tbuckley/cabot-search huggingface dataset:
The association of PSA levels and survival outcomes in patients with chemotherapy-naïve, castration-resistant prostate cancer (CRPC) who were treated with androgen receptor signaling axis targeting agent (ARAT): A Japanese cohort study.
Authors: Tatsuya Shimomura, Keiichiro Mori, Toshihiro Yamamoto, Hajime Onuma, Hiroyuki Inaba, Kenichi Hata, Takahiro Kimura, Shin Egawa
Journal: Journal of Clinical Oncology (2019)

315 Background: PSA decline is used as one of the treatment outcome of androgen receptor signaling axis targeting agent (ARAT) in general. However, correlation between PSA decline and survival outcome is not discussed enough. In this study we evaluated how PSA decline influence the survival outcome of ARAT against chemo-naive castration resistant prostate cancer (CRPC). Methods: A total of 200 chemo-naïve CRPC cases treated with ARAT (abiraterone acetate or enzalutamide) were included in this study. We investigated the relationship between PSA response rate and survival outcome (PSA progression free survival (PSA-PFS), Failure free survival (FFS) and overall survival (OS)). Results: PSA response rate correlated with PSA-PFA, TFS and OS significantly (p&lt;0.0001, &lt;0.0001, 0.0009, respectively). And we categorized PSA decline in four groups, group 1: no PSA decline, group 2: 0-50%, group 3: 50%-90%, group 4: over 90%. Median PSA-PFS were 2M (group 1), 4M (group 2), 10M (group 3) and 16M (group 4) (p&lt;0.0001). Median FFS were 3M (group 1), 6M (group 2), 12M (group 3) and 27M (group 4) (p&lt;0.0001). Median OS were 28M (group 1), 36M (group 2), not reached (group 3 and 4) (p=0.0056). In terms of OS, there is a big different between PSA decline &lt;50% and ≥50% in survival curve. And we compare the factors influencing PSA decline ≥50%. PSA and age at initiating ARAT are significant factors predicting PSA decline 50%. Lower PSA and lower age correlated PSA decline ≥50%. Conclusions: PSA decline strongly correlated with PSA-PFS, FFS and OS in this study. It would be a surrogate marker predicting survival outcomes of chemo-naïve CRPC cases treated with ARAT. Further investigation is warranted to confirm these results.
CD19 CAR T cell product and disease attributes predict leukemia remission durability
Authors: Olivia C. Finney, Hannah Brakke, Stephanie Rawlings-Rhea, Roxana Hicks, Danielle Doolittle, Marisa Lopez, Ben Futrell, Rimas J. Orentas, Daniel Li, Rebecca Gardner, Michael C. Jensen
Journal: Journal of Clinical Investigation (2019)

Chimeric antigen receptor (CAR) T cells can induce remission in highly refractory leukemia and lymphoma subjects, yet the parameters for achieving sustained relapse-free survival are not fully delineated.We analyzed 43 pediatric and young adult subjects participating in a Phase I trial of defined composition CD19CAR T cells (NCT02028455). CAR T cell phenotype, function and expansion, as well as starting material T cell repertoire, were analyzed in relation to therapeutic outcome (defined as achieving complete remission within 63 days) and duration of leukemia free survival and B cell aplasia.These analyses reveal that initial therapeutic failures (n = 5) were associated with attenuated CAR T cell expansion and/or rapid attrition of functional CAR effector cells following adoptive transfer. The CAR T products were similar in phenotype and function when compared to products resulting in sustained remissions. However, the initial apheresed peripheral blood T cells could be distinguished by an increased frequency of LAG-3+/TNF-αlow CD8 T cells and, following adoptive transfer, the rapid expression of exhaustion markers. For the 38 subjects who achieved an initial sustained MRD-neg remission, remission durability correlated with therapeutic products having increased frequencies of TNF-α-secreting CAR CD8+ T cells, and was dependent on a sufficiently high CD19+ antigen load at time of infusion to trigger CAR T cell proliferation.These parameters have the potential to prospectively identify patients at risk for therapeutic failure and support the development of approaches to boost CAR T cell activation and proliferation in patients with low levels of CD19 antigen.ClinicalTrials.gov NCT02028455.Partial funding for this study was provided by Stand Up to Cancer & St. Baldrick's Pediatric Dream Team Translational Research Grant (SU2C-AACR-DT1113), RO1 CA136551-05, Alex Lemonade Stand Phase I/II Infrastructure Grant, Conquer Cancer Foundation Career Development Award, Washington State Life Sciences Discovery Fund, Ben Towne Foundation, William Lawrence & Blanche Hughes Foundation, and Juno Therapeutics, Inc., a Celgene Company.
Combining vascular targeting and the local first pass provides 100-fold higher uptake of ICAM-1-targeted vs untargeted nanocarriers in the inflamed brain
Authors: Oscar A. Marcos-Contreras, Jacob S. Brenner, Raisa Y. Kiseleva, Viviana Zuluaga-Ramirez, Colin F. Greineder, Carlos H. Villa, Elizabeth D. Hood, Jacob W. Myerson, Silvia Muro, Yuri Persidsky, Vladimir R. Muzykantov
Journal: Journal of Controlled Release (2019)
Effect of Dapagliflozin on Heart Failure and Mortality in Type 2 Diabetes Mellitus
Authors: Eri T. Kato, Michael G. Silverman, Ofri Mosenzon, Thomas A. Zelniker, Avivit Cahn, Remo H.M. Furtado, Julia Kuder, Sabina A. Murphy, Deepak L. Bhatt, Lawrence A. Leiter, Darren K. McGuire, John P.H. Wilding, Marc P. Bonaca, Christian T. Ruff, Akshay S. Desai, Shinya Goto, Peter A. Johansson, Ingrid Gause-Nilsson, Per Johanson, Anna Maria Langkilde, Itamar Raz, Marc S. Sabatine, Stephen D. Wiviott
Journal: Circulation (2019)

