bluuebunny/crossref_metadata_2025_split huggingface dataset:
Central Line-Associated Venous Late Effects in Children without Any Prior History of Thrombosis - A Cross-Sectional Study of Children Previously Treated for Malignant or Hematological Diseases.
Authors: Ruud Ellen , Holmstrøm Henrik , Hopp Einar , Wesenberg Finn 
Published: October 2019

Abstract
Background: The frequency of asymptomatic central line-associated thromboses is high and well recognised among children with cancer, while the long-term consequences are mainly unknown. In a cross-sectional study, we have evaluated clinical and radiological venous outcome in children with previous long-standing intravascular catheters.
Methods: The study enrolled 71 children previously treated for malignant or haematological diseases, 4–180 (median 37) months after removal of their central lines. The central lines had been placed in a jugular vein for a minimum of six months, and none had a previously identified event of thrombosis. The children were clinically examined for post-thrombotic syndrome (PTS) and had Doppler ultrasonography of their central neck veins. In a subgroup of twelve children, venous magnetic resonance imaging (MRI) of the same area of interest was performed.
Results: We observed mild PTS with increased superficial collaterals in four children (6 %), but no cases of more severe PTS. None complained of symptoms related to venous late effects. By ultrasonography, post-thrombotic venous alterations were detected in 17 children (24 %), and five of these had complete occlusion of veins. The sensitivity for pathologically increased collaterals to identify occlusive thrombosis was 0.6, while the specificity was 0.98. Occlusive thrombosis was associated with previous central line-associated infections (p = 0.001) and duration of central lines in place (p = 0.042). MRI did not give any extra information, and only occlusive thromboses were confirmed at MRI.
Conclusions: In spite of no prior history of thrombosis, children with previous long-term jugular lines had often local thrombotic sequelae, while clinical symptoms of PTS were rare.
Evaluation of Progenitor Cells (CFU-GM, CFU-GEMM, BFU-E, CD34+ Cells) and White Blood Cells in Patients with Newly Diagnosed Diffuse Large B-Cell Lymphoma Treated with Rituximab-CHOP-14 and Supported with Pegfilgrastim.
Authors: Bonfichi Maurizio , Brusamolino Ercole , Marseglia Carmela , Rusconi Chiara , Lazzarino Mario 
Published: October 2019

Abstract
Purpose: To investigate the behavior of CFU-GM, CFU-GEMM, BFU-E, CD34+ cells and white blood cells before and during six courses of dose-dense immune-chemotherapy (R-CHOP-14) supported by pegfilgrastim in eight patients affected with newly diagnosed diffuse large B cell lymphoma (3 men, 5 women, aged 18–51).
Patients and Methods: The standard-dose CHOP chemotherapy was delivered every 14 days, preceded on day 1 by rituximab (375 mg/m2) and followed on day 3 by pegfilgrastim (6 mg per cycle). In each course of therapy, the evaluation was performed before treatment (day 1) and on days +3, +6, +8, +10 and +13. Hemopoietic progenitors were assayed in a complete StemCell medium (MethoCultTM GF H4434 StemCell, Canada) and counted with an inverted microscope after 14-day incubation at 37°C, in 5% CO2. CD34+ cells were evaluated with flow cytometry (EPICS XL, Beckman Coulter); WBC were evaluated with an automatic counter (ADVIA 120 Bayer).
Results: The peak of CFU-GM, CFU-GEMM, BFU-E colonies and of CD34+ cells was invariably reached on day +13 and the highest absolute values were detected after the first cycle of therapy: CFU-GM/ml 3704±738; CFU-GEMM/ml 199±62; BFU-E/ml 8848±3499; CD34+cells/μL 33±3. In the subsequent courses, the number of both hematopoietic colonies and of CD34+ cells progressively lowered; however, the median value of CD34+ cells was still over 20/μL (range 20–35/μL) before the start of the fourth cycle of R-CHOP-14. A significant direct correlation was found between the number of CFU-GM, CFU-GEMM and BFU-E colonies and that of CD34+ cells (p<0.05). The WBC peak was constantly reached on day +6, with a mean value, all cycles considered, of 32±14 x 109/l.
