bluuebunny/crossref_metadata_2025_split huggingface dataset:
Rare Instance and Pathophysiological Insights of Thrombotic Thrombocytopenic Purpura Following Pacemaker Implantation
Authors: Dhami Dana , Solowiej Singh Christopher , Dhami Sabina 
Published: December 2024

This is the case of a 71-year-old female with past medical history of atrial fibrillation status post ablation 2 months ago currently on apixaban, hypothyroidism, remote history of breast cancer treated with radiation therapy and mastectomy, thyroid cancer status post thyroidectomy, and non-hodgkin's lymphoma (marginal zone lymphoma) treated with bendamustine and rituximab chemotherapy in 2019 followed by rituximab maintenance through 2021. She initially presented with a 4-day history of progressively worsening weakness and altered mental status. She was noted to have significant expressive aphasia and was only oriented to person on admission. Eight days before admission, the patient had a pacemaker placed which she tolerated well. She denied any facial droop, facial weakness, or difficulty walking. She also endorsed a 4-day history of diarrhea with red-tinged bowel movements but denied associated abdominal pain, frank blood or melena.
Stroke workup was initiated and CT head was negative for acute findings. Labs revealed a hemoglobin of 11.4, platelet count of 16,000, GFR of 48, and bilirubin of 4.4. Coagulation studies and fibrinogen studies were within normal limits. LDH was elevated to 1019 and haptoglobin was low. ADAMTS 13 level was ordered, and the patient was subsequently started on high-dose steroids (solumedrol 1g daily) as well as plasma exchange with FFP transfusion due to concerns of thrombotic thrombocytopenic purpura (TTP). After the initiation of treatment, the patient had an uptrend in her platelets and resolution of neurologic symptoms. Repeat labs showed ADAMTS13 of &lt; 2.0 confirming the diagnosis of TTP.
Thrombotic thrombocytopenic purpura (TTP) following pacemaker implantation is a rare but potentially life-threatening complication. The pathophysiology of TTP involves the formation of microthrombi in small blood vessels leading to thrombocytopenia, hemolytic anemia, and organ damage. This condition is typically associated with a severe deficiency of ADAMTS13, a protease responsible for cleaving large von Willebrand factor (vWF) multimers. During pacemaker implantation, endothelial injury and increased shear stress promotes the release and accumulation of large vWF multimers, which leads to widespread microthrombosis in the presence of an ADAMTS13 deficiency.
The incidence of TTP after pacemaker implantation is extremely low, with few cases reported in the literature. This rarity underscores the importance of recognizing this potential complication as timely diagnosis and treatment with plasma exchange can be lifesaving.
Other potential causes of TTP include autoimmune disorders (e.g. systemic lupus erythematosus), infections, certain medications (e.g., quinine, ticlopidine, clopidogrel), malignancies, and pregnancy. In these cases, the underlying pathophysiological mechanisms often involve the production of autoantibodies against ADAMTS13, leading to its functional deficiency and subsequent microthrombi formation.
CRISPR Cas-9 Editing for Treating Sickle Cell Disease: A Systematic Review and Meta-Analysis
Authors: Desai Karna , Croce Phillip , Dadhania Nain , Mirza Wasique , Hanif Ahmad , Thalji Mousa , Sharma Rohit 
Published: December 2024

Introduction
Exagamglogene autotemcel (exa-cel) represents a novel nonviral cell therapy aimed at reactivating fetal hemoglobin synthesis through the ex vivo application of clustered regularly interspaced short palindromic repeats (CRISPR)-Cas9 gene editing. This process targets autologous CD34+ hematopoietic stem and progenitor cells (HSPCs) at the erythroid-specific enhancer region of BCL11A. We performed a systematic review and meta-analysis of all clinical studies related to this therapy to evaluate its efficacy and safety in treating sickle cell disease (SCD).
Methods
A comprehensive search strategy was employed, incorporating keywords such as “CRISPR,” “exagamglogene autotemcel,” and “sickle cell disease.” The databases PubMed, Embase, and Medline were utilized to identify relevant studies. Inclusion criteria were based on clinical trials involving CRISPR/Cas9 gene editing for SCD treatment.
