bluuebunny/crossref_metadata_2025_split huggingface dataset:
A Prospective Phase II Study of Radiotherapy Followed By Tiselizumab Combined with R-CHOP in the Untreated Follicular Lymphoma Patients with Bulky Disease in China
Authors: Li Wei , Zhang Ximei , Gao Fenghua , Yao Yixin , Wang Xianhuo , Zhang Huilai 
Published: December 2023

Background
Follicular lymphoma (FL) is the second most common B cell lymphoma subtype and chemoimmunotherapy treatment is the standard therapy for patients with high tumor burden. Bulky disease was associated with shorter median PFS compared to non-bulky disease in FL patients. Radiation and anti-programmed death-1 (PD-1) monoclonal antibody are both effective in FL and also have a synergistic effect. We assessed the potential benefit of Tiselizumab (a humanized monoclonal antibody targeting PD-1), radiotherapy combined with RCHOP as first-line treatment in FL patients with bulky disease.
Methods
This was a single center, single arm, phase II study. Patients with previously untreated follicular lymphoma were enrolled from the department of lymphoma, Tianjin Medical University Cancer Institute and Hospital. The bulky disease was received radiation (dose:18～24Gy) before RCHOP. Patients began chemoimmunotherapy 1～2 weeks later than radiation. Treatment included Tiselizumab (200 mg iv d1) plus R-CHOP (rituximab 375 mg/m 2 intravenous [IV] day 2, cyclophosphamide 750 mg/m 2 IV day 3, doxorubicin 50 mg/m 2 IV day 3, vincristine 1.4 mg/m 2 [maximum 2.0 mg total] IV day 3, and prednisone 100 mg oral days 3-7, 21～28 days for one cycle ) for six cycles. Rituximab was given every 2 months to patients who were complete metabolic response /partial metabolic response（CMR/PMR）after first-line chemo until 2 years. Response was assessed by PET/CT scan after cycle 4 and cycle 6. The primary endpoint was complete response rate (CRR).
R esults
FromFebruary 2021 to June 2023, 6 patients were enrolled. 4 patients finished all 6 cycles treatment. 1 patient was dead because of COVID-19 who was PMR after 5 cycles treatment. The last one with CMR stopped chemotherapy because of COVID-19 and only received 4 cycles treatment. The median follow-up is 15 months. 5 patients achieved CMR in the mid-term evaluation and were still on remission in June 2023. The CRR was 83.3% and the overall response rate was 100%. The common adverse events were nausea, vomiting, bloating, loss of appetite, constipation, and diarrhea. The most common grade 3/4 adverse events were neutropenia (66.7% ), thrombocytopenia (16.7% ), and leukopenia (66.7% ).
Conclusion
Tiselizumab, radiotherapy combined with RCHOP is effective and tolerable in the untreated FL patients with bulky disease. More patients will be enrolled to estimate the efficacy and safety.
Summary of the Best Evidence for Nutritional Support in Patients with Acute Gastrointestinal Graft-Versus-Host Disease
Authors: Wen Yanling , Yang Jingwen , Cai Zhen , Cheng Tao 
Published: December 2023

[Abstract]
Objective: To retrieve, evaluate and integrate the best evidence summary of nutritional support for patients with acute gastrointestinal graft-versus-host disease after hematopoietic stem cell transplantation at home and abroad. Methods: According to the “6S” model, domestic and foreign computer decision support systems, guideline networks, websites of relevant professional societies or institutions, professional books, and comprehensive databases were systematically searched to screen literatures related to nutritional support for patients with acute gastrointestinal graft-versus-host disease, including guidelines, clinical decision-making, evidence summary, expert consensus, expert opinion, systematic review, and original research. The search time limit was from the establishment of the database to March 2023. Five researchers evaluated the quality of the literature, extracted evidence and integrated it. Results: A total of 12 articles were included, including 1 clinical decision, 4 guidelines, 1 evidence summary, 1 expert consensus, 3 systematic reviews, 1 cohort study, 1 expert opinion,. A total of 14 best evidences were summarized from 4 aspects, including scientific diet and tolerance assessment, nutrient selection, nutritional support method selection, and multidisciplinary cooperation. Conclusions: This study systematically integrates the relevant evidence of nutritional support in patients with acute gastrointestinal graft-versus-host disease, and can provide evidence-based evidence for nutritional support in patients with acute gastrointestinal graft-versus-host disease. When applying evidence, it is recommended that clinical nurses comprehensively consider the actual clinical situation and the wishes of patients, and carefully select evidence.
