tbuckley/cabot-search huggingface dataset:
Hydroxyurea in sickle cell patients: A look at the correlation with hematologic malignancies.
Authors: Katharine Batt, Scott Isom, Andrew Matthew Farland, David Leedy, John Owen, Marcelo Raul Bonomi
Journal: Journal of Clinical Oncology (2015)

e12593 Background: Hydroxyurea (HU) is a chemotherapeutic agent used in sickle cell patients (SCP) to reduce the frequency and intensity of sickle pain crises. It is a myelosuppressive agent with proposed long-term carcinogenic and/or leukemic effects, particularly in myeloid malignancies. Current data has failed to conclusively demonstrate this outcome in its long-term use. Yet many SCP are maintained on HU for years and therefore, could provide evidence of the long-term neoplastic effects of HU. Methods: In a retrospective review of the Wake Forest Baptist Medical Center (WFBMC) Electronic Data Warehouse (EDW) capturing data from 1980 until present, we compared the prevalence of hematologic malignancies in SCP to the general population (GPop) using the appropriate ICD-9 codes (ICD-9 200-208.xx, 238.4, 238.71, 289.83, 277.30). We then examined the use of HU in the SCP versus the GPop to compare the difference in disease prevalence as it related to HU. Finally, the statistical significance was measured with the Fisher’s exact test. Results: Of the 3,874 SCP identified in the EDW, 163/3,874 (4.2%) were on HU. 153/3,874 (3.9%) had a diagnosis of a hematologic malignancy. In the GPop, 222.000 (1.04%) were diagnosed with a hematologic malignancy and 222/2,123,301 (0.01%) were on HU. 46 (1.19%) SCP were diagnosed with a lymphoid or histiocytic neoplasm versus 8,055 (0.37%) in the GPop; 4 (10.87%) SCP were on HU. 23 (0.59%) SCP versus 3,753 (0.18%) GPop had a lymphoid leukemia diagnosis; 4 (17.39%) SCP were on HU. 39 (1.01%) SCP had a myeloid leukemia diagnosis (4,957 (0.23%) GPop); 1 (0.03%) SCP was on HU (p < 0.5884). Conclusions: In a review of data collected over 35 years, there seems to be an increased prevalence of hematologic malignancies in the SCP population, predominantly of lymphoid origin; the use of HU seems to further influence this finding. In contrast, while there is a notable mild increase in myeloid leukemia diagnoses compared to the general population, there does not seem to be the same correlation with HU.
Clinical trial participation as part of end-of-life (EOL) cancer care: Associations with medical care near death and bereaved caregivers’ mental health.
Authors: Andrea Catherine Phelps, Baohui Zhang, Holly Gwen Prigerson
Journal: Journal of Clinical Oncology (2012)

9102 Background: Clinical trial participation is necessary to improve existing therapies, encouraged by national guidelines, and common among advanced cancer patients. The relationships between trial participation and important EOL outcomes such as aggressive care are unknown. Methods: Coping with Cancer Study, an NCI-funded multicenter prospective cohort study of advanced cancer patients and their caregivers, enrolled September 2002 – February 2008. Patients were interviewed at baseline, and clinical trial participation was documented by chart review. Patients were followed to death, (median 4.4 months from baseline). Medical care and quality of life (QOL) in the last week of life was assessed by caregiver interview and chart review. Caregiver interview 6 months post-bereavement assessed QOL and mental health (Structured Clinical Interview for the DSM-IV). The primary outcome was aggressive EOL care (ventilation, resuscitation, or chemotherapy in the last week of life). Secondary outcomes were bereaved caregivers’ mental health and QOL. Propensity-score weighting balanced patient characteristics (e.g. clinical variables, EOL preferences) that differed by trial participation. Propensity-score weighted regression models estimated the effect of trial participation on outcomes. Results: Of 246 patients followed to death with non-missing propensity scores, 27 were clinical trial participants. In propensity-score weighted analyses, trial participation was significantly associated with aggressive EOL care [29.6% v 9.1%; adjusted OR (AOR), 12.14; 95% CI, 3.65-40.36], ICU admission, mechanical ventilation, chemotherapy, and a trend toward inferior QOL near death (p = 0.069). Of 180 matched caregivers, trial participation predicted less mental illness [AOR, 0.15; 95% CI 0.04-0.57], major depression [AOR, 0.25; 95% CI, 0.08-0.80], but was unassociated with QOL (p = 0.15) in adjusted analyses. Conclusions: Clinical trial participation is associated with increased risk of aggressive EOL care for advanced cancer patients, but better mental health for bereaved caregivers.
A Step in the Direction of Health Insurance Reform
Authors: Ann E Mills, Patricia M Tereskerz
Journal: New England Journal of Medicine (2010)

