bluuebunny/crossref_metadata_2025_split huggingface dataset:
Nucleated red blood cells as a prognostic marker for mortality in patients with SARS-CoV-2-induced ARDS: an observational study
Authors: Kirsch Anna , Niebhagen Felix , Goldammer Miriam , Waske Sandra , Heubner Lars , Petrick Paul , Güldner Andreas , Koch Thea , Spieth Peter , Menk Mario 
Published: June 2024

Abstract
Background
The presence of nucleated red blood cells (NRBCs) in the peripheral blood of critically ill patients is associated with poor outcome. Evidence regarding the predictive value of NRBCs in patients with SARS-CoV-2-induced acute respiratory distress syndrome (ARDS) remains elusive. The aim of this study was to evaluate the predictive validity of NRBCs in these patients.

Methods
Daily NRBC values of adult patients with SARS-CoV-2-induced ARDS were assessed and their predictive validity for mortality was statistically evaluated.
A cut-off level based on the patient’s maximum NRBC value during ICU stay was calculated and further specified according to Youden’s method. Based on this cut-off value, further analyses such as logistic regression models and survival were performed.

Results
413 critically ill patients with SARS-CoV-2-induced ARDS were analyzed. Patients who did not survive had significantly higher NRBC values during their ICU stay compared to patients who survived (1090/µl [310; 3883] vs. 140/µl [20; 500]; p < 0.0001). Patients with severe ARDS (n = 374) had significantly higher NRBC values during ICU stay compared to patients with moderate ARDS (n = 38) (490/µl [120; 1890] vs. 30/µl [10; 476]; p < 0.0001).
A cut-off level of NRBC ≥ 500/µl was found to best stratify risk and was associated with a longer duration of ICU stay (12 [8; 18] vs. 18 [13; 27] days; p < 0.0001) and longer duration of mechanical ventilation (10 [6; 16] vs. 17 [12; 26] days; p < 0.0001). Logistic regression analysis with multivariate adjustment showed NRBCs ≥ 500/µl to be an independent risk factor of mortality (odds ratio (OR) 4.72; 95% confidence interval (CI) 2.95–7.62, p < 0.0001). Patients with NRBC values below the threshold of 500/µl had a significant survival advantage over those above the threshold (median survival 32 [95% CI 8.7–43.3] vs. 21 days [95% CI 18.2–23.8], log-rank test, p < 0.05).
Patients who once reached the NRBC threshold of ≥ 500/µl during their ICU stay had a significantly increased long-term mortality (median survival 489 days, log-rank test, p = 0.0029, hazard ratio (HR) 3.2, 95% CI 1.2–8.5).

Conclusions
NRBCs predict mortality in critically ill patients with SARS-CoV-2-induced ARDS with high prognostic power. Further studies are required to confirm the clinical impact of NRBCs to eventually enhance decision making.
Landscape analysis and oncologic outcomes in advanced urothelial carcinoma (UC) by NECTIN4 RNA expression.
Authors: Stewart Tyler F. , Fenton Sarah Elizabeth , Nazari Shayan , Elliott Andrew , Garje Rohan , Salmasi Amirali , Bagrodia Aditya , Nabhan Chadi , VanderWeele David James , McKay Rana R. 
Published: June 2024

