tbuckley/cabot-search huggingface dataset:
A randomized, triple negative breast cancer enrolling trial to confirm molecular profiling improves survival (ARTEMIS).
Authors: Clinton Yam, Kenneth R. Hess, Jennifer Keating Litton, Wei Tse Yang, Helen Piwnica-Worms, Elizabeth Ann Mittendorf, Naoto T. Ueno, Bora Lim, Rashmi Krishna Murthy, Senthil Kumar Damodaran, Thorunn Helgason, Lei Huo, Alastair Mark Thompson, Michael Gilcrease, Lumarie Santiago, Rosalind P Candelaria, Gaiane Rauch, Beatriz Adrada, William Fraser Symmans, Stacy L. Moulder
Journal: Journal of Clinical Oncology (2017)

TPS590 Background: Following neoadjuvant chemotherapy (NACT), patients (pts) with triple negative breast cancer (TNBC) achieving pathologic complete response/residual cancer burden-0 (pCR/RCB-0) or minimal residual disease (RCB-I) have an improved relapse free survival when compared to pts with more extensive residual disease (RCB-II/III) (Symmans et al, JCO 2017). Pts with chemo-resistant TNBC have a poor prognosis as there are currently no FDA-approved targeted agents available for TNBC. We previously reported the ability of a novel gene expression signature (GES) to predict sensitivity to NACT (Hatzis et al, JAMA 2011). Here we seek to prospectively validate the use of this GES in combination with imaging to predict response to NACT and establish the clinical impact of selecting pts predicted to have non-responsive disease (NRD) for enrollment in clinical trials of targeted therapy. Methods: All pts will undergo a biopsy of the primary tumor for molecular characterization (MC) and will be randomized 2:1 to know their MC results (intervention arm) or not (control arm). A maximum of 360 pts will be enrolled and randomized using a group sequential design with one-sided O’Brien-Fleming boundaries, with two equally spaced binding interim tests for futility and superiority and one final test, having an overall Type I error of 0.05 and power of 0.80 to detect an improvement in pCR/RCB-I from 50% to 64%. Secondary endpoints include rates of clinical trial enrollment, disease free survival and integrated biomarker analyses. All pts will receive 4 cycles of anthracycline-based NACT with imaging done every 2 cycles to assess response. After completion or progression on anthracycline-based NACT, pts predicted to have NRD based on MC/imaging (intervention arm) or imaging alone (control arm) will be offered enrollment on a clinical trial. Pts are eligible if they have stage I-III TNBC with a primary tumor that is ≥1.5cm. Pts with contraindications to anthracyclines and/or taxanes are excluded. Enrollment began in November 2015. 105 pts have been enrolled to date with 71 and 34 pts randomized to the intervention and control arms, respectively. Clinical trial information: NCT02276443.
Older patients with mental illness are less likely to be referred, study finds
Authors: Susan Mayor
Journal: BMJ (2017)

Older patients with common mental health problems are less likely than younger patients to be referred by GPs for psychological therapies but show greater benefit when offered these treatments, a large UK study has found.1

Researchers analysed 85 213 episodes of patient care provided by psychological therapists in southwest England from 2010 to 2011, …
Effectiveness of Senior Faculty Member's Didactic, Motivational, Multimedia Teaching Session in Developing Enthusiasm for Training in Transfusion Medicine at a Medical School in Saudi Arabia
Authors: Abdul Rehman Zia Zaidi, Shahid Iqbal, Ibraheem H Motabi, Imran K Tailor, Nawal Faiez Alshehry, Samer Mudaibigh, Atta Munawar Gill, Assem A Elghazaly, May Al-Moshary,, Imran Pukhta, Ali Muse Mohamoud, Syed Ziauddin A. Zaidi
Journal: Blood (2016)
High Prevalence of Pneumothorax on PET-CT Studies Performed in Lung Cancer Patients Following Post–Transthoracic Needle Biopsy Mandates Careful Scrutiny
Authors: Joseph Sommerfeldt, Timothy L. Miao, Lionel Sydney Zuckier, Ashish Gupta
Journal: Clinical Nuclear Medicine (2017)

