tbuckley/cabot-search huggingface dataset:
Abstract 19176: Mapping of Electrogram Morphology Recurrence Patterns during Atrial Fibrillation
Authors: Jason Ng, David Gordon, Vinod Sehgal, Rishi Arora, Jeffrey J Goldberger
Journal: Circulation (2012)

Introduction: Electrograms during atrial fibrillation (AF) are complex and seemingly chaotic. It is still unknown how to best analyze and utilize AF electrograms. Hypothesis: We hypothesize that the frequency and patterns of AF electrogram morphology recurrence determined by a modified recurrence plot (RP) analysis will show differences based on region in this pilot study. Methods: AF electrograms (&gt;16 s) recorded from documented left atrial (LA) and right atrial (RA) sites in 13 patients (10 male, 59±10 years old) prior to AF ablation were analyzed. A 100 ms window for each automatically detected activation was extracted and cross-correlated with every other activation in a 30-sec recording. The result was a set of NxN cross-correlation (CC) values, where N is the number of detected activations. These values were displayed in a two-dimensional RP. A recurrence index (RI), the percentage of the most common morphology, was also computed. A high RI likely indicates consistent activation directions at the site of bipolar electrogram recording. Results: Figure A is a RP example. The checker board pattern of alternating high and low CC values indicates periodic recurrences in morphologies (RI=70% for this example). The mean RI for all sites and all patients was 38±25%. The highest RI was found in the left superior LA in all 4 paroxysmal AF patients (85±18%, see Figure B). For 9 persistent AF patients, the highest RI was found in the RA (91±10%) in 5 patients and in the left superior LA (95±6%) in 4 patients. The persistent AF patients had higher maximum RIs in the RA than the paroxysmal AF patients (87±16 vs. 51±15%, p=0.01). Conclusion: Electrogram morphology with highest recurrence rates were most frequently found in the left superior LA, a common location for AF triggers. Further work is needed to determine whether high electrogram repeatability reflects AF driver activity and whether RPs could be used as part of an ablation strategy.
Abstract 10677: Erlier Reperfusion in Patients With St-elevation Myocardial Infarction by Use of Helicopter Compared to Ground Transportation
Authors: Lars Knudsen, Carsten Stengaard, Troels M Hansen, Jens F Lassen, Christian J Terkelsen
Journal: Circulation (2012)

Background:In patients with ST-elevation myocardial infarction (STEMI) reperfusion therapy should be initiated as soon as possible. This study evaluated whether use of helicopter for transportation...
Discussing end-of-life treatment options: advanced cancer vs. amyotrophic lateral sclerosis
Authors: A. B. Astrow, J. R. Sood, M. T. Nolan, P. B. Terry, M. T. Hughes, J. Kub, D. P. Sulmasy
Journal: Journal of Clinical Oncology (2005)

8065 Background: Patients with advanced cancer need information about treatment options if they are to make informed decisions about end-of-life care. Clinicians sometimes avoid these discussions. Methods: As part of a long-term longitudinal study, we interviewed patients with advanced gastrointestinal or lung cancer and an expected 2-year survival of < 50% (CA) and patients with recently diagnosed amyotrophic lateral sclerosis (ALS). We reviewed each patient’s out-patient chart at enrollment and at three months for evidence of discussion of patient wishes concerning ventilator support (VS), artificial nutrition and hydration (ANH), resuscitation (DNR), and hospice care (HC), comparing CA patients with ALS patients using the Fisher’s or the χ2 tests. We also performed a Kaplan-Meier analysis and calculated 2 year survival. Results: We enrolled 60 CA patients and 32 ALS patients. Mean patient age was 62 for CA and 62 for ALS. Sixty-two percent of CA patients were male vs. 56% for ALS (NS). Seventy-one percent of CA patients were white vs. 94% for ALS (p = .01). ALS patients were significantly more likely than CA patients to have evidence of a discussion about their wishes for VS (35% vs.0%, p < .001), ANH (40% vs. 0%, p < .001), DNR (29% vs. 0%, p < .001), and HC (25% v. 5%, p = .03). At six months, 91% of ALS patients were alive vs. 62% of CA; at two years 63% of ALS patients were alive vs. 23% of CA, (p < .001). Conclusions: CA patients were less likely than ALS patients to have had an out-patient discussion about VS, ANH, DNR, and HC despite having a significantly worse survival outcome. This may reflect a perception that ALS has a more predictable downhill course than advanced CA, a greater number of treatment options for advanced CA compared with ALS, or differing views about hope. The lack of documented discussion of end-of-life treatment options in this group of poor prognosis CA patients may nevertheless leave CA patients less adequately prepared for end-of-life decision-making and/or forced to confront these difficult issues only when hospitalized and close to death. No significant financial relationships to disclose.
Interactions of breast cancer cells and tumorantigen-reactive T-cells derived from bone marrow
Authors: F. Schuetz, C. Sachsenweger, J. Rom, A. Schneeweiss, V. Schirrmacher, P. Beckhove, C. Sohn
Journal: Journal of Clinical Oncology (2007)

