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Eric A Larson,1 Paul A Thompson,1,2 Zachary K Anderson,3 Keith A Anderson,4 Roxana A Lupu,1 Vicki Tigner,5 Wendell W Hoffman6,7 1Department of Internal Medicine, 2Department of Pediatrics, Sanford School of Medicine, University of South Dakota, Sioux Falls, SD, 3Department of Internal Medicine, Fairview Health Services, Edina, MN, 4Department of Laboratory Medicine, Sanford School of Medicine, University of South Dakota, 5Medical Staff Services, 6Department of Infectious Disease, Sanford Health, Sanford USD Medical Center, 7Department of Infectious Disease, Sanford School of Medicine, University of South Dakota, Sioux Falls, SD, USAAbstract: Red blood cell transfusions have been cited as one of the most overused therapeutic interventions in the USA. Excessively aggressive transfusion practices may be driven by mandatory physician notification of critical hemoglobin values that do not generally require transfusion. We examined the effect of decreasing the critical value of hemoglobin from 8 to 7 g/dL at our institution. Along with this change, mandatory provider notification for readings between 7 and 8 g/dL was rescinded. Transfusion rates were compared retrospectively during paired 5-month periods for patients presenting in three key hemoglobin ranges (6.00–6.99, 7.00–7.99, and 8.00–8.99 g/dL). A change in transfusion practices was hypothesized in the 7–8 g/dL range, which was no longer labeled critical and for which mandated physician calls were rescinded. Transfusion rates showed a statistically significant 8% decrease (P≤0.0001) during the 5-month period post change in our transfusion practices. This decrease in the 7.00–7.99 g/dL range was significantly greater than the 2% decrease observed in either the 6–6.99 g/dL (P=0.0017) or 8–8.99 g/dL (P≤0.0001) range. Cost savings of up to $700,000/year were extrapolated from our results showing 491 fewer units of red blood cells transfused during the 5-month post change. These cost savings do not take into account the additional impact of complications associated with blood transfusions.Keywords: transfusion, critical value, hemoglobin, cost savings, red blood cells, transfusion complications

“Brain-predicted age” quantifies apparent brain age compared to normative neuroimaging trajectories. Advanced brain-predicted age has been well established in symptomatic Alzheimer disease (AD), but is underexplored in preclinical AD. Prior brain-predicted age studies have typically used structural MRI, but resting-state functional connectivity (FC) remains underexplored. Our model predicted age from FC in 391 cognitively normal, amyloid-negative controls (ages 18–89). We applied the trained model to 145 amyloid-negative, 151 preclinical AD, and 156 symptomatic AD participants to test group differences. The model accurately predicted age in the training set. FC-predicted brain age gaps (FC-BAG) were significantly older in symptomatic AD and significantly younger in preclinical AD compared to controls. There was minimal correspondence between networks predictive of age and AD. Elevated FC-BAG may reflect network disruption during symptomatic AD. Reduced FC-BAG in preclinical AD was opposite to the expected direction, and may reflect a biphasic response to preclinical AD pathology or may be driven by inconsistency between age-related vs. AD-related networks. Overall, FC-predicted brain age may be a sensitive AD biomarker.

BackgroundT-cell prolymphocytic leukemia (T-PLL) is a rare and aggressive disease. In this study, we report our experience from 119 patients with T-PLL.Patients and methodsWe reviewed the clinico-pathologic records of 119 consecutive patients with T-PLL, who presented to our institution between 1990 and 2016.ResultsOne hundred and nineteen patients with T-PLL were analysed. Complex karyotype and aberrations in chromosome 14 were seen in 65% and 52% patients, respectively. Seventy-five patients (63%) were previously untreated and 43 (37%) were initially treated outside our institution. Sixty-three previously untreated patients (84%) received frontline therapies. Overall, 95 patients (80%) have died. Median overall survival (OS) from diagnosis was 19 months [95% confidence interval (CI) 16-26 months]. Using recursive partitioning (RP), we found that patients with hemoglobin

