bluuebunny/crossref_metadata_2025_split huggingface dataset:
Real-World Treatment Patterns Following Update to National Comprehensive Cancer Network Guidelines for Light-Chain Amyloidosis: Results from a Us Administrative Claims Database
Authors: Thompson Jeffrey , Wechalekar Ashutosh D. 
Published: December 2023

Background: Light-chain amyloidosis (AL) is a rare, multi-organ disease that can cause serious organ damage. In January 2021, a new therapy, daratumumab, was FDA-approved for the treatment of AL in combination with current standard-of-care (SoC) of bortezomib/cyclophosphamide/dexamethasone (CyBorD) and was classified as SoC according to the National Comprehensive Cancer Network (NCCN) guidelines. The objective of this study is to describe current real-world treatment patterns amongst patients with AL who newly initiated treatment January/2021 through June/2022.
Methods: This study included patients aged ≥18 identified in the IQVIA PharMetrics database (&gt;72 million lives 2021-2022 total) who were newly initiating pharmacological treatment with bendamustine, bortezomib, carfilzomib, cyclophosphamide, daratumumab, ixazomib, lenalidomide, melphalan, pomalidomide, or venetoclax 01Jan2021-30Jun2022 (date of first therapy classified as “index date”). Patients were required to have an ICD-10 diagnosis of AL (E85.81) identified during full study period (01Jan2020-30Sep2022) as well as continuous medical and prescription insurance enrollment from 1 year pre-treatment-index through 90-days post-treatment-index. Patients were excluded if they had any of the following: a claim indicating treatment with stem cell transplant; a diagnosis of familial mediterranean fever; a diagnosis of secondary, transthyretin, or hereditary amyloidosis; a diagnosis of a non-myeloma/non-lymphoma malignancy. Treatment patterns assessed included index treatment regimen and daratumumab adoption/use patterns at index, 30-days post-index, and 90-days post-index.
Results: A total of 194 patients met all eligibility criteria, out of which the majority were male (N=119; 61%), with the largest insurance coverage being self-insured (N=80; 41%), and a mean age of 62 years (SD=9.8). The most common index treatment regimen was CyBorD+daratumumab (N=53; 27%) followed by dexamethasone+daratumumab (N=24;12%) and daratumumab monotherapy (N=16; 8%) ( Table). Across all treatment regimens at index date, daratumumab was found to be utilized by 62% (N=121) of patients. Furthermore, 76% (N=148) and 80% (N=155) of patients were found to have utilized daratumumab within 30-days or 90-days of treatment initiation, respectively.
Discussion: AL is life threatening disease that impacts organ function and quality of life. Until 2021, there were no FDA approved therapies for AL. Daratumumab use was rapidly adopted to treat patients with AL following approval, in accordance with national guidelines, primarily in combination with other treatments such as CyBorD. This has changed the treatment paradigm providing hope to patients and clinicians to treat this devasting disease and should be informative for current and future clinical trial considerations in development of medications to treat AL.
Estrogens and Prolactin Do Not Regulate Maternal and Embryo Iron Homeostasis during Pregnancy
Authors: Sangkhae Veena , Zhang Vida , Ganz Tomas , Nemeth Elizabeta 
Published: December 2023

