bluuebunny/crossref_metadata_2025_split huggingface dataset:
Outcomes of Sarcoidosis on Patients with Sickle Cell Disease - a Review of the National Inpatient Database 2016-2020
Authors: El Sharu Husam , Zweigle Joshua , Jamil Maria , Singh Sukhvir , Cowles Sara , Liles Darla K. 
Published: December 2023

Introduction:
Sickle Cell Disease (SCD) is an inherited hemolytic disorder due to an autosomal recessive mutation affecting mainly African Americans. SCD can lead to various complications, including Sickle Cell Crisis (SCC), Acute Chest Syndrome (ACS), strokes, and different osseous complications. Notably, these complications can be provoked using steroids. Sarcoidosis is a multisystem inflammatory disorder that is characterized by the presence of bilateral hilar lymphadenopathy that is commonly treated with steroids. Unfortunately, it is also preferentially affecting African Americans. The complication rates in patients with both diseases have rarely been described. We aim to describe the effect of sarcoidosis on the mortality and complication rates of admitted patients with SCC.
Methods:
Using the National Inpatient Sample (NIS) 2016-2020, we analyzed adult SCC and ACS hospitalizations with and without sarcoidosis using International Classification of Diseases - 10 Clinical Modification (ICD-10-CM) codes. The primary outcome was inpatient mortality. Secondary outcomes were inpatient morbidities, mean length of stay (LOS), and mean total hospital charge (THC). A multivariate logistic regression and linear regression analyses were used to adjust for potential confounders.
Results:
Out of 359655 patients hospitalized with SCC, only 4.6% had concomitant sarcoidosis. Of these, 70% were females, with a mean age of 38.4 compared to an average age of 32 in patients without sarcoidosis (p-value &lt;0.05). The mean LOS for patients with sarcoidosis and SCC was 6.4 days, while it was 5.1 days for patients without sarcoidosis (p-value 0.001). While adjusting for common comorbidities and patients' characteristics, patients with SCC and sarcoidosis did not have a statistical mortality difference compared to patients without sarcoidosis [adjusted odds ratio (aOR): 2.3, CI: 0.4-14). On stratified analysis, patients with ACS and sarcoidosis had increased odds of mortality with an aOR of 6.68, CI: 1.1-39.7, and a p-value of 0.037. Moreover, amongst patients who had SCC, patients with concomitant sarcoidosis had a higher risk of acute coronary syndrome (aOR: 5.1, CI 1.24-21.0) and avascular necrosis (aOR: 1.57, CI: 1.12-2.20). There were no statistically significant differences in the odds of ischemic strokes, transient ischemic attacks, acute and chronic kidney disease, risk of intubation, pulmonary edema, osteoporosis, venous thrombosis, and THC. Figure 1 shows the Forrest plot for multivariate analysis of in-hospital morbidities when adjusted for patient demographics, comorbidities, and hospital characteristics.
Conclusion:
Patients admitted with ACS and sarcoidosis had higher odds of mortality. Patients with SCC and sarcoidosis also had higher odds of acute coronary syndrome, avascular necrosis, and mean LOS. Nevertheless, this has not impacted other inpatient comorbidity.
Effectiveness of Intensive Chemotherapy with 7+3 Versus Vidaza and Venetoclax in Acute Myeloid Leukemia with Sequential Stem Cell Transplant: Results from Real-World Cohorts
Authors: Fuqua Jacob , Abonofal Abdulrahman , Safi Salah Ud Din 
Published: December 2023

Introduction:
Intensive chemotherapy(IC) with cytarabine and anthracycline (7&3) has been the backbone therapy for medically fit patients for the last 50 years. The use of Venetoclax and hypomethylating agent combination has be used in older and unfit patient populations. The Venetoclax combination regimen has improved outcomes in the selected group but has been characterized to be inferior to 7&3 regimen among some studies. The role of stem cell transplant has not been previously discussed who receive IC versus Venetoclax based chemotehrapy
Methods:
Retrospective data was extracted using the TriNetX database. The primary endpoint was overall survival, and stem cell transplant in the two cohorts.
