bluuebunny/crossref_metadata_2025_split huggingface dataset:
Fluconazole Prophylaxis Significantly Reduce High Risk Invasive Fungal Infection in Immunocompromised Patients Stratified By a Risk Prediction Model
Authors: Ma Jiexian , Ma Xinyuan , Zuo Xinyu , Shen Shuhong 
Published: December 2024

Abstract:
Background: Patients on immunosuppressive drugs or those who are critically ill are at high risk for invasive fungal infections (IFIs). The assessment of IFI risk and the initiation of prophylaxis in these patients remain unclear.
Methods: A Nomogram model was developed to evaluate humoral and cellular immune indicators in relation to IFI risk. High-risk patients, as identified by the model, were selected for a prospective, randomized study to assess the efficacy and safety of fluconazole prophylaxis. Patients deemed high risk received either fluconazole prophylaxis or a placebo until IFI occurrence or risk downgrade for up to 90 days. We compared the incidence of IFI and mortality during treatment between the two groups.
Results: The Nomogram, created from a training cohort (n=384), included age, IgG level, and CD4+ cells count as predictive indicators of IFI, was validated in a separate cohort (n=281) with an area under the curve of 0.723. A total of 266 patients were recruited for the prospective study, with 158 high-risk patients randomly assigned to receive either fluconazole (n=78) or a placebo (n=80). Proven or probable IFI was reported in 8 patients in the fluconazole group and 39 patients in the placebo group (p=0.00). High risk IFI could be reduced to the low risk level with fluconazole prophylaxis. There was no significant difference in survival between the fluconazole and placebo groups (P=0.34). Adverse events potentially related to treatment were reported by 4 patients (4.9%) in the fluconazole group.
Conclusions: This nomogram model effectively and reliably predicts the risk of IFI in immunocompromised patients. Fluconazole prophylaxis significantly reduces the incidence of IFI, particularly yeast infections, and may help to prevent fungal colonization. (ChiCTR2400079810.)
The Burden of Cardiovascular-Related Mortality in Early-Onset Acute Myeloid Leukemia
Authors: Akpan Inemesit , Oluwadeyi Esther Yemisi , Sanni Abdulsabur , Igbenabor Christiana Aina , Gold-Olufadi Shakirat , Ilerhunmwuwa Nosakhare Paul 
Published: December 2024

Introduction
Acute myeloid leukemia (AML) is an aggressive hematological malignancy that is rare in individuals under 50 years old (early-onset AML) even though it constitutes approximately one-third of leukemia cases in adults. Cardiovascular-related death (CVD) remains a prevalent cause of mortality in the older population with AML. The epidemiology of CVD in individuals with early-onset AML is not well understood. This study examines the trends of CVD in early-onset AML compared to older individuals with the disease.
Method
Cases of AML diagnosed in individuals aged 15 years and older between 2000 and 2020 were extracted from the Surveillance, Epidemiology, and End Results (SEER) Research Plus Data 17 Registries. Descriptive statistics of sex and race were compared between early-onset AML (15-49 years) and adult-onset AML (diagnosed at age 50 years and older). Standardized mortality ratio (SMR), age-standardized incidence-based mortality rates (ASMR), and annual percentage change (APC) were used to compare mortality trends.
Results
A total of 70,824 patients with AML were diagnosed between 2000 and 2020. Early-onset AML accounted for 13,096 cases (18.5%). Among these, 1,966 patients (3.5%) died from cardiovascular diseases, with 129 deaths occurring in those with early-onset AML (6.6% vs. 93.4% in adult-onset AML). Among those with early-onset AML who died from CVD, the racial distribution was as follows: White individuals accounted for 72 deaths (55.8% vs. 75.2% in adult-onset AML), Black individuals - 25 deaths (19.4% vs. 8.1% in adult-onset AML), Hispanic individuals - 21 deaths (16.3% vs. 8.98% in adult-onset AML), Asian individuals - 10 deaths (7.75% vs. 7.13% in adult-onset AML), and Native Americans accounted for 1 death (0.775% vs. 0.44% in adult-onset AML).
