bluuebunny/crossref_metadata_2025_split huggingface dataset:
Retrospective Study of Intraarticular Synovectomy in Chronic Synovitis in Person with Hemophilia
Authors: Pechetty Priyanka , Shanmukhaiah Chandrakala , Mohanty Shubhranshu Shekhar , Pawar Shwetal Ghule , Patil Kirti Amol , Y Dileep 
Published: December 2024

Aim
To evaluate the safety and efficacy of Radiosynoviorthesis in Chronic Synovitis in Persons with Hemophilia.
Materials and Methods :
This retrospective observational study reviewed all radiosynoviorthesis conducted in persons with Hemophilia (PWH) from June 2016 to May 2024. Yttrium-90 (68%) was used for knee and shoulder joints. Lutetium-177(32%) was used for elbow, wrist and ankle joints.
The inclusion criteria were patients of any sex, ³8 years or older, with stage 2 and 3 haemophilic arthropathy and target joint. Exclusion criteria included patients &lt;8 years, pregnant females, those with acute bleeds, local infections, and stage 4 haemophilic arthropathy. Data were collected on resolution of target joints, functional (FISH and HJHS)and radiological score (Denver) before the procedure and at 1, 3, 6 months and 12 months post-procedure to assess the efficacy of the intervention.
Results
A total of 115 procedures were performed in 81 PWH. The median age of patients was 22 years (range: 8-62). Of all the cases, Haemophilia A were 85.3% (n=98), Haemophilia B were 10.4% (n=12), Hemophilia A with Inhibitor were 4.3% (n=5). Among all 94.4% were severe haemophiliacs and 5.6% were moderate haemophiliacs. Of 115 procedure, 57% (n=41) were knee, 25%(n=22) were elbow 13.8% (n=16) were Ankle, 3.4%(n=2) were shoulder joints. The majority 69% of patients had a good Caviglia score, while 31% had a poor score. Out of 81 PWH, 37 PWH with 56 (48.6%) procedures followed up regularly at the defined time-points and assessment was done accordingly. Out of 56 joints 50 had resolution of target joints. Median FISH, HJHS and VAS Scoring at pre procedure, 1 month, 3 months and 6 months are (27, 25, 25 and 24), (18,16,15 and 15) and (6, 5, 5 and 5) respectively with statistically significant improvement (P &lt;0.001). The Denver score didn't show any statistical difference post procedure. The procedure was safe, with two episodes of skin burns reported.
Conclusion : People who followed regularly has a decrease in the Annual Joint Bleed Rate. Radiosynovectomy is safe and effective intervention for patients with chronic haemophilic arthropathy irrespective of the type of radionuclide used
Effect of Monoferric Transferrins on Fetal Iron Homeostasis and Erythropoiesis
Authors: Shapleigh Benjamin , Ali Faris , George Nisha Ajit , Karahodzic Adin , Parrow Nermi L. , Fleming Robert E. 
Published: December 2024

