tbuckley/cabot-search huggingface dataset:
Switching Towards Monocytic Lineage and Discordancy between Flow Cytometric and PCR Minimal Residual Disease Results Is a Hallmark Feature of DUX4 Rearranged B-Cell Precursor Acute Lymphoblastic Leukemia
Authors: Michaela Novakova, Barbora Vakrmanova, Lucie Slamova, Alena Musilova, Monika Brüggemann, Matthias Ritgen, Eva Fronkova, Tomas Kalina, Jan Trka, Jan Stary, Martina Vaskova, Lucie Winkowska, Marketa Zaliova, Karel Fišer, Ondrej Hrusak, Ester Mejstrikova
Journal: Blood (2018)
Tumoral EHF predicts the efficacy of anti-PD1 therapy in pancreatic ductal adenocarcinoma
Authors: Jing Liu, Wenna Jiang, Kaili Zhao, Hongwei Wang, Tianxing Zhou, Weiwei Bai, Xiuchao Wang, Tiansuo Zhao, Chongbiao Huang, Song Gao, Tai Qin, Wenwen Yu, Bo Yang, Xin Li, Danqi Fu, Wei Tan, Shengyu Yang, He Ren, Jihui Hao
Journal: The Journal of Experimental Medicine (2019)

Pancreatic ductal adenocarcinoma (PDAC) is a highly immune-suppressive tumor with a low response rate to single checkpoint blockade therapy. ETS homologous factor (EHF) is a tumor suppressor in PDAC. Here, we report a novel function of EHF in pancreatic cancer immune microenvironment editing and efficacy prediction for anti-PD1 therapy. Our findings support that the deficiency of tumoral EHF induced the accumulation of regulatory T (T reg) cells and myeloid-derived suppressor cells (MDSCs) and a decrease in the number of tumor-infiltrating CD8+ T cells. Mechanistically, EHF deficiency induced the conversion and expansion of T reg cells and MDSCs through inhibiting tumor TGFβ1 and GM-CSF secretion. EHF suppressed the transcription of TGFB1 and CSF2 by directly binding to their promoters. Mice bearing EHF overexpression tumors exhibited significantly better response to anti-PD1 therapy than those with control tumors. Our findings delineate the immunosuppressive mechanism of EHF deficiency in PDAC and highlight that EHF overexpression may improve PDAC checkpoint immunotherapy.
Undertreatment of noncurative pancreatic adenocarcinoma?: A population-based analysis of patterns of care.
Authors: Michail Mavros, Laura Davis, Alyson L. Mahar, Kaitlyn Beyfuss, Craig Earle, Ying Liu, Natalie Coburn, Julie I. Hallet
Journal: Journal of Clinical Oncology (2019)

439 Background: Noncurative pancreatic adenocarcinoma (PA) portends a guarded prognosis. Advancements in systemic therapy have improved this outlook. It is unknown whether patients get access to these therapies. We sought to define patterns of access to care and therapy for noncurative PA. Methods: We conducted a population-based analysis of nonresected PA over 2005-2016 by linking administrative healthcare datasets. Primary outcome was nonreceipt of cancer-directed therapy (radiation/chemotherapy; NRCDT). The first contact and overall consultations with specialized care (surgery, medical, or radiation oncology) were examined. Multivariate models examined factors associated with NRCDT. Results: Of 10,881 patients surviving a mean of 3.3 months (IQR: 1.2-8.5), 62% had NRCDT. More of patients of older age (65% of 71-80 years old, 89% of ≥81 years old), high comorbidity burden (68%), and lower socioeconomic status (69%), had NRCDT. Distance from residence to nearest cancer centre did not differ based on NRCDT. 35% of all patients did not see medical oncology, including 56% of NRCDT patients; 17% had no consultation with specialists. First contact with specialized care was surgery for 55% of all patients, and 50% with NRCDT. Most patients saw palliative care (81%) at median 27 days (IQR: 9-75) after diagnosis. Older age (OR 0.42 [0.37-0.48], and OR 0.14 [0.12-0.16] for 71-80 and ≥81 years old respectively), lowest income quintile (OR 0.62 [0.54-0.71]) and rurality (OR 0.63 [0.56-0.71]) were independently associated with lower odds of seeing medical oncology. First contact with oncology was independently associated with higher odds of receiving therapy (OR 1.48 [1.34-1.62]), compared to surgery. Conclusions: The majority of patients with noncurative PA did not receive cancer-directed therapy. Of those, more than half did not see medical oncology. While some patients may not be eligible to therapy, we identified disparities in receipt of cancer-directed therapy that indicate potential gaps in assessment for therapy and undertreatment, especially for vulnerable populations. This information is important to optimize access to and delivery of evidence-based care, and improve PA outcomes.
