Log-epsilon-skew normal: A generalization of the log-normal distribution.

The log-normal distribution is widely used to model non-negative data in many areas of applied research. In this paper, we introduce and study a family of distributions with non-negative reals as support and termed the log-epsilon-skew normal (LESN) which includes the log-normal distributions as a special case. It is related to the epsilon-skew normal developed in Mudholkar and Hutson (2000) the way the log-normal is related to the normal distribution. We study its main properties, hazard function, moments, skewness and kurtosis coefficients, and discuss maximum likelihood estimation of model parameters. We summarize the results of a simulation study to examine the behavior of the maximum likelihood estimates, and we illustrate the maximum likelihood estimation of the LESN distribution parameters to two real world data sets.

Omalizumab versus Mepolizumab as add-on therapy in asthma patients not well controlled on at least an inhaled corticosteroid: A network meta-analysis.

OBJECTIVE: The purpose of this study is to examine the comparative efficacy of Omalizumab (OMA) and Mepolizumab (Mepo) in the treatment of severe asthma by performing a network meta-analysis. METHOD: Data Sources: A systematic review of the literature was performed through four databases from their inception to February 2016. STUDY SELECTIONS: Randomized control trials and cohort studies were considered if they addressed the individual efficacy of OMA and Mepo in the treatment of asthma that was not well controlled on inhaled corticosteroids (ICSs) with or without other agents. RESULTS: OMA was significantly better than Mepo in improving the Asthma Quality of Life Questionnaire with a mean difference of 0.38 and a confidence interval of (0.21-0.55), p < 0.0001, without reaching the minimal clinically important difference of 0.5. No significant difference was seen in Asthma Control Questionnaire, forced expiratory volume in second 1 (FEV1), and Peak Expiratory Flow Rate (PEFR) improvement from baseline. Both medications were successful in reducing the calculated annualized rates of asthma exacerbations (AEs) vs placebo by approximately 50%. The heterogeneity score for the different comparisons were elevated except for the PEFR. CONCLUSION: When compared indirectly via a network meta-analysis, the efficacy of OMA and Mepo was similar in the treatment of asthma that was not well controlled on at least high-dose ICS. The high heterogeneity observed and the different selection criteria for the use of the two drugs do not permit us to make any definitive recommendations for the preferential use of OMA vs Mepo in the patient populations studied. However, the current data do not suggest any major differences in efficacy.

Efficacy of 4 Irrigation Protocols in Killing Bacteria Colonized in Dentinal Tubules Examined by a Novel Confocal Laser Scanning Microscope Analysis.

INTRODUCTION: The aim of this study was to determine the efficiency of 4 irrigation systems in eliminating bacteria in root canals, particularly in dentinal tubules. METHODS: Roots of human teeth were prepared to 25/04, autoclaved, and inoculated with Enterococcus faecalis for 3 weeks. Canals were then disinfected by (1) standard needle irrigation, (2) sonically agitating with EndoActivator, (3) XP Endo finisher, or (4) erbium:yttrium aluminum garnet laser (PIPS) (15 roots/group). The bacterial reduction in the canal was determined by MTT assays. For measuring live versus dead bacteria in the dentinal tubules (4 teeth/group), teeth were split open and stained with LIVE/DEAD BackLight. Coronal, middle, and apical thirds of the canal dentin were scanned by using a confocal laser scanning microscope (CLSM) to determine the ratio of dead/total bacteria in the dentinal tubules at various depths. RESULTS: All 4 irrigation protocols significantly eliminated bacteria in the canal, ranging from 89.6% to 98.2% reduction (P < .001). XP Endo had the greatest bacterial reduction compared with other 3 techniques (P < .05). CLSM analysis showed that XP Endo had the highest level of dead bacteria in the coronal, middle, and apical segments at 50-µm depth. On the other hand, PIPS had the greatest bacterial killing efficiency at the 150-µm depth in all 3 root segments. CONCLUSIONS: XP Endo appears to be more efficient than other 3 techniques in disinfecting the main canal space and up to 50 µm deep into the dentinal tubules. PIPS appears to be most effective in killing the bacteria deep in the dentinal tubules.

Factors Associated With Problems for Adolescents Returning to the Classroom After Sport-Related Concussion.

