bluuebunny/crossref_metadata_2025_split huggingface dataset:
Incidence and Outcomes of Post-Transplant Erythrocytosis in Kidney Transplant Recipients: A Cohort Study in a Southeast Asian Country
Authors: Wannaphut Chalothorn , Skulratanasak Peenida , Saetan Suparat , Aiumtrakul Noppawit , Ponvilawan Ben , Larpparisuth Nuttasith , Ratchawang Nartsiri , Owattanapanich Weerapat 
Published: December 2024

Introduction: Post-kidney transplant erythrocytosis (PTE) is a common complication after kidney transplant, which can occur in 8-15% of transplant recipients. However, this condition, including the Thai population, has not been well studied in Southeast Asia.
Method: A single-center retrospective cohort was conducted among adult kidney transplant recipients who underwent transplantation between January 2010 and December 2020. Erythrocytosis is defined by hemoglobin levels &gt; 16.5 g/dl in males and &gt; 16.0 g/dl in females. We assessed the incidence and risk factors of PTE in this cohort and compared outcomes of PTE versus non-PTE patients.
Results: Of 399 kidney transplants, 84 (21%) developed PTE over a total follow-up time of 5.06 ± 2.16 years. The mean age was 44.36 ± 10.59 years, with 57.1% of male subjects. All PTE patients were asymptomatic during the clinical course of PTE. The median duration of PTE was 8.83 (5.55 - 18.17) months. In the multivariable analysis, male subjects were at a 1.92-time higher risk for PTE development than females (HR 1.92; 95%CI 1.16-3.20). Patients with pre-existing polycystic kidney disease (PKD) had a 3.87-time higher risk of developing PTE compared to those without PKD (HR 3.87; 95%CI 1.50-9.98). PTE patients significantly had a 50% lower risk for composite outcomes, including infection, new onset diabetes, transplant rejection, dialysis dependence, and death, compared to non-PTE groups (HR 0.50; 95%CI 0.27 - 0.9). Interestingly, none of the PTE patients underwent renal replacement therapy throughout the observation, while some non-PTE individuals became dialysis dependent.
Conclusion: Our study revealed the incidence rate of PTE was 0.05/person-year. PTE in Thai patients was strongly associated with male gender and pre-existing PKD. Patients with PTE tended to have higher eGFR. They had a significantly lower risk of developing composite outcomes, including infection, new-onset diabetes, rejection episodes, dialysis dependence, and mortality, compared to those without PTE.
What If the Erythrocyte Sedimentation Rate (ESR) Is Too Slow? New Parameters. New Explanations. New Applications
Authors: Darras Alexis , Qiao Min , Peikert Kevin , Hecksteden Anne , John Thomas , Stauffer Emeric , Muniansi Ingrid , Champigneulle Benoit , Pichon Aurelien , Furian Michael , Hancco Ivan , Brugniaux Julien V. , Nader Elie , Mühlbäck Alzbeta , Joly Philippe , Meyer Tim , Verges Samuel , Hermann Andreas , Connes Philippe , Wagner Christian , Kaestner Lars 
Published: December 2024

The erythrocyte sedimentation rate (ESR) is one of the oldest diagnostic tools already known by the ancient Greeks. When blood is placed in a tube, a phase separation between blood plasma and the remaining part of the blood containing the cells appears. The distance between the top of the liquid and the phase boundary determines the sedimentation height. Fast sedimentation, typically the height measured after one hour, is an unspecific parameter indicating inflammation. However, there is more to ESR than a single value for the sedimentation height. We investigated the physical dynamics of the cell aggregation occurring during erythrocyte sedimentation and devised a novel explanation. The formation of rouleaux actually extends to the formation of a percolating gel. Therefore, it is not the aggregate size that determines ESR but the permeability of this gel. The collapse of this gel is the base of the ESR. Hence the process of erythrocyte sedimentation can be described by a set of parameters determined by this gel. In addition to differences in height, the delay time, the maximal sedimentation speed and the final compaction resemble the most important ones.
In contrast to common clinical practice, where only a fast ESR is associated with pathologic conditions, we identified diseases and circumstances when the ESR is significantly slower. This includes the ESR of Sickle Cell Disease (SCD) patients, Chronic Mountain Sickness (CMS) patients, patients suffering from the Neuroacanthocytosis Syndromes (NAS) on the one hand and endurance elite athletes and highlanders on the other hand.
