bluuebunny/crossref_metadata_2025_split huggingface dataset:
FIB-4 Index Is Associated with Hepatocellular Carcinoma Risk in HIV-Infected Patients
Authors: Park Lesley S. , Tate Janet P. , Justice Amy C. , Lo Re Vincent , Lim Joseph K. , Bräu Norbert , Brown Sheldon T. , Butt Adeel A. , Gibert Cynthia , Goetz Matthew Bidwell , Rimland David , Rodriguez-Barradas Maria C. , Dubrow Robert 
Published: December 2011

Abstract
Background: Chronic inflammation caused by hepatitis B virus infection, hepatitis C virus infection, and/or heavy alcohol use can lead to fibrosis, cirrhosis, and eventually hepatocellular carcinoma (HCC). FIB-4 is an index score calculated from platelet count, alanine transaminase, aspartate transaminase, and age that predicts fibrosis and cirrhosis. We hypothesized that high FIB-4 would be associated with development of HCC in HIV-infected persons, who are at high risk due to high prevalence of viral hepatitis and alcohol consumption, and possibly due to HIV infection itself.
Methods: Using proportional hazards models, we tested this hypothesis among 22,980 HIV-infected men from the Veterans Aging Cohort Study. We identified incident HCC cases from the Veterans Affairs Central Cancer Registry.
Results: During follow-up, there were 112 incident HCC diagnoses. The age- and race/ethnic group-adjusted HR was 4.2 [95% confidence interval (CI), 2.4–7.4] for intermediate FIB-4 and 13.0 (95% CI, 7.2–23.4) for high FIB-4, compared with low FIB-4. After further adjustment for enrollment year, CD4 count, HIV-1 RNA level, antiretroviral therapy use, hepatitis B and C virus infection, alcohol abuse/dependency, and diabetes, FIB-4 remained a strong, significant, independent risk factor for HCC. The multivariate-adjusted HR was 3.6 (95% CI, 2.1–6.4) for intermediate FIB-4 and 9.6 (95% CI, 5.2–17.4) for high FIB-4.
Conclusions: Calculated from routine, noninvasive laboratory tests, FIB-4 is a strong, independent HCC risk factor in HIV-infected patients.
Impact: FIB-4 might prove valuable as an easily measured index to identify those at highest risk for HCC, even prior to development of clinical cirrhosis. Cancer Epidemiol Biomarkers Prev; 20(12); 2512–7. ©2011 AACR.
Melanoma Risk in Relation to Use of Sunscreen or Other Sun Protection Methods
Authors: Lazovich DeAnn , Vogel Rachel Isaksson , Berwick Marianne , Weinstock Martin A. , Warshaw Erin M. , Anderson Kristin E. 
Published: December 2011

Abstract
Background: Epidemiologic evidence supporting sunscreen for melanoma prevention is limited to one small trial; case–control studies report conflicting results. Sunscreen usage patterns or alternative sun protection methods have rarely been studied in relation to melanoma.
Methods: In a population-based case–control study, participants (1,167 cases; 1,101 controls) reported for each decade year of age outdoor activity-related sunscreen use, sunscreen patterns (SPF15+, amount, skin coverage, reapplication, routine use), and use of other sun protection methods (like hats, long-sleeved shirts, staying in the shade). Scores were averaged across activities and/or decades; scores in the most recent two decades were used to classify individuals as non-, inconsistent- or optimal users. Adjusted mean score differences between cases and controls, and ORs and 95% CIs for melanoma among optimal-, inconsistent- versus nonusers were calculated.
Results: Mean scores for sunscreen, sunscreen patterns or other sun protection methods were low, but higher among controls than cases for SPF15+ sunscreen (P = 0.03) and other sun protection methods (P = 0.006). Adjusted ORs for optimal use of sunscreen and most sunscreen patterns were null or relatively weak, except for routine sunscreen (adjusted OR = 0.44, 95% CI: 0.23–0.86). Optimal use of other sun protection methods was inversely associated with melanoma (adjusted OR = 0.59, 95% CI: 0.44–0.78).
Conclusions: Optimal use of routine sunscreen or other sun protection methods were most strongly associated with decreased melanoma risk; results are limited by the small number of subjects who used sunscreen routinely and lack of specificity regarding other sun protection methods.
Impact: Both improving sunscreen practices and encouraging sun avoidance strategies may be important for melanoma prevention. Cancer Epidemiol Biomarkers Prev; 20(12); 2583–93. ©2011 AACR.
Cataract and Ovarian Carcinoma: Is the Vitamin D Hypothesis Alive?
Authors: Lurie Galina , Matsuno Rayna K. , Wilkens Lynne R. , Thompson Pamela J. , Ollberding Nicholas J. , Carney Michael E. , Goodman Marc T. 
Published: December 2011

