Urticaria and Angioedema.

Urticaria and angioedema are caused by immunoglobulin E- and non-immunoglobulin E-mediated release of histamine and other inflammatory mediators from mast cells and basophils. Diagnosis is made clinically, and anaphylaxis must be ruled out if urticaria or angioedema is present. A limited nonspecific laboratory workup should be considered unless elements of the history or physical examination suggest specific underlying conditions. The mainstay of treatment is avoidance of triggers when and if triggers are identified. The first-line pharmacotherapy is second-generation H1 antihistamines, which can be titrated to greater than standard doses.

Impact of a Hands-on Knee Exam Workshop on Medical Student Clinical Examination Scores.

INTRODUCTION: The goal of this research project was to retrospectively evaluate the effect of a voluntary hands-on musculoskeletal knee exam workshop, presented to medical students in the family medicine rotation at the University of Toledo, on the outcomes of a required objective structured clinical examination (OSCE). METHODS: We analyzed student OSCE scores for both knee and back exams before (July 2011 to June 2012) and after (August 2013 to June 2015) the workshop was offered. The analysis was based on those who attended the voluntary knee exam workshop and those who did not. We compared scores between the two groups of students using two-tailed t testing and χ 2 testing, and assessed the correlation of attending the workshop to passing the knee OSCE. RESULTS: One hundred eighty-seven students attended the workshop and 279 did not. During the period when the workshop was offered, the overall mean score on the knee OSCE was 59.5% for the 187 who attended the workshop and 35.9% for the 116 who did not, which was significantly different (P<.001). A χ2 test with α=0.05 showed that attending the workshop correlated with completing at least 70% of maneuvers acceptably during the knee OSCE (P<.001). CONCLUSIONS: Our study yielded positive outcomes on OSCE scores, comparable to other studies that investigated the effect of similar teaching techniques. Comparison of the scores of those who attended the knee workshop on the simpler back exam OSCE, in which no workshop was offered, demonstrated the efficacy of the workshop.

Acute and Chronic Urticaria: Evaluation and Treatment.

Urticaria commonly presents with intensely pruritic wheals, sometimes with edema of the subcutaneous or interstitial tissue. It has a lifetime prevalence of about 20%. Although often self-limited and benign, it can cause significant discomfort, continue for months to years, and uncommonly represent a serious systemic disease or life-threatening allergic reaction. Urticaria is caused by immunoglobulin E- and non-immunoglobulin E-mediated release of histamine and other inflammatory mediators from mast cells and basophils. Diagnosis is made clinically; anaphylaxis must be ruled out. Chronic urticaria is idiopathic in 80% to 90% of cases. Only a limited nonspecific laboratory workup should be considered unless elements of the history or physical examination suggest specific underlying conditions. The mainstay of treatment is avoidance of triggers, if identified. The first-line pharmacotherapy is second-generation H1 antihistamines, which can be titrated to greater than standard doses. First-generation H1 antihistamines, H2 antihistamines, leukotriene receptor antagonists, high-potency antihistamines, and brief corticosteroid bursts may be used as adjunctive treatment. In refractory chronic urticaria, patients can be referred to subspecialists for additional treatments, such as omalizumab or cyclosporine. More than one-half of patients with chronic urticaria will have resolution or improvement of symptoms within a year.

Precision Medicine and Pancreatic Cancer: A Gemcitabine Pathway Approach.