In DECLARE-TIMI 58 (Dapagliflozin Effect on Cardiovascular Events-Thrombolysis in Myocardial Infarction 58), the sodium-glucose cotransporter 2 inhibitor dapagliflozin reduced the composite end point of cardiovascular death/hospitalization for heart failure (HHF) in a broad population of patients with type 2 diabetes mellitus. However, the impact of baseline left ventricular ejection fraction (EF) on the clinical benefit of sodium-glucose cotransporter 2 inhibition is unknown.In the DECLARE-TIMI 58 trial, baseline heart failure (HF) status was collected from all patients, and EF was collected when available. HF with reduced EF (HFrEF) was defined as EF <45%. Outcomes of interest were the composite of cardiovascular death/HHF, its components, and all-cause mortality.Of 17 160 patients, 671 (3.9%) had HFrEF, 1316 (7.7%) had HF without known reduced EF, and 15 173 (88.4%) had no history of HF at baseline. Dapagliflozin reduced cardiovascular death/HHF more in patients with HFrEF (hazard ratio [HR], 0.62 [95% CI, 0.45-0.86]) than in those without HFrEF (HR, 0.88 [95% CI, 0.76-1.02]; P for interaction=0.046), in whom the treatment effect of dapagliflozin was similar in those with HF without known reduced EF (HR, 0.88 [95% CI, 0.66-1.17]) and those without HF (HR, 0.88 [95% CI, 0.74-1.03]). Whereas dapagliflozin reduced HHF both in those with (HR, 0.64 [95% CI, 0.43-0.95]) and in those without HFrEF (HR, 0.76 [95% CI, 0.62-0.92]), it reduced cardiovascular death only in patients with HFrEF (HR, 0.55 [95% CI, 0.34-0.90]) but not in those without HFrEF (HR, 1.08 [95% CI, 0.89-1.31]; P for interaction=0.012). Likewise, dapagliflozin reduced all-cause mortality in patients with HFrEF (HR, 0.59 [95% CI, 0.40-0.88;) but not in those without HFrEF (HR, 0.97 [95% CI, 0.86-1.10]; P for interaction=0.016).In the first sodium-glucose cotransporter 2 inhibitor cardiovascular outcome trial to evaluate patients with type 2 diabetes mellitus stratified by EF, we found that dapagliflozin reduced HHF in patients with and without HFrEF and reduced cardiovascular death and all-cause mortality in patients with HFrEF.URL: https://www.clinicaltrials.gov . Unique identifier: NCT01730534.
The Association of Painful Crises with Patient Reported Outcomes in Sickle Cell Disease: The SHIP-HU Study
Authors: Donna k McClish, Wally R. Smith, Victoria Okhomiuna, Daniel Sop Mouaffo, Richard Lottenberg, Ian Chen, India Sisler, Shirley Johnson, Darla K Liles, Elizabeth Yang, Thokozeni Lipato
Journal: Blood (2018)
Scaling up a one-health model of conservation through public health: experiences in Uganda and the Democratic Republic of the Congo
Authors: Gladys Kalema-Zikusoka, Joseph Byonanebye
Journal: The Lancet Global Health (2019)

