bluuebunny/crossref_metadata_2025_split huggingface dataset:
Prognostic Risk Factors for Patients with Candida Tropicalis Fungemia Infections and Hematological Malignancies
Authors: Zhao Haisu , Fu Shan , Zhu Yuanyuan , Huang He , Zheng Weiyan 
Published: December 2023

Background: Candidemia is one of the most common nosocomial infections, contributing significantly to morbidity and mortality. The most commonly reported non-albicans Candida species is Candida tropicalis, which is currently spreading around the world. Clinical studies have suggested a particular susceptibility to C. tropicalis infection among patients with hematological malignancies, particularly leukemia.
Methods: We retrospectively analyzed 106 patients with both hematological malignancies and invasive candidiasis. Patient age, sex, medical history (basic disease and medication history), length of hospital stay, laboratory test results, and other clinical features were recorded. Drug sensitivity information was available for 90 of the 106 patients. Then we used logistic regression and some machine learning models to identify the prognostic factors related to patient death.
Findings: Of 106 patients, 35 (33.1%) died within one month after being diagnosed. Most patients (105/106) were diagnosed with C. tropicalis fungemia in the myelosuppressive phase, and were mainly concentrated in the first (35/106, 33%) and second (18/106, 17%) chemotherapy courses. Drug sensitivity information was available for 90 of the 106 patients. Resistance to voriconazole and fluconazole were observed in 52 and 51 patients, respectively. In addition, 73.3% of the patients were resistant to itraconazole. Multivariate logistic regression showed that the use of amphotericin B(OR=0.295 ,95% CI 0.100-0.877), sex(OR=0.263 ,95% CI 0.082-0.847), duration of fever before diagnosis(OR=4.053 ,95% CI 1.281-12.825), combined bacterial infection(OR=5.309 ,95% CI 1.701-16.573), decannulation(OR=0.0922 ,95% CI 0.013-0.636), and serum creatinine levels(OR=1.020 ,95% CI 1.001-1.038) were determined to be predictors of death(p &lt; 0.05). The random forest model, with an AUC value of 0.793, which showed the best performance of five machine learning models, suggested that serum creatinine level was the most important prognostic factor for candidemia.
Conclusion: In this study, we finded that the main predictors of death were found to be the use of amphotericin B, sex, duration of fever before diagnosis, combined bacterial infection, decannulation, and serum creatinine levels.
Immune Checkpoint Expression Patterns on T Cell Subsets in Light-Chain Amyloidosis: VISTA, PD-1, and Tigit As Potential Therapeutic Targets
Authors: Wang Jinghua , Zhao Yujie , Liao Yujie , Li Yangqiu , Zhong Liye , Chen Shaohua 
Published: December 2023

Abstract
Background: Systemic immunoglobulin light chain amyloidosis (AL amyloidosis) is a rare plasma cell dyscrasia with a poor prognosis. T-cell exhaustion can lead to impaired T cell-mediated antitumor immunity, but there is limited information available regarding the T-cell immunodeficiency status in AL amyloidosis. This study aims to investigate the T-cell immune checkpoint expression patterns in AL amyloidosis and its relationship with clinicobiological characteristics.
Methods: Using multi-color fluorescent flow cytometry, we examined the expression levels of V-domain immunoglobulin suppressor of T cell activation (VISTA), programmed death 1 (PD-1), T cell immunoglobulin and mucin-domain-containing-3 (Tim-3), T cell immunoreceptor with Ig and ITIM domains (TIGIT) on CD3+, CD4+, CD8+ T-cell, and regulatory T cell (Treg) in peripheral blood (PB) and bone marrow (BM) from 19 patients with newly diagnosed AL amyloidosis. We used 36 PB and BM samples from patients with newly diagnosed multiple myeloma (MM) and 19 PB and 10 BM samples from healthy individuals (HIs) as controls.