A phase II clinical trial platform for sensitization testing using total neoadjuvant therapy (TNT) in rectal cancer: Nrg-GI002.
Authors: Thomas J. George, Greg Yothers, Osama E. Rahma, Theodore S. Hong, Marcia McGory Russell, Y. Nancy You, William Parker, Samuel A. Jacobs, Peter C. Lucas, Marc Jeffrey Gollub, William Adrian Hall, Lisa A. Kachnic, Namrata Vijayvergia, Norman Wolmark
Journal: Journal of Clinical Oncology (2019)

TPS721 Background: Locally advanced rectal cancer (LARC) improvements have plateaued due to an inability to consistently deliver adjuvant therapy and effective novel therapies. Systematic testing of new chemotherapy and radiation sensitizers is needed to advance treatment outcomes. This NCTN multi-arm randomized phase II modular clinical trial platform utilizes TNT with parallel experimental arms (EA) in LARC. The EAs are not intended for direct comparison, but rather to test a variety of sensitizers or hypotheses in a consistent and homogenous high-risk patient (pt) population with correlative biomarkers. Success of any EA will be determined by achievement of pathologic endpoints compared to a control arm. Methods: The NRG-GI002 trial serves as a modular platform to assess novel sensitizers to neoadjuvant chemotherapy and/or chemoradiotherapy (chemoRT) in LARC. Eligibility includes LARC with any ONE of the following: distal location (cT3-4 ≤ 5 cm from anal verge, any N); bulky (any cT4 or tumor within 3 mm of the mesorectal fascia); high risk for metastatic disease (cN2); or not a candidate for sphincter-sparing surgical resection. After randomization, pts receive neoadjuvant FOLFOX x 4 mo→chemoRT (capecitabine with 50.4 Gy)→surgical resection 8-12 wks later. The first EA will assess activity of veliparib with standard chemoRT. Enrollment to this EA is complete (results anticipated late 2019). The second EA, testing pembrolizumab concurrently with and following chemoRT, is currently active, with several other EAs in development. Primary endpoint is demonstrated improvement in Neoadjuvant Rectal Cancer score for the EA v control representing a 20% relative risk reduction in DFS HR and 3-4% absolute OS improvement. Secondary endpoints include comparisons of OS, DFS, toxicity, pCR, cCR, therapy completion, negative surgical margins, sphincter preservation, sphincter function including QOL, and exploratory assessments of molecular and radiographic predictors of response and distant failure. Target accrual is 79 evaluable pts/arm with additional EAs added through protocol amendments. NCT02921256. Support: U10CA180868, -180822, UG1-189867, U24-196067; AbbVie, Merck. Clinical trial information: NCT02921256.