Abstract
Background: The major health benefit of exposure to solar UV radiation is the production of vitamin D, which is implicated in protection against several human cancers, including ovarian carcinoma. On the other hand, solar UV radiation is a recognized risk factor for cataract.
Methods: This population-based case–control study of 709 women with primary invasive ovarian carcinoma and 1,101 controls examined the association of ovarian carcinoma risk with self-reported history of cataract as an indicator of high long-term exposure to UV radiation. ORs and 95% confidence intervals (CI) were estimated using multivariate logistic regression models.
Results: Among controls, older age (P &lt; 0.0001), history of type 2 diabetes (P = 0.04), and skin cancer (P = 0.03) were significant cataract risk predictors. A history of cataract, reported by 14% of cases and 17% of controls, was significantly associated with a reduced ovarian carcinoma risk (OR = 0.6; 95% CI, 0.4–0.8; P = 0.002). No heterogeneity was observed by tumor histology, stage, grade, study site, body mass index, or other ovarian cancer risk factors (P &gt; 0.16).
Conclusion: These findings add indirect evidence to the hypothesis that lifetime vitamin D exposure may be inversely associated with risk of ovarian carcinoma.
Impact: The study suggests some potential new avenues for research. Additional studies are needed to further investigate the potential behavioral and biologic factors that might influence association of cataract with ovarian cancer. Cancer Epidemiol Biomarkers Prev; 20(12); 2507–11. ©2011 AACR.
A Prospective Cohort Study of Coffee Consumption and Risk of Endometrial Cancer over a 26-Year Follow-Up
Authors: Je Youjin , Hankinson Susan E. , Tworoger Shelley S. , DeVivo Immaculata , Giovannucci Edward 
Published: December 2011

Abstract
Background: Coffee has been reported to lower levels of estrogen and insulin, two hormones implicated in endometrial carcinogenesis, but prospective data on the relation between coffee consumption and risk of endometrial cancer are limited.
Methods: We prospectively assessed coffee consumption in relation to endometrial cancer risk in the Nurses' Health Study (NHS) with 67,470 female participants aged 34 to 59 in 1980. Cumulative average coffee intake was calculated with all available questionnaires to assess long-term effects. Cox regression models were used to calculate incidence rate ratios (RR), controlling for other risk factors.
Results: Fewer than 4 cups of coffee per day were not associated with endometrial cancer risk. However, women who consumed 4 or more cups of coffee had 25% lower risk of endometrial cancer than those who consumed less than 1 cup per day (multivariable RR = 0.75; 95% CI = 0.57–0.97; Ptrend = 0.02). We found the similar association with caffeinated coffee consumption (RR for ≥4 vs. &lt;1 cup/d = 0.70; 95% CI = 0.51–0.95). For decaffeinated coffee consumption, a suggestive inverse association was found among women who consumed 2 or more cups per day versus &lt;1 cup/mo. Tea consumption was not associated with endometrial cancer risk.
Conclusions: These prospective data suggest that four or more cups of coffee per day are associated with a lower risk of endometrial cancer.
Impact: Drinking of coffee, given its widespread consumption, might be an additional strategy to reduce endometrial cancer risk. However, addition of substantial sugar and cream to coffee could offset any potential benefits. Cancer Epidemiol Biomarkers Prev; 20(12); 2487–95. ©2011 AACR.
Use and Effectiveness of Intra-Aortic Balloon Pumps Among Patients Undergoing High Risk Percutaneous Coronary Intervention: Insights From the National Cardiovascular Data Registry
Authors: Curtis Jeptha P. , Rathore Saif S. , Wang Yongfei , Chen Jersey , Nallamothu Brahmajee K. , Krumholz Harlan M. 
Published: December 2011

Background—
Intra-aortic balloon pumps (IABP) frequently are used to provide hemodynamic support during high risk percutaneous coronary intervention (PCI), but clinical evidence to support their use is mixed. We examined hospital variation in IABP use among high risk PCI patients, and determined the association of IABP use on mortality in this population.