Results
A total of 34 patients were included in the analysis, comprising 26 males and 8 females with an average age of 25.51 years. The predominant genotype was βS/βS, observed in 30 patients. Key findings included an annualized rate of severe vaso-occlusive crises of 4.14, an average total hemoglobin level of 8.3 g/dL, and an average fetal hemoglobin level of 5.5 g/dL. The median number of mobilization cycles was 2. At 12 months, 32 out of 34 patients were free from vaso-occlusive crises, and 33 out of 34 were free from hospitalizations. The p-value for these outcomes was less than 0.0001, assuming a null hypothesis of a 50% response rate.
Discussion
Sickle cell disease (SCD) is a prevalent monogenic blood disorder characterized by severe pain, organ damage, and reduced life expectancy. Treatment options are notably limited, with hematopoietic stem cell transplantation from a matched related donor being the only curative approach. The ex vivo modification of autologous hematopoietic stem and progenitor cells, followed by transplantation of these genetically modified cells, offers a potential permanent cure applicable to all patients, regardless of donor availability or the risk of graft-vs-host disease. This review emphasizes the application of CRISPR/Cas9 gene editing in treating SCD, focusing on the correction of the β-globin (HBB) mutation and the induction of fetal hemoglobin to counteract cell sickling. We highlight significant accomplishments and challenges within this field, providing insights into the future potential of gene-editing therapies for curing SCD.
Investigating the Biomarker Role of Long Non-Coding RNAs in Pediatric Precursor B-Cell Acute Lymphoblastic Leukemia
Authors: Almási Laura , Horváth Ágoston , Oláhné Szabó Rita , Csanádi Krisztina , Pálóczi Krisztina , Kutszegi Nóra , Péterffy Borbála , Hegyesi Hargita , Erdelyi Daniel J 
Published: December 2024

Introduction:
The diagnosis of childhood acute lymphoblastic leukemia (ALL) typically relies on cell detection from bone marrow (BM) and cerebrospinal fluid (CSF). Existing BM-based methods, while sensitive, are invasive, time-consuming, and laborious.
Central nervous system (CNS) involvement in ALL negatively impacts prognosis. However, routine CNS diagnostic methods yield a high percentage of false negative results. While blasts primarily adhere to the meninges in CNS involvement, molecules secreted by blasts might escape and diffuse more easily into the CSF. Long non-coding RNAs (lncRNAs) are non-coding polynucleotides with specific expression patterns for different cell types, maturation stages, and diseases.
Methods:
De novo precursor-B cell (pre-B) ALL patients under 18 years of age, diagnosed between 2016 and 2023 and treated as per the ALL IC-BFM 2009 protocol were enrolled. Samples from bone marrow aspirate (BM), peripheral blood (PB), and cerebrospinal fluid (CSF) were collected, centrifuged, and separate cell-containing and cell-free aliquots were stored.
An 89-target screening QPCR plate was built after a comprehensive literature search to find lncRNAs significant in ALL and B-cell development. Multiple RNA isolation methods were tested to suit the different body fluids. The lncRNA expression was measured in two experimental setups: 1) The QPCR screening was executed on 11 patients' day 0 and day 33 cell-free BM samples. 2) Five lncRNAs significantly overexpressed on day 0 were selected for droplet digital PCR (ddPCR) measurements on cell-free BM, PB, and CSF samples.
Results:
In the screening, five lncRNA targets had significantly higher expression in day 0 cell-free BM samples compared to day 33 samples, namely LINC01013 (p=0.007), AC002464.1 (p=0.013), AC002454.1 (p=0.035), BX293535.1 (p=0.006), LINC00958 (p=0.036). The 5-lncRNAs were well detected by ddPCR in cell-free BM and PB samples, but no significant signals were gained from the 300-700 μl volume CSF samples.
Conclusions:
The transcriptomic exploration in cell-free BM identified five lncRNAs as potential pre-B ALL biomarkers for further research. Low CSF lncRNA concentrations question their suitability as biomarkers in this compartment.
Primary Pulmonary Follicular Lymphoma - a Rare Presentation of Non-Hodgkin Lymphoma
Authors: Panchal Megha , Arunachalam Janani , Memon Ahsan , Pilathodan Hashwin , Sripathi Keerthi , Rawal Shalin , Bagga Arindam , Sandhu Jujhar , Varma Samyukta , Atodaria Kuldeepsinh , Yarlagadda Bhavya Raja Gopal , Biswas Navanita , Parvataneni Tarun 
Published: December 2024

INTRODUCTION
Primary pulmonary lymphoma (PPL) is an uncommon form of non-Hodgkin lymphoma that begins in the lungs. PPL originates directly within the lung tissue, unlike more prevalent lymphomas that frequently metastasize to the lungs from other sites. Lung primary non-Hodgkin lymphoma (NHL) is an exceptionally uncommon condition, representing approximately 0.4% of all malignant lymphomas. Only 3-4% of non-Hodgkin lymphoma (NHL) that does not start in lymph nodes is primary pulmonary lymphoma (PPL). This is less than 1% of all NHL cases and 0.5-1% of all primary lung cancers. Here we present a rare case of primary pulmonary follicular lymphoma characterized by bilateral pleural effusion.