The SMR for early-onset AML was higher compared to adult-onset AML (3.00 [2.47-3.63] vs. 2.71 [2.56-2.87]).
From 2000 to 2020, the overall ASMR in early-onset AML increased more significantly compared to adult-onset AML (APC, 4.60% [0.99 to 9.41] vs. 2.40% [1.42 to 3.54]). The increase in ASMR among early-onset AML was more pronounced in males compared to females (APC, 2.71% [1.18 to 4.26] vs. 2.07% [0.66 to 3.49]), and higher in non-Hispanic Blacks compared to non-Hispanic Whites (APC, 3.76% [1.28 to 6.30] vs. 2.85% [1.70 to 4.01]). There was no significant change among other racial groups.
Conclusion
Although AML is uncommon in individuals under 50 years old, the rate of CVD mortality is rising faster in younger AML patients compared to older individuals with the disease, who are traditionally more predisposed to cardiovascular conditions. High surveillance for the onset of cardiovascular disease should be maintained in young people with AML to address this rising issue.
Single-Cell Multi-Omics Analysis Reveals Autologous Stem Cell Chemo-Mobilization with Etoposide +Cytarabine Plus G-CSF in Multiple Myeloma
Authors: Zhu Zhijuan , Zhu Jiali , Li Xiaofan , Zhu Ming , Dai Jinxian , Huang Jialiang , Li Nainong 
Published: December 2024

Introductions: We previously reported that autologous stem cell chem-mobilization with Etoposide +Cytarabine (EA) plus G-CSF was highly effective and safe for patients with multiple myeloma (MM). However, the state of mobilized CD34+ peripheral blood stem cells (PBSCs) and molecular mechanisms underlying its high-efficiency mobilization remain unknown.
Methods: Here, we employed matched single-cell transcriptome and chromatin accessibility sequencing to profile CD34+PBSCs of patients with MM(n=12) mobilized with EA+ G-CSF (n = 9), plerixafor + G-CSF (n = 3), along with healthy allo-donors (n = 5) mobilized with G-CSF. In addition, we integrated single-cell transcriptomic data with public CXCR4 inhibitors or G-CSF mobilized PBSC transcriptomic data to obtain a comprehensive map of seven mobilization strategies.
Results: The integrated map showed the alterations in the transcriptional landscape of mobilized PBSCs among mobilization strategies, revealing that EA plus G-CSF mobilized a higher fraction of hematopoietic stem cells (HSCs) and promoted a bias towards lymphoid differentiation compared to CXCR4 inhibitor and G-CSF. Meanwhile, CD34+ hematopoietic stem progenitor cells (HSPCs) mobilized by EA+G-CSF exhibited a higher proliferation capacity. We also explored the cellular and molecular basis of the high mobilization efficiency of CD34+ HSPCs by EA plus G-CSF in MM. Interestingly, we found that EA plus G-CSF mobilized CD34+ HSPCs exhibited significantly higher potential for cytarabine resistance, along with increased activity in the G-CSF signaling pathway and inflammatory response. The positive correlation between these three pathways suggested that chemotherapeutic agents may induce the endogenous G-CSF signaling pathway. Additionally, the JAK-STAT signaling pathway, which acts as a cross-talk mechanism between the G-CSF signaling pathway and the inflammatory response, also showed enhanced activity. Finally, we proposed the hypothesis of EA+G-CSF mobilization, suggesting that chemotherapeutic drug-induced changes in gene expression can either enhance (via the G-CSF pathway, RAC2, and ITGA4) or complement (via EGR1) the G-CSF mobilization process.
Conclusion: EA plus G-CSF mobilized a significantly higher fraction of CD34+ HSPCs favoring the lymphoid as well as proliferative capacity. EA-induced transcriptional changes might promote or complement G-CSF mobilization process to enhance PBSC mobilization efficacy in MM.