In our practice, FDG PET-CT studies are frequently performed within days of transthoracic needle biopsy, often revealing presence of pneumothorax (PTX), a "critical finding" that should be reported expeditiously. In our experience, prevalence of PTX at PET-CT performed 1 day following biopsy is greater than 40%. Of these, approximately a third are not visible on the postprocedure chest radiography, as in a case we describe. A high level of vigilance is therefore recommended to identify PTX in patients who have undergone recent transthoracic needle biopsy, even when no PTX is present immediately following the biopsy procedure.
Short Course of Bendamustine and Rituximab Followed By 90Y-Ibritumomab Tiuxetan in Patients with Chemotherapy-Naive Follicular Lymphoma (FOL-BRITe): Final Report of Response Rates and Progression Free Survival
Authors: Cristiana A Costa, Bassem I Zaki, Stephanie P Yen, Eric S Winer, Helen Ryan, Darcie Findley, Sara R Metzler, Lynn Shaw, Annie Tsui, Todd A MacKenzie, Anne W Beaven, Frederick Lansigan
Journal: Blood (2016)
A population-based analysis of treatment and outcomes in 2,500 metaplastic breast cancer patients.
Authors: Cecilia Tuongquang Ong, Samantha Marie Thomas, Brittany Morgan Campbell, Rachel Adams Greenup, Jennifer Kay Plichta, Laura Horst Rosenberger, Jeremy Meyer Force, Terry Hyslop, Eun-Sil Shelley Hwang, Oluwadamilola Motunrayo Fayanju
Journal: Journal of Clinical Oncology (2017)

532 Background: Metaplastic breast cancer (MBC) is a rare, aggressive variant that is often triple negative (TN). Current guidelines recommend use of standard receptor-based treatment for MBC despite evidence of chemoresistance. We sought to compare treatment patterns and outcomes of MBC and non-MBC. Methods: Women age &gt; 18 with stage I-III MBC and non-MBC histology diagnosed from 2010-2013 were identified in the National Cancer Database. Kaplan Meier and multivariate Cox proportional hazards models were used to estimate MBC association with overall survival (OS). Subgroup analyses were conducted for (1) MBC patients only and (2) TN MBC and TN non-MBC patients. Results: 2451 MBC and 568,057 non-MBC patients were included. 70.3% of MBC were TN vs 11.3% of non-MBC (p &lt; 0.001). 19.2% of MBC were luminal (i.e., ER+ and/or PR+, and HER2-). MBC presented with higher clinical T stage (cT4: 5.4% vs 1.8%) and grade (grade 3: 72.1% vs 29.7%) but was less frequently node-positive (19.1% vs 29.7%, all p &lt; 0.001). A higher proportion of MBC patients were treated with mastectomy (59.0% vs 44.9%), axillary dissection (ALND, 35.2% vs 32.2%), and chemotherapy (74.1% vs 43.1%, all p≤0.001). 5-year OS was reduced among MBC vs non-MBC patients for both the entire cohort (72.7% vs 87.5%) and the TN-only analysis (71.1% vs 77.8%, both log-rank p &lt; 0.001). Among MBC cases, TN subtype was not associated with worse OS than the luminal subtype (HR 1.16, p = 0.28). Chemotherapy (HR 0.69, p = 0.004) and/or radiotherapy (HR 0.52, p &lt; 0.001) improved OS in MBC, and the proportional benefit of chemotherapy did not vary with pathological T or N stage (interaction p &gt; 0.05 for both). Among TN patients, a higher proportion of TN MBC patients underwent mastectomy (58.4% vs 49.5%, p &lt; 0.001), but in contrast to the full cohort, a lower proportion of TN MBC patients received chemotherapy (76.6% vs. 78.7%, p = 0.008) and ALND (35.2% vs. 38.2%, p = 0.01) vs TN non-MBC patients. Conclusions: MBC had worse OS vs non-MBC, and unlike other histologies, outcome was not driven by receptor status. Multimodal therapy improved outcomes. Further investigation into MBC tumor biology and the development of MBC-specific guidelines could potentially improve treatment standardization and outcomes.
Diagnostic and Prognostic Implications of Exercise Treadmill and Rest First-Pass Radionuclide Angiography in Patients With Pulmonary Hypertension
Authors: Yen-Wen Wu, Pei-Ying Hsu, Yen-Hung Lin, Mei-Fang Cheng, Chi-Lun Ko, Yih-Hwen Huang, Ruoh-Fang Yen, Jin-Shing Chen, Jou-Wei Lin, Hsao-Hsun Hsu
Journal: Clinical Nuclear Medicine (2017)