Comments: Hemopoietic progenitor cells kynetic showed that colonies and CD34+ cells started to increase at the WBC nadir. Most important, the level of circulating CD34+ cells at day 13 of the first three cycles of therapy was above 20/μL which we consider permissive for a productive leukaferesis; this observation adds further evidence of the pegfilgrastim progenitor cells mobilizing capacity.
Potential for Mesenchymal Stem Cell Isolation from Human Placenta.
Authors: Atkinson Kerry , Chatterjee Konika , Barlow Sarah , Brooke Gary 
Published: October 2019

Abstract
Aims: To determine if mesenchymal stem cells (MSCs) can be isolated and cultured from human placenta.
Methods: Placentas were obtained at elective caesarean section from normal term pregnancies. Working from the foetal side, pieces of placenta were excised and washed in HBSS to remove excess blood. Tissue was then incubated in collagenase I and DNase I. After enzymatic digestion, a cell strainer was used to obtain a single cell suspension. The resulting cells were washed and centrifuged on a 1.073 g/ml Percoll density gradient and the interface collected. Cells were then cultured in DMEM (low glucose) with FCS. After 24 hours, non-adherent cells were removed and the remaining cells cultured until almost confluent before passage. Media was changed every 3–4 days. After two or more passages, the cells were analysed.
Results: Using this technique, placental plastic-adherent cells could be maintained in culture for long periods in a manner similar to bone marrow-derived MSC. The cells were large and exhibited an elongated, fibroblast-like morphology. In terms of phenotype, the cells were positive for CD29, CD44, CD73, CD90, CD105, CD166 and MHC class I expression, whilst negative for CD34, CD45 and MHC class II expression. The placental cells were shown to be capable of differentiating into cells of the mesenchymal lineage, namely osteocytes, chondrocytes and adipocytes and they could inhibit allogeneic T cell proliferation. However, some phenotypic differences, at both protein and mRNA level were noted between bone marrow and placental derived MSC, in particular only placental MSC showed expression of integrin VLA-4 and the chemokine receptor CXCR4.
Conclusions: The placental-derived cells exhibited characteristic MSC morphology and mesenchymal differentiation. Placental derived MSC therefore represent an alternative and more easily obtainable and abundant source of MSC than bone marrow.
Depletion of the Leukemic Fusion Protein MLL-AF4 with Short Interfering RNAs (siRNAs) Affects Post-Translational Modification of Aldolase A.
Authors: Greil Johann , Gessner Andreas , Thomas Maria , Heidenreich Olaf 
Published: October 2019

Abstract
The chromosomal translocation t(4;11) marks a therapy-resistant infant leukemia with very poor prognosis. It results in the expression of two fusion-proteins, MLL-AF4 and AF4-MLL. We addressed the role of MLL-AF4 in t(4;11) positive SEM cells by siRNA-mediated suppression. Depletion of MLL-AF4 results in induction of apoptosis, inhibition of proliferation, decrease in colony formation and diminished leukemic engraftment in vivo. Currently, we are analyzing global changes in protein expression. For that, we compare the proteome of MLL-AF4 depleted SEM cells with those of control cells. The analysis is performed by 2D-gelelectrophoresis followed by mass spectrometry identification and immunoblot validation of differentially expressed spots. One of these spots was identified as Aldolase A. Comparison of MLL-AF4 depleted SEM cells with control cells showed neither change in mRNA levels nor in absolute protein levels of Aldolase A. Two-dimensional western blotting, however, revealed differences in the protein pattern, suggesting changes in Aldolase A modifications upon MLL-AF4 depletion. These analyses will provide us with a better insight into the effects of siRNA-mediated MLL-AF4 knockdown on the proteome, and may enable us to identify new targets for molecular therapeutic approaches.