The primary objective of this study was to determine factors in the clinic setting associated with concussion-related problems in the school setting. A total of 91 student athletes, 13 to 19 years old, completed the SCAT2 and computerized testing during their initial visit to the clinic. During a follow-up telephone interview, one-third reported problems with return to school. The presence of problems reported in school was associated with severity of concussion as represented by recovery time and the overall number of symptoms at the first clinic visit. Gender, age, and previous concussions were not associated with school problems. Athletes with computerized test scores below the ninth percentile were more likely to report school problems. The current study offers some descriptive information for clinicians and ideas for future research related to adolescent athletes with concussion and problems with return to the classroom.

Does Suture Technique Affect Re-Rupture in Arthroscopic Rotator Cuff Repair? A Meta-analysis.

PURPOSE: To evaluate the effects of suture configuration, repair method, and tear size on rotator cuff (RC) repair healing. METHODS: We conducted a literature search of articles that examined surgical treatment of RC tears published between January 2003 and September 2014. For single-row (SR) repairs, we calculated rerupture rates for simple, mattress, and modified Mason-Allen sutures while stratifying by tear size. All double-row repairs-those using 2 rows of suture anchors (DA) and those using a suture bridge (SB)--were performed using mattress sutures, and we compared rerupture rates by repair method while stratifying by tear size. A random-effects model with pooled estimates for between-study variance was used to estimate the overall rerupture proportion and corresponding 95% confidence interval for each group. Statistical significance was defined as P < .05. RESULTS: A total of 682 RC repairs from 13 studies were included. For SR repairs of tears measuring less than 3 cm, there was no significant difference in rerupture rates for modified Mason-Allen sutures versus simple sutures (P = .18). For SR repairs of tears measuring 3 cm or more, there was no significant difference in rerupture rates for mattress sutures versus simple sutures (P = .23). The rates of rerupture did not differ between SB and DA repairs for tears measuring less than 3 cm (P = .29) and 3 cm or more (P = .50). CONCLUSIONS: For SR repairs, there were no significant differences in rerupture rates between suture techniques for any repair method or tear size. All DA and SB repairs were secured with mattress sutures, and there were no differences in the rates of rerupture between these methods for either size category. These findings suggest that suture technique may not affect rerupture rates after RC repair. LEVEL OF EVIDENCE: Level IV, systematic review of Level I through IV studies.

Measures of biomarker dependence using a copula-based multivariate epsilon-skew-normal family of distributions.

In this note we develop a new multivariate copula model based on epsilon-skew-normal marginal densities for the purpose of examining biomarker dependency structures. We illustrate the flexibility and utility of this model via a variety of graphical tools and a data analysis example pertaining to salivary biomarker. The multivariate normal model is a sub-model of the multivariate epsilon-skew-normal distribution.

Breast cancer resistance protein (BCRP) and excision repair cross complement-1 (ERCC1) expression in esophageal cancers and response to cisplatin and irinotecan based chemotherapy.

BACKGROUND: Esophageal cancer patients face a dismal outcome despite tri-modality management and median survival remains 15-18 months. Breast cancer resistance protein (BCRP) is an ATP-dependent efflux protein associated with chemotherapy resistance. The role of BCRP expression in esophageal cancer and normal esophageal cells is not known. Excision repair cross complement-1 (ERCC1) overexpression has been correlated with poorer response to cisplatin based chemotherapy. We examined the expression of BCRP and ERCC1 in patients with esophageal cancer and correlated it with survival in patients receiving irinotecan and cisplatin based chemotherapy. METHODS: With IRB approval, 40 cases of esophageal cancer diagnosed from 2004-2008, were stained for BCRP and ERCC1 expression by immunohistochemistry and scored by a pathologist blinded to clinical data. Baseline demographics, therapy given and survival data were collected and correlated with BCRP and ERCC1 expression. Fisher's exact test was used to determine association between BCRP and ERCC1 expression and demographics. Cox proportional hazards model was used for association of BCRP and ERCC1 with survival. RESULTS: On immunohistochemistry, 30/40 cancers (75%) expressed BCRP. Interestingly, down-regulation of BCRP expression in tumor compared with normal cells was seen in 40% of patients. ERCC1 positivity was seen in 15/30 cases (50%). Median overall survival (OS) was 19 months with no difference in survival between BCRP positive and negative patients (P=0.13) or ERCC1 positive and negative patients (P=0.85). Estimated hazard ratio (HR) of death for BRCP positive patients was 2.29 (95% CI: 0.79-6.64) and for ERCC1 positive patients was 1.09 (95% CI: 0.46-2.56). There was no association of BCRP and ERCC1 expression with disease stage, age, gender or histology. For patients who received cisplatin and irinotecan as first line chemotherapy, there was no difference in survival based on BCRP or ERCC1 status. CONCLUSIONS: BCRP expression is seen in a majority of esophageal cancers and normal esophageal mucosa. ERCC1 expression is seen in about half of the patients with esophageal cancer. Irinotecan based studies with esophageal and gastric cancer suggest response rates of 14-65%. Whether the 40% of tumors in our study found with down regulation of BCRP expression, constitute a majority of these responders needs to be prospectively validated in a larger data set. It should include markers such as ERCC1 predicting response to 5-fluorouracil and platinum based chemotherapy, to enable individualizing therapy for this cancer.

