bluuebunny/crossref_metadata_2025_split huggingface dataset:
Risk Factors of Clostridium Difficile Infection in Hematopoietic Stem Cell Transplant Recipients: A Systemic Review and Meta-Analysis
Authors: Tariq Raseen , Furqan Fateeha , Jamshed Saad , Khanna Sahil 
Published: October 2019

Abstract
Introduction:
C. difficile infection (CDI) is a common nosocomial infection. Immune suppression is thought to be a major risk factor for CDI. Hematopoietic stem cell transplant (HSCT) recipients represent a major subgroup of immunologically vulnerable patients. It is unclear if these patients have novel risk factors for CDI development. We, therefore, performed a systematic review and meta-analysis to evaluate the predictors of CDI in HSCT recipients.
Methods:
A systematic search of Medline, Embase, and Web of Science was performed from January 2000 up to June 2018. All studies that assessed risk factors associated with CDI development in HSCT recipients were eligible for inclusion. Data on clinical characteristics and risk factors associated with CDI development were collected. Study quality was assessed using the Newcastle-Ottawa scale. Meta-analyses were performed using random effects models and pooled odds ratios with 95% confidence interval (CI) for risk factors reported in ≥ 2 studies were calculated.
Results:
Overall, 17 studies, including 6328 HSCT patients were included. Of those 874 patients developed CDI. The rate of CDI development in these patients was 13.81% with a follow up ranging from 1- 36 months. A total of 34 different risk factors were studied, of which 20 were identified in ≥ 2 studies. Our analysis showed that cephalosporin use (Odds ratio [OR] 2.21, 95% confidence interval [CI] 1.26-3.87), cord blood transplant (OR 1.36, 95% CI 1.01-1.83), graft versus host disease (GVHD) (OR 1.63, 95% CI 1.07-2.48) & prior hospitalization within 90 days of HSCT (OR 1.85, 95% CI 1.21-2.83) were associated with statistically significant increased risk of CDI in HSCT patients (Figure 1). On the other hand, many characteristics of HSCT patients including age, diabetes, lung disease, fluoroquinolones, proton pump inhibitors, rituximab, mucositis, myeloablative therapy, melphalan use before BMT, total body irradiation, growth factor use during admission, neutropenia, autologous vs allogenic transplant and use of matched related donor were not associated with increased risk of CDI.
Conclusion:
HSCT recipients are at an increased risk of CDI compared to general population. In addition to the common risk factors like cephalosporin use and prior hospitalization, these patients have novel characteristics including presence of GVHD and cord blood transplant that puts them at a higher risk of CDI. HSCT patients with these risk factors may warrant a closer surveillance for early detection and treatment of CDI.
Table 1. Table 1.

Disclosures
No relevant conflicts of interest to declare.
Research of miR-30b in Cisplatin Resistance of Human NK/T Cell Lymphoma Lines SNK-6 and YTS Cells By Targeting CCL22
Authors: Liang Rong , Wang Jian hong , Liu Fang , Duan Xiao hui , Hao Xia Cai , Zhang Liang , Wang Michael , Liu Xiang -xiang , Guo Yan Hua , Wang Zhe , Tang Hailong , Yang Ljie 
Published: October 2019