BackgroundEndangered mountain gorillas are threatened by habitat destruction, wildlife poaching, and disease—factors exacerbated by high levels of human poverty and population growth rates in and around Bwindi Impenetrable National Park in Uganda. In 2003, Conservation Through Public Health (CTPH) was founded when fatal scabies skin disease outbreaks in Bwindi gorillas were traced to local communities who had inadequate access to basic health services. In 2007, CTPH implemented volunteer community-based family planning and later trained village health and conservation teams. These teams, using the one-health approach, promoted family planning, health, and conservation. The work resulted in a three-fold increase in family-planning users, reduced incidence of gorilla disease, and greater community support for conservation. Further, women become more involved in conservation and men become more involved in family planning. Here, we describe the scaling up of the one-health approach to protected areas in Africa.MethodsIn 2015, CTPH expanded the model of village health and conservation teams, sustained by village savings and loan associations, to a protected area with gorillas, at Mikeno and Mount Tshiabirimu sectors of Virunga National Park, Democratic Republic of the Congo, and to a non-protected gorilla area in Bukwo, Kween, and Bulambuli Districts of Mount Elgon National Park, Uganda. Both areas have high poverty levels and human population densities. Staff from CTPH monitored the project; village health and conservation teams collected data at household level.FindingsBetween 2015 and 2017, 81 000 people from 13 000 households in 139 villages in five districts were reached by 163 village health and conservation teams. Teams established ten financially stable networks that had group livestock to generate income that was reinvested in Village Savings and Loan Associations. Some households had improved water sanitation and hygiene, and 1597 patients with scabies were referred to the nearest health centre, as were 35 people with tuberculosis and 1674 with malnutrition. There was also an uptake of family planning services, including: implants (571 people), the contraceptive pill (479), intrauterine devices (119), tubal ligation (163), and side-effects management (749). At Mount Elgon, 9652 homes planted trees. Contraceptives from the Ministry of Health in Uganda, were provided free of charge to 3829 people in Mount Elgon and 285 people in Virunga.InterpretationCTPH's one-health approach has promoted better family planning, population, health, and conservation in Uganda and the Democratic Republic of the Congo. Scaling up requires more resources and dedicated organisational, governmental, professional, and community collaborations.FundingGlobal Development Network Japanese Social Development Fund.
The value of transperineal prostate apical zone biopsy in predicting urethral or apical margin status after radical prostatectomy in prostate cancer.
Authors: Jindong Dai, Pengfei Shen
Journal: Journal of Clinical Oncology (2019)

127 Background: To investigate potential preoperative predictors of positive surgical margin (PSM) after radical prostatectomy, and how to reduce the possibility of urethral or apical PSM with positive biopsy cores in the apical zone of prostate (AZP). Methods: 531 patients who had radical prostatectomy during 2010-2017 in West China hospital was enrolled. The logistic regression was used to assess the preoperative factors associated with PSM. 399 patients with high/very high risk prostate cancer were recognized by National comprehensive cancer Network guidelines and 339 patients were reported positive biopsy cores in the AZP. Results: The overall PSM rate of all patients was about 30.1% (160/531) and 117 of them were reported urethral or apical PSM. The occurrence rate of urethral or apical PSM in patients with positive cores in AZP was obviously higher than that in total group (p = 0.022). We further found that the addition of positive AZP to a standard multivariable model could significantly increase the predictive value of urethral or apical PSM (p = 0.016) in different groups. The analysis also showed that neo-adjuvant hormone therapy was an independent protective factor for urethral or apical PSM in positive AZP patients, but not all patients. Conclusions: This is the first study to investigate the necessity of getting cores in the apical zone by transperineal prostate biopsy to predict the possibility of apical or urethral PSM. In clinical practice, neo-adjuvant hormone therapy should be given when patients with AZP(+) to reduce the presence of PSM, especially patients with high/very high risk prostate cancer.
Impact of body mass index (BMI) on treatment outcomes to immune checkpoint blockade (ICB) in metastatic renal cell carcinoma (mRCC).
Authors: Aly-Khan A. Lalani, Wanling Xie, Ronan Flippot, John A. Steinharter, Lauren Christine Harshman, Bradley Alexander McGregor, Daniel Yick Chin Heng, Toni K. Choueiri
Journal: Journal of Clinical Oncology (2019)