Regional myocardial sympathetic denervation predicts the risk of sudden cardiac arrest in ischemic cardiomyopathy.

OBJECTIVES: The PAREPET (Prediction of ARrhythmic Events with Positron Emission Tomography) study sought to test the hypothesis that quantifying inhomogeneity in myocardial sympathetic innervation could identify patients at highest risk for sudden cardiac arrest (SCA). BACKGROUND: Left ventricular ejection fraction (LVEF) is the only parameter identifying patients at risk of SCA who benefit from an implantable cardiac defibrillator (ICD). METHODS: We prospectively enrolled 204 subjects with ischemic cardiomyopathy (LVEF ≤35%) eligible for primary prevention ICDs. Positron emission tomography (PET) was used to quantify myocardial sympathetic denervation ((11)C-meta-hydroxyephedrine [(11)C-HED]), perfusion ((13)N-ammonia) and viability (insulin-stimulated (18)F-2-deoxyglucose). The primary endpoint was SCA defined as arrhythmic death or ICD discharge for ventricular fibrillation or ventricular tachycardia >240 beats/min. RESULTS: After 4.1 years follow-up, cause-specific SCA was 16.2%. Infarct volume (22 ± 7% vs. 19 ± 9% of left ventricle [LV]) and LVEF (24 ± 8% vs. 28 ± 9%) were not predictors of SCA. In contrast, patients developing SCA had greater amounts of sympathetic denervation (33 ± 10% vs. 26 ± 11% of LV; p = 0.001) reflecting viable, denervated myocardium. The lower tertiles of sympathetic denervation had SCA rates of 1.2%/year and 2.2%/year, whereas the highest tertile had a rate of 6.7%/year. Multivariate predictors of SCA were PET sympathetic denervation, left ventricular end-diastolic volume index, creatinine, and no angiotensin inhibition. With optimized cut-points, the absence of all 4 risk factors identified low risk (44% of cohort; SCA <1%/year); whereas ≥2 factors identified high risk (20% of cohort; SCA ∼12%/year). CONCLUSIONS: In ischemic cardiomyopathy, sympathetic denervation assessed using (11)C-HED PET predicts cause-specific mortality from SCA independently of LVEF and infarct volume. This may provide an improved approach for the identification of patients most likely to benefit from an ICD. (Prediction of ARrhythmic Events With Positron Emission Tomography [PAREPET]; NCT01400334).

Computed tomography scans as an objective measure of disease severity in chronic rhinosinusitis.