Results: Our results showed that PB from patients with AL amyloidosis had significantly higher percentages of VISTA+ and PD-1+ subsets within CD3+, CD4+, CD8+ T cells and Tregs when compared to HIs. No statistical differences for frequency of VISTA+, PD-1+, Tim-3+ and TIGIT+ T-cell in BM were observed between the two groups. The percentages of double-positive VISTA+ PD-1+, VISTA+ Tim-3+, VISTA+ TIGIT+, PD-1+ Tim-3+ and PD-1+ TIGIT+ T cells in PB from the patients with AL amyloidosis were also considerably higher than those in the HIs. Moreover, we discovered that the patients with renal involvement had greater percentages of PD-1+ or TIGIT+ subsets within CD3+, CD4+ T cells and Tregs than the individuals without renal involvement. Additionally, PD-1+CD3+%, PD-1+CD4+%, and PD-1+Treg% were found to be positively correlated with 24-hour proteinuria levels. Furthermore, we observed that the AL amyloidosis patients had significantly higher counts of PD-1+ Treg in PB than the MM patients, while the MM patients had significantly higher counts of TIGIT+ subsets within CD3+, CD4+ and CD8+ T cells than the AL amyloidosis patients.
Conclusions: Our findings suggest that there are elevated proportions of VISTA+ and PD-1+ T cells in PB of AL amyloidosis patients, which are indicators of an immunosuppressive milieu. The rise in PD-1+ or TIGIT+ T cells was associated with renal damage. Notably, MM and AL amyloidosis have very distinct immunosuppressive patterns based on immune checkpoint alteration. Overall, VISTA, PD-1, and TIGIT may be considered as potential targets for reversing T cell exhaustion and enhancing T cell activity in AL amyloidosis.
Cerebrospinal Fluid IL-6 Plus IL-10 As Effective Diagnostic Biomarkers for Secondary Central Nervous System Lymphoma
Authors: Gu Jiayan , Jin Jie 
Published: December 2023

Background : Secondary central nervous system lymphoma (SCNSL) characterized by the involvement of the CNS at initial diagnosis of systemic lymphoma or in the setting of relapse. Accurate diagnosis and therapeutic response of SCNSL are particular challenges, which need to be improved. We aimed to evaluate the diagnostic and the post-therapeutic prognostic value of cerebrospinal fluid (CSF) cytokine in patients with SCNSL.
Methods: In this retrospective study involving 234 NHL patients and 53 other CNS patients, the NHL patients was divided into two sub-groups based on with and without CNS involvement: SCNSL (n=57) and non-SCNSL (n=177). The CSF cytokine profiles (interleukin (IL)-2, -4, -6, and -10, tumor necrosis factor-α, interferon-γ, and IL-17A) of these patients were measured by cytometric bead assay and evaluated the ability of CSF cytokine levels as diagnostic, therapeutic and prognostic biomarkers for SCNSL.
Results: CSF IL-6 and IL-10 levels were significantly higher in SCNSL patients than non-SCNSL and other CNS patients. CSF levels of IL-6 and IL-10 were significantly higher in patients with an stage at Ⅲ and Ⅳ, CSF WBC counts&gt;5/µL, CSF protein ≥0.45g/L.Using a CSF IL-6 cut-off value of 10.13 pg/ml yielded a diagnostic sensitivity and specificity was 62.34% and 87.57%, respectively (AUC, 0.7798; 95% CI, 0.7083 to 0.8514); For a CSF IL-10 cutoff value of 7.82, the sensitivity was 76.23%, and the specificity was 98.31% (AUC, 0.8164; 95% CI, 0.7466 to 0.8862). Combined CSF IL-6 and IL-10 significantly improved the diagnostic effect of SCNSL (AUC, 0.8959; 95% CI, 0.8371 to 0.9547). The levels of IL-6 and IL-10 in cerebrospinal fluid of SCNSL patients who responded to intrathecal chemotherapy were significantly decreased during follow-up, while the levels of these two cytokines showed fluctuating changes in patients with progressive SCNSL. Moreover, poor Progression free survival (PFS) for patients with SCNSL was associated with the increased CSF IL-10 level at diagnosis with CNS involvement (P=0.035), but not with the increased CSF IL-6 level.
