bluuebunny/crossref_metadata_2025_split huggingface dataset:
Ununited accessory caudal glenoid ossification centre and associated joint mouse as a cause of lameness in a cat
Authors: Serck Boris MA , Wouters Erik EG 
Published: October 2019

Case summary A 16-year-old neutered female domestic shorthair cat was evaluated for chronic lameness of the right thoracic limb. On clinical examination, pain was localised to the right glenohumeral joint. Radiography and arthrography of the right glenohumeral joint revealed an ununited accessory caudal glenoid ossification centre, abbreviated here to ununited caudal glenoid (UCG), and a joint mouse. The UCG and attached joint mouse were removed via arthroscopy and this resulted in complete resolution of the clinical signs. The cat was euthanased 3 years later, for an unrelated cause, having shown no recurrence of lameness. Relevance and novel information UCG should be considered as a differential diagnosis for cats with lameness of the thoracic limb. The clinical implications of a UCG have been described in dogs, but to our knowledge have not yet been described in cats. Excision of the UCG, as described in dogs, may be an effective treatment for this condition.
Cerebral gliosarcoma with perivascular involvement in a cat
Authors: Álvarez Patricia , Wessmann Annette , Pascual Mireia , Comas Oriol , Pi Dolors , Pumarola Martí 
Published: October 2019

Case summary A 5-year-old neutered male domestic shorthair cat presented with an 18-month history of facial tics, and progressive general ataxia, weakness, lethargy and anorexia of 2 weeks’ duration. MRI of the brain showed a well-defined heterogeneous hyperintense mass on T1-weighted and T2-weighted images, with central hypointensity in the rostral commissure and septum pellucidum, and perilesional hyperintensity in fluid-attenuated inversion recovery, suggestive of perilesional oedema. Gross examination in a transverse section of the brain at the level of the septum pellucidum revealed a 0.2 cm brown soft mass. Histopathological examination identified a biphasic neoplastic proliferation of mesenchymal and neuroepithelial cell populations. Fusiform cells were predominately distributed in bundles showing a high degree of anisocytosis and marked immune-positive reaction to vimentin immunochemistry, confirming a sarcomatous origin. Additionally, high numbers of astrocytic cells were identified by an intense immunopositive reaction to glial fibrillary acidic protein and negative reaction to oligodendrocyte transcription factor 2 immunochemistry. Vascular invasion of the neoplasia into the wall of a medium branch of the rostral cerebral artery was present (secondary Scherer structures). Based on these characteristics, the tumour was defined as a gliosarcoma. Gliosarcoma is a recognised astrocytoma grade IV anaplastic glial cell tumour with sarcomatous differentiation. Relevance and novel information To our knowledge, this is the first report describing a cerebral gliosarcoma in a cat including clinical, MRI, macroscopic and histopathological features and immunolabelling characteristics.
FDA Reported Use of Patient Experience Data in 2018 Drug Approvals
Authors: Kieffer Cameron M. , Miller Alexis Reisin , Chacko Benjamin , Robertson Andrew S. 
Published: October 2019

Background: “Patient experience data” (PED) refers to the systematic collection of meaningful data relating to the experiences, perspectives, needs, and priorities of patients. PED can augment traditional clinical trial data in the FDA’s review of product applications. Section 3001 of the 2016 21st Century Cures Act requires the FDA to make a public statement about the PED considered in the approval of a drug application. Here, we present one of the first assessments of PED consideration during drug application approval, as reported by the FDA under Sec. 3001 of the Cures Act. Methods: FDA reported use of PED in the Review Documentation of the 59 new molecular entities (NMEs) approved in 2018 were collected, indexed, and cross-referenced against information regarding FDA review and product regulatory designation. The data reported in the PED tables were quantitatively described and visualized. Results: Of the 59 approved NMEs in 2018, 48 include a table that summarized whether PED was or was not used during the FDA drug review. Thirty-four of those 48 approvals (70.8%) reported using PED in the drug review. Patient-reported outcomes (PROs) represented the most significant source of PED and were used in 60.4% of approved drug reviews. Additional findings, including PED use by FDA review division and by FDA regulatory designation, are described. Conclusions: This assessment is a first step to better understanding how FDA considers PED in regulatory decision making. This analysis should help develop a baseline regarding FDA use of PED and may inform decisions to ensure patients’ experiences are adequately heard in future drug development.
Atypical Lymphoproliferative Diseases
Authors: Greiner Timothy , Armitage James O. , Gross Thomas G. 
Published: October 2019

