tbuckley/cabot-search huggingface dataset:
Income Disparities in Absolute Cardiovascular Risk and Cardiovascular Risk Factors in the United States, 1999-2014
Authors: Ayodele Odutayo, Peter Gill, Shaun Shepherd, Aquila Akingbade, Sally Hopewell, Karthik Tennankore, Benjamin H. Hunn, Connor A. Emdin
Journal: JAMA Cardiology (2017)

<h3>Importance</h3> Large improvements in the control of risk factors for cardiovascular disease have been achieved in the United States, but it remains unclear whether adults in all socioeconomic strata have benefited equally. <h3>Objective</h3> To assess temporal trends in 10-year predicted absolute cardiovascular risk and cardiovascular risk factors among US adults in different socioeconomic strata. <h3>Design, Setting, and Participants</h3> A cross-sectional analysis was conducted using data on adults 40 to 79 years of age without established cardiovascular disease from the 1999 to 2014 National Health and Nutrition Examination Survey. <h3>Exposures</h3> Socioeconomic status was based on the family income to poverty ratio and participants were divided into the following 3 groups: high income (family income to poverty ratio, ≥4), middle income (&gt;1 and &lt;4), or at or below the federal poverty level (≤1). <h3>Main Outcomes and Measures</h3> We assessed predicted absolute cardiovascular risk using the pooled cohort equation. We assessed the following 4 risk factors: systolic blood pressure, smoking status, diabetes, and total cholesterol. <h3>Results</h3> Of the 17 199 adults whose data were included in the study (8828 women and 8371 men; mean age, 54.4 years), from 1999-2014, trends in the percentage of adults with predicted absolute cardiovascular risk of 20% or more, mean systolic blood pressure, and the percentage of current smokers varied by income strata (<i>P</i> ≤ .02 for interaction). For adults with incomes at or below the federal poverty level, there was little evidence of a change in any of these outcomes across survey years (cardiovascular risk ≥20%, 14.9% [95% CI, 12.9%-16.8%] in 1999-2004; 16.5% [95% CI, 13.7%-19.2%] in 2011-2014;<i>P</i> = .41; mean systolic blood pressure, 127.6 [95% CI, 126.1-129.0] mm Hg in 1999-2004; 126.8 [95% CI, 125.2-128.5] mm Hg in 2011-2014;<i>P</i> = .44; and smoking, 36.5% [95% CI, 32.1%-41.0%] in 1999-2004; 36.0% [95% CI, 31.1%-40.8%] in 2011-2014;<i>P</i> = .87). For adults in the high-income stratum, these variables decreased across survey years (cardiovascular risk ≥20%, 12.0% [95% CI, 10.7%-13.3%] in 1999-2004; 9.5% [95% CI, 8.2%-10.7%] in 2011-2014;<i>P</i> = .003; systolic blood pressure, 126.0 [95% CI, 125.0-126.9] mm Hg in 1999-2004; 122.3 [95% CI, 121.3-123.3] mm Hg in 2011-2014;<i>P</i> &lt; .001; and smoking, 14.1% [95% CI, 12.0%-16.2%] in 1999-2004; 8.8% [95% CI, 6.6%-11.0%] in 2011-2014;<i>P</i> = .001). Trends in the percentage of adults with diabetes and the mean total cholesterol level did not vary by income. <h3>Conclusions and Relevance</h3> Adults in each socioeconomic stratum have not benefited equally from efforts to control cardiovascular risk factors.
Quantifying the hepatotoxic risk of alcohol consumption in patients with rheumatoid arthritis taking methotrexate
Authors: Joel M Kremer, Michael E Weinblatt
Journal: Annals of the Rheumatic Diseases (2017)

As difficult as it may now be to believe, there was a time when it was unclear whether methotrexate (MTX) would be tolerated in the long-term treatment of patients with rheumatoid arthritis (RA). Data from Scandinavian patients with psoriasis indicated that there was an incidence of hepatic cirrhosis of 26%.1 There was thus a need to establish the actual risk of clinically significant liver disease (CSLD) in patients with RA treated for many years with the drug.