OBJECTIVES: There is a need for validated predictive markers of gemcitabine response to guide precision medicine treatment in pancreatic cancer. We previously validated human equilibrative nucleoside transporter 1 as a predictive marker of gemcitabine treatment response using Radiation Therapy Oncology Group 9704. Controversy exists about the predictive value of gemcitabine metabolism pathway biomarkers: deoxycytidine kinase (DCK), ribonucleotide reductase 1 (RRM1), RRM2, and p53R2. METHODS: Radiation Therapy Oncology Group 9704 prospectively randomized 538 patients after pancreatic resection to receive either 5-fluorouracil or gemcitabine. Tumor DCK, RRM1, RRM2, and p53R protein expressions were analyzed using a tissue microarray and immunohistochemistry and correlated with treatment outcome (overall survival and disease-free survival) by unconditional logistic regression analysis. RESULTS: There were 229 patients eligible for analysis from both the 5-fluorouracil and gemcitabine arms. Only RRM2 protein expression, and not DCK, RRM1, or p53R2 protein expression, was associated with survival in the gemcitabine treatment arm. CONCLUSIONS: Despite limited data from other nonrandomized treatment data, our data do not support the predictive value of DCK, RRM1, or p53R2. Efforts should focus on human equilibrative nucleoside transporter 1 and possibly RRM2 as valid predictive markers of the treatment response of gemcitabine in pancreatic cancer.

A Stress Management Program for Higher Risk Medical Students: Preliminary Findings.

Approximately 10 % of first year medical students have clinically relevant anxiety or depression which may affect academic success and quality of life. This study tested the effects of a stress management intervention on indicators of anxiety, depression and self-efficacy in self-selected first year medical students. Forty two medical students volunteered to participate and provided informed consent. An eight session intervention was offered and focused on building relaxation skills, adaptive coping, and basic nutrition. Anxiety, depression, and self-efficacy were assessed pre and post intervention. This group of students had significantly higher baseline values of depression and anxiety but lower self-efficacy compared to a previous study of medical students at the same institution (p < 0.03). After the intervention, statistically significant improvements were observed in anxiety (p < 0.05), and self-efficacy (p < 0.05), but not in depression. The entering levels of anxiety and depression in this group suggested that these students were at risk for later clinical syndromes. Intervention directed to decreasing the effects of stress was associated with improvement in indicators of distress and may modify the longer term risk.

Comparing and Validating Simple Measures of Patient-Reported Peripheral Neuropathy for Oncology Clinical Trials: NCCTG N0897 (Alliance) A Pooled Analysis of 2440 Patients.

INTRODUCTION: Current standard evaluation of Peripheral Neuropathy (PN) is based on an investigator-reported classification system that is commonly unable to correctly reflect the subjective symptoms for patients. Thus more reliable methods to assess PN are needed. This study assessed alternative methods of assessing patient-reported PN in 5 North Central Cancer Treatment Group (NCCTG) clinical trials. METHOD: Two single-item assessments relating to numbness and tingling were used to measure PN. Patients' Quality Of Life (QOL) was also assessed using the Uniscale, Symptom Distress Scale (SDS), Profile of Mood States (POMS), Brief Pain Inventory (BPI) and Subject Global Impression of Change (SGIC). Wilcoxon tests compared QOL scores between patients with PN (score > 50) vs. no PN (score ≤ 50). Changes from baseline in QOL were compared by Wilcoxon rank sum test with a 20-point change in PN defined as clinically meaningful. Both distribution-based and anchor-based approaches were used to derive estimates of Minimal Important Differences (MID). Standardized Response Means (SRM), Effect Sizes (ES) and Guyatt's responsiveness statistic were used to measure responsiveness. RESULTS: The proportion of patients reporting numbness (tingling) at baseline was 10.7% (10.0%) and 18.4% (17.8%) at last assessment. The correlation between numbness and tingling at baseline was 0.81, and at last assessment was 0.83. Patients with substantial PN reported an average of 10 points lower overall QOL, mood and worse symptom distress and 20 points lower in the BPI interference items. Patients having a ≤ 20 point worsening in PN score reported significantly worse in symptom distress and BPI worst pain, but not in POMS or overall QOL. The MID estimates were similar between numbness and tingling items but varied depending on the approach used. Responsiveness statistics indicated that the two PN assessments are sensitive and responsive instruments for cancer patients with PN. CONCLUSIONS: The two PN items for numbness and tingling were redundant. Evidence of criterion validity and responsiveness indicates that these simple measures of PN can be used successfully in cancer clinical trials.

Glycogen Synthase Kinase 3 Beta Predicts Survival in Resected Adenocarcinoma of the Pancreas.