Center Variation in Medicare Spending for Durable Left Ventricular Assist Device Implant Hospitalizations
Authors: Michael P. Thompson, Francis D. Pagani, Qixing Liang, Lynze R. Franko, Min Zhang, Jeffrey S. McCullough, Raymond J. Strobel, Keith D. Aaronson, Robert L. Kormos, Donald S. Likosky
Journal: JAMA Cardiology (2019)

Hospitalizations for durable left ventricular assist device (LVAD) implants are expensive and increasingly common. Insights into center-level variation in Medicare spending for these hospitalizations are needed to inform value improvement efforts.To examine center-level variation in Medicare spending for durable LVAD implant hospitalizations and its association with clinical outcomes.Retrospective cohort study of linked Medicare administrative claims and Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS) clinical data comprising 106 centers in the United States providing durable LVAD implant. Centers were grouped into quartiles based on the mean price-standardized Medicare spending of their patients. The study included Medicare beneficiaries receiving primary durable LVAD implant between January 2008 and December 2014. Data were analyzed between November 2017 and October 2018.Price-standardized Medicare payments and clinical outcomes. Overall and component (facility diagnosis-related group payments, outlier payments, physician services) payments and clinical outcomes (postimplant length of stay and adverse events) were compared across payment quartiles.The study sample included 4442 hospitalized patients, with mean (SD) age of 63.0 (10.8) years, 18.7% female, 27.2% nonwhite, and 6.1% Hispanic ethnicity. Among 4442 hospitalizations, the mean (SD) price-standardized Medicare payment was $176 825 ($60 286) and ranged from $122 953 to $271 472 across 106 centers. The difference in price-standardized payments between lowest and highest spending quartiles was $55 446 ($152 714 vs $208 160; 36%; P < .001), with outlier payments making up most of the difference ($42 742; 77%), followed by DRG ($6929; 13%) and physician services ($5774; 10%). After risk standardization, there was a modest decline in the difference in payments between quartiles ($53 221; 35%), with outlier payments accounting for a larger proportion of the difference (84%). After adjusting for patient characteristics, higher price-standardized payment quartiles were associated with longer postimplant length of stay but were not associated with any adverse events.Medicare payments for durable LVAD implant hospitalizations vary widely across centers; this was not well explained by prices or case mix. While associated with longer postimplant length of stay, increased spending was not associated with adverse events. As the supply and demand for durable LVAD therapy continues to rise, identifying opportunities to reduce variation in spending from both explained and unexplained sources will ensure high-value use.
Systems Biology Analyses to Delineate Mechanisms of Anti-CD20 Antibody Resistance in Non-Hodgkin Lymphoma (NHL): Influence of BCR Signaling and the Critical Importance of Calcium Polarization
Authors: Ravi Dashnamoorthy, Afshin Beheshti, Saheli Sarkar, Tali Konry, Michael Levin, Andrew M. Evens
Journal: Blood (2018)
Abstract 10905: Pulse Amplitude Changes During the Valsalva Maneuver Measured Using Finger Photoplethysmography Identify Elevated Pulmonary Capillary Wedge Pressure in Heart Failure Patients
Authors: Nisha A Gilotra, Brett L Wanamaker, Hussein Rahim, Katherine Kunkel, Saadia Rizvi, Gayane Yenokyan, Ilan S Wittstein, Ryan J Tedford, Stuart D Russell, Harry A Silber
Journal: Circulation (2015)

Introduction: Pulse amplitude ratio (PAR) (ratio of pulse pressure at end of Valsalva maneuver (VM) to before onset) correlates with filling pressure. We developed a noninvasive device to measure PAR using finger photoplethysmography (PPG). Hypothesis: PAR reflects PCWP in heart failure (HF) patients and can detect a change in volume status. Methods: Patients referred for right heart catheterization (RHC) or admitted for HF performed three 10-second trials of a standardized VM (at 20 mmH measured via a pressure transducer) while PPG waveforms were recorded. Results: Amongst 60 patients undergoing RHC (Table 1), PAR correlated with PCWP (Pearson correlation coefficient = 0.53, p&lt;0.0001; Fig 1A), particularly in the 25 patients with systolic HF (Pearson correlation coefficient = 0.60, p=0.002; Fig 1B). A multivariable linear model for PCWP including PAR, age, BMI, blood pressure and heart rate improved ability to predict PCWP (r2=0.54). Difference in mean PAR for patients with a PCWP &lt; 15 mmHg versus ≥ 15 mmHg was statistically significant (p=0.0001; Fig 1C). PAR ≥ 0.515 predicted PCWP ≥ 15 mmHg with 83% sensitivity and 80% specificity (85% PPV). Presence of a positive Kussmaul’s sign did not alter the correlation between PAR and PCWP (p=0.897 for interaction). In 8 patients admitted with HF, PAR decreased by a mean of 0.10 from admission to discharge (p=0.023, effect size=0.85). Conclusions: We demonstrate that the response of a finger PPG waveform to a standardized VM in HF patients can estimate PCWP and also detect changes after diuresis. The ability to detect elevated filling pressures noninvasively prior to development of symptomatic congestion could reduce HF hospitalizations.
