tbuckley/cabot-search huggingface dataset:
Casting Data on Wrist Fracture Outcomes
Authors: Jason Michael Johanning
Journal: JAMA Network Open (2021)

Kevin C. Chung, MD, MS; Hyungjin Myra Kim, ScD; Sunitha Malay, MPH; Melissa J. Shauver, MPH; WRIST Group; Steven C Haase; Jeffrey N Lawton; John R Lien; Adeyiza O Momoh; Kagan Ozer; Erika D Sears; Jennifer F Waljee; Matthew s Brown; Hoyune E Cho; Brett F MIchelotti; Tamara D Rozental; Paul T. Appleton; Edward K Rodriguez; Laura N. Deschamps; Lindsay Mattfolk; Katiri Wagner; Philip Blazar; Brandon E Earp; Emerson Floyd; Dexter L Louie; Fraser J. Leversedge; Marc J. Richard; David S Ruch; Suzanne Finley; Cameron Howe; Maria Manson; Janna Whitfield; Bertrand Perey; Kelly Apostle; Dory Boyer; Farhad Moola; Trevor Stone; Darous Viskontas; Mauri Zomar; Karyn Moon; Raely Moon; Loree K Kalliainen; Christina M Ward; James W Fletcher; Cherrie A Heinrich; Katharine S Pico; Ashish Y. Mahajan; Brian W Hill; Sandy Vang; Dawn M Laporte; Erik A Hasenboehler; Scott D Lifchez; Greg M Osgood; Babar Shafiq; Jaimie T Shores; Vaishali Laljani; Brent H Bamberger; Timothy W Harman; David W Martineau; Carla Robinson; Brandi Palmer; Ruby Grewal; Ken A Faber; Joy C MacDermid; Kate Kelly; Katrina Munro; Joshua I Vincent; David Ring; Jesse B Jupiter; Jilian S Gruber; Abigail Finger; Rakesh K Reddy; Taylor M Pong; Emily Thornton; David G Dennison; Sanjeev Kakar; Marco Rizzo; Alexander Y Shin; Tyson L Scrabeck; Kyle Chepla; Kevin Malone; Harry A Hoyen; Blaine Todd Bafus; Roderick B Jordan; Bram Kaufman; Ali Totonchil; Dana R Hromyak; Lisa Humbert; Sandeep Sebastin; Sally Tay; Kate W Nellans; Sara L Merwin; Ethan W Blackburn; Sandra J Hanlin; Barbara Patterson; Glenn R Gaston; Christopher R Chadderdon; Erika G Gantt; John S Gaul; Daniel R Lewis; Bryan J Leffler; Lois K Osier; Paul C Perlik; Alan W Ward; Tod A Clark; Sheila McRae; Jennifer M Wolf; Craig M Rodner; Katy Coyle; Thomas P Lehman; Yuri C Lansinger; Gavin D O’Mahony; Kathy Carl; Janet Wells; David J Bozentka; Scott L Levin; David P Steinberg; Robert Goitz; Annamarie D Horan; Denise Knox; Kara Napolitano; Cathy A Naccarelli; Joelle Tighe; Warren C Hammert; Allison W McIntyre; Krista L Noble; Kaili Waldrick; Jeffrey B Friedrich; David Bowman; Angela Wilson; Zhongyu LI; Andrew L Koman; Benjamin R Graves; Beth P Smith; Debra Bullard
Author Correction: Generation of model tissues with dendritic vascular networks via sacrificial laser-sintered carbohydrate templates
Authors: Ian S. Kinstlinger, Sarah H. Saxton, Gisele A. Calderon, Karen Vasquez Ruiz, David R. Yalacki, Palvasha R. Deme, Jessica E. Rosenkrantz, Jesse D. Louis-Rosenberg, Fredrik Johansson, Kevin D. Janson, Daniel W. Sazer, Saarang S. Panchavati, Karl-Dimiter Bissig, Kelly R. Stevens, Jordan S. Miller
Journal: Nature Biomedical Engineering (2021)
The prevalence of HLA LOH in Chinese pan-cancer patients and its correlation with genomic alterations.