13517 Breast cancer is an immunogenic tumor which is usually recognized by the cellular immunosystem via tumor-associated antigens (TAA) presented by antigen-presenting cells like dendritic cells. Although we were able to find tumorantigen-reactive CD8 + CD45R0 + T-memory cells (TMC) in the bone marrow of 67% of primary breast cancer patients by using interferon-?-ELISPOT-analysis there seem to be a minority of non-responers. In comparison to classic tumor characteristics non-responders can be find more often in non-differentiated, hormone-receptor negative tumors. In a phase-1 trial of a cellular immunotherapy with reactivated tumorantigen-reactive autologous TMC derived from bone marrow we measured CD4 + T-cell (TC) responses in stimulation cultures ex vivo to examine whether there are other immunological answers in non-responder. TC were activated by dendritic cells pulsed with TAA from MCF-7 lysate under IL-2 co-stimulation. We were able to show that next to a classic TH1-response with high levels of IFN-a there seems to exist TH2-responses mediated by high levels of TGF-β1 and low levels of IFN-a. The relation of both cytokines was directly related to the detection of tumorantigen-reactive TC and to tumor grading. Multiplex-cytokine analysis was able to confirm these findings. Additionally there seems to be an important impact of regulatory TC in responders as well as in non-responders. In patients with tumorantigen-reactive TC a combined active and passive vaccination therapy was done. These results may play an important role in further active and passive vaccination strategies. No significant financial relationships to disclose.
Long-term safety and overall survival update for BREAK-2, a phase 2, single-arm, open-label study of dabrafenib in previously treated metastatic melanoma (NCT01153763).
Authors: Paolo Antonio Ascierto, David R. Minor, Antoni Ribas, Celeste Lebbe, Anne O'Hagan, R. Suzanne Swann, Anita Scheuber, Dirk Schadendorf, Richard Kefford, Jean Jacques Grob, Omid Hamid, Lynn Mara Schuchter, Ester Simeone, Tabea Wilhelm, Kevin Kim, Gursel Aktan, Uwe Trefzer
Journal: Journal of Clinical Oncology (2014)

9034 Background: Dabrafenib is a potent inhibitor of mutated BRAF kinase in BRAF V600E/K mutation–positive metastatic melanoma (mut+ MM). This multicenter, single-arm phase 2 study assessed safety and clinical activity of dabrafenib in BRAF V600E/K mut+ MM. We previously reported the primary endpoint of investigator-assessed overall response rate in BRAF V600E mut+ MM patients and overall survival (OS; median follow-up 11.9 months). Here we report long term safety data and updated OS (median follow-up 13 months). Methods: 92 patients with histologically confirmed stage IV BRAF V600E/K mut+ MM received oral dabrafenib 150 mg twice daily until disease progression, death, or unacceptable adverse events (AEs). Secondary endpoints included safety and OS. AEs were summarized by duration of dabrafenib treatment. Results: 76 patients with BRAF V600E mut+ MM and 16 with BRAF V600K mut+ MM were enrolled from August 2010 to February 2011. As of December 2013, 11 patients (12%) had not experienced a progression event and 9 continued to receive dabrafenib. In the BRAF V600K group, median OS was 12.9 months (95% CI, 6.9-17.1); 4 patients (25%) were alive beyond 18.8 months (third quartile OS; 95% CI, 12.9-NR). In the BRAF V600E group, median OS was 13.1 months (95% CI, 10.4-21.9); 21 patients (28%) were alive beyond 30 months (third quartile OS, NR). The most common AEs in all patients were arthralgia (35%), hyperkeratosis (33%), and pyrexia (29%). Overall, 33 patients (36%) experienced a serious AE; 13 (14%) had cutaneous squamous cell carcinoma. New primary melanoma and other malignancies occurred in 2 patients (2%). For patients on dabrafenib > 24 months (n = 11), hyperkeratosis (64%), arthralgia (55%), and pyrexia (45%) were the most common AEs observed during treatment, and 2 patients (18%) experienced serious AEs during treatment. Conclusions: 25 patients were alive as of December 2013, and 9 of those patients were receiving treatment with dabrafenib. Median OS was > 1 year in patients with BRAF V600E/K mut+ MM treated with dabrafenib. The most common AEs in patients treated with dabrafenib > 24 months were the same as those in patients treated with dabrafenib < 24 months. Clinical trial information: NCT01153763.
Sphingosine-1-phosphate reduces ischaemia–reperfusion injury by phosphorylating the gap junction protein Connexin43
Authors: Sandrine Morel, Christina Christoffersen, Lene N. Axelsen, Fabrizio Montecucco, Viviane Rochemont, Miguel A. Frias, Francois Mach, Richard W. James, Christian C. Naus, Marc Chanson, Paul D. Lampe, Morten S. Nielsen, Lars B. Nielsen, Brenda R. Kwak
Journal: Cardiovascular Research (2016)