Erratum. Increased Prevalence of Type 2 Diabetes–Related Complications in Combined Type 2 Diabetes and Sickle Cell Trait. Diabetes Care 2018;41:2595—2602
Authors: Sarah C. Skinner, Mor Diaw, Vincent Pialoux, Maïmouna Ndour Mbaye, Pauline Mury, Philomène Lopez, Delphine Bousquet, Fatou Gueye, Demba Diedhiou, Philippe Joly, Céline Renoux, Djiby Sow, Saliou Diop, Brigitte Ranque, Agnès Vinet, Abdoulaye Samb, Nicolas Guillot, Philippe Connes
Journal: Diabetes Care (2019)

In the article cited above, the first sentence in the Results section of the abstract had the name of the group …
Planned Interim Analysis of a Phase 2 Study Evaluating the Combination of Pracinostat, a Histone Deacetylase Inhibitor (HDACi), and Azacitidine in Patients with High/Very High-Risk Myelodysplastic Syndrome (MDS)
Authors: Michael K Keng, Samer K. Khaled, Brenda Cooper, Erica D. Warlick, David Ramies, Silvia Mappa, Ehab L. Atallah
Journal: Blood (2018)
Impact of CD34 Cell Dose Infused on the Duration of Absolute Neutropenia after High Dose Melphalan and Autologous HCT for Myeloma
Authors: Lizamarie Bachier Rodriguez, Gunjan L. Shah, Andrea Knezevic, Sean M Devlin, Molly Maloy, Guenther Koehne, David J. Chung, Heather J. Landau, Sergio Giralt
Journal: Blood (2018)
Type 2 Diabetes, but Not Insulin (Analog) Treatment, Is Associated With More Advanced Stages of Breast Cancer: A National Linkage of Cancer and Pharmacy Registries
Authors: Jetty A. Overbeek, Myrthe P.P. van Herk-Sukel, Pauline A.J. Vissers, Amber A.W.A. van der Heijden, Heleen K. Bronsveld, Ron M.C. Herings, Marjanka K. Schmidt, Giel Nijpels
Journal: Diabetes Care (2019)

OBJECTIVE To investigate whether women with type 2 diabetes (T2D) develop a more advanced stage of breast cancer and whether treatment with insulin (analogs) is associated with specific breast cancer characteristics. RESEARCH DESIGN AND METHODS For this nested case-control study, women with breast cancer diagnosed in 2002–2014 were selected from the linked Netherlands Cancer Registry–PHARMO Database Network (N = 33,377). T2D was defined as receiving two or more dispensings of noninsulin blood glucose–lowering drugs prior to breast cancer diagnosis. Women with T2D were matched to women without diabetes. Among women with T2D, insulin users and nonusers were compared. Multivariable ordinal logistic regression was used to investigate the association between T2D/insulin and breast cancer characteristics, including TNM classification (tumor size, lymph node status, metastasis), morphology, grade, estrogen receptor and progesterone receptor (PR), human epidermal growth factor receptor 2, and molecular subtype. RESULTS Women with T2D (n = 1,567) were more often diagnosed with a more advanced tumor stage (odds ratio 1.28 [95% CI 13–1.44]) and a higher grade (1.22 [1.08–1.39]) though less often with a PR-negative breast tumor (0.77 [0.67–0.89]) than women without diabetes (n = 6,267). No associations were found for the other breast cancer characteristics. Women with T2D using insulin (n = 388) were not diagnosed with different breast cancer characteristics compared with women with T2D not using insulin (n = 1,179). CONCLUSIONS Our study suggests that women with T2D are at increased risk to be diagnosed with a more aggressive type of breast cancer than women without diabetes. No evidence was found that the use of insulin (analogs) is associated with developing more advanced breast cancer tumors.