Conclusion: Our study confirmed CSF level of IL-6 and IL-10 were potentially effective diagnostic biomarkers for SCNSL, and poor progression free survival (PFS) for patients with SCNSL was associated with the increased CSF IL-10 level.
Efficacy of Allogeneic Hematopoietic Stem Cell Transplantation in Young and High-Risk Multiple Myeloma Patients
Authors: Pan Pan , Jiang Erlie , Pang Aiming 
Published: December 2023

Objective: With the new therapeutic agents developed over last decades, the median survival of patients with multiple myeloma has approached 10 years. However, 15-20% of patients who are classified as High-risk multiple myeloma (HRMM) patients still have a median survival of less than 3 years, which leaves room for improvements. Simultaneously, transplantation related mortality (TRM) has been decreasing since progress of supportive care during these years. Thus, this study aims to evaluate the efficacy of allogeneic hematopoietic stem cell transplantation (allo-HSCT) in young high-risk multiple myeloma (HRMM) patients and to conduct statistical analysis of various prognostic factors in the new era.
Method: This retrospective study analyzed clinical data from 14 young multiple myeloma patients with high-risk cytogenetic abnormalities or high-risk disease biological factors who underwent allo-HSCT at the Hematopoietic Stem Cell Transplantation Center of the Institute of Hematology & Blood Diseases Hospital between November 2016 and November 2022.
Results: There were 7 males and 7 females involved in this study, with a median age of 39.5 (31- 50) years at the time of transplantation. The median number of treatment lines before transplantation was 2 (1-6). Before transplantation, 42.9% (6/14) of the patients did not achieve complete remission (CR), with 35.7% (5/14) of the patients performing MRD (+). After transplantation, all patients could be evaluated for treatment response, in which the overall response rate was 100% (14/14). All 14 patients successfully underwent transplantation, with median engraftment times for neutrophils and platelets of 11 (10-14) days and 13 (9-103) days, respectively. Acute graft-versus-host disease (GVHD) of grades II-IV occurred in 5 patients (35.7%), and 2 patients (14.3%) developed moderate to severe chronic GVHD. The median follow-up time after transplantation was 18.93 (4.1-72.53) months, with the 2-year TRM of 7.1% (95%CI 0-19.7%) and the expected 2-year overall survival (OS) rate of 92.9% (95% CI 80.3-100%). Meanwhile, the expected 1-year and 2-year progression-free survival rates were 85.7% (95% CI 69.2-100%) and 45.7% (95% CI 20.9-99.9%), respectively, and the presence of chronic GVHD might influence the outcome positively.
Conclusion: Allogeneic hematopoietic stem cell transplantation is an effective treatment to improve the prognosis of young and high-risk multiple myeloma patients.
Prevalence of MGUS in Rural Indian Population: Results of Simple (IMAGe-002A) Study
Authors: Raphael Celine , Yanamandra Uday , Bobdey Saurabh , Sharma Vaibhav , Bhatti V K , Muthukrishnan J , Malhotra Pankaj , Nair Velu 
Published: December 2023

Introduction: The incidence of monoclonal gammopathies is rising across the globe. Although the prevalence of monoclonal gammopathy of undetermined significance (MGUS) has been evaluated in two hospital-based studies in India, no data exists on its prevalence in community-based settings amongst the rural Indian population.
Objectives: To determine the prevalence of MGUS in a rural Indian population in a community-based setting.
Methods: A cross-sectional study was conducted in an agrarian village in India covering a perimeter of 24.76Km and 4588.3 hectares with an 89.2% population coverage for adults more than 45y spending 12096 man-hours as part of SIMPLe ( Screening Intervention for Myeloma and Prevention of Lifestyl e diseases) study under the aegis of Indian Myeloma Academic Group e (IMAGe) registered vide CTRI/2023/03/051220. For the complete study population, demographic details, medical history, and blood samples were collected after a thorough medical examination. Hemogram, biochemistry (Liver and renal function tests), and serum protein electrophoresis (SPEP) were universally performed in all individuals. Serum immunofixation electrophoresis (SIFE) was performed for those with abnormal SPEP graphs (those with M spike and those with abnormal bulges in beta-2 or gamma region suspicious of MGUS). Patients with monoclonal protein on SPEP or SIFE were further assessed for any features of smoldering/ multiple myeloma. The data was analyzed using JMP ver. 16.0.0.