OBJECTIVES: A truly objective method of measuring disease severity in chronic rhinosinusitis (CRS) has only recently existed. We evaluated computed tomography (CT) scans of CRS patients using this novel objective 3D computerized system and compared results with a novel 2D computerized analysis of a single coronal slice through the osteomeatal complex (OMC) and subjective methods including Lund-Mackay and Zinreich's modified Lund-Mackay. STUDY DESIGN: Prospective multicenter study. SETTING: Two academic tertiary referral centers. SUBJECTS AND METHODS: Forty-six adults with a diagnosis of CRS underwent CT examination and received an intramuscular triamcinolone injection, dosage weight dependent, followed by CT scan 4 to 5 weeks later. Recruitment lasted 21 months. Scans were evaluated with all 4 scoring methods over 5 months. RESULTS: The Lin's concordance class correlation (CCC) of the OMC method revealed the best correlation to the 3D volumetric computerized values (0.915), followed by the Zinreich (0.904) and Lund-Mackay methods (0.824). Posttreatment results demonstrated that both the OMC (0.824) and Zinreich's (0.778) methods had strong agreement with the 3D volumetric methods and were very sensitive to change, whereas the Lund-Mackay (0.545) had only moderate agreement. CONCLUSION: Computerized CT analysis provides the most comprehensive, objective, and reproducible method of measuring disease severity and is very sensitive to change induced by treatment intervention. A 2D coronal image through the OMC provides a valid, user-friendly method of assessing CRS and is representative of CRS severity in all sinuses. Zinreich's subjective method correlated well overall, but the Lund-Mackay method lagged behind in disease representation and sensitivity to change.

Management of comorbidities in diabetics with renal cell carcinoma: past utilization and current outcomes.

OBJECTIVES: This study evaluated whether particular diabetes mellitus (DM), hyperlipidemia, or hypertension pharmacotherapy was associated with improved renal cell carcinoma (RCC) outcomes in diabetics with emergent RCC. METHODS: All DM cases newly diagnosed with RCC at Roswell Park Cancer Institute (January 01, 2003-December 31, 2010) were included (n = 95). Baseline demographic information, clinical history, and cancer outcomes were documented after chart review. Fisher's test was used for the analysis of categorical outcomes across different treatment groups. Univariate and multivariate analyses for the comparisons of the overall survival and progression-free survival across treatment groups were assessed using Kaplan-Meier log-rank test and Cox proportional hazards models. RESULTS: We found that DM pharmacotherapy users, which may represent a more advanced disease as compared to those controlled by diet alone, displayed significantly greater mortality (P = .01). Additionally, we found that cholesterol-lowering pharmacotherapy use was associated with decreased RCC mortality (hazard ratio = 0.54, P = .06). Individuals receiving combined hypertension regimens had a lower chance to present with baseline metastasis; however, hypertension pharmacotherapy use added no survival benefit. CONCLUSION: Reinforcing guidelines compliance for hyperlipidemia management in patients with DM may provide a considerable cancer benefit if diagnosed with RCC. Studies evaluating the need for cholesterol-lowering pharmacotherapy in guidelines-noncompliant DM cases upon RCC diagnosis are currently needed.

A combined inspiratory and expiratory muscle training program improves respiratory muscle strength and fatigue in multiple sclerosis.

OBJECTIVE: To determine the effects of a short-duration, combined (inspiratory and expiratory), progressive resistance respiratory muscle training (RMT) protocol on respiratory muscle strength, fatigue, health-related quality of life, and functional performance in individuals with mild-to-moderate multiple sclerosis (MS). DESIGN: Quasi-experimental before-after trial. SETTING: University rehabilitation research laboratory. PARTICIPANTS: Volunteers with MS (N=21) were divided into 2 groups: RMT (n=11; 9 women, 2 men; mean age ± SD, 50.9 ± 5.7y, mean Expanded Disability Status Scale score ± SD, 3.2 ± 1.9) and a control group that did not train (n=10; 7 women, 3 men; mean age ± SD, 56.2 ± 8.8y, mean Expanded Disability Status Scale score ± SD, 4.4 ± 2.1). Expanded Disability Status Scale scores ranged from 1 to ≤6.5. No patients withdrew from the study. INTERVENTION: Training was a 5-week combined progressive resistance RMT program, 3d/wk, 30 minutes per session. MAIN OUTCOME MEASURES: The primary outcome measures were maximal inspiratory pressure and expiratory pressure and the Modified Fatigue Impact Scale. All subjects completed secondary measures of pulmonary function, the six-minute walk test, the timed stair climb, the Multiple Sclerosis Self-Efficacy Scale, the Medical Outcomes Study 36-Item Short-Form Health Survey, and the Physical Activity Disability Scale. RESULTS: Maximal inspiratory pressure and expiratory pressure (mean ± SD) increased 35% ± 22% (P<.001) and 26% ± 17% (P<.001), respectively, whereas no changes were noted in the control group (12% ± 23% and -4% ± 17%, respectively). RMT improved fatigue (Modified Fatigue Impact Scale, P<.029), with no change or worsening in the control group. No changes were noted in the six-minute walk test, stair climb, Multiple Sclerosis Self-Efficacy Scale, or Physical Activity Disability Scale in the RMT group. The control group had decreases in emotional well-being and general health (Medical Outcomes Study 36-Item Short-Form Health Survey). CONCLUSIONS: A short-duration, combined RMT program improved inspiratory and expiratory muscle strength and reduced fatigue in patients with mild to moderate MS.

