bluuebunny/crossref_metadata_2025_split huggingface dataset:
Sickle Cell Trait Is Associated with Adverse Clinical Outcomes in a Matched Case-Control Study at a Tertiary Care Center
Authors: Stafford Katherine , Osataphan Soravis , George Gemlyn , Patell Rushad 
Published: December 2023

Background:
Sickle cell trait (SCT) is a common condition affecting more than 300 million individuals worldwide and 3 million in the United States. Although generally believed to be an asymptomatic condition, there is growing data to suggest potential associations with morbidity, including risk for venous-thromboembolic events and chronic kidney disease.
Methods:
We conducted this retrospective cohort study using electronic health record data from the University of Colorado Health Data Compass data warehouse. Patients with a coded diagnosis of SCT were analyzed for SCT-related clinical outcomes compared against a 1:1 randomized matched sample of controls without a history of SCT (matched on age, race, sex). Individuals with sickle cell disease, Sickle-cell/Hb-C disease, sickle-thalassemia, other sickle cell disorders, and hemolytic anemias were excluded from both case and control groups. Outcomes included chronic kidney disease (CKD), deep vein thrombosis (DVT), pulmonary embolism (PE), hematuria, rhabdomyolysis, and splenic infarction. Multivariate logistic regression was used to examine the association of each condition based on SCT carrier status, adjusting for age, sex, and race.
Results:
We included 1447 SCT patients with complete demographic data, along with 1447 matched controls (n = 2894). There were 1019 (70.4%) women and 428 (29.6%) men in each case and control group. A majority (72.7%) were black or African American. The median age of the cohort was 36 years (IQR = 28 - 47). We found significant associations for CKD (OR = 2.95, 95% CI: 2.03 - 4.30), DVT (2.54, 95% CI: 1.42 - 4.54), PE (OR=4.25, 95% CI: 2.43 - 7.45), and hematuria (OR= 2.28, 95% CI: 1.57 - 3.31). (Table) Despite few overall events and wide confidence intervals, association remained significant for rhabdomyolysis (OR=3.32, 95% CI 1.07 - 10.24) and splenic infarction (OR=44.9, 95% CI 6.15 - 328.00). Male sex was strongly associated with splenic infarction (OR = 8.70, 95% CI 4.11 - 18.41) and rhabdomyolysis (OR = 19.14, 95% CI 4.35 - 84.18).
Conclusion:
In this case-control cohort study we found significantly increased risk for CKD, DVT, PE, hematuria, rhabdomyolysis, and splenic infarction for patients with sickle cell trait with odds ratios similar to those seen in other study cohorts. The significant morbidity associated with this common genotype warrants further research into primary prevention of SCT associated adverse outcomes.
Changes in Cardiovascular Magnetic Resonanse T1 and T2 Mapping in Patients Undergoing Autologous Hematopoietic Stem Cell Transplantation
Authors: Vaitiekiene Audrone , Kulboke Migle , Bieseviciene Monika , Jankauskas Antanas , Strazdiene Igne , Lidziute Emilija , Jankauskaite Darija , Gaidamavicius Ignas , Gerbutavicius Rolandas , Vaskelyte Jolanta Justina , Vaitiekus Domas , Sakalyte Gintare , Niederwieser Dietger W. 
Published: December 2023

Introduction
Despite the significant improvement in survival afforded by hematopoietic stem cell transplantation (HSCT), the therapy is associated with many complications, cardiovascular being one of them. Cardiovascular magnetic resonance (CMR) can depict changes at the tissue level, which could be a reflection of physiology and pathophysiology. In our study we aimed to evaluate the level and progress of diffuse myocardial fibrosis and edema in the heart using T1 and T2 mapping in patients one year after autologous HSCT.
Methods
Data of 26 patients undergoing autologous HSCT at the Department of Oncology and Hematology in the Hospital of Lithuanian University of Health Sciences Kaunas Clinics between 2021 October and 2022 July was evaluated. Bioethics approvement for prospective study was obtained (No BE-2-96). Cardiac evaluation including cardiovascular magnetic resonance (CMR) was performed before stem cell mobilization and 12 ± 1 months after HSCT. CMR was performed using 3T MRI Siemens Magnetom Skyra, T1 and T2 mapping MOLLI (modified Look-Locker Inversion Recovery) sequences with motion correction (MOCO) were analysed using Syngo.via. Baseline mapping values were compered to values one year after transplantation. SPSS statistics 20 was used for statistical analysis (paired samples T test). Qualitative data is presented as absolute value (N) and percentage (%), quantitative parameters are given as average (m ± standard deviation).
Results
The mean age of patients was 56,7 ± 13,7 years (ranging from 18 to 74). Out of 26 patients there were 14 men (53,8%) and 12 women (46,2%). Mean T1 mapping value representing diffuse fibrosis significantly increased 12 months after transplantation. Mean T1 mapping value before HSCT was 1215,02 ± 35,2 ms and after 1243,07 ± 46,2 ms (p=0,014). Mean T2 mapping value representing edema did not change significantly. Mean T2 mapping value before HSCT was 38,28 ± 2,1 ms and 39,05 ± 1,8 ms after HSCT. (p=0,059).
Conclusions
The extent of diffuse fibrosis in the heart represented by elevation of T1 mapping value tend to increase one year after autologous HSCT. This may lead to further remodelling of the heart.
Response to Dabrafenib and Tramatenib in an Extra-Cranial Avm with BRAF V600E Mutation
Authors: Fraustro Milena , Olsen Braden , Khatib Ziad 
Published: December 2023

