bluuebunny/crossref_metadata_2025_split huggingface dataset:
A T2* MRI Prospective Survey on Cardiac and Hepatic Iron in Non-Trasfusion-Dependent Thalassemia Intermedia Patients Treated with Desferrioxamine
Authors: Meloni Antonella , Maggio Aurelio , Cosmi Carlo , D'Ambrosio Alfonso , Facchini Elena , Chiari Roberta , Sardella Leonardo , Grassedonio Emanuele , Valeri Gianluca , Neri Maria Giovanna , Positano Vincenzo , Pepe Alessia 
Published: October 2019

Abstract
Background. In thalassemia intermedia (TI) patients no observational study prospectively evaluated in the real life the efficacy of the desferrioxamine (DFO) therapy in removing or preventing iron overload from the heart and the liver by T2* Magnetic Resonance Imaging (MRI). The efficacy endpoint of this study is represented by the changes in cardiac T2* and MRI LIC (liver iron concentration) values in non-transfusion dependent (NTD) TI patients after 18 months of desferrioxamine therapy.
Methods. Among the 325 TI patients enrolled in the MIOT (Myocardial Iron Overload in Thalassemia) network, we selected 129 TI patients NTD. We considered 29 patients who had been received DFO alone between the two MRI scans. Cardiac iron overload was assessed by the T2* multiecho technique. Hepatic T2* values were converted into liver iron concentration (LIC) values.
Results. Mean age was 39.69 ± 8.12 years and 14 (48.3%) patients were females. Patients started regular chelation therapy at a mean age of 21.92 ± 15.89 years. The mean administered dosage of DFO via subcutaneous route was 38.46 ± 10.27 mg/kg body weight on 3.32 ± 1.54 days/week. The percentage of patients with excellent/good levels of compliance to the chelation treatment was 82.1%.
At baseline only one patient showed cardiac iron overload (global heart T2*=15.23 ms) but he recovered at the FU (global heart T2*=26.93 ms). All patients without cardiac iron maintained the same status at the follow-up (FU).
Eighteen patients (62.1%) had hepatic iron overload (MRI LIC ≥3 mg/g/dw) at the baseline.
For this subgroup, the baseline and the FU LIC values were, respectively, 9.15 ± 7.97 mg/g/dw and 7.41 ± 6.28 mg/g/dw. The reduction in MRI LIC values was not significant (P=0.102). Out of the 11 patients with a baseline MRI LIC <3 mg/g/dw, only one (9.1%) showed hepatic iron at the FU. The Figure shows the evolution of different hepatic iron overload risk classes between the baseline and the FU.
Conclusions. In this small population of sporadically or non transfused TI patients, DFO showed 100% efficacy in maintaining a normal global heart T2* value. As regards as the hepatic iron overload, the DFO therapy did not prevent the transition to a worst class in 2 patients.
Figure 1 Figure 1.

Disclosures
Pepe: Chiesi: Speakers Bureau; ApoPharma Inc.: Speakers Bureau; Novartis: Speakers Bureau.
Lack of Cardiac Iron in SCD Patients Despite Severe Iron Overload
Authors: Ahmad Rasha I , Keyrouz Sara , Arabi Mariam , Bitar Fadi , al Jaroudi Wael , Abboud Miguel 
Published: October 2019