High Carbon Monoxide Levels from Charcoal Combustion Mask Acute Endothelial Dysfunction Induced by Hookah (Waterpipe) Smoking in Young Adults
Authors: Mary Rezk-Hanna, Zab Mosenifar, Neal L. Benowitz, Florian Rader, Mohamad Rashid, Katherine Davoren, Norma B. Moy, Lynn Doering, Wendie Robbins, Linda Sarna, Ning Li, L. Cindy Chang, Robert M. Elashoff, Ronald G. Victor
Journal: Circulation (2019)

Hookah smoking is marketed to youth as a harmless alternative to cigarettes. Although cigarette smoking acutely impairs endothelial function, the effect of smoking fruit-flavored hookah tobacco is unknown. Because charcoal traditionally is used to heat the hookah tobacco in the waterpipe, hookah smoke delivers tobacco toxicants and nicotine plus charcoal combustion products: not only carbon-rich nanoparticles, oxidants that may destroy nitric oxide and impair endothelial function, but also large amounts of carbon monoxide (CO), a putative vasodilator molecule.To test the acute effect of hookah smoking on endothelial function, in young adult hookah smokers (n=30, age 26±1 years, mean±SE), we measured plasma nicotine, exhaled CO, and brachial artery flow-mediated dilation (FMD) before and after charcoal-heated hookah smoking. To remove the effect of charcoal combustion, the same measurements were performed when the same flavored hookah tobacco product was heated electrically (n=20). As a positive internal control, we studied age-matched cigarette smokers (n=15) who smoked 1 cigarette. To isolate the effect of the CO boost on FMD, hookah smokers (n=8) inhaled a 0.1% CO gas mixture to approximate their CO boost achieved with charcoal-heated hookah smoking.Nicotine levels increased similarly with all types of smoking, whereas exhaled CO increased 9- to 10-fold more after charcoal-heated hookah than after either electrically heated hookah or cigarette smoking. FMD did not decrease after smoking charcoal-heated hookah but instead increased by +43±7% ( P<0.001). In contrast, FMD decreased by -27±4% ( P<0.001) after smoking electrically heated hookah, comparable to the decrease after cigarette smoking. FMD increased markedly by 138±71% ( P<0.001) after breathing CO gas, 2.8 times more than the increase induced in the same subjects after smoking charcoal-heated hookah ( P<0.001), despite comparable increases in exhaled CO (24±1 versus 28±3 ppm, hookah versus CO).Smoking hookah tobacco, similar to cigarette tobacco, acutely impairs endothelial function. With traditional charcoal-heated hookah smoking, the acute endothelial dysfunction is masked by high levels of carbon monoxide, a potent vasodilator molecule generated by charcoal combustion. With respect to large-artery endothelial function, smoking hookah is not harmless.URL: https://www.clinicaltrials.gov . Unique identifiers: NCT03616002 and NCT03067701.
Diagnostic Relevance of 18F-FDG PET/CT in Newly Diagnosed Patients with Monoclonal Gammopathy of Undetermined Significance (MGUS) : Single- Center Experience
Authors: Viera Sandecka, Ludek Pour, Zdenek Adam, Martin Stork, Marta Krejci, Jana Michalcova, Zdenek Kral, Sabina Sevcikova, Zdeněk Řehák, Renata Koukalova
Journal: Blood (2018)
Polymorphisms in the telomerase complex to predict outcome in patients (pts) with metastatic colorectal cancer (mCRC): Data from TRIBE and FIRE-3 phase III trials.