Background:A 15-country study of nuclear workers reported significantly increased radiation-related risks of all cancers excluding leukaemia, with Canadian data a major factor behind the pooled results. We analysed mortality (1956-1994) in the updated Cana

The ornithine decarboxylase-1 ( ODC1 ) polymorphism at position +316 affects binding by transcriptional activators and repressors and modulates the risk of metachronous colorectal adenomas, particularly in association with aspirin use. We investigated the effects of ODC1 after treatment with difluoromethylornithine (eflornithine)/sulindac or placebo. Two hundred twenty-eight colorectal adenoma patients in a randomized phase III trial were genotyped for ODC1 . We used Wilcoxon rank sums tests on non-normally distributed continuous variables across two genotype groups, χ 2 or Fisher exact test to assess the association between baseline categorical variables and genotype group, and log binomial regression for the primary (adenoma recurrence) and secondary outcomes (tissue polyamine response, cardiovascular toxicity, gastrointestinal toxicity, and ototoxicity). All statistical tests were two-sided. In binomial regression models with variables age, sex, race, aspirin use, treatment, and ODC1 genotype, treatment was the only statistically significant factor associated with differences in adenoma recurrence or tissue polyamine response. A statistically significant interaction was detected between ODC1 genotype and treatment with respect to adenoma recurrence (placebo group: GG, 50%, AA/GA: 34%; treatment group: GG, 11%, AA/GA, 21%; Pinteraction = .038). Excess ototoxicity was observed among ODC1 AA patients receiving treatment, but the interaction of genotype and treatment on ototoxicity was not statistically significant ( P = .45).

Background & Aims: Combination of polyamine and prostaglandin E2 (PGE2)synthesis inhibitors reduced the risk of colorectal adenoma (CRA) by 70% in patients who received polypectomies. We studied effects of the combination of difluoromethylornithine (DFMO) and sulindac on biomarkers and investigated factors that modify their efficacy. Methods: We analyzed rectal mucosal levels of polyamines (spermidine, spermine, and putrescine) and PGE2, treatment regimens, and risk of CRA in 267 participants of a phase IIb/III chemoprevention trial of DFMO/sulindac. Results: In the group that received DFMO/sulindac, spermidine-to-spermine ratio (Spd:Spm) in rectal mucosa decreased between baseline and 12- and 36-month follow-up examinations (0.30, 0.23, and 0.24, respectively; P < .001 for both comparisons to baseline). Putrescine levels decreased between baseline and 12 months (0.46 vs 0.15 nmol/mg protein; P < .001) but rebounded between 12 and 36 months (0.15 vs 0.36 nmol/mg protein; P = .001). PGE2 levels did not change, although aspirin use was significantly associated with lower baseline levels of PGE2. No significant associations were observed between changes in biomarker levels and efficacy. However, drug efficacy was greatest in subjects with low Spd:Spm and high PGE2 at baseline; none of these subjects, versus 39% of those given placebo, developed CRA (P < .001). Efficacy was lowest in subjects with high Spd:Spm and low PGE2 at baseline; 28% developed CRA, compared with 36% of patients given placebo (P = .563). Conclusions: A combination of DFMO and sulindac significantly suppressed production of rectal mucosal polyamines but not PGE2. No relationship was found between changes in biomarker levels and response. However, baseline biomarker levels modified the effect of DFMO/sulindac for CRA prevention. © 2010 by the AGA Institute.

We used polyclonal antisera and monoclonal antibodies (mAbs) to inhibit the growth of clonal populations of two strains of Borrelia burgdorferi, the Lyme disease agent, and thereby select for antibody-resistant mutants. mAbs were directed at the outer membrane proteins, OspA or OspB. Mutants resistant to the growth-inhibiting properties of the antibodies were present in the populations at frequencies ranging from 10(-5) to 10(-2). The several escape variants that were examined were of four classes. Class I mutants were resistant to all mAbs; they lacked OspA and OspB and the linear plasmid that encodes them. Two other proteins were expressed in larger amounts in class I mutants; mAbs to these proteins inhibited the mutant but not the wild-type cells. Class II mutants were resistant to some but not all mAbs; they had truncated OspA and/or OspB proteins. Class III mutants were resistant only to the selecting mAb; they had full-length Osp proteins that were not bound by the selecting antibody in Western blots. In two class III mutants resistant to different anti-OspA mAbs, missense mutations were demonstrated in the ospA genes. Class IV mutants were likewise resistant only to selecting antibody, but in this case the selecting antibody still bound in Western blots.

