tbuckley/cabot-search huggingface dataset:
Fractional Flow Reserve and Quality-of-Life Improvement After Percutaneous Coronary Intervention in Patients With Stable Coronary Artery Disease
Authors: Takeshi Nishi, Zsolt Piroth, Bernard De Bruyne, Nikola Jagic, Sven Möbius-Winkler, Yuhei Kobayashi, François Derimay, Stephane Fournier, Emanuele Barbato, Pim Tonino, Peter Jüni, Nico H.J. Pijls, William F. Fearon
Journal: Circulation (2018)

Whether the benefit in quality of life (QOL) after percutaneous coronary intervention depends on the severity of the stenosis as determined by fractional flow reserve (FFR) remains unknown. This study sought to investigate the relationship between FFR values and improvement in QOL. From the FAME 1 and 2 trials (Fractional Flow Reserve Versus Angiography for Multivessel Evaluation), we identified 706 stable patients with coronary artery disease who had at least 1 lesion with an FFR≤0.80 that was treated with percutaneous coronary intervention and 185 patients with coronary artery disease who had no lesion with an FFR≤0.80 and were treated medically who served as a reference group. QOL was assessed by the European Quality of Life-5 Dimensions index at baseline, 1 month, and 1 year. We assessed the relationship between QOL improvement (defined as the change in European Quality of Life-5 Dimensions index from baseline) and FFR as a continuous value and according to abnormal FFR tertile. QOL improved significantly after percutaneous coronary intervention in each abnormal FFR tertile, whereas it did not change in the reference group. The lowest abnormal FFR subgroup had the greatest improvement in QOL at 1 month ( P<0.001). In mixed-effects models for repeated measures, lower FFR ( P=0.002 for 1 month and 0.049 for 1 year), greater delta FFR ( P=0.021 for 1 month and 0.025 for 1 year), and higher angina class ( P=0.001 for 1 month and <0.001 for 1 year) were associated with the greatest magnitude of QOL improvement at both 1 month and 1 year. Among patients with stable coronary artery disease, FFR and angina severity predict QOL improvement after percutaneous coronary intervention. URL: https://www.clinicaltrials.gov . Unique identifiers: NCT00267774 and NCT01132495.
Abstract 16852: Left Ventricular Hypertrophy and Cognitive Decline in Dementia-free Older Subjects at Risk of Cardiovascular Disease
Authors: Behnam Sabayan
Journal: Circulation (2015)

Background: Impaired cardiac function in patients with heart failure has been linked with structural and functional alterations in the brain. Left ventricular hypertrophy (LVH) is associated with lower cardiac output which can jeopardize cerebral perfusion. In this study, we investigated whether LVH is related with accelerated cognitive decline in dementia-free older subjects at risk of cardiovascular disease. Methods: We studied 4240 men and women dementia-free subjects, mean age 75.1 years, who were enrolled in PROSPER (PROspective Study of Pravastatin in the Elderly at Risk). From baseline electrocardiograms Sokolow-Lyon Product, a measure of LVH, was calculated. Four domains of cognitive functional testing reaction time, processing speed and immediate and delayed memory were assessed at baseline and repeated during a mean follow-up of 3.2 years. The association between Sokolow-Lyon Product and annual decline in various cognitive domains were evaluated using linear regression models adjusted for socio-demographic and cardiovascular factors. Results: At baseline higher Sokolow-Lyon Product, indicating higher degrees of LVH, was associated lower cognitive scores in reaction time (p&lt;0.001) and processing speed (p&lt;0.001). However, the associations attenuated after adjustments for demographic and cardiovascular factors. In the longitudinal analyses, higher Sokolow-Lyon Product was associated with steeper decline in processing speed (p=0.001), immediate (p=0.001) and delayed (p=0.003) memory function. All these associations were independent of cardiovascular factors and events during follow up. Conclusion: Higher degrees of LVH are independently associated with steeper cognitive decline, in particular in processing speed and memory domains. Older subjects with LVH need to be recognized as high risk groups for cognitive impairment.
Efficacy and tolerance of immune-checkpoint inhibitors in EGR, ALK/ROS 1 non-small-cell-lung-cancer (NSCLC): GFPC 03-2016 IMAD study.
Authors: Olivier Bylicki, Florian Guisier, Isabelle Monnet, Helene Doubre, Radj Gervais, Henri Janicot, Maurice Perol, Pierre Fournel, Jacques henri Le Treut, Régine Lamy, Hervé Le Caer, Lionel Falchero, Sabine Vieillot, Renaud Descourt, Chantal Decroisette, Thierry Urban, Chrystele Locher, Marie Marcq, Jean-Bernard Auliac, Christos Chouaid
Journal: Journal of Clinical Oncology (2018)