Mouse mammary gland is refractory to the effects of ethanol after natural lactation.

Ethanol is a dietary factor that dose-dependently increases breast cancer risk in women. We previously have shown that ethanol increases mammary epithelial density through increased branching after dietary exposure during puberty in CD2/F1 mice. To extend these studies to parous mice in a breast cancer model, we used a transgenic mouse model of human parity-associated breast cancer, the FVB-MMTV-Her2/Neu mouse, which overexpresses wildtype EGFR2, resulting in constitutive activation of growth signaling in the mammary epithelium. Here we describe the short-term effects of ethanol feeding on progression through involution. Mice were fed diets supplemented with 0%, 0.5%, 1%, or 2% ethanol for 4, 9, or 14 d starting on day 21 of lactation (that is, at the start of natural postlactational involution). Unlike peripubertal mice exposed to ethanol, postlactational dams showed no changes in body weight; liver, spleen, and kidney weights; and pathology. Ethanol exposure had no effect on mammary gland lobular density and adipocyte size throughout involution. Likewise, the infiltration of inflammatory cells and serum oxidized lipid species were unchanged by diet, suggesting that ethanol feeding had no effect on local inflammation (leukocyte infiltration) or systemic inflammation (oxidized lipids). In conclusion, ethanol exposure of parous dams had no effect on mammary gland structure or the regression of the lactating mammary gland to a resting state. The period of involution that follows natural lactation appears to be refractory to developmental effects of ethanol on mammary epithelium.

Risk of colorectal adenomas in women with prior breast cancer.

BACKGROUND AND AIMS: Longer life expectancy in patients with prior breast cancer may increase their risk of developing other primary cancers, including colorectal cancer (CRC). Whether the risk of developing CRC in this patient population is higher in comparison to those with no prior cancer remains unclear. The purpose of this study was to compare the prevalence of colorectal adenomas and any CRC in breast cancer survivors with those who have no history of prior cancer and assess any difference with use of antiestrogen therapy. METHODS: We compared the prevalence of colorectal cancer and adenomas in breast cancer survivors with that of a group of matched controls. Eligible survivors were ≤85 years of age; had initially been diagnosed with stage 0, I, II, or III breast cancer; had completed all cancer treatments with the exception of adjuvant antiestrogen therapy; and had no evidence of recurrence on follow-up. We used the screening colonoscopy database at our institution to identify age-, sex-, and race-matched controls with no history of cancer. RESULTS: We identified 302 study-eligible breast cancer survivors and 302 matched controls. No colorectal cancers were found in either group. Forty-one breast cancer survivors and 30 controls had tubular adenomas; four survivors and three controls had villous adenoma; and eight survivors and ten controls had advanced adenoma. Multivariate regression analysis revealed that adjuvant antiestrogen therapy was not significantly associated with an increased risk of advanced adenoma. CONCLUSIONS: The prevalence of colorectal adenomas in breast cancer survivors and controls was similar. Breast cancer survivors, including those receiving adjuvant antiestrogen therapies may follow the colorectal screening guidelines used for average-risk population.

Folate exacerbates the effects of ethanol on peripubertal mouse mammary gland development.

Alcohol consumption is linked with increased breast cancer risk in women, even at low levels of ingestion. The proposed mechanisms whereby ethanol exerts its effects include decreased folate levels resulting in diminished DNA synthesis and repair, and/or acetaldehyde-generated DNA damage. Based on these proposed mechanisms, we hypothesized that ethanol would have increased deleterious effects during periods of rapid mammary gland epithelial proliferation, such as peripuberty, and that folate deficiency alone might mimic and/or exacerbate the effects of ethanol. To test this hypothesis, weight-matched 28-35 day old CD2F1 female mice were pair-fed liquid diets ±3.2% ethanol, ±0.1% folate for 4 weeks. Folate status was confirmed by assay of liver and kidney tissues. In folate deficient mice, no significant ethanol-induced changes to the mammary gland were observed. Folate replete mice fed ethanol had an increased number of ducts per section, due to an increased number of terminal short branches. Serum estrogen levels were increased by ethanol, but only in folate replete mice. These results demonstrate that folate deficiency alone does not mimic the effects of ethanol, and that folate deficiency in the presence of ethanol blocks proliferative effects of ethanol on the mammary ductal tree.