Increasing evidence points to lipoprotein composition rather than reverse cholesterol transport in the cardioprotective properties of high-density lipoproteins (HDLs). HDL binding to receptors at the surface of cardiomyocytes activates signalling pathways promoting survival, but downstream targets are largely unknown. Here, we investigate the pathways by which the sphingosine-1-phosphate (S1P) constituent of HDL limits cell death induced by cardiac ischaemia–reperfusion (I/R). Apolipoprotein M (ApoM) transgenic (Apom-Tg) mice, in which plasma S1P is increased by 296%, and wild-type (WT) mice were subjected to in vivo I/R. Infarct size, neutrophil infiltration into the infarcted area, and serum Troponin I were less pronounced in Apom-Tg mice. In vitro experiments suggest that this cardioprotection depends on direct effects of S1P on cardiomyocytes, whereas leucocyte recruitment seems only indirectly affected. Importantly, short-term S1P treatment at the onset of reperfusion was sufficient to reduce I/R injury in isolated perfused hearts. Mechanistic in vitro and ex vivo studies revealed that 5 min of S1P treatment induced phosphorylation of the gap junction protein Connexin43 (Cx43) on Serine368 (S368), which was mediated by S1P2 and S1P3, but not by S1P1, receptors in cardiomyocytes. Finally, S1P-induced reduction of infarct size after ex vivo I/R was lost in hearts of mice with a truncated C-terminus of Cx43 (Cx43K258/KO) or in which the S368 is mutated to a non-phosphorylatable alanine (Cx43S368A/S368A). Our study reveals an important molecular pathway by which modulating the apoM/S1P axis has a therapeutic potential in the fight against I/R injury in the heart.
Determinants of prostate volume changes following iodine-125 interstitial prostate implant
Authors: E. Bieniek, H. Ashamalla, A. Guirguis
Journal: Journal of Clinical Oncology (2007)