e21022 Background: Patients with molecular alterations are considered to be poor candidates for immune-checkpoint inhibitors (ICI) on the second-line phase III trials. Here, we analyze the efficacy of ICI in EGFR /ALK/ROS1 NSCLC patients in real world setting. Methods: This retrospective, multicentric study in EGFR, ALK and ROS1 NSCLC treated by ICI, analyzed clinical characteristics and outcomes (progression free survival (PFS), duration of ICI treatment and overall survival (OS), since initiation of ICI. Results: 51 patients were included from 20 centers in France: 100% adenocarcinoma, 60.7% never smokers, 58.8% female, 58 ± 8.8 years age at diagnosis (36-83), 82.3% EGFR mutated, 15.7 % and 2% ALK and ROS 1 translocated respectively. ICI was a third line treatment in 35,3% of cases, a fourth and more lines treatment in 64,7% of cases. Median PFS was 2.1. [95% CI: 1.5-3.2] months for the whole population, 2.15 [95% CI: 1.4-3;2], for EGFR patients and 2.4 [95% CI: 2.1; NR] for ALK tranlocated patients; 3 months-PFS were 37,3% [95% CI: 26.1; 53.2]; 8 weeks ORR were 19.6% (10 pts with partial response). The median OS for the whole population was 14.7.[95%CI: 12.1-19.2] months, 13.9 [95% CI: 8.8-20] for EGFR patients, 19.2. [95% CI: 13.1-NR] for ALK tranlocated; 7 (13.7%) patients were treated more than 9 months by ICI; 21.6% (11/51) of patients reported toxicities, all < grade3. Conclusions: In this real-world setting analysis, efficacy of ICI in EGFR, ALK, ROS1 NSCLC patients appears close to the efficacy observed in pretreated unselected NSCLC patients. Large prospective studies are needed in these populations.
The relationship between chemotherapy-induced neuropathy and quality of life in breast cancer survivors.
Authors: Barbara Sharon Gordon, Bolanle Gbadamosi, Ishmael A. Jaiyesimi
Journal: Journal of Clinical Oncology (2018)

