tbuckley/cabot-search huggingface dataset:
Regorafenib Plus for third-line treatment in metastatic colorectal cancer: A real-world study.
Authors: Patiguli Yisilamu, Jiannan Yao, Yang Ge
Journal: Journal of Clinical Oncology (2024)

e15562 Background: Regorafenib, approved as a monotherapy for refractory metastatic colorectal cancer (mCRC), is recognized for its potential immunomodulatory effects and ability to reverse chemotherapeutic resistance. In response to this, a combination regimen known as regorafenib Plus has been customized for specific patients. This study aims to evaluate the effectiveness and safety of regorafenib as a standalone treatment and in combination with other therapies (including concurrent/sequential chemotherapy, immunotherapy, transarterial chemoembolization [TACE]) in the real-world setting. The goal is to present viable treatment options for patients with mCRC. Methods: In this retrospective study, patients with chemo-refractory metastatic colorectal cancer (mCRC) who underwent regorafenib treatment at Beijing Chaoyang Hospital between January 2018 and October 2023 were stratified into two cohorts: monotherapy (Rego Mono) and concurrent/sequential combination therapy (Rego Plus). Index date was the initiation of regorafenib therapy in a sequence and median follow-up was 19.1 months. The clinical outcomes included progression-free survival (PFS), overall survival (OS), and 1/2-year OS rates. Results: A total of 67 pts were included (n = 39 Rego Mono; n = 28 Rego Plus). Baseline characteristics were comparable between cohorts. The median progression-free survival (PFS) was significantly extended in the Rego Plus group compared to Rego Mono (8.0 vs. 3.6 months, P = 0.000), and overall survival (OS) was also notably prolonged (24.4 vs. 19.1 months, P = 0.046). The 1/2-year OS rates were also improved by Rego Plus (63% vs 37.1%, 25.5% vs 11.4%). However, there were no statistical differences in PFS between concurrent and sequential combination therapies (8.4 vs 8.0 mont). Notably, under sequential therapy, after 3.7 months of PFS with regorafenib alone, an additional 4.7 months of PFS was observed when combined therapy was introduced. Regarding safety, Rego Plus was associated with an increased rate of adverse events (AEs) without an escalation in severity. Common AEs included rash, hand-foot syndrome, hypertension, and diarrhea. Conclusions: Rego Plus significantly prolonged PFS and OS in patients with chemo-refractory mCRC. Particularly when tumor stabilization is evident during monotherapy, the introduction of Rego Plus can offer a comparable or even longer PFS benefit, nearly doubling the PFS. Despite an elevated rate of AEs, the severity of these events did not increase, suggesting good tolerability. This approach has the potential to enhance the effectiveness of existing third-line therapies for mCRC, ultimately contributing to an improved prognosis for patients.
Socioeconomic status and fertility counseling in patients with early onset colorectal cancer.
Authors: Dalia Littman, Chengwei Peng, Lena Masri, Scott Sherman, Danil V. Makarov, Daniel Jacob Becker
Journal: Journal of Clinical Oncology (2024)

e15654 Background: The incidence of early onset colorectal cancer (EOCRC) has increased over the past several decades, with a corresponding need to counsel younger patients about options for fertility counseling. The characteristics of patients at risk for going without fertility counseling are unknown. Methods: We conducted a single site retrospective review of all patients diagnosed with colorectal cancer between 2012 and 2019 who were men age 55 or younger or women age 50 or younger. Clinical data and documentation of fertility counseling were extracted from the electronic medical record by explicit chart review. Median household income (MHI) by zip code was gathered from census data and assigned to each patient based on home address. Results: 194 subjects were identified, of whom 69% had colon cancer and 31% had rectal cancer. 61% were male with average age 44 and 39% were female with average age 42. 55% were White, 11% were Black, 14% were Asian, and 10% were Hispanic. 13% had stage II disease, 44% had stage III disease and 40% had stage IV disease. 15.5% had documented fertility counseling, of whom 43% were male and 57% were female. In univariate analysis, age less than 40 years old, female sex, curative intent treatment, and home address in areas of higher MHI were associated with higher rates of fertility counseling. Race, tumor type, stage of disease, and year of diagnosis were not associated with differences in rates of fertility counseling. Conclusions: We found low overall rates of fertility counseling in patients with EOCRC, and consistent with prior analyses, lower counseling of men and those over age 40. We found that patients who live in areas of relative poverty were less likely to receive fertility counseling. Limited fertility counseling and high out-of-pocket costs of fertility preservation may combine to deny vulnerable patients an essential service. Given the increasing diagnosis of EOCRC, efforts are needed to increase the rates of fertility counseling both systemically and equitably. [Table: see text]
Characterization of necroptosis activators in colorectal cancer.
Authors: Karam Ashouri, Joanne Xiu, Yan Yang, Joshua Millstein, Shivani Soni, Sandra Algaze, Pooja Mittal, Alexandra Wong, Jae Ho Lo, Lesly Torres-Gonzalez, Anthony F. Shields, Richard M. Goldberg, Emil Lou, Benjamin Adam Weinberg, John Marshall, Alexander Hoffmann, Lin Zhang, Jian Yu, Francesca Battaglin, Heinz-Josef Lenz
Journal: Journal of Clinical Oncology (2024)