Abstract
This review addresses the clinical presentation, pathology, and therapy of several uncommon lymphoid proliferations. Because these lymphoproliferations span the characteristics of reactive polymorphous proliferations to clonal malignant neoplasms, they are often difficult to diagnose and treat effectively.
In Section I, Dr. Greiner describes the pathology of the spectrum of atypical lymphoid disorders including Castleman's disease, angioimmunoblastic lymphadenopathy, lymphadenopathy in autoimmune diseases, posttransplant lymphoproliferative disorders, and X-linked lymphoproliferative disorder. The relationship to Epstein-Barr virus (EBV) and human herpsesvirus-8 (HHV-8) is discussed, and molecular diagnostic assays and principles for obtaining proper diagnostic evaluation are emphasized.
In Section II, Dr. Armitage presents a practical approach to the management of Castleman's disease. The discussion includes the importance of confirmation of the histological diagnosis and careful staging evaluation, therapeutic options, and the increased risks for infection and lymphoma. The appropriate roles of surgical excision, corticosteroids, and combination chemotherapy are addressed along with alternative strategies such as anti-interleukin-6 and bone marrow transplantation.
In Section III, Dr. Gross reviews the treatment of EBV-associated lymphoproliferative disorders in primary immunodeficiencies and in post-transplant patients. He gives an update on the recent molecular discoveries in X-linked lymphoproliferative disorder. Preliminary results of a phase II trial of low-dose cyclophosphamide in posttransplant lymphoproliferative disorders and the use of GM-CSF as preemptive therapy are presented.
Atypical Lymphoproliferative Diseases
Authors: Greiner Timothy , Armitage James O. , Gross Thomas G. 
Published: October 2019

This review addresses the clinical presentation, pathology, and therapy of several uncommon lymphoid proliferations. Because these lymphoproliferations span the characteristics of reactive polymorphous proliferations to clonal malignant neoplasms, they are often difficult to diagnose and treat effectively.In Section I, Dr. Greiner describes the pathology of the spectrum of atypical lymphoid disorders including Castleman's disease, angioimmunoblastic lymphadenopathy, lymphadenopathy in autoimmune diseases, posttransplant lymphoproliferative disorders, and X-linked lymphoproliferative disorder. The relationship to Epstein-Barr virus (EBV) and human herpsesvirus-8 (HHV-8) is discussed, and molecular diagnostic assays and principles for obtaining proper diagnostic evaluation are emphasized.In Section II, Dr. Armitage presents a practical approach to the management of Castleman's disease. The discussion includes the importance of confirmation of the histological diagnosis and careful staging evaluation, therapeutic options, and the increased risks for infection and lymphoma. The appropriate roles of surgical excision, corticosteroids, and combination chemotherapy are addressed along with alternative strategies such as anti-interleukin-6 and bone marrow transplantation.In Section III, Dr. Gross reviews the treatment of EBV-associated lymphoproliferative disorders in primary immunodeficiencies and in post-transplant patients. He gives an update on the recent molecular discoveries in X-linked lymphoproliferative disorder. Preliminary results of a phase II trial of low-dose cyclophosphamide in posttransplant lymphoproliferative disorders and the use of GM-CSF as preemptive therapy are presented.
Hodgkin's Lymphoma
Authors: Linch David C. , Gosden Roger G. , Tulandi Togas , Tan Seang-Lin , Hancock Stephen L. 
Published: October 2019