4585 Background: Advanced UC is a devastating disease, however recent advances with antibody drug conjugates (ADCs), including enfortumab vedotin (EV), have improved outcomes significantly. Currently no biomarkers are clinically available to predict response to therapy. We hypothesized that benefit from EV may correlate with mRNA expression of NECTIN4, the gene encoding the relevant cell surface antigen for EV. Therefore, we performed a landscape analysis of NECTIN4 in advanced UC and correlated expression with oncologic outcomes. Methods: Bladder and upper tract UC samples were tested at Caris Life Sciences (Phoenix, AZ) with NextGen Sequencing on DNA (592 genes or whole exome) and NovaSeq on RNA (whole transcriptome). UC samples were stratified by NECTIN4 mRNA levels into four quartiles. Tumor mutational burden (TMB) totaled somatic nonsynonymous mutations per tumor (high >10 mut/Mb). Insurance claims data were used to calculate survival outcomes using Kaplan-Meier estimates. Overall survival (OS) was calculated from the date of sample collection and date of treatment initiation to date of last follow up. Time on treatment (TOT) was calculated from date of treatment initiation to date of last treatment.Survival analysis was performed between top and bottom quartiles of NECTIN4 expression. Results: A total of 6,395 patient samples were analyzed [n=4335 from primary tumor (3496 bladder/urethra, 839 upper tract), n= 2060 from metastases]. Expression of NECTIN4 was associated with higher rates of mutations in FGFR3 (18.9% vs 6.9%), ERBB2 (11.8% vs 5.9%), pTERT (77.3% vs 62.6%), CCNE1 (5.6% vs 1.7%), SDHC (8.3% vs 0.6%) and with TMB-H status (46.2% vs 35.8%) but lower rates of TP53 mutations (54.6% vs 67.7%). NECTIN4 expression positively correlated with expression of TACSTD2 (TROP2), ERBB2 (HER2) and SLITRK6. Interestingly, NECTIN4 expression inversely correlated with PDL1 expression by IHC (22c3, 26.9% vs 59.2%). Similar findings were found when analysis was performed by primary bladder versus primary upper tract, as well as primary versus metastatic site. NECTIN4 expression was associated with longer OS in the overall population, and improvement in TOT (HR 0.53) and OS (HR 0.67) for patients treated with EV (Table). NECTIN4 expression was not associated with benefit with anti-PD1/L1 therapy. Conclusions: In the largest study investigating NECTIN4 expression in UC, we demonstrate co-expression of TACSTD2 (TROP2), ERBB2 (HER2) and SLITRK6 with NECTIN4. Expression of NECTIN4 correlated with favorable prognosis and predicted benefit from EV. NECTIN4 RNA expression could be a potential biomarker for selecting patients for treatment with EV. Further validation is required. [Table: see text]
Single agent axitinib in the management of patients with progressive pheochromocytoma and paraganglioma.
Authors: Fojo Antonio Tito , Apolo Andrea B , Edgerly Maureen , Pacak Karel , Figg William Douglas , Bates Susan Elaine , Del Rivero Jaydira 
Published: June 2024

4602 Background: Malignant pheochromocytomas and paragangliomas remain diseases that present those caring for patients with these diseases the dual challenges of hormonal excess and malignant behavior. Radiolabeled therapy with meta-iodobenzguanine (MIBG) and chemotherapy with a combination of cyclophosphamide, vincristine and dacarbazine can help in the management of patients whose disease has metastasized, but additional options are needed. The phase II FIRSTMAPPP study provided support for use of the tyrosine kinase inhibitor, sunitinib, in these malignancies with median PFS values of 8.9 vs. 3.6 months and ORRs of 31% vs. 8% for sunitinib vs placebo.Median duration of sunitinib therapy was 11 months. Concurrent with this study we launched a single arm trial to examine the activity of a similar TKI, axitinib. We report here the results of that study. Methods: Axitinib was self-administered at a dose of 5 mg every 12 hours continuously in a 28-day cycle. All patients were evaluated for dose adjustments to levels of 2, 3, 7, and 10 mg bid as options with intervals of at least 4 weeks between any dose escalations. Efficacy evaluations using conventional imaging were performed every 12 weeks. Documented evidence of disease progression was required prior to study entry. Results: Nineteen patients were enrolled; two did not receive treatment or less than one week of treatment. A partial response was achieved in 35.3% of patients, with a median reduction of tumor measurements of 34% and a median duration of response of 7.4 months. Median PFS was 7.9 months. Median duration of treatment was 9.5 months. Median OS was 29 months. Axitinib was well-tolerated with treatment-emergent adverse events with an attribution of possible, probable, and definite similar to those previously reported for the agent, including G1/2 fatigue, diarrhea, mucositis, and PPE in 42% to 63% and G1/2/3 hypertension in 79%, all managed with adjustments in antihypertensive medications No patient discontinued axitinib for an adverse event, nor had a prolonged suspension of treatment. Unfortunately, the study has been prematurely terminated by the sponsor. Conclusions: These results together with similar results reported recently with sunitinib provide strong evidence for the efficacy of sunitinib and axitinib, two VEGF tyrosine kinase inhibitors with similar characteristics, in the management of malignant pheochromocytoma and paragangliomas. Axitinib should be started at a dose of 5 mg bid and adjusted as tolerated. Despite its use in individuals with often difficult to treat hypertension, blood pressure management did not present a difficult challenge. Clinical trial information: NCT03839498 .
Comparing treatment modalities for T2N0M0 muscle invasive bladder cancer: A propensity score analysis with the National Cancer Database.
Authors: Pieretti Alberto , Mohanna Mohamed , Sabbagh Saad , Muruve Nicolas , Liang Hong , Fleming Christopher , Weight Christopher , Almassi Nima , Haber Georges-Pascal , Kamat Ashish M. , Arteta-Bulos Rafael , Dinney Colin P.N. 
Published: June 2024