Cognitive and Psychological Recovery from the Immune Effector Cell Associated Neurotoxicity Syndrome Following Chimeric Antigen Receptor T-Cell (CAR-T) Therapy
Authors: Kuznetsova Valeriya , Oza Harsh , Rosenfeld Hannah , Sales Carmela , van der Linde Sam , Roos Izanne , Roberts Stefanie , D'Aprano Fiore , Loi Samantha M. , Dowling Mark R , Dickinson Michael J. , Kalincik Tomas , Harrison Simon J , Malpas Charles B. , Anderson Mary Ann 
Published: December 2024

Introduction:
Chimeric antigen receptor T-cell therapy has become standard of care treatment for several types of haematological malignancies. Immune effector cell associated neurotoxicity syndrome (ICANS) is a serious side-effect, with diverse neurocognitive symptom presentation. ICANS is typically considered an acute condition, however, the recovery trajectory has not been well-defined. The study aimed to investigate cognitive and psychological recovery from ICANS in adult haematology patients over 1 year after CAR-T therapy.
Methods:
Twenty patients completed a comprehensive cognitive assessment and a self-report measure of psychopathology and cognitive concerns before receiving commercial CAR-T for treatment of lymphoma (95%) or leukaemia (5%). The assessment was repeated 1-month, 6-months, and 1-year post-CAR-T. Seven (35%) patients experienced ICANS acutely. Bayesian repeated measures analysis of covariance examined the effect of interaction between ICANS group and time of the assessment on change in cognition and psychopathology. Models were adjusted for age, education, and sex.
Results:
ICANS patients declined in executive function post-CAR-T, while non-ICANS patients remained stable (BF10=524.0). The ICANS group had lower mean scores at the 1-month review (BF10=9.5, η2=0.4). No group difference was detected at 6-months or 1-year. Three (43%) ICANS patients had a clinically evident executive function impairment at 1-month, returning to baseline at 6-months and remaining normal at 1-year. In the non-ICANS group, all patients had normal executive function across all assessments. There was no evidence for an effect of ICANS group over time in any other cognitive domain. Analyses of individual psychometric measures, revealed evidence for an effect of ICANS group over time for tests of strategic lexical retrieval (BF10=8.1), verbal memory (BF10=67.3), and auditory attention span (BF10=9.2). The lowest mean scores were observed at 1-month in the ICANS group. There was no change in patient-reported cognitive concerns or symptoms of psychopathology over time, irrespective of ICANS group.
Conclusions:
ICANS patients had a reduction in executive function, verbal memory, and the auditory attention span 1-month post-CAR-T. There was no effect of ICANS on cognitive change at 6-months or 1-year, suggesting complete resolution of cognitive manifestation of ICANS. Stable self-reported symptoms of psychopathology indicate good psychological tolerance of neurological toxicity. Our findings provide a positive outlook for long-term cognitive recovery following CAR-T therapy. Cognitive monitoring, however, is indicated for ICANS patients for up to 6-months post-infusion.
Incidence of ITP before and after COVID-19: A Nationwide Inpatient Sample Study
Authors: Obeidat Khaldun , Turk Ekrem , Olafimihan Ayobami , Zia Maryam 
Published: December 2024

Background/Purpose:
Since the onset of the coronavirus disease-2019 (COVID-19) pandemic in December 2019, the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has been postulated as a potential trigger for numerous autoimmune disorders. Specifically, immune thrombocytopenia (ITP) has been reported following SARS-CoV-2 infection and vaccination. In this study, our objective was to compare the incidence of ITP in the pre- and post-COVID eras.
Methods:
The Healthcare Cost and Utilization Project National Inpatient Sample (HCUP-NIS) database were queried to identify admissions for ITP in 2018 and 2020, using ICD-10 codes for a primary diagnosis of ITP. The primary outcomes analyzed included mortality, length of stay (LOS), and total hospital charges (THC). Secondary outcomes encompassed acute kidney injury (AKI), intensive care unit (ICU) admission, and the need for blood transfusion. Statistical analyses were performed using t-tests, univariate and multivariate logistic regression analysis in Stata.