Keywords acute gastrointestinal graft-versus-host disease，nutritional support，malnutrition，evidence-based nursing
Risk Factors and Prognostic Scoring Model for 28-Day Mortality in Hematologic Patients with Stenotrophomonas M altophilia Bacteremia
Authors: Guo Wenjing , Jiang Erlie , Feng Sizhou 
Published: December 2023

Objective: Patients with hematologic diseases are at a higher risk for Stenotrophomonas maltophilia(SM) bacteremia, which poses significant burden on morbidity and mortality. The aim of this study was to evaluate the early predictors of 28-day mortality in hematologic patients with SM bacteremia and to construct a reliable prediction model which can be used to identify patients at higher risk for mortality.
Methods: This retrospective analysis of 131 hospitalized patients diagnosed with SM bacteremia was conducted in a tertiary blood disease center in Tianjin, China, from January 2012 to June 2023. Univariate analysis and multivariate logistic regression analysis were used to identify prognostic risk factors and develop a prognostic mortality scoring system and internally validated by bootstrap method (resampling = 1000).
Results: The overall 28-day mortality rate in our study was 29.77% (39/131). The mean age was 45 (IQR 30.5-56.0) years and 70 individuals (53.44%) were diagnosed with myeloid malignancies. The existing condition severity-related scores did not perform well in predicting 28-day mortality for the patients in our population (AUROC values: SOFA: 0.842; ECOG: 0.831; APACHE Ⅱ: 0.709; SAPS Ⅱ: 0.675; aCCI: 0.654; Pitt score: 0.629).
Through univariate and multivariate analysis, we identified four independent risk factors associated with 28-day mortality: SOFA score (OR = 3.67, 95% CI 1.99-6.78, P &lt; 0.001; score = corresponding SOFA score), age ≥ 60 years (OR = 6.95, 95% CI 1.44-33.55, P = 0.0158; score = 2), bloody sputum or hemoptysis (OR = 5.32, 95% CI 1.08-26.29, P = 0.0402; score = 2) and neutropenia duration ≥ 25 days (OR = 3.92, 95% CI 1.01-15.26, P = 0.0487; score = 1). These factors were used to develop a prognostic scoring model, which yielded good discrimination (AUC = 0.889, 95% CI: 0.829-0.949) and calibration (Hosmer-Lemeshow goodness-of-fit test P = 0.998), with similar performance in the internal bootstrap validation (AUC = 0.888). Furthermore, all patients were divided into the high-risk group (≥ 7 points) and the low-risk group (&lt; 7 points) based on the model and compared using Kaplan-Meier curves and log-rank tests. Additionally, we founded that the use of trimethoprim-sulfamethoxazole (TMP/SMX) after infection was associated with a better prognosis ( P = 0.012).
Conclusions: The prediction model, utilizing SOFA score, age, bloody sputum or hemoptysis and neutropenia duration, proves to be an effective tool for early identification of hematologic patients with SM bacteremia at high risk of mortality.
The Prognostic Value of Common Cardiovascular Biomarkers in the Survival of Patients with DLBCL
Authors: Xu Yi , Shi Yuanfei , Sun Jianai , Zheng Xiaolong , Li Xueying , Wang Jinghan , Yu Wenjuan , Tong Hongyan , Jin Jie , Xie Wanzhuo 
Published: December 2023

Background
Diffused large B-cell lymphoma (DLBCL) is a subgroup of highly heterogenous and aggressive hematological malignancy. IPI scoring tools have been used to predict survival in DLBCL patients retrospectively. Moreover, it is indicated that cardiovascular biomarkers can predict long-term survival in myelodysplastic syndrome. To structure a more accurate prognostic model directing survival, we constructed retrospective research in our clinical institution with common cardiovascular biomarkers, for instance, IL-6, Troponin I, BNP, hydroxybutyrate dehydrogenase and creatine phosphokinase. Besides, other risk factors of cardiovascular diseases such as lipids are also taken into consideration.
Method
We retrospectively researched a total of 284 patients who were first diagnosed with DLBCL from January 2011 to November 2022, among whom 205 patients were sequenced by next-generation sequencing (NGS) before receiving therapy. Characteristics of democracy and clinical data were collected and analyzed. The primary objective is to investigate the prognostic value of common cardiovascular biomarkers in the long-term survival of DLBCL patients.
