bluuebunny/crossref_metadata_2025_split huggingface dataset:
Reducing Preventable Bleeding Visits and Institutional Factor Costs for Patients with Bleeding Disorders with a Prospective Quality Improvement Project
Authors: Merrill Sam , Webber Sylvia , Merrill Laura , Varvoutis Megan , Shmookler Aaron Daniel 
Published: December 2023

Providing optimal care to patients with bleeding disorders requires specialized physician, laboratory, pharmacy, nursing, and institutional resources best achieved at Hemophilia Treatment Centers (HTCs). Current systems for managing the care of a resource intensive patient population may be suboptimal. We observed frequent bleeding related hospitalizations and emergency room (ER) visits in patients with bleeding disorders treated at our HTC that could have been potentially prevented by changes in outpatient care delivery.
We initiated a prospective quality improvement (QI) project to improve care delivery and to reduce preventable bleeding related hospitalizations and ER visits for adult patients treated at our HTC. The interventions targeted patient-level and systems-level factors contributing to preventable visits, and barriers to care in our patient population. We compared preventable bleeding related hospitalizations and ER visits, institutional factor cost, use of prophylaxis in severe hemophilia, primary care physician attainment, and patient electronic portal enrollment before and after the QI intervention.
In our population of adult patients with bleeding disorders (N=88), the intervention significantly reduced the primary outcome of preventable bleeding hospitalization or ER visit (P=0.0082, Figure), and reduced such visits by 85.4%, meeting the pre-specified criteria for success. Institutional factor acquisition costs to treat preventable bleeding were reduced by 94.5%, from $11,800 to $640 per patient per year; a projected savings of $982,088 yearly. Use of factor prophylaxis in patients with severe hemophilia increased from 58.8% to 100%, attainment of a primary care physician increased from 69.4% to 86.4%, and use of the electronic patient portal increased from 53.2% to 83%; all secondary outcomes met pre-specified criteria of success and were statistically significant. HTC clinic visit attendance was low at 55.2%. The majority of patients (71.6%) had at least one outpatient urgent episode (mean 0.72 episode per year), and 93% had non-urgent management (mean 9.3 episodes per year) occurring outside of a clinic visit.
These data demonstrate that concerted outpatient management of patients with bleeding disorders with a quality improvement framework can reduce preventable hospitalization and ER visits. Decreased inpatient utilization resulted in substantial reductions in factor costs at the health system level. The clinical effort required to achieve these results was substantial, and required frequent provider engagement outside of regular clinic visits. The HTC can improve patient outcomes and reduce institutional costs from preventable bleeding episodes by supporting a collaborative quality improvement process led by physician, nursing, and laboratory coagulation experts.
Good Prognosis of Adult Immune Thrombocytopenia in a Provincial Hospital
Authors: Jutiamornlerd Siriporn , Uaprasert Noppacharn , Rojnuckarin Ponlapat 
Published: December 2023