Results: The prevalence of MGUS in the study population was 1.75%. The mean age of individuals with MGUS was 63.4±5.2y with male preponderance (60%). The mean Hb was 12.39±1.8g/dL with none of the patients having any renal dysfunction. None of the patients fit into the criteria for smoldering or multiple myeloma using IMWG criteria. Among those with MGUS, the distribution of Heavy and light chains was IgG - 83.33%, IgA - 16.67% with none having IgM/ IgD paraprotein, Kappa - 50%, and Lambda - 50%. Two individuals only had light chain MGUS.
Conclusion: Our study provides a comprehensive description of the prevalence of MGUS in a rural community setting in India. The background prevalence is much less compared to the Western (both USA ~3% and European~5%) population.
Acute Myeloid Leukemia in Elderly, Unfit Patients: Analysis of Turkish AML Prospective Registry Database, on Behalf of Acute Leukemia Working Group of Turkish Society of Hematology
Authors: Urlu Selin Merih , Cengiz Seval Guldane , Erdogan Yücel Elçin , Mehtap Ozgur , Yenihayat Emel Merve , Polat Merve Gokcen , Malkan Umit Yavuz , Ozbalci Demircan , Yigit Kaya Sureyya , Durusoy Salih Sertac , Akdeniz Aydan , Kirkizlar Onur , Dogan Ali , Pinar Ibrahim Ethem , Kacmaz Murat , Afacan Ozturk Hacer Berna , Atas Unal , Deveci Burak , Korkmaz Akat Gulten , Guven Zeynep Tugba , Sevindik Omur Gokmen , Demirkan Fatih , Alacacioglu Inci , Karakus Volkan 
Published: December 2023

Objective: Low dose Ara-C and hypomethylating agents (HMAs) - decitabine (DEC) and azacitidine (AZA) - have made it possible to treat more elderly patients with acute myeloid leukemia (AML). Both HMAs demonstrated efficacy in monotherapy and in combination with targeted therapies. We analyzed the outcomes of elderly and unfit patients with newly diagnosed AML in our population.
Methods: Analyses of our database revealed 222 eligible AML patients from diagnosed between January 2013 to December 2020. All patients were received low intensity treatments including AZA +/- venetoclax, DEC and low dose Ara-C. The effects of cytogenetic risk group, response rate, treatment type on overall survival (OS) and PFS (progression-free survival) were evaluated. Survival analyses were performed with the Kaplan-Meier method and log-rank test. A p-value of &lt;0.05 was considered statistically significant.
Results: Median age was 73 years (51-89). Eastern Cooperative Oncology Group (ECOG) performance score was &lt;2 and ≥2 for 75 patients (36.8%) and 147 patients (63.2%), respectively. Of the patients 8.2% had favorable, 76.9% intermediate and 15.0% adverse risk according to European Leukemia Network (ELN) risk classification. Extramedullary involvement was present in 4.5%. Low dose treatment regimens included AZA in 119 patients (53.6%), DEC in 38 (17.6%), low dose ARA-C in 26 (11.7%) and AZA + venetoclax in 39 (17.1%). Complete remission was achieved in 61 patients (27.5%), whereas 39 patients (17.6%) had partial remission (PR) and 64 (28.8%) had stable/progressive disease (SD/PD). Overall response rate was 48.1%. CR rate was higher with AZA + venetoclax (44.7%, p=0,005) and other regimens had similar outcomes. Median OS was 10.3 months. No significant difference difference in PFS was observed between the regimens. However, the lowest PFS was observed with low-dose Ara-C (p=0.33). ELN risk groups revealed no significant effect on PFS and OS (p=0.77 and p=0.82, respectively). Infections were the most common cause of death (42.7%).