Purpose Pulmonary hypertension (PH) is characterized by abnormally increased pulmonary vascular pressure, leading to deteriorated right ventricular function and premature death. Pulmonary mean transit time (PMTT) and biventricular function response to exercise in first-pass radionuclide angiography (FP-RNA) may provide early detection and timely disease monitoring of PH. This study aimed to investigate the diagnostic and prognostic values of this imaging modality in PH patients. Methods Left and right ventricular ejection fraction (LVEF/RVEF) and PMTT at rest and immediately after exercise treadmill test were measured by FP-RNA in 77 consecutive patients with clinical presentations suggestive of PH (aged 46 ± 15 years, 33 men), mostly with symptoms of unexplained progressive dyspnea. These parameters, along with other clinical variables, were correlated with right-sided heart catheterization data and clinical outcomes. Results Fifty patients (64.9%) were diagnosed as having definite PH. Besides higher N-terminal pro–B-type natriuretic peptide levels, right atrial pressure, and pulmonary vascular resistance, PH patients had significantly longer PMTT, lower LVEF after exercise and rest, and lower poststress RVEF (all P < 0.05), compared with non-PH subjects. Moreover, PH patients exhibited stress-induced right ventricular dysfunction and stationary poststress PMTT. Poststress PMTT and echocardiography had comparable diagnostic utility (area under the curve, 0.80 vs 0.84, respectively). Eighteen patients died during a median follow-up period of 380 days. Failure of exercise treadmill test, lower peak heart rate response, and stress/rest LVEF ratio of less than 90% using exercise treadmill FP-RNA were independent predictors of mortality in PH patients. Conclusions Exercise treadmill and rest FP-RNA provided diagnostic value and had prognostic implications in patients with PH.
Abstract P198: Aberrant Activation of γ2-AMPK Causes Cardiac Hypertrophy Independent of Glycogen Storage
Authors: Maengjo Kim, Roger Hunter, Kei Sakamoto, Christine E Seidman, Jonathan G Seidman, Lorena Garcia Menendez, Rong Tian
Journal: Circulation Research (2011)

AMP-activated protein kinase (AMPK) is an energy sensor and a key regulator of cell metabolism, hence a promising drug target. The cardiac functions of AMPK have not been understood. Point mutations in the regulatory γ2-subunit (encoded by PRKAG2 gene) have been shown to cause a unique form of cardiomyopathy in humans characterized by cardiac hypertrophy, arrhythmias and glycogen storage. We have previously shown that PRKAG2 mutation caused aberrant activation of AMPK in the absence of energy deficit and subsequently triggered re-routing of excessive glucose into glycogen pool. In this study, we addressed two questions: 1) whether cardiac hypertrophy in PRKAG2 cardiomyopathy was secondary of glycogen storage; 2) which hypertrophic signaling pathways are involved. We sought to reduce glycogen storage in transgenic mice expressing a mutant PRKAG2 (N488I) in the heart (TGγ2 N488I ) by crossing them to knock-in mice harboring a mutation in the muscle form of glycogen synthase (GYS1 KI ) that greatly reduced GYS activity in response to glucose-6-phosphate. Compared to TGγ2 N488I , TGγ2 N488I -GYS1-KI (double mutant) hearts showed lower GYS activity (0.7 ± 0.07 vs. 6.9 ± 0.49 nmol/min/mg, p&lt;0.0001) and reduced glycogen content (35 ± 4.5 vs. 169 ± 40 umol/g, p&lt;0.0001). Nonetheless, cardiac hypertrophy remained in the double mutant. The heart weight to body weight ratios were 6.8 ± 0.7 mg/g for TGγ2 N488I , 6.7 ± 0.5 mg/g for the double mutant compared to 4.0 ± 0.2 mg/g in the wild type. Furthermore, we have observed significant changes in FOXO (forkhead-O transcription factor) and mTOR (mammalian target of rapamycin) pathways in the TGγ2 N488I hearts. Increased phosphorylation of FOXO3a (Ser321, Ser253) and FoxO1a (Ser256) led to nuclear exclusion and degradation of FOXO proteins. Increased mTOR activity was evidenced by enhanced phosphorylation of Ser2448 as well as its downstream targets S6 and 4E-BP. Taken together these data indicate that aberrant γ2-AMPK activation causes cardiac hypertrophy independent of excessive glycogen accumulation. We found that increased mTOR activity and decreased FOXO signaling contributes to cardiac hypertrophy in TGγ2 N488I mice, suggesting novel mechanisms underlying cardiac hypertrophy caused by abnormal γ2-AMPK activity.
Efficacy and safety of the biosimilar ABP 501 compared with adalimumab in patients with moderate to severe rheumatoid arthritis: a randomised, double-blind, phase III equivalence study
Authors: Stanley Cohen, Mark C Genovese, Ernest Choy, Fernando Perez-Ruiz, Alan Matsumoto, Karel Pavelka, Jose L Pablos, Warren Rizzo, Pawel Hrycaj, Nan Zhang, William Shergy, Primal Kaur
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Objectives</h3> ABP 501 is a Food and Drug Administration-approved biosimilar to adalimumab; structural, functional and pharmacokinetic evaluations have shown that the two are highly similar. We report results from a phase III study comparing efficacy, safety and immunogenicity between ABP 501 and adalimumab. <h3>Methods</h3> In this randomised, double-blind, active comparator-controlled, 26-week equivalence study, patients with moderate to severe active rheumatoid arthritis (RA) despite methotrexate were randomised (1:1) to ABP 501 or adalimumab (40 mg) every 2 weeks. Primary endpoint was risk ratio (RR) of ACR20 between groups at week 24. Primary hypothesis that the treatments were equivalent would be confirmed if the 90% CI for RR of ACR20 at week 24 fell between 0.738 and 1.355, demonstrating that ABP 501 is similar to adalimumab. Secondary endpoints included Disease Activity Score 28-joint count-C reactive protein (DAS28-CRP). Safety was assessed via adverse events (AEs) and laboratory evaluations. Antidrug antibodies were assessed to determine immunogenicity. <h3>Results</h3> A total of 526 patients were randomised (n=264, ABP 501; n=262 adalimumab) and 494 completed the study. ACR20 response at week 24 was 74.6% (ABP 501) and 72.4% (adalimumab). At week 24, the RR of ACR20 (90% CI) between groups was 1.039 (0.954, 1.133), confirming the primary hypothesis. Changes from baseline in DAS28-CRP, ACR50 and ACR70 were similar. There were no clinically meaningful differences in AEs and laboratory abnormalities. A total of 38.3% (ABP 501) and 38.2% (adalimumab) of patients tested positive for binding antidrug antibodies. <h3>Conclusions</h3> Results from this study demonstrate that ABP 501 is similar to adalimumab in clinical efficacy, safety and immunogenicity in patients with moderate to severe RA. <h3>Trial registration number</h3> NCT01970475; Results.
Abstract 18580: Living in a Food Desert Fails to Predict Heart Failure Readmissions
Authors: Benjamin DeMoss, Sujoy Phookan, Muhammad Hammadah, Heval Kelli, Divya Gupta
Journal: Circulation (2016)