Results:
A total of 22,840 ITP patients were admitted in our study group, comprising 12,160 in 2018 and 10,680 in 2020 (53.2% and 46.7%, respectively). No significant differences were observed in patient sex (43% males and 56.8% females, P = 0.74), mean age (56.4 in 2018 and 55.8 in 2020), or race, except for a higher incidence among Native Americans in 2020 (0.2% vs. 0.6%, P = 0.004). There were no significant differences in medium household income, insurance, bed size, location/teaching status, and the region of the hospital.
In primary outcomes, total deaths in the main group numbered 264 (1.16%), with non-significantly higher mortality in 2020 (1.36% vs. 0.99%, OR 1.37, P = 0.24). Females had significantly lower odds of mortality (OR 0.46, P = 0.007, CI 0.26-0.80). Regarding secondary outcomes, there was no significant difference in the length of hospital stay. The incidence of AKI was non-significantly higher in 2020 (9.6% vs. 7.9%, P = 0.054) with a high need for ICU admission (1.1% vs. 0.7%, OR = 1.6, P = 0.14) and no significant need for blood transfusion.
Conclusion:
Despite multiple reported cases of ITP triggered by the virus and vaccines during the COVID-19 pandemic, our study did not reveal a significant increase in ITP cases in 2020 compared to 2018. Further studies are warranted to confirm the causality between COVID-19 and ITP, including analyses of incidence in years after 2020, considering the initiation of vaccinations at the end of that year.
Feasibility of Longitudinal Circulating Tumor DNA (ctDNA) Assessment in Patients with Peripheral and Cutaneous T-Cell Lymphomas
Authors: William Basem M. , Efebera Yvonne A. 
Published: December 2024

T-cell lymphomas are a heterogeneous group of mature T-cell neoplasms. Outcomes of majority of peripheral T-cell lymphoma (PTCL) and advanced stage cutaneous T-cell lymphomas (CTCL) are poor. The value of ctDNA as a prognostic marker of chemosensitivity and disease-free survival has been validated in aggressive B-cell lymphomas but remain unclear in PTCL/CTCL and can be a useful tool for disease risk stratification and monitoring of treatment.
We performed a retrospective review of PTCL and CTCL patients treated at our center between April 2022 and June 2024; plasma samples were analyzed using a tumor-informed ctDNA assay as part of clinical care during diagnosis, treatment, and surveillance. Whole exome sequencing was performed on tumor tissue and matched normal blood samples to identify up to 16 patient- and tumor-specific, somatic single nucleotide variants using a clinically validated, tumor-informed mPCR NGS assay (SignateraTM). These variants were monitored in patients' subsequent plasma samples.
A total of 75 plasma samples were analyzed from 10 patients with PTCL/CTCL; lymphoblastic lymphoma (n=2), enteropathy associated T-cell lymphoma (n=2), ALK+ anaplastic large T-cell lymphoma (n=1), PTCL-NOS (n=1), angioimmunoblastic T-cell lymphoma (n=1), hepatosplenic T-cell lymphoma (n=1), and CTCL (n=2). After a median duration of follow-up of 6 (2-24) months, 7 (70%) patients remained alive. In patients with PTCL (n-8), persistence of ctDNA was strongly associated with disease progression and death (relative risk=6; 95% CI=1-35; p=0.04). In 5 patients with PTCL, ctDNA negativity showed 100% concordance with negative PET-CT results.
Our results, albeit with small numbers, suggest that ctDNA is strongly associated with clinical outcomes in patients with PTCL; ctDNA may serve as a useful tool to monitor and prognosticate patients with PTCL when validated in a large cohort of patients.