Methods and Results—
We analyzed data submitted to the CathPCI Registry between January 2005 and December 2007. High risk PCI was defined as having at least 1 of the following features: unprotected left main artery as the target vessel, cardiogenic shock, severely depressed left ventricular function, or ST segment elevation myocardial infarction. Hospitals were categorized into quartiles by their proportional use of IABP. We examined differences in in-hospital mortality across hospital quartiles using a hierarchical logistic regression model to adjust for differences in patient and hospital characteristics across hospital quartiles of IABP use. IABPs were used in 18 990 (10.5%) of 181 599 high risk PCIs. Proportional use of IABP varied significantly across hospital quartiles: Q1, 0.0 to 6.5%; Q2, 6.6 to 9.2%; Q3, 9.3 to 14.1%; Q4, 14.2 to 40.0%. In multivariable analysis, after adjustment for differences in patient and hospital characteristics, in-hospital mortality was comparable across quartiles of hospital IABP usage (Q1, Ref; Q2, odds ratio 1.11, 95% CI 0.99–1.24; Q3, OR 1.03, 95% CI 0.92–1.15; Q4, OR 1.06, 95% CI 0.94–1.18).

Conclusions—
IABP use varied significantly across hospitals for high risk PCI. However, this variation in IABP use was not associated with differences in in-hospital mortality.
Rates of Cardiac Catheterization Cancelation for ST-Segment Elevation Myocardial Infarction After Activation by Emergency Medical Services or Emergency Physicians
Authors: Garvey J. Lee , Monk Lisa , Granger Christopher B. , Studnek Jonathan R. , Roettig Mayme Lou , Corbett Claire C. , Jollis James G. 
Published: December 2011

Background—
For patients with an acute ST-segment elevation myocardial infarction, cardiac catheterization laboratory (CCL) activation by emergency medical technicians or emergency physicians has been shown to substantially reduce treatment times. One drawback to this approach involves overtriage, whereby CCL staffs are activated for patients who ultimately do not require emergent coronary angiography or for patients who undergo angiography but are not found to have coronary artery occlusion.

Methods and Results—
We examined CCL activation at 14 primary angioplasty hospitals to determine the course of management, including the rate of inappropriate activation. Among 3973 activations (29% by emergency medical technicians, 71% by emergency physicians) between December 2008 and December 2009, appropriate CCL activations occurred for 3377 patients (85%), with 2598 patients (76.9% of appropriate activations) receiving primary percutaneous coronary intervention. Reasons for inappropriate activations (596 patients; 15%) included ECG reinterpretations (427 patients; 72%) or the fact that the patient was not a CCL candidate (169 patients; 28%). The rate of cancellation because of reinterpretation of emergency medical technicians' ECG (6% of all activations) was more common than for cancellation because of reinterpretation of emergency physicians' ECG (4.6%).

Conclusions—
This represents the first report of the rates of CCL cancellation for ST-segment elevation myocardial infarction system activation by emergency medical technicians and emergency physicians in a large group of hospitals organized within a statewide program. The high rate of coronary intervention and relatively low rate of inappropriate activation suggest that systematic CCL activation by emergency personnel on a broad scale is feasible and accurate, and these rates set a benchmark for ST-segment elevation myocardial infarction systems.
Is Thrombophilia Testing Useful?
Authors: Middeldorp Saskia 
Published: December 2011

Abstract
Thrombophilia is found in many patients presenting with venous thromboembolism (VTE). However, whether the results of such tests help in the clinical management of such patients has not been determined. Thrombophilia testing in asymptomatic relatives may be useful in families with antithrombin, protein C, or protein S deficiency or homozygosity for factor V Leiden, but is limited to women who intend to become pregnant or who would like to use oral contraceptives. Careful counseling with knowledge of absolute risks helps patients in making an informed decision in which their own preferences can be taken into account. Observational studies show that patients who have had VTE and have thrombophilia are at most at a slightly increased risk for recurrence. In an observational study, the risk of recurrent VTE in patients who had been tested for inherited thrombophilia was not lower than in patients who had not been tested. In the absence of trials comparing routine and prolonged anticoagulant treatment in patients testing positive for thrombophilia, testing for such defects to prolong anticoagulant therapy cannot be justified. Diagnosing antiphospholipid syndrome (APS) in women with recurrent miscarriage usually leads to treatment with aspirin and low-molecular-weight heparin (LMWH), although the evidence to support this treatment is limited. Because testing for thrombophilia serves a limited purpose, this test should not be performed on a routine basis.
Approach to Hemophagocytic Syndromes
Authors: Weitzman Sheila 
Published: December 2011