Authors: Jian Zhao, Xiaoxiong Xiao, Yue Li, Xuan Gao, Xiuqin Zhang, Zeyi Liu, Yuting Yi, Xiaorui Fu, Han Wang, Yan-Fang Guan, Xuefeng Xia, Weixing Zhang, jian'An Huang
Journal: Journal of Clinical Oncology (2021)

e14521 Background: Human leukocyte antigen (HLA) molecules are essential components involved in tumor antigen presentation. Loss of heterozygosity in HLA (HLA LOH) may facilitate tumor immune evasion. However, the large population study of HLALOH in Chinese pan-cancer patients remains to be explored. Methods: In this study, analysis were performed in 1504 advanced patients across 12 cancer types and 134 early-stage NSCLC patientsusing a 1021-gene panel. HLA LOH were analysis using LOHHLA algorithm. The consistency between target sequencing by 1021-gene panel and whole-exome sequencing (WES) was evaluated in 45 samples. Results: In 45 samples processed with both approaches, 95.6% (43/45) obtained concordant results. Among the 1638 patients, 24 were excluded due to homozygosity at all three HLA-Iloci. The prevalence of HLALOH in advanced patients presented considerable differences among cancer typeswith an average incidence of 45.6% (676/1482), ranging from 12.2% (prostate adenocarcinoma) to 68.0% (cervical squamous cell carcinoma). In NSCLC patients, there was an enrichment of HLALOH in both early-stage (I-IIIa) LUSC (24/88 [27.3%] of LUAD vs. 26/42 [61.9%] of LUSC, p&lt;0.001) and advanced (IIIb-IV) LUSC. In 43.3% (293/676) patients harboring HLALOH, LOH co-occurred in HLA-A, B, and C. Consistent with previous studies, the occurrence of HLALOH was relevant to an elevated TMB level(median TMB 6.72 vs. 5.76, p&lt;0.0001). In addition, the TMB level of patients with LOH at all three HLA-I loci was higher than those with LOH at only one HLA-I locus (median TMB 7.68 vs. 6.72, p=0.027).However, despite that MSI-H patients presented the highest incidence of TMB-H (TMB≥10.56), the incidence of HLALOH decreased in these patients. Alterations of multiple signaling pathways are enriched in HLALOH patients, including CPF (checkpoint factor) pathway, FA (Fanconi anemia) pathway, p53 pathway, RTK/RAS pathway, Notch pathway, Hippo pathway and Nrf2 pathway(p&lt;0.0001, p=0.023, p&lt;0.0001, p&lt;0.0001, p=0.032, p=0.013, p=0.003, respectively, Table).Several oncogenes, such as TP53 and LRP1B, had higher alteration frequencies in the HLALOH group(p&lt;0.001 for TP53,p&lt;0.05 for LRP1B, Table 1). Conclusions: The 1021-gene panel could be applied for HLALOH analysis, provided that the relevant regions are well captured. The prevalence of HLALOH in Chinese cancer patients presents considerable differences across cancer types. Besides, the occurrence of HLA LOH was accompanied by higher alteration frequencies in several oncogenes and oncogenic signaling pathways. These insights may provide valuable information for clinical practice and follow-up research.[Table: see text]
Primacy in Kidney Allocation: Does It Alleviate the Barriers to Transplantation?
Authors: John S. Gill, Catherine R. Butler, Neil R. Powe
Journal: Journal of the American Society of Nephrology (2021)

Receiving a kidney from a deceased organ donor remains the best opportunity for improved quality and length of life for manypatients with kidney failure. The transplant journey can be long, especially for minority groups, women, socioeconomicallydisadvantaged populations, and those with pre-existing
Accessibility of Telehealth services for cancer care at cancer hospital in the United States.