On February 24, 2010, the U.S. House of Representatives passed the Health Insurance Industry Fair Competition Act, which would eliminate the antitrust exemptions granted to health insurers under the McCarran–Ferguson Act of 1945.1 The goal of the bill is to promote competition and so to improve quality and consumer access and ultimately drive down costs. There is debate as to whether or not the act, if passed by the Senate, will achieve these goals. Karen Ignagni, president and chief executive officer of the trade organization America's Health Insurance Plans, argues that states already regulate health insurers, and state law does . . .
QUANTITATIVE STUDIES ON THE MIXED LYMPHOCYTE INTERACTION IN RATS
Authors: Darcy B. Wilson, Janet L. Blyth, Peter C. Nowell
Journal: The Journal of Experimental Medicine (1968)

The proliferative interaction of cultured rat lymphocytes of immunogenetically disparate origin—the mixed lymphocyte interaction—was employed as an experimental model to examine the initial stages of the immune response mechanism. Using mixed cultures of cells derived from parental strain and F1 hybrid rats, in which only the parental lymphocytes respond, the following observations were made on the magnitude and kinetics of the reaction. After initiation of the cultures, there was a latent period of approximately 40 hours during which time no mitotic activity was detected. This inactive phase was followed by a period of proliferation in which previously nondividing cells entered the mitotic cycle for the first time. Activity in the cultures, as detected by incorporation of radioactive thymidine and measured by radioautography or scintillation spectrometry, increased exponentially with a doubling time (T2) of 9–10 hr. In this exponential proliferative phase, lasting approximately 100 hr, the dividing cells underwent a series of rapid sequential divisions with a generation time (Tc) of 8 hr, and few, if any, dropped out of the mitotic cycle. In addition to the cells which first entered mitosis at the beginning of the proliferative phase and then proceeded through multiple divisions, significant numbers of new, previously nondividing cells continued to enter the mitotic cycle during the entire exponential growth phase. The total number of these newly responsive, first division cells throughout the total culture period amounted to 1–3% of the original parental cell inoculum. This is a surprisingly large proportion of peripheral blood lymphocytes with demonstrable reactivity to a particular antigen system, if it is assumed that these first division cells in vitro are functionally related to the hypothetical antigen-sensitive cells which proliferate and differentiate into immunological effector cells. At present there is no entirely satisfactory explanation for this large number of reactive cells in the mixed lymphocyte interaction.
EPIDEMIOLOGICAL STUDY OF TAEKWONDO INJURIES: 1-YEAR PROSPECTIVE STUDY
Authors: Bo Ae Son, Hee Seong Jeong, In Deok Kong, Sae Yong Lee
Journal: British Journal of Sports Medicine (2017)

Background Taekwondo black belt population of Korea is among nation's best. However, there is no well-organized injury surveillance system (ISS) in Korea. Objective To analyse epidemiological data of youth Taekwondo injury to compare and examine injury incidence of adult athletes. Design Prospective epidemiological study. Setting Taekwondo competition and practice of 2016 season in Korea. Patients (or Participants) Eighty two middle, 76 high school, and 82 university Taekwondo athletes who registered officially for Korea Taekwondo Association participated in the study. Interventions (or Assessment of Risk Factors) The athletes with injuries to examine potential risk factors. Main Outcome Measurements Chi-square tests were used to compare rate of injury between gender and level. Injury rates per athletic exposure (A-E), odds ratios (OR) and 95% confidential intervals (CI) were conducted. Results Among the 243 registered athletes (33.5% female), a total of 155 injuries, 117 injuries occurred during 476,983 A-E 0.24 injuries per 1,000 AEs during training and 38 injuries during 1,036 per 1,063 AEs; 38.6 per 1,000 A-E during competition were reported. The majority of injury location was ankle (23.4%). Contusion (22.7%) was the most common types of injury. Injury rate was not significantly different between male and female. Youth athletes demonstrated significantly higher injury incidence (OR 2.16; CI: 1.24 to 3.78) as compared to that of adult athletes. However, adult athletes are more likely to have more severe injuries (OR 3.57; CI: 1.46 to 8.70). Conclusions This injury surveillance study provides an essential epidemiological information that will help clinicians to consider and develop prevention strategies to reduce injuries for both youth and adult athletes during training/competitions. Future research should evaluate injuries during match with same athletic population based on prospectively collecting ISS data.
Existence of a platelet-adhesion defect in patients with cirrhosis independent of hematocrit: Studies under flow conditions
Authors: A Ordinas, G Escolar, I Cirera, M Vinas, F Cobo, J Bosch, J Teres, J Rodés
Journal: Hepatology (1996)