Background: Immune thrombocytopenia (ITP) is an autoimmune disease resulting from platelet destruction and impaired platelet production. Some patients experience relapses or refractoriness after corticosteroid treatment, necessitating second-line treatments. The majority of adult ITP cases become chronic or relapsing. The aim of this study was to assess the clinical course and identify factors related to sustained responses to treatment in patients with ITP.
Methods: This observational retrospective cohort study was conducted from January 2013 to December 2022 at Trang Hospital, Trang Province, Thailand.
Results: A total of 125 newly diagnosed ITP patients were enrolled, with an average follow-up duration of 48.49 ± 41.49 (mean ± SD) months. The average age was 42.34 ± 18.44 years, the average platelet count was 11.66 ± 14.39 x 10 9 /L, and the average platelet recovery time after treatment was 43.14 ± 101.32 days. The mean response duration after the first-line treatment was 25.99 ± 29.39 months. The characteristics of the patients were as follows: age below 60 years (78.4%), female sex (75.2%), pregnancy (1.6%), primary ITP (67.2%), secondary ITP (32.8%), bleeding symptoms (54.4%), platelet count &lt;10 x 10 9 /L (64%), platelet count 10-30 x 10 9 /L (28.8%), platelet count 30-50 x 10 9 /L (5.6%), platelet count &gt;50 x 10 9 /L (1.6%), splenectomy (4%), observation only (2.4%), loss to follow-up (10.4%), and death (4%). The most common cause of secondary ITP was systemic lupus erythematosus (63%). The first-line treatment consisted of dexamethasone (70.4%), prednisolone (23.2%), and/or intravenous immunoglobulin (4%).
The clinical courses were as follows: recovery within 3 months in 68.8%, persistence in 13.6%, and chronic ITP in 17.6%. The sustained responses to corticosteroid treatment at 6 months included complete response (CR) (58.4%) and response (R) (9.6%), as shown in Table 1. Second-line treatments were required in 22.4% of cases, including colchicine (60.7%), azathioprine (35.7%), cyclophosphamide (25%), dapsone (17.8%), vincristine (10.7%), mycophenolate mofetil (7.1%), cyclosporine (3.5%), and/or eltrombopag (3.5%). The sustained responses to second-line treatments at 6 months were CR in 12% and R in 8.8%. Female sex ( P-value 0.007) and primary ITP ( P-value 0.046) were significantly associated with the sustained response (CR+R) to corticosteroids at 6 months. Secondary ITP ( P-value 0.036) was also associated with the sustained response (CR+R) to second-line treatments at 6 months (Table 2).
Conclusions: This study reveals a favorable prognosis for ITP, with a majority of patients showing sustained response (CR+R), which differs from findings in studies conducted at referral centers. Female patients and those with primary ITP are more likely to respond. Further confirmation is needed through a large prospective cohort study in community hospitals.
Gpibα Caar-T Cells Induce Autoreactive B Cells Elimination to Treat Immune Thrombocytopenia
Authors: Zhou Jie , Mei Heng , Xu Yanyan , Shu Jinhui , Huang Linlin , Xu Min , Jiang Haojie , Liu Junling , Hu Yu 
Published: December 2023

Background: Immune thrombocytopenia (ITP) is a bleeding disorder caused by autoantibodies against platelet glycoproteins (GPs). A key attempt to treat ITP is to eliminate the autoreactive B cells. Here, we proposed a new strategy for B cell-depletion therapy of ITP, chimeric autoantibody receptors T cells (CAAR-T), which could trap autoreactive B cells and perform specific killing. GPIbα is a significant autoantigen found in ITP patients and indicates a poor response to standard immunosuppressive treatments. We developed GPIbα-based CAARs in this study.
Aim: To precisely eliminate the autoreactive B cells to treat ITP.
Methods: We constructed various lengths of the native GPIbα ectodomain into the ligand-binding domain of a second-generation CAR structure and expressed the CAAR structure on the HEK293 cell surface to verify its conformational epitope. We immunized BALB/C mice with human platelet lysates to obtain anti-GPIbα hybridomas and performed a binding assay to confirm selected hybridoma antibodies' binding ability to GPIbα CAAR. We performed cytotoxicity assays to assess GPIbα CAAR-T-cell selective cytolysis against anti-GPIbα B cells in vitro and developed a xenograft model to assess the cytolytic efficiency and security of GPIbα CAAR-T cells in vivo. A plasma antibody binding assay was used to test GPIbα CAAR-T cells' ability in reaction with native GPIbα autoantibodies from ITP patients. We applied an enzyme-linked immunospot (ELISpot) assay to verify GPIbα CAAR-T cells' potential in eradicating autoreactive B cells of ITP patients.
Results: We successfully expressed GPIbα CAAR structure on the cell surface and proved that the conformational epitope of GPIbα CAAR is consistent with that of the native human platelet GPIbα. The Schematic of GPIbα CAAR structure is presented in Figure 1A. By immunizing BALB/C mice with human platelet lysates, we obtained four anti-GPIbα hybridomas with different CAAR binding sites. Vitro cytotoxicity assays confirmed GPIbα CAAR-T-cell selective cytolysis of anti-GPIbα hybridoma cells. In a hybridoma xenograft model, we verified that the CAAR-T cells could persist and selectively lyse autoreactive B cells and subsequently reduce autoantibody titers without apparent off-target organ toxicity. Through the plasma antibody binding assay, we demonstrated that GPIbα CAAR could react with sera from ITP patients with anti-GPIbα antibodies (Figure 1B). ELISpot analysis showed that GPIbα CAAR-T cells successfully eliminated anti-GPIbα B cells from a patient with refractory ITP, and normal B cells were not destroyed compared to anti-CD19 CAR-T cells.
Conclusion: Our study provides a proof of concept for CAAR-T cell therapy to eradicate autoimmune B cells while sparing healthy B cells, which would compensate for the defects of traditional B cell depletion therapy in ITP. GPIbα CAAR-T therapy would be a promising treatment for refractory and relapsed ITP patients.
Relationship between Sarcopenia and the Heterogeneity and Microenvironment of Acute Myeloid Leukemia Based on Single-Cell Transcriptome Sequencing
Authors: Sun Qian , Liu Wenjie , Hong Ming , Zhu Yu , Li Jianyong , Qian Sixuan 
Published: December 2023

