bluuebunny/crossref_metadata_2025_split huggingface dataset:
Family History of Breast Cancer in Relation to Tumor Characteristics and Mortality in a Population-Based Study of Young Women with Invasive Breast Cancer
Authors: Malone Kathleen E. , Daling Janet R. , Doody David R. , O'Brien Cecilia , Resler Alexa , Ostrander Elaine A. , Porter Peggy L. 
Published: December 2011

Abstract
Background: Inherited predisposition may be associated with distinctive breast cancer phenotypes and/or mortality. Past studies have had inconsistent results and little is known about the contributions of screening and treatment.
Methods: Within a population-based cohort of 1,260 women diagnosed with invasive breast cancer before age 46, we assessed how family history of breast cancer relates to mortality and tumor characteristics. Analyses were repeated excluding BRCA1/BRCA2 carriers. Medical records were reviewed for treatment history and tumors were centrally reviewed and tested. Cox proportional hazard modeling was used to assess the risk of dying in relation to family history; logistic regression was used to assess the association of family history to tumor characteristics.
Results: Compared with women with no family history, women with first-degree family history of breast cancer had a 40% reduction (95% CI: 0.5–0.8) in the risk of dying. Mortality in women with only a second-degree family history was similar to those with no family history. The risk of dying was further reduced in those with a greater number of affected relatives. These relationships did not seem to be attributable to differences in screening, detection method, or treatment. Tumors in women with a first-degree family history had generally more favorable prognostic profiles.
Conclusion: Our findings suggest that breast cancer patients with a first-degree family history, compared with their counterparts without such a profile, may have a better prognosis.
Impact: These findings support the need for future research directed at replicating these results and identifying factors underlying this possible relationship. Cancer Epidemiol Biomarkers Prev; 20(12); 2560–71. ©2011 AACR.
Telomere Length and TERT Functional Polymorphisms Are Not Associated with Risk of Squamous Cell Carcinoma of the Head and Neck
Authors: Liu Zhensheng , Ma Hongxia , Wei Sheng , Li Guojun , Sturgis Erich M. , Wei Qingyi 
Published: December 2011

Abstract
Background: Recent studies reported associations of the relative telomere length (RTL) and TERT variants with risk of several cancers, which have not been comprehensively investigated in squamous cell carcinoma of the head and neck (SCCHN).
Methods: We detected RTL in peripheral blood lymphocytes and genotyped six selected functional single-nucleotide polymorphisms (SNP) of the TERT gene in 888 SCCHN cases and 885 cancer-free controls of non-Hispanic whites.
Results: Overall, we did not observe significant associations between RTL and SCCHN risk (adjusted OR = 0.97; 95% CI = 0.80–1.17 for below versus above the median; Ptrend = 0.618) nor between the six TERT SNPs and SCCHN risk. We also found no associations between RTL and TERT SNPs.
Conclusions: Our results suggest that RTL and TERT functional polymorphisms may not play a major role in the etiology of SCCHN. Large prospective studies are needed to validate our findings.
Impact: Although our results suggest no association among RTL, TERT functional polymorphisms, and SCCHN risk, this study may contribute to future meta-analysis. Cancer Epidemiol Biomarkers Prev; 20(12); 2642–5. ©2011 AACR.
Catheter Ablation of Right Atrial Ganglionated Plexi in Patients With Vagal Paroxysmal Atrial Fibrillation
Authors: Calò Leonardo , Rebecchi Marco , Sciarra Luigi , De Luca Lucia , Fagagnini Alessandro , Zuccaro Lorenzo Maria , Pitrone Pietro , Dottori Serena , Porfirio Maurizio , de Ruvo Ermenegildo , Lioy Ernesto 
Published: December 2011

Background—
Catheter ablation of ganglionated plexi (GP) in the left atrium has been proposed in different subgroup of patients with atrial fibrillation (AF). Anatomic studies found a high prevalence of GP in the posterior surface of the right atrium (RA). Experimental data suggested the potential role of right atrial GP in the AF initiation and maintenance. The aim of our study was to assess the efficacy of GP ablation in RA in patients with vagal AF.