PURPOSE: GSK3ß is a protein kinase that can suppress a number of key oncoproteins. We have previously shown in preclinical models of pancreatic ductal adenocarcinoma (PDAC) that inhibition of GSK3ß causes stabilization and nuclear translocation of ß-catenin, poor differentiation, proliferation, and resistance to radiation. The objective of this study was to determine its utility as a biomarker of clinical outcomes. EXPERIMENTAL DESIGN: Automated Quantitative Immunofluorescence Analysis (AQUA) of GSK3ß was performed on a tissue microarray with samples from 163 patients treated on RTOG 9704. On the basis of findings in an exploratory cohort, GSK3ß was analyzed as a categorical variable using its upper quartile (>Q3) as a cut point. Overall survival (OS) and disease-free survival (DFS) were estimated with the Kaplan-Meier method, and GSK3ß groupings were compared using the log-rank test. Univariable and multivariable Cox proportional hazards models were used to determine associations between GSK3ß and OS/DFS. RESULTS: The 3-year OS rates for GSK3ß≤Q3 versus GSK3ß >Q3 were 16% (95% confidence intervals; CI, 10%-23%) and 30% (95% CI, 17%-44%), respectively, P = 0.0082. The 3-year DFS rates were 9% (95% CI, 5%-15%) and 20% (95% CI, 9%-33%) respectively, P value = 0.0081. On multivariable analysis, GSK3ß was a significant predictor of OS. Patients with GSK3ß >Q3 had a 46% reduced risk of dying of pancreatic cancer (HR, 0.54; 95% CI, 0.31-0.96, P value = 0.034). The HR for DFS was 0.65 (95% CI, 0.39-1.07; P value = 0.092). CONCLUSIONS: GSK3ß expression is a strong prognosticator in PDAC, independent of other known factors such as tumor (T) stage, nodal status, surgical margins and CA19-9. Clin Cancer Res; 21(24); 5612-8. ©2015 AACR.

(7E,11E)-3,5,9,11-Tetramethyltridecadienal: Sex Pheromone of the Strepsipteran Xenos peckii.

Xenos peckii is a strepsipteran parasitoid of the common North American paper wasp, Polistes fuscatus. Mate-seeking X. peckii males respond to a long-range sex pheromone emitted by the female, which remains permanently embedded within the abdomen of a mobile host wasp. During peak pheromone signalling, we excised the female from her host, severed the cephalothorax containing the pheromone gland, extracted it in hexane, and analyzed aliquots of combined extracts by coupled gas chromatographic-electroantennographic detection (GC-EAD). These analyses revealed a candidate pheromone component (CPC) that consistently elicited strong responses from male antennae. We identified the CPC as (7E,11E)-3,5,9,11-tetramethyltridecadienal based on its retention indices (RI) on three GC-columns, RI inter-column differentials, mass and NMR spectra, and synthesis of an authentic standard that matched the GC-retention and spectrometric characteristics of the CPC. For a field experiment, we prepared (7E,11E)-3,5,9R,11-tetramethyltridecadienal and (7E,11E)-3,5,9S,11-tetramethyltridecadienal. Xenos peckii males were caught in traps baited with either compound singly or a 1:1 mixture of the two but not in unbaited control traps. The sex pheromone of X. peckii resembles that reported for the strepsipterans Stylops mellittae and S. muelleri, (R,R,R)-3,5,9-trimethyldodecanal, suggesting a common biosynthetic pathway across taxonomic genera.

The Complementary Nature of Patient-Reported Outcomes and Adverse Event Reporting in Cooperative Group Oncology Clinical Trials: A Pooled Analysis (NCCTG N0591).