Results:
5590 patients were identified in cohort-1 (7+3 cohort) and 2944 patients were identified in cohort-2 (Vidaza with Venetoclax cohort). Table-1 shows patient characteristics at baseline. Propensity-score-matching was used to balance the two cohorts. Patient count in each group after matching was 1393 (Table-2). Overall survival was 43.78% in cohort-1 versus 16.56 % in cohort-2, with HR of 0.510 (95% CI 0.457, 0.569) in favor of cohort 1 (Figure-1) at 5-year mark. Median OS for cohort-1 was 1055 days versus 289 days for cohort-2. Additional analysis was performed to determine number of patients who underwent a Stem Cell Transplant in each cohort and the effect of transplant on outcomes. 462 patients in cohort-1 and 358 patients in cohort-2 underwent transplant respectively. Overall survival was 51.29% in cohort-1 versus 61.64% in cohort-2, with HR of 1.180 (95% CI 1.027, 1.254) in favor of cohort-2 at 5-year mark. Median overall survival was not reached for either cohort at the data cut-off.
Conclusions:
Our retrospective analysis of a large patient cohort showed improved OS and decreased risk of death in patient's undergoing 7&3 induction therapy as compared to Vidaza with Venetoclax. In patients who underwent stem cell transplant, the overall survival was statistically better in Vidaza with Venetoclax cohort as compared to 7&3 induction therapy cohort. To the best of our knowledge, this is the first large database based study evaluating these two induction regimens accounting for stem cell transplantation.
No Improvement in the Age Adjusted Mortality of Older Adults with Acute Lymphoblastic Leukemia Despite the Availability of Blinatumumab, Inotuzumab and Novel TKIs : A 1999-2020 Analysis in the United States
Authors: Varughese Tony , Kabat Maciej , Zolotov Eli , Koprivnikar Jamie 
Published: December 2023

Introduction: Acute Lymphoblastic Leukemia (ALL) has a bimodal distribution and while it is the most common malignancy in children, it can also present in adults 55 years of age and older. Adverse disease biology and comorbidities that preclude delivering curative regimens are factors that underlie the markedly disparate outcomes seen between childhood and older adult ALL. Advancements in therapy have improved prognosis in children, however in adults' treatment outcomes are worse. Our study aims to compare mortality trends in older adults compared to children within the United States with ALL.
Methods: Using the Center for Disease Control and Prevention Wide-Ranging Online Data for Epidemiologic Research database, we reviewed death certificate data for ALL patients from 1999 to 2020, age 55 and older in the United States. ICD code C91.0 (Acute lymphoblastic leukemia - Malignant neoplasms) was used to identify patients with ALL. Age-adjusted mortality rates (AAMRs) were calculated per 1,000,000 people and stratified patients by sex, race/ethnicity, and census region (Northeast, Midwest, South, and West). A comparison group between ages 0 and 15 was added with an identical stratification of sub-group data.
Results: In the United States from 1999 to 2020 there were 17,238 deaths in ALL patients 55 and older. For this population there was not an improvement in mortality over the last twenty years (10.8, AAMR 1999) and (10.6, AAMR 2020). Further subgroup analysis did not reveal a significant difference over the years by reported sex, race, and US census region. Men and hispanic patients had the highest AAMR consistently, 12 and 13.6 in 2020. There was a statistically significant improvement in ages 0-15 for overall AAMR, 3.5 in 1999 to 2.2 in 2020 (Table 1).
Conclusion:
There has not been a significant improvement in AAMR for adults 55+ with ALL despite improvements seen in the pediatric patient population. Over the last twenty years AAMR in the older adult population has unfortunately been stagnant. This is despite the approval of several new therapies for adult patients with ALL including blinatumumab, inotuzumab, and the increased recognition of the importance of targeted tyrosine kinase inhibitor-based therapy for patients with Ph+ ALL, which is certainly much more prevalent in the older adult ALL population. The lack of AAMR despite the numerous seemingly therapeutic advances made in the adult population underscores the need to specifically study new therapeutics, their outcomes, utilization, and toxicities, in the sub-population of older adults with ALL in order to understand the lack of collective benefit seen in this unique patient population. Continued monitoring of the AAMR trends in this patient population will soon begin to reflect the availability of CART therapy.
