workplace exposures or other undefined gender variables not defined in this study cannot be determined. These data do not suggest that special limitations for women are warranted for respiratory health reasons in these industries, but the issue of upper respiratory irritation and disease warrants further study.

Ten Essential Practices for Developing or Reforming a Biostatistics Core for a NCI Designated Cancer Center.

There are 69 National Cancer Institute (NCI) designated Cancer Centers (CCs) in the United States. Biostatistical collaboration is pivotal in cancer research, and support for a cancer biostatistics shared resource facility (C-BSRF) is included in the award. Although the services and staff needed in a C-BSRF have been outlined in general terms and best practices for biostatistical consultations and collaboration in an academic health center have been agreed upon, implementing these practices in the demanding setting of cancer centers interested in pursuing or maintaining NCI designation remains challenging. We surveyed all C-BSRF websites to assess their organizational charts, governance, size, services provided, and financial models and have identified 10 essential practices for the development of a successful C-BSRF. Here, we share our success with, and barriers to, implementation of these practices. Showcasing development plans for these essential practices resulted in an NCI score of "Excellent to Outstanding" for our C-BSRF in 2015, and performance metrics in 2016-2017 demonstrated notable improvement since our original Cancer Center Support Grant (CCSG) application in 2014. We believe that the essential practices described here can be adapted and adjusted, as needed, for CCs of various sizes and with different types of cancer research programs.

Neurologic injury and patient displacement in gynecologic laparoscopic surgery using a beanbag and shoulder supports.

OBJECTIVE: To quantify the incidence of peripheral neuropathy in gynecologic laparoscopic surgery using a combination of beanbag, eggcrate foam, and shoulder supports; and to assess patient displacement during surgery in a steep Trendelenburg position and determine variables correlated with displacement. METHODS: A retrospective study included all gynecologic laparoscopic surgeries performed by one high-volume surgeon at a US center between September 15, 2007, and September 15, 2012. Data included neurologic deficits or extremity pain, any other complications, and-for the final study year-surgical time as well as patient and beanbag displacement. RESULTS: Among 967 patients, no long-term neuropathy was reported, 6 (0.6%) patients had transient shoulder pain beyond the first 24 hours (resolved by initial postoperative visit), and 7 (0.7%) were lost to follow-up. No neurologic complications were reported. Median beanbag and total patient displacement were 0 cm (interquartile range 0-0) and 0 cm (interquartile range 0-2), respectively. Patient displacement relative to the table was correlated with the total surgical time (P=0.025) and patient weight (P=0.023). The median displacement was greater in hysterectomy than non-hysterectomy procedures (P=0.003). CONCLUSION: Use of beanbags with shoulder supports and convoluted foam armboard pads was associated with minimal patient displacement and risk of arm and leg neurologic injury.