3522 Background: Necroptosis is a pro-inflammatory form of programmed cell death triggered by cellular stresses and extrinsic cytokines. It is a potential therapeutic target for immunotherapy (IO) in colorectal cancer (CRC). Here, we present comprehensive clinical and molecular characterization of key necroptosis regulators in CRC. Methods: 24,257 samples of CRC tested at Caris Life Sciences (Phoenix, AZ) with WTS (Illumina NovaSeq), NextGen DNA sequencing (NextSeq, 592 Genes and NovaSEQ, WES), and PD-L1 expression (22C3 clone; TPS ≥1%) were analyzed. Expression of activators in the necroptosis pathway ( RIPK3, MLKL, CYLD, and ZBP1) was categorized as either high (H) or low (L) using median expression as the cutoff. CRCs with high expression of all four activators were considered to have high propensity for necroptosis activity (NA-H, N=4595) compared to tumors with low expression in all activators (NA-L, N = 4946). RNA deconvolution analysis with QuantiSEQ estimated immune cell infiltration in the tumor microenvironment (TME). Differences in overall survival (OS) were analyzed from insurance claims data and calculated from treatment initiation using Kaplan-Meier estimates. Statistical significance was set as a P-value adjusted for multiple comparisons ( q&lt;0.05). Results: NA-H was associated with increased PD-L1 positivity (4.0% vs 2.3%), immune cell infiltration, and T-cell inflamed score (all q&lt;0.001). TP53 mutations were more frequent in NA-H, while SMAD2, SMAD4, KRAS, and NRAS mutations were associated with NA-L (all q&lt;0.01). NA-H was associated with activation of KRAS signaling, allograft rejection, inflammatory/interferon gamma response, and pancreatic beta cell function pathways (all q&lt;0.05). NA-H showed significantly improved OS in FOLFOX/FOLFIRI (F/F) (NA-L: 34.3 vs NA-H: 39.6 months [mo], P &lt; 0.001; HR = 0.83, 95% CI 0.77 – 0.90) and those treated with IO (15.3 vs 22.4 mo, P = 0.018; HR = 0.77, 95% CI 0.62– 0.96) treated CRC patients. The benefit remained in TP53-mutated CRC treated with F/F (34.6 vs 41.0 mo, P &lt; 0.001; HR = 0.82, 95% CI 0.74-0.90) and IO (10.0 vs 21.8 mo, P = 0.027; HR = 0.68, 95% CI 0.48-0.96) but not in the TP53-wild-type subgroup. Improved OS was observed with increased expression of CYLD and ZBP1(Table). The benefit remained in TP53-mutated CRC but not in the TP53 wildtype subgroup. Conclusions: This is the largest molecular and clinical characterization of necroptotic genes in CRC. Our data shows that activation of the necroptosis pathway is associated with immune cell infiltration/pathway activation, PD-L1 expression, and improved OS on F/F and IO. This benefit is more pronounced in TP53-mutated CRC, suggesting possible novel therapeutic targets.[Table: see text]
A nationwide, population‐based study on specialized care for acute heart failure throughout the <scp>COVID</scp>‐19 pandemic
Authors: Antonio Cannata, Mehrdad A. Mizani, Daniel I. Bromage, Susan E. Piper, Suzanna M.C. Hardman, Cathie Sudlow, Mark de Belder, John Deanfield, Roy S. Gardner, Andrew L. Clark, John G.F. Cleland, Theresa A. McDonagh
Journal: European Journal of Heart Failure (2024)