Anti-BCMA Dual Epitope-Binding CAR-Marrow Infiltrating Lymphocytes (MILs) Could Offer a Potent Innovative Immunotherapeutic Tool Against Multiple Myeloma
Authors: Vo Manh-Cuong , Jung Sung-Hoon , Nguyen Van-Tan , Tran Van-Dinh-Huan , Kim Sang-Ki , Bae Woo Kyun , Kim Hyeoung-Joon , Wang Lin , Lee Je-Jung 
Published: December 2023

Introduction: Chimeric antigen receptor (CAR) T cells are a promising new treatment for multiple myeloma (MM). Marrow-infiltrating lymphocytes (MILs) derived from MM patient's bone marrow are another potential innovative T cell source for CAR-based cell therapy, capable of robustly and specifically targeting myeloma cells through polyclonal targets. MILs possess polyclonal central memory T cell populations, which could be as effective MM killings via polyantigenic cytotoxic T cells with greater recognitions of broad range of tumor antigens via the polyclonal memory TCR as well as the CAR pathway with strong recognition of tumor antigens. Nanobodies are currently the smallest stable antibody molecules having high affinity for antigen, allowing them to strongly penetrate tumor tissue and even directly to the blood-brain barrier while remaining low toxicity and immunogenicity. With the peculiar properties, nanobodies have been widely used as the antigen biding domain of CAR-T cell. In this study, we investigated anti-B-cell maturation antigen (BCMA) dual epitope-binding CAR-MILs against MM.
Methods: CD3 + T cells isolated from bone marrow mononuclear cells of MM patients were stimulated with Ex Vivo CD3/CD28 in the presence of recombinant human IL-2. The nanobodies VHH01 and VHH02 were provided as dual epitope-binding for BCMA (Senlang, China). After expansion and activation for 2 days, anti-BCMA dual epitope-binding CAR was transduced to the activated MILs and, they were stimulated with Ex Vivo CD3/CD28 in the presence of recombinant human IL-2, IL-7, IL-15, and IL-21. Expanded and activated BCMA dual epitope-binding CAR-MILs (BCMA CAR-MILs) were harvested on days 7, 14, and 21 for further experiments.
Results: The transduction efficiency of BCMA CAR-MILs was approximately 34%, and the expansion of BCMA CAR-MILs was &gt; 100 folds over 21-day culture period. Additionally, BCMA CAR-MILs showed a dramatically increased proportion of CD8 + T cells, while the proportion of CD4 + T cells decreased. Moreover, BCMA CAR-MILs were enriched with a higher proportion of central memory T cells (Tcm) (80%), while the proportions of regulatory T cells (Tregs) and checkpoint molecules (TIGIT, TIM3, and CD73) were not so high. The BCMA CAR-MILs showed potent cytotoxicity, particularly high levels of CD107a degranulation against BCMA-expressing target cancer cell lines, such as Daudi, Raji, RPMI8226, and U266B1 cells, and autologous CD138 + primary myeloma cells.
Conclusion: This study suggested that BCMA dual epitope-binding CAR-MILs were easily expanded and activated using bone marrow mononuclear cells from MM patients with high transduction efficiency and induced a potent anti-myeloma immune response, which may offer an alternative innovative immunotherapeutic approach against MM patients in the future.
Letermovir Prophylaxis for Cytomegalovirus Reactivation in β Thalassemia Major Children after Hematopoietic Cell Transplantation
Authors: Shi Lingling , Liu Rongrong , Zhang Zhongming , Huang Cuifeng , Liu Lianjin , Yao Yibin , Wei Zhenbin , Wei Shuyi , Gan Zhaoping , Sun Na , Liu Beicai , Huang Rui , Zhou Xuemei , Chen Yinghua , Liu Qifa , Lai Yongrong 
Published: December 2023

Background: Cytomegalovirus(CMV) is one of the most important infections following allogeneic haematopoietic stem cell transplantation (HSCT). Although Letermovir is licensed for prophylaxis of CMV infection in allogeneic hematopoietic cell transplant adult CMV seropositive patients. There are limited data for letermovir as primary CMV prophylaxis in pediatric patients . The objective of the study was to analyze the the use of letermovir for prophylaxis from CMV infection in β thalassemia major children undergoing allo-HSCT in a single center.
M ethods : This study was an retrospective, single-center evaluation of β thalassemia major pediatric recipients treated by allo-HSCT in the First Affiliated Hospital of Guangxi Medical University. 34 patients included in the study were CMV-seropositive, underwent allo-HSCT, and were started on letermovir for primary CMV prophylaxis between June 2022 and July 2023. CMV monitoring was performed 2 times a week until day +100 after HSCT. The primary end point was CMV reactivation on days +100.