CONTEXT: Clinical trials use clinician-graded adverse events (AEs) and patient-reported outcomes (PROs) to describe symptoms. OBJECTIVES: The aim of the study was to examine the agreement between PROs and AEs in the clinical trial setting. METHODS: Patient-level data were pooled from seven North Central Cancer Treatment Group, two Southwest Oncology Group, and three Radiation Therapy Oncology Group lung studies that included both PROs and AE data. Ten-point changes (on a 0-100 scale) in PRO scores were considered clinically significant differences (CSDs). PRO score changes were compared to AE grade (Gr) categories (2+ yes vs. no and 3+ yes vs. no) using Wilcoxon rank-sum or two-sample t-tests between Gr categories. Incidence rates and concordance of CSD in PRO scores and AE Gr categories were compiled. Spearman correlations were computed between PRO scores and AE severity. RESULTS: PROs completed by patients (n = 1013) were the Uniscale, Lung Cancer Symptom Scale (LCSS), Functional Assessment of Cancer Therapy-Lung (FACT-L), Symptom Distress Scale, and/or Functional Living Index-Cancer. Significantly worse PRO score changes were found for the FACT-L in patients with Gr 2+ AEs. Worse scores were seen for the Uniscale for patients with Gr 2+ AEs (P = 0.07) and LCSS for patients with Gr 3+ AEs (P = 0.09). Agreement between incidence of any Gr 2+ (Gr 3+) AE and a CSD in PROs ranged from 27% to 67% (36%-61%). Correlations between PRO scores and AE severity were low: -0.06 Uniscale, -0.03 LCSS, 0.10 FACT-L, -0.11 Symptom Distress Scale, and -0.51 Functional Living Index-Cancer. CONCLUSION: These results support previous work and an a priori hypothesis that AEs and PROs measure differing aspects of the disease experience and are complementary.

Aspirin and COX-2 inhibitor use in patients with stage III colon cancer.

We conducted a prospective, observational study of aspirin and COX-2 inhibitor use and survival in stage III colon cancer patients enrolled in an adjuvant chemotherapy trial. Among 799 eligible patients, aspirin use was associated with improved recurrence-free survival (RFS) (multivariable hazard ratio [HR] = 0.51, 95% confidence interval [CI] = 0.28 to 0.95), disease-free survival (DFS) (HR = 0.68, 95% CI = 0.42 to 1.11), and overall survival (OS) (HR = 0.63, 95% CI = 0.35 to 1.12). Adjusted HRs for DFS and OS censored at five years (in an attempt to minimize misclassification from noncancer death) were 0.61 (95% CI = 0.36 to 1.04) and 0.48 (95% CI = 0.23 to 0.99). Among 843 eligible patients, those who used COX-2 inhibitors had multivariable HRs for RFS, DFS, and OS of 0.53 (95% CI = 0.27 to 1.04), 0.60 (95% CI = 0.33 to 1.08), and 0.50 (95% CI = 0.23 to 1.07), and HRs of 0.47 (95% CI = 0.24 to 0.91) and 0.26 (95% CI = 0.08 to 0.81) for DFS and OS censored at five years. Aspirin and COX-2 inhibitor use may be associated with improved outcomes in stage III colon cancer patients.

Integrin alpha4 blockade sensitizes drug resistant pre-B acute lymphoblastic leukemia to chemotherapy.

Bone marrow (BM) provides chemoprotection for acute lymphoblastic leukemia (ALL) cells, contributing to lack of efficacy of current therapies. Integrin alpha4 (alpha4) mediates stromal adhesion of normal and malignant B-cell precursors, and according to gene expression analyses from 207 children with minimal residual disease, is highly associated with poorest outcome. We tested whether interference with alpha4-mediated stromal adhesion might be a new ALL treatment. Two models of leukemia were used, one genetic (conditional alpha4 ablation of BCR-ABL1 [p210(+)] leukemia) and one pharmacological (anti-functional alpha4 antibody treatment of primary ALL). Conditional deletion of alpha4 sensitized leukemia cell to nilotinib. Adhesion of primary pre-B ALL cells was alpha4-dependent; alpha4 blockade sensitized primary ALL cells toward chemotherapy. Chemotherapy combined with Natalizumab prolonged survival of NOD/SCID recipients of primary ALL, suggesting adjuvant alpha4 inhibition as a novel strategy for pre-B ALL.

An alternative reproductive tactic: a parasitoid wasp gathers and guards a harem by pheromone-tagging virgins.