Abstract
Objective: To investigate the role and mechanism of miR-30b underlying cisplatin resistance of human NK/T cell lymphoma lines SNK-6 and YTS cells. Methods: Normal NK cells and SNK-6 and YTS cells were cultured, the levels of miR-30b and CCL22 were detected by real-time PCR assay, CCL22 expression was detected by western blot analysis. Transfected with miR-30b mimics and inhibitor in SNK-6 and YTS cells respectively, and then measured the effect of cisplatin resistance in SNK-6 and YTS cells by MTT assay, the activity of caspase-3 was detected by caspase-3 kit assay, the cells apoptosis ratio was detected using flow cytometry analysis. The target relationship of miR-30b and CCL22 were determined by dual-luciferase reporter gene assay. The expressions of CCL22. Furthermore, the effect of CCL22 on cisplatin resistance and caspase-3 were also evaluated. Results: The levels of miR-30b were significantly decreased in both SNK-6 and YTS cells, but with the increase in CCL22 expression. MiR-30b mimics decreased the cells activity, down-regulated the cisplatin resistance, increased cells apoptosis ratio and caspase-3 activity. The effects of miR-30b inhibitor were contrary to the mimics. Up-regulated miR-30b significantly decreased the luciferase activity in CCL22 3'-UTR transfected NK cells, but not in Mut-CCL22 3'UTR group, suggesting that CCL22 could act as a direct target of miR-30b. The expressions of CCL22 pathway proteins were down-regulated after SNK-6 cells transfected with miR-30b mimics, while the effects were restored by overexpression of CCL22. Moreover, CCL22 overexpression also increased the cells activity and decreased caspase-3 activity when SNK-6 cells were transfected with miR-30b mimics. Conclusion: MiR-30b inhibited cisplatin resistance of human NKTCL in SNK-6 and YTS cells by targeting CCL22.

Disclosures
Wang: Novartis: Research Funding; Kite Pharma: Research Funding; MoreHealth: Consultancy; AstraZeneca: Consultancy, Research Funding; Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Dava Oncology: Honoraria; Juno: Research Funding; Janssen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Acerta Pharma: Honoraria, Research Funding; Pharmacyclics: Honoraria, Research Funding.
A Clinico-Genotypic Prognostic Index for De Novo Composite Diffuse Large B-Cell Lymphoma Arising from Follicular Lymphoma in the Rituximab Era
Authors: Lim Ryan Mao Heng , Chan Natalie Pei Xin , Khoo Lay Poh , Cheng Chee Leong , Tan Leonard , Poon Eileen Yi Ling , Somasundaram Nagavalli , Farid Mohamad , Tang Tiffany , Tao Miriam , Lim Soon Thye , Chan Jason Yongsheng 
Published: October 2019

Abstract
Aim
Composite follicular lymphoma with diffuse large B-cell lymphoma (FL/DLBCL) is an uncommon hematological neoplasm. The aim of this study was to examine clinico-pathological features of patients with FL/DLBCL and investigate relevant predictors of survival outcome.
Methodology
Patients with histologically-proven FL/DLBCL at diagnosis (n=106) and who were subsequently treated with Rituximab-based chemotherapy from 2002-2017 at the National Cancer Centre Singapore were retrospectively analyzed. Survival analyses were performed using the Kaplan-Meier method and multivariate Cox proportional models.
Results
The cohort consisted of 72 men and 34 women with a median age of 59 years (range, 24-82). The cell of origin by Han's algorithm was GCB in 37.7%, ABC in 58.5% and unknown in 3.8%. Eight patients (7.5%) were double-hit for c-MYC, BCL2 and/or BCL6 rearrangements. In a multivariate model inclusive of known clinico-pathological parameters at diagnosis, presence of B symptoms (p = 0.0122), stage 3 or 4 lymphoma (p = 0.0166) and double-hit genotype (p = 0.0045) were independently prognostic for worse overall survival (OS). These factors, excluding B symptoms, were similarly prognostic for progression-free survival (PFS). Including first-line treatment data in the multivariate model, lack of complete response (p < 0.0001) and use of chemotherapy regimens other than R-CHOP (p = 0.0360) alongside presence of B symptoms (p = 0.0022), were the only remaining independent prognostic variables for worse OS. Classification by cell of origin was not prognostic. A Clinico-Genotypic Index derived from point-wise addition of all five adverse parameters (score of 0, 1, 2, 3-4) revealed four prognostic risk groups accounting for 25%, 30%, 25% and 20% of the cohort, with a predicted 5-year OS of 100%, 95%, 57% and 19% respectively (p < 0.0001).
Conclusion
A Clinico-Genotypic Index derived from clinical and molecular factors can classify patients with composite FL/DLBCL into distinct prognostic groups. Han's algorithm has no prognostic value in this disease entity.
Figure. Figure.