A defect in hemostasis has been repeatedly reported in patients with cirrhosis. However, the nature of this defect has not been fully characterized. We explored adhesive and cohesive functions of platelets from cirrhotic patients at different stages of disease development. The response of platelets to standard activating agents was tested by aggregometric procedures. The interaction of platelets with subendothelial components was explored in a perfusion system in which blood was exposed (shear rate, 800/s; 10 minutes) to denuded segments of rabbit aorta. Platelet interactions in these perfusions were analyzed morphometrically. Results were always compared with those obtained in similar studies using blood obtained from healthy subjects. Aggregation studies showed abnormal responses for single or several agonists. Abnormalities in aggregation were more evident in patients with severe disease (Child–Pugh class C), although they occasionally were abnormal for single agonists (ADP or U46619) in patients with less severe disease (Child–Pugh classes A or B). All the patient classes showed impaired platelet–subendothelial interactions ( P &lt; .01 vs. healthy subjects) that were not justified by the relative thrombocytopenia present in the more severely affected patients. Experimental increases in hematocrit in patients at stages B and C did not improve platelet–subendothelial interactions. Platelets from cirrhotic patients interact defectively with subendothelial components under flow conditions. The adhesion defect is more evident and consistent than the aggregation defects and may already be present in patients with mild liver failure. This adhesion defect may contribute to the defective hemostasis observed in cirrhotic patients.
Disturbed grief: prolonged grief disorder and persistent complex bereavement disorder
Authors: Paul A Boelen, Geert E Smid
Journal: BMJ (2017)

Each individual's grief process is unique.The concept of stages of grief occurring in a specific order is a popular, yet inadequate representation of what grieving people go through. 1 Traditional models developed to understand grief therefore often unhelpfully suggest that all bereaved individual do, and even should, follow the same process towards recovery from loss.The newer grief task model 2 offers a more neutral framework to describe normal and disturbed grief.The model proposes that normal grief is the successful achievement of certain "grief tasks," whereas complications in managing these tasks might indicate disturbed grief.There is no recommended or specific order in which to achieve these tasks.Grief tasks include: to accept the reality of the loss; to process the associated pain; to adjust to a world without the deceased; and to find an enduring connection with the deceased in the midst of embarking on a new life.The model also describes challenges faced following losses other than bereavement (Box 'Grief following events other than bereavement').Doctors from any specialty can identify bereaved patients who are struggling for longer, or more severely than most.Defining when this grief becomes disturbed or pathological is difficult, and has been the subject of recent classification and debate (box 1).
Bedaquiline for the treatment of multidrug-resistant tuberculosis: another missed opportunity?
Authors: Lorenzo Guglielmetti
Journal: European Respiratory Journal (2017)

5 years after its first approval by a stringent regulatory authority, the role of bedaquiline in the treatment of multidrug-resistant tuberculosis (MDR-TB) and extensively drug-resistant tuberculosis (XDR-TB) is well established, and acknowledged by existing guidance. However, in many regards, the global introduction of bedaquiline can hardly be considered as a success. Scale-up of introduction of bedaquiline, as part of optimised treatment regimens, is supported by growing evidence <http://ow.ly/JCEV30aPLmq>
Brugada Syndrome: Report of the Second Consensus Conference
Authors: Charles Antzelevitch, Pedro Brugada, Martin Borggrefe, Josep Brugada, Ramon Brugada, Domenico Corrado, Ihor Gussak, Herve LeMarec, Koonlawee Nademanee, Andres Ricardo Perez Riera, Wataru Shimizu, Eric Schulze-Bahr, Hanno Tan, Arthur Wilde
Journal: Circulation (2005)