Alternative reproductive tactics (ARTs) are the outcome of decisions to obtain copulations in reproductive competition. Mating tactics male insects exhibit can be based on their competitive ability, or be dependent on conditions such as a competitive setting and the spatial and temporal distribution of receptive females. When females are clustered and numerous, two or more mating tactics can coexist. We predicted that this concept is applicable to the egg parasitoid wasp Ooencyrtus kuvanae (Hymenoptera: Encyrtidae), because wasps emerge en masse as sexually mature adults from gypsy moth, Lymantria dispar, egg masses. We reveal that male O. kuvanae exhibit two ARTs, a mate-at-once (MAO) tactic, and a harem-gathering and -guarding (HGG) tactic. MAO males invariably and immediately mate females they encounter. HGG males (i) typically mate the first receptive female they encounter, (ii) then find and assess other females, (iii) tag those without prior male contact, and finally (iv) return to, and mate with, all females they themselves have tagged. Females do not incur a direct fitness cost by mating with multiply-mated males. HGG males rely on their speed, unique tag pheromone, and on the females' rejection of HGG males except the one that pheromone-tagged them. The tagging pheromone mediates mate recognition and assessment.

Acute otitis externa: an update.

Acute otitis externa is a common condition involving inflammation of the ear canal. The acute form is caused primarily by bacterial infection, with Pseudomonas aeruginosa and Staphylococcus aureus the most common pathogens. Acute otitis externa presents with the rapid onset of ear canal inflammation, resulting in otalgia, itching, canal edema, canal erythema, and otorrhea, and often occurs following swimming or minor trauma from inappropriate cleaning. Tenderness with movement of the tragus or pinna is a classic finding. Topical antimicrobials or antibiotics such as acetic acid, aminoglycosides, polymyxin B, and quinolones are the treatment of choice in uncomplicated cases. These agents come in preparations with or without topical corticosteroids; the addition of corticosteroids may help resolve symptoms more quickly. However, there is no good evidence that any one antimicrobial or antibiotic preparation is clinically superior to another. The choice of treatment is based on a number of factors, including tympanic membrane status, adverse effect profiles, adherence issues, and cost. Neomycin/polymyxin B/hydrocortisone preparations are a reasonable first-line therapy when the tympanic membrane is intact. Oral antibiotics are reserved for cases in which the infection has spread beyond the ear canal or in patients at risk of a rapidly progressing infection. Chronic otitis externa is often caused by allergies or underlying inflammatory dermatologic conditions, and is treated by addressing the underlying causes.

Common medical problems of instrumental athletes.

The fields of sports medicine and performing arts medicine have begun recent initiatives to collaborate more closely and to share information pertinent to the treatment of athletes and performing artists. This article provides a review of the common musculoskeletal and neurological problems encountered among performing artists who play instruments. Approaches to history, examination, diagnosis, and treatment are offered, based on literature reviews, expert opinion, and the authors' own experiences in a musician's clinic. Treatments focus on conservative management within a multidisciplinary framework, and indications are given for appropriate surgical referral. Providers are encouraged to build an understanding of the unique issues affecting instrumental athletes.

Does the stereochemistry of methylated cuticular hydrocarbons contribute to mate recognition in the egg parasitoid wasp Ooencyrtus kuvanae?