Oral Quinolone Switch after 8 Days of Aminoside Is an Efficient and Safe Antibiotherapeutic Strategy for Febrile Neutropenia after Hematopoetic Stem Cell Transplantation.
Authors: Prebet Thomas , Bilger Karin , Gomez Fréderic , Sebban Catherine , Soumelis Valérie , Furhman Catherine , Michallet Mauricette , Biron Pierre 
Published: October 2019

Abstract
Management of febrile neutropenia is one of the important points during the management of autologous or allogeneic hematopoietic stem cell transplantation (HSCT). In this study, we prospectively evaluated the safety and effectiveness of an empiric antibiotherapeutic scheme that associated ticarcillin-clavulanic acid (TIM) and isepamycin (ISE) for 7 days followed by a switch at day 8 to TIM and ofloxacin (OFX), additional therapy (glycopeptide or antifungal therapy) was allowed according to clinical features or documented infection. All the steps of the strategy were evaluated. Ninety six patients (73 autologous HSCT and 23 allogeneic HSCT) were enrolled. Fifty three percents of the patients presented a Fever of Unknown Origin. Bacteriologically proven infections were documented in 32 patients mainly on blood cultures (66%) with an high frequency of gram positive bacterias (71%: 38% of coagulase negative staphylococci, 16% of streptococci, 6% of S. aureus). Median time to neutrophil recovery was 14 days and 24 days respectively for autologous and allogeneic HSCT. We observed an overall effectiveness of the strategy in 78% of the cases. First step strategy was successful in 64 patients (65%) but only 26 patients kept the TIM/ISE bi therapy alone (Glycopeptide and antifungal therapy added in 29 and 7 patients). Quinolone switch was performed in 57 patients (59%) and was effective in 35 patients (61%). The success rate of TIM/OFX after success of TIM/ISE was 95%. Forty five percents of the patient could keep an oral form of OFX. Glycopeptide and antifungal therapy were necessary in 58% and 16% of cases with an effectiveness of 79% and 57% respectively. Failures were mainly observed after front-line treatment (TIM/ISE: 34 Failures) with addition of other kind of antibiotics in 95% of the cases. In 11 patients (32%) the additional antibiotic was netromidazole for clinical symptoms conclusive with anaerobic bacteria. A significantly better effectiveness was found in short duration aplasia (<15days, p=0.008) and in autologous HSCT (p=0.0041). Tolerance was good with only 6 grade III toxicities, no severe nephrotoxicity (8 grade I events, 7 in allogeneic setting) and no infectious death was observed. These results showed
(i) that the choice of the first-line beta lactamin molecule should be discussed
(ii) that oral quinolone switch is safe and effective and
(iii) furthermore pointed out the importance of different antibiotic strategies in autologous (and allogeneic HSCT using Reduced Intensity conditioning) in comparison to standard myeloablative allogeneic HSCT.
Long-Term Outcome after LACE (Lomustine, Ara-C, Cyclophosphamide, Etoposide) Conditioned Autologous Stem Cell Transplantation for Relapsed or Refractory Hodgkin’s Lymphoma: A Single Centre Experience.
Authors: Perz Jolanta B. , Giles Chrissy M. , MacDonald Donald , Apperley Jane F. , Kanfer Edward J. 
Published: October 2019

Abstract
Introduction: The majority of patients with Hodgkin’s lymphoma are cured with initial therapy. However, in patients with primary refractory or relapsed disease, high-dose therapy followed by autologous stem cell transplantation has been shown to be the best option. We analysed patients (pts) who underwent autologous stem cell transplantation (ASCT) following LACE (Lomustine 200 mg/m2, Ara-C 4 g/m2, Cyclophosphamide 4.8 g/m2, Etoposide 1 g/m2) conditioning for relapsed or refractory Hodgkin’s lymphoma at the Hammersmith Hospital, London, between 1991 and 2004.