Background:
Arteriovenous malformations (AVMs) are blood vessel malformations characterized by shunting of blood through dilated veins and arteries. KRAS is an effector molecule in a MAPK pathway that mediates activation of downstream processes such as BRAF production related to known proliferative disorders such as AVMs. Similarly MAP2K1 mutations that encodes for MEK have recently been implicated in sporadic intracranial and extracranial AVMs. Inhibition of the RAS/MAPK pathway is of interest in treatment of vascular malformations.
Objective: We report a case of treatment response of a BRAF mutated arteriovenous malformation with MEK and RAF inhibitors.
Description of the case:
A 22 year old male presented initially at 6 years of age with swelling of the left face involving the cheek and mandible area, the area continued to grow in size with associated pain and rarely intermittent bleeding from the left buccal mucosa. US and MRI showed evidence of an AVM. He underwent 2 embolizations followed by debulking with some improvement of the swelling. Pathology revealed a BRAF V600 mutation by molecular testing. He was treated with oral Dafrafenib 150 mg twice daily and Trametinib 2 mg daily, showing improvement of the swelling with a 3 month old follow up.
Conclusion:
AVMs continue to present treatment challenges for hematologists, surgeons and other care providers. Treatment with target directed therapies with inhibitors of the RAS-RAF-MEK-ERK pathway such as Trametinib and Dafrafenib have the potential to make a positive impact in the current management of these entities. Further studies are required to explore safety and impact of long term effects of these drugs in pediatric patients.
As Fast As We Can: Rational Design of Rapid Chimeric Antigen Receptor T Cell Manufacturing
Authors: Jiang Pengfei , Cao Shih-Ting , Wang Haiying , Xiong Qinghui , Gu Mingyuan , Fu Chengbing , Li Xiu , Zhang Mian , Li Na , Li Jing , Xu Xin , Gong Yiwei 
Published: December 2023

Background
Chimeric antigen receptor T cell proved to be a promising approach to treat hematological malignancies. There are six autologous CAR-T drugs approved by FDA in US. The production of autologous CAR-T cells is carried out by a time-consuming manufacture process typically need 2-3 weeks. Unfortunately, about 25% patients died while awaiting their CAR-T product. Rapid manufacturing CAR-T cells still is an unmet clinical need for fast processing diseases. We developed the “DASH CAR-T” manufacturing platform which harvested CAR-T cell in two-three days. Our first product, autologous DASH CD19 CAR-T demonstrated greater anti-tumor efficacy in murine study correlated with higher T cell expansion compared with conventional CAR-T. In this study, we designed a simplified novel CAR-T manufacturing process with optimized culture and harvest time between 48 hours to 72 hours.
Methods
Rapid manufacturing CAR-T cells comprising common key steps as the conventional CAR-T product : select T cells from PBMC, activated T cells by CD3/28 Dynabeads, transduced with retroviral vector expressed CD19-28z CAR construct, and then the CAR-T cells harvested and cryopreserved for clinical use. We investigated the shortest time for each steps by various reagents, medium and process. Then we compressed the whole process and our novel approaches completed all manufacturing process less than 72 hours.
Results
First, we compared the harvest timing based 3 batches CAR-T cells from health donors. A various factors, such as cell viability, CD3+%, Annexin V-/PI- population, percentage of residual CD19+ cells, and naïve T cell proportion were very similarly between 48 hours CAR-T cells and 72 hours CAR-T cells, indicated comparable harvest timing for manufacture. Second, we investigated 3 batches of CAR-T cells manufactured from B cell malignancy patients. In this scenario, 72 hours CAR-T exhibited better cell viability, increased naïve T cell population, and more Annexin V-/PI- cells in the culture compared to 48 hours CAR-T. The different performance of patient cells and healthy donor cells suggested the importance of the choice of starting material for process development of cell therapy. All batches successfully manufactured in 72 hours. Tumor cell-xenograft NOG mice models were confirmed the anti-tumor activity of DASH CD19 CAR-T cells in vivo.
Conclusions
This study reported an optimized DASH CAR-T process with 48 hours and 72 hours manufacturing. Cell viability, stemness of T cells, CAR expression, and removal of impurity were improved in the CAR-T product manufactured by this novel process. Based on the preclinical study results, an investigator-initiated trial (IIT) has launched to explore the safety, efficacy, pharmacokinetic/pharmacodynamics characteristics in patients with relapsed/refractory B-cell acute lymphoblastic leukemia (B-ALL).
Accuracy of the Diagnosis of Subsegmental Pulmonary Embolism Among General Radiologists
Authors: Batayneh Osama , Ijaz Ambreen , Toumar Ahmad , Meek Jessica , Abdelrahman Houda , Haddad Stephanie , Minami Taro 
Published: December 2023