Since its introduction as a clinical entity in 1992, the Brugada syndrome has progressed from being a rare disease to one that is second only to automobile accidents as a cause of death among young adults in some countries. Electrocardiographically characterized by a distinct ST-segment elevation in the right precordial leads, the syndrome is associated with a high risk for sudden cardiac death in young and otherwise healthy adults, and less frequently in infants and children. Patients with a spontaneously appearing Brugada ECG have a high risk for sudden arrhythmic death secondary to ventricular tachycardia/fibrillation. The ECG manifestations of Brugada syndrome are often dynamic or concealed and may be unmasked or modulated by sodium channel blockers, a febrile state, vagotonic agents, α-adrenergic agonists, β-adrenergic blockers, tricyclic or tetracyclic antidepressants, a combination of glucose and insulin, hypo- and hyperkalemia, hypercalcemia, and alcohol and cocaine toxicity. In recent years, an exponential rise in the number of reported cases and a striking proliferation of articles defining the clinical, genetic, cellular, ionic, and molecular aspects of the disease have occurred. The report of the first consensus conference, published in 2002, focused on diagnostic criteria. The present report, which emanated from the second consensus conference held in September 2003, elaborates further on the diagnostic criteria and examines risk stratification schemes and device and pharmacological approaches to therapy on the basis of the available clinical and basic science data.
Patients criteria determining difficulty of the laparoscopic lateral transperitoneal adrenalectomy. A retrospective cohort study
Authors: Michał Natkaniec, Jadwiga Dworak, Michał Pędziwiatr, Magdalena Pisarska, Piotr Major, Marcin Dembiński, Marek Winiarski, Andrzej Budzyński
Journal: International Journal of Surgery (2017)
Benefit of Ezetimibe Added to Simvastatin in Reduced Kidney Function
Authors: John W. Stanifer, David M. Charytan, Jennifer White, Yuliya Lokhnygina, Christopher P. Cannon, Matthew T. Roe, Michael A. Blazing
Journal: Journal of the American Society of Nephrology (2017)

Efficacy of statin-based therapies in reducing cardiovascular mortality in individuals with CKD seems to diminish as eGFR declines. The strongest evidence supporting the cardiovascular benefit of statins in individuals with CKD was shown with ezetimibe plus simvastatin versus placebo. However, whether combination therapy or statin alone resulted in cardiovascular benefit is uncertain. Therefore, we estimated GFR in 18,015 individuals from the IMPROVE-IT (ezetimibe plus simvastatin versus simvastatin alone in individuals with cardiovascular disease and creatinine clearance &gt;30 ml/min) and examined post hoc the relationship of eGFR with end points across treatment arms. For the primary end point of cardiovascular death, major coronary event, or nonfatal stroke, the relative risk reduction of combination therapy compared with monotherapy differed by eGFR ( P =0.04). The difference in treatment effect was observed at eGFR≤75 ml/min per 1.73 m 2 and most apparent at levels ≤60 ml/min per 1.73 m 2 . Compared with individuals receiving monotherapy, individuals receiving combination therapy with a baseline eGFR of 60 ml/min per 1.73 m 2 experienced a 12% risk reduction (hazard ratio [HR], 0.88; 95% confidence interval [95% CI], 0.82 to 0.95); those with a baseline eGFR of 45 ml/min per 1.73 m 2 had a 13% risk reduction (HR, 0.87; 95% CI, 0.78 to 0.98). In stabilized individuals within 10 days of acute coronary syndrome, combination therapy seemed to be more effective than monotherapy in individuals with moderately reduced eGFR (30–60 ml/min per 1.73 m 2 ). Further studies examining potential benefits of combination lipid-lowering therapy in individuals with CKD are needed.
Bile Acids in Health and Disease: Update on Cholesterol Gallstones and Bile Acid Diarrhoea
Authors: Malcolm C Bateson
Journal: Journal of the Royal Society of Medicine (1988)