4604 Background: Muscle-invasive Bladder Cancer (MIBC) constitutes 25% of bladder malignancies. Per NCCN guidelines, the primary treatment for stage II (T2N0M0) MIBC is neoadjuvant chemotherapy (NAC) followed by radical cystectomy (RC), RC alone, or bladder preservation chemoradiotherapy (BPCRT). This study aims to compare the overall survival between different treatment modalities with an emphasis on patients considered to be best candidates for BPCRT (No hydronephrosis, extensive or multifocal carcinoma in situ (CIS), and tumor size <6cm, ”low-risk”) versus those who are not (“high-risk”). Methods: We queried 12510 patients from the National Cancer Database from 2004-2020 for stage II T2N0M0 MIBC. Patients were divided in low-risk (< 6 cm and no evidence of CIS) or high-risk MIBC. The propensity score matched (PSM) sample was constructed greedy nearest neighbor matching on the logit of the propensity score using a caliper of width equal to 0.2 of the standard deviation of the logit of the propensity score. We used standardized differences (SD) to evaluate how well the covariates were balanced and a value of < 0.1 was considered negligible. The Cox proportional hazards model was performed to compare the survivorships between the PSM paired samples. All data analyses were conducted using SAS version 9.4. Results: Following PSM and risk factor stratification, we found that median overall survival (OS) was lower with BPRCT compared to RC alone or NAC+RC in both risk groups. In the low-risk group, the median OS of BPRCT compared to NAC+RC was 34 and 76 months, respectively (HR = 1.81, 95%CI = (1.25-2.62), p=0.0017 and there was no statistical significant difference in RC compared to NAC+RC median OS (p=0.3459). In the high-risk group, the median OS of BPRCT compared to NAC+RC was 22 and 68 months, respectively (HR = 2.19, 95%CI = (1.86-2.59), p<0.0001) (Table) and the median OS of RC compared to NAC+RC was 79 and 99 months respectively (HR=1.2, 95%CI = (1.11-1.3), p<0.001 (Table). Conclusions: This nationwide study showed that RC was the optimal treatment for low-risk stage 2 MIBC, with improved OS compared with BPCRT and equivalent OR with NAC+RC, without the added cost or morbidity. For high-risk patients NAC+RC was associated with a significant improvement of OS compared to BPCRT and RC alone.[Table: see text]
Association of elevated pulmonary artery systolic pressure with hematologic progression in myeloproliferative neoplasms.
Authors: Leiva Orly , Soo Steven , How Chi-Joan , Smilowitz Nathaniel , Shah Binita , Reynolds Harmony , Hobbs Gabriela , Bernard Samuel 
Published: June 2024

6575 Background: Pulmonary hypertension (PH) is associated with myeloproliferative neoplasms (MPN), including essential thrombocythemia (ET), polycythemia vera (PV), and myelofibrosis (MF). Prior studies have suggested that patients with MPN and cardiovascular disease (CVD) with PH are at increased risk of progression of MPN to secondary MF or acute leukemia. Further characterization of risk of hematologic progression among all-comers with MPN is lacking. Methods: In this single-center, retrospective cohort study, patients with MPN and ≥ 1 transthoracic echocardiogram (TTE) after diagnosis were identified. PH was defined as an estimated pulmonary artery systolic pressure (PASP) ≥ 40 mmHg on first TTE after MPN diagnosis. Primary outcome was hematologic end-point, composite of progression of MPN to secondary MF, acute leukemia, death related to MPN, or bone marrow transplantation (BMT). Secondary endpoint was major adverse cardiovascular events (MACE), composite of arterial thrombosis, venous thromboembolism, heart failure (HF) and CV death. Multivariable Fine-Gray competing-risk regression (with non-hematologic death and non-CV death as competing-risks for hematologic endpoint and MACE, respectively) were used to estimate risk of outcomes. Results: Of 272 patients with MPN identified, 69 (25.4%) had PH on first TTE. Patients with PH were older at MPN diagnosis, had more MF (27.5% vs 11.8%, p = 0.004), and prior HF (18.8% vs 6.4%, p = 0.004). Patients with PH had higher rates of secondary mutations (24.6% vs 13.3%, p = 0.024), particularly in ASXL1 (8.7% vs 2.5%, p = 0.034) and RUNX1(4.3% vs 0, p = 0.016). After a median follow-up of 46.2 months (IQR 29.3, 69.1), hematologic endpoint (30.4% vs 8.4%, p < 0.001 and MACE (53.6% vs 23.6%, p < 0.001) were higher in PH group. Rates of secondary MF (13.0% vs 4.9%, p = 0.030), acute leukemia (13.0% vs 0.5%, p < 0.001), and death related to MPN (8.7% vs 1.5%, p = 0.01) but not BMT (2.9% vs 3.4%, p = 1.00) were higher in PH. After adjusting for age, sex, MPN type, mutation, and time from MPN to first TTE, PH was associated with higher risk of hematologic endpoint (aSHR 3.70, 95% CI 1.55 – 8.82). After adjusting for the same variables as well as LVEF, left atrial size, prior CVD, PH was associated with increased risk of MACE (aSHR 2.38, 95% CI 1.42 – 3.97). Conclusions: Among patients with MPN, PH on TTE was associated with increased risk of hematologic progression and MACE. Prospective studies are needed to confirm our findings. Further investigation into the underlying mechanisms of PH in MPN should be conducted. [Table: see text]
Real-world treatment patterns and outcomes in patients with myelofibrosis treated with pacritinib in the United States.
Authors: Marrone Michael , Geller Robert , Oladapo Abiola , Suthar Purvi , Vasudevan Anupama , Vredenburg Michael , Zeng Jia , Rampal Raajit , Mascarenhas John 
Published: June 2024