Results
A total of 284 patients were enrolled with a median follow-up time of 21.8 months. The inclusive criteria are: patients who are newly diagnosed with DLBCL and clinical data of cardiovascular mark can be retrospect, moreover, to eliminate the influence of cardiac failure we excluded those whose ejection fraction was lower than 30%.
There are 78 patients with high levels of BNP (HIGH-BNP group) and 119 patients with high levels of IL-6 (HIGH-IL6 group). In the HIGH-BNP group, overall survival is poorer than the control group (p&lt;0.001, HR=3.07, 95%CI 1.97-4.78). Besides, in the HIGH-IL6 group, the tendency shows similitude, with a lower survival ratio (p=0.025, HR=2.65, 95%CI 1.30-5.40). Among 205 patients who received NGS sequencing, 2270 genes mutation have been detected. the most frequently detected genes are PIM1 (324, 14.3%), KMT2D (73, 3.2%), BCL6 (80, 3.5%), TP53 (63, 2.8%) and MYD88 (57, 2.5%).
Conclusion
Cardiovascular biomarkers can properly predict DLBCL patient survival.
Association of Hypometilating Agents (HMA) + Venetoclax (VEN) in the Therapy of Acute Myeloid Leukemias Evolved from Myelodysplastic Syndromes (AML-MDS) Already Treated with Azacytidine
Authors: Latagliata Roberto , Cambò Benedetta , Piccioni Anna Lina , Federico Vincenzo , Cristiano Gianluca , Lugli Elisabetta , Rizzo Lorenzo , Santopietro Michelina , Mazzone Carla , Bonifacio Massimiliano , Palmieri Raffaele , Poloni Antonella , Biagi Annalisa , Binotto Gianni , Delfina Marzia , Annunziata Mario , Molteni Alfredo , Piedimonte Monica , Carmosino Ida , Di Veroli Ambra , Niscola Pasquale , Riva Marta , Capodanno Isabella , Curti Antonio , Di Rienzo Nicola , Fenu Susanna , Crugnola Monica 
Published: December 2023

Background Survival of high-risk Myelodysplastic Syndromes (MDS) treated with azacytidine during the dysplastic phase and then evolved in Acute Myeloid Leukemia (AML-MDS) is very poor. While the association of hypometilating agents (HMA) and venetoclax (VEN) is widely used in de novo AML not eligible for intensive chemotherapy, very few data are available in patients (pts) with AML-MDS.
Methods Data of 42 pts with AML-MDS treated frontline with HMA+VEN in 19 hematologic Centres in Italy outside clinical trials from 5/2018 to 3/2023 were retrospectively collected and analysed. Composite overall response rate [ORR; complete remission (CR) + CR with incomplete hematologic recovery (iCR) + partial remission (PR) + hematologic improvement (HI)], duration of response and overall survival (OS) were assessed.
Results: Baseline characteristics at evolution in AML are reported in the Table. Median interval from initial MDS diagnosis to evolution was 16.7 months [interquartile range (IQR) 8.2-30.1]. Pts were treated for a median of 3 courses (IQR 2-6): HMA were administered at standard dosage, VEN daily doses in the 1 st cycle are reported in the Table. On the whole, 34 pts (81.0%) had at least one hematologic toxicity of grade 3-4: in particular, severe neutropenia (PMN &lt; 0.5 x 10 9/l) was reported in 32 pts (76.1%). Eighteen pts (42.8%) had at least one infective episode during the treatment: pulmonary infections were reported in 9 pts (21.4%). Response to treatment is shown in the Table: ORR was 52.4%, with a median response duration of 17.8 months (95%CI 3.3-32.2). After a median follow-up from AML evolution of 6.1 months (IQR 2.2-11.6), 31 pts (73.8%) died and 11 (26.2%) were alive. Median OS from AML evolution of the whole cohort was 6.9 months (95%CI 4.7-9.1), Pts with any response to HMA+VEN had a significantly longer OS compared to pts with progressive/stable disease [15.6 (95%CI 11.3-19.8) versus 3.3 (95%CI 0.7-5.8) months, respectively (p&lt;0.001)] (Figure).