Authors: Victoria A. Marks, Walter R. Hsiang, James Nie, Waez Umer, Afash Haleem, Bayan Galal, Irene Pak, Dana Kim, Patrick Aloysius Kenney, Michael S. Leapman
Journal: Journal of Clinical Oncology (2021)

6535 Background: The COVID-19 pandemic has dramatically accelerated the availability of telehealth services for patients with cancer. However, little national cross-sectional data is available to inform potential gaps in access. We aimed to characterize overall access to and trends in telehealth availability for new cancer care patients at hospitals across the United States. Methods: We performed a cross sectional secret-shopper study to evaluate the availability of telehealth services for new patients for three major cancer types—colorectal, breast, and skin cancer—at Commission on Cancer accredited hospitals during the period of April to November 2020. American Hospital Association and Center for Medicare and Medicaid Service databases were queried to determine hospital characteristics. We described hospital variation in access to telehealth services using descriptive statistics. Univariable and multivariable logistic regression were used to identify factors associated with telehealth availability. Results: Of 334 successfully contacted facilities, 248 (74%) offered new patient telehealth services for at least one cancer type. However, access differed by cancer site: telehealth availability for new patients with skin, colorectal, and breast cancer was 47%, 42%, and 38%, respectively. Of the facilities sampled, 47% offered telehealth for one cancer type, 40% for two cancer types, and 14% for all three cancer types. Rates of any telehealth access among the cancer types ranged from 61% at Community Cancer Programs to 100% at NCI Designated Programs. In multivariable logistic regression, facility type was significantly associated with telehealth access while factors such as bed size, ownership, and volume were not significantly associated. Conclusions: Although access to telehealth services for patients with cancer has increased, overall gaps in access remain. Within facility differences in telehealth access imply opportunities to better align services within institutions, though further investigation is warranted as these offerings mature.[Table: see text]
Identification of signal transduction pathway activity with potential clinical target in high-grade serous ovarian and tubal carcinoma.
Authors: Phyllis van der Ploeg, Laura A.M. van Lieshout, Yvonne J.W. Wesseling-Rozendaal, Anja Van De Stolpe, Steven L. Bosch, Marjolein H.F.M. Lentjes-Beer, Paul J. van Diest, M.Caroline Vos, Joanne De Hullu, Ruud L.M. Bekkers, Jurgen M.J. Piek
Journal: Journal of Clinical Oncology (2021)

e17541 Background: High-grade serous carcinoma (HGSC) is the most common subtype of epithelial ovarian and tubal cancer. It has a high mortality rate, even after successful first-line treatment with debulking surgery and chemotherapy. Although therapeutic options for targeted therapy are rapidly expanding, identification of patients who respond to these therapies remains a challenge. In recognition of the importance of the functional phenotype of cancer cells, Verhaegh et al. (Cancer Res 2014) developed assays to measure functional activity of signal transduction pathways (STPs) based on mRNA expression levels of pathway-specific target genes. In this study, we aimed to identify HGSCs with STP activity with potential clinical target by comparing their activity assessment with STP activity in normal Fallopian tube epithelium (FTE), the tissue of origin of most HGSCs. Methods: We included 67 primary tumor samples taken prior to start of chemotherapy of postmenopausal patients diagnosed with advanced stage HGSC and 8 morphologically normal FTE samples of healthy postmenopausal women. Using OncoSignal pathway assays, we assessed functional pathway activity of the androgen receptor (AR), estrogen receptor (ER), PI3K, Hedgehog, TGF-𝛽 and Wnt pathways. Differences in STP activity between groups were compared with Mann-Whitney U tests. Cut-off value for aberrant STP activity was defined as two standard deviations above the mean value of STP activity measured in FTE samples. Results: In the HGSC group we observed lower median ER (p &lt; 0.001) and Wnt (p = 0.046) pathway activity and higher median PI3K (p = 0.025) and TGF-𝛽 pathway (p = 0.030) activity as compared to the normal FTE group. In individual HGSC samples, aberrant activity was identified for the AR (n = 14), PI3K (n = 16), Hedgehog (n = 4), TGF-𝛽 (n = 36) and Wnt (n = 10) pathways. Frequently observed combinations of aberrant STP activity were AR/TGF-𝛽 (n = 8), TGF-𝛽/Wnt (n = 6) and PI3K/Hedgehog (n = 3). In total, we identified at least one STP with potential clinical target in 52 of the 67 HGSC samples. Conclusions: Our analysis enabled the identification of STP activity with potential clinical target in 78% of the analyzed HGSC samples. Differentiation between normal and aberrant STP activity could have clinical utility in the selection of HGSC patients for targeted therapy.