Patients and methods: 67 pts (46 m, 21 f) initially diagnosed with Hodgkin’s lymphoma (stage I; n=2, stage II; n=29, stage III; n=22 and stage IV; n=14) received first-line chemotherapy with ABVD or COP/ABVD (n=20), BEMOP-CA (n=29), COPP or similar (n=14) or mantle radiotherapy alone (n=4). High dose chemotherapy (HDC) with LACE and ASCT was undertaken in 45 of these pts in 1st relapse, 15 pts in 2nd or subsequent relapse and 7 pts with refractory disease. Median age at the time of HDC was 32 y (17 – 70 y). Prior to ASCT further chemotherapy achieved a complete or partial remission in 41 pts (chemosensitive), but 26 pts had no significant response (chemoresistant). Stem cells were mobilised with Etoposide (1.8 g/m2) and G-CSF in 56 pts, and bone marrow harvest was performed in the other 11 pts.
Results: Two pts suffered a treatment-related mortality (TRM) within the first 100 days (3%). Two pts (3%) developed secondary malignancy (acute myeloid leukaemia). With a median follow-up of 43.3 months (range 0.5 – 145.5 months) the cumulative probabilities of overall survival (OS) and progression free survival (PFS) at both 5 and 10 years was 70% and 62% respectively. Pts who had chemosensitive disease at the time of ASCT had a better OS (p=0.008) and PFS (p=0.08) when compared with pts who had chemoresistant disease. Median PFS has not yet been reached for chemosensitive pts but was 23.4 months for chemoresistant pts. Median OS has not yet been reached for either group.
Conclusions: The outcome for patients with relapsed or refractory Hodgkin’s lymphoma following high dose chemotherapy and ASCT has been sufficiently encouraging to suggest that ASCT should be considered early in chemosensitive patients. However, new therapeutic strategies are needed to improve the clinical outcome of patients with chemoresistant disease.
Evaluation of Costs of Healthcare in HIV Patients with Anemia.
Authors: Dickson Michael , Mody Samir H. , Zilberbeg Marya 
Published: October 2019

Abstract
Background: Although the prevalence of mild to moderate anemia in HIV+ patients (pts) is approximately 22% in the HAART era, the incremental economic burden of anemia is not well understood. This study provides an estimate of the incremental cost of care for anemia in HIV+ pts.
Methods: A longitudinal, retrospective, cohort design was employed to identify subjects in a commercial database of medical and pharmacy claims who were ≥18 years, HIV+, and enrolled in 1 healthcare plan continuously for 18 months from 1996 to 2004. Pts with anemia (A+) were identified using ICD-9 diagnosis codes or receipt of transfusion(s) in the absence of major GI bleeding, trauma or surgery. A control period of 6 months immediately prior to the 12-month study period served to evaluate comorbidity burden and disease severity. To isolate health care costs, including in- and out-patient visits and pharmacy costs, specific to anemia, multivariate regression analyses were conducted to control for demographics, comorbidities, and disease burden.
Results: Of the 2,195 HIV+ subjects identified, 364 (17%) were A+. While there was no significant gender effect, each 1-year increase in age was associated with a 2.1% rise in average monthly cost. A+ cohort was associated with a 118.5% higher average cost compared to A−. The unadjusted average monthly cost for A− subjects in the post-index period was $466 compared with $1,200 for the A+ cohort. In a regression model, anemia maintained an independent and significant association with increased costs (p < 0.0001).
Conclusion: The presence of anemia is associated with a substantial increase in costs among HIV+ patients, independent of demographic differences, disease severity and comorbidity burden. Prospective studies are needed to evaluate the effect of anemia correction on healthcare costs in this population.