Significant differences can be detected between healthy controls and the patients listed using the aforementioned parameters. However, diagnostic value is only given if a clear discrimination between patients and healthy controls is possible. We found such discrimination for NAS patients with 8% false negative and 11% false positive among healthy controls. For differential diagnosis, we also tested patients with neurodegenerative diseases different from NAS, namely Parkinson's disease patients, Huntington's disease patients and amyotrophic lateral sclerosis patients. None of them showed a difference in the ESR compared to healthy controls, but all of them presented a significant difference to NAS patients.
Considering the low expenses required for ESR measurements and that they are automated in many central laboratories on the one hand and the difficulty and often very late diagnosis of NAS (sometimes years after the onset of symptoms), we recommend an ESR screening for NAS (slow sedimentation) as a routine in the frame of ordinary health checks of adults.
Phase II Clinical Trial on Chidamide, Rituximab and High-Dose Methotrexate (C-R-HDMTX) in Newly Diagnosed Primary CNS Lymphoma
Authors: Chen Guang-Liang , Jin Jia , Sun Hui , Liu Yizhen , Zhang Qunling , Xia Zuguang , Cao Junning , Hong Xiaonan , Lv Fangfang 
Published: December 2024

Abstract
Background:
Primary Central Nervous System Lymphoma (PCNSL) is an aggressive non-Hodgkin lymphoma variant confined to the central nervous system. Current treatment primarily uses high-dose methotrexate (MTX) with rituximab, but incomplete responses and relapse are common. Chidamide, an oral histone deacetylase (HDAC) inhibitor, can cross the blood-brain barrier, achieving therapeutic concentrations in cerebrospinal fluid. In addition, it enhances MTX efficacy by promoting its polyglutamylation and regulating key genes. This study investigates the potential of combining chidamide with rituximab and high-dose MTX (C-R-HDMTX) in PCNSL treatment.
Methods:
This single-center, open-label, phase II trial administered C-R-HDMTX every three-week for six courses unless disease progression, death, or intolerable toxicity. The primary endpoint was complete remission (CR) rate. Progression-free survival (PFS) was also assessed. Treatment included chidamide (20 mg orally, twice weekly for two weeks, followed by a one-week break), rituximab (375 mg/m² IV, day 1), and MTX (3.5 g/m² IV, day 2) per 21-day cycle. Responses were evaluated using the international PCNSL collaborative group (IPCG) criteria after 2-4 cycles.
Results:
Between September 7, 2020, and August 26, 2023, ten patients (7 males, 3 females) were enrolled. The median age was 62 years (range, 50-76). Overall, 8 patients had non-germinal center B-cell-like (non-GCB) subtype, 2 patients had GCB subtype. Nine patients were evaluable for efficacy. Six patients exhibited multiple enhancing lesions. The overall response rate at the end of induction was 89%, with a CR rate of 78% (7/9 patients). With a median follow-up of 16.5 months (range 11.0-46.5)，the median PFS was 13 months, with the longest ongoing at 46.5 months. The median OS was not achieved. Grade 3/4 hematologic toxicities included neutropenia and thrombocytopenia (20% each). Common non-hematologic adverse events were mild, including hypocalcemia (80%), hyponatremia and elevated AST (50% each), and increased ALT (30%).
Conclusions:
The C-R-HDMTX regimen demonstrated high efficacy and manageable toxicity in PCNSL patients, warranting further investigation as a potential treatment option for this aggressive lymphoma.
Clinical trial information: NCT04516655
Novel Nilotinib Tablet Formulation: Pharmacokinetic Characterization and Effects of Food
Authors: Mauro Michael J. , Radich Jerald P. , Jain Paras , Sequeira David , Douer Dan 
Published: December 2024

Introduction: Nilotinib is a BCR-ABL1 tyrosine kinase inhibitor with demonstrated efficacy in patients with Philadelphia chromosome-positive chronic myeloid leukemia (CML). Use of the drug is limited by a boxed warning and a specific dosing regimen that increases treatment complexity. The prescribing information for nilotinib capsules states that they should be administered on an empty stomach and with no food consumed for ≥2 hours (h) before and ≥1 h after dosing. A novel reduced-dose tablet formulation of nilotinib has been developed to provide equivalent bioavailability (BA) under fasted conditions and minimize the effect of food on pharmacokinetics (PK).
Objective: To characterize the PK profile of a novel film-coated tablet formulation of nilotinib, assess the effects of food on nilotinib relative BA, and compare its PK profile to that for nilotinib capsules.