Abstract
In sickle cell disease (SCD), transfusions improve blood flow by reducing the proportion of red cells capable of forming sickle hemoglobin polymer. The major and unavoidable complication of transfusions in SCD is iron overload. Patients with significant transfusion load and iron siderosis, often have iron deposit into multi organs, including liver, pancreas and heart. However, patients with SCD may be relatively protected from iron mediated cardiac toxicity as compared to patients with thalassemia and similar transfusion load. Nonetheless while patients with SCD have less iron deposition in the heart it is presumed that severe loading will eventually lead to cardiac involvement. We report here two patients with scd with severe iron overload who had no cardiac involvement.
These are an 18 year old female and her 20 year old male sibling, known to have SCD (HbSS) with significant blood transfusions history, once a month or every two weeks for 12 years duration. Both had undergone splenectomy, and multiple hospitalizations for pain crises and acute chest syndrome. They had received intermittent iron chelation therapy for only 2 years. Examination revealed marked hepatomegaly and highly elevated ferritin levels, 11964ng/ml and 7098ng/ml respectively, suggestive of iron overload. Both patients had unremarkable electrocardiogram and echocardiogram. SGPT and SGOT are normal. Both patients are below the 5thpercentile for height, and l the 18 year old girl is pre-pubertal, has growth hormone deficiency and is on treatment.
Cardiac, liver and pancreas magnetic resonance imaging with T2* showed normal cardiac structure and function without siderosis ( heart T2*32 ms and 35 ms in the female and male siblings, respectively [normal >20 ms]). There was however considerable liver siderosis with estimated liver iron content 16.6±4.4 mg/g dry weight (female sibling) and 13.9±1.8 mg/g dry weight (male sibling). The corresponding R2* were 646±165 HZ and 541±62 Hz, respectively. Also, there was mild to moderate pancreatic siderosis in the 18 year old female (R2* 111 HZ) and mild pancreatic siderosis in her sibling (R2* 55 Hz)
These two cases while consistent with what has been reported are unusual because of the degree of iron ovreloead. It is an unexepected finding that despite such extensive iron deposits in the liver, there is no evidence of cardiac iron. It thus seems that in patients with sickle cell disease, even with extensive liver siderosis and endocrine dysfunction there is sparing of the heart. Collecting and studying such cases may shed light on the mecahins of cardiac protection from iron overload in sickle cell disease.

Disclosures
No relevant conflicts of interest to declare.
High Concentration of Immunoglobulin Allows Long-Lasting Suppression of Allo-Immune Reaction By Directly Inhibiting T-Cell Activation
Authors: Maeba Hideaki , Kuroda Rie , Fukuda Masaki , Fujiki Toshihiro , Mase Shintaro , Araki Raita , Ikawa Yasuhiro , Koizumi Shoichi , Yachie Akihiro , Nishimura Ryosei 
Published: October 2019

Abstract
Intravenous immunoglobulin (IVIg) has been used after allogeneic stem cell transplants (HSCT) mainly to prevent infections. In addition, some studies have also demonstrated that IVIg reduced GVHD and GVHD-related mortality, but others failed to show these effects. To answer whether IVIg could reduce GVHD and/or has preventive effects, as a first step, we compared the mixed lymphocyte reactions (MLRs) between a variety of responder and stimulator combinations (Balb/c and C57BL/6) with/without immunoglobulin (Ig). We showed that the MLR was strongly inhibited when high concentration of Ig was added to the cocluture (Stimulator (S): bone marrow-derived dendritic cells (BM-DCs) obtained from C57BL/6 using GM-CSF, Responder (R): splenocytes obtained from Balb/c). Interestingly, dose dependent inhibition was not observed only when high concentration of Ig could suppresses allo-reaction. The next concern was whether Ig could suppresse MLR via modulation of DCs or T-cell directly, or both. To test this, splenocytes were stimulated with phytohemagglutinin (PHA) in the presence of various Ig concentrations. We observed that Ig suppressed PHA-induced T-cell proliferation in a dose dependent manner. To eliminate the possibility that Ig might have direct cytotoxicity against lymphocytes and consequently allo-immune reaction seemed to be inhibited, we performed dead cell analysis by flowcytometry using 7-AAD and annexin V on T-cells in the various concentrations of Ig. Even in high concentration of Ig, the frequency of apoptotic or dead cells were observed as same levels as in low concentration or absence of Ig, suggesting that Ig inhibited T-lymphocyte activation directly. Next concern was when Ig allowed tolerogenic function to T-cells and/or DCs. That is, only pretreatment of Ig before MLR was enough to suppress allo-reaction or persistent high concentration of Ig exposure was needed during MLR. To test this, splenocytes and BM-DCs were cultured with Ig for 24 hours before MLRs, and then washed twice and we compared the MLRs. Ig pretreatment to either splenocytes or BM-DCs or both did not show any suppression of MLRs as shown in the figure below, indicating that persistent high levels of Ig during interaction were needed to induce maximum inhibiting effects. In conclusion, we have clearly demonstrated that Ig has a strong capacity to suppress allo-immune reaction. Repetitive high dose IVIg treatment would be a promising approach to reduce or prevent sever acute GVHD, only if serum Ig concentration could be kept in high level. In addition, to apply this in clinical settings, disadvantage of high dose IVIg should be further investigated.
Figure 1 Figure 1.

