bluuebunny/crossref_metadata_2025_split huggingface dataset:
Optimal Use of Prognostic Factors in Non-Hodgkin Lymphoma
Authors: Sehn Laurie H. 
Published: November 2006

AbstractThe management of non-Hodgkin lymphoma is complicated by wide heterogeneity within recognized subtypes. Patients with supposedly similar diagnoses can have remarkably varied clinical presentations, molecular profiles and clinical outcomes. Reliable prognostic markers could allow the identification of patient subsets that may benefit from alternate approaches. Historically, a large number of clinical and molecular prognostic factors have been elucidated. However, the recent introduction of new therapies such as monoclonal antibodies has revolutionized treatment practices and greatly improved outcomes. This has called into question the value of previously recognized prognostic factors that need to be revalidated in the era of immunochemotherapy. It would appear that the commonly used clinical indices (IPI and FLIPI) retain predictive capacity, although they may have limited ability to identify a very poor outcome group. Currently there are no molecular markers that have been revalidated and shown to retain significance in the setting of current treatment practices for diffuse large B-cell lymphoma or follicular lymphoma. The biologic insights provided by molecular studies should allow for more targeted therapies to be developed, which will increase treatment choice and the possibility of tailored therapy in the future. It is imperative that future steps forward be made in the context of well-designed clinical trials with prospective correlative studies of clinical and biologic markers. This will allow us to continuously assess outcome predictors in the context of treatment change and to rationally design tailored treatment algorithms.
Primary Cutaneous T-Cell Lymphomas
Authors: Rosen Steven T. , Querfeld Christiane 
Published: November 2006

Abstract
Primary cutaneous T-cell lymphomas (CTCLs) encompass a clinically and biologically heterogeneous group of non-Hodgkin lymphomas (NHLs) defined by clonal proliferation of skin-homing malignant T lymphocytes and natural killer cells. They account for up to 75% to 80% of all cutaneous lymphomas. The current WHO-EORTC classification of cutaneous lymphomas with primary cutaneous manifestations lists 13 entities. The most common subtypes—mycosis fungoides, Sézary syndrome, primary cutaneous anaplastic large cell lymphoma, and lymphomatoid papulosis—which represent approximately 95% of CTCLs, will be discussed in the following review. Each entity has unique biological characteristics and clinical course. Topical and/or systemic therapies are employed based on the stage of the disease and the tempo of progression.
Thrombotic Complications of Myeloma Therapy
Authors: Zonder Jeffrey A. 
Published: November 2006

AbstractPatients with multiple myeloma are at relatively high baseline risk of developing thromboembolic events (TEE), usually deep vein thromboses. There are numerous contributing factors, among them certain treatment regimens that include thalidomide or related compounds such as lenalidomide combined with glucocorticoids and/or cytotoxic chemotherapy. The risk of developing TEE appears to be particularly high when these immunomodulatory agents are combined with anthracyclines as treatment of newly-diagnosed disease. Up-front combinations including thalidomide plus pulse dexamethasone and/or alkylating agents are associated with an intermediate risk, whereas the same regimens for relapsed/refractory myeloma seem to be associated with the lowest risk. Several different thromboprophylaxis strategies have been effective in lowering the risk of developing clots: daily aspirin (81–325 mg/day), full-intensity warfarin (INR 2–3), and prophylactic enoxaparin (40 mg SQ daily). Low, fixed-dose warfarin may also reduce the risk of TEE, but the data on this are disputable. None of these TEE prevention strategies have been prospectively compared head-to-head, so the choice often reflects physician and/or patient preferences. The available evidence upon which one might make such a decision is reviewed here.
Current Approaches to the Management of Hemochromatosis
Authors: Brissot Pierre , de Bels Frédéric 
Published: November 2006