15563 Purpose: Prostate brachytherapy (PB) has been linked with increase in prostate volume (PV). This study evaluates post- operative PV changes and the variables that might affect prostate swelling. Methods: Twenty four patients (pts) were analyzed. Twelve were treated with PB only, 8 with external beam radiation (EBRT) prior to implant, and 4 with EBRT after PB. Pre-treatment PSA and Gleason score ranges were 1.9–10.8 and 5–8 respectively. Pre- implant and post-implant day 1, 9, 30, and 60 (PV0, PV1, PV9, PV30, and PV60) measurements were done using computed tomography. Univariate analysis of PV change and the following was done: PV0, number of needles, seeds, and needle insertion attempts, seed activity (0.3 vs 0.5mCi), hormonal ablation therapy, and prior EBRT. Urinary symptoms were assessed using International Prostate Scoring System (IPSS). Results: Ninety six PV measurements were done by a single observer. PV0 ranged from 27.1 to 89.4 cc (mean 48.2). Largest PV was observed on day 1 (40.1–118.7, mean 67.1). Successive PV measurements afterwards continued to decrease. Mean PV values on day 9, 30, and 60 were 58.6, 51.5, and 42.3cc respectively. The differences between PV0 and all successive PV’s were statistically significant. Mean increase in PV1 from PV0 was 18.9±16.8cc (p&lt;0.001), PV0 and PV9 9.7cc, PV0 and PV30 2.6cc. PV60 was smaller than PV0 by an average of 6.6cc. Statistically significant positive correlation was found between PV increase and seed activity (p=0.02) while treatment with EBRT prior to PB was associated with less prostate swelling (p=0.043). Other variables were not significantly correlated with PV changes. Although the mean IPSS score increased from pre-implant value of 9.2 to 13.7 on day 60, the differences between IPSS values were not statistically significant. Conclusions: Maximum prostate size is observed on the first day after implant. Prostate begins to decrease in size between day 1 and day 9 and reaches pre-procedure volume after day 30. Higher seed activity results in greater prostate swelling, while less brachytherapy- induced swelling is observed in patients treated with external radiation prior to implant. Resolution of prostate swelling does not appear to parallel with improvement in urinary symptoms in the first 2 months after implant. No significant financial relationships to disclose.
The effect of androgen deprivation therapy on CD4/CD8 T cells in HIV-negative patients receiving definitive 3D radiation treatment for their prostate carcinoma: Final report of a prospective study
Authors: M. A. Elshaikh, Z. Abdel Hafeez, M. Lu, D. Ibrahim, T. El Masry, A. Yousef
Journal: Journal of Clinical Oncology (2009)

11056 Background: CD4 and CD8 T cells play critical roles in human immunity. The aim of this prospective study is to explore the correlation of the absolute CD4/CD8 T cell counts and total testosterone in patients receiving androgen deprivation therapy (ADT) with goserelin acetate and definitive radiation treatment (RT) for their prostate cancer. Methods: Thirty-four HIV-negative patients were included in this study between June 2006 and January 2007. All patients had a baseline total testosterone level (T), PSA, CD4 and CD8 T cell counts. CD4/8 T cells count was measured using flow cytometry. All patients received 6 months of ADT prior to (baseline) and during RT to the prostate. Subsequent blood samples were taken at 2, 8, 12 and 24 months. Blood samples were taken between 8–10 am to control for diurnal variations in CD4/CD8 T cell counts and T levels. To study the correlation of T with CD4/8 T cell changes, the Spearman correlation coefficient was calculated. The study was approved by the appropriate Ethics Committee. Results: Median age for the study patients was 68 years. At baseline, median testosterone level was 350 ng/dL, median CD4 T cell count was 1055 mm 3 , and median CD8 T cell count was 644 mm 3 . None of the patients received anti-androgens. At two months, testosterone was at the castrate and subnormal levels in 85% and 100% of the patients, respectively. The lower testosterone levels resulted in significant reduction of CD4 and CD8 T cell counts at 2, 8, 12 and 24 months compared to baseline counts. This effect was more pronounced for CD4 T cells at all time points (p=&lt;0.02). At 24 months, when total testosterone levels were increasing, CD4 and CD8 T cell counts were also following these upward trends. The seen correlation between lower testosterone and decline in CD4 and CD8 T cells was only statistically significant in older patients (&gt;65 years) and was not associated with significant decline in total white blood cell counts. Conclusions: CD4/CD8 T cell counts are sensitive to changes in total testosterone levels. Lower testosterone levels negatively affecting CD4/CD8 T cells counts at all study time points. Since CD4/CD8 T cells play major roles in cellular immunity, further studies are warranted No significant financial relationships to disclose.
Phase II study of ‘hybrid‘ biochemotherapy for advanced melanoma
Authors: N. E. Papadopoulos, O. Eton, K. B. Kim, L. H. Camacho, P. Hwu, A. Y. Bedikian
Journal: Journal of Clinical Oncology (2006)

