bluuebunny/crossref_metadata_2025_split huggingface dataset:
Kikuchi Disease in Korean Children: Clinical Features and Disease Courses.
Authors: Park Jun Eun , Jung Hyun Joo , Kim Chul-Ho , Hong Jeong , Han Jae Ho 
Published: October 2019

Abstract
OBJECTIVES: Kikuchi’s disease (KD) is a benign, self-limiting disorder of unknown origin with lymphadenopathy and fever, and prevalent in young Asian women. The initial presentations mimic malignancies or other serious infections, and the biopsy of lymph nodes affected is the only definite diagnostic tool of KD. We analyzed data from a series of pediatric cases collected at a single medical center and suggest proper guideline of management for patients with KD.
METHODS: The medical records of children under 16 years of age, who underwent lymph node biopsies and received histiopathologic diagnosis of KD at Ajou University Hospital, South Korea from January 2000 to June 2007, were retrospectively reviewed.
RESULTS: Twenty six pediatric patients with KD included 10 boys and 16 girls. In all cases except two, the cervical lymph nodes were involved. Twenty (76.9%) patients had fever as a presenting symptom, and 5 patients (19.2%) had various skin rash. Leukopenia was noted in 8 cases (30.8%), but there was no case of leukocytosis. The levels of ESR and LDH were slightly elevated, but CRP and liver enzymes were within normal range. No KD patients in this study developed any other autoimmune disorders during follow-up period. Eleven (55%) cases with fever improved immediately after excision biopsy of affected lymph nodes. Eight (30.8%) cases treated with steroid showed dramatic responses. Six patients (23.1%) had resolutions of symptoms simply with symptomatic treatments. The recurrence happened in 6 (23.1%) children within a few weeks from the first episode.
CONCLUSIONS: Contrary to previous reports on Asian cases, KD in Korean children is not rare in young boys, and fever is more common presenting symptoms. It’s relationship with autoimmune diseases or infection of EBV is not clear. Symptoms such as fever improved in some cases only by the removal of affected lymph node for excision biopsy. In agreement with previous reports, patients treated with steroid recovered dramatically. Therefore, we suggest an earlier excision biopsy for patients suspicious with KD and an immediate treatment of cases with severe symptoms with steroid. The recurrence rate in this study was higher than that in previous studies, therefore, a spell of follow-up period after disappearance of symptoms is advisable for patients with original diagnosis of KD.
The Brain Transcription Factor OTX1 Is Activated in Specific Non-Hodgkin Lymphoma Subtypes and Normally Expressed in a Germinal Center-Restricted Small Subpopulation of CD138+ Plasmacell-Like Cells.
Authors: Russo Filippo , Omodei Daniela , Acampora Dario , De Filippi Rosaria , Severino Valeria , Di Francia Raffaele , Frigeri Ferdinando , Mancuso Pietro , De Chiara Anna , Franco Renato , Casola Stefano , Pinto Antonio , Simeone Antonio 
Published: October 2019

Abstract
OTX1 and OTX2 are transcription factors containing a bicoid-like homeodomain and play crucial roles in brain development and in few other body districts as in the case of OTX1, which is required in hematopoiesis for development of the erythroid compartment. Previous studies indicated that in human OTX2 is functionally involved in the generation of anaplastic medulloblastomas; OTX1 expression strongly correlates with nodular/desmoplastic medulloblastomas; and none of them is expressed in other brain tumors. Here we have investigated whether OTX1 and/or OTX2 may potentially be involved in tumors of nonneural origin by focusing on human B-cell non-Hodgkin’s lymphomas (NHLs). We analyzed 184 cases (fig 1)encompassing different NHL subtypes according to the World Health Organization classification and discovered that, while OTX2 expression was never detected, OTX1 was selectively activated in virtually all cases of Diffuse Large B Cell Lymphoma, Burkitt Lymphoma and a relevant fraction of Follicular Cell Lymphomas. In DLBCL lymph nodes and tissue infiltrations, OTX1 protein was detected in the nucleus of PAX5+-CD20+ cancer cells. Conversely, in nonmalignant lymph nodes and tonsils, OTX1 was expressed in a numerically very small and non-proliferating cell population restricted to the germinal center. These OTX1+ cells were CD138+-IgG+, about 50% of them also co-expressed both CD10 and CD20 and none of them exhibited PAX5 or BCL6 expression, thus suggesting that OTX1 expression identifies a subset of GC-restricted plasmacell-like cells (fig 2). Interestingly, in contrast with lymphomas, in these cells the OTX1 protein was prevalently localized to the cytoplasm. Collectively, our data suggest that activation of OTX1 expression and its nuclear localization represent together a newly described molecular event occurring in specific NHL subtypes of GC and early post-GC origin (FCL, DLBCL, BL), and lead us to hypothesize that it may be potentially involved (directly or indirectly) in the initiation and/or maintenance of these tumors.
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Discrimination Indices as Screening Tests for Beta-Thalassemic Trait.
Authors: Ntaios George , Chatzinikolaou Anastasia , Saouli Zoi , Girtovitis Fotios , Kaiafa Georgia , Kontoninas Zisis , Agapakis Dimitrios , Savopoulos Christos , Papadopoulos Athanasios 
Published: October 2019