Authors: Francesca Battaglin, Fotios Loupakis, Sebastian Stintzing, Shu Cao, Alberto Puccini, Ryuma Tokunaga, Madiha Naseem, Martin D. Berger, Shivani Soni, Jae Ho Lo, Francesca Bergamo, Sara Lonardi, Joshua Millstein, Wu Zhang, Vittorina Zagonel, Chiara Cremolini, Alfredo Falcone, Volker Heinemann, Heinz-Josef Lenz
Journal: Journal of Clinical Oncology (2019)

566 Background: Telomere/telomerase interplay is involved in the regulation of genomic stability and cellular replicative potential. In CRC, shortening of telomeres promotes early steps of carcinogenesis but the prognostic role of telomere length is debated. High circulating levels of telomerase reverse transcriptase (TERT) appear to be a negative prognostic biomarker and polymorphisms in the telomerase RNA component (TERC) are associated with increased cancer risk. We hypothesized that genetic variants in the telomerase/telomere capping complex may predict first-line treatment outcome in mCRC pts. Methods: The impact on outcome of 21 selected SNPs within 13 genes ( TERT, TERC, CLPTM1L, TERF1/2, POT1, ACD, NOP10, NHP2, GAR1, STN1, CTC1) was analyzed through the OncoArray, a custom array manufactured by Illumina, on genomic DNA from blood samples of 451 pts enrolled in two independent randomized trials. TRIBE FOLFIRI/bevacizumab (bev) arm (n=215, mPFS/OS: 9.7/26.2 mo) served as discovery cohort, FIRE-3 FOLFIRI/bev arm (n=107, mPFS/OS: 11.5/31.4 mo) as validation and FOLFIRI/cetuximab (cet) arm (n=129, mPFS/OS: 12.8/49.8 mo) as control. Results: In the discovery cohort, pts carrying any A allele of TERT rs2075786 showed longer mPFS (11.1 vs 9.3 mo, P= .021) and OS (33.5 vs 25 mo, P= .005) compared to the G/G genotype in multivariable analysis. Same results were observed for pts carrying any T allele of CLPTM1L rs401681 compared to the C/C genotype ( P= .022). Any C allele carriers of TERC rs2293607 also showed longer mOS in multivariable analysis ( P= .041) and the A/A genotype of ACD rs6979 was associated with longer mPFS in both uni- and multivariable analysis. Interestingly, the T/T genotype of CLPTM1L rs401681 was associated with shorter mPFS (7.8 vs 13.5 mo) in the cet cohort in uni- ( P= .003) and multivariable analysis ( P= .041). In subgroup analyses based on RAS mutational status several SNPs in additional genes were associated with PFS and/or OS in different cohorts. Conclusions: Our results suggest that SNPs in core telomerase/telomere capping complex genes may have a predictive and prognostic value in mCRC pts receiving targeted first-line treatments.
Incidence and prognosis of multiple organ involvement at gastric MALT lymphoma.
Authors: Tae Hun Kwon, In Seok Lee
Journal: Journal of Clinical Oncology (2019)

18 Background: MALT (mucosa-associated lymphoid tissue) lymphoma usually occurs in stomach but various MALT organs can be afflicted including salivary glands, ocular adnexa, lung, intestine and thyroid. In this study, we aimed to evaluate the prevalence and characteristics of gastric MALT lymphoma with multi-organ involvement. Methods: We retrospectively analyzed a total of 174 consecutive patients who had been diagnosed with gastric MALT lymphoma at Seoul St. Mary’s Hospital from January 2009 to May 2018. Clinical data were obtained from the medical records. At the time of diagnosis, neck, chest, abdominal CT, PET-CT and bone marrow biopsy were performed for the purpose of staging work-up. Organ involvement was identified by biopsy. Results: Nine out of 174 (5.2%) gastric MALT lymphoma patients were found to have multi-organ involvement. Three patients had biopsy proven lymphoma at lung, two patients had colon involvement, and two patients had ocular involvement. A patient with involvement at small bowel and duodenum were found, respectively. Seven patients were examined for Helicobacter infection. Two of them were positive for H. pylori infection and received eradication treatment. Except one patient treated with palliative care, eight patients underwent chemotherapy, in which two of them received additional radiation therapy and other two patients underwent bone marrow transplantation. Except one patient died of pneumonia during chemotherapy and one patient underwent palliative treatment, 7 patients had maintained complete remission. Conclusions: The overall prevalence of gastric MALT lymphoma with multi-organ involvement was 5.2%. The result suggests that the gastric MALT lymphoma patients require a careful investigation of other MALT organs. [Table: see text]
Mediterranean diet and risk of heart failure: results from the PREDIMED randomized controlled trial. <i>Eur J Heart Fail</i> 2017;<b>19</b>:1179–1185. doi: 10.1002/ejhf.750
Authors: Angeliki Papadaki, Miguel Ángel Martínez‐González, Angel Alonso‐Gómez, Javier Rekondo, Jordi Salas‐Salvadó, Dolores Corella, Emilio Ros, Montse Fitó, Ramon Estruch, José Lapetra, Antonio García‐Rodriguez, Miquel Fiol, Lluís Serra‐Majem, Xavier Pintó, Miguel Ruiz‐Canela, Monica Bulló, Mercè Serra‐Mir, Jose V. Sorlí, Fernando Arós
Journal: European Journal of Heart Failure (2019)