Methods and Results—

Thirty-four patients without structural heart diseases were randomly assigned for a selective ablation procedure targeted on the elimination of vagal reflex evoked by high frequency stimulation or an extensive approach at anatomic sites of GP. All patients underwent Holter ECG and heart rate variability evaluation at baseline and at 3, 6, 12, and 18 months of follow-up. At a mean follow-up of 19.7±5.2 months, AF recurred in 5 of 17 patients with anatomic ablation and in 13 of 17 patients with a selective approach (
P
=0.01). No patient had major complications. After ablation, heart rate variability parameters showed a significant parasympathetic (and sympathetic) denervation in the first 6 months, which was more prominent in patients with anatomic GP ablation and in those without AF recurrence.

Conclusions—
This study demonstrates that in a selected population of vagal paroxysmal AF, the anatomic ablation of GPs in the RA is effective in about 70% of patients. These results confirm that atrial vagal denervation can abolish AF, as suggested by experimental and clinical data.
Retrospective Description and Analysis of Consecutive Catheterization Laboratory ST-Segment Elevation Myocardial Infarction Activations With Proposal, Rationale, and Use of a New Classification Scheme
Authors: Mixon Timothy A. , Suhr Eunice , Caldwell Gerald , Greenberg Robert D. , Colato Fernando , Blackwell Jeffry , Jo Chan-Hee , Dehmer Gregory J. 
Published: December 2011

Background—
Rapid activation of a cardiac catheterization laboratory (CCL) has reduced door-to-balloon times in ST-segment elevation myocardial infarction (STEMI), leading to lower mortality. This process is accelerated with prehospital electrocardiography and notification. False activations of the CCL occur at an unknown rate and have been poorly described.

Methods and Results—
We analyzed 345 consecutive CCL activations for suspected STEMI over 18 months (March 2009–August 2010). We retrospectively reviewed the ECGs that prompted activation, as well as the clinical course and final diagnoses. Among all CCL activations, STEMI was not confirmed in 28%. On review, 301 (87.2%) had appropriate ECG criteria for activation. However, even among the ECG-appropriate patients, only 247 (82%) had a final diagnosis of STEMI. The inclusion of clinical characteristics did not improve the ability to identify patients with STEMI. Activations were modestly more accurate when made by emergency department physicians than by emergency medical service personnel, but door-to-balloon time was noticeably shorter when emergency medical service personnel requested prehospital activation.

Conclusions—
If all CCL activations are considered, the occurrence of false activations is surprisingly high. Although still the gold standard for diagnosis, these data reveal the inherent limitations of clinical evaluation and the ECG in identifying patients with STEMI. Within our retrospective review, we used a 2-tiered classification for STEMI activations based on ECG appropriateness and final clinical diagnosis to give a complete picture of false activations and assist in quality improvement.
A Percutaneous Coronary Intervention Lab in Every Hospital?
Authors: Concannon Thomas W. , Nelson Jason , Goetz Jessica , Griffith John L. 
Published: December 2011

Background—
In 2001, 1176 US hospitals were capable of performing primary percutaneous coronary intervention (PCI), and 79% of the population lived within 60-minute ground transport of these hospitals. We compared these estimates with data from 2006 to explore how hospital PCI capability and population access have changed over time.

Methods and Results—
We estimated the proportion of the population 18 years of age or older, living in 2006 within a 60-minute drive of a PCI-capable hospital, and we compared our estimate with a previously published report on 2001 data. Over the 5-year period, the number of PCI-capable hospitals grew from 1176 to 1695 hospitals, a relative increase of 44%; access to the procedure grew from 79.0% to 79.9% of the population, a relative increase of 1%.

Conclusions—
Our data indicate a large increase in the number of hospitals capable of performing PCI from 2001 to 2006, but this increase was not associated with an appreciable change in the proportion of the population with access to the procedure. In the future, more attention is needed on changes in PCI capacity over time and on the effects of these changes on outcomes of interest such as service utilization, expenditures, patient outcomes, and population health.
Comprehensive Use of Cardiopulmonary Exercise Testing Identifies Adults With Congenital Heart Disease at Increased Mortality Risk in the Medium Term
Authors: Inuzuka Ryo , Diller Gerhard-Paul , Borgia Francesco , Benson Leah , Tay Edgar L.W. , Alonso-Gonzalez Rafael , Silva Margarida , Charalambides Menelaos , Swan Lorna , Dimopoulos Konstantinos , Gatzoulis Michael A. 
Published: December 2011

Background—
Parameters of cardiopulmonary exercise testing were recently identified as strong predictors of mortality in adults with congenital heart disease. We hypothesized that combinations of cardiopulmonary exercise testing parameters may provide optimal prognostic information on midterm survival in this population.

