bluuebunny/crossref_metadata_2025_split huggingface dataset:
Optimizing Fresh Frozen Plasma Use: A Quality Improvement Initiative in a Community Healthcare Setting
Authors: Sanikommu Dhruvi Reddy , Nadeem Ahmed , Lussier Amanda , Mohamed Nida , Iannuccilli Jenna , Boyle Kerri 
Published: December 2024

Introduction:
Blood products, including packed red blood cells, fresh frozen plasma (FFP), platelets, and cryoprecipitate, play a critical role in the clinical setting. However, there is a growing concern regarding the overuse of these products in community hospitals, often deviating from established transfusion guidelines. This practice not only increases the risk of transfusion-related reactions but also imposes a financial burden on the healthcare system. This study aims to assess the utilization of FFP and implement interventions to optimize the use of these essential blood products.
Methods:
A retrospective population study was conducted at Landmark Medical Center, Rhode Island. We identified patients who received FFP transfusions between 2021 and 2024 from blood bank records. Data were extracted from the EPIC electronic medical record (EMR) system, including the number of FFP units ordered and administered, pre-transfusion INR values, and the clinical indications recorded in the EMR. A proportional analysis was conducted to evaluate the concordance of FFP use with transfusion guidelines.
Results:
Among the 112 patients analyzed, 67.36% were above 65 years of age. The majority (81.42%) were White non-Hispanic, with a nearly equal gender distribution (57.52% male, 42.48% female). FFP transfusions were administered in accordance with EMR indications in 61.61% of cases, while 38.39% did not meet the documented indications. Notably, of the 69 patients (61.61%) who received FFP transfusions per EMR indications, 44 patients (63.77%) did not adhere to established transfusion criteria, suggesting these cases could have been managed without transfusion.
Conclusion:
This study identifies a significant discrepancy between the use of FFP and transfusion guidelines. Interventions, including provider education, enhanced oversight by the blood bank, and potential modifications to the EMR system, are being considered to improve guideline adherence and optimize the utilization of blood products. These measures are currently under discussion at our community hospital, and further evaluation will be necessary to assess their impact.
Severe Anemia and Neutropenia in a Patient with Gollop Wolfgang Syndrome: Implications of Malabsorption-Induced Micronutrient Deficiency. a Case Report
Authors: Olaosebikan Rasaq , Smink Gayle M 
Published: December 2024

Introduction: Gollop-Wolfgang Complex syndrome is a rare congenital limb anomaly characterized by distal bifid femur and tibial agenesis. The etiology of this syndrome is unknown. Copper deficiency, an uncommon cause of severe anemia and cytopenia, results from malabsorption, issues with copper metabolism, or other nutritional deficiencies. Severe anemia and neutropenia due to copper deficiency have been documented in case reports and retrospective studies. Copper is vital for hematopoiesis, particularly in hemoglobin synthesis and red blood cell maturation. We present a case of Gollop-Wolfgang Complex presenting with severe copper deficiency.
Case Presentation: A 3-year-old female with Gollop-Wolfgang syndrome, spina bifida occulta, and a history of iron deficiency anemia who was being admitted for elective amputation of a bifid left femur presented with fatigue and chronic diarrhea. On admission, she exhibited significant anemia (Hb 2.3 g/dL), macrocytosis (MCV 100 fL), Neutropenia (500 K/µL), and an elevated Vitamin B12 (1,025 mcg). She was treated with blood transfusions and responded well. Comprehensive evaluation for viral infections, malabsorption, and inherited bone marrow failure syndromes was negative. Persistent severe anemia and neutropenia led to testing for micronutrient deficiencies, revealing undetectable copper, ceruloplasmin, and vitamin C, with normal zinc levels. Copper supplementation with IV Cupric Chloride improved anemia (Hb 9.5 g/dL), and neutrophil count (4,760 K/µL), and the patient became transfusion-independent. Genetic testing identified a homozygous variant of uncertain significance in the WDPCP gene associated with Bardet-Biedl Syndrome (BBS), though the patient's phenotype did not align with BBS.
Discussion: Gollop-Wolfgang syndrome, marked by tibial agenesis and bifurcated femur, has not been associated with hematologic abnormalities. Our patient had severe copper and vitamin C deficiency. Copper deficiency can lead to significant hematologic issues, including anemia and neutropenia. Our patient's chronic diarrhea suggested malabsorption despite normal endoscopic findings. Excessive cow's milk intake, known to interfere with copper absorption, was identified as a contributing factor. Copper deficiency should be considered in patients with unexplained severe anemia and neutropenia, especially when typical causes are ruled out.
Conclusion: Copper deficiency, though rare, should be evaluated in patients with severe anemia and neutropenia. Early recognition and supplementation can prevent severe hematologic complications. This case highlights the need for awareness and further research on copper deficiency, particularly in rare syndromes like Gollop-Wolfgang. A multidisciplinary approach is crucial for accurate diagnosis and management.
Response of Thrombocytosis after Iron Replacement Therapy in Patients with Iron Deficiency Anemia
Authors: Bhatta Ghanshyam , Meseeha Marcelle , Khan Muneer , Richards Julie , Poulose Joyson , Talamo Giampaolo 
Published: December 2024