Abstract Aims The COVID‐19 pandemic disrupted the delivery of care for patients with heart failure (HF), leading to fewer HF hospitalizations and increased mortality. However, nationwide data on quality of care and long‐term outcomes across the pandemic are scarce. Methods and results We used data from the National Heart Failure Audit (NHFA) linked to national records for hospitalization and deaths. We compared pre‐COVID (2018–2019), COVID (2020), and late/post‐COVID (2021–2022) periods. Data for 227 250 patients admitted to hospital with HF were analysed and grouped according to the admission year and the presence of HF with (HFrEF) or without reduced ejection fraction (non‐HFrEF). The median age at admission was 81 years (interquartile range 72–88), 55% were men ( n = 125 975), 87% were of white ethnicity ( n = 102 805), and 51% had HFrEF ( n = 116 990). In‐hospital management and specialized cardiology care were maintained throughout the pandemic with an increasing percentage of patients discharged on disease‐modifying medications over time ( p &lt; 0.001). Long‐term outcomes improved over time (hazard ratio [HR] 0.92, 95% confidence interval [CI] 0.90–0.95, p &lt; 0.001), mainly driven by a reduction in cardiovascular death. Receiving specialized cardiology care was associated with better long‐term outcomes both for those who had HFrEF (HR 0.79, 95% CI 0.77–0.82, p &lt; 0.001) and for those who had non‐HFrEF (HR 0.87, 95% CI 0.85–0.90, p &lt; 0.001). Conclusions Despite the disruption of healthcare systems, the clinical characteristics of patients admitted with HF were similar and the overall standard of care was maintained throughout the pandemic. Long‐term survival of patients hospitalized with HF continued to improve after COVID‐19, especially for HFrEF.
Peripheral Exudative Hemorrhagic Chorioretinopathy Simulating Choroidal Metastases
Authors: Nan Zhou, Lihong Yang, Wenbin Wei
Journal: Ophthalmology (2024)

A 56-year-old woman was referred for tumors in her eye. Visual acuity was 20/50 in her right eye. Dilated fundus examination revealed a peripheral nonpigmented, dome-shaped mass with a second flat, orange-colored lesion at 7 o'clock (A). Color Doppler ultrasonography (B) showed 2 mostly hyporeflective cystic masses without choroidal excavation. Indocyanine green angiography showed a polyp-like choroidal telangiectasis (C, yellow arrows) at the nasal border of a bullous pigment epithelium detachment. Swept-source-OCT of this area showed the double-layer sign for choroidal neovascular membranes (D, white arrows). Systemic examination excluded primary malignancy. A diagnosis of peripheral exudative hemorrhagic chorioretinopathy was made and intravitreal anti-VEGF therapy was initiated. The lesions regressed and vision had improved to 20/25 at the last follow-up. (Magnified version of Figure A-D is available online at www.aaojournal.org).
Deciphering tertiary lymphoid structure heterogeneity reveals prognostic signature and therapeutic potentials for colorectal cancer: a multicenter retrospective cohort study
Authors: Jia-Xin Lei, Runxian Wang, Chuling Hu, Xiaoying Lou, Min-Yi Lv, Chenghang Li, Baowen Gai, Xiao-Jian Wu, Ruoxu Dou, Du Cai, Feng Gao
Journal: International Journal of Surgery (2024)