First-MIND: A phase Ib, open-label, randomized study to assess safety of tafasitamab (tafa) or tafa + lenalidomide (LEN) in addition to R-CHOP in patients with newly diagnosed DLBCL.
Authors: David Belada, Katerina Kopeckova, Juan Miguel Bergua, Marc André, Ernesto Perez Persona, Petra Pichler, Pia Klöpfer, Bettina Brackertz, Emanuel Lohrmann, Anirban Lahiry, Neha Shah, Wolfram Brugger, John M. Burke, Grzegorz S. Nowakowski
Journal: Journal of Clinical Oncology (2021)

7540 Background: Tafasitamab is a humanized, Fc-modified anti-CD19 monoclonal antibody that enhances antibody-dependent cellular cytotoxicity and phagocytosis. It is FDA-approved with LEN for adult patients (pts) with relapsed/refractory (R/R) DLBCL ineligible for autologous stem cell transplantation. First-MIND (NCT04134936) is a Phase Ib, open-label, randomized study of tafa + R-CHOP or tafa + LEN + R-CHOP in newly diagnosed DLBCL. Methods: Eligible pts were ≥18 years, treatment-naïve, with histologically confirmed DLBCL not otherwise specified, international prognostic index (IPI) 2–5 and ECOG performance status (PS) 0–2. Pts with known double- or triple-hit and transformed lymphoma were excluded. Treatment (Tx) comprised six 21-day cycles of tafa (12 mg/kg IV, Day [D] 1, 8, 15) + R-CHOP (arm A) or tafa (12 mg/kg IV, D1, 8, 15) + LEN (25 mg orally, D1–10) + R-CHOP (arm B). G-CSF and VTE prophylaxis was mandatory. Primary objective is safety; secondary objectives are ORR, PET-CR rate at end of Tx, PFS, long-term safety, pharmacokinetics, immunogenicity. Results: From Dec 2019 to Aug 2020, 83 pts were screened in Europe and the US; 66 were randomized (33 per arm). Data cut-off for this analysis: 9 Dec 2020; study is ongoing. Median age was 64.5 years (range 20–86). Overall, 30% (20/66) of pts were ≥70 years and many had high-risk disease: IPI 2 29%, IPI 3 46%, IPI 4 26%. ECOG PS: 47% of pts were ECOG PS 0, 44% PS 1, 9% PS 2. Most pts had stage III/IV disease (92%); 46% had bulky disease. All pts experienced a treatment-emergent adverse event (TEAE). Grade ≥3 neutropenia and thrombocytopenia occurred in 54.5% and 12.1% (arm A) and 66.7% and 30.3% (arm B) of pts, respectively (Table). Serious TEAEs occurred in 42.4% (arm A) and 51.5% (arm B) of pts. There were three deaths, unrelated to tafa and/or LEN (sepsis, urosepsis, and COVID-19 pneumonia). R-CHOP dose intensity was maintained in both arms. Among 60 pts who completed tumor assessments after cycle 3, ORR was 89.7% (arm A) and 93.5% (arm B). Conclusions: These data suggest R-CHOP + tafa or tafa + LEN is tolerable in pts with Tx-naïve DLBCL and that R-CHOP dosing is not affected. Toxicities are similar to those expected with R-CHOP or R-CHOP + LEN. Updated safety and early efficacy data will be presented at the conference. Clinical trial information: NCT04134936. [Table: see text]
Comparison of clinician and model estimates of risk for hospitalization during systemic therapy for advanced cancer.