Iron is essential for maternal and fetal health but the molecular mechanisms ensuring increased iron availability during pregnancy are not well understood. Hepcidin is the key iron-regulatory hormone and functions by blocking iron absorption, recycling and mobilization from stores, effectively decreasing plasma iron levels. In healthy human and rodent pregnancies, maternal hepcidin decreases starting in the second trimester and is nearly undetectable by late pregnancy. This decrease in hepcidin allows for greater iron availability for transfer to the fetus. If hepcidin is not appropriately suppressed during pregnancy, it results in fetal anemia, intrauterine growth restriction, and even fetal demise in severe cases 1.
Unrelated to pregnancy, hormones estrogen and prolactin have been previously implicated in hepcidin regulation 2,3, although with conflicting results on the direction of hepcidin change 4-6. The levels of both hormones increase dramatically over the course of pregnancy, thus we hypothesized that they may modulate iron homeostasis during pregnancy. Studying the role of estrogens and prolactin during pregnancy is challenging as both hormones are required for pregnancy. Additionally, mice with global knockout (KO) of either estrogen receptor alpha or prolactin receptor are infertile. Thus, to determine the contribution of estrogens and prolactin on maternal hepcidin suppression during pregnancy, we generated liver-specific knockouts of either estrogen receptor alpha ( Er- α f/f;Alb-Cre +) or prolactin receptor ( Prlr f/f;Alb-Cre +), here abbreviated as ER-α KO and PRLR KO. Female ER-α KO, PRLR KO and WT mice were set up for timed pregnancy, and liver hepcidin mRNA, as well as maternal and embryo iron and hematological parameters were measured at E18.5 . Hepcidin suppression in ER-α KO and PRLR KO dams was not different from that in WT dams, suggesting that estrogens and prolactin are not major mediators of maternal hepcidin suppression. Additionally, maternal and embryo hematological parameters and liver iron concentrations were similar between WT, ER-α KO, PRLR KO pregnancies, further supporting our observation that estrogens and prolactin do not regulate iron homeostasis in pregnancy. The mechanisms by which maternal hepcidin is suppressed during pregnancy remain to be determined.
1Sangkhae V et al, Blood, 2020
2Yang Q et al, Endocrinology, 2012
3Wang J et al, Nanomedicine: nanotechnology, biology and medicine, 2015
4Zhen et al, Hepatology, 2013
5Ikeda Y et al, PloS one, 2012
6Lehtihet M et al, PloS one, 2016
Sickle Cell Disease Electronic Health Record Population Management Approach to Support Delivery of High-Quality Care: Leaving Paper Lists behind
Authors: Smith-Whitley Kim , Brooks Elizabeth , Brandemarte Alicia , Norris Cynthia 
Published: December 2023

Children and young adults with sickle cell disease (SCD) require complex health care services to screen for early signs of disease-related complications and to initiate and monitor disease-modifying therapies. Care coordination is challenging as it involves multiple team members across multiple subspecialties. Evidence-based clinical protocols and quality metrics are essential for SCD programs to deliver high-quality care. Systems to track this care delivery are crucial to ensure equitable, accessible care is consistently provided.
In 2016, the Comprehensive Sickle Cell Center (CSCC) and the Population Health Innovation Team at Children's Hospital of Philadelphia (CHOP) developed and implemented an electronic health record (EHR)-based system, the SCD patient registry and proactive care outreach tools, to facilitate processes needed to ensure patient service delivery in a timely fashion. We selected Transcranial Doppler (TCD) ultrasounds, hydroxyurea therapy initiation, and annual clinic visits to monitor stroke risk screening, disease-modification therapy, and general chronic illness care. Between January 2015 and June 2023, approximately 1400 patients with SCD were tracked across two CHOP outpatient clinics, the CHOP Philadelphia and CHOP Voorhees campuses. We tracked TCD completion, hydroxyurea prescriptions, and clinic visits per year for age-eligible patients with SS and SB0thal.
Prior to implementation of the EHR-based tools and new workflows in October 2016, for age-eligible patients, on average 75% of patients had received annual TCD screening, 55% of patients had received hydroxyurea prescriptions within the prior 6 months, and 85% had attended outpatient hematology clinic at least twice within the year. As of June 2023, on average, completed TCD visits had increased to 91%, patients prescribed hydroxyurea had increased to 78%, and patients attending 2 clinic visits within a year had increased to 89%. These metrics remained consistent and improvement was sustained despite the COVID-19 pandemic. Table 1 describes the drivers influencing these improvements, which included various interventions involving social work, nursing, community health workers, registrars, care coordinators, and physicians. Figure 1 illustrates the changes achieved over time in rates of TCD completion, hydroxyurea prescriptions, and clinic visit attendance.
This implementation of an SCD EHR-based population health tool and new care team workflows facilitated more efficient processes for various care team members and improved our ability to consistently provide timely services to children and young adults with SCD. This resulted in sustained improvement in all metrics and high-quality care for our patients.
Late Effects of Allogeneic Stem Cell Transplantation for Non-Hodgkin Lymphoma. Swiss Cohort Analysis 1997-2021
Authors: Rebmann Ekaterina , von Werdt Alexander , Künzi Arnaud , Wolfensberger Nathan , Baldomero Helen , Medinger Michael , Passweg Jakob R. , Nair Gayathri , Masouridi-Levrat Stavroula , Chalandon Yves , Rovó Alicia 
Published: December 2023