lipid-lowering properties.High levels of consumption of these fatty acids leads to a replacement of arachidonic acid in the membrane phospholipids of diverse cell types and a modulation ofthe production of eicosanoids including prostaglandins, prostacyclins, thromboxanes and leukotrienes.Earlier work had suggested potent effects of these fatty acids on platelets in vitro.However consumption of these fatty acids had more modest effects on platelets, but they may still be of value in the treatment ofthrombogenic disorders.Maxepa in doses of 10-15 g per day is particularly effective in lowering plasma triglyceride concentrations.At this intake, plasma cholesterol concentrations are not changed significantly.However, the potent tri- glyceride lowering properties may be of considerable significance when treating conditions wherecardiovascular disease is exacerbated by high concentrations of the triglyceride-rich lipoproteins (VLDL and IDL).The meeting was well attended indicating the growing interest in this area of research.It is clear that much more can be learned about the interactions of lipids with soluble coagulation factors, platelets and the endothelium.
Cancer and Bone*
Authors: Theresa A. Guise, Gregory R. Mundy
Journal: Endocrine Reviews (1998)

I. Introduction II. Normal Calcium and Bone Homeostasis A. Bone remodeling B. Calcium homeostasis C. Defenses against hyper- and hypocalcemia III. Humoral Mechanisms by Which Solid Tumors Affect the Skeleton A. Hypercalcemia B. Oncogenic osteomalacia C. Tumor lysis syndrome IV. Local Mechanisms by Which Tumors Affect the Skeleton A. Clinical manifestations B. Pathophysiology of the metastatic process to bone C. Local tumor syndromes in bone D. Therapy of tumor in bone
Identification of a minimal region of genetic loss at 8p23.1 and investigation of GATA4 as a candidate tumor suppressor gene in medulloblastoma
Authors: Yuan Lu, Debbie K. Scott, Ho K. Ng, David W. Ellison, Steven C. Clifford
Journal: Cancer Research (2006)

3271  Genetic losses affecting the short arm of chromosome 8 are frequent events in the development of medulloblastoma (MB), the most common malignant brain tumor of childhood, and suggest the presence of critical tumor suppressor gene(s) (TSGs) in this region. To map critical regions of genetic loss on 8p in MB, we performed loss of heterozygosity (LOH) analysis using a panel of 23 polymorphic microsatellite makers, in 30 primary medulloblastoma and 11 MB cell lines. LOH on 8p was found in 26% of cases and a 1.6Mb common region of genetic loss was identified at 8p23.1, defined by polymorphic markers D8S520 and D8S1130. Among the genes contained in this region, GATA4 (encoding the transcription factor, GATA binding protein 4) has recently been found to be hypermethylated and epigenetically silenced in other cancer types, and thus represents a promising candidate TSG at 8p23.1. We therefore assessed the promoter hypermethylation and transcript expression status of GATA4 in MB. Evidence of GATA4 promoter hypermethylation was found in 2 of 11 MB cell lines, following bisulphite treatment and methylation specific PCR (MSP) analysis. Reduced GATA4 transcript levels were observed in both cell lines, which were restored following treatment with the DNA methyltransferase inhibitor, 5-aza-2’deoxycytidine (5azaCdR), indicating that GATA4 promoter hypermethylation in MB cell lines is associated with its methylation-dependent transcriptional silencing. However, no consistent evidence of GATA4 hypermethylation was found in a cohort of 27 primary MBs. In another cell line, the GATA4 transcript was absent, but its expression was unaffected by 5azaCdR treatment, indicating a potential role for methylation-independent mechanisms of GATA4 silencing in MB. Based on these data, promoter hypermethylation of GATA4 is unlikely to play a major role in MB development. However, a methylation-independent mechanism of GATA4 inactivation cannot be excluded. Extensive analysis of GATA4 genetic mutation and deletion are therefore currently ongoing in our primary tumour panel, to investigate further its role as a candidate TSG at 8p23.1 in MB.
Global Burden of Disease Attributable to Hypertension
Authors: Richard S. Cooper, Jay S. Kaufman, Pascal Bovet
Journal: JAMA (2017)

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