Conclusions: The prognosis of AML in the elderly remains poor. HMA monotherapy is effective among elderly and unfit patients. However, combination therapies may be more effective and safe. The incorporation of targeted therapies may provide additional benefit in this patient group. However, the accessibility of several novel targeted drugs is still very limited in many countries.
The Important Role of Egfr Change in Patients with Multiple Myeloma
Authors: Liu Xiang , Tang Wenjiao , Niu Ting 
Published: December 2023

Background. Renal impairment is a common complication in multiple myeloma (MM) patients and related to a higher mortality. However, whether the change of estimated glomerular filtration rate (eGFR) is associated with prognosis is not clear currently.
Patients and Methods. A total of 1552 myeloma patients in West China Hospital from July 1, 2008 to September 1, 2022 were retrospectively included in this study, patients with dialysis or complicated with other malignancy were excluded. All patients had at least 3 measurements of creatinine and eGFR between 6 months and 2 years after baseline. The 1-year change in eGFR (slope) was calculated by linear regression, patients were divided into 3 groups by the eGFR slope (sustained group: eGFR slope was -5 ~ 5 ml/min per 1.73 m2 per year over 2 years; increased group: eGFR Slope &gt; 5 ml/min per 1.73 m2 per year over 2 years; decreased group: eGFR Slope &lt; -5 ml/min per 1.73 m2 per year over 2 years ), the Kaplan-Meier survival analysis, multiple Cox regression model and Restricted cubic spline (RCS) analysis were applied to explore the association of eGFR slope with the best efficacy and progression of myeloma patients.
Results. After a median follow-up of 21 months, 977(62.95%) patients had reached VGPR or CR (the best efficacy), 24.1% patients experienced progression, the survival status is currently being followed up. The eGFR decline more than 5 ml/min per 1.73 m2 per year over 2 years (decreased group) was showed to have a higher risk of disease progression (P=0.01, Figure 1a) and to be an independent risk factor for disease progression, both in patients with (eGFR&lt;60 ml/min per 1.73 m2) or without (eGFR&gt;60 ml/min per 1.73 m2) renal failure (Table 1). The RCS analysis showed that the decline of eGFR within 2 years was positively related to the risk of disease progression, while the eGFR rise with a certain range could reduce the risk of progression (0-6.4 ml/min per 1.73 m2 per year) (Figure 1b). Inversely, the eGFR increased group showed a higher possibility of acquiring very good partial remission (VGPR) or complete remission (CR) (Figure 1c, P&lt;0.001), and was a beneficial factor of reaching VGPR or CR for MM patients (HR 1.3, 95%CI 1.05-1.62, P=0.015, Table 1). The RCS analysis showed that eGFR slope was linearly correlated with patients' VGPR or CR rate (Figure 1d). Notably, in patients without renal insufficiency at baseline (eGFR&gt;60 ml/min per 1.73 m2), eGFR improvement did not increase the rate of VGPR or CR (Table 1).
Conclusions. eGFR decreasing &gt;5 ml/min per 1.73 m2 per year over 2 years could increase the risk of disease progression in MM patients with or without renal impairment, while eGFR increasing at a certain range could reduce progression risk. For myeloma patients with renal impairment, eGFR increasing may improve the rate of VGRP or CR in MM patients.
Retinoic Acid and Ascorbate Remodel the Epigenome of Leukemia Cells to Improve Therapeutic Efficacy By Enhancing TET Activity
Authors: Leesang Tiffany , Yap Yoon Sing , Brabson John P , Klimas Abigail , Ahearn Emily L , Barbieri Daniela A , Lam Minh Quang , Lyon Peter D , Figueroa Maria Ken E. , Beckedorff Felipe , Cimmino Luisa 
Published: December 2023

Ten-eleven translocation (TET) enzymes are commonly mutated in leukemia, leading to aberrant DNA methylation and impaired hydroxymethylation. All-trans retinoic acid (ATRA) is a vitamin A derivative and cofactor of retinoic acid receptors (RARs) which, in combination with arsenic trioxide, can curatively treat acute promyelocytic leukemia. ATRA has also been shown to upregulate expression of Tet2 and Tet3 in murine embryonic stem cells, and retinol and ascorbic acid (vitamin C) have been shown to enhance pluripotent stem cell reprogramming through increasing hydroxymethylcytosine and promoting DNA demethylation. Our previous work has demonstrated ascorbate can slow disease progression in vivo and, combined with the PARP inhibitor Olaparib, promote cell cycle dysregulation and induce cellular differentiation in acute myeloid leukemia (AML) models both in vitro and in vivo.