Background: Tertiary lymphoid structures (TLSs) exert a crucial role in the tumor microenvironment (TME), impacting tumor development, immune escape, and drug resistance. Nonetheless, the heterogeneity of TLSs in colorectal cancer (CRC) and their impact on prognosis and treatment response remain unclear. Methods: The authors collected genome, transcriptome, clinicopathological information, and digital pathology images from multiple sources. An unsupervised clustering algorithm was implemented to determine diverse TLS patterns in CRC based on the expression levels of 39 TLS signature genes (TSGs). Comprehensive explorations of heterogeneity encompassing mutation landscape, TME, biological characteristics, response to immunotherapy, and drug resistance were conducted using multiomics data. TLSscore was then developed to quantitatively assess TLS patterns of individuals for further clinical applicability. Results: Three distinct TLS patterns were identified in CRC. Cluster 1 exhibited upregulation of proliferation-related pathways, high metabolic activity, and intermediate prognosis, while Cluster 2 displayed activation of stromal and carcinogenic pathways and a worse prognosis. Both Cluster 1 and Cluster 2 may potentially benefit from adjuvant chemotherapy. Cluster 3, characterized by the activation of immune regulation and activation pathways, demonstrated a favorable prognosis and enhanced responsiveness to immunotherapy. The authors subsequently employed a regularization algorithm to construct the TLSscore based on nine core genes. Patients with lower TLSscore trended to prolonged prognosis and a more prominent presence of TLSs, which may benefit from immunotherapy. Conversely, those with higher TLSscore exhibited increased benefits from adjuvant chemotherapy. Conclusions: The authors identified distinct TLS patterns in CRC and characterized their heterogeneity through multiomics analyses. The TLSscore held promise for guiding clinical decision-making and further advancing the field of personalized medicine in CRC.
Anti‐<scp>CD19</scp> chimeric antigen receptor T‐cell therapy in older patients with relapsed or refractory large B‐cell lymphoma: A multicenter study
Authors: Aung M. Tun, Romil D. Patel, Frederique St‐Pierre, Evguenia Ouchveridze, Alex Niu, Thorunn Thordardottir, Jennifer Obasi, Allison Rosenthal, Priyanka A. Pophali, Timothy S. Fenske, Reem Karmali, Sairah Ahmed, Patrick B. Johnston
Journal: American Journal of Hematology (2024)

Chimeric antigen receptor T-cell (CAR-T) therapy, despite being a potentially curative therapy in relapsed or refractory (RR) large B-cell lymphoma (LBCL), remains underutilized in older patients due to limited clinical data. We therefore studied the safety and efficacy of CAR-T therapy in older patients with RR LBCL in the real-world setting. Patients aged ≥65 years with RR LBCL, treated with anti-CD19 CAR-T therapy at 7 US institutions were included in this multicenter, retrospective, observational study. In total, 226 patients were included. Median age at infusion was 71 years (range 65-89). Best objective and complete response rates were 86% and 62%, respectively. Median follow-up after infusion was 18.3 months. The median progression-free survival (PFS) was 6.9 months, with 6- and 12-month PFS estimates of 54% and 44%, respectively. The nonrelapse mortality (NRM) rate was 10.9% at day 180, primarily due to infections, and not impacted by the age groups. Grade ≥3 cytokine release syndrome and neurotoxicity occurred in 7% and 26%, respectively. In univariate analysis, no significant difference in PFS was seen regardless of the age groups or CAR-T type, whereas ECOG PS ≥2, elevated LDH, bulky disease, advanced stage, extranodal involvement, the need for bridging therapy, and prior bendamustine exposure were associated with shorter PFS. These findings support the use of CAR-T in older patients, including those aged ≥80 years. The age at CAR-T therapy did not influence safety, survival, and NRM outcomes. Older patients should not be excluded from receiving CAR-T therapy solely based on their chronological age.
New augmented reality remote for virtual guidance and education of fracture surgery: a retrospective, non-inferiority, multicenter cohort study
Authors: Songxiang Liu, Mao Xie, Fei Gao, Ying Fang, Mingdi Xue, Bingran Zuo, Junwen Wang, Jialang Hu, Rong Liu, Jiayao Zhang, Tongtong Huo, Pengran Liu, Cheng Zeng, Andy Yew, Heng-Gui Chen, Zhewei Ye
Journal: International Journal of Surgery (2024)