Results: 34 patients were analyzed. 20 patients were transplanted from haploidentical donor, 9 patients were transplanted from matched-related donor, 5 patients were transplanted from matched-unrelated donor. The median followed-up was 129 days (range, 50-405 days).The median age was 9 years (range, 2-16 years). The GVHD prophylaxis for matched-related donor group was cyclosporine-based , and the GVHD prophylaxisfor haploidentical and matched-unrelated donor groups were tacrolimus-based. Letermovir start at median 21 days (range 10-35 days) after HSCT. The median weight at the initiation of letermovir was 18.8 kg (range, 12-25 kg). The dose of letermovir was 240mg and 120mg orally once daily in tacrolimus co-administration and cyclosporine co-administration, respectively. During the follow-up period , CMV reactivation was observed in 8 patients totally (23.5%). Among them, 6 patients(17.6%) were in haploidentical donor group. 1 patient (2.9%) in matched-related group and 1 patient (2.9%) in matched-unrelated donor group was CMV reactivated, respectively. Throughout letermovir prophylaxis, the median CMV DNAemia level was 1945 copies (range,526-3800 copies), and the CMV DNAemia lasting time were 17.5 days (range,15-59 days). No patients developed clinically significant CMV infection. 1 patient died because of pulmonary infection of mucor. No serious hepatotoxicity, nephrotoxicity or letermovir intolerance was described.
Conclusion: Our data support letermovir prophylaxis efficacy and safety in β thalassemia major children after allo-HSCT.
Preclinical Efficacy of a Novel CD8-Targeted Fusosome for In Vivo CAR T Cell Therapy
Authors: Chaturvedi Vandana , Green Jesse , Zipp Garrett , Lampano Aaron , Liang Ouwen , O'Rourke Allison , Granger Brian , Elpek Kutlu G , van Hoeven Neal , Fry Terry 
Published: December 2023

SG299 is a CD8-targeted fusosome; a self-inactivating (SIN) lentiviral vector (LVV) pseudotyped with a CD8-targeted fusogen, which carries a transgene encoding a CD19-directed chimeric antigen receptor (CAR). We evaluated the preclinical efficacy of a representative CD8/CD19CAR fusosome comparable to SG299 for its ability to control tumor growth in vivo in an NSG mouse model engrafted with human CD19 positive tumor cells and human peripheral blood mononuclear cells (PBMC). We compared direct intravenous (IV) administration and ex vivo exposure of fusosome to resting T cells followed by IV injection of vector-cell mixtures, as has been proposed for extracorporeal delivery (ECD) methods. We have also evaluated the performance of multiple lots of fusosomes to assess consistency in manufacturing and have evaluated donor-to-donor variability in five PBMC donors in this model.
To measure anti-tumor efficacy, immunodeficient NSG mice were challenged IV with NALM6 tumors expressing firefly luciferase (5E5 cells/mouse) on day 4. For direct IV, PBMC (1E7 cells/mouse) were injected IV on day -1 followed by CD8/CD19CAR fusosome (1E7 IU/mouse) on day 0. For ECD, PBMC were incubated with CD8/CD19CAR fusosome for 1 hr and the cell and fusosome mix were injected IV on day 1. Tumor growth was monitored by bioluminescence imaging over a 28-day period. In addition, we have investigated both pharmacokinetics of fusosome induced CAR T cells and NALM6 tumors by flow cytometry.
CD8/CD19CAR fusosome demonstrated statistically significant control of NALM6 tumors by both direct IV and ECD routes of delivery. Kinetic analysis of peripheral blood demonstrated tumor control and in vivo CART cell generation were dose dependent. The peak CAR T cell response was at D14. CARs detected at all timepoints were CD8+ specific; no CD4 + CAR T cells were observed. In addition, all mice that received fusosome demonstrated protection from morbidity and mortality as measured by reduced weight loss and improved survival compared to control or tumor only mice. Lot-to-lot performance variability of fusosomes was minimal; three lots of fusosome that had similar physical and functional attributes showed efficient and equivalent tumor control with multiple PBMC donors. Finally, an assessment of donor-to-donor variability across five PBMC donors using a single lot of fusosome showed donor-specific variations in tumor control as measured by BLI but demonstrated a consistent protection from morbidity and mortality. Collectively, these studies demonstrate preclinical efficacy of our CD8/CD19CAR candidate, lot consistency and verify our ability to generate CD19-directed CAR T cells in vivo using a specifically targeted platform.