Abstract
The term hemochromatosis encompasses at least four types of genetic iron overload conditions, most of them recently distinguished from one another as a result of the identification of a series of genes related to iron metabolism. At least three of these entities (HFE hemochromatosis, juvenile hemochromatosis and transferrin receptor 2 hemochromatosis) involve systemic hepcidin deficiency as a key pathogenetic factor. Major advances in the management of hemochromatosis influence the diagnostic approach to the disease, with the development of an overall non invasive strategy, mainly based on clinical, biological (iron parameters and genetic testing), and imaging (especially magnetic resonance imaging) data. Therapeutic management remains, on the curative side, dominated by phlebotomy (venesection), practical aspects of which have been recently revisited by the Guidelines Department of the French “Haute Autorité de Santé.” However, innovative treatment approaches, based on the improved pathophysiological understanding of these diseases and the progress in iron chelation therapy, are emerging. Preventive therapy, focused on family screening, remains a key part of the management of hemochromatosis.
Viral Hepatitis: Manifestations and Management Strategy
Authors: Firpi Roberto J. , Nelson David R. 
Published: November 2006

AbstractViral hepatitis is the third most common cause of liver disease in allogeneic transplant recipients and causes significant morbidity and mortality. When treating patients with hematological malignancies, an emphasis should be placed on identification of patients at risk for viral hepatitis with appropriate screening. Initial screening serology should include anti-HCV, HBsAg, anti-HBs, and anti-HBc testing. When hepatitis B exposure has been documented, prophylaxis of viral reactivation for all HBsAg-positive patients with a nucleoside analogue should be implemented. HCV infection appears to have little short-term impact on survival after bone marrow transplantation, but is a risk factor for veno-occlusive disease (VOD) and graft-versus-host disease (GVHD). In the long-term survivor, HCV infection can lead to significant morbidity and mortality due to the development of cirrhosis, decompensation, and liver cancer. Since effective antiviral therapies are available for both hepatitis B and C, routine screening and selected intervention is recommended once reactivation and disease recurrence is documented. In this chapter we will highlight the mechanisms of virus reactivation, clinical manifestations, and management strategies to minimize acute and chronic morbidity in this population.
Reduced-Intensity Regimens in Allogeneic Hematopoietic Stem Cell Transplantation for Hemoglobinopathies
Authors: Locatelli Franco 
Published: November 2006

AbstractThe only well-established curative therapy for patients with hemoglobinopathies is allogeneic hematopoietic stem cell transplantation (HSCT), which, in the last 20 years, has been mainly performed from an HLA-matched, related donor, using bone marrow as source of hematopoietic progenitors. More recent studies indicate that HSCT from unrelated donors may offer results comparable to those obtained with HLA-identical family donors, provided that stringent criteria of compatibility are employed for selecting the donor. Cord blood transplantation was also suggested to be an equally effective, but safer, procedure than bone marrow transplantation, due to the lower incidence and severity of both acute and chronic graft-versus-host disease. In view of the early, as well as late, morbidity and mortality associated with conventional myeloablative transplantation in patients with hemoglobinopathies, it is not surprising that great interest and relevant expectations for patients with hemoglobinopathies have been raised by the introduction in the clinical practice of reduced-intensity preparative regimens. However, few reports have demonstrated the feasibility of using reduced-intensity preparative regimens for successfully treating these patients and many treatment failures, mainly due to the lack of sustained donor engraftment, have been reported. Despite these limitations, some of the concepts obtained from the use of reduced intensity regimens, such as the substitution of fludarabine for cyclophosphamide, may be important to further improve the outcome of patients with hemoglobinopathies, especially of those with poor prognostic characteristics, given HSCT.
Management of Hereditary Hypercoagulable Disorders
Authors: Bockenstedt Paula L. 
Published: November 2006

AbstractThe clinical management of individuals with hereditary hypercoaguable disorders has evolved from initial broad recommendations of lifelong anticoagulation after first event of venous thromboembolism to a more intricate individualized risk-benefit analysis as studies have begun to delineate the complexity of interactions of acquired and hereditary factors which determine the predilection to thrombosis. The contribution of thrombophilic disorders to risk of thrombotic complications of pregnancy, organ transplantation, central venous catheter and dialysis access placement have been increasingly recognized. The risk of thrombosis must be weighed against risk of long-term anticoagulation in patients with venous thromboembolism. Thrombophilia screening in select populations may enhance outcome.
Prevention of Venous Thromboembolism in High-Risk Patients
Authors: Geerts William H. 
Published: November 2006