Background: despite rapid development of new highly efficient targeted and cellular-therapies, allogeneic stem cell transplantation (allo-HSCT) represents so far the only potentially curable treatment according to a longest follow-up in a setting of relapse/refractory Non-Hodgkin lymphoma (rrNHL). However, late effect (LE) issues of allo-HSCT in rrNHL seem to be underexplored. Here, we present the first analysis of a retrospective, multicenter, registry-based analysis (Swiss Blood Stem Cell Transplantation and Cellular Therapy, SBST) of LE in patients who underwent allo-HSCT for rrNHL in Switzerland.
Methods: We retrospectively collected data from 109 patients with all types of rrNHL who underwent allo-HSCT in 3 University Hospitals of Switzerland (Zurich, Basel and Geneva) between May 1997 and November 2021. The inclusion criteria was 2 years survival after allo-HSCT. The primary endpoint was the cumulative incidence (CI) of LE and secondary endpoint were overall survival (OS), relapse incidence (RI) and type of LE according to organ/systems involved.
Results: median of follow-up was 6.5 years. Patients who survived 2 years after allo-HSCT presented 5 and 10 years OS of 94% [95% CI 86.3 - 97.5] and 86% [95% CI 75 - 92.4] respectively. RI and CI of LE were 18.3% and 44% at 5 years and 34.4% and 58% at 10 years post allo-HSCT. A total of 79/109 (72%) of patients experienced any type of LE during the follow-up period. Renal dysfunction (21%), secondary malignancies (18%), cardiovascular disease (18%), osteoporosis (18%) and thyroid dysfunction (17%) were the most frequently observed. CI of secondary malignancies was 6.1% and 20% at 5 and 10 years respectively.
Conclusions: Our analysis of a mixed-type rrNHL cohort confirms the efficacy of allo-HSCT in heavily pretreated/refractory patients, showing excellent OS at 5 and 10 years for those who survived 2 years. Both RI and LE present a competitive risk for survival benefit beyond 2 years after allo-HSCT. Secondary malignancies, renal and cardiovascular disease appear to be the most frequent types of LE, revealing the toxicity accumulated prior to allo-HSCT in the setting of rrNHL. These results should be interpreted with caution due to a retrospective nature of the analysis, the heterogeneity of the conditioning regimen and the NHL cohort.
Figure 1. a) Overall survival (KM-estimate) b) cumulative incidence of late effects
Spatial Multiomics Profiling of Angioimmunoblastic T-Cell Lymphoma
Authors: Xu Mina , Halene Stephanie , Fan Rong , Enninful Archibald 
Published: December 2023

Introduction:
Angioimmunoblastic T-cell lymphoma (AITL) is a subtype of non-Hodgkin lymphoma (NHL) characterized primarily by a T follicular helper cell (TFH) phenotype. AITL presents with a highly complex tumor microenvironment with the tumor cells on a scaffold of highly arborized CD21+ follicular dendritic cells found in proximity to high endothelial venules (HEVs). The organized structure of the lymph node with distinct B cell and T cell zones is disrupted in the lymph node samples from patients with AITL. Lymphoid follicles in most AITL cases tend to be depleted, not hyperplastic as in other lymphomas. AITL tumor cells express CD10, BCL6, PD1, CXCL13, C-X-C motif chemokine receptor 5 (CXCR5), ICOS, and signaling lymphocytic activation molecule-associated protein (SAP) with diagnosis based on the expression of at least 2 of these markers. Our study uses novel spatial omics technology (Deterministic Barcoding in Tissue (DBiT-seq) and multiplexed immunofluorescence staining (CODEX)) to fully characterize the transcriptional and proteomic landscape of AITL.
Methods:
In this study, initial FFPE biopsy specimens from 22 patients with AITL were collected from archives. 10 µm thick tissue sections on poly-L-lysine coated slides were prepared for the performance of multiplexed immunofluorescence imaging (CODEX) for 12 immune-related markers: Podoplanin, CD20, CD4, CD8, CD68, CD45RO, CD3e, GranzymeB, PD1, Ki67, CD21 and CD34 using the PhenoCycler-Fusion system. We also validated anti-EBV Latent Membrane Protein 1 antibody. Cell segmentation was performed using a Stardist-based model in QuPath and downstream analysis done using the Seurat package. On an adjacent tissue section, we used Spatial CITE-seq to co-map the whole transcriptome and ~160 proteins.
Results:
From the multiplexed immunofluorescence staining, we observed CD21+ Follicular dendritic cells in close proximity to HEVs as expected from the spatial architecture of AITL. We also found 11 spatially distinct clusters differentially expressing the marker proteins. We observed a lower number of CD8+ cytotoxic T cells relative to CD4+ Helper T cells. We also identified cellular neighborhoods and their composition found a population of FDCs that directly interact with the tumor cells. From spatial CITE-seq, we average of ~670 genes were found in each spot. We also found the expression of CXCL13, TET2, DNMT3A and PDCP1 which are markers associated with AITL. There was a strong correlation between the transcript signals detected in Spatial CITE-seq and the protein expression from CODEX.
Conclusions:
Our study revealed the spatial organization of the tumor microenvironment of AITL. We envision that combining multiplexed immunofluorescence and Spatial CITE-seq will further our understanding of the AITL tumor environment and could lead to the discovery of novel clinical targets.
Incidence and Outcomes of Pneumocystis Pneumonia Following Chimeric Antigen Receptor T-Cell Therapy: A Real-World Analysis
Authors: Wang Jiasheng , Daunov Michael , Cooper Brenda W 
Published: December 2023