Background:
Diagnosis and treatment of subsegmental pulmonary embolism (SSPE) are challenging. Contrary to segmental PE, little is known about the accuracy of the diagnosis of SSPE
Methods
A retrospective matched cohort study was conducted at a university-affiliated community hospital. Computed tomographic angiography (CTAs) were reviewed from August 2018 to December 2021. Patients who were 18-year-old or older with the diagnosis of SSPE were included. Patients with a concurrent segmental PE or deep venous thrombosis (DVT) were excluded. Another radiologist reviewed each CTA.
Results
Total of 43 patients with SSPE without segmental PE were identified. The mean age of subjects was 67 years. 24 (56%) patients were males, and 41 (95%) were white. 42 (97%) of CTAs were performed for suspected PE. One case was found incidentally. Forty patients (93%) received therapeutic anticoagulation. Three patients (7%) were discharged from the Emergency Department (ED) without therapeutic anticoagulation. The average duration of anticoagulation therapy was four-months. Another radiologist's review of the CTA on admission revealed a discordant diagnosis: 13 out of 43 (30%) cases were reported negative for SSPE. One case was reported for segmental PE
Conclusion
The accuracy of the diagnosis of SSPE is low as the discordance rate by different radiologists is high.More studies are needed to establish the diagnosis and guide treatment of SSPE.
Frailty Predicts Worse Outcomes in Tumor Lysis Syndrome
Authors: Kamal Ashna , Vikash Sindhu , Vikash Fnu 
Published: December 2023

DISCUSSION
Tumor lysis syndrome (TLS) is a potentially life-threatening complication that occurs in the setting of rapid tumor cell destruction. The Hospital Frailty Risk Score (HFRS) is a valuable tool to identify frailty in older individuals, signifying a decline in physiological reserves and coping ability due to age-related deterioration, and it has gained recognition as a crucial factor linked to adverse events, including mortality, hospitalization, and diminished functional outcomes. We aimed to assess the impact of HFRS on individuals admitted with a primary diagnosis of TLS.
Using weighted data from the Nationwide Inpatient Sample (NIS) database from 2016 to 2020, we assessed the outcomes (mortality, hospital utilization, total healthcare charges, complications) of individuals admitted with a primary diagnosis of TLS stratified by the presence and absence of Frailty (determined by the combination of 109 ICD-10 codes each with a different score) (table 1). Baseline characteristics were analyzed using T-test and Chi-Square, and a multivariate regression analysis was used to estimate outcomes between races, adjusted for patient and hospital confounders. Data analysis was performed using STATA® Version 17.0/SE Software, with statistical significance set at p &lt; 0.05.
A total of 4,340 were admitted with a primary diagnosis of TLS from 2016 to 2020, among these, we selected 1,330 admissions aged 75 years or older; these admissions included 59% (N=785) with frailty, and 41% (N=545) without frailty. Frailty was associated with increased length of stay (adjusted mean difference (aMD) = 2.5 days, 95%CI: 1.2 - 3.8 days), and total healthcare expenditures (aMD = 22,541 U.S. dollars (USD), 95%CI: 2,175 - 42,908 USD). Pertaining to the outcomes, a 9- fold increase in the odds of mortality were noted among individuals with frailty, as opposed to those without frailty (adjusted Odds Ratio (aOR) = 8.93, 95%CI: 1.79 - 44.74).
Our study depicts the significant impact of frailty on individuals hospitalized with TLS, revealing associations with elevated mortality rates, prolonged length of hospital stay, and increased healthcare costs. Considering a considerable portion of cancer patients fall within the elderly demographic and often present with multiple comorbidities, the Hospital Frailty Risk Score (HFRS) is a potential valuable tool for assessing the appropriateness of chemotherapy in conjunction with other scores like the Eastern Cooperative Oncology Group (ECOG). Moreover, the HFRS may aid in prognosticating disease outcomes, offering clinicians valuable insights to inform treatment decisions and improve patient care.
Clinical Characteristics of Shwachman-Diamond Syndrome in China - Result from Childhood Bone Marrow Failure Diseases Register of China Alliance for Blood Diseases(cBMFR-CABD)
Authors: Wan Yang , Qin Xia , Tan Shengjiang , Liu Jianping , He Hailong , Ju Xiuli , Liu Yufeng , Jie Yu , Yuan Sun , Hu Qun , Wu Xiaoyan , Liu Rong , Ma Jie , Chen Jing , Warren Alan , Zhu Xiaofan , Tang Xiangfeng 
Published: December 2023