AbstractThe prevention of venous thromboembolism (VTE) in patients recovering from major trauma, spinal cord injury (SCI), or other critical illness is often challenging. These patient groups share a high risk for VTE, they often have at least a temporary high bleeding risk, and there are relatively few thromboprophylaxis trials specific to these populations. A systematic literature review has been conducted to summarize the risks and prevention of VTE in these three groups. It is concluded that routine thromboprophylaxis should be provided to major trauma, SCI and critical care patients based on an individual assessment of their thrombosis and bleeding risks. For patients at high risk for VTE, including those recovering from major trauma and SCI, prophylaxis with a low molecular weight heparin (LMWH) should commence as soon as hemostasis has been demonstrated. For critical care patients at lower thrombosis risk, either LMWH or low-dose heparin is recommended. For those with a very high risk of bleeding, mechanical prophylaxis should be instituted as early as possible and continued until pharmacologic prophylaxis can be initiated. The use of prophylactic inferior vena caval filters is strongly discouraged because their potential benefit has not been shown to outweigh the risks or substantial costs. Implementation of thromboprophylaxis in these patients requires a local commitment to this important patient safety priority as well as a highly functional delivery system, based on the use of pre-printed orders, computer prompts, regular audit and feedback, and ongoing quality improvement efforts.
Prevention and Management of Stroke in Sickle Cell Anemia
Authors: Platt Orah S. 
Published: November 2006

AbstractAs the overall health of patients with sickle cell anemia (SS) improves and diagnostic techniques become more sensitive, physicians are seeing patients with an increasingly wide range of subtle and not-so-subtle brain injury. The major breakthrough in the field of sickle-related brain injury has been the unprecedented success of transcranial Doppler ultrasonography (TCD) to identify asymptomatic patients at high risk of stroke, coupled with chronic transfusion therapy to prevent it. The evidence for TCD screening and preventive treatment is strong and compelling, but there are still important unanswered questions regarding the implications of “silent infarcts” found in the magnetic resonance images (MRIs) of asymptomatic individuals, and the growing awareness of the burden of neuropsychiatric dysfunction in otherwise apparently healthy individuals.
Pathophysiologic Mechanisms in Acquired Aplastic Anemia
Authors: Young Neal S. 
Published: November 2006

Abstract
Aplastic anemia, an unusual hematologic disease, is the paradigm of the human bone marrow failure syndromes. Absence of hematopoietic cells has been recognized from the characteristic morphology for a century; an immune pathophysiology has been inferred from improvement in blood counts with immunosuppressive therapy in the majority of patients. Molecular mechanisms underlying both T cell effector cells and the target marrow stem and progenitor cells are now being identified. Activated type 1 cytotoxic T cells and type 1 cytokines have been implicated in cell culture experiments; clues to the molecular basis of the aberrant immune response include cytokine gene polymorphisms and abnormalities in the regulatory pathways for γ-interferon. For stem cell depletion, mutations in genes of the telomere repair complex are present in some patients with apparently acquired aplastic anemia. Telomerase deficiency is associated with short telomeres and a quantitative reduction in marrow progenitors and likely also a qualitative deficiency in the repair capacity of hematopoietic tissue.
Making Therapeutic Decisions in Adults with Aplastic Anemia
Authors: Marsh Judith 
Published: November 2006