Abstract
Introduction: The two most frequent microcytic anemias are β-thalassemic trait (β-TT) and iron deficiency anemia (IDA). Several discrimination indices have been proposed in order to distinguish between these two conditions. These indices are derived from several simple red blood cell indices, like RBC count, mean cell volume and RBC distribution width (RDW), as these are provided by electronic cell counters. Purpose of the study is to examine the diagnostic accuracy of six discrimination indices in the differentiation between IDA and β-TT.
Methods: The six discrimination indices that were examined were: Mentzer Index, Green & King Index, RDW Index, England & Fraser Index, RDW and RBC count. We calculated these indices on 373 patients (205 males, 168 females) with β-TT and 120 patients (50 males, 70 females) with IDA, as well as their sensitivity, specificity, positive and negative prognostic value, efficiency and Youden’s index.
Results: G&K shows the highest reliability, followed by E&F, RBC count, MI and RDWI. On the contrary, RDW completely failed to differentiate between IDA and β-TT. G & K proved to be the most reliable index, since it had the highest sensitivity (75.06%), efficiency (80.12%) and YI (70.86%) for the detection of β-TT.
Conclusion: These six discrimination indices cannot be relied on for a safe differential diagnosis between β-TT and IDA. They do have high specificity, but their sensitivity for the detection of β-TT is not satisfactory. Consequently, they cannot be used neither as a screening tool for β-thalassemic trait, since they could result in a significant number of false negative results.
Spectrum of Thromboses in Patients with Methylenetetrahydrofolate Reductase (MTHFR) Polymorphisms: Continuing Controversy.
Authors: Sullivan Kevin , Kempin Sanford , Li Zujun , Cook William , Marionneaux Steve 
Published: October 2019

Abstract
Thromboembolic disease is common with an annual incidence of 1–3/1000 individuals. Both acquired and genetic risk factors are responsible. A risk factor for thrombosis can now be identified in over 80 percent of patients. Fifty percent of thrombotic events in patients with inherited thrombophilia are associated with an acquired risk factor. Patients with multiple inherited risk factors are at a greater risk. Two common variations of the MTHFR gene (677CàT and 1298AàC) result in amino acid substitutions and enhanced thermolability of the enzyme. The latter, in the presence of folic acid deficiency, results in elevated homocysteine levels. Thrombosis has been observed in these patients, but there is still controversy whether there is a direct association (Bezemer I, et al. Arch Int Med167, 497–501, 2007; den Heijer M et al. J Thromb Haemost3:292–299, 2005). In the present study, we describe the spectrum of thromboembolic disease observed in 39 patients with a variety of MTHFR polymorphisms referred to a specialty center with a personal or family history of thromboses or obstetrical loss, 18 of these patients having no other risk factor other than MTHFR polymorphisms. These polymorphisms include 18 heterozygotes (11 with 677CàT; 7 with 1298AàC), 9 homozygotes (5 with 677CàT; 4 with 1298AàC) and 12 compound heterozygotes (677CàT and 1298AàC). Concomitant risk factors were found in twenty-one patients (factor V Leiden - 6; prothrombin G20210A - 3; protein C deficiency - 1; protein S deficiency - 1; PAI-1 polymorphism - 2; activated protein C resistance - 2; antiphospholipid antibody syndrome - 5; malignancy - 3; coronary artery disease - 1; hemolytic anemia - 1; factor VIII deficiency - 1). Types of thromboembolic manifestations observed in the 39 patients include venous thromboembolism (22), obstetrical loss (7), arterial thrombosis (3), myocardial infarction (3), ischemic CNS lesions (2), and palpable purpura (1), for a total of 38 manifestations. Seven of the patients had a family history of thromboembolic disease. Patients with only MTHFR polymorphisms suffered 16 types of thromboembolic events (16/38=42%). Our observations suggest that MTHFR polymorphisms alone do play a role in clinically relevant thrombotic disease and probably increase the incidence of these diseases in patients harboring other causes of thrombophilia. Therefore, continuing surveillance for this polymorphism as part of a clinical thrombophilia assessment is recommended, particularly if homocysteine levels are elevated.
Correlation of Thrombosis and Prothrombotic Markers with Outcome in Lung Adenocarcinoma Patients: A Prospective Study.
Authors: de Meis Ernesto , Zamboni Mauro M. , Pinheiro Vera R. , Guedes Maria T.S. , Lima Luize G. , Castilho Ilda A.M. , Sousa Amanda F. , Silveira Neura P.R. , Loures Maria A.L. , Levy Roger A. , Monteiro Robson Q. 
Published: October 2019