Background: High intratumoral heterogeneity heterogeneity (ITH) and changes in bone marrow microenvironment (BMM) components are important for drug resistance and recurrence in patients with acute myeloid leukemia (AML), and may also influence the phenotype of sarcopenia. This study aims to determine the relationship between sarcopenia and the heterogeneity and microenvironment of AML.
Method: Body composition was assessed by bioelectrical impedance analysis before treatment. Sarcopenia was diagnosed by low muscle quantity according to European Working Group on Sarcopenia in Older People 2 (EWGSOP2). Bone marrow samples from 9 patients with relapsed or refractory AML were used to perform single-cell transcriptome sequencing (scRNA-seq) to analyze the differences in tumor cell subsets and microenvironmental components between AML patients with or without sarcopenia. The samples of 19 newly diagnosed AML patients were further collected for bulk RNA-seq, and deconvolution was done. Bioinformatics methods were used to verify the differences in cell subsets of microenvironmental components in patients with and without sarcopenia, as well as the genes and signaling pathways of tumor cells with differential expression.
Results: Nine leukemia-like cell subsets were identified in AML patients by scRNA-seq. In AML patients with sarcopenia, hematopoietic stem cell (HSC) subsets accounted for a significantly higher proportion of malignant cells, while progenitor cells and monocytes showed a higher proportion in patients without sarcopenia. In sarcopenic group, there were significantly fewer neutrophils, megakaryocytes, and CD8 + Tcm cells in the microenvironment component, while significantly more immunosuppressed Treg cells. After deconvolution of bulk RNA-seq data from 19 newly diagnosed AML patients, it was confirmed that Treg cells were more distributed in sarcopenic patients. Among them, 167 genes were significantly up-regulated, and the most significantly up-regulated 5 genes were ME3, UBE2E3, PCSK5, LAMC1 and PTPRF. A total of 224 significantly down-regulated genes were identified, including RNF18B, TNFAIP3, GALNT2, ORM2 and IL1R2. Pathway enrichment of differentially expressed genes was found, including signaling pathways regulating pluripotency of stem cells, Hippo signaling pathway, protein digestion and absorption pathway, etc.
Conclusion: Sarcopenia may be related to immunosuppressive microenvironment and affect the prognosis of AML patients.
First Report of Asymptomatic Solitary High-Grade B-Cell Lymphoma NOS: An Enigmatic Entity
Authors: Bugazia Seif , Gandhi Nakul , Weerakoon Niluka , Kukreja Geetika 
Published: December 2023

Background
High-grade B cell lymphoma (HGBL) is a new disease entity introduced by WHO in 2016, including two types: HGBL with a double hit (DH) or triple hit (TH) and HGBL, not otherwise specified (NOS). HGBL DH/TH are defined by genetic rearrangements of specific oncogenes MYC, BCL2 and/or BCL6, while HGBL NOS is defined purely base on morphology in the absence of these genes. HGBL DH/TH is known for its poor prognostication given its propensity to rapidly progress and disseminate, however HGBL NOS remains ill-defined and poorly understood with no tangible literature describing its clinical nature and therapeutic susceptibility.
Case presentation
A 76-year-old post-menopausal woman with no significant PMH presented for evaluation of painless hematuria during a routine office visit. Evaluation with imaging showed a suspicious incidental liver mass concerning for possible metastatic or primary liver cancer. Obtained labs were unremarkable, including serum LDH, serological testing for hepatitis B/C and HIV1/2, and typical tumor markers. PET scan showed focal uptake of tracer in liver with no nodal involvement. Liver biopsy revealed diffuse infiltration by atypical lymphocytes. Immunohistochemical analysis showed CD20 and CD10 positivity, negative CD30, and high Ki-67 proliferation rate of 100%, however the absence of MYC, BCL6, BCL2, and t(8;14) rearrangements on FISH ruled out Burkitt and DH/TH lymphoma, consistent with HGBL-NOS. Following discussions with Henry Ford Lymphoma Tumor Board, patient was treated with six cycles of R-CHOP, where follow-up imaging indicated remission of her lymphoma.
Conclusion
This represents an extraordinary first report of HGBL NOS manifesting as an isolated primary hepatic lymphoma in the complete absence of clinical symptoms. The significance of this case lies in its atypical extra-nodal site of involvement and total absence of clinical symptoms and serological markers, underscoring the unfulfilled need to further describe this enigmatic entity.
Complete Blood Count Reporting Among Hospitals in the United States
Authors: Go Lewis T , Go Lucas T , Gunaratne Madugodaralalaage DSK , Abeykoon Jithma Prasad 
Published: December 2023