e22111 Background: There are nearly 3 million survivors of breast cancer and the number continues to grow as advancements in treatments improve overall survival. This increase in survivorship necessitates a focus on quality of life (QOL) for breast cancer survivors. A major factor implicated in decreased QOL in cancer survivors is chemotherapy-induced peripheral neuropathy (CIPN), which is a known side effect of commonly used chemotherapy agents. This study aims to understand the relationship between symptoms of CIPN and QOL in breast cancer survivors. Methods: A survey of CIPN status was prepared based on the Quality of Life scale of the European Organization for Research and Treatment of Cancer (EORTC-QOL) and the CIPN20 sub-scales. Qualtrics was used to email the survey to 3524 patients diagnosed with breast cancer between 2004 and 2014. Patient responses were recorded, and response was used as consent to query medical records for chemotherapy status. Surveys were scored using standard methods for EORTC-QOL, and for CIPN20 subscales for i) motor, ii) sensory, and iii) autonomic functioning. Then, correlations between these subscale scores and QOL scores were computed using the scipy.stats Python toolbox for non-parametric Spearman correlation (ρ), and corresponding significance values. Results: The online survey was completed by 770 participants (22% response rate); 362 of these patients were found to have received chemotherapy. After completing the standard scoring of QOL and CIPN20 subscales, the correlations with QOL were: i) motor, ρ = -0.53 (p < .0005), ii) sensory, ρ = -0.50 (p < .0005), and iii) autonomic, ρ = -0.47 (p < .0005). Conclusions: We found a highly significant inverse correlation between CIPN symptoms and QOL as reported by breast cancer survivors. Motor and sensory symptoms were strongly associated with decreased QOL. More prospective research is needed to develop effective prevention and/or treatment methods for CIPN to improve QOL and the global health status of breast cancer survivors.
Abstract 15970: Importance of Vascular Factors on Long-term Integrity of Valvular Grafts Following a Ross Procedure in a Young Adult Population
Authors: Louis Simard, Jean Perron, Mylène Shen, Lionel Tastet, Siamak Mohammadi, Marine Clisson, Élizabeth Martin, Anthony Poulin, Marie-Annick Clavel
Journal: Circulation (2016)

Introduction: Valves degeneration after Ross procedure is not yet predictable in young adult. We thus aimed to identify determinants of echocardiographic degeneration of autograft and homograft. Me...
Generic imatinib therapy among Jordanians: An observational assessment of safety and efficacy in routine clinical practice.
Authors: Abdallah Awidi, Salah Y. Abbasi, Kamal Hosni Al-Rabi, Khalid Kheirallah
Journal: Journal of Clinical Oncology (2017)

e18548 Background: Generic imatinib therapy is being globally considered due to cost considerations. Evidence about its efficacy and safety in developing country settings, however, is scarce. Methods: The efficacy and safety of generic imatinib among Jordanian patients diagnosed with chronic myeloid leukemia (CML) was assessed utilizing an observational, multicenter, prospective study design. All patients (N = 91) were adults with CML treated with generic imatinib, mainly 400 mg/day, who either received generic imatinib (n = 33) as first-line therapy “first-line patients “or switched from patented imatinib to generic imatinib “switched patients” (n = 58). The primary objective was to measure proportions (95% Confidence Interval (CI)) of optimal response for first-line and switched patients at 12 months of treatment with generic imatinib, as defined in the 2009 ELN guidelines (CCyR [no Ph+ metaphases], or MMR [a ratio of BCR-ABL1 to ABL1 ≤0.1% on the International Scale]) and assessed by complete blood counts, fluorescence in situ hybridization and real-time quantitative PCR. Results: A total of 84.8% (n = 28/33) of the first-line patients achieved complete hematologic response (CHR) within 3 months of starting generic imatinib therapy (100% after 6 months). Out of the 23 evaluable first-line patients, [(87%, 95% CI = 73% - 100%), (n = 20)] in the per-protocol population (60.6 %, 95% CI = 51% - 86%) of the 33 patients in the intention-to-treat (ITT) population) achieved an optimal response at 12 months. All 58 switched patients had CHR at enrollment. Out of the 55 evaluable switched patients, [(96.4%, 95% CI = 91%-100%), (n = 53)] in the PP population (91.4%, 95% CI = 83%-98%) of the 58 patients in the ITT population) gained or maintained an optimal response at 12 months after switching to generic imatinib therapy. Most (84.7%, n = 144 out of 170) adverse events (AEs) were mild. Frequencies of drug-related AEs were similar to patented imatinib. Conclusions: Efficacy and safety of generic imatinib among middle eastern population in routine clinical practice is comparable to that of patented imatinib, and to that of the global population. Clinical trial information: NCT02977312.
P04.77 Death receptor 6 (DR6) is overexpressed in astrocytomas
Authors: S Stegmann, J Werner, S Kuhl, G Röhn, R Goldbrunner, M Timmer
Journal: Neuro-Oncology (2018)