OBJECTIVE
This study aimed to identify the clinical features of 73 children diagnosed with SDS from 22 centres in China.
METHODS
Childhood Bone Marrow Failure Diseases Register of China Alliance for Blood Diseases (cBMFR-CABD) was a bidirectional multicenter cohort study that collected data from 22 paediatric blood disease treatment centres from all over China. Patients were enrolled in the sub-centres from 1.1.2011 that were aged &lt; 18 years at diagnosis and met the diagnostic criteria for an inherited bone marrow failure disorder. The clinical data for the 73 SDS patients analyzed in this study were collected between 1.1.2011 and 31.12.2022.
RESULTS
Among the 73 SDS children, 38 were male and 35 were female. Short stature (height&lt;-2SD) was found in 53.4 % (39/73) patients. Chronic diarrhea was observed in 24.7 % (18/73) patients. In children evaluated for intellectual and physical malformations, 7 patients (17.3 %,6/52) had mental retardation and 14 (20.5 %, 15/73) patients had physical deformities.
Genetic testing was available in 63 patients. seventeen (27.0 %) patients carry bi-allelic c.258+2T&gt;C and c.183-184TA&gt;CT SBDS mutations. Eleven patients (17.5%) are homozygous for the c.258+2T&gt;C mutation. Four patients (6.3%) were compound heterozygous for c.258+2T&gt;C and exon 2 deletions. One patient carries bi-allelic mutation of DNAJC21. This patient had a history of repeated infections and pancytopenia.Bone marrow smear shows multilineage dysplasia.
Bone marrow results were available for evaluation in 54 patients including 67 % (36/54) BMF, 30 %(16/54) MDS, 4 % (2/54) AML.TP53 mutation testing was available in 15 patinets with eight (53.3%) patients carry TP53 mutation.Karyotype analysis was available in 36 patinets with 5 patients were complex karyotype.
Among the 56 patients available for follow-up, 17 patients underwent haematopoietic stem cell transplantation, 5 patients died (one infection,three transplant-related death and one relapse). Among the 39 non-HSCT patients, 3 patients died of AML transformation.
Three-year overall survival of all patients were 91.7%(95%CI 99.5 %~ 83.9% ), BMF patients were 100.0%(95%CI 100.0%~100.0% ), MDS/AML patients were 67.7%(95%CI 94.0%~ 41.4% ).
CONCLUSION
Our results provide the clinical features of the largest SDS cohort in China. A high incidence of short stature was observed. Bi-allelic c.258+2T&gt;C with c. 183-184 TA &gt; CT SBDS mutations were the most common mutation type. HSCT is an effective treatment modality in SDS. However, AML transformation is still a major risk factor for children with SDS.
Hemophagocytic Lymphohistiocytosis As an Immune-Related Adverse Events in a Patient with Advanced Lung Adenocarcinoma
Authors: Lu Kai , Polly Oshuare , Achhal El Kadmiri Mohammed Amine 
Published: December 2023