Introduction: Marked changes in maternal iron metabolism and erythropoietic activity are required to meet fetal iron needs in pregnancy. Maternal iron deficiency, with or without anemia, is common despite prescribed iron supplementation. Dysregulated fetal iron accrual occurs in multiple conditions despite adequate maternal iron status and absence of anemia. These include maternal diabetes, placental insufficiency and fetal liver disease. Abnormal fetal iron status is associated with negative fetal outcomes. The processes regulating fetal/maternal iron transfer are incompletely understood. We hypothesize that signaling properties of transferrin regulate fetal-maternal iron homeostasis and fetal erythropoiesis.
Methods: We investigated the effect of lobe specificity of iron binding to the transferrin (Tf) N or C lobe on fetal iron homeostasis. We utilized female mice homozygous for either the wild-type TF allele, N-blocked TF allele (permitting iron binding only to the TF C-lobe), or C-blocked TF allele (permitting iron binding to only the TF N lobe). These were mated to mice which were either wild-type or heterozygous for the TF N-blocked or the C-blocked TF allele. At E17.5 pregnant dams were sacrificed. Placenta and fetuses were genotyped and analyzed for tissue iron concentration, expression of selected genes participating in iron homeostasis, and hematologic parameters.
Results: Litter sizes, distribution of genotypes, fetal weights and placental weights were similar in pregnancies of wild-type, N-blocked and C-blocked mice. Homozygous N-blocked fetuses (N/N) had lower hematocrits (27.5% +/-6.3) compared with homozygous C-blocked (C/C) fetuses (33.7+/-5.8%; p&lt;0.05) and wild type (WT) fetuses (42.0% +/- 3.7, p&lt;0.001). N/N fetuses had significantly higher liver iron concentrations (484.9+/-24.4 µg Fe/g dry wt) compared with C/C (322.1+/-40.1) and WT (345+/-41.0), p&lt;0.002. N/N fetuses had significantly higher hepatic Bmp6 and Hamp1 mRNA expression compared with C/C and WT fetuses. Although no significant differences were detected in placental ferroportin protein across strains, N/N fetuses had higher placental ferroportin mRNA expression compared to C/C.
Conclusions: Whereas placental iron concentration is unaffected, iron distribution across fetal hepatic and erythroid compartments is strongly influenced by the transferrin lobe occupied by iron. Despite blunted iron utilization for hemoglobin production, N/N mice accrue iron–leading to fetal hepatic iron loading, and consequently increased liver Bmp6 and Hamp1 expression. Despite the higher liver Hamp1 expression in N/N fetuses, placental ferroportin protein is similar to that observed in placentas from C/C fetuses. We speculate that any inhibitory effect of hepcidin on ferroportin protein might be offset by a hypoxia mediated upregulation of ferroportin gene expression in the setting of fetal anemia.
Racial Disparities in Survival Outcomes of Diffuse Large B Cell Lymphoma: A Retrospective Cohort Study from 2000 to 2021
Authors: Ogedegbe Oboseh John , Cheema Asfand Yar , Sukhera Ahmed Bashir , Erazo Gloria , Rodriguez Vazquez Jorge , Unlu Serhan , Godfrey Tabowei 
Published: December 2024

Introduction
Diffuse Large B Cell Lymphoma (DLBCL) is the most common type of non-Hodgkin lymphoma (NHL), accounting for 25-30% of all cases of NHL. DLBCL is an aggressive disease that can be cured in up to 50% of the patients who achieve complete remission following treatment with first-line therapy.
In this study, we described the effect of race/ethnicity on survival outcomes among patients with DLBCL in the United States.
Methods
We extracted data on patients with a primary diagnosis of DLBCL from the Surveillance, Epidemiology and End Results (SEER) Registry. These patients had a primary diagnosis of DLBCL. We excluded patients with missing or unknown deaths, and Kaplan-Meier methods were used to estimate 5-year survival rates. Cox proportional hazards regression was used for multi-variable modelling of the survival database. The difference between the observed number of events between each group was compared using a log-rank statistical test.
Results
Our analysis revealed 99,415 patients with DLCBL. 82.8% (82,356) of patients were white, 7.2% (7244) of patients were black, 0.6% (602) were American Indian/Alaska Native, and 9.3% (9213) were Asian or Pacific Islanders. The one and five-year survival by race/ethnicity was White (75.9%, 64.0%), Black (72.6%, 60.6%), American Indian/Alaska Native (72.6%,61.1%) and Asian/Pacific Islander (76.5%,63.5%). Race/ethnicity proved to be a predictor of worse outcomes, with Asian/Pacific Islander HR 0.96 (95% CI; 0.92-0.99, p = &lt;0.001), Black HR 1.01 (95% CI; 0.98-1.04, p = 0.629), American Indian/Alaska Native HR 1.06 (95% CI; 0.95-1.18, p = 0.294). There was no survival disparity by sex, male, HR 1.00 (0.98-1.02) p = 0.93.
Conclusion
Race plays a significant role in survival outcomes, with certain races associated with improved outcomes in patients with DLBCL. Asian/Pacific Islanders demonstrated a statistically significant improved survival outcome compared to whites. Of note, there was no disparity in survival outcomes by sex.
Ph− ALL: immunotherapy in upfront treatment
Authors: Stelljes Matthias 
Published: December 2024

Abstract
Antibody-based and cell-based novel immunotherapies, such as bispecific T-cell engagers (BiTE), antibody-drug conjugates, or chimeric antigen receptor (CAR) T cells are currently standard treatment options for patients with relapsed or refractory (R/R) B-cell precursor acute lymphoblastic leukemia (ALL). To date, CD20-targeting monoclonal antibodies and the CD19-targeting BiTE's blinatumomab have been established elements of frontline therapy, either in patients with CD20+ ALL or in patients with measurable disease (MRD) following conventional chemotherapy. Recently, blinatumomab has also demonstrated a survival benefit in patients with MRD-negative ALL. Based on the observed high response rates and improved survival outcomes in patients with R/R ALL, antibody-based immunotherapies are being prospectively studied in the upfront setting, particularly in older adult patients, where even age-adapted conventional chemotherapies are still associated with significant rates of early death, treatment-related toxicity, and poor prognosis. In these approaches, conventional chemotherapy has been replaced or reduced and supplemented by immunotherapeutic agents, resulting in promising outcomes that form the basis for evaluating and defining new treatment standards.
Transplant in ALL: who, when, and how?
Authors: Marcoux Curtis , Kebriaei Partow 
Published: December 2024