Methods: The PK of nilotinib capsules (300 or 400 mg) and/or novel film-coated tablets (142 or 190 mg) were evaluated in 6 open-label, randomized, single-dose, crossover studies that enrolled a total 384 healthy volunteers. Nilotinib tablets were administered under prandial conditions defined as: (1) fasting, (2) high-fat meal: fasting for 10 h overnight and administration of study drug 2 h after the start of a high-fat, high-calorie, non-vegetarian breakfast, and (3) low-fat meal: fasting for 10 h overnight and administration of study drug 2 h after the start of a low-fat, low-calorie breakfast. Comparison of the PK profiles and formal statistical evaluation was conducted for bioequivalence (BE) of the nilotinib tablet to nilotinib capsule for all of these conditions.
Results: In the fasted state, BE was established for a 142 mg dose of nilotinib tablet with the 300 mg dose nilotinib capsule and for the 190 mg dose of nilotinib tablet with 400 mg dose nilotinib capsule. Nilotinib tablets (142 mg and 190 mg dose) administered in both fed conditions resulted in higher maximum plasma concentrations (Cmax) and areas under the time vs. plasma concentration curve from administration extrapolated to infinity (AUC0-inf) than the observed fasted state. For nilotinib tablets, the increases in Cmax and AUC0-inf were 55% and 59%, respectively for the 190 mg dose when delivered with a low-fat meal and 66% and 64% when delivered with a high-fat meal. The respective values for 400 mg nilotinib capsules delivered with a low-fat meal were 122% and 101% and those for administration with a high-fat meal were 275% and 210%.
Conclusions: Reduced-dose nilotinib film-coated tablets (142 and 190 mg) provide exposures comparable to 300 and 400 mg nilotinib capsules in the fasted state. The PK profile for nilotinib film-coated tablets also results in much smaller increases in exposure vs. the capsules when the drug is taken with food.
Artificial Intelligence-Based Algorithm for the Diagnosis of Idiopathic Multicentric Castleman's Disease in a Lower-Middle Income Country
Authors: Brandão Antonio Adolfo Guerra Soares , De Farias Danielle Leão Cordeiro , Konopelko Michał , Amtmański Wojciech , Mroz Mikolaj , Jurczuk Aleksandra , Majewski Maciej , Szukalski Lukasz , Basak Grzegorz , Verboski Bianca Milena , de Assunção Caio Lopes , Lis Karol , Dabrowski Michal Jerzy , Dudziński Marek 
Published: December 2024

Introduction
Idiopathic multicentric Castleman's disease (iMCD) is an ultra rare lymphoproliferative disorder difficult to diagnose due to its rarity (prevalence of 6.9-9.7 cases per million in the United States) and the lack of awareness among physicians. Median time between symptoms onset and the diagnosis of iMCD in Brazil is estimated to be 18 months. We propose that an artificial intelligence (AI)-based algorithm working on electronic health records may help to identify patients suspected of Castleman disease that were missed during medical evaluation.
Methods
Firstly, symptoms listed in the CDCN iMCD criteria [Fajgenbaum DC, et al. Blood. 2017;129(12):1646-57] were defined by medical terms. Medical definition contained ICD - 10 codes, lab test results and phrases that may be found in the medical texts (descriptions of imaging tests, interviews, epicrisis). SPACY models with in house developed regular expressions (regex) were used to identify phrases (entities) assigned to symptoms in the unstructured medical texts. Entity context defined as negation, family relation, historical or hypothetical event was determined by the BERTH model that went through additional training on the Saventic database. Patients were ranked based on the symptoms they possessed. Patients were ranked only when lymphadenopathy was identified and patients already diagnosed with iMCD (four cases) were excluded. Physicians with expertise in iMCD led the review of patients' charts with the highest score.
Results
594 953 patients' charts from a tertiary Brazilian hospital were screened by the algorithm and iMCD clinical and/or laboratory features were identified in 102 patients, which had higher probability of having iMCD. Of those, 12 had mimicker conditions with overlapping iMCD features and three others required further assessment.
Conclusion
This AI driven tool was able to identify patients who have iMCD features. Screening with this tool found at least three candidates for additional evaluation. In the future, algorithms like the one we present may facilitate screening for iMCD.