Predictive Value of Free Light Chain Burden in Patients Newly Diagnosed with AL Amyloidosis Treated with Cybord or Daracybord
Authors: Saunders Brendan , Theodorakakou Foteini , Evans Benjamin , Boullt Samuel , Fotiou Despina , Dimopoulos Meletios , Kastritis Efstathios , Bianchi Giada 
Published: December 2024

Background: A difference between involved and non-involved free light chain (dFLC) exceeding 180 mg/L is part of the 2012 Mayo staging system. However, none of the 758 patients evaluated to develop this staging system received a bortezomib-containing regimen. We hypothesized that depth of response and overall survival in AL amyloidosis patients are independent of free light chain burden in the era of CyBorD and DaraCyBorD.
Methods: This is a retrospective, multicentre study including 223 newly diagnosed AL amyloidosis patients seen at our institutions between 2012 and 2024. In patient cohorts receiving CyBorD or DaraCyBorD therapy, we investigated 1) the relationship between baseline iFLC and dFLC at completion of cycle 1 (day 28) and 3, 6, 9 and 12 months ; 2) the overall survival of patients with baseline low (&lt;180mg/L), medium (180-400 mg/L) and high (&gt;400 mg/L) dFLC ; and 3) the validity of the 2004 and 2012 Mayo staging guidelines. The study was IRB approved.
Results: We identified 132 patients treated with CyBorD and 91 treated with DaraCyBorD. Forty patients in the CyBorD cohort and 3 in the DaraCyBorD cohort did not respond to therapy. Lack of response was independent of baseline iFLC. Following completion of cycle 1, we identified no correlation (r2=0.02) between baseline iFLC and dFLC response in the DaraCyBorD group and a moderate correlation (r2=0.53) in the CyBorD group. Similar trends were noted at 3, 6, 9 and 12 months from therapy start. Kaplan-Meier survival curves based on baseline iFLC were overlapping with a median follow up of 12.5 months. Mayo 2012 staging did not impact OS.
Conclusion: Overall survival, depth and rapidity of response appear to be independent from baseline iFLC in patients treated with bortezomib containing regimens. Our data questions the prognostic impact of free light chain burden in the era of CyBorD and DaraCyBorD.
Selinexor Synergizes with Decitabine in Mantle Cell Lymphoma through MAPK Signaling Pathway
Authors: Chen Yingtong , Yang Ping , Zhang Weilong , Wang Jing , Gao Shuang , Yang Yuan , Liu Shuozi , Li Chunyuan , Jing Hongmei 
Published: December 2024

Background: Mantle cell lymphoma (MCL) is an incurable malignance, and MCL patients usually have high recurrence rate and poor prognosis. Additional therapeutic targets need to be discovered to improve the clinical outcome of MCL patients. This study aimed to explore the combined therapeutic effect of selinexor and decitabine in MCL.
Method s : MCL cells (Jeko, Mino, Rec1, and Z138) were treated with selinexor, decitabine, or in combination, and then cell proliferation, cell apoptosis, cell cycle were determined by CCK-8 and flow cytometry. RNA-seq was performed to elucidate the potential mechanism of the synergistic effect of selinexor and decitabine.
Result s : Monotherapy with either selinexor or decitabine could inhibit cell proliferation, promote cell apoptosis, and induce cell cycle arrest in MCL cells. The combined treatment of selinexor and decitabine achieved greater inhibitory effect of cell proliferation and significantly increased cell apoptosis rate compared to their single treatment. RNA-seq confirmed that the synergistic effect of selinexor and decitabine could activate the MAPK signaling pathway.
Conclusion s : The synergistic anti-tumor therapy of selinexor and decitabine is expected to be a powerful strategy for MCL treatment, which provides a new perspective for MCL patients.
Safety and Efficacy of Luspatercept for the Treatment of Refractory Anemia in Patients with Myelofibrosis
Authors: Wen Ziyu , Zhou Xuan , Lin Bingyu , Liu Xiaoli , Wang Qiang , Xu Na 
Published: December 2024

BackgroundMyelofbrosis (MF) is a chronic and progressive myeloproliferative neoplasm accompanied by symptoms including, splenomegaly, fatigue, night sweats, fever, pruritis and anemia, and the treatment of myelofbrosis-associated anemia remains suboptimal, with no improved therapies.