Death receptor 6 (DR6), a member of the tumor necrosis superfamily, is overexpressed in different kind of tumors like prostate, ovarian and breast cancer and facilitates tumor angiogenesis. A therapeutic approach in colorectal cancer inhibits tumor growth via upregulation of DR6 in vivo. Therefore, we investigated the expression of DR6 in gliomas to evaluate its suitability as diagnostic marker or as potential therapeutic approach. Tumor samples were extracted during neurosurgery, frozen in liquid nitrogen and stored at -80°C. The analyzed groups were the following: control group, grade II, grade III, secondary glioblastoma (sGBM) and primary glioblastoma (pGBM) with and without temozolomide-treatment. Western Blots (WB) were performed with a primary DR6 antibody and a secondary peroxidase-conjugated antibody. ß-Actin was used to normalize the results. Immunofluorescence staining was done with a DR6 primary antibody and a secondary Cy3-anti rabbit antibody. DAPI was used to stain nuclei. Quantitative real-time PCR was performed with CYBR green and SDHA was used as housekeeping gene. For statistical analysis, Kruskal-Wallis and Mann-Whitney- U test were performed, as well as ANOVA and t-test. DR6 expression is increased in astrocytomas compared to control samples (WB control 0.12 ± 0.12 vs astrocytomas 0.32 ± 0.29; p≤ 0.05; PCR p = 0.0175). Western Blots show an enhanced expression of the receptor in high grade astrocytomas compared to low grades (high grade 0.38 ± 0.3 vs low grade 0.13 ± 0.08; p≤ 0.05). Grade III samples significantly differ from every other group except secondary glioblastomas. Treatment with temozolomide reduces DR6 expression in secondary glioblastomas (sGBM 0.37 ± 0.37 vs pGBM 0.07 ± 0.05; p≤ 0.05). PCR and Immunostaining show a high expression of DR6 in primary glioblastomas (pGBM 0,49 ± 0,3519 vs control 0,35 ± 0,059; p < 0.001). DR6 expression level is enhanced in astrocytomas and rises with increasing malignancy. Temozolomide reduces the expression of the receptor in secondary glioblastomas. Therefore, DR6 may be targetable as therapeutic approach.
Morphological correlates of oxaliplatin induced peripheral neuropathy assessed by magnetic resonance neurography.
Authors: Leonidas Apostolidis, Daniel Schwarz, Annie Xia, Markus Weiler, Sabine Heiland, Heinz-Peter Schlemmer, Dirk Jaeger, Martin Bendszus, Philipp Baumer
Journal: Journal of Clinical Oncology (2017)