Diving Suit: Sterile, Ambulatory, Personnal Device for Protective and Preventive Isolation of Nosocomial Invasive Fungal Infections (IFI) in Neutropenic Patients Hospitalised in Laminar Air Flow Room Who Need a Disruption of Isolation.
Authors: Thiebaut Anne , Perraud Michel , Lyonnet Denis , Ozil Samuel 
Published: October 2019

Abstract
BACKGROUND : Patients with long neutropenia present high risk to develop invasive pulmonary aspergillosis (API) of poor prognosis. Pulmonary computed tomographic Scan (CT scan) allows earlier diagnosis of API and improve management in these patients (D. Caillot, JCO, 1997). However, CT scan need an isolation breaking which is potentially dangerous. We propose a diving suit to maintain the preventive isolation.
MATERIAL AND METHODS : The diving suit is sterile, personnal, ambulatory and transparent to permit monitoring, visual and conversational contact. It is supplied with air with a self-contained station of ventilation (12 hours). The Air contamination is controlled with 2 HEPA filters. Fithteen patients treated for hematologic malignancies like acute leukaemia have tested it after giving inform consent.
RESULTS : The diving suit has been validated for air contamination, physiological (CO2), CT scan feasibility and patients acceptation. All patients (5 male, 10 females) presented a severe neutropenia (PMN < 0.5 G/l during more than 10 days) at time of CT scan. Three patients have had already pulmonary CT scan before using diving suit and 2 claimed to be claustrophobic. No patient describe dyspnea, either pain nor discomfort. All patients feelt reassured and agreed for a new CT scan with this clothing. Two patients have had another CT scan with diving suit for suspicion of pulmonary aspergillosis. Diving suit was very easy to manipulate and did not disrupt monitoring or treatments administration. Diving suit was also compatible with Doppler and Radio Magnetic Nuclear.
CONCLUSION : Pulmonary CT scan needs very often to be performed in neutropenic patients to assess API diagnosis. An ambulatory, personnal protective clothing allows no disruption of isolation for immunocompromized patients during a CT scan. It can also be proposed for medical staff protection when treating patients with SARS or other highly contagious agents.
A Novel Splicing Factor RBM-9 Regulates Protein 4.1R Exon 16 Splicing.
Authors: Yang Guang , Huang Shu-Ching , Benz Edward J. 
Published: October 2019

Abstract
Protein 4.1R (4.1R), a vital component of the red cell membrane cytoskeleton, stabilizes the spectrin-actin lattice and attaches it to embedded membrane proteins. A regulated splicing event, the inclusion of exon 16 that encodes for peptides critical for spectrin/actin binding, occurs during late erythroid differentiation. We showed earlier that an intricate combination of enhancer and silencer elements direct exon 16 splicing. Regulated expression of splicing factors, SF2/ASF and hnRNP A/B, has also been implicated in mediating exon 16 splicing. In this study, we attempted to characterize the mechanism involved in exon 16 splicing through UGCAUG, an intronic splicing enhancer present in three copies in the intron downstream of exon 16. We first used a wild-type minigene construct consisting of exons 13, 16, 17 and their respective flanking introns that mimics endogenous exon 16 splicing during the induced differentiation of mouse erythroleukemia cells (MELC). Mutational analysis showed a dose-dependent effect of UGCAUG on exon 16 splicing: the presence of all three copies had the most effect. These results were recapitulated with an internal chimeric exon in a test neutral reporter system “DUP4-1”, suggesting that the enhancing effect could be attributed directly to UGCAUG. Furthermore, we identified a novel splicing factor, RBM-9, from MELC that enhanced the internal exon splicing in an UGCAUG-dependent manner in both the exon 16 minigene and DUP4-1 reporter systems. Our characterization of RBM-9 revealed that diverse isoforms of RBM-9 are generated by the utilization of alternative translation initiation sites and tissue-specific alternative splicing; different isoforms from various tissues exhibited differential exon 16 splicing enhancing activities. MELC-RBM-9 enhanced exon 16 splicing the most among all RBM-9 isoforms tested. Inhibition of RBM-9 expression by RBM-9-shRNA reversed its enhancing activity on exon 16 inclusion in MELC. RBM-9-shRNA also reduced exon 16 splicing in a dose-dependent manner in HeLa cells. Furthermore, purified RBM-9 specifically binds to the UGCAUG sequence in a gel-mobility shift assay. Finally, expression of RBM-9 is upregulated and correlates with exon 16 inclusion during MELC differentiation. These results suggest that a novel splicing factor, RBM-9, enhances erythroid differentiation stage-specific exon 16 splicing by interacting with the splicing enhancer UGCAUG.