Because of the obvious clinical effectiveness of MTX, and the absence of effective alternatives in the first few decades of its widespread use, there was a need to demonstrate the ability to sustain treatment without creating a population of subjects with chronic liver disease.

Thus, studies of hepatic safety were performed that included both baseline and annual liver biopsies.2 3 This experience along with other publications on hepatic safety of MTX4 lead to the publication of suggested guidelines for the hepatic monitoring of MTX.5 The guidelines were derived from the experience from baseline and annual liver biopsies prospectively performed over a period of many years along with regular monitoring of hepatic transaminase enzymes and serum albumin with a mean interval of 37.7 days between the sequential laboratory measures.6 

It was thus possible to seek correlations of any elevation in transaminase enzymes with the evolution of hepatic histological changes by different grading systems, with particular attention paid to early fibrosis.2 In doing so, we …
Association between ER±36 and PR A/B overexpression in trastuzumab resistant HER2+ breast cancer cell lines.
Authors: Sergio Contreras, Eduardo Rey Torres, José Anselmo López, Eric Alejandro García, José Luis Ventura, Ernesto Badillo, Cesar Lara - Torres, Diana Elodia Aguilar, María de los Ángeles Ibarra, Alejandro Zentella Dehesa, Alvaro Aguayo
Journal: Journal of Clinical Oncology (2017)

e12501 Background: Clinical importance of the ERa36 isoform is poorly understood. It is present in 40% of the cells that lack the ERa66 and has also been linked to proliferation and invasion. It is also related to expression of phospho-src. Coincidently, phospho-src over-expression is associated to trastuzumab-resistance. We analyzed the possible link between trastuzumab-resistance and over expression of estrogen and progesterone receptors in HER2+ cell lines with trastuzumabTM chronic treatment. Methods: BT-474 and SKBR-3 cells were treated with trastuzumabTM with 4 ug/ml for 8 weeks, then 10 ug/ml for 2 weeks and with 20 ug/ml for the last 2 weeks. Protein extracts for western blot analysis where obtained from paternal cell lines and at 4, 8 and 12 weeks during treatment. Western blots were done for total and phosphorylated HER2, total and phosphorylated Src, aER and PR A/B. Densitometry analysis was applied to the western blots with the image-jTM software. Surface HER2 status was determined by flow citometry. Results: Treatment led to increase in T-HER but no changes in p-HER, T-Src and p-Src where increased, 5.27% and 18.01% respectively compared to baseline. 36KDa and 46KD aER isoforms increased with treatment. The most significant increase was in PR A expression. Western Blot for total HER2 and flow citometry for surface HER2 status revealed a link between HER2 and hormone receptor over-expression in TrastuzumabTM resistant BT-474 cells while both where absent in trastuzumabTM resistant SKBR-3 cells. Conclusions: A variety of trastuzumabTM-resistance mechanisms have been established, some of which include over-expression of p-Src. So far, none of them had been associated with expression of hormone receptors. We observed two molecular phenotypes associated to trastuzumabTM resistance: over-expression of HER2 linked to over-expression of hormone receptors in BT-474 cell and down-regulation of HER2 with no change in the hormone receptor status in the SKBR-3 cells. Our results suggest that over-expression of ERa36, ERa46 and PR A/B could represent a novel mechanism of trastuzumabTM resistance.
9 weeks vs 1 year adjuvant trastuzumab in combination with chemotherapy: Results of the phase III multicentric Italian study Short-HER.
Authors: Pier Franco Conte, Giancarlo Bisagni, Antonio Frassoldati, Alba Ariela Brandes, Elisa Anselmi, Francesco Giotta, Michele Aieta, Vittorio Gebbia, Antonino Musolino, Ornella Garrone, Cristiana Taverniti, Giovanna Cavazzini, Anna Turletti, Daniela Rubino, Elisa Picardo, Antonella Ferro, Federico Piacentini, Sara Balduzzi, Roberto D'Amico, Valentina Guarneri
Journal: Journal of Clinical Oncology (2017)