Abstract
The management of adults presenting with aplastic anemia (AA) requires careful exclusion of other causes of bone marrow failure. Late-onset inherited forms of AA may present in adulthood with subclinical disease. Recent long-term studies of HLA identical sibling donor BMT show excellent survival for patients under the age of 40 years, but chronic graft-versus-host disease (GVHD) is still a major problem, impacting on quality of life. Recent improvements in outcome after matched unrelated donor BMT may reflect better donor matching and use of reduced intensity conditioning regimens. For patients treated with immunosuppressive therapy (IST), antithymocyte globulin (ATG) and cyclosporin (CSA) remain the standard regimen with excellent overall survival but less impressive failure-free survival due to nonresponse, relapse and later clonal disorders. The benefit of adding granulocyte colony-stimulating factor (G-CSF) to ATG and CSA is unclear and being assessed in a further prospective European study. Patients who are refractory to conventional IST and currently ineligible for BMT represent difficult management problems. For these patients, new approaches to transplantation are being evaluated, such as fludarabine-based conditioning regimens and the potential use of double umbilical cord blood transplants, but there is a need for new immunosuppressive agents. Improved supportive care is likely to be a major factor in improved outcome of all AA patients whether treated with IST or BMT. Robust predictive factors for response to IST are needed to help in decision making at diagnosis and to help justify exploring novel approaches to therapy.
The growth factor fusion construct containing B-lymphocyte stimulator (BLyS) and the toxin rGel induces apoptosis specifically in BAFF-R–positive CLL cells
Authors: Nimmanapalli Ramadevi , Lyu Mi-Ae , Du Min , Keating Michael J. , Rosenblum Michael G. , Gandhi Varsha 
Published: November 2006

AbstractThe cytokine B lymphocyte stimulator (BLyS) mediates its effect through cell-surface receptors BAFF-R, TACI, and BCMA. BLyS receptors are expressed only on B cells and not present in other normal cells including normal T lymphocytes. Chronic lymphocytic leukemia (CLL) is a B-cell disease and CLL lymphocytes express BLyS receptors. Gelonin, a type 1 ribosome-inactivating toxin, lacks cell membrane binding domain and hence is nontoxic to intact cells. We generated a construct of recombinant gelonin (rGel) fused to BLyS to specifically target quiescent B-CLL lymphocytes. The construct rGel/BLyS specifically binds and internalizes through BAFF-R into CD19+ B-CLL lymphocytes and induces apoptosis at nanomolar concentrations. In contrast, rGel alone was not able to internalize into these leukemic lymphocytes. Mechanistically, the rGel/BLyS construct inhibits protein synthesis with an IC50 of less than 3 nM compared with more than 5000 nM for rGel toxin alone. This rGel/BLyS-mediated decrease in protein synthesis was associated with a decline in short-lived proteins such as MCL-1 and XIAP, the 2 survival proteins in B-CLL. There was a strong relationship between a decrease in these proteins and the cleavage of PARP, a hallmark feature of apoptosis. Taken together, these data suggest that the rGel/BLyS fusion toxin may have potential therapeutic efficacy for B-CLL patients.
Simultaneous host and parasite expression profiling identifies tissue-specific transcriptional programs associated with susceptibility or resistance to experimental cerebral malaria
Authors: Lovegrove Fiona E , Peña-Castillo Lourdes , Mohammad Naveed , Liles W Conrad , Hughes Timothy R , Kain Kevin C 
Published: November 2006

AbstractBackgroundThe development and outcome of cerebral malaria (CM) reflects a complex interplay between parasite-expressed virulence factors and host response to infection. The murine CM model,Plasmodium bergheiANKA (PbA), which simulates many of the features of human CM, provides an excellent system to study this host/parasite interface. We designed "combination" microarrays that concurrently detect genome-wide transcripts of both PbA and mouse, and examined parasite and host transcriptional programs during infection of CM-susceptible (C57BL/6) and CM-resistant (BALB/c) mice.ResultsAnalysis of expression data from brain, lung, liver, and spleen of PbA infected mice showed that both host and parasite gene expression can be examined using a single microarray, and parasite transcripts can be detected within whole organs at a time when peripheral blood parasitemia is low. Parasites display a unique transcriptional signature in each tissue, and lung appears to be a large reservoir for metabolically active parasites. In comparisons of susceptible versus resistant animals, both host and parasite display distinct, organ-specific transcriptional profiles. Differentially expressed mouse genes were related to humoral immune response, complement activation, or cell-cell interactions. PbA displayed differential expression of genes related to biosynthetic activities.ConclusionThese data show that host and parasite gene expression profiles can be simultaneously analysed using a single "combination" microarray, and that both the mouse and malaria parasite display distinct tissue- and strain-specific responses during infection. This technology facilitates the dissection of host-pathogen interactions in experimental cerebral malaria and could be extended to other disease models.
Distinct cellular responses differentiating alcohol- and hepatitis C virus-induced liver cirrhosis
Authors: Lederer Sharon L , Walters Kathie-Anne , Proll Sean , Paeper Bryan , Robinzon Shahar , Boix Loreto , Fausto Nelson , Bruix Jordi , Katze Michael G 
Published: November 2006