Background: Pneumocystis Pneumonia (PCP) is a known opportunistic infection after chimeric antigen receptor (CAR) T-cell therapy. However, the incidence and outcomes of PCP are poorly understood, and there has been no clear consensus on the optimal duration for PCP prophylaxis post-CAR T-cell treatment.
Methods: From a large real-world database, TriNetX Research Network, we identified patients who underwent commercial anti-CD19 and anti-BCMA CAR T-cell therapy between January 2019 and January 2023. The diagnosis of PCP was established using the ICD-10-CM code B59 (pneumocystosis) or through Logical Observation Identifiers Names and Codes (LOINC) documentation of positive microbiologic tests from respiratory samples.
Results: Among the 1,107 and 280 patients who received anti-CD19 and anti-BCMA CAR T-cell therapies, 19 (1.7%) and 4 (1.4%) patients developed PCP, respectively. Altogether, a total of 23 (1.7%) patients developed PCP within a median of 139 days (range 19 to 732 days) post-infusion. (Figure) Demographics, the incidence and severity of cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS), and the initial choice for PCP prophylaxis, were similar for patients with and without PCP. Patients who developed PCP were more likely to have used dexamethasone (65 vs 43%, p=0.02) and have a shorter duration of trimethoprim/sulfamethoxazole (TMP/SMX) prophylaxis (median 9 [range 1 to 45] vs 19 [range 1 to 106] weeks, p=0.002). In the univariate analysis, patients who received TMP/SMX prophylaxis for less than 3 months showed a trend of a higher incidence of PCP compared to those who received it for more than 3 months (hazard ratio [HR] 3.54, 95% confidence interval [CI] 0.87 to 14.3, p=0.06). (Table) Regarding survival outcomes, patients with and without PCP had similar time-to-next-treatment or death (median 84 vs 68 days, HR 0.96, 95%CI 0.61 to 1.51) and overall survival (median 518 days vs not-reached, HR 1.61, 95%CI 0.91 to 2.88).
Conclusions: In real-world conditions with routine prophylaxis, PCP is an infrequent opportunistic infection following anti-CD19 or anti-BCMA CAR T-cell therapy. Patients with and without PCP were associated with similar survival outcomes.
Survival of Hematopoietic Stem Cell Transplantation in the National Institute of Neoplastic Diseases, Lima-Perú between 2012 to 2022: 10 Years of Experience
Authors: Quintana Shirley , López Córdova Naty , Lopez Chavez Lourdes ISABEL , Alcarraz Cindy , Mallma Soto Victor IVAN , Calderon Monica , Chavez Sharon , Vidaurre Tatiana , Flores Claudio , Vasquez Jule F 
Published: December 2023

