Citations

A rapid method for measuring nicotine concentration in serum and urine is described. Deuterated nicotine is used as an internal standard. Nicotine and deuterated nicotine are extracted using a copolymeric-bonded phase silica column. The extract is analysed by gas chromatography coupled with mass spectrometry (GC/MS) operating in selected ion monitoring mode. The method has a lower limit of detection of approximately 2 μg/L and is linear to at least 2000 μg/L. Within-run percentage coefficients of variation (% CV) are < 4 in both assays over a nicotine concentration range of 10–2000 μg/L. Between-run %CV in the serum assay are 5.4, 5.2, 4.8 and 5.9, respectively, at nicotine concentrations of 10, 15, 25, and 50 μg/L. Between-run %CV in the urine assay are 5.9, 4.5, 2.7 and 5.2, respectively, at nicotine concentrations of 100, 250, 500, and 2000 μg/L. The absolute recovery of nicotine is 61±+6% (mean±SD) over the range of 10–250 μg/L. The assay has been used to measure serum nicotine concentrations and 24-h urinary excretion of nicotine to monitor the extent of replacement in subjects receiving transdermal nicotine therapy for smoking cessation.

Background—Doppler-echocardiography provides quantitative imaging of systolic and diastolic left ventricular (LV) function, functional mitral regurgitation (FMR), and pulmonary hypertension (PH) in patients with LV systolic dysfunction. Whether PH is linked to survival independently of LV features and FMR in symptomatic and asymptomatic patients is unknown.Methods and Results—Patients with LV ejection fraction ≤40% and quantitative Doppler-echocardiography assessment of FMR and PH were studied. Patients were frequency matched for those with Doppler-echocardiography estimated pulmonary systolic pressure ≥45 mm Hg (n=692) and those without PH (n=692; pulmonary systolic pressure, <45 mm Hg) for age, sex, LV ejection fraction, and quantified FMR severity and analyzed for long-term survival after diagnosis. During follow-up (median, 8.9 years), 885 deaths (63.5%) occurred, with PH being associated with higher 5-year mortality: 51±2% versus 37±2%,P<0.001. In multivariate analysis, PH demonstrated increased mortality risk independent of age, sex, severity of diastolic and systolic LV dysfunction, FMR, comorbidities, and symptom (hazard ratio, 1.34; 95% confidence limit, 1.17–1.53;P<0.001). Subgroup analysis, stratified by symptoms, degree of FMR, and severity of LV dysfunction, demonstrated that PH was associated with excess mortality in all subgroups.Conclusions—In this large cohort of patients with LV systolic dysfunction, in whom FMR and LV characteristics were quantified and matched between those with and without PH, the presence of PH was an independent factor for excess mortality and not a surrogate for the severity of LV systolic dysfunction or FMR. In asymptomatic or symptomatic patients with or without FMR, PH is a critical marker for poor outcomes.

Abstract The presence of regulatory T cells (Treg) in solid tumors is known to play a role in patient survival in ovarian cancer and other malignancies. We assessed inherited genetic variations via 749 tag single-nucleotide polymorphisms (SNP) in 25 Treg-associated genes (CD28, CTLA4, FOXP3, IDO1, IL10, IL10RA, IL15, 1L17RA, IL23A, IL23R, IL2RA, IL6, IL6R, IL8, LGALS1, LGALS9, MAP3K8, STAT5A, STAT5B, TGFB1, TGFB2, TGFB3, TGFBR1, TGRBR2, and TGFBR3) in relation to ovarian cancer survival. We analyzed genotype and overall survival in 10,084 women with invasive epithelial ovarian cancer, including 5,248 high-grade serous, 1,452 endometrioid, 795 clear cell, and 661 mucinous carcinoma cases of European descent across 28 studies from the Ovarian Cancer Association Consortium (OCAC). The strongest associations were found for endometrioid carcinoma and IL2RA SNPs rs11256497 [HR, 1.42; 95% confidence interval (CI), 1.22–1.64; P = 5.7 × 10−6], rs791587 (HR, 1.36; 95% CI, 1.17–1.57; P = 6.2 × 10−5), rs2476491 (HR, = 1.40; 95% CI, 1.19–1.64; P = 5.6 × 10−5), and rs10795763 (HR, 1.35; 95% CI, 1.17–1.57; P = 7.9 × 10−5), and for clear cell carcinoma and CTLA4 SNP rs231775 (HR, 0.67; 95% CI, 0.54–0.82; P = 9.3 × 10−5) after adjustment for age, study site, population stratification, stage, grade, and oral contraceptive use. The rs231775 allele associated with improved survival in our study also results in an amino acid change in CTLA4 and previously has been reported to be associated with autoimmune conditions. Thus, we found evidence that SNPs in genes related to Tregs seem to play a role in ovarian cancer survival, particularly in patients with clear cell and endometrioid epithelial ovarian cancer. Cancer Immunol Res; 2(4); 332–40. ©2014 AACR.