566 Background: An elevated BMI is associated with improved survival in mRCC patients treated with oral targeted therapies (TT); however, this relationship in the contemporary treatment landscape is unknown. We investigated the effect of BMI on outcomes in mRCC patients treated with PD-1/PD-L1 ICB. Methods: We analyzed 147 patients with mRCC who received ICB alone or in combination with VEGF or other therapies. The association of BMI with objective response rate (ORR), progression-free survival (PFS), and overall survival (OS) was evaluated using logistic and Cox regression models, adjusted for known prognostic factors including International Metastatic RCC Database Consortium (IMDC) risk groups, line of therapy, ECOG (0 vs ≥1), and histology. Results: Median follow up was 25.5 (4.3-78.6) months (mos). Median time on ICB was 5.1 ( &lt; 0.1-69.7) mos. Overall, most patients were male (71%), had clear cell histology (85%), and were intermediate risk (60%). 43% received first-line ICB and 45% received ICB in combination therapy (37% with VEGF inhibition, 8% with other therapies). At ICB initiation, 46 (31%) patients were considered underweight/normal weight (BMI &lt; 25 kg/m 2 ), 56 (38%) overweight (BMI 25-30 kg/m 2 ), and 45 (31%) obese (BMI &gt; 30 kg/m 2 ). Patients with high BMI (≥ 25) had improved OS (median 34.3 vs 16.7 mos, 2-yr OS 61 vs 42%, p = 0.016) compared to those with low BMI ( &lt; 25), with an adjusted hazard ratio (HR) = 0.74 (0.44-1.26). ORR (33 vs 28%, p = 0.7) and PFS (median 8.2 vs 5.9 mos, p = 0.4) did not statistically differ. Patients who experienced a BMI change from ≥ 25 at start of first-line TT to &lt; 25 at start of subsequent-line ICB displayed shorter OS (adjusted HR = 2.25 (0.94-5.35)) compared to those with no change. Conclusions: High BMI appears to be associated with improved OS in mRCC patients treated with ICB. This contemporary data is consistent with the “obesity paradox” demonstrated in the TT era. Validation with the IMDC database and examination of underlying mechanisms are ongoing.
Phase II study of high-sensitivity genotyping of KRAS, NRAS, BRAF and PIK3CA to ultra-select metastatic colorectal cancer patients for panitumumab plus FOLFIRI: the ULTRA trial
Authors: C. Santos, D. Azuara, J.M. Viéitez, D. Páez, E. Falcó, E. Élez, C. López-López, M. Valladares, L. Robles-Díaz, P. García-Alfonso, C. Bugés, G. Durán, A. Salud, V. Navarro, G. Capellá, E. Aranda, R. Salazar
Journal: Annals of Oncology (2019)
Quantitative Integrative Prediction of Survival Probability in Multiple Myeloma Using Molecular and Clinical Prognostic Factors in 657 Patients Treated with Bortezomib-Based Induction, High-Dose Therapy and Autologous Stem Cell Transplantation
Authors: Manuela Hummel, Thomas Hielscher, Hans Jürgen Salwender, Christof Scheid, Hans Martin, Uta Bertsch, Hartmut Goldschmidt, Anja Seckinger, Dirk Hose
Journal: Blood (2018)
Refining Antithrombotic Therapy for Atrial Fibrillation and Acute Coronary Syndromes or PCI
Authors: Shamir R. Mehta
Journal: New England Journal of Medicine (2019)

An editorial focusing on the findings reported by Lopes et al. discusses early discontinuation of aspirin therapy after an acute coronary syndrome or PCI, recommending continued assessment of competing risks and avoidance of a one-size-fits-all policy.
Treatment disparities among patients in the National Cancer Database (NCDB) with clinical TIa and TIb renal masses.
Authors: Joshua Sterling, Zorimar Rivera-Nunez, Nicholas Farber, Parth K. Modi, Kushan Dilip Radadia, Sinae Kim, Goyal Sharad, Parikh Rahul, Robert E. Weiss, Isaac Kim, Sammy Elsamra, Thomas Jang, Eric Singer
Journal: Journal of Clinical Oncology (2019)