Method We retrospectively collected MF with refractory anemia with luspatercept.
Result32 patients with MF treated with luspatercept were enrolled. Median age was 59 years (range, 48-83 years), and 62.5% were males. 28 (87.5%) of patients with hemoglobin below 60g/L. All patients previously were treated with a PTD regimen (prednisone, danazol, thalidomide). 20 (62.5%) were classified as intermediate-1 risk, and 12 (37.5%) as intermediate-2 risk based on Dynamic International Prognostic Scoring System (DIPSS). The median follow-up was 7.5 (3-16) months. 28 (87.5%) patients received luspatercept 50mg every three weeks, of these, 2 patients increased the dose due to poor response; and another 4 patients received luspatercept 25mg every three weeks. Erythroid response occurred in 18 patients (56.3%) at week 12, another 6 patients (18.8%) at week 24, and 25 (78.1%) at the end of follow-up. Patients had a significantly higher hemoglobin level at 12 weeks, 24 weeks, and at the end of follow-up, than at baseline (P=0.002, P=0.005, and P=0.01, respectively). Treatment-related adverse events occurred in 5 (15.6%) patients, with no serious adverse events. 3 (9.4%) patients treatment failure, and 4 (12.5%) patients relapse at week 21 and 24. No patient progressed to acute myeloid leukemia. No patients died by the end of follow-up.
Conclusion In patients with myelofibrosis, luspatercept improved anemia with a low relapse rate and good tolerance.
Keyword Luspatercept; refractory anemia; myelofbrosis
Evaluating the Effectiveness and Tolerability of Chimeric Antigen Receptor (CAR) T Cells Therapy in Patient with Systemic Lupus Erythematosus: A Systematic Review
Authors: Devi Amirta , Kumar Arun , Sah Ranjit , Shah Sangam , Paudel Amita , Sah Sanjit , Shah Ghulam , Solangi Ahda , Mirza Usama , Solangi Zeeshan 
Published: December 2024

Background
Systemic Lupus Erythematosus (SLE) is a complex auto-immune disorder characterized by immune dysregulation leading to formation of autoantibodies and multiple organ dysfunction. Monoclonal antibodies targeting CD19 and CD20 on the B lymphocytes have demonstrated benefit, however, relapse is common. Chimeric antigen receptor (CAR) T cells targeting CD19 on B lymphocytes have shown to eliminate B lymphocytes both from the circulation and lymphoid organs leading to durable responses and have been approved for treatment for different forms of cancer including acute lymphoblastic leukemia, multiple myeloma and non-Hodgkin lymphoma. More recently, clinical trials are evaluating the effectiveness of CAR T-cell therapy in patients with SLE refractory to current lupus therapeutics.
Method
We did electronic search of the literature using Central Line (PubMed), EMBASE, and google scholar databases until July 2024. We searched for case-series, observational studies and randomized clinical trials to investigate the effectiveness of CAR-T therapy in SLE. PRISMA guideline was followed to conduct the study. Studies were filtered based on title and abstract, followed by the full text. Data extraction was done in Microsoft Excel.
Results
We evaluated a total of 3 studies which included a total number of 25 patients who received CART- Therapy for refractory SLE. All the included studies were case series. SLEDAI-2K score ranged from 1.5 to 0 and DORIS remission was achieved in all patients. C3 level was normalized, and dsDNA level were below cutoff for all the patients reflecting good treatment response. Most of the patients tolerated the treatment well and only mild cytokine release syndrome was reported. Immune-Effector Cell Associated Neurotoxicity Syndrome (IECANS) and infections rate were negligible.
Conclusion
Anti-CD19 CAR-T therapy has shown promising result in a small population to prevent relapses in patients with SLE by eliminating CD19 positive B lymphocytes and is relatively well tolerated with mild adverse effects. Future large studies including controlled clinical trials are expected to further evaluate safety and tolerability of CAR-T therapy in autoimmune conditions including SLE.