Background: The demand for telesurgery is rapidly increasing. Augmented reality (AR) remote surgery is a promising alternative, fulfilling a worldwide need in fracture surgery. However, previous AR endoscopic and Google Glass remotes remain unsuitable for fracture surgery, and the application of remote fracture surgery has not been reported. The authors aimed to evaluate the safety and clinical effectiveness of a new AR remote in fracture surgery. Materials and methods: This retrospective non-inferiority cohort study was conducted at three centres. Between 1 January 2018 and 31 March 2022, 800 patients who underwent fracture surgery were eligible for participation. The study enroled 551 patients with fractures (132 patellae, 128 elbows, 126 tibial plateaus, and 165 ankles) divided into an AR group (specialists used AR to remotely guide junior doctors to perform surgeries) and a traditional non-remote group (specialists performed the surgery themselves). Results: Among 364 patients (182 per group) matched by propensity score, seven (3.8%) in the AR group and six (3%) in the non-remote group developed complications. The 0.005 risk difference (95% CI: −0.033 to 0.044) was below the pre-defined non-inferiority margin of a 10% absolute increase. A similar distribution in the individual components of all complications was found between the groups. Hierarchical analysis following propensity score matching revealed no statistical difference between the two groups regarding functional results at 1-year follow-up, operative time, amount of bleeding, number of fluoroscopies, and injury surgery interval. A Likert scale questionnaire showed positive results (median scores: 4–5) for safety, efficiency, and education. Conclusion: This study is the first to report that AR remote surgery can be as safe and effective as that performed by a specialist in person for fracture surgery, even without the physical presence of a specialist, and is associated with improving the skills and increasing the confidence of junior surgeons. This technique is promising for remote fracture surgery and other open surgeries, offering a new strategy to address inadequate medical care in remote areas.
Machine learning guided prediction of warfarin blood levels for personalized medicine based on clinical longitudinal data from cardiac surgery patients: a prospective observational study
Authors: Ling Xue, Shan He, Rajeev K. Singla, Qiong Qin, Yinglong Ding, Linsheng Liu, Xiaoliang Ding, Harbil Bediaga-Bañeres, Sonia Arrasate, Aliuska Durado-Sanchez, Yuzhen Zhang, Zhenya Shen, Bairong Shen, Liyan Miao, Humberto González-Díaz
Journal: International Journal of Surgery (2024)

Background: Warfarin is a common oral anticoagulant, and its effects vary widely among individuals. Numerous dose-prediction algorithms have been reported based on cross-sectional data generated via multiple linear regression or machine learning. This study aimed to construct an information fusion perturbation theory and machine learning prediction model of warfarin blood levels based on clinical longitudinal data from cardiac surgery patients. Methods and Material: The data of 246 patients were obtained from electronic medical records. Continuous variables were processed by calculating the distance of the raw data with the moving average (MA ∆v ki ( s j )), and categorical variables in different attribute groups were processed using Euclidean distance (ED ǁ∆v k ( s j )ǁ). Regression and classification analyses were performed on the raw data, MA ∆v ki ( s j ), and ED ǁ∆v k ( s j )ǁ. Different machine-learning algorithms were chosen for the STATISTICA and WEKA software. Results: The random forest (RF) algorithm was the best for predicting continuous outputs using the raw data. The correlation coefficients of the RF algorithm were 0.978 and 0.595 for the training and validation sets, respectively, and the mean absolute errors were 0.135 and 0.362 for the training and validation sets, respectively. The proportion of ideal predictions of the RF algorithm was 59.0%. General discriminant analysis (GDA) was the best algorithm for predicting the categorical outputs using the MA ∆v ki ( s j ) data. The GDA algorithm’s total true positive rate (TPR) was 95.4% and 95.6% for the training and validation sets, respectively, with MA ∆v ki ( s j ) data. Conclusions: An information fusion perturbation theory and machine learning model for predicting warfarin blood levels was established. A model based on the RF algorithm could be used to predict the target international normalized ratio (INR), and a model based on the GDA algorithm could be used to predict the probability of being within the target INR range under different clinical scenarios.
PECARN prediction rule for cervical spine imaging of children presenting to the emergency department with blunt trauma: a multicentre prospective observational study
Authors: Julie C Leonard, Monica Harding, Lawrence J Cook, Jeffrey R Leonard, Kathleen M Adelgais, Fahd A Ahmad, Lorin R Browne, Rebecca K Burger, Pradip P Chaudhari, Daniel J Corwin, Nicolaus W Glomb, Lois K Lee, Sylvia Owusu-Ansah, Lauren C Riney, Alexander J Rogers, Daniel M Rubalcava, Robert E Sapien, Matthew A Szadkowski, Leah Tzimenatos, Caleb E Ward, Kenneth Yen, Nathan Kuppermann
Journal: The Lancet Child & Adolescent Health (2024)