Pre-Clinical Evaluation of AZD5492, a Novel CD8-Guided T Cell Engager, for B-Non Hodgkin Lymphoma Indications
Authors: Lawrence Rachel , Cayatte Corinne , Izuzquiza Fernandez Macarena , Rata Scott , Ciucci Thomas , Lin Wen , Lara Abigail , Jafarzadeh Nazli , Foreman Taylor , Payne Sterling , Shandilya Harini , Sambamurthy Nisha , Luo Haibin , Stebbings Richard , Dovedi Simon , Gorgun Gullu , Mato Anthony , Cemerski Saso , Cobbold Mark , Younes Anas 
Published: December 2024

Introduction
Non-Hodgkin lymphomas (NHL) include diverse neoplasms of the lymphoid compartment, with the majority originating from the B-cell lineage. Bispecific CD20xCD3 T cell engagers (TCEs), both monovalent and bivalent, have shown promising rates of ORRs and CRs in the clinic leading to several FDA approvals for the treatment of R/R DLBCL and FL. However, these treatments are still associated with significant toxicities, including CRS and ICANS, limiting their therapeutic window and potential for clinical combinations.
Methods
We engineered a first-in-class CD8-guided TCE, AZD5492, for B-NHL malignancies. AZD5492 is an asymmetric, trispecific monoclonal IgG1 antibody which harbors two Fab binding domains to CD20, one VHH binding domain to TCR, one VHH binding domain to CD8 co-receptor. AZD5492 binding, cytolytic activity, and efficacy were extensively interrogated in vitro and in vivo, in murine models and in non-human primates (NHP).
Results
The VHH domains of AZD5492 allow preferential engagement of CD8+ T cells through CD8/TCR binding, leading to the formation of an artificial immunological synapse with CD20+ target cells, T-cell activation and target B cell killing. Compared to conventional CD20xCD3 TCEs, which equally engage and activate CD4+ and CD8+ T cells, AZD5492 drives potent B cell killing through preferential engagement of CD8+ T cells, with reduced CD4+ T cell activation and associated cytokine production. In NSG humanized mice engrafted subcutaneously or intravenously with B cell tumors, AZD5492 conferred potent and dose-dependent anti-tumor efficacy. When compared to conventional bivalent CD20xCD3 TCEs, comparable anti-tumor efficacy was achieved with significantly less systemic cytokine production. Importantly, repeated dosing of AZD5492 was also evaluated in cynomolgus monkey for up to 1 month and induced a marked and prolonged decrease in CD19+ and CD20+ B cells in the blood and in tissues (lymph nodes, spleen, and bone marrow). Transient cytokine increases were observed post-first dose of AZD5492 but was not associated with notable toxicity. Overall, AZD5492 was well tolerated in cynomolgus monkeys and a NOAEL was established at 3 mg/kg.
Conclusions
AZD5492 represents a first-in-class T cell engager for the treatment of B cell lymphomas. Compared to conventional CD3-based T cell engagers, AZD5492 anti-tumor activity in murine models was associated with low cytokine release and this favorable safety profile was recapitulated in NHP. AZD5492 has therefore the potential to significantly improve therapeutic index. AZD5492 IND has been approved by the FDA and a FIH study in patients with R/R NHL and CLL is ongoing.
The Effect of Alpha-Thalassemia on HbA1c Levels
Authors: Kerdsinchai Pasiri , Tantiworawit Adisak , Manosroi Worapaka , Niprapan Piangrawee , Punnachet Teerachat , Hantrakun Nonthakorn , Piriyakhuntorn Pokpong , Rattanathammethee Thanawat , Hantrakool Sasinee , Chai-Adisaksopha Chatree , Rattarittamrong Ekarat , Norasetthada Lalita , Charoenkwan Pimlak 
Published: December 2024

Abstract
Background: Beta-thalassemia patients have shown that HbA1c levels are lower in patients and correlate with lower hemoglobin (Hb) levels. The findings are possibly due to the shortening of red blood cell lifespan and elevated fetal hemoglobin (Hb F) levels. Alpha-thalassemia is common in Southeast Asia. Patients with alpha-thalassemia also experience chronic hemolytic anemia that may affect HbA1c levels.
Objective: To investigate the effect of alpha-thalassemia on HbA1c levels and the correlation between Hb and HbA1c levels.
Methods: This cross-sectional study enrolled patients with alpha-thalassemia and a control group from September 2022 to April 2024 from the Tertiary care University Hospital. Thalassemia patients and control subjects were confirmed through hemoglobin typing (HPLC) and PCR for alpha-thalassemia. Inclusion criteria included individuals aged ≥ 15 years with confirmed non-diabetes mellitus status by fasting blood sugar (FBS) and hemoglobin A1c level (HbA1c). Exclusion criteria included anemia resulting from other hemoglobinopathies and anemia from other causes. An analysis of variance (ANOVA) test was employed for the statistical analysis, dependent on the distribution of data. Linear correlation analysis was employed to explore the association between anemia and HbA1c levels in the HbH disease group.