AbstractHemophagocytic lymphohistiocytosis (HLH) is a potentially fatal hyperinflammatory condition. It may occur as a primary (genetic) condition due to mutations in genes important in the cytolytic secretory pathway that cause perforin and granzymes to induce apoptosis in target cells. Primary HLH is divided into familial HLH (FHLH1-5), in which HLH is the only manifestation of disease, and other genetic causes in which HLH is one of several clinical manifestations. The identical clinical findings may arise secondary to infectious, rheumatologic, malignant, or metabolic conditions. Whether primary or secondary, HLH therapy needs to be instituted promptly to prevent irreversible tissue damage. It is helpful to think of HLH as the severe end of the spectrum of hyperinflammatory disorders when the immune system starts to damage host tissues (immunopathology). Therefore, no single clinical feature alone is diagnostic for HLH, and it is important that the entire clinical presentation be considered in making the diagnosis. This article contains a discussion of the genetic background, clinical presentation, diagnostic dilemmas, and features that are helpful in making the diagnosis of HLH, along with a discussion of common problems in its management.
Management of Essential Thrombocythemia
Authors: Cervantes Francisco 
Published: December 2011

Abstract
Essential thrombocythemia (ET) is a Philadelphia chromosome (Ph)–negative myeloproliferative neoplasm (MPN) characterized by thrombocytosis and megakaryocytic hyperplasia of the bone marrow, with presence of the JAK2 V617F mutation in 50%-60% of patients. ET evolves to myelofibrosis in a minority of cases, whereas transformation to acute leukemia is rare and increases in association with the use of certain therapies. Survival of ET patients does not substantially differ from that of the general population. However, important morbidity is derived from vascular complications, including thrombosis, microvascular disturbances, and bleeding. Because of this, treatment of ET must be aimed at preventing thrombosis and bleeding without increasing the risk of transformation of the disease. Patients are considered at high risk of thrombosis if they are older than 60 years or have a previous history of thrombosis and at high risk of bleeding if platelet counts are > 1500 × 109/L. Patients with low-risk ET are usually managed with low-dose aspirin, whereas treatment of high-risk ET is based on the use of cytoreductive therapy, with hydroxyurea as the drug of choice and IFN-α being reserved for young patients or pregnant women. For patients resistant or intolerant to hydroxyurea, anagrelide is recommended as second-line therapy. Strict control of coexistent cardiovascular risk factors is mandatory for all patients. The role in ET therapy of new drugs such as pegylated IFN or the JAK2 inhibitors is currently under investigation.
Genomics of AML: Clinical Applications of Next-Generation Sequencing
Authors: Welch John S. , Link Daniel C. 
Published: December 2011

Abstract
In the past decade, a series of technological advances have revolutionized our ability to interrogate cancer genomes, culminating in whole-genome sequencing, which provides genome-wide coverage at a single base-pair resolution. As sequencing technologies improve and costs decrease, it is likely that whole-genome sequencing of cancer cells will become commonplace in the diagnostic workup of patients with acute myelogenous leukemia (AML) and other cancers. The unprecedented molecular characterization provided by whole-genome sequencing offers the potential for an individualized approach to treatment in AML, bringing us one step closer to personalized medicine. In this chapter, we discuss how next-generation sequencing is being used to study cancer genomes. Recent publications of whole-genome sequencing in AML are reviewed and current limitations of whole-genome sequencing are examined, as well as current and potential future clinical applications of whole-genome sequencing.
Pediatric Acute Leukemia Therapies Informed by Molecular Analysis of High-Risk Disease
Authors: Winter Stuart S. 
Published: December 2011

Abstract
The acute leukemias are the most common cancer of children, adolescents, and young adults. These diseases are characterized by a tremendous variability in clinical course, prompting a continuing search for accurate predictors of outcome. Using algorithms based on clinical features at presentation, response to therapy, and several molecular analyses, some patients are diagnosed with features of high-risk disease and comparatively greater risk for relapse. Molecular analyses of patients with high-risk acute leukemias have resulted in an improved understanding of how dysregulated cellular signaling can affect resistance to conventional therapy. Whereas exciting discoveries continue to be made in the identification of relevant molecular biomarkers and targeted therapies, the challenges and opportunities associated with these findings remain to be clearly defined in future clinical trials.
What To Do When You Suspect an Inherited Platelet Disorder
Authors: Lambert Michele P. 
Published: December 2011