Disclosures
No relevant conflicts of interest to declare.
Gorham's Disease: A Case of Vanishing Ribs and Its Effective Treatment with Sirolimus
Authors: Hall Nathan Scott , Carpenter Shannon L. 
Published: October 2019

Abstract
Introduction: Gorham’s disease, also known as Gorham-Stout syndrome or the vanishing bone disease, is a rare clinical entity characterized by a non-neoplastic proliferation of vascular and/or lymphatic vasculature with resultant osteolysis of adjacent bone1.With just over 200 reported cases, the etiology of Gorham’s disease is no better understood than when originally described by Dr. Jackson in 18382. Due to the rarity of Gorham’s disease, no standard treatment algorithm exists. Many therapeutic options have been proposed, however, the efficacy and success of these options is limited due to the lack of randomized controlled trials.
Case Presentation: Our patient is a 10 year old Caucasian female with past medical history significant for abnormal CXR (8months prior) showing absence of right sided 9th rib, who presented with right lateral abdominal pain, swelling and erythema. She denied fever, shortness of breath, malaise, decreased appetite, weight loss, recent travel, TB exposure or recent trauma. Laboratory work showed a normal CBC, BMP, LFTs, lipase, PT/PTT, and urinalysis. CT scan of the abdomen showed a right side pleural effusion as well as edema and fluid in the right anterior abdominal wall and subcutaneous fat. A chest tube was placed and 1.5 liters of fluid drained. An infectious and oncologic workup was initiated. Chest tube output was shown to be chylous and rib radiographs demonstrated absence of the complete right ninth rib, partial absence of the right eighth and tenth ribs. A rib biopsy was performed and showed of lymphatic proliferation with erosion/effacement of surrounding bone with no increased or abnormal osteoclastic activity, and no evidence of infectious or malignant etiology. This confirmed the previously presumed diagnosis of Gorham’s Disease.
Management and Outcome: Our patient was initially treated with bisphosphonate and interferon alpha 2b with minimal success. It was not until initiation of treatment and achieving a steady state of sirolimus that her disease was able to be controlled. She is now over two year in remission and continues on sirolimus therapy.
Disccussion:The rare diagnosis of Gorham disease unveils the difficulty in treating vascular and lymphatic malformations that medical providers encounter. The successful use of sirolimus in our patient adds another potentially useful medication in the treatment of vascular malformations. There are clinical trials currently being conducted to evaluate the safety and efficacy of sirolimus use in complex vascular malformations. Franchi, A, Bertoni, F, Bacchini, P, Mourmouras, V, & Miracco, C. CD105/endoglin expression in Gorham disease of bone. J Clin Pathol. 2009;62:163–167.Jackson JBS. A boneless arm. Boston Med Surg J. 1838;18:368-369.

Disclosures
No relevant conflicts of interest to declare.
the Diagnostic Value of Plasma Level, Activity, Ratios between von Willebrand Factor and ADAMTS13 in Patients with Cerebral Infarction
Authors: Qu Le , Ruan Changgeng , Zhao Yiming 
Published: October 2019