10092 Background: Oxaliplatin induced peripheral neuropathy (OXA-PNP) is a frequent side effect of oxaliplatin containing chemotherapy protocols. It is commonly assessed clinically via physical examination and patient reported symptoms. Research has been impeded by the lack of objective tests to quantify OXA-PNP. Neurophysiological examination is time-consuming and can only cover a selected part of the examined nerve. The aim of this study was to investigate in-vivo morphological correlates of OXA-PNP by magnetic resonance neurography (MRN). Methods: 20 patients with mild to moderate OXA-PNP and 20 matched controls were prospectively enrolled. All patients underwent a detailed neurophysiology examination prior to neuroimaging. A standardized MRN imaging protocol at 3.0 Tesla with large-coverage included the lumbosacral plexus, as well as both sciatic nerves and their branches using T2-weighted fat-saturated sequences at high resolution. Qualitative evaluation of sciatic, tibial, and peroneal nerves were performed by two readers regarding the presence, degree, and distribution of nerve lesions. Quantitative assessment included volumetry of the dorsal root ganglia (DRG) and sciatic nerve normalized T2 (nT2) signal and caliber. Results: Significant DRG hypertrophy in OXA-PNP patients (207.3±47.7mm 3 vs. 153.0±47.1mm 3 in controls, p = 0.001) was found as morphological correlate of the sensory neuronopathy. Peripheral nerves only exhibited slight morphological alterations qualitatively. Quantitatively, sciatic nerve caliber was unchanged (26.0±5.1mm 2 vs. 27.4±7.4mm 2 , p = 0.19) while sciatic nerve nT2 signal was slightly and non-significantly elevated in patients (1.32±0.22 vs. 1.22±0.26, p = 0.19). Conclusions: OXA-PNP leads to morphological correlates that can be detected in-vivo by MRN. Significant hypertrophy of the DRG was observed, a phenomenon which has not been described in OXA-PNP previously. DRG volume should be investigated as a biomarker in other sensory peripheral neuropathies and ganglionopathies as well as in studies evaluating neuroprotective strategies for OXA-PNP.
Multidrug analyses in cancer patients via intratumoral microdosing with CIVO: A microinjection technology for phase 0 drug investigation.
Authors: Richard Klinghoffer, Matthew J Thompson, Darin J Davidson, Jessica A Bertout, Kimberly H W Sottero, Marc O Grenley, Emily Beirne, Seth Pollack
Journal: Journal of Clinical Oncology (2018)

e23569 Background: The vision of a precision medicine-guided approach to novel cancer drug development is challenged by high intra-tumor heterogeneity, interpatient diversity, and complex interactions between tumor cells and the surrounding microenvironment. Attempts to model this complexity through the use of ex vivo systems have failed to accurately represent tumor biology, and resulting predictions of clinical drug efficacy have met with limited success. Methods: To overcome these issues, we developed CIVO (Comparative In Vivo Oncology), an arrayed microinjection technology that evaluates tumor responsiveness to microdoses of multiple drugs simultaneously and directly in a patient's tumor. CIVO consists of a multidrug injection device, fluorescent tracking microspheres which accurately denote the position of each drug injection site, and automated image analysis tools capable of quantifying both tumor cell and microenvironmental biomarkers of response to local drug exposure. Results: Here we present preliminary data on the first 5 patients from our clinical feasibility study in soft tissue sarcoma. No unexpected adverse events related to microdose injection were observed. Consistent with historical clinical data, front line agent doxorubicin induced localized increases in markers for DNA damage, tumor cell apoptosis, and macrophage infiltration, whereas gemcitabine did not induce any observable local responses. Doxorubicin also induced tumor cell responses that suggest potential mechanisms of resistance to single agent therapy, including increased phosphorylation of PDGFaR, ERK and STAT3. Conclusions: Multidrug investigation via intratumoral microinjection with CIVO in patients with soft tissue sarcoma appears safe and feasible. The ability to evaluate and cross-compare multiple drugs and drug combinations simultaneously in living tumors across a diverse immune competent patient population provides an innovative and exciting functional approach to complement current precision oncology strategies and enables deep characterization of cancer biology in early drug development. Clinical trial information: NCT03056599.
Abstract B093: Development and validation of a novel automated Gleason grade and molecular profile that define a highly predictive prostate cancer progression algorithm-based test
Authors: Michael Joseph Donovan, Gerardo Fernandez, Richard Scott, Jack Zeineh, Giovanni Koll, Faisal Khan, Nataliya Gladoun, Elizabeth Charytonowicz, Ash Tewari, Carlos Cordon-Cardo
Journal: Cancer Research (2018)