6579 Background: Pacritinib (PAC), a JAK1 sparing JAK2/IRAK1/ACVR1 inhibitor, has shown clinically significant activity in spleen volume and symptom reduction in patients (pts) with thrombocytopenic myelofibrosis (MF). Thrombocytopenic MF is challenging to manage and pts with platelets (PLT) <50 x109/L have limited median overall survival (OS) of 15 months (mo) (Masarova 2018). Since approval as the only agent for thrombocytopenic MF, real-world evidence of PAC use is limited. This study aims to assess treatment patterns, hematological outcomes, and survival in pts with MF treated with PAC in the US. Methods: For this retrospective study, Integra-PrecisionQ de-identified database was used to locate pts with MF (ICD-10: 75.81, D47.4) treated with PAC from 6/1/2022 to 8/31/2023. Treatment-related outcomes include PLT and hemoglobin (Hb) levels from PAC initiation (index) and 30-day intervals post-index. OS was assessed from index through the end of the study period. Data are presented as medians and interquartile ranges (IQR). Results: 142 pts with MF were treated with PAC, the majority being male (60%) or White (66%), with a median age at MF diagnosis of 72 years and median of 13.4 mo from diagnosis to index. In pts receiving ≥2nd line (2L) PAC (65.5%), the median time from the end of prior MF therapy to PAC initiation was 1 day. Median follow up from index was 6 mo and median exposure to PAC during the observation period was 5.3 mo. In pts with PLT and Hb levels at index and follow up, 28.5% (34/119) had severe thrombocytopenia (PLT<50 x109/L) at index and 29% (35/119) had severe anemia (Hb <8.0 g/dL). Median PLT count was 81 x109/L (47.5,179) at index (n=119) and 96 x109/L (68.5,125) at post-index day 360 (n=15). Median Hb level was 8.8 g/dL (7.9,10.3) at index (n=119) and 10.4g/dL (9.2,11.6) at post-index day 360 (n=15). Increases in PLT and Hb were observed across index PLT and Hb groups over follow up (Table 1). 1-year OS probability was 69.4% (95% CI=56.8-79.0) overall, 77.3% (95% CI=61.5-87.3) in pts treated with 1L PAC, and 75.2% (95% CI=46.3-90.0) for pts treated with 1L PAC with PLT <50 x109/L. Conclusions: In addition to spleen and symptom benefits, real-world outcomes demonstrate stability or improvement in thrombocytopenia and anemia in MF pts treated with PAC, with OS in the 1L setting comparing favorably with other JAK inhibitor historical controls. [Table: see text]
Lisocabtagene maraleucel (liso-cel) vs standard of care (SOC) with salvage chemotherapy (CT) followed by autologous stem cell transplantation (ASCT) as second-line (2L) treatment in patients (pt) with R/R large B-cell lymphoma (LBCL): 3-year follow-up (FU) from the randomized, phase 3 TRANSFORM study.
Authors: Kamdar Manali Kirtikumar , Solomon Scott R. , Arnason Jon , Johnston Patrick B. , Glaß Bertram , Bachanova Veronika , Ibrahimi Sami , Mielke Stephan , Mutsaers Pim , Hernandez-Ilizaliturri Francisco J. , Izutsu Koji , Morschhauser Franck , Lunning Matthew Alexander , Chow Victor A. , Santamaria Josu , Colicino Silvia , Ogasawara Ken , Stepan Lara , Abramson Jeremy S. 
Published: June 2024