Disclosures
No relevant conflicts of interest to declare.
Role of Rhoa G17V in Cell Migration and Transformation in Angioimmunoblastic T-Cell Lymphoma
Authors: Palomero Teresa , Cortes Jose R. , Cooke Anisha R. , Belver Laura , Bhagat Govind , Ferrando Adolfo A. 
Published: October 2019

Abstract
Angioimmunoblastic T-cell lymphoma (AITL) is an aggressive form of peripheral T-cell lymphoma derived from the malignant transformation of follicular helper T-cells (TFH), frequently associated with autoimmune disease and characterized by resistance to chemotherapy and poor prognosis. A recurrent RHOA G17V mutation in the RHOA small GTPase gene is characteristically present in 70% of AITL cases, frequently in association with loss of function mutations in the Tet2 epigenetic regulator. Expression of Rhoa G17V in CD4+ T cells in a conditional Rhoaco-G17V/+ knockin mice induces TFH cell specification and increased proliferation. A pathogenic role for Rhoa G17V in cooperation with loss of Tet2 is demonstrated by the development of AITL in a CD4+ specific Rhoa G17V Tet2 knockout mice. However, the specific effector mechanisms driving TFH specification and T-cell transformation downstream of Rhoa G17V remain largely unknown. Here we demonstrate a novel role for Rhoa G17V as a modulator of signaling cascades initiated by sphingosine-1-phosphate (S1P), an important lipid mediator of lymphocyte trafficking. Specifically we show that expression of Rhoa G17V results in impaired S1P receptor internalization with the consequent up-regulation of S1P-dependent signaling pathways. In addition, and of potential therapeutic relevance, targeted inhibition of S1P signaling in Tet2-/-RHOA G17V mouse AITL cells induces apoptosis and reduces tumor load in vivo. In all, these results uncover a previously unrecognized role for S1P signaling downstream of Rhoa G17V in AITL tumor cell migration and survival, and support the role of S1P receptors as potential therapeutic target for the treatment of this disease.

Disclosures
No relevant conflicts of interest to declare.
Impact of Early Rasburicase on Incidence and Outcomes of Clinical Tumor Lysis Syndrome in Lymphoma
Authors: Personett Heather A , Barreto Erin F , McCullough Kristen , Dierkhising Ross , Leung Nelson , Habermann Thomas M. 
Published: October 2019

Abstract
Introduction: Clinical tumor lysis syndrome (TLS), which manifests most often as acute kidney injury (AKI) is a common and devastating complication of rapidly proliferating hematologic malignancies. Epidemiologic studies of attributable risk factors for AKI in this setting are small, focus on only aggressive lymphomas rather than the more prevalent intermediate risk disease subtypes, and predate contemporary risk stratification, diagnostic criteria, and supportive care. Additionally, early administration of rasburicase to enhance uric acid (UA) elimination has been adopted without robust evidence in support of its impact on clinical outcomes, specifically, prevention of AKI.
Methods: This was a retrospective cohort study of adult lymphoma patients at intermediate or high risk for TLS treated at Mayo Clinic between 2009 and 2017. Patients were excluded if they had AKI at hospital admission, received pre-admission rasburicase, or were on dialysis. Consensus definitions were used to stratify TLS risk and stage AKI. The incidence of new AKI in the setting of TLS was described along with predictors of its development, including early rasburicase use.
Results: Of the 461 patients with a new lymphoma diagnosis during the study timeframe at intermediate or high risk of TLS, 78 were excluded, primarily due to prevalent AKI at hospital admission. The 383 included patients were predominantly at intermediate risk for TLS (73%) and had a diagnosis of Diffuse Large B-cell Lymphoma (64%). Incidence of new onset AKI during hospitalization was 6% and 91% of cases were stage 1. All new onset AKI occurred within the first 5 days of hospital admission. Independent predictors of new AKI included age > 60 years, history of chronic kidney disease or cardiovascular disease, and UA >8 mg/dL at any time during hospital admission. Rasburicase was given to 48 patients, 6 (13%) of whom still went on to develop AKI. Rapid UA reduction with rasburicase did not impact the risk of developing AKI (HR 2.3; p = 0.11). Uric acid level at the time of administration did not modify the effect of rasburicase on prevention of AKI (p = 0.36 for the interaction term).
Conclusion: In conclusion, for lymphoma patients at intermediate or high risk for TLS, if not present at admission, AKI only infrequently developed during the course of a patient's hospitalization. Predictors of AKI included advanced age, comorbid conditions, and elevated UA levels. Early rasburicase administration, regardless of UA level, did not alter AKI risk.