Introduction:  Limited access to healthy food has been linked to an unfavorable cardiovascular risk profile. This study sought to determine whether living in a food desert or an area with low access to fresh food impacts 30-day readmissions and total hospitalizations for heart failure patients.   Hypothesis:  Living in a food desert is associated with heart failure readmissions.   Methods:  We identified patients admitted to a university hospital between 01/01/2013 and 12/31/2013 with a primary diagnosis of heart failure. We entered patients’ zip codes into the USDA Food Access Research Atlas to identify patients who live in areas with low access to fresh food or food deserts. Low-access areas are defined as regions where ≥ 33% of the population live > 1 mile (in urban areas) or > 10 miles (in rural areas) from a supermarket. Food deserts have the additional stipulation of areas where median income is ≤ 80% of statewide median. We used regression analysis to compare 30-day readmissions and total hospitalizations for patients living in low-access or food deserts vs. living in adequate-access areas. Additional variables including poverty level, health insurance status, and education level were also examined for each zip code.   Results:  There was 2063 hospitalizations from 1598 unique patients in this sample (54% male, 41.1% African American, mean age 65±17 years, mean EF 41±19%). 789 (49.4%) patients lived in low-access areas and 318 (19.9%) lived in food deserts. 211 (13.2%) patients had at least one 30-day readmission. Living in a low-access area or a food desert was not associated with a 30-day readmission or the total number of heart failure-related hospitalizations (p > 0.05). Living in zip codes with levels of poverty, high school dropout rate, and uninsured status above the national average did not correlate with 30-day readmissions or total heart failure-related hospitalizations for our sample (p > 0.05).   Conclusion:  Living in a food desert or low-access area is not predictive of 30-day heart failure readmissions or total heart failure-related hospitalizations in this population. Further investigation examining additional outcome measures with a larger cohort and broader geography is necessary to substantiate these findings.
Characteristics of HER2 3+ metastatic breast cancer patients with long-term benefit of trastuzumab.
Authors: Zoran Tomasevic, Zorica Tomasevic, Ivana Minic, Daniela Kolarevic
Journal: Journal of Clinical Oncology (2017)