Background
Complete blood count (CBC) is the most common test performed in hematology-oncology. A typical CBC report contains over 10 elements. Simplifying the report by removing nonessential elements may benefit clinicians and patients. Little is known about what elements are reported by various hospitals in the US. The objective of our study was to describe how hospitals in the US report CBC.
Methods
After approval from the Mayo Clinic institutional review board, we obtained hospital CBC reported elements from the Epic electronic medical records Care Everywhere health information exchange. CBCs from 2020-2023 were included. For each hospital, we determined the city and state where it's located. We obtained the number and type of elements reported in the CBC and compared the findings between academic and community hospitals.
Results
We collected CBC data from 139 hospitals across 43 states and 102 cities (Figure 1). Fifty-four percent were community hospitals while 46% were academic hospitals. The median number of elements reported by all hospitals was 21 (range, 12-24). This was not different (P=0.98) between academic (median 22 [range, 12-24]) and community hospitals (median 21 [range, 14-24]; Figure 2). The distribution of hospitals according to the number of CBC elements reported were as follows: 12-15 (6%), 16-19 (13%), 20 (25%), 21(6%), 22 (18%), 23 (19%), and 24 (13%). A minority of the hospitals did not report % white blood cell differential count (9.4%) or mean platelet volume (20.9%). Nucleated red blood cell and immature granulocyte count were reported frequently, 46.0% and 56.8%, respectively. However, the frequency of reporting these four elements were similar between academic and community hospitals.
Conclusions
We found substantial variations in CBC reporting among US hospitals even within academic and community hospitals. Most hospitals reported 20 or more elements, twice as many as the hospitals reporting the least number of elements. There is an opportunity to simplify and standardize CBC reporting, which will minimize physician burnout and distraction as well as decrease patient concern and query.
Interactive Pathology Tutorial in Neoplastic Hematology Disorders for Medical Hematology-Oncology Fellows
Authors: Alkhasawneh Ahmad N , Baskovich Brett , Gopinath Arun , Allan Robert W. , Mohamed Abdullah , Quan Walter JR 
Published: December 2023

Context: Hematology-Oncology (HO) fellows receive limited instruction in the process of establishing a diagnosis for hematologic neoplasms. Learning neoplastic hematology often occurs in limited encounters such as reviewing slides with pathologists or during a tumor board where the diagnosis has already been established. In the current study, we developed a web-based interactive pathology tutorial in neoplastic hematology disorders for HO fellows to work up simulated cases and establish the diagnosis.
Design: An online system (“Pathology Playground”) was utilized to load case materials including microscopic images and ancillary studies. Twelve high-yield simulated cases of common leukemias and lymphomas likely to be encountered in the daily practice, such as acute promyelocytic leukemia, were included (www.drdoubleb.com/crowdunknowns/study-set/30). At the beginning of each case, trainees review the clinical history and slide images (image 1), and then they are given the option to request additional work up, such as flow cytometry, immunohistochemistry, karyotype and/or molecular studies. Based on the results, they can enter their diagnostic impression. If the diagnosis is correct, the user is shown a short educational presentation about the entity with the key pathology findings.
Results: The tutorial was integrated in the educational curriculum of our HO fellowship program, and bimonthly teaching sessions were held to review two cases each time. During the sessions, trainees request ancillary studies to complete the diagnostic work-up using the software, and interpret the findings. As the case is being worked up by the trainee, the hematopathologists and HO fellowship program director discuss the requested work up findings, the appropriate work-up tools of the case as well as the clinical picture and the implications on the patient management. All of our six HO fellows attended the sessions, and a survey from the trainees showed high ease of use of the system and they viewed it as a very useful educational tool.
Conclusions: The interactive tutorial in hematopathology was highly received by our HO fellows, and they found it beneficial for their education. Expanding the use of this online interactive tutorial and incorporating additional cases would enhance its value as a learning resource.
Leukostasis Twist in Mantle Cell Lymphoma: Systematic Review and Case Report
Authors: Chiu Jodi , Crowther Mark A. 
Published: December 2023