Disclosures
No relevant conflicts of interest to declare.
Outcomes of T-Cell Depleted Haploidentical Peripheral Blood Stem Cell Transplantation for Adult Acute Leukemia: A Meta-Analysis
Authors: Durer Seren , Durer Ceren , Katsanis Emmanuel , Comba Isin Yagmur , Jamil Faiza , Aslam Shehroz , Shah Zunairah , Malik Mustafa Nadeem , Selene Insija Ilyas , Fraz Muhammad Asad , Jose Jemin Aby , Qureshi Anum , Yasir Muhammad , Amin Saher Nasir , Anwer Faiz 
Published: October 2019

Abstract
Background: Ex-vivo T-cell-depleted graft is used to prevent acute and chronic GVHD for haploidentical hematopoietic SCT (HSCT). We conducted a systematic review and meta-analysis to evaluate the outcomes of T-cell-depleted grafts for peripheral blood haploidentical stem cell transplantation in patients with acute lymphoblastic leukemia (ALL) and acute myeloid leukemia (AML).
Method: A comprehensive literature search on PubMed, Embase, Cochrane and Web of Science was conducted up to July 25, 2018. Two independent reviewers screened the literature and extracted data. The methodological quality was assessed using modified Newcastle-Ottawa Scale. CMA software v.3 was used for the analysis. Heterogeneity among studies was assessed using the I2 test. Random-effect model was applied.
Results: The search strategy identified over 550 articles; three studies (n = 404 patients; 1 prospective; 1 multi-center) were selected for this meta-analysis. The sample size of the studies varied between 34 and 266 patients. The median follow-up ranged from 6 to 47 months. Two studies (Aversa, F. et al. 2005)(n=104 patients); (Ciceri, F. et al. 2008)(n=266 patients) used CD34+ selected cells and other study used TCR-αβ depleted PBSC graft (Kaynar, L. et al. 2016) (n=34). All studies used myeloablative (MA) conditioning. In vivo T-cell-depletion by ATG was used in two studies. Two studies using mega-dose of CD34+ did not use GVHD prophylaxis and other study with αβ T-cell depleted graft used mycophenolate mofetil (MMF). Engraftment rates ranged from 91% to 98%. Pooled rates (95%CI) of grade II-IV, III-IV aGVHD and chronic GVHD were 9% (4-20; I2=82%), 4.8% (1.7-13.1; I2=78%) and 10.7% (6.3-17.6; I2=64%), respectively. The pooled estimates (95%CI) showed a 2-year disease-free survival (DFS) rate of 30.8% (24.2-38.3; I2=54%), 2-year relapse incidence of 21.5% (17.4-26.2; I2=85%). The results are shown in figure 1.
Conclusion: T-cell-depleted peripheral blood stem cell graft for haploidentical transplantation in acute leukemia may be an alternative treatment option. Larger prospective studies are needed to evaluate the outcomes of different manipulation techniques.

Disclosures
No relevant conflicts of interest to declare.
Intraepithelial Lymphocytosis of the Resection Margin in the Monomorphic Epitheliotropic Intestinal T-Cell Lymphoma
Authors: Heo Mi Hwa , Jung Hye Ra , Do Young Rok , Ha Jung-Sook , Kim Hyera , Kim Do-Hoon , Kim Jin Young 
Published: October 2019