Abstract
Introduction: Large population studies have revealed that higher levels of von Willebrand Factor (VWF) and lower levels of ADAMTS13 activity (ADAMTS13) are associated with a risk of thrombosis. In this study, we aimed to investigate the relationship among the plasma levels of VWF, ADAMTS13 and the occurrence of cerebral infarction in patients.
Methods: In a case-control study of 94 cerebral infarction patients (CIP) and 103 age-matched healthy controls (Control), the plasma levels of VWF antigen (VWF:Ag ), VWF ristocetin cofactor activity (VWF:Rcof), and VWF collagen binding activity (VWF:CB) were measured using ELISA. ADAMTS13 activity (ADAMTS13) was measured with FREST-VWF73. The study was approved by the institutional Ethics Committee at the First Affiliated Hospital of Soochow University, China. All participants were given write informed consents.
Results: The levels of VWF:Ag and VWF:Rcof in cerebral infraction patients (mean±SEM, 223±15% and 256±20%) were significantly higher compared with controls (117±8% and 128±9%). Levels of ADAMTS13 and ratios of VWF:CB/VWF:Ag, ADAMTS13/VWF:Ag and ADAMTS13/VWF:Rcof in patients (107±4%, 0.73±0.08, 0.76±0.07 and 0.86±0.10, respectively) were significantly lower compared with controls (125±3%, 1.37±0.08, 1.69±0.14 and 1.45±0.10, P<0.001, respectively). However, there was no difference between cerebral infarction patients and controls in the levels of VWF:CB, VWF:Rcof/VWF:Ag and ADAMTS13/VWF:CB (P>0.05). Unconditional logistic regression analysis demonstrated the highest quartile of VWF:Ag (odds ratio [OR] = 5.11, 95% confidence interval [CI], 1.49-17.50), VWF:Rcof (OR = 5.04, 95% CI, 1.62-15.66), and the lowest quartile of VWF:CB/VWF:Ag (OR = 5.91, 95% CI, 1.95-17.93), ADAMTS13/VWF:Ag (OR = 9.11, 95% CI, 2.49-33.33), ADAMTS13/VWF:Rcof (OR = 3.73, 95% CI, 1.39-10.03) were associated with cerebral infarction (P<0.01). The receiver operating characteristic (ROC) curves analysis demonstrated the cutoff values of VWF:Ag (137.88%), VWF:Rcof (135.88%) and VWF:CB/VWF:Ag (0.538), ADAMTS13/VWF:Ag (0.974), ADAMTS13/VWF:Rcof (0.946) showed a better diagnostic value of cerebral infarction (AUC > 0.7).
Conclusions: High levels of VWF:Ag, VWF:Rcof and lower levels of VWF:CB/VWF:Ag, ADAMTS13/VWF:Ag, ADAMTS13/VWF:Rcof are relative risk factors. The threshold of VWF:Ag ( > 137.88%), VWF:Rcof ( > 135.88%), VWF:CB/VWF:Ag ( ≤ 0.538), ADAMTS13/VWF:Ag ( ≤ 0.974), ADAMTS13/VWF:Rcof ( ≤ 0.946) can be diagnostic indicators of cerebral infarction.
Research funding: This work was supported by grants from National Scientific Foundation of China (NSFC) (81270593), Jiangsu Provincial Special Program of Medical Science (BL2012005) and Jiangsu Province’s Key Medical Center (ZX201102), China

Disclosures
No relevant conflicts of interest to declare.
Recombinant Human Thrombopoietin: a Novel Therapeutic Option for Patients with Immune Thrombocytopenia in Pregnancy
Authors: Kong Zhangyuan , Qin Ping , Wang Xin , Hou Ming 
Published: October 2019