AIM
The main objective in managing primary pulmonary lymphoma (PPL) is to promptly identify, precisely diagnose, and efficiently treat the condition to enhance patient outcomes. This entails increasing knowledge, employing sophisticated diagnostic methods, precisely determining the stage of the disease, and creating personalized treatment strategies.
CASE REPORT
A 74-year-old male patient presented with shortness of breath that was progressively worsening for 3 to 4 weeks. The patient denied having fever, chills, sweating, unexpected weight loss, or lymphadenopathy in the armpit, neck, or groin. The patient had no prior history of lung disease, and he did not use home oxygen or inhalers. The patient smoked up to 1 pack of cigarettes daily for 10 years but quit in 1995. He was initially treated with antibiotics, but the dyspnea persisted. A chest X-ray and CT angiogram were done at the time, which displayed bilateral pleural effusions, moderate on the right and small on the left, and no evidence of pulmonary thromboembolic disease. Therapeutic and diagnostic aspirations had been made. The cytology of the fluid was suggestive of exudative and found negative for malignant cells. Despite initial negative cytology for malignant cells, the patient returned 2 weeks later with dyspnea and increased bilateral pleural effusions from prior studies. A second thoracocentesis and analysis of the fluid, using flow cytometry and FISH, showed a single group of B cells that were positive for lambda CD10. This is a sign of follicular lymphoma, which is supported by changes in BCL6, BCL2, and t(14:18)/IGH-BCL2.
CONCLUSION
In summary, this case adds to the existing knowledge about the various ways NHL can present and supports the need for a comprehensive approach to caring for patients with pleural effusion. It also highlights the importance of early detection and prompt initiation of treatment for unexpected cancer cases, improving results through focused therapeutic approaches.
Brentuximab Vedotin-Based Treatment in Patients with CD30-Positive Lymphoma: A Retrospective Analysis
Authors: Li Yixue , Zeng Ruolan , Xia Chen , Li Yajun , He Yizi , Wang Caiqin , Zhou Hui 
Published: December 2024

Background:
Brentuximab vedotin (BV) is an antibody-drug conjugate targeting CD30 which has been approved for the treatment of adult patients with CD30-positive lymphomas, specifically relapsed or refractory systemic anaplastic large cell lymphoma (sALCL) and classical Hodgkin lymphoma (cHL). This study presents a retrospective analysis of BV's efficacy and safety in CD30-positive lymphoma patients at our institution.
Methods:
This study included CD30-positive lymphoma patients treated with BV from July 2020 to April 2024. The primary endpoint was the overall response rate (ORR). The secondary endpoints were complete response (CR) rate, progression-free survival (PFS), overall survival (OS) and adverse events (AEs). Efficacy was assessed based on the 2014 Lugano Conference, and treatment-related AEs were evaluated according to CTCAE5.0.
Results:
A total of 66 patients were analyzed. The median age at diagnosis was 40 years (range: 15-79 years), with 43 (65.1%) being male. The patient cohort included 39 (59.1%) with cHL, 26 (39.4%) with peripheral T-cell lymphoma (PTCL), and 1 (1.5%) with primary mediastinal large B-cell lymphoma (PMBL). Two (3.0%) had previously undergone stem cell transplantation. The median number of prior chemotherapy lines was 0.5 (range: 0-7). B symptoms were present in 24 (36.4%). 5 (7.6%) had an ECOG score ≥ 2 and 43 (65.2%) exhibited extranodal disease. 22 patients (33.3%) had spleen involvement and 38 (57.6%) had elevated erythrocyte sedimentation rate at diagnosis. Disease progression was noted in 26 (39.4%) prior to BV treatment. BV was combined with chemotherapy in 65 patients (98.5%), while 1 patient (1.5%) received BV monotherapy. The median follow-up time was 13.75 months. There were 6 deaths due to tumor progression, 1 due to low platelet count, and 1 patient due to pulmonary embolism. The median PFS and OS were not reached. The ORR was 89.4% (59/66) and the CR rate was 66.7% (44/66). Common AEs included leukopenia (30.3%) and anemia (10.6%), with other AEs being abnormal liver function, nausea, fatigue, gastrointestinal reactions, numbness of the limbs, rash, decreased appetite, etc. Grade 3-4 AEs comprised of leukopenia (15.1%).