ABSTRACT
Background: Iron deficiency anemia (IDA) is the most common cause of anemia worldwide. Patient with IDA often present thrombocytosis (defined as platelet count &gt;450 x103/mL), but little is known about its degree and prevalence in this condition, and the response of platelet levels after iron replacement therapy.
Methods: We conducted a retrospective review of laboratory data of 24 consecutive patient with anemia secondary only to iron deficiency, both at baseline and at 3 months after either oral or intravenous iron replacement therapy.
Results: The mean age of the patients was 51 years (range, 24-83 years), and 17 of 24 (71%) patients were females. The causes of IDA were blood losses (n=12), poor gastrointestinal absorption (n=6), pregnancy (n=4), and unidentified (n=2). The iron replacement therapy consisted of oral FeSO4 (n=2), intravenous iron (n=9), or both (n=11). The mean Hb and ferritin levels at baseline and at 3 months after the iron replacement were 9.0 g/dL and 20.2 mg/dL, and 12.3 g/dL (p&lt;0.001) and 176.2 mg/dL (p&lt;0.001), respectively. Thrombocytosis at baseline was found in 5 of 24 (21%) patients, and after the iron administration it resolved in all patients (except one, who was found to have another condition causing thrombocytosis). The mean platelet level at baseline and at 3 months after the iron replacement was 380 and 288 x103/mL (p=0.002).
Conclusion: Thrombocytosis is found in about one fifth of patients with IDA, and it resolves within 3 months of adequate iron replacement therapy.
Dexamethasone Versus Prednisolone in Adults with Newly Diagnosed Immune Thrombocytopenia: A Systematic Review and Meta-Analysis
Authors: Srisurapanont Karan , Uawithya Ekdanai , Danpanichkul Pojsakorn , Worapongpaiboon Rinrada , Chai-Adisaksopha Chatree 
Published: December 2024

Whether dexamethasone or prednisolone is the optimal first-line treatment in adults with newly diagnosed immune thrombocytopenia (ITP) remains controversial. We aimed to compare the efficacy and safety of dexamethasone and prednisolone in adults with newly diagnosed ITP. A systematic review and meta-analysis of randomized controlled trials (RCTs).
We searched Pubmed, Scopus, Cochrane Central Register of Controlled Trials, and Embase to identify relevant citations until May 16, 2024. RCTs comparing dexamethasone to prednisolone in adults with newly diagnosed ITP were included. The outcomes included early response (ER) at 1 week, initial response (IR) at 1 month, durable response (DR) at 6 months, persistent response (PR) at 12 months, and adverse events. The outcomes were pooled using the random-effect Mantel-Haenszel meta-analysis and reported as relative risks (RRs) alongside corresponding 95% confidence intervals (CIs). The certain of evidence of each outcome was evaluated using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach.
We included 8 RCTs with 427 and 404 participants receiving dexamethasone and prednisolone, respectively. Dexamethasone yielded higher IR rates than prednisolone (RR 1.21, 95% CI 1.09-1.34). However, there was no improvement in terms of ER, DR, and PR. No significant difference was observed between 1-2 cycles and 3 cycles of dexamethasone in terms of IR (p=0.23), DR (p=0.64), and PR (p=0.88). Adverse events occurred more frequently in the prednisolone arm (141 events) than the dexamethasone arm (71 events), but the number of patients who discontinued the treatment was similar between both arms.
Very low certainty of evidence suggests that dexamethasone may be preferred compared to prednisolone in newly diagnosed adults with immune thrombocytopenia. Our findings suggested that one cycle of dexamethasone with a possible rescue course could be the optimal dosage.
Changes in Intensive Care Unit Mortality and Treatment Patterns in Acute Leukemia Patients over a 16-Year Period in China
Authors: Lu Linli , Cheng Qian , Li Xin 
Published: December 2024