Methods and Results—

A total of 1375 consecutive adult patients with congenital heart disease (age, 33±13 years) underwent cardiopulmonary exercise testing at a single center over a period of 10 years. Peak oxygen consumption (peak V̇
o
2
), ventilation per unit of carbon dioxide production (V̇
e
/V̇
co
2
slope), and heart rate reserve were measured. During a median follow-up of 5.8 years, 117 patients died. Peak V̇
o
2
, heart rate reserve, and V̇
e
/V̇
co
2
slope were related to midterm survival in adult patients with congenital heart disease. Risk of death increased with lower peak V̇
o
2
and heart rate reserve. A higher V̇
e
/V̇
co
2
slope was also related to increased risk of death in noncyanotic patients, whereas the V̇
e
/V̇
co
2
slope was not predictive of mortality in cyanotic patients. The combination of peak V̇
o
2
and heart rate reserve provided the greatest predictive information after adjustment for clinical parameters such as negative chronotropic agents, age, and presence of cyanosis. However, the incremental value of these exercise parameters was reduced in patients with peak respiratory exchange ratio <1.0.

Conclusions—
Cardiopulmonary exercise testing provides strong prognostic information in adult patients with congenital heart disease. Prognostication should be approached differently, depending on the presence of cyanosis, use of rate-lowering medications, and achieved level of exercise. We provide 5-year survival prospects based on cardiopulmonary exercise testing parameters in this growing population.
The Impacts of “Growing Our Own”
Authors: Kahn Linda S. , Tumiel-Berhalter Laurene , D’Aniello Rona , Danzo Andy , Fox Chester H. , Taylor John , Holland Shannon , Glaser Kathryn , Patel Vinod , Glick Myron 
Published: December 2011

Purpose The purpose of the study was to examine the impact of incorporating certified diabetes educator trainees into medical practices on patient diabetes outcomes. Methods This was a mixed methods practice-based evaluation study undertaken in 2 primary care practices in high-poverty neighborhoods in Buffalo, New York. The evaluation entailed a physician-referred patient cohort with pre- and postanalysis of chart review data corresponding to the American Diabetes Association’s diabetes indicators. Patient charts were reviewed at baseline and 12 months. A brief survey was administered to the providers and staff to ascertain the extent to which the certified diabetes educator trainees were perceived as useful as part of the medical practice team. Results Among 74 patients enrolled in diabetes classes, A1C levels decreased from a mean of 8.8% to 8.3%. Among a subset of patients (35%) with poorly controlled diabetes at baseline (A1C ≥ 9), there was a 15% decrease in A1C levels. Overall improvement in A1C was observed among 219 patients seen by a diabetes educator, in either a diabetes education class or a one-on-one visit. Conclusions Results suggest that having a certified diabetes educator trainee as part of the primary care practice team may advance diabetes care, as evidenced by improvements in glucose control. Responses from providers and staff suggest that the certified diabetes educator trainees were well integrated into the practices and were perceived as instrumental in educating patients to better manage their diabetes.
The Multiple Sclerosis Work Difficulties Questionnaire
Authors: Honan Cynthia A , Brown Rhonda F , Hine Donald W , Vowels Lindsay , Wollin Judy A , Simmons Rex D , Pollard John D 
Published: December 2011

Background: A better understanding of the workplace difficulties experienced by people with multiple sclerosis (PwMS) may be critical to developing appropriate vocational and rehabilitative programs. Objective: We aimed to assess the factor structure, internal consistency and validity of the new Multiple Sclerosis Work Difficulties Questionnaire (MSWDQ). Methods: Work difficulty items were developed and reviewed by a panel of experts. Using the MSWDQ, cross-sectional self-report data of work difficulties were obtained in addition to employment status and MS disease information, in a community-based sample of 189 PwMS. Results: Exploratory Maximum Likelihood Factor Analysis on the draft questionnaire yielded 50 items measuring 12 factors. Subscale internal consistencies ranged from 0.74 to 0.92, indicating adequate to excellent internal consistency reliability. The MSWDQ explained 40% of the variance in reduced work hours since diagnosis, 40% of the variance in expectations about withdrawing from work, 34% of the variance in expectations about reducing work hours, and 39% of the variance in expectations about changing type of work due to MS. Conclusion: The MSWDQ is a valid and internally reliable measure of workplace difficulties in PwMS. Physical difficulties, as well as cognitive and psychological difficulties were important predictors of workplace outcomes and expectations about future employment.
Angiogenesis: A Target in Solid Tumors, Also in Leukemia?
Authors: Schmidt Thomas , Carmeliet Peter 
Published: December 2011