Variables Affecting Kinetics of Minimal Residual Disease Clearance in Children with Lymphoblastic Leukaemia; Results of the United Kingdom Medical Research Council (UK MRC) Protocols ALL97, ALL97/99 and ALL2003.
Authors: Vora9 Ajay J. , Richards S. , Hancock J. , Mitchell C. , Eden O. B. , Kinsey S. , Hann I. , Lilleyman J. S. , Goulden N. 
Published: October 2019

Abstract
We studied the influence of patient, leukaemia and treatment characteristics on the kinetics of Minimal Residual Disease (MRD) clearance in children with lymphoblastic leukaemia treated using an intensive risk stratified approach. UK MRC protocol ALL97 (1997–1999), and its amended version ALL 97/99 (1999–2002), compared the efficacy and toxicity of dexamethasone (DEX) with prednisolone (PRED), and 6-thioguanine (TG) with 6-Mercaptopurine (MP) in a randomised fashion. The trial produced a 5 year event-free survival (EFS) of 80%, with better systemic and Central Nervous System outcomes in DEX compared with PRED recipients but no difference between TG and MP recipients. Several changes to the risk stratification and treatment regimens during the period of the trial provided an opportunity to determine their impact on MRD clearance. We compared this with clearance in those treated on the successor trial ALL 2003 (more intensive induction containing DEX and Pegylated Asparaginase). The variables investigated for their potential influence on MRD status at the end of induction (EOI) were: NCI Risk; Asparaginase intensity (Erwinia Asparaginase [ERW] in ALL 97 and early part of ALL97/99 vs native or Pegylated E. Coli Asparaginase [E. Coli] in later part of ALL 97/99 and ALL2003); DEX vs PRED; and marrow response at day 8/15 of induction (Slow Early Response [SER] >25% blasts vs Rapid Early Response [RER] ⩽ 25% blasts). MRD was assessed using either a semi-quantitative sequence-specific PCR (ALL97) or Real-Time Quantitative PCR (ALL99 and ALL 2003) of antigen receptor gene re-arrangements at EOI. MRD status was defined as NEG if no MRD was detected by two markers sensitive to 10−4; POS if > 10−4, and Positive Outside Quantitative Range (POQR) if positive < 10−4. Results were available from retrospective testing in 66 ALL97 and 76 ALL97/99 patients, and 204 ALL2003 patients monitored prospectively. There was no significant difference in the proportions of patients MRD NEG, POS or POQR in steroid or NCI sub-groups. Significantly more ERW Asparaginase recipients were MRD POS compared with E.Coli (p< 0.0005). Although SER was predictive of slow MRD clearance, 80/235 (34%) RERs were MRD POS and 9/27(33%) SERs were MRD NEG. Relapse risk at 4 years is 8% in NEG v 28% in POS group in ALL97, 0% in NEG/POQR, versus 15% in POS group in ALL97/99 (p=.001) 2 of the ALL2003 patients have relapsed; one was POS and the other POQR. In the context of intensive risk stratified treatment of childhood ALL, type of Asparaginase influenced rapidity of MRD clearance, whilst NCI risk and type of steroid had no significant influence. Patients with detectable MRD < 10−4 at EOI have the same low risk of relapse as those who have undetectable MRD.