Bortezomib mitigates adverse prognosis conferred by Bcl-2 overexpression in patients with relapsed/refractory multiple myeloma.

Overexpression of the Bcl-2 family of genes results in increased transcription of anti-apoptotic proteins. In vitro data suggest that this may enhance acquired chemoresistance and correlate with extramedullary invasion. This has led to pursuing the Bcl-2 family of proteins as therapeutic targets in several malignant disorders, including multiple myeloma (MM). The impact of novel therapeutic agents such as bortezomib on these molecular markers is not known. We investigated the association between the expression of anti-apoptotic members of the Bcl-2 family and the efficacy of bortezomib in patients with relapsed/refractory MM. Gene expression data generated prospectively from large clinical trials were utilized. Hypothesis testing using a multisample test for equivalence was performed. The association between Bcl-2 expression levels and clinical response was negated in bortezomib-treated patients (p = 0.014), while not so in dexamethasone-treated patients (p = 0.92). Similar results were noted for variant 2 of the Mcl-1 gene (p = 0.003). Results for Bcl-xl did not meet the level of significance. Thus, the importance of the Bcl-2 family of proteins as prognostic markers in MM should be reassessed in the novel therapeutic agent era. Our data suggest that bortezomib may overcome the prognostic effect conferred by overexpression of some of the anti-apoptotic Bcl-2 family of genes in patients with relapsed/refractory MM.

Biological effects and clinical significance of lenalidomide-induced tumour flare reaction in patients with chronic lymphocytic leukaemia: in vivo evidence of immune activation and antitumour response.

Lenalidomide has demonstrated impressive antileukaemic effects in patients with chronic lymphocytic leukaemia (CLL). The mechanism(s) by which it mediates these effects remain unclear. Clinically, CLL patients treated with lenalidomide demonstrate an acute inflammatory reaction, the tumour flare reaction that is suggestive of an immune activation phenomenon. Samples from CLL patients treated with lenalidomide were used to evaluate its effect on the tumour cell and components of its microenvironment (immune cellular and cytokine). Lenalidomide was unable to directly induce apoptosis in CLL cells in vitro, however it modulated costimulatory (CD80, CD83, CD86) surface molecules on CLL cells in vitro and in vivo. Concurrently, we demonstrated that NK cell proliferation was induced by lenalidomide treatment in patients and correlated with clinical response. Cytokine analysis showed increase in levels of TNF-α post-lenalidomide treatment, consistent with acute inflammatory reaction. Furthermore, the basal cytokine profile (high IL-8, MIG, IP-10 and IL-4 levels and low IL-5, MIP1a, MIP1b, IL12/p70) was predictive of clinical response to lenalidomide. Collectively, our correlative studies provide further evidence that the antileukaemic effect of lenalidomide in CLL is mediated not only through modulation of the leukaemic clone but also through elements of the tumour microenvironment.

Improved survival following surgery and radiation therapy for olfactory neuroblastoma: analysis of the SEER database.

BACKGROUND: Olfactory Neuroblastoma is a rare malignant tumor of the olfactory tract. Reports in the literature comparing treatment modalities for this tumor are limited. METHODS: The SEER database (1973-2006) was queried by diagnosis code to identify patients with Olfactory Neuroblastoma. Kaplan-Meier was used to estimate survival distributions based on treatment modality. Differences in survival distributions were determined by the log-rank test. A Cox multiple regression analysis was then performed using treatment, race, SEER historic stage, sex, age at diagnosis, year at diagnosis and SEER geographic registry. RESULTS: A total of 511 Olfactory Neuroblastoma cases were reported. Five year overall survival, stratified by treatment modality was: 73% for surgery with radiotherapy, 68% for surgery only, 35% for radiotherapy only, and 26% for neither surgery nor radiotherapy. There was a significant difference in overall survival between the four treatment groups (p < 0.01). At ten years, overall survival stratified by treatment modality and stage, there was no significant improvement in survival with the addition of radiation to surgery. CONCLUSIONS: Best survival results were obtained for surgery with radiotherapy.