Abstract
Targeting angiogenesis has become an established therapeutic approach to fighting solid tumor growth in cancer patients. Even though increased angiogenesis has long been recognized in various types of hematologic malignancies, the molecular basis underlying this angiogenic switch in leukemias remains poorly understood. The BM stroma is gaining increasing attention for its role in promoting leukemia growth and resistance against current treatments with tyrosine kinase inhibitors. This article provides a brief overview of the role of angiogenesis in leukemias, discusses recent insights into the role of placenta growth factor (PlGF), a VEGF family member, as a novel disease candidate in chronic myeloid leukemia (CML), and highlights the therapeutic potential of PlGF blockade for imatinib-resistant CML.
How I Diagnose and Manage HIT
Authors: Warkentin Theodore E. 
Published: December 2011

Abstract
Heparin-induced thrombocytopenia (HIT) is a prothrombotic drug reaction caused by platelet-activating IgG antibodies that recognize platelet factor 4 (PF4)/polyanion complexes. Platelet activation assays, such as the serotonin-release assay, are superior to PF4-dependent immunoassays in discerning which heparin-induced antibodies are clinically relevant. When HIT is strongly suspected, standard practice includes substituting heparin with an alternative anticoagulant; the 2 US-approved agents are the direct thrombin inhibitors (DTIs) lepirudin and argatroban, which are “niche” agents used only to manage HIT. However, only ∼ 10% of patients who undergo serological investigation for HIT actually have this diagnosis. Indeed, depending on the clinical setting, only 10%-50% of patients with positive PF4-dependent immunoassays have platelet-activating antibodies. Therefore, overdiagnosis of HIT can be minimized by insisting that a positive platelet activation assay be required for definitive diagnosis of HIT. For these reasons, a management strategy that considers the real possibility of non-HIT thrombocytopenia is warranted. One approach that I suggest is to administer an indirect, antithrombin (AT)–dependent factor Xa inhibitor (danaparoid or fondaparinux) based upon the following rationale: (1) effectiveness in treating and preventing HIT-associated thrombosis; (2) effectiveness in treating and preventing thrombosis in diverse non-HIT situations; (3) both prophylactic- and therapeutic-dose protocols exist, permitting dosing appropriate for the clinical situation; (4) body weight–adjusted dosing protocols and availability of specific anti-factor Xa monitoring reduce risk of under- or overdosing (as can occur with partial thromboplastin time [PTT]–adjusted DTI therapy); (5) their long half-lives reduce risk of rebound hypercoagulability; (6) easy coumarin overlap; and (7) relatively low cost.
Atypical Hemolytic Uremic Syndrome, Genetic Basis, and Clinical Manifestations
Authors: Kavanagh David , Goodship Timothy H. J. 
Published: December 2011

AbstractAtypical hemolytic uremic syndrome (aHUS) is now well recognized to be a disease characterized by excessive complement activation in the microvasculature. In both the familial and sporadic forms, inherited and acquired abnormalities affecting components of the alternative complement pathway are found in ∼ 60% of patients. These include mutations in the genes encoding both complement regulators (factor H, factor I, membrane cofactor protein, and thrombomodulin) and activators (factors B and C3) and autoantibodies against factor H. Multiple hits are necessary for the disease to manifest, including a trigger, mutations, and at-risk haplotypes in complement genes. The prognosis for aHUS is poor, with most patients developing end-stage renal failure. Renal transplantation in most patients also has a poor prognosis, with frequent loss of the allograft to recurrent disease. However, improving results with combined liver-kidney transplantation and the advent of complement inhibitors such as eculizumab offer hope that the prognosis for aHUS will improve in future years.
Genetic and Epigenetic Complexity in Myeloproliferative Neoplasms
Authors: Cross Nicholas C. P. 
Published: December 2011