Background: Acute leukemia (AL) can lead to life-threatening complications and often requires treatment in the Intensive Care Unit (ICU). Our previous study found that patients with AL showed a poor prognosis after ICU admission. The aim of this study was to assess the prognostic changes of AL patients admitted to the intensive care unit in recent years, to analyze the basic characteristics of ICU patients, changes in treatment patterns, and to identify risk factors affecting patient prognosis, thereby providing further guidance for the clinical management of critically ill leukemia patients.
Methods: This was a single-center, retrospective study, including 126 patients diagnosed with AL and admitted to the ICU between 2008 and 2023, with the study period divided into four-year intervals.
Results: A total of 37 patients with acute lymphoblastic leukemia (ALL) and 89 patients with acute myeloid leukemia (AML) were included, with a median age of 40 years (14-81). The most common reason for ICU admission was respiratory failure (46%), followed by shock (17.5%). The average age of patients admitted to the ICU was similar during the study period, but there was a trend towards a decrease in criticality scores, including APACHE Ⅱ and SOFA scores, and a prolongation of the mean length of stay in the ICU at the time of ICU admission. The ICU mortality rate for the entire cohort of patients was 57.9%, ICU mortality decreasing from 72.7% in 2008-2011 to 46.5% in 2020-2023, and similarly, the 1-month mortality rate (90% to 46.5%) and the 6-month mortality rate (90% to 46.5%) have also decreased. The use of invasive ventilation and vasopressor drugs decreased (72.7% and 86.4% to 51.2% and 62.8%), while use of non-invasive ventilation (22.7% to 32.5%) and dialysis increased (0% to 20.9%). It should be emphasized that the detection rate of pathogens in infected patients rose from 36.4% to 74.4%, which were due to the application of bronchoalveolar lavage fluid and next-generation sequencing (NGS) in detecting the pathogens. Notably, despite the reduction in invasive ventilation, there was a significant increase in the mean duration of invasive ventilation. Multivariate analysis showed that the independent risk factor associated with ICU mortality was invasive ventilation treatment (OR=13.068), whereas ICU length of stay longer than 7 days (OR=0.18), direct admission to the ICU (OR=0.155), and disease remission status at ICU admission (OR=0.071) were protective factors.
Conclusion: In conclusion, ICU mortality and 6-month mortality for AL patients with ICU admission were decreased from 2008 to 2023. Concurrently, ICU treatment patterns changed, with prolonged stay in the ICU, increased use of non-invasive ventilation treatment, decreased use of invasive treatments, and a significant increase in pathogen detection rates in infected patients.
BEAT Chemofree Regimen for Relapsed/Refractory and De Novo T-ALL
Authors: Lin Jieping , Zhou Xuan , Wang Zhixiang , Lin Dainan , Zhan Yu , Li Zan , Huang Jiwei , Li Yonghua , Ma Xudong , Liu Qifa , Xuan Li , Xu Yang , Zhou Hongsheng 
Published: December 2024

Background: Relapsed or refractory (R/R) and unfit T-cell acute lymphoblastic leukemia (T-ALL) have limited therapeutic options and a poor prognosis, with a 5-year overall survival rate of 20% and a complete response (CR) rate around 36%. Our previous study found that tucidinostat plus pediatric-inspired chemotherapy improves the survival of T-ALL. Venetoclax demonstrated high sensitivity in vitro and in vivo for T-ALL, particularly early T-cell precursor lymphoblastic leukemia (ETP-ALL), and exhibited synergistic therapeutic effects with l-asparaginase and dexamethasone. Therefore, we hypothesized that the BEAT chemofree regimen (Bcl-2 inhibitor, dExamethasone, Aaspargase, and Tucidinostat) would be safe and effective for R/R and de novo T-ALL.
Methods: BEAT chemofree regimen consists of bcl-2 inhibitor, dexamethasone, aspargase, and tucidinostat. Patients with R/R and de novo T-ALL were enrolled in this study and received BEAT chemofree regimen including venetoclax (100 mg on day 1, 200 mg on day 2, and 400 mg on days 3-14), tucidinostat and dexamethasone (10 mg on days 1-14) and pegaspargase (2000IU on day 3). This is a pilot study and we intend to conduct a multicenter randomized controlled trial in order to investigate and validate the efficacy and safety of the chemofree regimen in T-ALL.
Results: From January 2023 to June 2024, 6 patients with R/R T-ALL and 6 patients with de novo T-ALL were enrolled. For R/R T-ALL, the median age was 26 years (range 19-34 years), 67% were male, 100% were Asian, 4 had a diagnosis of ETP-ALL and 2 of Non ETP-ALL, 6 (100%) had received more than two lines of chemotherapy and 1 had received CD7 CAR-T therapy. For de novo T-ALL, the median age was 53 years (range 18-62 years), 73% were male, 100% were Asian, 4 had a diagnosis of ETP-ALL and 2 of Non ETP-ALL. Among the R/R T-ALL patients, 3 (50%) patients CR or CR with incomplete count recovery (CRi), including 2 (33%) patients achieved MRD &lt;10-4. One (17%) patient achieved partial remission (PR). The overall response rate (ORR) for R/R T-ALL is 67%. Among the de novo patients, 6 (100%) achieved CR/CRi including 4 (67%) achieved MRD&lt;10-4. The ORR for de novo T-ALL is 100%. The safety profile of BEAT regimen is well-tolerated in both R/R and de novo T-ALL. The most common grade 3-4 adverse events (AEs) of R/R T-ALL were neutropenia (67%), anemia (67%), thrombocytopenia (67%), febrile neutropenia (33%), lung infection (17%), septicemia (17%) and hypocalcemia (33%). The most common grade 3-4 AEs of de novo T-ALL were neutropenia (83%), anemia (67%), thrombocytopenia (34%), febrile neutropenia (17%), lung infection (17%) and ALT increased (17%). There were no gastrointestinal disorders of grade 3-4 or serious AEs of grade 5.
Conclusion: BEAT chemofree regimen is a promising and well-tolerated regimen in R/R and de novo T-ALL, with high CRc and ORR.
Transmembrane Thiol Isomerase TMX1 Inhibits Fibrin Formation By Down-Regulation of Platelet Phosphatidylserine Exposure
Authors: Zhao Zhenzhen , Lv Keyu , Cheng Yixin , Fang Chao , Wu Yi , Yang Aizhen 
Published: December 2024