Authors: Lukas P Emery, Sivraj Muralikrishnan, Anna Tosteson, Deborah Schrag, Gabriel A. Brooks
Journal: Journal of Clinical Oncology (2021)

1530 Background: Patients receiving treatment for advanced cancer are at substantial risk for unplanned hospitalization. A validated two-variable risk model can identify patients at increased risk for hospitalization. However, little is known about how model-based estimates of hospitalization risk compare with assessments of treating clinicians. Methods: We identified patients initiating a new line of systemic therapy for advanced non-hematologic cancer. For each patient, we assigned three categorical estimates of 30-day hospitalization risk. The first risk estimate was generated by a validated two-variable risk prediction model with inputs of pretreatment plasma sodium and albumin (PMID: 30995122); continuous risk scores were converted to risk tertiles. We solicited a second risk estimate by real-time survey of a treating oncology clinician; clinicians were instructed to estimate hospitalization risk as low, intermediate, or high, as compared with other patients. A third hybrid risk estimate retained the highest risk category from either the clinician or model risk assessment. We describe the agreement of clinician and model-based estimates of 30-day hospitalization risk, and we compare the sensitivity and specificity of clinician, model, and hybrid high-risk assessments, using McNemar’s test. We compared discrimination of the three risk estimates via the area under the ROC curve (AUC). Results: We identified 104 patients with valid clinician and model hospitalization risk estimates and complete 30-day follow-up. The most common cancer type was lung cancer (27%), the median age was 68 years, and 62% of patients were male. 30-day hospitalization occurred in 21 patients (20.2%). There was moderate to poor agreement between clinician and model categorical estimates of hospitalization risk (weighted kappa = 0.245). The proportion of patients identified as high-risk by the clinician, model, and hybrid assessments was 15.4%, 26.0%, and 33.7%. Sensitivity and specificity of the high-risk categorization for 30-day hospitalization were 38% and 90% for the clinician assessment, 57% and 82% for the model assessment (NSS for comparison with clinician assessment), and 76% and 77% for the hybrid assessment (greater sensitivity [p = 0.008] and lesser specificity [p = 0.001] than clinician assessment). The AUC values for the clinician, model, and hybrid assessments were 0.674, 0.757, and 0.764, respectively. Conclusions: Compared with the estimate of a treating clinician, a two-variable risk model exhibited similar sensitivity and specificity for 30-day hospitalization risk. A hybrid risk assessment incorporating information from the risk model significantly improved on the sensitivity of the clinician risk assessment. Future research should test strategies to prevent hospitalizations by targeting interventions to high-risk patients.
CORONET; COVID-19 in Oncology evaluatiON Tool: Use of machine learning to inform management of COVID-19 in patients with cancer.
Authors: Rebecca Lee, Oskar Wysocki, Cong Zhou, Antonio Calles, Leonie Eastlake, Sarju Ganatra, Michelle Harrison, Laura Horsley, Prerana Huddar, Khurum Khan, Hayley Mckenzie, Carlo Palmieri, Jacobo Rogado Revuelta, Anne Thomas, Caroline Wilson, Tim Cooksley, Caroline Dive, Andre Freitas, Anne Caroline Armstrong
Journal: Journal of Clinical Oncology (2021)

1505 Background: Patients (pts) with cancer are at increased risk of severe COVID-19 infection and death. Due to COVID-19 outcome heterogeneity, accurate assessment of pts is crucial. Early identification of pts who are likely to deteriorate allows timely discussions regarding escalation of care. Likewise, safe home management will reduce risk of nosocomial infection. To aid clinical decision-making, we developed a model to help determine which pts should be admitted vs. managed as an outpatient and which pts are likely to have severe COVID-19. Methods: Pts with active solid or haematological cancer presenting with symptoms/asymptomatic and testing positive for SARS-CoV-2 in Europe and USA were identified following institutional board approval. Clinical and laboratory data were extracted from pt records. Clinical outcome measures were discharge within 24 hours, requirement for oxygen at any stage during admission and death. Random Forest (RF) algorithm was used for model derivation as it compared favourably vs. lasso regression. Relevant clinical features were identified using recursive feature elimination based on SHAP. Internal validation (bootstrapping) with multiple imputations for missing data (maximum ≤2) were used for performance evaluation. Cost function determined cut-offs were defined for admission/death. The final CORONET model was trained on the entire cohort. Results: Model derivation set comprised 672 pts (393 male, 279 female, median age 71). 