Close-range sexual communication of the egg parasitoid wasp Ooencyrtus kuvanae (Hymenoptera: Encyrtidae) takes place on host gypsy moth, Lymantria dispar (Lepidoptera: Lymantriidae), egg masses. We tested the hypothesis that mate recognition in O. kuvanae is mediated, in part, by low-volatility cuticular hydrocarbon (CHC) pheromone components. Gas chromatographic and GC-mass spectrometric analyses of body surface extracts of male and female wasps revealed no sex-specific components, but 5-methylheptacosane (5-me-27Hy) and 5,17-dimethylheptacosane (5,17-dime-27Hy) were consistently more abundant in extracts of males. The ratio of 5-me-27Hy and 5,17-dime-27Hy was similar in extracts of males and females, and quantitative differences alone seemed insufficient to impart sex-specific CHC profiles. Therefore, we further hypothesized that the absolute configuration of 5-me-27Hy and 5,17-dime-27Hy contributes to mate recognition or attraction. As the stereoisomers of 5-me-27Hy and 5,17-dime-27Hy cannot currently be separated chromatographically, we could not determine the stereochemistry of the insect-produced components. Instead, we synthesized all stereoisomers and bioassayed synthetic blends in laboratory experiments. Of eight 2-component blends, each blend containing one of the two enantiomers of 5-me-27Hy and one of the four stereoisomers of 5,17-dime-27Hy, the blend of (5S)-methylheptacosane and (5R,17S)-dimethylheptacosane attracted males, whereas the blend of (5R)-methylheptacosane and (5R,17R)-dimethylheptacosane repelled males. Apparent recognition of both pheromone components and pheromone antagonists by males supports the hypothesis that the stereochemistry of 5-me-27Hy and 5,17-dime-27Hy, and possibly other methylated CHCs, may differ between male and female O. kuvanae, and that these differences may serve in mate attraction and recognition.

In the nick of time: males of the parasitoid wasp Pimpla disparis respond to semiochemicals from emerging mates.

Males of the parasitoid wasp Pimpla disparis Viereck (Hymenoptera: Ichneumonidae) aggregate on parasitized gypsy moth, Lymantria dispar, host pupae when the emergence of a prospective mate is imminent or under way. We tested the hypotheses that the developing parasitoid ("DePa") inside the host pupal case produces a pheromone that attracts and arrests mate-seeking males, and that the pheromone is most effective during the emergence of the parasitoid from the host. Results obtained in two-choice laboratory experiments, with 4-7-d-old virgin males, indicate that (1) DePa-derived semiochemicals arrest males, (2) the opening of a host pupal case strongly arrests males, and (3) the arrestment cue emanates from oral fluid secreted by both female and male parasitoids while they chew their way out of a host pupal case. This phenomenon implies that emerging females, which are haplodiploid and can reproduce without mating, do not engage in active pheromone signaling to attract males, and that mate-seeking males co-opt chemicals involved in eclosion as a mate-finding cue, taking a 50% chance that the prospective mate is a female.

Predictive and prognostic roles of BRAF mutation in stage III colon cancer: results from intergroup trial CALGB 89803.

PURPOSE: Alterations in the RAS-RAF-MAP2K (MEK)-MAPK signaling pathway are major drivers in colorectal carcinogenesis. In colorectal cancer, BRAF mutation is associated with microsatellite instability (MSI), and typically predicts inferior prognosis. We examined the effect of BRAF mutation on survival and treatment efficacy in patients with stage III colon cancer. METHODS: We assessed status of BRAF c.1799T>A (p.V600E) mutation and MSI in 506 stage III colon cancer patients enrolled in a randomized adjuvant chemotherapy trial [5-fluorouracil and leucovorin (FU/LV) vs. irinotecan (CPT11), FU and LV (IFL); CALGB 89803]. Cox proportional hazards model was used to assess the prognostic role of BRAF mutation, adjusting for clinical features, adjuvant chemotherapy arm, and MSI status. RESULTS: Compared with 431 BRAF wild-type patients, 75 BRAF-mutated patients experienced significantly worse overall survival [OS; log-rank P = 0.015; multivariate HR = 1.66; 95% CI: 1.05-2.63]. By assessing combined status of BRAF and MSI, it seemed that BRAF-mutated MSS (microsatellite stable) tumor was an unfavorable subtype, whereas BRAF wild-type MSI-high tumor was a favorable subtype, and BRAF-mutated MSI-high tumor and BRAF wild-type MSS tumor were intermediate subtypes. Among patients with BRAF-mutated tumors, a nonsignificant trend toward improved OS was observed for IFL versus FU/LV arm (multivariate HR = 0.52; 95% CI: 0.25-1.10). Among patients with BRAF wild-type cancer, IFL conferred no suggestion of benefit beyond FU/LV alone (multivariate HR = 1.02; 95% CI: 0.72-1.46). CONCLUSIONS: BRAF mutation is associated with inferior survival in stage III colon cancer. Additional studies are necessary to assess whether there is any predictive role of BRAF mutation for irinotecan-based therapy.