Abstract
The past 7 years have witnessed remarkable progress in our understanding of the genetics of BCR-ABL–negative myeloproliferative neoplasms (MPNs) and has revealed layers of unexpected complexity. Deregulation of JAK2 signaling has emerged as a central feature, but despite having biological activities that recapitulate the cardinal features MPNs in model systems, JAK2 mutations are often secondary events. Several other mutated genes have been identified with a common theme of involvement in the epigenetic control of gene expression. Remarkably, the somatic mutations identified to date do not seem to be acquired in any preferred order, and it is possible that the disease-initiating events remain to be identified. The finding of complex clonal hierarchies in many cases suggests genetic instability that, in principle, may be inherited or acquired. A common haplotype has been identified that is strongly associated with the acquisition of JAK2 mutations, but the cause of relatively high-penetrance familial predisposition to MPNs remains elusive. This review summarizes the established facts relating to the genetics of MPNs, but highlights recent findings and areas of controversy.
Late Effects of Acute Lymphoblastic Leukemia Therapy in Patients Diagnosed at 0-20 Years of Age
Authors: Robison Leslie L. 
Published: December 2011

Abstract
Survival rates for children with acute lymphoblastic leukemia (ALL) have increased dramatically over the past 4 decades, with 5-year survival rates of > 90% in recent trials. With the increasing number of children and adolescents cured of ALL, identifying and characterizing the occurrence of long-term adverse late effects has become increasingly important. In this young population, successful treatment of ALL is associated with increased risk of adverse outcomes such as late mortality, second neoplasms, chronic health conditions, endocrine dysfunction, and psychological function. Research efforts conducted through large survivor cohorts, such as the Childhood Cancer Survivor Study, are providing new and important insights into the very long-term consequences of ALL therapy, while providing direction for screening recommendations and intervention-based approaches for reducing late morbidity and mortality.
World Health Organization Classification, Evaluation, and Genetics of the Myeloproliferative Neoplasm Variants
Authors: Vardiman James , Hyjek Elizabeth 
Published: December 2011

AbstractThere is no single category in the fourth edition (2008) of the World Health Organization (WHO) classification of myeloid neoplasms that encompasses all of the diseases referred to by some authors as the myeloproliferative neoplasm (MPN) “variants.” Instead, they are considered as distinct entities and are distributed among various subgroups of myeloid neoplasms in the classification scheme. These relatively uncommon neoplasms do not meet the criteria for any so-called “classical” MPN (chronic myelogenous leukemia, polycythemia vera, primary myelofibrosis, or essential thrombocythemia) and, although some exhibit myelodysplasia, none meets the criteria for any myelodysplastic syndrome (MDS). They are a diverse group of neoplasms ranging from fairly well-characterized disorders such as chronic myelomonocytic leukemia to rare and thus poorly characterized disorders such as chronic neutrophilic leukemia. Recently, however, there has been a surge of information regarding the genetic infrastructure of neoplastic cells in the MPN variants, allowing some to be molecularly defined. Nevertheless, in most cases, correlation of clinical, genetic, and morphologic findings is required for diagnosis and classification. The fourth edition of the WHO classification provides a framework to incorporate those neoplasms in which a genetic abnormality is a major defining criterion of the disease, such as those associated with eosinophilia and abnormalities of PDGFRA, PDGFRB, and FGFR1, as well as for those in which no specific genetic defect has yet been discovered and which remain clinically and pathologically defined. An understanding of the clinical, morphologic, and genetic features of the MPN variants will facilitate their diagnosis.
Eosinophilic Myeloproliferative Disorders
Authors: Klion Amy D. 
Published: December 2011

AbstractDespite recent attempts to define and classify patients with marked eosinophilia and features consistent with myeloproliferative disease, areas of controversy remain. These are particularly apparent in situations in which multiple lineages are involved in a clonal process and clinical manifestations are overlapping. Although the introduction of new molecular diagnostics and targeted therapies has begun to clarify the boundaries between some of these disorders, several questions remain with respect to the classification of patients with myeloproliferative hypereosinophilic syndrome (HES) of unknown etiology.