Association of Autoimmune Diseases and Their Effect on Outcomes of Heparin-Induced Thrombocytopenia: An Analysis of the National Inpatient Sample (2016-2020)
Authors: Srivastava Arnav , Jain Tripti , Mahmoud Amir , Kharel Himal , Orakzai Abdullah , Eltaher Basant , Piplani Shobhit 
Published: December 2023

Introduction: Heparin-Induced Thrombocytopenia (HIT) is a prothrombotic reaction to heparin exposure caused by antibodies directed towards heparin-platelet protein platelet factor 4 complexes. This thrombocytopenia is associated with and can lead to fatal venous and arterial thrombosis. This study aims to compare outcomes and assess the association of autoimmune diseases with HIT.
Methods: A query of the National Inpatient Sample (2016-2020) was performed for index admissions with a principal diagnosis of HIT and concurrent autoimmune diseases using ICD 10 codes. Patient demographics and outcomes were identified. Univariate analysis with t-test or chi-squared was performed where appropriate. A multivariate regression analysis was used to generate adjusted odds ratios (AOR), adjusting for age, race, sex, and Charlson Comorbidity Index (CCI) score. The P-value significance was set at &lt;0.05. All analysis was performed in STATA MP version 14.2.
Results: A total of 72,935 patients with HIT met the inclusion criteria, of which, 2.88% had an underlying autoimmune disease. Those with auto-immune disease had a greater proportion of Caucasians, females, and younger patients. While there were no statistically significant differences in mortality, embolic, or bleeding events, patients with autoimmune disease were 43% less likely to become septic (AOR 0.57, p-value 0.006). Additionally, patients with autoimmune diseases had a lower mean hospital services charge and length of stay (p&lt;0.001).
Conclusion: Patients with HIT and autoimmune disease showed better outcomes in terms of sepsis, mean length of stay, and hospital services charge without any significant difference in embolic or bleeding outcomes. Underlying autoimmune disease likely does not confer any additional risk to HIT hospitalizations. This might be speculated to be due to the different underlying pathology driving HIT or accompanying immunosuppressants treatment in autoimmune diseases hindering the aggressiveness of immune response.
Safety and Efficacy of Venetoclax Salvage Therapy in Relapsed/Refractory Multiple Myeloma with and without t(11;14)
Authors: Steinhardt Maximilian J , Bittrich Max , Zhou Xiang , Noderer Julia , Riedhammer Christine , Xiao Xianghui , Gawlas Sophia , Weis Philipp , Eisele Florian , Munawar Umair , Han Seungbin , Mersi Julia , Waldschmidt Johannes M , Einsele Hermann , Rasche Leo , Kortüm K. Martin 
Published: December 2023

Background:
The BCL2 inhibitor Venetoclax (Ven) is an effective treatment option in multiple myeloma (MM). However, despite the recent inclusion in European MM treatment guidelines, no approval has yet been granted for the treatment of MM and the optimal dosage, combination partners and timing of treatment remain under investigation.
Methods:
We conducted an analysis of 40 MM patients treated with Ven at our institution from November 2017 until June 2022. 64% of them had a t(11;14), all were heavily pretreated with a median of 7 lines of prior lines of therapy, and 75% were penta-refractory. High-risk features were enriched in the cohort (47% for all 38 with FISH available via IMWG criteria). Risk was evenly distributed between patients with and without t(11;14). Patients received either Ven alone or in combination with other MM drugs over a median of 5 cycles.
Results:
The full cohort overall response rate reached 53%, ten patients (25%) achieved partial remission (PR), seven patients (17.5%) went into VGPR and four patients (10%) had a complete remission (CR). Moreover, stable disease (SD) for three months or longer was achieved in seven patients (18%). The median progression-free survival was 5.1 months and the duration of response reached 9.6 months.
Subgroup analysis revealed that patients harboring t(11;14) had significantly increased PFS and OS: Median PFS reached 11.2 vs. 4.4 months and median OS was not reached vs. 12.8 months, respectively.
Overall, hematological AEs grade 3 or higher were documented in 65% of patients and three high-grade infectious complications (7.5%) occurred. Two of these patients died from sepsis, another recovered from pneumonia with severe sequelae. Interestingly, in contradiction to the BELLINI experience, all high-grade infectious complications occurred in the t(11;14) positive cohort.
Conclusion:
In our real-world analysis, Ven demonstrated to be an effective MM treatment option for t(11;14) positive relapsed/refractory MM. However, the significant infectious complications suggest antibiotic prophylaxis and careful monitoring of patients undergoing Ven treatment.