This review focuses on the different treatment options available for the treatment of Hodgkin's disease, with an emphasis on the importance of the long-term sequelae of these therapies.
In Section I, Dr. Linch reviews the current status of Hodgkin's disease treatment. Survival rates have improved over the last three decades due both to better initial therapies and associated supportive care and to the success of salvage therapy. Unlike most other malignancies, a similar survival endpoint can be achieved by different means, e.g., intensive initial therapy resulting in a low relapse rate or less intensive initial therapy and more reliance on salvage therapy. Overall survival has thus become a difficult end-point for clinical trials of primary therapy, and the value of disease-free survival as an end-point can also be questioned. Quality-of-life issues are to the fore of clinical decision and include the psychological trauma of relapse and fertility status. Patient choice is increasingly important. The high level of success in treating Hodgkin's disease also means that attention must be focused on the very long term results and in this context the occurrence of second malignancies is a major issue.
In Section II, Dr. Gosden with Dr. Tulandi and Dr. Tan review the risks of infertility following radio-therapy and chemotherapy and address the actions that can be taken to overcome this problem, particularly for females and prepubertal boys and girls. Particular attention is paid to the recent developments in ovarian cryopreservation and harvesting immature germ cells.
In Section III, Dr. Hancock gives a comprehensive update of the incidence of secondary acute leukemia, non-Hodgkin's lymphoma and solid tumors in a large population of patients treated for Hodgkin's disease. The roles of radiotherapy, chemotherapy and combined modality treatment as risk factors contributing to the development of these secondary malignancies are reviewed. The importance of efforts to prevent late-occurring solid tumors such as lung cancer through smoking cessation programs and early detection by screening for cancers of the breast, thyroid and skin are emphasized.
Bone Marrow Transplantation for Non-Malignant Disease
Authors: Sullivan Keith M. , Parkman Robertson , Walters Mark C. 
Published: October 2019

AbstractThis article reviews the experience in hematopoietic stem cell transplantation (HSCT) for non-malignant disease. HSCT has long been applied as treatment of life-threatening congenital immunodeficiency and metabolic diseases. In Section I, Dr. Parkman reviews that experience for severe combined immunodeficiency, Wiscott-Aldrich syndrome, hyper IGM syndrome, Chédiak-Higashi disease and hereditary lymphohistiocytosis. The value of HSCT in genetic metabolic diseases such as osteopetrosis, osteogenesis imperfecta and the storage diseases are reviewed. In Section II, Dr. Walters reviews the experience over the last decade with allogeneic stem cell transplantation in patients with thalassemia major and sickle cell disease. In Section III, Dr. Sullivan reviews the more recent investigations using stem cell transplantation in patients with advanced autoimmune diseases such as systemic sclerosis, systemic lupus erythematosus, multiple sclerosis and juvenile rheumatoid arthritis. The pathogenesis and outcome with conventional care of these patients, the selection criteria and current results for HSCT, and the future directions in clinical research and patient care using this modality are addressed.
Platelets and Thrombosis in Myeloproliferative Diseases
Authors: Harrison Claire N. 
Published: October 2019

Abstract
The myeloproliferative disorders have been the “poor cousins” in the family of hematological malignancies for some time. Recently this field has advanced considerably with the description of a mutation in the JAK2 kinase detectable in the majority of patients and the publication of two landmark clinical trials—ECLAP and MRC PT1. But although both ECLAP and MRC PT1 inform clinical management and allude to the complexities of thrombosis we still lack fundamental knowledge, and our understanding of thrombosis in these conditions has not paralleled advances in the field of thrombosis and vascular biology. The predominant clinical complications of essential thrombocythemia and polycythemia vera are thrombotic and hemorrhagic; these significantly impact upon prognosis and quality of life. Here the current status of our knowledge is reviewed with specific emphasis upon the role of the platelet in the pathogenesis of thrombosis as well as the impact of recent data from ECLAP and MRC PT1.
Bleeding scores: are they really useful?
Authors: O'Brien Sarah H. 
Published: October 2019