Abstract
BACKGROUND:
Thrombopoietin (TPO), the major physiological regulator of platelet formation, binds to and activates TPO receptor on megakaryocytes, thereby promoting platelet production. Recombinant human thrombopoietin (rhTPO) is a novel therapeutic option for patients with immune thrombocytopenia (ITP) in China. However, the safety and efficacy of rhTPO for ITP patients in pregnancy is unclear. We report two ITP patients in pregnancy successfully treated with rhTPO.
METHODS:
Patient one, who was diagnosed as ITP according to the ASH guidelines two years ago, was a 28-year-old G2P1 pregnant woman, with a platelet count of 10×109/L and gingival bleeding. Before rhTPO therapy her TPO level was 231pg/mL. Patient two, who was diagnosed as ITP one year ago, was a 23-year-old primigravid woman with gross hematuria at 22-week gestation. Her platelet count was 19×109/L and the level of TPO in her plasma was 107pg/mL before rhTPO admission. Both patients failed to respond to prednisone (1mg/kg, 14d) and intravenous immunoglobulin (IVIG, 0.4g/kg, 5d). Due to persistent hemorrhage, they received rhTPO at a daily dose of 300U/kg daily (3SBIO Pharmaceutical Co., LTD, Shenyang, China). When their platelet counts rose above 50×109/L, maintenance therapy (rhTPO 300U/kg, every other day) started. This treatment protocol was approved by the Medical Ethical Committee of Qilu Hospital, Shandong University.
RESULTS:
The platelet count of patient one rose to 165×109/L after 10 days of rhTPO therapy. Then rhTPO maintenance therapy was applied. On the 39th week, she vaginally delivered a female infant with normal platelet count. The TPO level of the newborn was 127pg/mL. In the second case, after seven days of rhTPO therapy, her platelet count rose to 58×109/L, then we started rhTPO maintenance therapy. On the 40th week, she delivered a female infant without any signs of neonatal ITP. The level of TPO in the infant's plasma was 174pg/mL. Maintenance therapy continued after delivery with a dose of 300U/kg per week. The platelet counts of patients during treatment were illustrated in Figure 1. At a 1-month follow-up visit, no adverse events were observed in both infants.
CONCLUSION:
RhTPO may be an effective and fast-onset treatment for ITP in pregnancy. Future studies are necessary to investigate the safety and efficacy of rhTPO in this clinical setting.
Figure 1 Figure 1.

Disclosures
No relevant conflicts of interest to declare.
Analysis of the Quality of Life in Children and Their Parents with Immune Thrombocytopenia in China
Authors: Zhou Min , Li Xiao-jing , Shu Hui-ying , Meng Fan-yi , Yang Mo 
Published: October 2019

Abstract
In this study, we assessed the health-related quality of life (QoL) in children with immune thrombocytopenia (ITP) and their parents in China using a disease-specific QoL measure, the Kids' ITP Tools (KIT). Forty-three Children less than 18 years of age with newly diagnosed ITP and their parents were recruited to complete the KIT study. The children’s version of the KIT consisted of 26 items which divided into 5 domains: treatment side effects, intervention-related, disease-related, activity-related, and family-related concerns. Parental version of KIT consisted of 26 items which divided into 6 domains: diagnosis-related, monitoring-related, child’s restricted activity-related, daily life-related, disease outcome, and emotional impact. Each item was rated on a 6-point Likert scale from 1 (not at all) to 6 (a great deal). A high score represented a high concern level. Scores for the individual domains were summed to yield a total KIT score. The reliability of KIT was found to be high in assessing QoL of children with ITP and their parents in China (children’s version: Cronbach’s a=0.933, parents’ version: Cronbach’s a=0.905). Parent KIT scores was significantly higher than child KIT scores, (31.46±14.58）vs（79.05±14.99）Z=7.625，P=0.000. Which suggested that QoL of parents was significantly lower than children’s. Among the children KIT, the highest mean score was noted in the “intervention-related” (1.92±1.30) and “activity related (1.82±1.47)”. Among the parents KIT, the highest mean score was noted in the “emotional impact（4.88±0.97)” and “disease outcome (4.78±1.01)”; (3) The KIT scores for different age groups of children with ITP were significantly different which showed that the older the children were, they cared for more and worried more about the disease. But the KIT scores for parents were no different in different age groups, which suggested that whatever their children are old or young, Chinese parents worried about ITP disease in the same degree. The QoL of children with ITP and their parents were remarkably lower in Chinese, especially for parents. The cross-culturally translated KIT was a valid and reliable disease-specific measure of health-related quality of life for children with ITP. KIT could be used as an tool in clinical trials and management of childhood ITP.