83% had solid cancers, 17% haematological. Predictive features were selected based on clinical relevance and data availability, supported by recursive feature elimination based on SHAP. RF model using haematological cancer, solid cancer stage, no of comorbidities, National Early Warning Score 2 (NEWS2), neutrophil:lymphocyte ratio, platelets, CRP and albumin achieved AUROC for admission 0.79 (+/-0.03) and death 0.75 (+/-0.02). RF explanation using SHAP revealed NEWS2 and C-reactive protein as the most important features predicting COVID-19 severity. In the entire cohort, CORONET recommended admission of 96% of patients requiring oxygen and 99% of patients who died. We then built a decision support tool using the model, which aids clinical decisions by presenting model predictions and explaining key contributing features. Conclusions: We have developed a model and tool available at https://coronet.manchester.ac.uk/ to predict which pts with cancer and COVID-19 require hospital admission and are likely to have a severe disease course. CORONET is being continuously refined and validated over time.
Neuropsychiatric disorders in hospitalized patients undergoing chimeric antigen receptor T-cell therapy for aggressive lymphomas and acute lymphoblastic leukemia: A national study.
Authors: Josephine Emole, Odunayo Susan Lawal, Oleksandra Lupak, Itoro Udo
Journal: Journal of Clinical Oncology (2021)

12118 Background: Chimeric antigen receptor T cell therapy (CART) has shown efficacy in acute lymphoblastic leukemia (ALL), diffuse large B cell lymphoma (DLBCL), and primary mediastinal B cell lymphoma (PMBCL). While neurological toxicities of CART are known, neuropsychiatric disorders (NPD) in patients undergoing CART has not been well described. Our study assessed the prevalence of NPD in hospitalized patients (pts) undergoing CART, and explored association of NPD with clinical variables. Methods: Using the National Inpatient Sample database, we conducted a retrospective study of pts with ALL, DLBCL and PMLCL aged ≥ 18 years who underwent CART in 2018. Hospitalizations were selected using International Classification of Disease, Tenth Revision (ICD-10) codes. NPD of interest included anxiety, depression, adjustment disorder, insomnia, psychosis, dementia, bipolar disorder. Delirium was not included in the inventory of NPD since delirium is a neurotoxicity of CART, and inclusion of delirium as NPD would confound results. Patient, disease, and CART complications were extracted from hospitalization records. Regression analyses were used to assess association of NPD with clinical variables. Results: 945 CART procedures met the inclusion criteria (56 % males and 60% Caucasians). Majority of CART (88%) were performed for DLBCL and PMBCL. NPD was diagnosed in 31 % of pts. Anxiety was the most common NPD, followed by insomnia and depression. ALL pts were more likely to have NPD compared to pts with lymphoma (52% versus 28%, p&lt;0.05). More females had NPD compared to males (40% versus 25%, p&lt;0.05). Univariable analysis showed association of NPD with female gender [Odds ratio (OR)=2.03, 95% CI = 1.05-3.93] and ALL (OR=2.76, 95% CI = 1.03-7.43). In a multivariable model, NPD was associated with ALL (OR =3.57, 95% CI= 1.01-12.55), while the association of NPD with female gender was less certain (OR =1.41, 95% CI=0.73 - 2.74). There was no association between NPD and mortality, neurotoxicity, systemic inflammatory response syndrome or hemophagocytic lymphohistiocytosis. Conclusions: One in every 3 pts who underwent in-hospital CART for ALL or aggressive B cell lymphoma in 2018 had comorbid NPD. Females and ALL pts were at higher risk for NPD. As CART pts transition into longer follow up and survivorship, ours and similar results should inform the planning and allocation of psychosocial services.