Abstract Background: In patients with Barrett's esophagus, chronic reflux injury and inflammation are associated with esophageal adenocarcinoma, one of the most rapidly increasing lethal cancers. Epidemiological and preclinical studies support decreased risk of esophageal adenocarcinoma with NSAID use. Gastroesophageal refluxate contents can promote carcinogenesis in Barrett's metaplasia by activating AKT, which up regulates COX-2 expression and prostaglandin biosynthesis. We recently noted that neoplastic transformation in Barrett's esophagus is associated with increased AKT expression, particularly isoform AKT1. The AIM of this study is to investigate the effect of NSAID (Aspirin) use in patients with Barrett's esophagus on AKT1 expression using frozen tissue from the randomized, phase II trial of aspirin and esomeprazole for esophageal cancer chemoprevention in Barrett's esophagus patients and to assess the functional consequences of AKT1 expression in-vitro. Methods and Results: In a subset of patients (12 of 120 patients) with Barrett's esophagus who were randomized to placebo, lower dose (81 mg) or higher dose (325 mg) Aspirin for 4 weeks, both PCR and Western blot revealed marked reduction in AKT1 expression in patients who received 325 mg of Aspirin daily compared to patients who received placebo. Our in-vitro experiments support that AKT1 expression is functionally relevant to the process of carcinogenesis in Barrett's epithelial cells. Using adenovirus to induce AKT1 expression, we show that increased AKT1 expression increases Barrett's epithelial cell growth, facilitates RAS-mediated transformation of pre-neoplastic epithelial cells and promotes colony formation. Since AKT1 is known as Warburg kinase and regulates cellular glucose uptake to support aerobic glycolysis during growth de-regulation and neoplasia, we examined the uptake of fluorescent deoxyglucose analog (2-NBDG) in Barrett's epithelial cells transduced with AKT1 adenovirus. At 48 hrs, compared to control, AKT1 overexpression resulted in increased glucose uptake both by metaplastic and neoplastic Barrett's epithelial cells. Transcriptional repression of AKT1 abrogated the 2-NBDG uptake by these cells. Finally, we did pathway specific qPCRs and noted that use of Aspirin is associated with altered expression of chromatin remodelers that could down-regulate AKT1 expression. Conclusion: Collectively, our results demonstrate that Aspirin mediated down-regulation of Warburg kinase AKT1 in patients with Barrett?s esophagus is a novel mechanism for the regulation of Barrett?s epithelial cell growth. The in-depth characterization of molecular mechanisms is currently underway. This abstract is also presented as Poster A82. Citation Format: Navtej S. Buttar, Gary W. Falk, Cathrine J. DeMars, Sonia Chowdhury, Ahmed Elebiary, Anamay Sharma, Sidhartha Chaudhry, Nathan R. Foster, Katie L. Allen Ziegler, Yvonne Romero, Norman E. Marcon, Thomas Schnell, Douglas A. Corley, Prateek Sharma, Marcia R. Cruz-Correa, Chin Hur, David E. Fleischer, Amitabh Chak, Kenneth R. DeVault, David S. Weinberg, Gary Della’Zanna, Ellen Richmond, Thomas C. Smyrk, Sumithra Mandrekar, Paul J. Limburg. Aspirin mediated downregulation of Warburg kinase AKT1 in patients with Barrett's esophagus: Implications in neoplastic transformation. [abstract]. In: Proceedings of the Eleventh Annual AACR International Conference on Frontiers in Cancer Prevention Research; 2012 Oct 16-19; Anaheim, CA. Philadelphia (PA): AACR; Cancer Prev Res 2012;5(11 Suppl):Abstract nr PR-03.

Objective: The objective of this investigation was to assess whether a new electronic health (e-health) platform, combining mobile computing and a content management system, could effectively deliver modular and “just-in-time” education to older patients following cardiac surgery. Subjects and Methods: Patients were provided with iPad ® (Apple ® , Cupertino, CA) tablets that delivered educational modules as part of a daily “to do” list in a plan of care. The tablet communicated wirelessly to a dashboard where data were aggregated and displayed for providers. Results: A surgical population of 149 patients with a mean age of 68 years utilized 5,267 of 6,295 (84%) of education modules delivered over a 5.3-day hospitalization. Increased age was not associated with decreased use. Conclusions: We demonstrate that age, hospitalization, and major surgery are not significant barriers to effective patient education if content is highly consumable and relevant to patients' daily care experience. We also show that mobile technology, even if unfamiliar to many older patients, makes this possible. The combination of mobile computing with a content management system allows for dynamic, modular, personalized, and “just-in-time” education in a highly consumable format. This approach presents a means by which patients may become informed participants in new healthcare models.