Abstract
Background: It is largely accepted that cancer patients have a high incidence of thrombosis which is strictly related to prognosis of cancer. Aim: We prospectively evaluated 81 consecutively lung adenocarcinoma patients in order to identify prothrombotic factors and thrombosis incidence.
Methods: Patients were submitted to Doppler examination of arms and limbs every three months or in case of thrombosis suspicion. Additional image evaluations were made in case of inconclusive diagnosis. Levels of C protein, platelets, and fibrinogen, factor VIII and IX, D-dimmer, antitrombin and apoptotic microparticles were evaluated each six months. Samples were also tested for lupus anticoagulant (LA) antibodies and levels of IL-1, IL-6 and Tumor Necrosis Factor (TNF). A group of 30 healthy blood donors was used as control.
Results: From the studied patients 21% had thrombosis, 38% had fibrinogen above 500 mg/dl, 42% had FVIII activity above 200%, 63% had increased D-dimmer, 60% had more than 1x106 microparticles/ml serum, and none of them have decreased levels of C protein or antitrombin. A small fraction of patients had increase of platelet counts. At immunological evaluation 52% of patients had LA detection and 63% showed increased leves of IL-6. Patients with at least one of the variables thrombosis, high levels of IL-6 (p<0.001), FVIII (p=0.05) and LA p=0.02) detection had a worst prognostic. Patients with increased FVIII levels (p=0,05) or LA detection (p=0,028) showed a significant increase in the thrombosis risk, whereas patients with more than 1x106 microparticles/ml showed only a tendency to increased risk of thrombosis (p=0,09).
Conclusion: There is a high incidence of thrombosis in lung adenocarcinoma patients, on which FVIII and LA significantly influenced and microparticles only showed a tendency. However, presence of LA, thrombosis or increased levels of IL-6 or FVIII showed directly interfered with patient’s survival.
Venous Thromboembolic Events in Women Using the NuvaRing®.
Authors: Shum Merrill K. , Rajagopalan Kumar , Lachant Neil A. 
Published: October 2019

Venous thromboembolic events (VTEs) are serious adverse effects seen in some women using oral contraceptives. Although the novel vaginal ring, (NuvaRing®) has been reported to be effective and well tolerated, the risks of VTEs are unknown. We report 3 women who developed potentially life-threatening VTEs (2 with pulmonary emboli and 1 inferior vena cava thrombus) while on the NuvaRing®. VTEs occurred 22 days, 3 months and 3 months after NuvaRing® insertion. None had a personal or family history of VTEs. Extensive thrombophilia evaluation showed 1 with heterozygous factor V Leiden and 2 with a transient lupus anticoagulant. 2 had a personal history of multiple miscarriages and all 3 had an elevated body mass index > 26. Searching Pubmed, Ovid and Medline, there have been 10 other reported cases of VTEs, in women using the vaginal ring (see table below). Risk factors reported by other authors include anticardiolipin antibodies, protein S deficiency, heterozygous prothrombin 20210, heterozygous factor V Leiden and prolonged air travel. With limited follow up, the true incidence of VTEs in women using the NuvaRing® is difficult to determine. However, in 2005 the Swedish Medical Products Agency reported a relative incidence of 5.3 cases per 10,000 women years for VTE complications. In summary, we report 3 women who had life-threatening VTEs associated with the use of the NuvaRing®. Longer follow-up of safety studies and post-marketing adverse event reporting are needed to determine VTE risks and incidence while using the NuvaRing®.
Studies reporting VTEs in women using the NuvaRing® Source Number of patients VTE risk factors Family history Site Bjarnadottir et al, 2002 1/121 Unknown Unknown LE DVT Tuppurainen el al, 2004 1/40 Unknown Unknown LE DVT Oddsson et al, 2005 1/512 Unknown Unknown LE DVT Miller et al, 2005 1/429 Anticardiolipin antibodies, protein S deficiency Grandmother with DVT LE DVT Ahrendt et al, 2006 1/499 Double heterozygous factor V Leiden/prothrombin 20210, prolonged air travel Unknown LE DVT Roumen et al, 2006 1/854 Unknown Unknown Cerebral sinus thrombosis Samuelsson et al, 2007 1 Heterozygous prothrombin 20210 None Axillary vein DVT Swedish Medical Products Agency, 2005 4/? Unknown Unknown DVTs Shum et al, 2007 3 Obesity (3), Personal history of miscarriages (2), heterozygous factor V Leiden (1) 1 sister with miscarriage Bilateral pulmonary emboli (2), Iliac vein-IVC thrombus (1)
A NUP98-HOXD13 Fusion Gene Induces a Transplantable Myelodysplastic Syndrome in Mice.
Authors: Chung Yang Jo , Choi Chul Won , Slape Christopher , Fry Terry , Aplan Peter D. 
Published: October 2019