Hypoxia-inducible factor-1α protein expression is associated with poor survival in normal karyotype adult acute myeloid leukemia.

We examined the predictive impact of HIF-1α protein expression on clinical outcome of 84 normal karyotype acute myeloid leukemia (NK-AML) patients (median age 66.5 years) at our institute. Thirty percent of NK-AML cells expressed cytoplasmic HIF-1α. In univariate analysis, low HIF-1α (≤ 5%, n = 66) was associated with improved event-free survival (p = 0.0453, HR = 0.22). Multivariate analysis incorporating age, complete remission, FLT3-ITD mutation, and marrow blast percentage demonstrated that HIF-1α was independently associated with poorer overall and event-free survival. HIF-1α expression correlated with VEGF-C but not VEGF-A, marrow angiogenesis, FLT3 ITD or NPM1 mutations. These results support HIF-1α as an outcome marker for NK-AML.

Does circular stapled esophagogastric anastomotic size affect the incidence of postoperative strictures?

BACKGROUND: Postoperative anastomotic strictures produce significant morbidity after esophagectomy. Previous reports have described a variable association between the diameter of the circular end-to-end anastomosis (EEA) stapler commonly used in esophagogastric anastomoses and the incidence of stricture formation. Stapler technology has improved. We investigated an association between stapler diameter and the incidence of postoperative anastomotic strictures in a contemporary series. This has renewed importance given the limited diameter of trans-oral staplers that are being increasingly used. METHODS: Retrospective chart review revealed that of 194 patients undergoing an esophagectomy over a 10-y period (10/1998-8/2008) at our institution, an EEA stapler was used in 91. EEA size information and follow-up were available in 89 patients. Patients were divided into two groups based on EEA size: 'small' = 23-25 mm (n = 24) and 'large' = 28-33 mm (n = 65). Patients with strictures were identified based on symptoms of dysphagia requiring an esophageal dilation procedure. Patients with postoperative leaks were excluded when analyzing for the association of stricture with EEA size, as postoperative leaks are known to be associated with stricture. Wilcoxon and Fisher's exact tests were used for statistical analysis; a 5% α error was accepted. RESULTS: Fifteen (16.8%) of 89 patients developed a stricture postoperatively. The anastomotic leak rate was 3.3%. There was no statistically significant association between EEA size group and stricture formation (P = 0.7506). CONCLUSIONS: No association was found between the size of the EEA stapler used and stricture formation. EEA size should be determined at surgery by the native esophageal diameter.

Effect of 25-hydroxyvitamin D status on serological response to influenza vaccine in prostate cancer patients.

BACKGROUND: Epidemiologic data suggest that there is an association between vitamin D deficiency and influenza infection. We conducted a prospective influenza vaccination study to determine the influence of vitamin D status on serological response to influenza vaccine in prostate cancer (CaP) patients. METHODS: During the 2006-2007 influenza season, CaP patients treated at Roswell Park Cancer Institute were offered vaccination with the trivalent influenza vaccine (Fluzone®, 2006-2007) and sera collected for hemagglutination inhibition (HI) assay titers before and 3 months after vaccination. Response to vaccination was defined as ≥1:40 titer ratio or a fourfold increase in titer at 3 months, against any of the three strains. Serum 25-hydroxyvitamin D (25-D3) levels were measured using DiaSorin ¹²5I radioimmunoassay kits. RESULTS: Thirty-five patients with CaP participated in the study. Median baseline 25-D3 level was 44.88 ng/ml (range: 9.16-71.98 ng/ml) Serological response against any of the three strains was noted in 80%. There was a significant effect of baseline 25-D3 level when tested as a continuous variable in relation to serological response (P = 0.0446). All patients in the upper quartile of 25-D3 level responded by mounting a serological response (P = 0.0344). None of the other baseline variables (age, race, chemotherapy status, or white cell count) had an effect on serological response. CONCLUSIONS: In this study in CaP patients, a replete vitamin D status was associated with more frequent serological response to influenza vaccine.