18007 Background: The clinical activity of a hybrid biochemotherapy regimen was determined. This regimen incorporated important elements of previously studied sequential and concurrent biochemotherapy regimens in order to potentially increase dose intensity of the antitumor agents while decreasing morbidity, complexity of in-patient management, and length of hospital days. Methods: The antitumor agents and starting doses in the hybrid regimen were: cisplatin (25 mg/m 2 ) IV on days 2–5, vinblastine (1.4–1.6 mg/m 2 ) IV on days 1–5, dacarbazine (800 mg/m 2 ) IV day 1 only, rIL-2 (12 MIU/m 2 ) SC on days 6–10, and interferon-a2b (10 MU/m 2 ) SC on days 2–6. Thirty-seven patients (pts) with a median age of 49 (range 19–63) yrs and Zubrod’s PS of 0–2 were treated. Patients with prior chemotherapy, rIL-2, active brain metastases were excluded. All cycles were 21 days or longer and the median number of courses delivered per patient was 4 (range 1–6). Results: Thirty-five pts were evaluated for response. There were 3/35 (9%) complete responses (CRs) and 17/35 (49%) partial responses (PRs). One CR and one PR were confirmed pathologically. The median overall survival was 12.6 months (95% CI: 9.9, 20.3). The median time to progression for all patients was 5.7 months (95% CI: 4.3, 9.8), while the TTP of responders was 7.2 months (95% CI: 5.1, 18.9). Brain metastases developed in 13 pts, -either while receiving treatment and responding systemically (5 pts) -or post-treatment with progressive systemic disease (8 pts). There were 2/12 (17%) early deaths in pts receiving vinblastine (1.6 mg/m 2 ), one with typhlitis and the other with sepsis. Therefore, the vinblastine dose was reduced to 1.4 mg/m 2 for patients #13–35. Neutropenia, with a median lowest neutrophil count of 0.08 (range 0–3) on day 13 (range day 6–16), and fever during rIL-2 treatment, increased the median days of hospitalization of all patients to 15 (range 12–23) for the first cycle. Conclusions: Hybrid biochemotherapy produced a high response rate and an overall survival similar to previously reported schedules. Length of hospital stay was significantly increased compared to the concurrent schedule. Development of brain metastases in responding pts resulted in early withdrawal from the program. Hybrid biochemotherapy with reduced doses of vinblastine was better tolerated. No significant financial relationships to disclose.
Influence of response shift on the perception of fatigue in patients with advanced cancer
Authors: A. Vielhaber, P. Homel, S. Malamud, V. T. Chang, S. S. Hwang, J. Cogswell, R. K. Portenoy, A. B. Kornblith
Journal: Journal of Clinical Oncology (2004)

8116 Background: Fatigue is experienced by up to 75% of cancer patients (pts) and has a profound impact on their quality of life (QoL). Symptom assessment over time is fundamental to both patient care and clinical trials. There are many influences on this assessment, among which are the internal standards that pts apply when evaluating symptom intensity or distress. A change in internal standards is known as 'response shift' and may be important in the evaluation of symptoms or their impact on QoL over time. The present study was performed to empirically quantify the extent to which response shift may influence pts' perception of fatigue. Methods: Eligible pts had to have advanced incurable cancer, a fatigue-rating of at least 4 on a 0–10 scale, life expectancy of ≥ 3 months, and no brain metastases or cognitive impairment. Pts were interviewed at both baseline and 8 weeks, using a battery of measures which included the Brief Fatigue Inventory and Karnofsky Performance Status (KPS) as well as medical and sociodemographic characteristics. Response shift was assessed using the 'thentest' approach (i.e. difference between pts' retrospective assessment of baseline fatigue at follow-up and their pretest scores at study entry). Results: At present, 48 pts completed the study (M/F = 24/24, median age = 59 yrs, range 35–84, median KPS = 70%, range 40–80). During the study period, fatigue increased in 22 pts (mean pretest-posttest Δ= −1.42), decreased in 16 pts (mean pretest-posttest Δ= +2.56) and remained stable in 10 pts. Pts who reported greater fatigue over time had significantly lower mean thentest scores (mean=4.1) than their initial pretest scores (mean=5.48; t=3.46, p<0.005). No significant difference was found between thentest (mean=7.19) and pretest scores (mean=6.5) in pts whose fatigue decreased over time. Conclusions: These data suggest that pts who experience increasing fatigue change their internal standards over time. They retrospectively minimize their baseline fatigue score, thus magnifying the degree to which their fatigue has worsened. Such changes in internal standards may jeopardize the validity of data that are based on a conventional pretest-posttest approach. No significant financial relationships to disclose.