Here, we show ATRA can induce TET2 and/or TET3 expression in AML cells, and, combined with ascorbate, increase genome-wide oxidized methylcytosine in a TET-dependent manner. Combination treatment with ATRA and ascorbate also induces transcriptional reprogramming, leading to upregulation of DNA repair genes and pathways leading to increased expression of myeloid differentiation markers. Additionally, we observe chromatin remodeling associated with an enrichment for ETS motifs including genes and regions regulated by the transcription factor PU.1, an essential modulator of hematopoietic cell fate. We also show enrichment of retinoic acid receptor A (RARA) at the TET2 locus and at several RAR elements in response to ATRA in AML cells. Using very low dose ascorbate and ATRA, we show that the combination treatment can enhance the efficacy of Olaparib and Venetoclax to alter the cell cycle, promote differentiation, and induce apoptosis of AML cells. These data demonstrate the potential for ATRA and ascorbate to increase TET activity and drive myeloid differentiation and death of AML cells that can be exploited as an adjuvant therapy for the treatment leukemia.
Clinically Significant CMV Infection in Allogeneic Stem-Cell Transplant Recipients: A Single Center Experience
Authors: Gulied Amaal , Alasmar Aya , Bakr Mohammad , Shawayli Hawra , Ghasoub Rola , Fadul Afraa Mustafa Sulieman , Gameil Amna , Mudawi Deena SIDEEG , Hamad Anas Ahmad , Gaziev Javid 
Published: December 2023

Introduction:
Cytomegalovirus (CMV) infection is one of the major causes of concern in allogeneic stem cell transplantation (allo-HSCT). Here we report the clinically significant CMV infections among allo-HSCT recipients at the National Center for Cancer Care and Research (NCCCR) in Qatar.
Methods:
A retrospective review of the electronic health records of all malignant hematology patients who underwent allo-HSCT at NCCCR was performed from September 2017 to December 2022.
Results:
Fifty-one malignant hematology patients have been transplanted during the data collection period. Patient characteristics are summarized in Table 1. The median age was 34 years (range 14-53 years). CMV-serostatus was positive in fifty recipients (98%) and all donors. Thirty-two patients (62.7%) have received matched-related grafts. The most frequent indication for HSCT was acute myeloid leukemia, followed by acute lymphoblastic leukemia. Forty-six patients (92%) underwent myeloablative conditioning therapy. Graft-versus-host disease (GvHD) prophylaxis used in the non-haploidentical group was cyclosporine and short-course methotrexate while haploidentical recipients received cyclosporine, mycophenolate mofetil, and post-transplant cyclophosphamide. Letermovir prophylaxis was accessible for use for high-risk patients from February 2022. CMV-PCR was monitored twice per week for all patients until day +100. The clinically significant CMV infection rate was 51%. The cumulative incidence of CMV infection in haploidentical and non-haploidentical groups was 70% and 30%, respectively (figure 1). The median CMV-PCR viral load was 1783.5 IU/mL (range 133- 9600 IU/mL), with the earliest CMV reactivation on day -1 of transplantation. The clinically significant CMV infection incidence was significantly higher in patients who did not receive letermovir prophylaxis. Preemptive antiviral therapy was initiated to prevent CMV disease in all indicated recipients. Foscarnet was the preferred first-line pre-emptive treatment option for patients during cytopenia. No CMV disease or CMV-related mortality occurred in our population.
Conclusion:
This is the first report from Qatar to report CMV infection post-allogeneic stem cell transplantation. Future in-depth analysis of our population and treatment responses is needed.