Abstract
Background: Monomorphic epitheliotropic intestinal T-cell lymphoma (MEITL) is a disease involving the intestine and is often diagnosed in surgically resected specimens. The disease prognosis of MEITL is fatal because of rapid recurrence and leakage after excision. Recently, in microscopic finding of MEITL, intraepithelial lymphocytosis in mucosa that were grossly intact has been reported. In this study, we evaluated the intraepithelial lymphocytosis of the resection margin to determine the reason for the early recurrence or leakage in MEITL.
Materials and Methods: We reviewed the medical records of all patients who were diagnosed with small intestine lymphoma from January 1995 to June 2018 at our medical center. We analyzed a tissue array from 8 patients diagnosed with MEITL. The expression of CD3, CD5, and CD8 were analyzed by immunohistochemistry.
Results: A total of 8 cases of small intestine lymphoma were collected in this period. There were three men (37.5%) and five women (mean age 55 years). Two patients died without initiation of chemotherapy. Six patients received chemotherapy after resection of MEITL (4 patients received CHOP regimens, 2 patients received ProMACE-CyBOM regimens), but five patients died within 6 months (mean survival time 4.1 months, range 0.3-12.1 months). Only one patient survived for 5 years. On gross examination, the distance to the resection margin was 7.58 cm (3.8-14.0 cm) on average. Microscopic examination revealed intraepithelial lymphocytosis at least of one of the resected margins in all case. Immunohistochemical staining for CD3, CD5, and CD8 was performed on the resection margins. As a result, severe intraepithelial lymphocytosis accompanied by aberrant loss of CD5 was observed in 6 cases (75%).
Conclusion: In the MEITL, an intraepithelial lymphocytosis accompanied by aberrant CD5 loss is frequently observed in the resection margin, even if the resection margin is grossly intact, and there is no clear microscopic involvement of the lymphoma especially on low power. This fact is thought to be related to the early recurrence or leakage of MEITL at the surgical site.

Disclosures
No relevant conflicts of interest to declare.
Efficacy of Low-Dose Decitabine in the Early Relapse of AML/MDS after Allogeneic Hematopoietic Stem Cell Transplantation
Authors: Guo-Fa Xu , Ting Chen , Huanfeng Liu , Shijia Lin , Gao Lei , Zhang Cheng , Liu Yao , Zhang Xi , Zeng Defu , Peiyan Kong 
Published: October 2019

Abstract
Objectives: Retrospective analysis of the efficacy and adverse effects of low-dose Decitabine(DAC) in patients with early relapse of acute myeloid leukemia/myelodysplastic syndrome(AML/MDS) after allogeneic hematopoietic stem cell transplantation (allo-HSCT).
Methods:Fifteen patients with AML/MDS, which were early recurrence after transplantation, received low-dose DAC treatment. The evidence of early recurrence included engraftment index(FISH detection of sex chromosomes, or STR) <95%, MRD (+), fusion gene positive or positive bone marrow blast cells (between 5%~10%). DAC was given (5-10) mg·m2-1·d-1×5 days, every 6∼8 weeks, a maximum for 8 cycles. The treatment outcome, adverse reaction and graft-versus-host disease (GVHD) were analyzed. Fifteen patients included 13 with AML,1 with MDS-RAEB-2, and 1 with chronic myelogenous leukemia (CMML).
Results: The total complete remission (CR) rate was 66.67%(10/15), the Objective response rate (ORR) was 86.67% (13/15); 5 cases of relapse in the effective patients, in which 3 cases with PR was relapse eventually, and 2 CR patients has extramedullary recurrence and bone marrow relapse, respectively, the recurrence rate was 38.46%(5/13). Grade 3 and 4 hepatic dysfunction was 26.67%, Grade 3 and 4 hematological toxicities was 60%.
Conclusion:low-dose of DAC was effective and safe in controlling early recurrence, reducing GVHD symptoms, reducing recurrence rate and prolonging patient survival time.