Conclusions:
BV shows significant efficacy in treating CD30-positive lymphoma with acceptable safety, supporting its role as a valuable therapeutic option for these patients.
Bone Marrow Endothelial Progenitor Cells Are Involved in Resistance to Tyrosine Kinase Inhibitors in Chronic Myeloid Leukemia
Authors: Yu Shunjie , Yuan Mengyao , Bao Mei , Zhang Xiaoshuai , Jiang Qian 
Published: December 2024

Background Tyrosine kinase inhibitor (TKI) resistance is a significant challenge in chronic myeloid leukemia (CML). Data of endothelial progenitor cells (EPCs) from bone marrow microenvironment in TKI resistance are limited.
Aims To explore whether EPCs are associated with TKI resistance in patients with CML.
Methods EPCs were isolated from TKI-sensitive or resistant patients with CML using Ficoll-Hypaque density-gradient centrifugation for co-culture with K562 cells ± TKIs. The number of EPCs and apoptosis level of K562 were detected by flow cytometry. Tube formation and migration assays were performed to evaluate the functions of EPCs. RNA sequencing was employed to analyze gene expression profiles of EPCs and K562 cells.
Results Compared with those from TKI-sensitive patients, the number of EPCs from TKI-resistant patients was reduced (0.07% ± 0.01% vs. 0.11% ± 0.02%, p = 0.139), tube formation (17005 ± 3561 vs. 41084 ± 3693, p = 0.003) and migration ability of the EPCs were impaired (103.2 ± 17.41 vs. 202.0 ± 14.59, p &lt; 0.001). Moreover, EPCs from TKI-resistant patients exhibited higher level of reactive oxygen species (2683 ± 158 vs. 2170 ± 320, p = 0.211). Co-culture experiments demonstrated that contact-dependent endothelial-mediated resistance to imatinib was observed in the EPCs from TKI-resistant patients, characterized by reduced K562 apoptosis (22.51% ± 1.52% vs. 36.58% ± 1.88%, p &lt; 0.001) and G0/G1 phase (31.30% ± 3.05% vs. 43.10% ± 3.59%) compared with that from TKI-sensitive patients, and similar phenomenon also occurred when nilotinib or ponatinib replaced imatinib. KEGG pathway enrichment analyses showed that cell adhesion, immune and inflammatory related pathways were enriched in EPCs from TKI-resistant patients and K562 cells co-cultured with TKI-resistant EPCs.
Conclusions Our findings suggested that EPCs from TKI resistant CML patients were dysfunctional which might contribute to TKI resistance.
Ptcy Overcomes HLA Mismatch in Unrelated Donor Transplant for Acute Lymphoblastic Leukemia: A Study from the ALWP of the EBMT
Authors: Sanz Jaime , Ferhat Allain-Thibeault , Kulagin Aleksander , Kröger Nicolaus , Rovira Montserrat , Lazzari Lorenzo , Arat Mutlu , Montoro Juan , Versluis Jurjen , Reményi Péter Pál , Sica Simona , Blaise Didier , Saif Muhammad , Vydra Jan , Fagioli Franca , Nur Erfan , Giebel Sebastian , Piemontese Simona , Mohty Mohamad , Ciceri Fabio 
Published: December 2024

Background: Post-transplant cyclophosphamide (PTCy) seems to mitigate the disparity in outcomes between use of matched (MUD) or mismatched Unrelated Donors (MMUD) hematopoietic stem cell transplantation (HSCT), but there are no specific studies in patients with acute lymphoblastic leukemia (ALL).
Methods: We retrospectively analyzed the characteristics of 8/8 MUD and 7/8 MMUD that may affect transplant outcomes in patients with ALL in complete remission (CR) who received a first peripheral blood allogeneic HSCT with PTCy between January 2010 and December 2022, registered in the EBMT database. The primary endpoint was leukemia-free survival (LFS).