Background: The current study was conducted to determine the frequency and association between recurrence-free survival (RFS) and MET and catalytic subunit of phosphoinositide-3-kinase (PIK3CA) copy number elevations in patients with early stage breast cancer.Methods: Tumor DNA was extracted from 971 formalin-fixed, paraffin-embedded early breast cancers for molecular inversion probes arrays. Data were segmented using the single-nucleotide polymorphism (SNP)-FASST2 segmentation algorithm. Copy number gains were called when the copy number of each segment was greater than 2.3 or 1.7, respectively. RFS was estimated by the Kaplan-Meier method. Cox proportional hazards models were fit to determine independent associations between copy number and RFS.Results: Of the 971 tumors studied, 82 (8.44%) and 134 (13.8%) had an elevation of the MET or PIK3CA copy number, respectively, and 25.6% of tumors with a MET copy number elevation had a PIK3CA copy number elevation. Patients with either a MET or PI3KCA high copy number tended to have poorer prognostic features (larger tumor size, higher tumor grade, and hormone receptor negativity). Both MET and PIK3CA high copy numbers were more likely to occur in patients with triple receptor-negative disease (P = .019 and P < .001, respectively). At a median follow-up of 7.4 years, there were 252 cases of disease recurrence. The 5-year RFS rates were 63.5% and 83.1% for MET high copy number and MET normal/low copy number, respectively (P = .06) and 73.1%, and 82.3% for PIK3CA high copy number and PIK3CA normal/low copy number, respectively (P = .15). A high copy number for either gene was not found to be an independent predictor of RFS.Conclusions: A high copy number of MET or PIK3CA was found to be associated with poorer prognostic features and triple receptor-negative disease. Coamplification was frequent. Patients with tumors with high MET copy numbers tended to have a worse RFS. [ABSTRACT FROM AUTHOR]

Objective: This study examined factors that influence mammography use and breast cancer detection, including education, health insurance, and acculturation, among Mexican-American (MA) and African-American (AA) women.Methods: The study included 670 breast cancer cases (388 MAs and 282 AAs), aged 40-86 years at diagnosis. Data on mammography use, detection, and delay in seeking care were collected via questionnaires and medical records. Using a language-based bidimensional acculturation measure, MAs were classified as English-dominant (n = 67), bilingual (n = 173), and Spanish-dominant (n = 148). Mammography prior to diagnosis was assessed by racial/ethnic acculturation subgroup using logistic regression.Results: In age-adjusted models, mammography use was non-significantly lower among English-dominant (OR = 0.84; 95% CI: 0.45-1.59) and bilingual (OR = 0.86; 95% CI: 0.55-1.35) MAs and significantly lower among Spanish-dominant MAs (OR = 0.53; 95% CI: 0.34-0.83) than among AA women. After adjustment for education or insurance, there was no difference in mammography use by race/ethnicity and acculturation subgroup. Despite high self-reported mammography use (75%), a large proportion of cases reported self-detection (59%) and delay in seeking care >90 days (17%).Conclusions: These findings favor promoting culturally appropriate messaging about the benefits and limitations of mammography, education about breast awareness, and prompt reporting of findings to a health professional. [ABSTRACT FROM AUTHOR]

Chief nursing officers (CNOs) develop environments in which quality patient care is delivered and nurses enjoy professional practice. Because of the growing turbulence in this vital role, the American Organization of Nurse Executives conducted a study to examine CNO turnover as described in interviews with CNOs and healthcare recruiters to inform the development of strategies to improve CNO recruitment and retention and ease transition for those who turn over. The authors present the findings from this research and describe American Organization of Nurse Executives' initiatives to address the identified needs. [ABSTRACT FROM AUTHOR]