Abstract
Allogeneic hematopoietic stem cell transplantation (allo-HCT) remains a cornerstone in the treatment of high-risk acute lymphoblastic leukemia (ALL), yet optimal patient selection is challenging in the era of rapidly changing modern therapy. Refined molecular characterization allows for better risk assessment, sparing low-risk patients from allo-HCT toxicity while identifying those who may benefit from intensified approaches. Measurable residual disease (MRD) has emerged as a powerful predictor of relapse irrespective of treatment strategy, challenging the necessity of transplant in MRD-negative patients. Further, expanded donor options, particularly haploidentical transplantation coupled with reduced intensity conditioning, have extended the applicability of allo-HCT to a broader range of patients. Finally, immunotherapies and targeted treatments are increasingly integrated into both initial and relapsed treatment protocols yielding deep remission and allowing for successful transplant in patients with a history of advanced disease. In this review, we provide an overview of the contemporary role of transplant in adult patients with ALL, focusing on indications for allo-HCT in first remission, optimal sequencing of transplant with novel therapies, and advancements in donor selection and conditioning regimens.
Mitigating and managing infection risk in adults treated with CAR T-cell therapy
Authors: Tabbara Nadeem , Dioverti-Prono M. Veronica , Jain Tania 
Published: December 2024

Abstract
Chimeric antigen receptor T-cell therapy (CAR-T) has transformed the treatment paradigm of relapsed/refractory B-cell malignancies. Yet, this therapy is not without toxicities. While the early inflammation-mediated toxicities are now better understood, delayed hematopoietic recovery and infections result in morbidity and mortality risks that persist for months following CAR-T. The predisposition to infections is a consequence of immunosuppression from the underlying disease, prior therapies, lymphodepletion chemotherapy, delayed hematopoietic recovery, B-cell aplasia, and delayed T-cell immune reconstitution. These risks and epidemiology can vary over a post-CAR-T timeline of early (&lt;30 days), prolonged (30-90 days), or late (&gt;90 days) follow-up. Antibacterial, antiviral, and antifungal prophylaxis; growth factors and stem cell boost to expedite count recovery; immunoglobulin replacement therapy; and possibly revaccination programs are important prevention strategies to consider for infection mitigation. Assessment of risk factors, evaluation, and treatment for pathogen(s) prevalent in a particular time frame post-CAR-T are important clinical considerations in patients presenting with clinical features suggestive of infectious pathology. As more data emerge on the topic, personalized risk assessments to inform the type and duration of prophylaxis use and planning interventions will continue to emerge. Herein, we review our current approach toward infection mitigation while recognizing that this continues to evolve and that there are differences among practices stemming from data availability limitations.
Patient-reported outcomes after CAR T-cell therapy in patients with hematological malignancies
Authors: Wang Xin Shelley , Srour Samer A. 
Published: December 2024

Abstract
The remarkable improvement in survival among individuals with hematological malignancies receiving chimeric antigen receptor (CAR) T-cell therapy has highlighted the growing unmet need to incorporate patient-centered assessments in management guidelines for these patients. That CAR T-cell therapy is associated with unique toxicities and relatively high symptom burden in the first few weeks after cell infusion is well known. Magnifying the patient's voice by using patient-reported outcomes (PROs) might support personalized intervention in the acute-care setting, optimize the use of medical resources, improve satisfaction with therapy, and enhance survival benefit. However, various factors impede PRO use in routine patient care: (1) the feasibility of PRO assessment during the acute phase of treatment, especially in patients experiencing neurological toxicities, is not well established; (2) although PROs are widely used in drug- development trials, the assessment tools used in clinical trials primarily inform quality-of-life or safety comparisons among study arms and are rarely the proper tools for assessing and capturing clinically meaningful adverse events that should be monitored in routine patient care; (3) PRO data that could guide how best to monitor and capture the delayed effects of CAR T-cell therapy in long-term survivors are limited. There is a pressing need to overcome these barriers to integrating evidence-based PROs into standard-of-care guidelines for patients receiving CAR T-cell therapy. In this review, we present the current state of PRO utilization in CAR T-cell therapy. We also discuss practical approaches and future directions for successful implementation of PROs in the care of patients receiving CAR T-cell therapy.
Beyond FAScinating: advances in diagnosis and management of autoimmune lymphoproliferative syndrome and activated PI3 kinase δ syndrome
Authors: Rao V. Koneti , Pittaluga Stefania , Uzel Gulbu 
Published: December 2024