AbstractBackgroundWell‐differentiated thyroid cancer (WDTC) recurs in up to 30% of patients. Guidelines from the American Thyroid Association (ATA) and the National Comprehensive Cancer Network (NCCN) provide valuable parameters for the management of recurrent disease, but fail to guide the clinician as to the multitude of factors that should be taken into account. The Thyroid Cancer Care Collaborative (TCCC) is a web‐based repository of a patient's clinical information. Ten clinical decision‐making modules (CDMMs) process this information and display individualized treatment recommendations.MethodsWe conducted a review of the literature and analysis of the management of patients with recurrent/persistent WDTC.ResultsSurgery remains the most common treatment in recurrent/persistent WDTC and can be performed with limited morbidity in experienced hands. However, careful observation may be the recommended course in select patients. Reoperation yields biochemical remission rates between 21% and 66%. There is a reported 1.2% incidence of permanent unexpected nerve paralysis and a 3.5% incidence of permanent hypoparathyroidism. External beam radiotherapy and percutaneous ethanol ablation have been reported as therapeutic alternatives. Radioactive iodine as a primary therapy has been reported previously for metastatic lymph nodes, but is currently advocated by the ATA as an adjuvant to surgery.ConclusionThe management of recurrent lymph nodes is a multifactorial decision and is best determined by a multidisciplinary team. The CDMMs allow for easy adoption of contemporary knowledge, making this information accessible to both patient and clinician. © 2014 Wiley Periodicals, Inc. Head Neck 37: 605–614, 2015

Background and Purpose— Hemicraniectomy and Durotomy Upon Deterioration From Infarction-Related Swelling Trial (HeADDFIRST) was a randomized pilot study to obtain information necessary to design a Phase III trial to evaluate the benefit of surgical decompression for brain swelling from large supratentorial cerebral hemispheric infarction. Methods— All patients with stroke were screened for eligibility (age 18–75 years, National Institutes of Health Stroke Scale ≥18 with Item 1a<2 [responsive to minor stimulation], and CT demonstrating unilateral, complete middle cerebral artery territory infarction by specific imaging criteria). All enrolled patients were treated using a standardized medical treatment protocol. Those with both ≥4 mm of pineal shift and deterioration in level of arousal or ≥7.5 mm of anteroseptal shift within 96 hours of stroke onset were randomized to continued medical treatment only or medical treatment plus surgery. Death at 21 days was the primary outcome measure. Results— Among 4909 screened patients, only 66 (1.3%) patients were eligible for HeADDFIRST. Forty patients were enrolled, and 26 patients developed the requisite brain swelling for randomization. All who failed to meet randomization criteria were alive at 21 days. Mortality at 21 and 180 days was 40% (4/10) in the medical treatment only and 21% (3/14) and 36% (5/14) in the medical treatment plus surgery arms, respectively. Conclusions— HeADDFIRST randomization criteria effectively distinguished low from high risk of death from large supratentorial cerebral hemispheric infarction. Lower mortality in the medical treatment only group than in other published trials suggests a possible benefit to standardizing medical management. These results can inform the interpretation of recently completed European trials concerning patient selection and medical management. Clinical Trial Registration— This trial was not registered because enrollment began before July 1, 2005.

Patients with dysglycemia related to known or unrecognized diabetes, stress hyperglycemia, or hypoglycemia in the presence or absence of exogenous insulin routinely require care during the perioperative period or critical illness. Recent single and multicenter studies, a large multinational study, and three meta-analyses evaluated the safety of routine tight glycemic control (80–110 mg/dl) in critically ill adults. Results led to a call for more modest treatment goals (initiation of insulin at a blood glucose >180 mg/dl with a goal of ∼150 mg/dl). In this symposium, an international group of multidisciplinary experts discusses the role of tight glycemic control, glucose measurement technique and its accuracy, glucose variability, hypoglycemia, and innovative methods to facilitate glucose homeostasis in this heterogeneous patient population.

Abdominal paracentesis complicated by perforation of a penetrating arterial branch is an extremely rare complication. We report 2 patients who presented with abdominal wall pseudoaneurysms following abdominal paracentesis for the evaluation and treatment of their hepatic dysfunction. We subsequently review the treatment modalities and interventions performed in each case.