Conclusions: Our real-life data suggested that HMA+ VEN combination could be useful also in AML-MDS already treated with azacytidine in the dysplastic phase, with an ORR of about 50% in pts unfit for intensive approaches: however, hematologic and infective toxicities were severe and the response duration was short, with a persistently poor median OS. As a consequence, addition of other targeted therapies driven by NGS should be explored in the next future.
KLF2 Regulates NLRP3 Inflammasome Priming and Activation in Murine Myeloid Cells
Authors: Mukherjee Devashis , Satyavolu Sriram , Thomas Asha , Li Yuexin , Nayak Lalitha 
Published: December 2023

Introduction: Krüppel-like factor-2 (KLF2) is a critical nodal transcription factor and a tonic repressor of myeloid cell activation. Loss of KLF2 is associated with a pro-inflammatory and pro-thrombotic state. Mice deficient in myeloid-KLF2 (MK2KO) experience significantly higher mortality from lipopolysaccharide (LPS), and have increased serum and tissue levels of pro-inflammatory cytokines such as IL-1β. IL-1β is a product of NLRP3 inflammasome priming and activation, which has been implicated in numerous inflammatory and immune-mediated diseases. Neutrophils are the first responders of the innate immune system and are responsible for bacterial antigen detection. We thus aimed to elucidate the role of KLF2 in the regulation of NLRP3 inflammasome activation and subsequent IL-1β release in the neutrophil compartment.
Methods: 8-week old adult MK2KO ( Lyz2Cre/ Klf2fl/fl) and control ( Lyz2Cre) mice were used for obtaining neutrophils from the bone marrow. Neutrophils were plated in RPMI-1640 media and stimulated with 10 ng/mL of LPS for 1 hour (h) and 2 h, followed by nigericin for 30 minutes. LPS acts as a priming agent for NLRP3 inflammasome assembly, and nigericin is a potassium ionophore which enables the activation step and subsequent IL-1β release. Supernatant was used for IL-1β ELISA and cell lysate was used for protein extraction and Western blotting to quantify NLRP3 protein expression. GraphPad Prism was used for statistical analyses.
Results: Neutrophils from both MK2KO and Cre mice have significantly increased production of IL-1β when stimulated with LPS followed by nigericin (Figure 1), and loss of KLF2 leads to significantly increased IL-1B release from neutrophils. MK2KO neutrophils also have significantly more NLRP3 protein expression as compared to Cre neutrophils at baseline, and in response to LPS and nigericin (Figure 2). This increase in NLRP3 protein expression was time dependent and dose-dependent (Figure 2).
Conclusion: KLF2 negatively regulates the transcriptional expression of NLRP3 and loss of KLF2 leads to increased NLRP3 inflammasome priming, at baseline and in response to LPS. Loss of KLF2 also affects the second step of the NLRP3 inflammasome pathway - the activation step, leading to increased IL-1β release in neutrophils in adult mice. Ongoing studies are examining the mechanisms underlying KLF2 control of NLRP3 transcription and other aspects of inflammasome activation. Inflammasome activation has been implicated in sepsis-related mortality due to the pro-inflammatory cytokine storm, and thus modulating KLF2 might help in developing novel targets to reduce this burden of mortality.
CREB1 Promotes Immune Escape of Multiple Myeloma Cells By Inducing HLA-E
Authors: Ismael Aya , Robinette Allen , Dona Kameron , Kudalkar Ruchi , Manning Vincent , Galloway Joshua , Cocucci Emanuele , Cottini Francesca 
Published: December 2023

Introduction: Multiple Myeloma (MM) is a disease of clonal plasma cells, which accumulate in the bone marrow (BM) and rely on the support of the microenvironment to survive. Immune escape is a common resistance mechanism employed by tumor cells to avoid cytotoxicity by effector immune cells. HLA-E, a non-classical major histocompatibility complex (MHC) class I molecule, inhibits the function of specific subtypes of Natural Killer (NK) and T cells, leading to tumor immune escape. HLA-E expression correlates with worse progression-free survival in newly diagnosed patients with MM. Therefore, we decided to better elucidate the function and regulation of HLA-E expression in MM.