501 Background: 1-year trastuzumab with chemotherapy is the standard adjuvant treatment for HER2+ breast cancer patients (pts). The efficacy of less extended trastuzumab exposure is still under investigation. The Short-HER study is an independent, non-profit study aimed to test the non-inferiority of 9 weeks vs 1 year of adjuvant trastuzumab. Methods: This is a phase III, multicenter, Italian trial where pts with HER2+ breast cancer were randomly assigned to: Arm A (Long) AC or ECx4 followed by 4 courses of 3-weekly docetaxel in combination with trastuzumab, followed by 14 additional courses of 3-weekly trastuzumab; or Arm B (Short) 3 courses of 3-weekly docetaxel plus weekly trastuzumab for 9 doses followed by FEC x3. When indicated, radiation therapy was administered after the completion of chemotherapy. Hormonal therapy started at the completion of chemotherapy for pts with hormone receptor positive tumors. This is a non-inferiority trial with disease-free survival (DFS) as primary end-point.Overall survival (OS) is evaluated as second primary analysis outcome. The sample size of 1250 pts has been estimated based on a hazard ratio &lt;1.29 for the short arm to be non-inferior. The definitive analysis will take place after 198 DFS events. Secondary aims include 2-yrs failure rate, cardiac toxicity, correlative biomarkers analyses. Hazard ratio for DFS and OS (90% CI) will be estimated according to the Cox model. Data will also be analyzed by the Bayesian approach. Results: from Dec-2007 to Oct-2013, 1254 pts from 82 centers have been randomized. Pts characteristics are the following: median age 55 yrs (25-78), stage I 37.3%, IIA 40%, IIB 20.6%, III 2.1%. 30% of the pts had 1-3 positive nodes, 16% &gt;=4. Sixty-eight% of the pts had ER+ tumors. Characteristics were balanced between the two arms. At the time of this writing, 95% of the planned DFS events have been reported. 105 Grade ≥2 cardiac events have been reported, 78 in arm A (long) and 27 in arm B (short). Grade 3-4 cardiac events were 20 in arm A and 11 in arm B. Conclusions: Shorter trastuzumab administration almost halves the rate of severe cardiac toxicity. Final DFS data will be available at the time of the meeting. Clinical trial information: NCT00629278.
A phase II study of glembatumumab vedotin (GV), an antibody-drug conjugate (ADC) targeting gpNMB, in advanced melanoma.
Authors: Patrick Alexander Ott, Anna C. Pavlick, Douglas Buckner Johnson, Lowell L. Hart, Jeffrey R. Infante, Jason John Luke, Jose Lutzky, Neal Evan Rothschild, Lynn E. Spitler, Charles Lance Cowey, Aaron Alizadeh, April K. Salama, Xiaoyan Yin, Rebecca G. Bagley, Ying Wang, Omid Hamid
Journal: Journal of Clinical Oncology (2017)