Objective: Membrane exposure of phosphatidylserine (PS) on platelets is critical for the binding of coagulation factors leading to coagulation activation, however, the mechanism controlling PS exposure remains largely unknown. Using genetically modified mouse models, we previously reported that a transmembrane disulfide isomerase TMX1 inhibited integrin αIIbβ3 outside-in signaling which is important for PS exposure on platelets. In this study, we investigated the role of TMX1 in PS exposure and coagulation.
Approach and Results: We found that the deficiency of TMX1 in platelets enhanced fibrin formation and PS exposure at the site of injury. In vitro, TMX1 inhibited thrombin generation mediated by activated platelets, and attenuated PS exposure on platelets, the effect of which was prevented when integrin αIIbβ3 outside-in signaling was blocked, suggesting that TMX1 inhibition of integrin αIIbβ3 outside-in signaling suppresses PS exposure. Moreover, TMX1 deficiency increased the free thiols of TMEM16F in platelets including Cys338, Cys349 and Cys352. In HEK293T cell overexpressing C338S-, C349S-mutated TMEM16F, the PS exposure was increased, suggesting that TMX1 oxidizes these disulfide bonds of TMEM16F, decreasing its activity to externalize PS on the membrane.
Conclusion: Together, our observations for the first time demonstrate that TMX1 inhibits PS exposure in platelets downregulating the procoagulant activity, by which TMX1 plays a critical role in maintaining vascular quiescence.
A Retrospective Analysis of Orelabrutinib-Containing Regimen for Marginal Zone Lymphoma
Authors: Wang Hua , Liang Yang , Liang Dong , Feng Demei 
Published: December 2024