AbstractGiven the commonality of bleeding symptoms in the general population and the diagnostic limitations of available laboratory testing for mild bleeding disorders, there has been increasing interest in a more precise quantification of bleeding symptoms. The Vicenza bleeding score (and its successor, Molecular and Clinical Markers for the Diagnosis and Management of Type 1 von Willebrand disease [MCMDM-1 VWD]) and its pediatric counterpart, the Pediatric Bleeding Questionnaire, are validated research tools that have demonstrated their ability to discriminate between healthy subjects and those with VWD. These instruments collect data regarding both the presence and severity of a variety of bleeding symptoms and generate a bleeding score by summing the severity of all symptoms reported by a subject. More recent work demonstrates the promise of these tools as a diagnostic aid in the evaluation of patients with a suspected inherited mild bleeding disorder, as well as the development of a condensed score with increased clinical applicability. This review focuses on the development of these bleeding assessment tools, recent publications applying and refining these instruments, and current limitations of bleeding scores. Needed research studies and potential clinical applications of bleeding scores are also discussed. The ultimate goal would be for bleeding scores to be integrated with the results of standardized laboratory testing to allow for a universal diagnostic approach to patients with suspected bleeding disorders.
How to approach chronic anemia
Authors: Koury Mark J. , Rhodes Melissa 
Published: October 2019

Abstract
We present herein an approach to diagnosing the cause of chronic anemia based on a patient's history and complete blood cell count (CBC). Four patterns that are encountered frequently in CBCs associated with chronic anemias are considered: (1) anemia with abnormal platelet and/or leukocyte counts, (2) anemia with increased reticulocyte counts, (3) life-long history of chronic anemia, and (4) anemia with inappropriately low reticulocytes. The pathophysiologic bases for some chronic anemias with low reticulocyte production are reviewed in terms of the bone marrow (BM) events that reduce normal rates of erythropoiesis. These events include: apoptosis of erythroid progenitor and precursor cells by intrinsic and extrinsic factors, development of macrocytosis when erythroblast DNA replication is impaired, and development of microcytosis due to heme-regulated eIF2α kinase inhibition of protein synthesis in iron-deficient or thalassemic erythroblasts.
Thrombosis in pregnancy: updates in diagnosis and management
Authors: Greer Ian A. 
Published: October 2019

Abstract
Acute venous thromboembolism poses significant problems in pregnancy, a time when objective diagnosis and prompt treatment are essential. Events can occur at any stage in pregnancy, but the period of greatest risk is in the weeks after delivery. Ultrasound venography remains the diagnostic technique of choice for deep venous thrombosis. For pulmonary thromboembolism, ventilation perfusion lung scan is usually preferred more than computerized tomography pulmonary angiography because of the lower maternal radiation dose and the lower prevalence of coexisting pulmonary problems. Low-molecular-weight heparin is the agent of choice for treatment of venous thromboembolism in pregnancy, and treatment should be provided for a minimum of 3 months and for at least 6 weeks after delivery. New anticoagulant agents such as dabigatran, rivaroxaban, or apixaban are not recommended for use in pregnancy.
Baby on board: what you need to know about pregnancy in the hemoglobinopathies
Authors: Naik Rakhi P. , Lanzkron Sophie 
Published: October 2019

Abstract
Pregnancy poses a unique challenge to patients with sickle cell disease and β-thalassemia, who often have exacerbations of hemolysis or anemia during the gestational period, experience higher rates of obstetric and fetal complications, and may have distinct underlying comorbidities related to vasculopathy and iron overload that can endanger maternal health. Optimal management of pregnant women with hemoglobinopathies requires both an understanding of the physiologic demands of pregnancy and the pathophysiology of disease-specific complications of inherited blood disorders. A multidisciplinary team of expert hematologists and high-risk obstetricians is therefore essential to ensuring appropriate antenatal maternal screening, adequate fetal surveillance, and early recognition of complications. Fortunately, with integrated and targeted care, most women with sickle cell disease and β-thalassemia can achieve successful pregnancy outcomes.
Haploidentical transplantation for hematologic malignancies: where do we stand?
Authors: Fuchs Ephraim J. 
Published: October 2019