109 Background: gpNMB is an internalizable transmembrane glycoprotein expressed in melanoma and multiple other tumor types. The ADC GV (CDX-011) delivers the potent cytotoxin MMAE to gpNMB+ cells. GV has shown promising activity in advanced melanoma and breast cancer. Methods: This Phase II study (CDX011-05) assessed the efficacy and safety of GV monotherapy (1.9 mg/kg q3w) for patients (pts) with advanced melanoma progressive after ≤1 chemotherapy, ≥1 checkpoint inhibitor (CPI) and if BRAF V600 mutated, ≥1 BRAF/MEK inhibitor. Central IHC determined gpNMB expression in archival and/or pre-treatment tumor. Primary endpoint was objective response rate (ORR) (RECIST 1.1) with ≥6 responders out of 52 evaluable pts as threshold for antitumor activity. Additional endpoints: progression free survival (PFS), overall survival (OS), duration of response (DOR), safety, PK/PD and correlation of tumor gpNMB expression with efficacy. Results: 62 pts enrolled (all evaluable) had median age of 67 years; 55% male; 21% BRAF V600 mutated; 63% with ≥3 lines prior therapy; 100% had prior CPI; 100% Stage IV; 89% M1c. One confirmed complete response (CR) and 6 confirmed partial responses (PR, including 1 unconfirmed CR) were seen (confirmed ORR = 11%, p = 0.035 comparing to reference ORR 5%); 33 pts had stable disease including 3 unconfirmed PR. Median DOR = 6.0 (range: 4.1, 14+) months (mos), median PFS = 4.3 mos and median OS = 9.8 mos; 26 pts continue to be followed for survival. All pts with available tissue (60/60) had gpNMB+ tumors; 47/60 had 100% gpNMB+ epithelial cells; no clear correlation with outcome was seen in this population with consistent high expression. Toxicities included alopecia, neuropathy, rash, fatigue and neutropenia. Treatment-related rash in cycle 1 was associated with improved ORR (rash = 22%; no rash = 7%), PFS (p = 0.007) and OS (p = 0.035). Conclusions: GV has promising activity (primary endpoint of ORR was met) with a manageable safety profile in heavily pre-treated melanoma pts. Additional cohorts evaluating GV with either varlilumab, an activating anti-CD27 monoclonal antibody, or PD-1 inhibitors are open to accrual to provide further insights into the synergy of ADC and immunotherapy. Clinical trial information: NCT02302339.
Improving pathological response in locally advanced triple negative breast cancer: Comparison between CbD and AC-T regimens.
Authors: Daniel Enriquez, Nathaly Poma Nieto, Hugo Alejandro Fuentes, Henry Guerra, Rossana Esther Ruiz Mendoza, Henry Leonidas Gomez
Journal: Journal of Clinical Oncology (2017)

585 Background: Pathological complete response (pCR) is a well-known surrogate for DFS and OS in triple negative breast cancer (TNBC). New approaches are being tested to increase pCR rate. We compared the standard of care (AC-T) vs Carboplatin/Docetaxel (CbD) for locally-advanced TNBC. Our objective is to determine whether CbD will increase the pCR rate, with PFS and OS as secondary objectives. Methods: A single arm phase II prospective trial with historical controls. 61 stage II-III TNBC patients were included between 2013-2014 at Instituto Nacional de Enfermedades Neoplasicas (Peru). 27 patients received Carboplatin 6AUC + Docetaxel 75mg/m 2 q21d for 6cy, and 34pts, Adriamycin 60mg/m 2 + Cyclophosphamide 600mg/m 2 q21d for 4cy followed by weekly paclitaxel 80mg/m 2 for 12 weeks. The Miller and Payne method was used to evaluate pathological response after definitive surgery. Results: Median age was 47 years, most patients were premenopausal (55.7%), median tumor size was 61 mm (T3=32.8%, T4=50.8%) and most patients had LN+ve (77%). There was a significantly greater tumor size in the CbD arm (mean 72.8 vs 52.2mm, p=0.007), no toxicity differences were noted. Only pCR was independently associated with OS/PFS on multivariate analysis. pCR was achieved in 37% (n=10) and 23.5% (n=8) in the CbD and AC-T groups, respectively (p=0.44). Partial pathological response was achieved in 37% (n=10) and 38.2% (n=13) patients in AC-T and CbD respectively. No characteristics were associated to pCR on logistic regression. At 2-year follow-up, all patients with pCR were alive and without recurrence, while patients with partial response achieved a 2-year PFS of 75% and, 2-year OS of 83.5%. The non-respondent group had the worse outcomes (2-year PFS: 32.7%, 2-year OS: 58.7%). The CbD group had a better 2-year PFS and OS (73.1% and 84%, respectively) than the AC-T group (59.3% and 71%, respectively), however no-statistical difference was found. Conclusions: CbD is an effective and promising neoadjuvant chemotherapy regimen for TNBC. Despite a larger mean tumor size in the CbD group, a non-significant trend towards higher pCR rate and longer PFS and OS was observed and warrants further exploration.
A Brain Model of Disturbed Self-Appraisal in Depression
Authors: Christopher G. Davey, Michael Breakspear, Jesus Pujol, Ben J. Harrison
Journal: American Journal of Psychiatry (2017)