I ntroduction: Immune checkpoint inhibitors (ICIs) have been approved as single agents or in combination with cytotoxic chemotherapy for use in the treatment of different tumor types including skin, lung, kidney, endometrium, bladder..., especially in advanced stages. ICIs are usually well tolerated and despite their demonstrated clinical benefit, severe immune-related adverse events (irAEs) can sometimes occur, including colitis, hepatitis, myocarditis, glomerulonephritis, pneumonitis, hypophysitis... Here we are reporting a case of hemophagocytic lymphohistiocytosis (HLH), a rare but potentially life-threatening complication of ICI therapy.
Case presentation: We present the case of a 60-year-old female with metastatic adenocarcinoma of left lung who presented to the emergency room with a week history of generalized weakness, worsening dyspnea on exertion and decreased appetite while on maintenance ICI with pembrolizumab for approximately 1 year.
On admission vital signs were a blood pressure of 88/70mmhg, pulse rate of 139 beats per minute, respiratory rate of 20 cycles per minute, temperature of 98.3°F and oxygen saturation of 98% on room air. Physical exam was unremarkable. A complete blood count revealed leukopenia of 2.7k/uL, hemoglobin of 11.8 g/dL, and mild thrombocytopenia of 131k/uL. A basic metabolic panel was significant for hyponatremia of 133 mmol/L, blood urea nitrogen of 43mg/dL, and creatinine of 1.71mg/dL. She was started on empiric broad-spectrum antibiotics with IV vancomycin and cefepime due to concern for infection in the setting of recurrent febrile episodes and neutropenia. Worsening pancytopenia prompted further work-up and showed elevated ferritin of 19581, lactate dehydrogenase of 2380, folate &gt; 20, vitamin B 12 of 1645, iron level of 62, elevated total and direct bilirubin of 6.3 and 2.9 mg/dL, haptoglobin &lt; 10 mg/dL, fibrinogen level of 174, C- reactive protein of 73.9. Elevated soluble IL2- receptor elevated at 10336.7, d-dimer &gt; 20, elevated partial thromboplastin time of 51.1, Prothrombin Time of 20.5, INR of 1.7. Peripheral blood smear was unremarkable.
Hemophagocytic lymphohistiocytosis was suspected and a bone marrow was performed prior to initiation of intravenous steroids. Bone marrow showed evidence of abundant histiocytes with hemophagocytosis of nucleated cells. She was discharged on an oral steroid taper. She has since been well without evidence of tumor progression off therapy for over 2 years now.
Discussion: HLH is a rare but potentially life-threatening complication of ICI therapy that requires prompt recognition and management. Our patient responded well to steroids and did not require cytotoxic chemotherapy with etoposide.
Treatment of Acute Lymphoblastic Leukemia with PDT Regimen Improves the Prognosis of Newly Diagnosed Central Nervous System Leukemia
Authors: Liang Haimei , Liu Qifa , Zhou Hongsheng 
Published: December 2023

Objective
To investigate whether pediatric-like regimen can improve the prognosis of newly diagnosed acute lymphoblastic leukemia (ALL) complicated with central nervous system leukemia (CNSL) and reduce the occurrence of CNSL during treatment compared with the adult regimen.
Methods
We collected the clinical data and survival data of 1023 patients with newly diagnosed ALL in the hematology department of Nanfang Hospital from January 2006 to December 2021. The adult regimen cohort included 612 patients (age≥14 years) diagnosed between January 2006 and December 2015, all of whom were treated with the Hyper-CVAD regimen. The pediatric-like regimen cohort included 411 patients diagnosed between January 2016 and December 2021, all of whom were treated with the PDT-ALL-2016 regimen (a GRAALL2003 backbone, pediatric-inspired regimen therapy). Newly dignosed central nervous system leukemia(Ndx CNSL) is defined as the presence of leukemia cells on cytological examination of the cerebrospinal fluid or significant neurological signs. Differences between OS and EFS in Kaplan-Meier curves were determined using the log-rank test in the R package “survival”.
Results
Among 1023 patients, a total of 59 patients had Ndx CNSL, including 35 patients (5.72%) in the adult regimen cohort and 24 patients (5.84%) in the PDT-ALL-2016 cohort. There were no statistically significant differences in baseline characteristics between the two groups. In the cohort of Ndx CNSL, after a median follow-up of 42.48 months, overall survival (OS) and event-free survival (EFS) of the adult cohort were significantly inferior than the PDT-ALL-2016 cohort (3-year OS, 14.26%vs38.2%, P=0.044; 3-year EFS, 12.42%vs37.1%, P=0.039). During the chemotherapy treatment, CNSL occurred in 69 patients (11.27%) in the adult regimen cohort and 29 patients (7.06%) in the PDT-ALL-2016 cohort, with a significant difference (P=0.032).
Conclusion
Compared with the adult regimen, the pediatric-like regimen PDT-ALL-2016 improves the prognosis of ALL patients with newly diagnosed CNSL and reduces the occurrence of CNSL during the chemotherapy treatment.
This research was supported by the National Natural Science Foundation of China(NFSC82170163, 81970147), Clinical Study of Nanfang Hospital(LC2016ZD009/2019CR012).