e12523 Background: Because there is no cumulative dose, trastuzumab could be given until disease progression. However, characteristics of patients with long term benefit of trastuzumab treatment are seldom reported. Methods: Trastuzumab become available for HER2 3+ MBC at November 2005 at the Institute for Oncology and Radiology of Serbia. Since then, we have registered 42 patients with HER2 3+ MBC and/or inoperable loco-regional recurrent BC treated with first line trastuzumab for at least 24 months (range 24-123+). Results: Median age was 53 years (range 35-76). 30/42 patients (71%) had ER/PR positive BC. MBC was initial presentation in 14 patients (33%), and as relapse in 28 (67%) patients. Only 7/28 (25%) patients received neoadjuvant/adjuvant trastuzumab, therefore majority have been trastuzumab naive (83.3%). Metastases were present in the liver (9), lungs (9), bones (16), soft tissue (6), CNS (1), while 20 (48%) patients had multiple metastatic sites. After antracyclines based chemotherapy, patients have been treated with first line weekly taxane concurrently with three weekly trastuzumab. After taxanes (up to 24 doses), trastuzumab was continued +/-hormonal therapy. Objective response was achieved in 29 (69%) patients with 17 patients (40%) achieving complete response. Median duration of response was 32+ months; 11 patients are still in remission 5 years after trastuzumab initiation. The longest complete remission duration is 123+ months, in patient with initially inoperable BC and solitary cerebellar metastasis. During observational period 10 patients stopped trastuzumab predominantly because of disease progression (8/42 19%) and 2 (4.8%) because of decreased ejection fraction (EF≤ 50%) that occurred as a rather late effect, after 34 and 49 months of continuous trastuzumab treatment. Three patients are lost from follow-up (7%); 39 (93%) patients included in this analysis are alive, still receiving trastuzumab for median 37 cycles (range 29-172+). Conclusions: A subgroup of patient with HER2 3+ MBC has a long-term benefit of trastuzumab treatment. In this analysis majority (71%) had also ER/PR positive MBC and majority have not been treated with neoadjuvant/adjuvant trastuzumab (83.3%).
Results of treatment with 5-azacytidine in patients treated for myelodysplastic syndrome or secondary acute myeloid leukemia associated with a concomitant active cancer.
Authors: Maxime Annereau, Romain Desmaris, Jean Baptiste Micol, Julien Lazarovici, Catherine Chenailler, Veronique Saada, Veronique Verge, Oumar Balde, Francois Lemare, Christophe Willekens, Stephane De Botton
Journal: Journal of Clinical Oncology (2014)

e18029 Background: 5-azacytidine (AZA) is recognized as a standard of care for patients with high risk myelodysplastic syndrome (MDS) and secondary acute myeloid leukemia (AML) to MDS with less than 30% blasts. However, even if all phase III studies with AZA have included patients with therapy-related MDS, AZA has not been studied in patients with a concomitant active solid cancer to MDS. To address this question, we retrospectively compared response rate and overall survival of MDS/AML patients with a concomitant cancer treated by AZA to patients with therapy-related MDS/AML treated by AZA. Methods: From January 2007 to January 2013, 11 patients with MDS and less than 30% blasts on bone marrow and second simultaneous cancer (Group A) were treated with AZA 75mg/m²/d for 7 days each 4 weeks in Gustave Roussy Hospital. Response rate according to IWG 2006, overall survival, transfusion independence and treatment intercourse of these patients were compared to 26 patients treated with AZA for secondary MDS or LAM to previous chemotherapy (Group B). Results: Global responses i.e. Complete Responses (CR) and Partial Responses (PR) rates were similar. in Group A, 63.36% (7/11 patients) (27.27% of CR and 36.36% of PR) were responders versus 69.23% (18/26 patients) in group B (38.46% of CR and 26.92% of PR) (p =0.74 Chi² test). Median overall survival in group A was 9.12 months versus 11.62 in group B (p = 0.93 log rank test). Temporary transfusion independence was observed for 7/11 patients (63.36% and were the responders) in Group A versus15/26 (57.7%) patients in group B. The median duration of transfusion independence was 241 days in group A and 148 days in group B. Treatment intercourse was similar in the two groups. Conclusions: Our data suggest that AZA is feasible in patients with MDS/AML and simultaneous active cancer. The treatment is well tolerated and could improve the quality of life through transfusion independence. The prognosis of patients appears to be similar to that of conventionally treated patients after a first cancer and suggests the need of specific treatment of MDS/AML compared to best supportive care in this situation.