Disclosures
No relevant conflicts of interest to declare.
Metabolomic Profile in Patients with Autoimmune Hemolytic Anemia
Authors: Rabelo Iara Baldim , Chiba Akemi Kuroda , Moritz Elyse , Barros Melca Oliveira , Silva Ismael Dale Cotrim Guerreiro , Bordin Jose Orlando , Chauffaille Maria de Lourdes , Yamamoto Mihoko , Arrais Celso 
Published: October 2019

Abstract
Introduction: autoimmune hemolytic anemia (AIHA) is a rare clinical condition with hemolysis mediated by immunoglobulin binding on the surface of erythrocytes with or without complement activation. Metaboloma is the sum of the genetic configuration of an organism to the external factors. The metabolic profile involved in AIHA has not yet been described and may be the key to new findings about the mechanism of autoimmune hemolysis.
Objectives: To describe a profile of AIHA related metabolites, increased hemolysis and risk of relapse.
Patients and Method: we analyzed the plasma from 31 patients with primary AIHA compared to plasma from 150 healthy subjects using mass spectrometry (Kit AbsoluteIDQ p180, Biocrates, Austria). The statistical analysis was performed by the software available at http://www.metaboanalyst.ca/.
Results: of the 95 metabolites found in patients with AIHA, four acylcarnitines, two phosphatidylcholines (PC), asymmetric dimethylarginine (ADMA) and three sphingomyelins were increased with great statistical significance. There was an increase in PCs and polyamines (spermine and spermidine) in the AIHA group in hemolytic activity. The relationship between PCs "PC ae 34: 3 / PC ae 40: 2" seen only in the 12-months relapsed group was predictor of relapse with specificity of 81% and sensitivity of 100%.
Discussion: Increased sphingomyelin in AIHA patients may perpetuate deficient regulatory T lymphocytes in the recognition of erythrocytes as self. Accumulation of ADMA can cause downregulation of NF-kβ from macrophages by inducing one of the already known autoimmune mechanisms. Excess PCs in patients with AIHA and increased hemolysis may perpetuate effector T lymphocytes with increased susceptibility to autoimmunity and increase the production of antibodies against erythrocyte antigens. The increase of polyamines in the higher hemolysis group may induce autoimmunogenicity of DNA and interfere with the differentiation of macrophages. Finally, the presence of PC to 34: 3 / PC to 40: 2 as a predictor of relapse may help to identify cases that require follow-up more frequently or second-line therapies earlier.
Conclusion: Our data demonstrate a distinct profile of metabolites in AIHA patients, as well as in individuals with higher hemolytic activity. There was a relationship of phosphatidylcholines strongly predictive of AIHA relapse.

Disclosures
No relevant conflicts of interest to declare.
Analysis of Differential Circrnas Expression Profile Identifies Novel Biomarkers for Acute Monocytic Leukemia
Authors: Wu Balu , Pan Yunbao , Jin Yanxia , Zhao Mingfeng , Zhou Fuling 
Published: October 2019

Abstract
Malignant acute monocytic leukemia (AML-M5) is a subtype of AML that is associated with hyperleukocytosis, extramedullary disease, and abnormal coagulation. Accumulating evidence has revealed that aberrant circular RNAs (circRNAs) expression play important roles in carcinogenesis and tumor progression. However, the roles of circRNAs in AML-M5 remains unclear. In this study, next-generation deep sequencing was performed to identify the circRNAs profiles in bone marrow from 6 AML-M5 patients and 3 healthy donors. A total of 78 circRNAs were identified to be associated with AML-M5 carcinogenesis. Two circRNAs (hsa_circ_0100160 and hsa_circ_0012152) were selected for further validation by real-time quantitative reverse transcription-polymerase chain reaction (qRT-PCR) in 30 AML patients and healthy control. Both of them were significantly upregulated in AML patients (P < 0.05). The AUC value of ROC curve was 0.934 with sensitivity of 90.9% and specificity of 81.8%, suggesting that hsa_circ_0012152 could distinguish the AML-M5 patients from healthy donors. Bioinformatics analysis predicted that hsa_circ_0012152 interact with hsa-miR-4763-3p and its corresponding mRNAs, which will be our further study. In summary, Our study provides an overview of the circRNA profiles in AML-M5, which will facilitate future investigations into the function of hsa_circ_0012152.

Disclosures
No relevant conflicts of interest to declare.