648 Background: AUA guidelines on the management of renal cell carcinoma (RCC) recommend prioritizing partial nephrectomy (PN) for the treatment of clinical T1a (cT1a) tumors, using PN for clinical T1b (cT1b) tumors when feasible, and performing minimally invasive surgery (MIS) when possible. Since cT1 RCC is a heterogeneous disease, we evaluated patterns of care in this population to examine factors associated with receipt of PN and MIS. Methods: We queried the NCDB from 2010-2014 to identify patients treated surgically for cT1N0M0 RCC. Patient socio-demographics, clinical characteristics, and treatment parameters were compared between cT1a and cT1b patients. Logistic regression models examined factors associated with receiving MIS. Results: Our population included 69,694 patients (44,043 cT1a and 25,651 cT1b). For cT1a tumors, 70% of patients received PN, while 30% received RN; 35% of patients underwent an open procedure and 65% underwent MIS. For cT1b tumors, 32% of patients received PN and 68% received RN; 38% of patients underwent an open operation and 62% underwent MIS. In both cohorts, African Americans and those earning &lt;$62,000 were less likely to have MIS. Distance to treatment was not significant in cT1b patients, but cT1a patients who traveled &gt;31 miles were more likely to undergo MIS. Patients treated at a community hospital were less likely to receive MIS compared to those treated at academic centers (cT1a OR: 0.48, 95% CI: 0.44-0.53 and cT1b OR: 0.63, 95% CI: 0.56-0.7). cT1a patients without private insurance were less likely to receive MIS (OR range: 0.58-0.93). However, only uninsured cT1b patients were less likely to undergo MIS (OR: 0.74, 95% CI: 0.64-0.86). Conclusions: PN occurred more frequently for cT1a (70%) vs. cT1b (32%) tumors. Most cT1 tumors received MIS; 35% of cT1a patients and 38% of cT1b patients underwent an open procedure, presenting an opportunity for improvement. cT1a and cT1b patients with lower household income, without private insurance, and those treated outside academic centers were less likely to receive MIS. Based on these findings additional research on the impact of regionalization of RCC surgery on utilization of PN vs. RN, receipt of MIS, and outcomes is warranted.
Active Surveillance for Newly Diagnosed Nodular Lymphocyte-Predominant Hodgkin Lymphoma
Authors: Sven Borchmann, Erel Joffe, Craig H. Moskowitz, Andrew D. Zelenetz, Ariela Noy, Carol S Portlock, John F Gerecitano, Connie Batlevi, Philip Caron, Pamela Drullinsky, Audrey Hamilton, Paul A Hamlin, Steven M Horwitz, Anita Kumar, Matthew J. Matasar, Alison J. Moskowitz, Colette N Owens, Lia Palomba, Anas Younes, David J. Straus
Journal: Blood (2017)
Development and Performance of a Checklist for Initial Triage After an Anthrax Mass Exposure Event
Authors: Nathaniel Hupert, Marissa Person, Dan Hanfling, Rita M. Traxler, William A. Bower, Katherine Hendricks
Journal: Annals of Internal Medicine (2019)

Population exposure to Bacillus anthracis spores could cause mass casualties requiring complex medical care. Rapid identification of patients needing anthrax-specific therapies will improve patient outcomes and resource use.To develop a checklist that rapidly distinguishes most anthrax from nonanthrax illnesses on the basis of clinical presentation and identifies patients requiring diagnostic testing after a population exposure.Comparison of published anthrax case reports from 1880 through 2013 that included patients seeking anthrax-related care at 2 epicenters of the 2001 U.S. anthrax attacks.Outpatient and inpatient.408 case patients with inhalation, ingestion, and cutaneous anthrax and primary anthrax meningitis, and 657 control patients.Diagnostic test characteristics, including positive and negative likelihood ratios (LRs) and patient triage assignation.Checklist-directed triage without diagnostic testing correctly classified 95% (95% CI, 93% to 97%) of 353 adult anthrax case patients and 76% (CI, 73% to 79%) of 647 control patients (positive LR, 3.96 [CI, 3.45 to 4.55]; negative LR, 0.07 [CI, 0.04 to 0.11]; false-negative rate, 5%; false-positive rate, 24%). Diagnostic testing was needed for triage in up to 5% of case patients and 15% of control patients and improved overall test characteristics (positive LR, 8.90 [CI, 7.05 to 11.24]; negative LR, 0.06 [CI, 0.04 to 0.09]; false-negative rate, 5%; false-positive rate, 11%). Checklist sensitivity and specificity were minimally affected by inclusion of pediatric patients. Sensitivity increased to 97% (CI, 94% to 100%) and 98% (CI, 96% to 100%), respectively, when only inhalation anthrax cases or higher-quality case reports were investigated.Data on case patients were limited to nonstandardized, published observational reports, many of which lacked complete data on symptoms and signs of interest. Reporting bias favoring more severe cases and lack of intercurrent outbreaks (such as influenza) in the control populations may have improved test characteristics.A brief checklist covering symptoms and signs can distinguish anthrax from other conditions with minimal need for diagnostic testing after known or suspected population exposure.U.S. Department of Health and Human Services.