Results: We observed that HLA-E mRNA expression increases in the transformation from normal plasma cells to MM. Since INF-gamma induces HLA-E in MM cells and CREB1 itself promotes the production of IFN-gamma, we hypothesize that CREB1 could regulate HLA-E expression in MM. We first analyzed RNA-sequencing data from patients with MM in the CoMMpass database: gene set enrichment analysis (GSEA) showed increased expression of several pathways related to interferon signaling in patients with high CREB1 expression. We then specifically looked at differences in HLA-E and we confirmed that patients with high CREB1 expression had statistically significant higher HLA-E levels compared with patients with low CREB1 expression. CHIP-sequencing assays in MM cell lines demonstrated that CREB1 can directly influence HLA-E expression by binding to HLA-E promoter. To further prove these data, we evaluated HLA-E levels in gain-of and loss-of function models of CREB1. We observed an increase of HLA-E levels by overexpression of wild type CREB1 and reduction of HLA-E levels by CREB1 silencing or pharmacological inhibition of CREB1 with 666-15 (CREBi).
We then investigated the relationship between CREB1 and STAT1. Indeed, IFN-gamma signals through the STAT1-JAK pathway. Interestingly, while treatment with IFN-gamma strongly induces HLA-E without affecting CREB1 levels or its function, CREBi + INF-gamma reduces HLA-E, STAT1, and phospho-STAT1 levels. Conversely, immunomodulatory drugs (lenalidomide-LEN and pomalidomide-POM) and HDAC inhibitor, Panobinostat, promote the phosphorylation of STAT1, resulting in the transcription of IFN-target genes, including HLA-E. The increase in HLA-E was then reverted by CREB1 inhibition. Since HLA-E impairs NK cell function, we treated MM cells in the presence of NK cells with CREBi alone or in combination with immunomodulatory drugs (IMiDs). Treatment with CREBi or CREBi + IMiDs potentiated the killing effects of NK cells. Animal studies are ongoing to confirm these data in vivo.
Conclusion: In conclusion, our study defines the role of CREB1 in modulating HLA-E expression; CREB1 inhibition improves NK cell-mediated cytotoxicity in MM, representing a novel strategy to tackle immune escape.
Real Event Analysis of the Efficacy and Safety of Polatuzumab Vedotin Combination Regimen in Patients with Relapsed/Refractory Diffuse Large B-Cell Lymphoma
Authors: Shi Yuanfei , Xu Yi , Wang Jinghan , Zheng Xiaolong , Li Xueying , Jin Jie , Tong Hongyan , Xie Wanzhuo 
Published: December 2023

Abstract：
Objective Diffuse large B-cell lymphoma (DLBCL) is the most common non-Hodges lymphoma (NHL) subtype, although R⁃CHOP treatment cured about 60% of patients. However, 40%-45% of patients do not respond to first-line therapy or relapse after an initial response, and this segment of patients has a poor prognosis. Therefore, the use of targeted drugs and the exploration of drug combination schemes are particularly important, among them, anti-CD79B antibody-drug conjugate (ADC) polatuzumab vedotin (Pola) combined with Bendamustine-Rituximab (BR) and Pola combined with R-CHOP are promising therapeutic options. To analyze the efficacy and safety of Pola combined with BR and Pola combined with R-CHOP in the treatment of relapsed/refractory DLBCL (R/R DLBCL).
Methods The single-arm, Phase II clinical study commenced at our center in May 2023. Eligible patients were R/R DLBCL patients with Ann Arbor stages 3-4, ages 36 to 88 years, who had received at least one previous standard chemotherapy regimen. The clinical data of 17 patients enrolled in our center from May 2023 to August 2023 were retrospectively analyzed, including 10 males and 7 females. The median age was 69 (ranged 36-88) years. 12 patients were treated with Pola-BR and 5 with Pola-R-CHOP, the clinical characteristics, medication regimen, efficacy and occurrence of adverse reactions were analyzed. To explore the causes of adverse reactions between the Polar-BR group and the Polar-R-CHOP group.
Results Data as of August 1, 2023, in the efficacy evaluation of 17 patients, the overall response rate (OR) was 71% (12/17) and the complete response (CR) rate was 53% (9/17). Progressive free survival (PFS), median follow-up of 45 days, with 3 cases (12%) experiencing disease progression. Compared with the Pola-BR group, the Pola-RCHOP group had a lower incidence of adverse reactions. The main adverse event was a pulmonary infection, of which 33% (4/12) were in the Polar-BR group and 25% (1/5) were in the Polar-R-CHOP group, and no severe pneumonia occurred in either group.
Conclusion Compared with the traditional R-CHOP regimen, Polar+BR/RCHOP has better therapeutic effect and a better application prospects for R/R DLBCL patients.