Introduction:
Hematopoietic stem cell transplantation (HSCT) is part of standard treatment in a great number of hematologic malignancies and some solid tumors. The National Institute of Neoplastic Diseases (INEN) started the HSCT program in 2012, performing over 600 HSCT so far. In this study, we report the overall survival (OS) at 5 years of patients who undergone this procedure in our institution through 10 years of experience.
Methods:
We analyzed retrospectively the survival of all patients admitted to the HCST program at INEN between 2012 and 2022. Clinical and pathological data were collected from the medical records and the unit's transplant patient registry. The OS was determined through the Kaplan-Meier method and the comparisons of survival curves were performed using the log-rank or Breslow test.
Results:
During the study period, a total of 647 transplants were performed. The median age was 39 years (range: 1 - 70), 73.4% of patients were between 18 and 60 years, and 57.1% were men.
Most transplants (n = 591, 91.3%) were performed in the adult population and 8.6% (n = 56) in pediatric population. According to the type of transplant, 68% (n=440) were autologous and 32% (n=207) allogeneic from related donor.
The most frequent diagnosis were acute leukemia (n = 221, 34.2%), multiple myeloma (n = 190, 29.3%), non-Hodgkin lymphoma (n = 105, 16,2%; of these, 22 were T- cell lymphomas), Hodgkin lymphoma (n = 69, 10.7%) and germinal cell tumor (n = 33, 5.1%); in the pediatric population, leukemia was the most common diagnosis (66.1%).
The median follow-up of the patients was 3.7 years (95% CI: 3.4, 3.9), 25.2% (n = 163) of the patients died due to disease progression. The median overall survival (OS) for the entire cohort was not reached and the OS rate at 5 years was 68.3%. The 5-year OS rate by transplant subtype was 53.9% and 75.3% (p &lt; 0.001) for allogeneic and autologous transplants, respectively; and according to the pathology, the patients who had a better 5-year OS were HL (87.5%) and NHL (77.5%), while in leukemias it was 56.1%. Survival by age group (&lt;40 vs &gt;40) and sex (female vs. male) did not present a significant difference (p &gt; 0.05).
Conclusions:
The survival of the transplanted patients was similar to that reported in other series. Leukemia was the most frequent hematological malignancy admitted to the HSCT program. HL and NHL were the malignant tumors with the highest survival rates at 5 years. Nearly a third of transplants were allogeneic, all from matched related donors. HSCT in our series has shown an improvement in OS at 5 years in both autologous and allogeneic transplant patients compared to non-transplanted patients, according to international reports.
Global research trends in CRISPR-related technologies associated with extracellular vesicles from 2015 to 2022: a bibliometric, dynamic, and visualized study
Authors: Lin Jianjing , Jia Shicheng , Jiao Zilu , Chen Jiayou , Li Wei , Cao Fuyang , Zhang Xintao 
Published: December 2023

Abstract
Purpose
This study aims to explore the emerging trends, dynamic development, and research hotspots of clustered regularly interspaced short palindromic repeats (CRISPR) technology associated with extracellular vesicles during the past 7 years and demonstrate them by visualization.

Methods
A total of 219 records related to CRISPR technology associated with extracellular vesicles from 2015 to 2022 in the Web of Science Core Collection (WoSCC) database were collected. R language, VOSviewer, CiteSpace, and GraphpadPrism software packages were used to analyze the history of this research, the general characteristics of the literature, and keywords. Finally, the hotspots and latest trends in CRISPR technology associated with extracellular vesicles are predicted.

Results
A total of 219 articles were collected for this study. The production of publications about CRISPR technology associated with extracellular vesicles has increased annually. Researchers from China, the USA, and Germany made the most important contributions to this trend, while RLUK Research Libraries UK offers the largest amount of literature in this field. Shenzhen University, Nanjing Medicine University, and Peking University exhibited the closest cooperation. Additionally, active topics burst during different periods, as identified according to 317 keywords belonging to 39 disciplines. Keywords were clustered into seven research subareas, namely exosome, nanovesicles, DNA, gene editing, gene therapy, cancer therapy, and endometrial stromal cells. The alluvial map of keywords reveals that the most enduring concepts are gene therapy, nanovesicles, etc., while the emerging keywords are genome, protein delivery, plasma, etc.

Conclusions
We reviewed 219 previous publications and conducted the first bibliometric study of CRISPR technology related to extracellular vesicles from 2015 to 2022. This comprehensive summary constructed a knowledge map and demonstrates the trends in this area. The current trends and potential hotpots for this topic are also identified, which will be a great help for researchers in the future.