Introduction:
Mantle cell lymphoma (MCL) is an aggressive B-cell non-Hodgkin lymphoma. Patients often present with lymphadenopathy, early satiety, and B-symptoms. Despite up to 92% of MCL patients having peripheral blood involvement by flow cytometry, presentation with leukemic involvement and hyperleukocytosis are uncommon.
Hyperleukocytosis, marked by a white blood count (WBC) &gt;100 x 10 9/L, often leads to symptomatic leukostasis due to tissue hypoxia, generally found in acute leukemias. We conducted a systematic review of leukostasis in MCL, and present a case we encountered in our clinical practice of a non-nodal MCL variant showing leukostasis, spontaneous tumour lysis syndrome (TLS), and severe anemia to identify treatment strategies and outcomes.
Methods:
We searched PubMed for peer-reviewed articles and abstracts on “mantle cell lymphoma,” “hyperleukocytosis,” and “leukostasis.” All articles and abstracts that discuss hyperleukocytosis leading to leukostasis in MCL were included.
Results:
The search yielded eight results. After exclusions, five case reports and abstracts were included. These studies featured different MCL variants, presenting WBCs ranging from 121 to 1227 x 10 9/L, and various leukostasis symptoms. Leukapheresis was used in all five published cases, leading to lower WBCs and symptom improvement. Results are summarized in Table 1.
Our patient was found to have the small lymphocyte variant of MCL, with WBC of 543.3 x 10 9/L on presentation. Our facility does not have leukapheresis capability. As a result, our initial treatment consisted of only supportive care and escalating doses of corticosteroids, with close monitoring for TLS. To our knowledge, this report is the first demonstration that IV methylprednisolone, without leukapheresis, is effective for acute management of leukostasis. Our patient's WBC reduced from 543.3 x 10 9/L to 230 x 10 9/L, leading to improved neurological function and oxygenation. Steroids were particularly useful in our patient with secondary, MCL-related warm autoimmune hemolytic anemia.
Conclusion:
This review highlights the importance of recognizing non-specific leukostasis symptoms, even in patients with mature B-cell lymphoproliferative disorders. Leukapheresis is effective in treating leukostasis in MCL patients. In hospitals without leukapheresis, escalating doses of IV methylprednisolone can be considered as a safe and effective strategy.
Opoid Use Disorder and Vaso-Occlusive Crisis Outcomes: A Retrospective Assesement
Authors: Sanni Abdulsabur , Goble Spencer , Linzer Mark 
Published: December 2023

Introduction
Concerns by providers for addiction can lead to under-treatment of pain in patients with sickle cell disease presenting with vaso-occlusive crisis. In patients who experience frequent vaso-occlusive crises, opioid dependence may be due to the need for pain control as opposed to addiction and the clinical meaning of a diagnosis of opioid use disorder and its impact on outcomes in this population is not known.
Methods
We retrospectively assessed hospitalizations in the United States for vaso-occlusive crisis in adult patients afflicted with Sickle cell disease from 2016-2019 using the National Inpatient Sample database. Outcomes were compared between those with and without a diagnosis of opioid use disorder using linear and logistical regression.
Results
In total, there were 273,460 hospitalizations for vaso-occlusive crisis, 23,120 (8.5%) of which involved a secondary diagnosis of opioid use disorder. Black Race was associated with opioid use disorder, but age, sex and income were not. After adjusting for confounders, hospital length of stay was increased in patients with opioid use disorder by 1.23 days (95% CI: 1.02 to 1.45, p&lt;0.001) and total hospital charges were increased by $5,566 (95% CI: 3,863 to 7,269, p&lt;0.001) (Table 1). Mortality was decreased in vaso-occulsive crisis hospitalizations in those with opioid use disorder, but the difference was not significant (OR=0.58, 95% CI: 0.026-1.33, p=0.199).
Conclusion
Opioid use disorder is associated with an increased length of stay and cost in patients with vaso-occlusive crisis. Providers should consider under-treatment of pain as a potential diagnosis when addiction concerns are present and individualized pain plans should be explored.