Relationship between statin use and colon cancer recurrence and survival: results from CALGB 89803.

BACKGROUND: Although preclinical and epidemiological data suggest that statins may have antineoplastic properties, the impact of statin use on patient survival after a curative resection of stage III colon cancer is unknown. METHODS: We conducted a prospective observational study of 842 patients with stage III colon cancer enrolled in a randomized adjuvant chemotherapy trial from April 1999 to May 2001 to investigate the relationship between statin use and survival. Disease-free survival (DFS), recurrence-free survival (RFS), and overall survival (OS) were investigated by Kaplan-Meier curves and log-rank tests in the overall study population and in a subset of patients stratified by KRAS mutation status (n = 394), and Cox proportional hazards regression was used to assess the simultaneous impact of confounding variables. All statistical tests were two-sided. RESULTS: Among 842 patients, 134 (15.9%) reported statin use after completing adjuvant chemotherapy. DFS among statin users and nonusers was similar (hazard ratio [HR] of cancer recurrence or death = 1.04, 95% confidence interval [CI] = 0.73 to 1.49). RFS and OS were also similar between statin users and nonusers (adjusted HR of cancer recurrence = 1.14, 95% CI = 0.77 to 1.69; adjusted HR of death = 1.15, 95% CI = 0.77 to 1.71). Survival outcomes were similar regardless of increasing duration of statin use before cancer diagnosis (P(trend) = .63, .63, and .59 for DFS, RFS, and OS, respectively). The impact of statin use did not differ by tumor KRAS mutation status, with similar DFS, RFS, and OS for statin use among mutant and wild-type subgroups (P(interaction) = .84, .67, and .98 for DFS, RFS, and OS, respectively). CONCLUSION: Statin use during and after adjuvant chemotherapy was not associated with improved DFS, RFS, or OS in patients with stage III colon cancer, regardless of KRAS mutation status.

Targeting survivin overcomes drug resistance in acute lymphoblastic leukemia.

Relapse of drug-resistant acute lymphoblastic leukemia (ALL) has been associated with increased expression of survivin/BIRC5, an inhibitor of apoptosis protein, suggesting a survival advantage for ALL cells. In the present study, we report that inhibition of survivin in patient-derived ALL can eradicate leukemia. Targeting survivin with shRNA in combination with chemotherapy resulted in no detectable minimal residual disease in a xenograft model of primary ALL. Similarly, pharmacologic knock-down of survivin using EZN-3042, a novel locked nucleic acid antisense oligonucleotide, in combination with chemotherapy eliminated drug-resistant ALL cells. These findings show the importance of survivin expression in drug resistance and demonstrate that survivin inhibition may represent a powerful approach to overcoming drug resistance and preventing relapse in patients with ALL.

Urticaria: evaluation and treatment.

Urticaria involves intensely pruritic, raised wheals, with or without edema of the deeper cutis. It is usually a self-limited, benign reaction, but can be chronic. Rarely, it may represent serious systemic disease or a life-threatening allergic reaction. Urticaria has a lifetime prevalence of approximately 20 percent in the general population. It is caused by immunoglobulin E- and nonimmunoglobulin E-mediated mast cell and basophil release of histamine and other inflammatory mediators. Diagnosis is made clinically. Chronic urticaria is usually idiopathic and requires only a simple laboratory workup unless elements of the history or physical examination suggest specific underlying conditions. Treatment includes avoidance of triggers, although these can be identified in only 10 to 20 percent of patients with chronic urticaria. First-line pharmacotherapy for acute and chronic urticaria is nonsedating second-generation antihistamines (histamine H1 blockers), which can be titrated to larger than standard doses. First-generation antihistamines, histamine H2 blockers, leukotriene receptor antagonists, and brief corticosteroid bursts may be used as adjunctive treatment. More than one-half of patients with chronic urticaria will have resolution or improvement of symptoms within one year.