Objective: A disturbed sense of self is a core feature of depression. The medial prefrontal cortex, which has a central role in self-appraisal processes, is often implicated in the illness, although it remains unclear how functional alterations of the region contribute to the observed disturbances. The aim of this study was to clarify the role of the medial prefrontal cortex in self-appraisal processes in depression. Method: The authors applied a recently developed dynamic network model of self-directed cognition to functional MRI data from 71 adolescents and young adults with moderate to severe major depressive disorder, none of whom were being treated with medication, and 88 healthy control participants. Bayesian model averaging was used to determine parameter estimates for the dynamic causal models, which were compared between groups. Results: While self-directed cognitive processes in the depression group were shown to rely on the same dynamic network as in the healthy control group, the medial prefrontal cortex had a "hyperregulatory" effect on the posterior cingulate cortex in the depressed group, with self-appraisal causing significantly more negative modulation of connectivity between the medial prefrontal cortex and the posterior cingulate cortex than in the control group (odds ratio=0.54, 95% CI=0.38, 0.77). This parameter was significantly inversely related with a depression factor related to poor concentration and inner tension (r=−0.32; 95% CI=−0.51, −0.08). Conclusions: The exaggerated influence of the medial prefrontal cortex on the posterior cingulate cortex in depression is a neural correlate of the disturbed self-appraisal that is characteristic of the illness.
Assessment of interstitial lung disease associated with chemotherapy alone and chemoradiation therapy in patients with pancreatic cancer.
Authors: Hironari Sueyoshi, Tatsuya Ioka, Ryoji Takada, Nobuko Ishida, Takuo Yamai, Nobuyasu Fukutake, Reiko Ashida, Hiroyuki Uehara, Kazumi Nishino, Junji Uchida, Toru Kumagai, Fumio Imamura, Kazuhiro Katayama
Journal: Journal of Clinical Oncology (2014)