Abstract
Inherited platelet disorders (IPDs) comprise a heterogenous group of diseases that include defects in platelet function and disordered megakaryopoiesis. Some IPDs overlap as both defects in function and thrombopoiesis, resulting in both altered aggregation and/or secretion and thrombocytopenia. This review examines the key features of the presentation of IPDs in children and adults and presents a diagnostic algorithm for the evaluation of these patients. In addition, recent advances in our understanding of the pathophysiology of platelet disorders are addressed, with attention given to some of the novel genetic associations. Finally, treatment options and future therapies are briefly discussed.
What is the Evidence for the Use of Immunomodulatory Agents to Eradicate Inhibitory Antibodies in Patients with Severe Hemophilia A Who Have Previously Failed to Respond to Immune Tolerance Induction?
Authors: Callaghan Michael U. , Fogarty Patrick F. 
Published: December 2011

Abstract
An 18-year-old man has severe hemophilia A that has been complicated by a high-titer inhibitory antibody (peak 170 BU/mL). He had previously failed a trial of immune tolerance induction (ITI) using daily high-dose (100 units/kg/d) factor VIII (FVIII) for 20 months and would like to know if immunomodulatory agents, with or without another course of ITI, might eradicate the inhibitor.
Secondary Prevention of Overt Strokes in Sickle Cell Disease: Therapeutic Strategies and Efficacy
Authors: DeBaun Michael R. 
Published: December 2011

AbstractOvert strokes, previously one of the most common neurological complications in sickle cell disease (SCD), have become far less frequent with routine transcranial Doppler (TCD) assessment followed by regular blood transfusion therapy. Nevertheless, children and adults with SCD continue to have overt strokes, and in the foreseeable future will continue to require secondary prevention of strokes. With the exception of the most recently completed “Stroke With Transfusions Changing to Hydroxyurea” Trial (SWiTCH; NCT00122980), randomized trials providing best evidence for long-term management of overt strokes in SCD is lacking. Instead of randomized clinical trials, a series of observational and single-arm studies have predominated. This review assesses the best available evidence for acute and chronic management of overt stroke and the efficacy of regular blood transfusion therapy, hydroxyurea therapy, and hematopoietic stem cell transplantation (HSCT), including matched sibling donor and unrelated HSCT.
Targeted Therapeutic Strategies for Fetal Hemoglobin Induction
Authors: Sankaran Vijay G. 
Published: December 2011

AbstractIncreased levels of fetal hemoglobin (HbF) can ameliorate the severity of the β-hemoglobin disorders, sickle cell disease (SCD) and β-thalassemia, which are major sources of morbidity and mortality worldwide. As a result, there has been a longstanding interest in developing therapeutic approaches for inducing HbF. For more than 3 decades, the majority of HbF inducers developed were based on empiric observations and have had limited success. Recently, human genetic approaches have provided insight into previously unappreciated regulators of the fetal-to-adult hemoglobin switch and HbF silencing, revealing molecular targets to induce HbF. This article reviews these developments and discusses how molecules including BCL11A, KLF1, MYB, SOX6, miRNAs 15a and 16-1, and histone deacetylase 1 and 2 (HDAC1/2) could be important targets for HbF induction in humans. The current understanding of how these molecules function and the benefits and drawbacks of each of these potential therapeutic targets are also examined. The identification of these regulators of HbF expression is extremely promising and suggests that rationally designed approaches targeting the very mechanisms mediating this switching process could lead to better, less toxic, and more effective strategies for HbF induction.
Diamond Blackfan Anemia
Authors: Ball Sarah 
Published: December 2011

Abstract
Mutations affecting genes encoding ribosomal proteins cause Diamond Blackfan anemia (DBA), a rare congenital syndrome associated with physical anomalies, short stature, red cell aplasia, and an increased risk of malignancy. p53 activation has been identified as a key component in the pathophysiology of DBA after cellular and molecular studies of knockdown cellular and animal models of DBA and other disorders affecting ribosomal assembly or function. Other potential mechanisms that warrant further investigation include impaired translation as the result of ribosomal insufficiency, which may be ameliorated by leucine supplementation, and alternative splicing leading to reduced expression of a cytoplasmic heme exporter, the human homolog of the receptor for feline leukemia virus C (FVLCR). However, the molecular basis for the characteristic steroid responsiveness of the erythroid failure in DBA remains unknown. This review explores the clinical and therapeutic implications of the current state of knowledge and delineates important but as-yet-unanswered questions.