7013 Background: Liso-cel is an autologous, CD19-directed, 4-1BB CAR T cell product. In prespecified interim and primary analyses of TRANSFORM (NCT03575351), liso-cel showed significant improvements in efficacy vs SOC in pts with R/R LBCL. Here we report results after ~3-y FU. Methods: TRANSFORM is a randomized phase 3 study comparing liso-cel vs SOC (CT [R-DHAP, R-ICE, or R-GDP] then high-dose CT [HDCT] + ASCT) in adults aged ≤ 75 y with LBCL primary refractory to or relapsed ≤ 12 mo after first-line therapy and eligible for ASCT. Liso-cel arm pts underwent lymphodepletion followed by liso-cel (100 × 106 CAR+ T cells). Bridging therapy was allowed. SOC arm pts received 3 cycles of CT; responding pts proceeded to HDCT + ASCT. Crossover to receive liso-cel was allowed for SOC arm pts if criteria were met. The primary endpoint was event-free survival (EFS) per independent review committee (IRC). Key secondary endpoints included CR rate and PFS per IRC, and OS. Endpoints were not statistically retested and are reported descriptively. Results: In total, 184 pts were randomized (92 per arm); baseline characteristics were reported (Abramson et al. Blood 2023). Median (range) FU was 33.9 mo (0.9–53.0). Median EFS, PFS, and duration of response (DOR) were longer for liso-cel vs SOC, similar to the primary analysis (Table). A total of 61 (66%) SOC arm pts crossed over to receive liso-cel. Median OS was not reached (NR) in either arm; 36-mo OS rates were numerically higher for liso-cel. Of 76 total deaths (liso-cel, n = 34; SOC, n = 42 [crossover pts, n = 33]), 10 occurred since the primary analysis (liso-cel, n = 6; SOC, n = 4 [all crossover pts]); most were due to disease progression or complications (n = 6). Safety results were consistent with the primary analysis. Cellular kinetics and B-cell aplasia will be presented. Conclusions: After median FU of 33.9 mo, liso-cel as 2L treatment in pts with primary refractory or early relapsed LBCL resulted in deepening of response and continued improvement in efficacy endpoints over SOC, confirming the ongoing benefit of liso-cel. Clinical trial information: NCT03575351 . [Table: see text]
Cost analysis of targeted and immunotherapies in operable esophageal and non-small cell lung cancers.
Authors: Alwatari Yahya , Shanshal Mohamed , Johnson Nate C , Thao Viengneesee , Borah Bijan J. , Shen Robert 
Published: June 2024

8051 Background: The National Comprehensive Cancer Network (NCCN) currently recommends the use of Atezolizumab, Nivolumab, Osimertinib, and Pembrolizumab in the perioperative management of non-small cell lung cancers (NSCLC) and esophageal cancers (EC). As the therapeutic landscape evolves, we aim to evaluate the cost implications of these guidelines for eligible patients in the United States. Methods: The Medicare Part B payment allowance limits of each medication were ascertained except Osimertinib for which an approximate wholesale acquisition cost (WAC) was reported due to privately administered Medicare Part D coverage. Using national data and published literature, we estimated the annual incidence of patients with newly diagnosed EC and NSCLC who would be eligible for surgery combined with neoadjuvant and/or adjuvant immune and targeted therapy. We applied the estimated cost of the medication based on dosing and duration of treatment, which spanned 1 year for all but adjuvant Osimertinib, which spanned 3 years. Using these data, the cost per patient and the total cost for an incident cohort were estimated. Results: We estimated that 8,602 patients with newly diagnosed EC would be eligible for adjuvant Nivolumab; the cost to treat one patient was $248,529, and the cost to treat one incident cohort was approximately $2 billion (Table). We estimated that 50,409 patients with NSCLC will meet the criteria for neoadjuvant Nivolumab with a total cost of three cycles of $32,894 per patient and $1.7 billion per cohort. Among NSCLC patients who may undergo resection and qualify for adjuvant therapy (Stage IB – IIA with high-risk features or IIB-IIIA), 85,063 patients are anticipated to be EGFR-negative and treated with adjuvant Atezolizumab or Pembrolizumab. Treatment costs range from $178,584 – $197,320 per patient with up to $16 billion cost per cohort. The cost to treat one patient with adjuvant Osimertinib was $556,720, and the cost to treat one incident cohort was close to $10 billion. In total, the cost to treat an incident cohort of eligible operable thoracic malignancies could exceed $30 billion. Conclusions: Neoadjuvant and adjuvant immune and targeted therapy in operable thoracic patients is associated with a significant cost burden. Prospective large-scale studies are needed to assess cost-effectiveness, particularly given the paucity of superior overall survival data with these agents. [Table: see text]