e15194 Background: For pancreatic cancer (PC), the regimens which have been approved in Japan are gemcitabine(G), S-1(S), erlotinib combined with G(GE),and GS. And we have conducted chemoradiation therapy (CRT) for locally advanced PC (LAPC) and for border line resectable (BRPC) with the previously mentioned regimens.Some papers report interstitial lung disease (ILD) which occurred during treatments for PC ; the incidence of ILD by G, GE, S, GS as 0.4%, 2.1%, 0.3%, 0.7% respectively. Methods: We searched for patients who were examined and/or treated for PC from Jan 2012 to Dec 2013. Diagnoses of ILD were conducted by CT image. And then, we evaluated their smoking history, blood test data, and treatment options for ILD. Results: Of the 435 patients assessed for the study, 353 pts (M:F = 200:153) were included in the analysis. Of 353 pts, 20pts (5.7%) reported drug-related ILD, with 2 patients experiencing serious ILD resulting in death.Baseline characteristics of all pts included: male 56.7%; median age 66yrs; any smoking history 49.5%. ILD events occurred throughout the observation period with an incidence of 5 of 20 pts within 4 weeks, 3 pts from 4–8 weeks, 10 pts from 8–12 weeks, and 2 pts >12 weeks from the start of therapy. In the 20 patients suffering from ILD, the number of pts for each regimen they received was as follows; G was 8, GE was 3, GS was 3, S was 2, and chemoradiation therapy combined with G was 4. ILD caused death in 2 of the 20 ILD, while the remaining 18 recovered due to treatments. After the recovery from ILD, 11 of 18 pts were prescribed S. Conclusions: The regimens including G tended to cause ILD. And most of the cases happened in 3 months after the start of therapy. After the recovery from ILD, most pts could take S treatment. This analysis may provide the predictive factors of ILD in the treatments for PC, and the treatment profile of this population after recovering from ILD.
Data sharing statements for clinical trials
Authors: Darren B Taichman, Peush Sahni, Anja Pinborg, Larry Peiperl, Christine Laine, Astrid James, Sung-Tae Hong, Abraham Haileamlak, Laragh Gollogly, Fiona Godlee, Frank A Frizelle, Fernando Florenzano, Jeffrey M Drazen, Howard Bauchner, Christopher Baethge, Joyce Backus
Journal: BMJ (2017)
Novel Fatty Acid Oxidation Inhibitor Avocatinb Induces AMPK-Dependent Apoptosis of AML Cells Co-Cultured with BM-Adipocytes
Authors: Yoko Tabe, Kazumasa Sekihara, Kaori Saitoh, Vivian Ruvolo, Takashi Miida, Michael Andreeff, Paul A Spagnuolo, Marina Konopleva
Journal: Blood (2016)
Caregiver burden is increased in Parkinson’s disease with mild cognitive impairment (PD-MCI)
Authors: Ann J. Jones, Roeline G. Kuijer, Leslie Livingston, Daniel Myall, Kyla Horne, Michael MacAskill, Toni Pitcher, Paul T. Barrett, Tim J. Anderson, John C. Dalrymple-Alford
Journal: Translational Neurodegeneration (2017)

There is limited evidence on caregiver outcomes associated with mild cognitive impairment in patients with Parkinson’s disease (PD-MCI) and the coping strategies used by these caregivers. To investigate this relationship, we examined levels of burden, depression, anxiety, coping strategies and positive aspects of caregiving in the informal caregivers of 96 PD patients. The PD patients were classified using MDS-Task Force Level II criteria as showing either normal cognition (PD-N; n = 51), PD-MCI (n = 30) or with dementia (PDD; n = 15). Mean Zarit Burden Interview (ZBI) score increased significantly between carers of PD-N (M = 13.39, SD = 12.22) compared to those of PD-MCI patients (M = 22.00, SD = 10.8), and between carers of PD-MCI and PDD patients (M = 29.33, SD = 9.59). Moreover, the proportion of carers showing clinically significant levels of burden (ZBI score ≥ 21) also increased as the patients’ cognitive status declined (18% for PD-N; 60% for PD-MCI; and 80% for PDD) and was mirrored by an increasing amount of time spent providing care by the caregivers. Caregiver ZBI score was independent of patient neuropsychiatric symptoms, motor function, disease duration and time that caregivers spent caregiving. Caregiver use of different coping strategies increased with worsening cognition. However, we found only equivocal evidence that the use of problem-focused, emotion-focused and dysfunctional coping mediated the association between patient cognitive status and caregiver burden, because the inverse models that used caregiver burden as the mediator were also significant. The study highlights the impact of Parkinson’s disease on those providing care when the patient’s cognition is poor, including those with MCI. Caregiver well-being has important implications for caregiver support, nursing home placement and disease course.
Studies Utilizing the Portable Electromagnetic Ballistocardiograph
Authors: HARRY MANDELBAUM, ROBERT A. MANDELBAUM
Journal: Circulation (1952)

Persons who have failed to habituate to the cardiovascular effects of nicotine will demonstrate changes in their ballistocardiogram after smoking. These ballistocardiographic changes produced by smoking are of more abnormal quality and are found more frequently in patients with coronary artery and hypertensive heart disease than in normal subjects. The ballistocardiograph provides an accurate objective means of determining whether nicotine has a deleterious effect upon the myocardial function of a patient. In a significant proportion of patients with heart disease who demonstrated an abnormal ballistocardiographic response to smoking, clinical improvement was obtained after a period of tobacco abstention.