Abstract Background: Postoperative risk assessment remains an important variable in the treatment of prostate cancer. We aimed to develop and validate a tissue-based on-slide prognostic risk model test to identify which patients would benefit most from early intervention. Methods: Prospectively designed retrospective study utilizing 892 patients, post radical prostatectomy, followed for a median of 8 years. We constructed a matched 50:50 training and test cohort to identify compound features using protein multiplex immunofluorescence combined with novel morphometry generated by advanced image analysis and machine learning tools. The primary endpoint was the development of a postoperative clinical failure (CF) including PSA rise post-adjuvant treatment, or metastasis or prostate cancer specific mortality. Time to event C-index and Kaplan-Meier were used to assess accuracy. Results: The Precise postop model in training (n=306) selected 4 compound imaging features and one clinical variable to predict CF with a performance C-index of 0.82, [95%CI: 0.76-0.86], HR:6.7, [95%CI: 3.59-12.45], p &amp;lt;0.00001. Of importance, the derived androgen receptor/Ki67/morphometric imaging features successfully replaced the subjective clinical Gleason grading in the final model. In validation, increasing Precise postop scores predicted shortened time to disease progression (n=284) with a C-index 0.77 [95%CI: 0.72-0.81], HR=5.4, [95%CI: 2.74-10.52], p &amp;lt;0.00001. Conclusion: Patients with high Precise postop scores had a higher likelihood of having disease progression within 8 years with a reduced durable response to androgen-deprivation therapy. The Precise postop algorithm-based model guided by machine learning replaces subjective Gleason grading with novel image features that combine morphometry with biologic attributes that more accurately reflect disease potential. Citation Format: Michael Joseph Donovan, Gerardo Fernandez, Richard Scott, Jack Zeineh, Giovanni Koll, Faisal Khan, Nataliya Gladoun, Elizabeth Charytonowicz, Ash Tewari, Carlos Cordon-Cardo. Development and validation of a novel automated Gleason grade and molecular profile that define a highly predictive prostate cancer progression algorithm-based test [abstract]. In: Proceedings of the AACR Special Conference: Prostate Cancer: Advances in Basic, Translational, and Clinical Research; 2017 Dec 2-5; Orlando, Florida. Philadelphia (PA): AACR; Cancer Res 2018;78(16 Suppl):Abstract nr B093.
Urinary creatinine excretion is related to short-term and long-term mortality in critically ill patients
Authors: Lara Hessels, Niels Koopmans, Antonio W. Gomes Neto, Meint Volbeda, Jacqueline Koeze, Annemieke Oude Lansink-Hartgring, Stephan J. Bakker, Heleen M. Oudemans-van Straaten, Maarten W. Nijsten
Journal: Intensive Care Medicine (2018)

Patients with reduced muscle mass have a worse outcome, but muscle mass is difficult to quantify in the ICU. Urinary creatinine excretion (UCE) reflects muscle mass, but has not been studied in critically ill patients. We evaluated the relation of baseline UCE with short-term and long-term mortality in patients admitted to our ICU. Patients who stayed ≥ 24 h in the ICU with UCE measured within 3 days of admission were included. We excluded patients who developed acute kidney injury stage 3 during the first week of ICU stay. As muscle mass is considerably higher in men than women, we used sex-stratified UCE quintiles. We assessed the relation of UCE with both in-hospital mortality and long-term mortality. From 37,283 patients, 6151 patients with 11,198 UCE measurements were included. Mean UCE was 54% higher in males compared to females. In-hospital mortality was 17%, while at 5-year follow-up, 1299 (25%) patients had died. After adjustment for age, sex, estimated glomerular filtration rate, body mass index, reason for admission and disease severity, patients in the lowest UCE quintile had an increased in-hospital mortality compared to the patients in the highest UCE quintile (OR 2.56, 95% CI 1.96–3.34). For long-term mortality, the highest risk was also observed for patients in the lowest UCE quintile (HR 2.32, 95% CI 1.89–2.85), independent of confounders. In ICU patients without severe renal dysfunction, low urinary creatinine excretion is associated with short-term and long-term mortality, independent of age, sex, renal function and disease characteristics, underscoring the role of muscle mass as risk factor for mortality and UCE as relevant biomarker.