Abstract
The fundamental obstacle to the successful application of partially HLA-mismatched related donor, or HLA-haploidentical stem cell transplantation, is the strength of the host and donor T-cell response to allogeneic HLA molecules, which results in increased incidences of graft failure, GVHD, and nonrelapse mortality. The holy grail of haplo-SCT is to mitigate host-versus-graft and graft-versus-host responses while preserving immune responses to infection and the patient's malignancy. Two strategies have been taken to achieve this goal. The first strategy is to supplement a T cell–depleted graft with pathogen-specific T cells or populations of T cells in which alloreactivity can be controlled. The second strategy is to eliminate alloreactive T cells selectively from a T cell–replete graft. Substantial progress has been made with both approaches so that the safety of haplo-SCT now approaches that of SCT using grafts of umbilical cord blood or from HLA-matched donors. In light of the rapid and near universal availability of HLA-haploidentical related donors, it should now be possible to identify and mobilize a donor for every patient referred for allogeneic SCT. Prospective comparisons between haploidentical SCT and unrelated donor SCT should be performed to identify the most efficacious approach to alternative donor transplantation.
Do different conditioning regimens really make a difference?
Authors: Blaise Didier , Castagna Luca 
Published: October 2019

Abstract
Over the past 15 years, the use of reduced-intensity/nonmyeloablative conditioning regimens before allogeneic hematopoietic stem cell transplantation has been increasing. Despite major disparities in the level of myeloablation, intensity of immunosuppression (including great diversity of in vivo T-cell depletion), and postgraft immunomodulation, the different approaches have contributed jointly to a modification of the stage of allogeneic stem cell transplantation: transplantation-related procedure mortality has been decreased dramatically, allowing allogeneic immunotherapy to be used in previously excluded populations, including elderly patients, young but clinically unsuitable patients, patients with lymphoid malignancies or solid tumors, and patients without an HLA-identical related or unrelated donor. Together, these diverse regimens have provided one of the biggest breakthroughs since the birth of allogeneic BM transplantation. However, consensus on how to reach the optimal goal of minimal transplantation-related mortality with maximum graft-versus-tumor effect is far from being reached, and further studies are needed to define optimal conditioning and immunomodulatory regimens that can be integrated to reach this goal. These developments, which will most likely vary according to different clinical situations, have to be compared continuously with advances achieved in traditional allogeneic transplantation and nontransplantation treatments. However, the lack of prospective comparative trials is and will continue to make this task challenging.
Does antithymocyte globulin have a place in reduced-intensity conditioning for allogeneic hematopoietic stem cell transplantation?
Authors: Siddiqi Tanya , Blaise Didier 
Published: October 2019

Abstract
A 63-year-old male patient without siblings is treated for acute myeloid leukemia with poor prognostic cytogenetics. Despite achieving a first complete remission, he relapsed within the first year of diagnosis. He then achieved a second complete remission. A search for an HLA-identical unrelated donor identified a 10/10 possible match. The patient has several comorbidities (hematopoietic stem cell comorbidity index = 3) and it is recommended that he undergo a reduced-intensity conditioning regimen for allogeneic peripheral blood stem cell transplantation. The patient is well-read on allogeneic stem cell transplantation and asks you the merits of antithymocyte globulin that you propose to include in the conditioning regimen.
Delayed opportunistic infections in hematopoietic stem cell transplantation patients: a surmountable challenge
Authors: Marr Kieren A. 
Published: October 2019

Abstract
Changes in the transplantation procedure and the implementation of effective supportive care strategies have decreased the incidence of infectious complications early after conditioning therapy for allogeneic hematopoietic stem cell transplantation (HCT) and have extended the duration of risks later. Therefore, the types of infections that cause significant morbidity and the timing of risks have changed. These late infections are caused by all types of organisms, bacterial, viral, and fungal, but risks are predictable and surmountable with the use of tailored prevention strategies. Specifically, recent studies document prolonged risks for bacterial infections in the setting of GVHD, especially those caused by encapsulated organisms and those secondary to impaired Ab responses. Both prophylaxis and vaccination strategies can be used as a means to prevent infections, which typically manifest in the respiratory tract. Multiple viruses cause infection later after HCT, including several herpesviruses (eg, CMV and varicella zoster virus) and other respiratory viruses such as influenza and adenovirus. These infections can cause severe disease with diagnostic challenges, but prevention strategies using enhanced monitoring and/or prophylaxis may be effective. Finally, fungi also cause disease late after HCT, especially filamentous fungi (eg, Aspergillus species and Mucormycoses) and Pneumocystis jiroveci; prophylactic strategies may be used successfully to prevent invasive infection. Late infections and methods to prevent them are reviewed herein.