Background: Marginal zone lymphoma (MZL) is the second most prevalent B-cell lymphoma in China, with a proportion of 12.4%. To date, there is no established standard systemic treatment for MZL. Traditional immunochemotherapy regimens such as BR and R-CHOP are commonly used, but they are associated with a high incidence (60-70%) of grade 3 or higher adverse events, which severely limits patient benefit. There is an urgent need for safer and effective treatment strategy. Orelabrutinib, a novel Bruton's tyrosine kinase inhibitor, offers higher kinase selectivity and a favorable safety profile. A phase II study of orelabrutinib monotherapy for relapsed/refractory MZL showed an objective response rate (ORR) of 58.9%, with a median duration of response of 34.3 months, and orelabrutinb has been approved in China for the treatment of previously treated MZL. This study retrospectively analyzed the efficacy and safety of treatment orelabrutinib-containing regimens for MZL.
Methods: This retrospective study included 15 MZL patients treated with orelabrutinib-containing regimens at our center between April 2023 and June 2024. Each treatment cycle was 28 days. The regimens included orelabrutinib monotherapy (O), orelabrutinib combined with rituximab (OR), orelabrutinib combined with rituximab and lenalidomide (OR2), and orelabrutinib combined with rituximab and pomalidomide (POR), every 28 day for a cycle. The specific dosages were: orelabrutinib 150 mg, once daily; rituximab 375 mg/m2, d1; lenalidomide 20 mg, d1-d21; pomalidomide 4 mg, d1-d21. The primary endpoint was objective response rate (ORR), and secondary endpoints included complete response rate (CR), progression-free survival (PFS), overall survival (OS), and safety.
Results: Fifteen patients (6 males, median age 60, range 33-69) were included in the study, comprising 14(93.3%) cases of extranodal MZL and 1(6.7%) case of nodal MZL. Nine(60.0%) patients were in stages III-IV, 3(20%) patients had an MZL-IPI score ≥3, 3(20%) had Hepatitis B virus, 1(6.7%) had Epstein Barr virus, and 1(6.7%) had Helicobacter pylori(Hp). One(6.7%) patient had received local treatment (anti-Hp therapy), and 6(40%) had received systemic treatment. For the current regimens, 2(13.3%) patients received orelabrutinib monotherapy, 4(26.7%) received OR treatment, 7(46.7%) received OR2 treatment, and 2(13.3%) received POR treatment. Among the 10 evaluable patients, the ORR was 80.0% (5 CR, 3 PR), with 2 (20.0%) cases of disease progression. Three (20.0%) patients experienced adverse events: 1 had neutropenia (Grade 3) and lymphopenia (Grade 2), 1 had a rash (Grade 2), and 1 had a hemoptysis (Grade 2). No BTKi-related adverse events were observed.
Conclusion:This retrospective study preliminarily confirmed that orelabrutinib-containing regimens are effective and safe for treating MZL. Further long-term follow-up and additional studies are anticipated to validate these findings.
Treatment with a Novel Small Molecule Dual Factor IIa/Xa Inhibitor Protects Against Coagulopathy and Organ Dysfunction in a Baboon Model of Staphylococcus Aureus Sepsis
Authors: Silasi Robert , Keshari Ravi Shankar , Abe Tomohiro , Regmi Girija , Lupu Cristina , Simmons Joe , Pfaff Nils , Heitmeier Stefan , Lupu Florea 
Published: December 2024

Background: Sepsis-associated coagulopathy and disseminated intravascular coagulation (DIC) significantly contribute to organ failure and mortality in sepsis patients. Factors IIa and Xa are pivotal in the coagulation cascade, and their over-activation in sepsis leads to systemic hypercoagulable states. We hypothesized that in intensive care settings, comprehensive and controllable anticoagulation and organ protection can be achieved by targeting these two key proteases in the common coagulation pathway with the short-lived dual inhibitor BAY 3389934.
Objective: To assess the efficacy and safety of BAY 3389934, a novel short-lived, small molecule dual FIIa/Xa inhibitor, in reducing coagulopathy and protecting organ function in a baboon model of Staphylococcus aureus (S. aureus) sepsis.
Methods: The study employed a baboon model infused with heat-inactivated S. aureus (3.3 x 1010 bacteria/kg bw). Baboons were treated with BAY 3389934 (1-2 mg/kg bw, continuous IV infusion up to 8 hours post-bacterial challenge) starting at T0 (before) or 2 hours post-bacterial challenge. Various parameters, including markers of coagulation, fibrinolysis, organ function, and bleeding time, were assessed. Animals were kept in anesthesia for 9 hours and subsequently followed up to 48 hours after the start of bacterial challenge.
Results: S. aureus infusion induced robust activation of coagulation, as reflected by plasma levels of protease-serpin complexes (FXIIa-AT, Kal-AT, FXIa-AT, FVIIa-AT, and T-AT) and mirrored by fibrinogen and platelet consumption. S. aureus infusion led to organ dysfunction, as indicated by elevated vital signs, increased plasma ALT, total bilirubin, pancreatic amylase, plasma creatinine, and blood urea nitrogen, as well as histological evidence of kidney damage.
Treatment with BAY 3389934 significantly decreased the coagulation markers, blocking the activation of coagulation when given at T0 and strongly reducing it when given 2 hours after the challenge. Importantly, the treatment mitigated fibrinogen and platelet consumption without causing bleeding throughout the experiment. ROTEM analysis confirmed these findings.
Additionally, BAY 3389934 protected against organ dysfunction, as evidenced by reduced markers of liver (ALT), pancreas (amylase), and kidney (BUN, creatinine) damage, and decreased lactate levels. Histological analysis showed that the treatment prevented fibrin deposition in the kidney and lungs and necrosis of the kidney's tubular epithelium.
Conclusion: In a model of sepsis-induced coagulopathy in baboons, the dual FIIa/Xa inhibitor BAY 3389934 reduced the hypercoagulable state strongly and protected from organ damage. Further studies are warranted to explore its full therapeutic potential in the treatment of sepsis-associated DIC.