Results: Overall, 350 patients were included with a median age of 37 years (range, 18-76), and 231 (66%) were in first CR. 280 (80%) patients had B-cell ALL of which 101 (29%) were Philadelphia positive. Regarding donors, median age was 28.8 years (range, 18-57), 237 (68%) were MUDs and 113 (32%) were MMUDs. Patient, donor and transplant characteristics were equally distributed across donor types except for older donor age, more frequent recipient male sex (58%) and use of TBI containing myeloablative conditioning in MMUD transplants (55%). The 180-day cumulative incidence of acute graft-versus-host disease (GVHD) grade II-IV and III-IV was 28% (95% CI 23-33) and 9% (95% CI 6-12), respectively, while the 2-year cumulative incidence of chronic and chronic extensive GVHD was 28% (95% CI 23-34) and 12% (95% CI 9-17), respectively. After a median follow-up of 24 months, the cumulative incidence of relapse and non-relapse mortality and the probabilities of LFS, overall survival (OS) and GVHD-free, relapse-free survival (GRFS) were 24% (95% CI 19-29), 15% (95% CI 11-19), 62% (95% CI 56-67), 73% (95% CI 67-78) and 48% (95% CI 42-54), respectively. The use of MUD or MMUD did not have a significant impact on LFS (hazard ratio [HR] 0.84; 95% CI 0.56-1.24) or any other transplant outcomes. Considering other donor related variables, the use of female donor to male recipient increased the risk of acute GvHD grade II-IV (HR 1.78; 95% CI 1.05-3, p=0.03) and the use of older donor age increased grade III-IV (HR 1.7; 95% CI 1.1-2.64, p=0.02). Additionally, CMV-neg donor for CMV-neg recipient was associated with improved LFS (HR 0.55; 95% CI 0.32-0.96, p=0.034) and overall survival (HR 0.52; 95% CI 0.28-1,p=0.49).
Conclusions: For patients undergoing HSCT from an unrelated donor with PTCy for ALL in CR the use of MMUDs does not negatively affect outcomes. Other donor related variables such as age, gender and CMV serostatus might be prioritized over HLA match considerations.
Comparative Efficacy of Carfilzomib, Lenalidomide and Dexamethasone (KRD) Vs. Daratumumab, Bortezomib, Lenalidomide and Dexamethasone (DVRD) in Newly Diagnosed Multiple Myeloma: A Systematic Review and Meta-Analysis
Authors: Wang Yuqi , Huan Chen , Hanzhen Zhang , Zhang Shanshan , Yuan Youhai , Feng Ru , Wei Yongqiang , Wei Xiaolei 
Published: December 2024

Background: Daratumumab in combined with bortezomib, lenalidomide and dexamethasone (DVRD) or carfilzomib, lenalidomide and dexamethasone (KRD) has been recommended as first-line induction regimen in patients with newly diagnosed multiple myeloma (NDMM). However, the superiority of these two regimens remains unknown. Given the lack of head-to-head clinical trials, this study systematically reviewed the clinical studies regarding DVRD and RVD regimen in the treatment of NDMM to explore the better choose of the first-line therapy.
Methods: We searched in the Cochrane Library, PubMed, Embase, and Web of Science databases to collect studies containing DVRD or KRD for NDMM, then we performed pooled and meta-analysis to compare overall response rate (ORR), complete remission(CR) rate, stringent complete remission (sCR) rate, minimal residual disease (MRD)-negative status, progression-free survival (PFS), overall survival (OS) and treatment-related discontinuation rate, grade 3-4 adverse events rate between DVRD and KRD regimen by using R 4.3.3 software.
Results: Of 3570 studies screened, 6 randomized controlled trial and 8 single-arm clinical trial were eligible including 483 patients treated with DVRD and 1509 treated with KRD. We found a statistically non-significant difference in therapeutic response including ORR, CR, sCR and MRD-negative status between DVRD and KRD regimen. Compared to KRD regimen, patients treated with DVRD were associated with improved PFS (not reached vs. 58.24 months, pool HR 0.41; 95%CI 0.32-0.53) and OS (both were not reached, pool HR 0.64, 95%CI 0.45-0.90). The grade 3-4 adverse events rate between DVRD and KRD regimen was non-significant statistical different while the therapy discontinuation rate led by adverse events was significantly lower in patients treated with DVRD than those treated with KRD (2% vs. 6%, P=0.01).
Conclusion: This meta-analysis indicated that DVRD regimen as first-line induction treatments could bring patients with NDMM with better outcomes and lower treatment-related discontinuation rate than KRD regimen.