Abstract
Refractory autoimmune mutilineage cytopenias can present in childhood associated with chronic nonmalignant lymphoproliferation (splenomegaly, hepatomegaly, and/or lymphadenopathy). Cytopenias due to peripheral destruction and sequestration have been well recognized since the 1950s and are often lumped together as eponymous syndromes, such as Evans syndrome and Canale-Smith syndrome. Though their clinical and genetic diagnostic workup may appear daunting, it can provide the basis for early intervention, genetic counseling, and empirical and targeted therapies. Autoimmune lymphoproliferative syndrome (ALPS), activated phosphatidylinositol 3-kinase delta syndrome (APDS), and many other related genetic disorders are otherwise collectively known as inborn errors of immunity (IEI). They present in early childhood as refractory autoimmune cytopenias due to immune dysregulation leading to lymphadenopathy, splenomegaly, and increased susceptibility to lymphoma. More recently, controlled clinical trials have shown that some of these immune system disorders with hematological manifestations might be more readily amenable to specific targeted treatments, thus preventing end-organ damage and associated comorbidities. Over the last 20 years, both rapamycin and mycophenolate mofetil have been successfully used as steroid-sparing long-term measures in ALPS. Current therapeutic options for APDS/PASLI (phosphoinositide 3-kinase [PI3K]-associated senescent T lymphocytes, lymphadenopathy, and immunodeficiency) include the orally bioavailable PI3Kδ inhibitor, leniolisib, which was licensed by the US Food and Drug Administration (FDA) in 2023 for use in individuals older than 12 years as a targeted treatment. Paradigms learned from patients with rare genetic disorders like ALPS and APDS may help in exploring and streamlining molecular therapy strategies in the wider group of IEIs presenting with refractory cytopenias and lymphoproliferation.
Large granular lymphocyte leukemia: a clonal disorder with autoimmune manifestations
Authors: Marchand Tony , Pastoret Cédric , Moignet Aline , Roussel Mikael , Lamy Thierry 
Published: December 2024

Abstract
Large granular lymphocyte (LGL) leukemia is a rare lymphoproliferative disorder characterized by an expansion of clonal T or natural killer lymphocytes. Neutropenia-related infections and anemia represent the main manifestations. LGL leukemia is frequently associated with autoimmune disorders such as rheumatoid arthritis, Sjögren's syndrome, autoimmune endocrinopathies, vasculitis, or autoimmune cytopenia. Recent advances in the phenotypic and molecular characterization of LGL clones have underscored the pivotal role of a chronic antigenic stimulation and a dysregulation of the Jak/STAT signaling pathway in the pathophysiology linking leukemic-cell expansion and autoimmunity. In more than half of patients, there is a somatic STAT3 mutation. The disease is characterized by an indolent course, but approximately half of all patients will eventually require therapy. The first-line treatment for LGL leukemia is historically based on immunosuppressive agents (methotrexate, cyclophosphamide, or cyclosporine). However, cytokines blocking molecules or Jak/STAT inhibitors represent a new conceptual therapeutic approach for LGL leukemia. In this review, we present an overview of the spectrum of LGL proliferations, potential links between LGL expansion and autoimmunity, and therapeutic approaches.
Mutation- and MRD-informed treatment decisions for the transplant-eligible AML patient
Authors: Heuser Michael , Shahswar Rabia 
Published: December 2024