Abstract
The myelodysplastic syndromes (MDSs) are a group of hematologic stem cell disorders characterized by ineffective hematopoiesis and dysplasia. A large number of chromosomal aberrations including deletions, amplifications, inversions, and translocations, some of which involve the NUP98 gene, have been associated with MDS. Recently an MDS mouse model expressing a NUP98-HOXD13 (NHD13) fusion gene was developed, which faithfully recapitulates all of the key features of MDS. Although it is well-established that acute myeloid leukemia (AML) is transplantable, there is no evidence that MDS is a transplantable condition. Therefore, in order to develop evidence for MDS as a hematopoietic stem cell (HSC) disease, we attempted to transfer MDS to normal recipients through bone marrow transplantation (BMT). All the recipients transplanted with bone marrow (BM) cells from NHD13 mice with MDS showed anemia, leukopenia, lymphopenia, and neutropenia when compared to recipients of wild-type (WT) littermates. The homing efficiency of the NHD13 primitive progenitor cells (Lineage negative [Lin−], Sca-1+) was about 2 fold higher than WT, and there was no significant difference in BM cellularity between the recipients of NHD13 and WT BM, indicating that the NHD13 recipients had ineffective hematopoiesis. These phenomena were reproduced in secondary recipients using primary recipients of NHD13 BM as donor mice. In secondary transplantation assays, 3 out of 5 recipients developed acute myeloid leukemia (AML) at 16 weeks post-transplantation. Morphological features of MDS, including nuclear-cytoplasmic asynchrony, binucleate cells, hypersegmented neutrophils, and giant platelets were detected in BM and peripheral blood of NHD13 donor, primary and secondary recipients by cytospin preparations. In competitive repopulation assays, mice transplanted with equal numbers of WT and NHD13 BM cells showed a decreased percentage of NHD13 cells in the peripheral blood, but an increased percentage of NHD13 cells in the BM, again providing evidence of ineffective hematopoiesis of the NHD13 cells. The transplantation of lineage depleted cells from BM has shown that the transplantable cells for MDS reside in the Lin− population of NHD13 BM. These findings demonstrate that MDS can be transferred to healthy recipients by BMT, supporting the concept that MDS originates in a transplantable multilineage hematopoietic stem cell.
Universal Thrombophilia Screening with Risk Stratification and Anticoagulation Management in Pediatric Renal Transplant Recipients.
Authors: Saxena Kapil , Turman Martin , McNall-Knapp Rene Y. , Rianthavorn Pornpimol , Kropp Bradley P. , Sindhwani Puneet , Meyer William H. 
Published: October 2019