AbstractBackgroundLittle is known at the molecular level concerning the differences and/or similarities between alcohol and hepatitis C virus induced liver disease. Global transcriptional profiling using oligonucleotide microarrays was therefore performed on liver biopsies from patients with cirrhosis caused by either chronic alcohol consumption or chronic hepatitis C virus (HCV).ResultsGlobal gene expression patterns varied significantly depending upon etiology of liver disease, with a greater number of differentially regulated genes seen in HCV-infected patients. Many of the gene expression changes specifically observed in HCV-infected cirrhotic livers were expectedly associated with activation of the innate antiviral immune response. We also compared severity (CTP class) of cirrhosis for each etiology and identified gene expression patterns that differentiated ethanol-induced cirrhosis by class. CTP class A ethanol-cirrhotic livers showed unique expression patterns for genes implicated in the inflammatory response, including those related to macrophage activation and migration, as well as lipid metabolism and oxidative stress genes.ConclusionStages of liver cirrhosis could be differentiated based on gene expression patterns in ethanol-induced, but not HCV-induced, disease. In addition to genes specifically regulating the innate antiviral immune response, mechanisms responsible for differentiating chronic liver damage due to HCV or ethanol may be closely related to regulation of lipid metabolism and to effects of macrophage activation on deposition of extracellular matrix components.
Impact of concomitant DMARD therapy on adherence to treatment with etanercept and infliximab in rheumatoid arthritis. Results from a six-year observational study in southern Sweden
Authors: Kristensen Lars Erik , Saxne Tore , Nilsson Jan-Åke , Geborek Pierre 
Published: November 2006

AbstractThe objective of this work is to compare the adherence to therapy of patients receiving etanercept and infliximab during first tumour necrosis factor (TNF)-blocking treatment course in rheumatoid arthritis. Special emphasis is placed on potential predictors for treatment termination and the impact of concomitant methotrexate (MTX) or other disease-modifying antirheumatic drugs (DMARDs). Patients (n = 1,161) with active rheumatoid arthritis, not responding to at least two DMARDs including MTX starting etanercept or infliximab therapy for the first time, were included in a structured clinical follow-up protocol. Information on diagnosis, disease duration, previous and ongoing DMARDs, treatment start and termination, as well as cause of withdrawal was prospectively collected during the period of March 1999 through December 2004. Patients were divided into six groups according to TNF-blocking drugs and concomitant DMARDs. Five-year level (one-year) of adherence to therapy was 36% (69%) for patients receiving infliximab in combination with MTX compared with 65% (89%) for patients treated with etanercept and MTX (p < 0.001). Cox regression models showed that the risk for premature treatment termination of patients treated with infliximab was threefold higher than for etanercept (p < 0.001). Also, the regression analysis showed that patients receiving concomitant MTX had better treatment continuation than patients treated solely with TNF blockers (p < 0.001). Moreover, patients receiving concomitant MTX had superior drug survival than patients receiving other concomitant DMARDs (p < 0.010). The superior effect of MTX was associated primarily with fewer treatment terminations because of adverse events. In addition, the study identifies low C-reactive protein level, high age, elevated health assessment questionnaire score, and higher previous number of DMARDs as predictors of premature treatment termination. In summary, treatment with etanercept has higher adherence to therapy than treatment with infliximab. Concomitant MTX is associated with improved treatment continuation of biologics when compared with both TNF blockers as monotherapy and TNF blockers combined with other DMARDs.