Abstract
Acute myeloid leukemia (AML) is classified by risk groups according to a number of genetic mutations, which may occur alone or in combination with other mutations and chromosomal abnormalities. Prognosis and appropriate therapy can vary significantly based on a patient's genetic risk group, making mutation-informed decisions crucial to successful management. However, the presence of measurable residual disease (MRD) after induction and consolidation therapy, before hematopoietic cell transplant, and during posttransplant monitoring can be even more significant to patient prognosis than their genetic subtype. Clinicians must select MRD-monitoring methods most appropriate for a patient's genetic profile and a treatment regimen that considers both a patient's primary genetic subgroup and other risk factors, including MRD information. Recent clinical trial data and drug approvals, together with advances in the validation of MRD using next-generation sequencing, require a deeper understanding of the complex AML mutation and MRD matrix, enabling more insightful monitoring and treatment decisions for intensively treated AML patients. Here, we provide an overview on methods and clinical consequences of MRD monitoring in genetic subgroups of patients with AML. As treatment options become more personalized, on-treatment MRD monitoring will become even more important to effective AML care.
Atypical hemolytic uremic syndrome: diagnosis, management, and discontinuation of therapy
Authors: Java Anuja 
Published: December 2024

Abstract
Atypical hemolytic uremic syndrome (aHUS) is a thrombotic microangiopathy typically characterized by anemia, thrombocytopenia, and end-organ injury. aHUS occurs due to endothelial injury resulting from overactivation of the alternative pathway of the complement system. The etiology of the dysregulated complement system is either a genetic mutation in 1 or more complement proteins or an acquired deficiency due to autoantibodies. Over the past decade, advancements in our understanding of the role of complement in the pathophysiology of aHUS as well as the availability of anticomplement drugs has been a game-changer for our patients. These drugs have revolutionized the clinical course, outcome, and prognosis of this disease. Therefore, all patients in whom aHUS is suspected should undergo testing for complement genetic variants and autoantibodies. In approximately 30% to 40% of patients, a genetic variant of uncertain significance (VUS) may be identified. Such patients should undergo further testing to define the significance of the VUS. A combination of antigenic, functional, and biomarker analyses can assist in establishing the significance of the variants and thereby define the etiology in most patients. These analyses will also help to determine the duration of treatment based on the individual's genetic alteration. This review aims to shed light on the diagnosis and management of aHUS and discusses how to stratify patients to determine who can safely discontinue anticomplement therapy.
To consolidate or not to consolidate: the role of autologous stem cell transplantation in MCL
Authors: Silkenstedt E. , Dreyling M. 
Published: December 2024

Abstract
An Ara-C-containing intensified induction therapy followed by autologous stem cell transplantation (ASCT) is considered a highly effective treatment strategy in younger mantle cell lymphoma (MCL) patients, inducing long-lasting remissions. However, ASCT is also hampered by acute and delayed toxicity. Thus, alternative first-line treatment strategies without ASCT but including novel agents are under investigation. With the recently published results of the TRIANGLE trial, showing superiority of an ibrutinib-containing immunochemotherapy induction followed by ASCT compared with the standard therapy and, more strikingly, a noninferiority of an ibrutinib-containing regimen without ASCT compared with the standard regimen with ASCT, we consider the addition of ibrutinib to first-line therapy in younger MCL patients as a new standard of care. Whether ASCT, with additional toxicity, still adds benefit to ibrutinib-based treatment in subsets of patients is not yet determined. In addition, it remains unclear how effective Bruton's tyrosine kinase inhibitor (BTKi) therapy will be in the relapsed setting for patients who received BTKi as part of first-line therapy. It also remains unclear whether the TRIANGLE data can be extrapolated to other BTKi, which is particularly relevant considering it is no longer FDA approved for MCL. Until then, individual patient characteristics and preferences, disease biology, and estimation of risk of toxicity needs to be taken into account when deciding about the addition of ASCT to an ibrutinib-containing induction therapy. For patients with TP53 aberrations, ASCT should not be recommended due to potential toxicity and limited efficacy in this high-risk subgroup. Large randomized clinical trials such as ECOG-ACRIN 4151 will help to ultimately clarify the role of ASCT.
Trousseau syndrome: management of refractory VTE
Authors: Zwicker Jeffrey I. 
Published: December 2024

Abstract
Managing recurrent and refractory venous thromboembolism (VTE) in patients with cancer presents unique challenges. This review outlines the complexities and therapeutic strategies for recurrent VTE in cancer patients, which includes distinguishing thrombus acuity, differentiating between tumor and bland thrombi, and evaluating potential contributing factors including anticoagulant adherence, extrinsic tumor compression, drug interactions, and anticoagulant-specific considerations such as heparin-induced thrombocytopenia or antithrombin deficiency. Different anticoagulation strategies are discussed, including the administration of escalated-dose low molecular weight heparin (LMWH) as well as the indications and rationale for switching between direct oral anticoagulants or LMWH.