Abstract
Objective To identify renal transplant patients at a higher risk for allograft thrombosis and develop a risk stratification protocol for post-operative anticoagulation.
Background According to the North American Pediatric Renal Transplant Cooperative Study data, vascular thrombosis is responsible for 12% of renal transplant failures. Congenital and acquired prothrombotic disorders have recently been found to play a major role in defining outcome of the renal transplants.
Methods In 2007, we initiated universal screening for acquired and congenital thrombophilic risk factors for all renal transplant patients prior to transplant. They were assigned a risk category (Level I-IV) based on the presence of thrombophilic risk factors and their post-operative anticoagulation plan was pre-determined based on their risk level (Table). Low-dose unfractionated heparin drip was initiated a few hours after the transplant and titrated to achieve a 1.5 fold aPTT level. Anticoagulation was changed to low molecular weight heparin (LMWH) on day 2–4, when the risk of major bleed was over, and the serum creatinine had normalized.
Result Nine patients have been screened and 8/9 were found to be at high risk for thrombosis (Level II or III). The prothrombotic risk factors identified were Prothrombin gene mutation (2), MTHFR (8), Lupus anticoagulant (2) and low protein S (2). Five patients have undergone renal transplant, and have been treated with LMWH post-operatively as per plan, with successful outcome. No patient has developed allograft thrombosis. 1/5 patients developed a peri-renal hematoma requiring evacuation, but completed prophylactic LMWH therapy.
Conclusion Renal allograft thrombosis is preventable. Universal screening can stratify risk and allow an effective intervention to reduce that risk. Our Institution has developed a unique risk stratification protocol to identify patients at high risk for allograft thrombosis and prevent this complication by post-operative anticoagulation.
Risk Categorization and Management Plan Risk Level Thrombophilia Management Level I Evidence of Thrombophilia (other than MTHFR) and previous thrombosis Heparin postoperatively and then LMWH bid for 6 months Level II Evidence of Thrombophilia (other than MTHFR), No history of thrombosis Heparin postoperatively, LMWH bid for 3 months, then qd for 3 months Level III MTHFR with normal homocysteine Heparin postoperatively, then LMWH qd for 3 months Level IV No evidence of thrombophilia No anticoagulation
HLA B*1402, Cw*0802 Haplotype and DRB1*1501 Allele Are Significantly Increased in Italian Paroxysmal Nocturnal Hemoglobinuria Affected Patients.
Authors: Alfinito Fiorella , Cosentini Elena , Camerlengo Rosa , Terrazzano Giuseppe , Sica Michela , Risitano Antonio , Costagliola Stefania , Pepa Roberta Della , Palladino Carmela , Luzzatto Lucio , Rotoli Bruno , Notaro Rosario , Ruggiero Giuseppina 
Published: October 2019

Abstract
Paroxysmal Nocturnal Hemoglobinuria (PNH) is an acquired disorder characterized by the emergence and expansion of a GPI-defective clonal haematopoiesis. Its clinical features are haemolytic anaemia, cytopenia and thrombosis. Several data suggests the pathogenetic relevance for auto-immune-mediated mechanisms in the expansion of the mutated clone. Since HLA genes represent a susceptibility factor for autoimmunity, we have investigated HLA genotypes in 42 Italian patients with PNH. This study analyzed the HLA class I and class II genes in a cohort of 42 Italian PNH patients. Data indicate the occurrence of a significant increase of A*33 (9.5% in PNH patients versus 2.3% in controls; p<0.05), A*0201 (52.5% versus 32.2%; p<0.05), B*1402 (23.8% versus 5.3%; p<0.0005) and Cw*0802 alleles (23.8% versus 5.9%; p<0.001) in the PNH patient cohort, as compared with a population of 301 healthy controls of the same ethnical origin. In addition, an increased frequency of DRB1*1501 (21.1% versus 5.3%; p<0.005) and DRB1*01 (31.6% versus 10.9%; p<0.005), without specific association with the DRB1*0101 or DRB1*0102 allele, has been revealed. Notably, the B*1402, Cw*0802 (23.8% versus 5.3%; p<0.0005) HLA -B,-C haplotype was significantly increased. Moreover, the A*33, B*1402, Cw*0802, DRB1*0102 HLA-A, -B, -C, -DR haplotype shows a fifteen times increased frequency in PNH patients, if compared with controls (10.5% versus 0.66%; p<0.005). HLA polymorphism represents a main autoimmune susceptibility factor. In this context, our results suggest that specific peptide/s could be relevant for the selection/dominance of PIG-A mutated clones in our cohort of Italian PNH patients. Alternatively, the linkage of the described allele/s and haplotype with not yet characterized genes and/or with gene/s likely involved in pro-inflammatory cytokine productopn might be hypothesized. The association between certain HLA types and the occurrence of PNH may provide further insight into the mechanism for selective damage to normal (GPI+) hematopoiesis, which is responsible for the clonal expansion of GPI-defective hematopoiesis that ultimately gives rise to clinical PNH.