Results: A total of 158 patients were enrolled, comprising 56 control patients, 72 HbH disease patients, and 30 patients with alpha-thalassemia trait 1. Patient characteristics, including sex, fasting blood glucose, creatinine, and GFR, did not differ significantly between the groups. The mean ± SD of HbA1c compared between the control, alpha-thalassemia 1 trait, and HbH disease groups was 5.3% ± 0.4 mmol/mol, 5.3% ± 0.4 mmol/mol, and 4.1% ± 0.6 mmol/mol, respectively (P &lt; 0.001). Significant differences in the mean HbA1c level ± SD [95% CI] were observed between the HbH disease and control groups (-1.25 ± 0.09 mmol/mol [95% CI -1.44 to -1.05] P &lt; 0.001), whereas no significant difference was found in the alpha-thalassemia trait 1 group compared with the control group (0.06 ± 0.09 mmol/mol [95% CI -0.11 to 0.24] P= 0.476). Furthermore, no statistically significant linear correlation was observed between the degree of anemia and HbA1c levels in the HbH disease group.
Conclusion: In summary, HbH patients demonstrated notably lower HbA1c levels than the control group while levels were similar between the alpha-thalassemia trait 1 and control group.
CD38 Expression As an Additional Prognostic Marker in Mantle Cell Lymphoma
Authors: D'Addona Matteo , Pezzullo Luca , Giudice Valentina , De Novellis Danilo , Ferrara Idalucia , Fontana Raffaele , Guariglia Roberto , Luponio Serena , Mettivier Laura , Martorelli Maria Carmen , Gigantiello Andrea , Morini Denise , Rizzo Michela , Buonanno Maria Teresa , Ciancia Giuseppe , Gorrese Marisa , Serio Bianca , Selleri Carmine 
Published: December 2024

Mantle-cell lymphoma (MCL) is an aggressive B-cell lymphoma characterized by a t(11;14)(q13;q32) occurring in pre-B cells and determining uncontrolled cell proliferation. MCL cell immunophenotype is typically CD19+CD20+CD5+CD22+CD24+CD79a+CD43+FMC7+BCL2+CD10-CD11c-CD23-CD200-BCL6-CyclinD1+SOX11+; however, neoplastic clones could aberrantly express adhesion molecules that can augment tumor aggressiveness.
In this study, we evaluated the prognostic impact in MCL of several surface markers currently used for immunophenotyping in other B-cell lymphomas.
In this retrospective observational real-life study, a total of 46 newly diagnosed MCL patients (M/F, 35/11; mean age, 67 years old; range, 44-87 years) were enrolled from 2000 to 2023 followed at the Hematology Unit, University Hospital of Salerno, Italy. Most patients (n = 41, 89%) had advanced (III-IV) disease, and high MIPI score (94% of subjects). Ki-67, an immunohistochemistry proliferation marker, was increased in 59% (expression &gt;30%) and in 4% was decreased (≤30%). Flow cytometry immunophenotyping was performed on bone marrow and/or peripheral in all subjects using the following antibody panels: CD19, CD20, CD5, CD23, CD10, CD11c, CD43, CD103, CD200, SmIg, CD22, CD79, FMC7, CD27, CD49d, CD38, CD25, CD56, CD16, CD2.
In our cohort, CD38 was frequently absent in MCL patients (positivity in N = 8, 17%; negativity in N = 16, 36%) patients. However, CD38- subjects tended to have a shorter overall survival (OS) compared to those patients with CD38 expression (median OS, 14 months vs not reached, CD38- vs CD38+ patients; P = 0.0591), as well as for progression-free survival (PFS) (median PFS, 26 months vs not reached, CD38- vs CD38+ patients; P = 0.0391), especially in patients aged 65 or older (median OS, 238 months vs 14 months, younger CD38- vs older CD38- MCL patients; P = 0.1252). Moreover, we investigated the impact of CD38 expression in patients that have Ki-67 expression between 30 and 70%. Despite falling in the high-risk MIPI categories because the patients have Ki-67 expression &gt;30%, CD38+ MCL patients showed better clinical outcomes compared to CD38- subjects with Ki-67 expression between 30-70% (median OS, not reached vs 14 months, respectively; P = 0.0055; and median PFS, not reached vs 14 months, respectively; P = 0.0127).
In conclusions, CD38 negativity is frequent in MCL; however, this condition could be associated with worse outcomes, especially in older patients (&gt;65 years old) and in subjects with intermediated Ki-67 expression (30-70%). Therefore, our results indicated that CD38 could be a potential prognostic biomarker in MCL and could be included in current prognostic scoring systems for better risk stratification.