Disclosures
No relevant conflicts of interest to declare.
Complications of Central Venous Therapy in Children with Hemophilia in Poland
Authors: Laguna Pawel , Klukowska Anna , Pawelec Katarzyna , Matysiak Michal 
Published: October 2019

Abstract
Introduction
Central venous catheters (CVC) are essential in the management of children with hemophilia who need frequent infusions. Peripheral access is usually sufficient but the use of a central venous line is necessary in many cases.
Methods
CVCs have been used in our department since 1997. During this time 75 CVCs (port-a-cath) have been inserted in 54 patients aged 3 months to 18 years. 52 patients had hemophilia A and 2 had hemophilia B.
21 out of 52 had hemophilia A complicated by high-titre inhibitors. CVCs were inserted 3 times in 2 patients and twice in 11 patients. In the remaining patients 47 they were inserted once. All the ports were inserted on the left side of the body and replacements were inserted on the right side. CVCs were used for ITI in 10 patients.
Results
The period of vascuport use ranged from 2 to 103 months CVL injections were observed 17 times in 13 children. All infected ports were successfully treated with antibiotics. Trombotic complications occurred in 8 boys 11 times. In 2 cases the ends of the CVCs got torn and moved to the heart, while in 2 other cases the reservoir stated leaking.
Conclusion
Our investigations show that CVLs are convenient in use but complications can occur.

Disclosures
No relevant conflicts of interest to declare.
The Effect of Tanshinone-IIa on IL-1β Induced-Thrombocytosis in an Immune Vasculitis Model
Authors: Zhou Min , Zhou Li-xia , Shu Hui-ying , Li Xiao-jing , Lian Qi-zhou , Meng Fan-yi , Yang Mo 
Published: October 2019

Abstract
Inflammation cytokines may be involved in the pathogenesis of thrombocytosis with vasculitis. Our previous study showed that inflammation cytokine IL-1β plays an important role on in-vitro megakaryopoiesis (Yang M et al, Br J Haematol 2000). The role of IL-1β and Tanshinone IIA (TIIA) (Isolated from Danshen, Radix Salviae Miltiorrhiza Bge) on platelets and megakaryocytes (MKs) in immune vasculitis model was investigated in this study. Rabbit model with immune vasculitis was established by injection (iv) of BSA. After treatment with BSA for 7 days, the platelet count, platelet aggregation and the expression of AnnexinⅤ were significantly increased in this vasculitis model group compared with normal control group (n=7). IL-1β levels was also significantly higher in vasculitis model. There were positive correlations between platelet count and IL-1β levels (R=0.65), platelet aggregation and IL-1β levels (R=0.60). Treatment with TIIA (5 mg/kg/day, iv) and aspirin significantly decreased all these parameters. MKs and CFU-MK number were also significantly increased in vasculitis group as compared to normal group. Treatment with TIIA and aspirin significantly reduced the number of MKs and CFU-MK in this model. Study further demonstrated that IL-1β alone or in combination with TPO induced in-vitro CFU-MK formation. The mRNA of of IL-1 type I and type II receptors (IL-1 RI and RII) were detected in cultured MK (CD61+ CD41+) cells. The expression of IL-1 RI and RII was also confirmed by immunofluorescence staining in bone marrow MKs. Moreover, the IL-1R bloker can reduced IL-1β induced megakaryopoiesis. TIIA on in-vitro megakaryopoiesis was also investigated. TIIA at 10-30 ug/ml significantly inhibited CFU-MK formation. TIIA also induced the apoptosis of MKs in a dose dependent manner by Anexin V assay. Caspase 3 assay showed the activation of Caspase 3 increased from 5% to 16%. Using JC-1 assay found that the depolarized cells increased from 9% to 17% suggesting the involvement of intrinsic apoptotic pathway. IL-1β may play an important role in the thrombocytosis of immune vasculitis by inducing megakaryopoiesis. TIIA has anti-platelet effect in this model which may be mediated via inhibiting IL-1β induced-megakaryopoiesis.

Disclosures
No relevant conflicts of interest to declare.