tbuckley/cabot-search huggingface dataset:
Abstract 17062: Can Automated Rate-only CPR Feedback be Detrimental to Chest Compression Depth? A CPR Simulation Study of 141 Untrained Operators
Authors: Hannah Torney, Peter O'Hare, Laura Davis, Bruno Delafont, Ben McCartney, Hannah McReynolds, Rebecca Di Maio, Raymond Bond, David McEneaney
Journal: Circulation (2015)

Introduction: A number of public access defibrillators incorporate computerised audio-visual feedback mechanisms to help responders deliver cardiopulmonary resuscitation (CPR) according to current guidelines. A 2013 American Heart Association statement suggested that chest compression fraction (CCF) and compression rate should be prioritised over compression depth, chest recoil and ventilations. This usability study assessed the effect of real-time rate-only feedback on chest compression depth. Methods: Randomly selected users were recruited in a shopping mall (n=141; 15-65+ years) to deliver CPR using a public access defibrillator in a simulated scenario. Participants were randomly assigned one of two devices - (1) with CPR rate feedback in the form of a machine-interface comprising of audio-voice prompts and light emitting diodes; (2) without CPR feedback. Participants were instructed to turn on the device and follow the prompts, with no information on how to perform CPR provided. CPR rate and depth were captured by measuring displacement of a potentiometer contained in a specially designed manikin. The device was connected to the manikin via the electrode leads. The effect of rate-only feedback on compression depth and CPR fraction were assessed. Results: ANCOVA analysis between the two devices provided a mean difference (Standard Error; SE) of 4.52mm (1.38mm) indicating a statistically significant difference (p-value=0.001) between measured CPR depth favouring the device with CPR rate feedback. There was no significant difference in CCF between the devices. ANCOVA analysis provided a mean difference (SE) of 2.9% (1.9%) for the device with CPR rate feedback compared to the device without CPR rate feedback. Conclusion: The incorporation of clear, intuitive, audio-visual machine-interface that delivers CPR feedback can assist trained and untrained users in the optimisation of chest compression rate and maintain a high CCF. In conclusion, CPR rate-only feedback was not detrimental to chest compression depth and suggests rate-only feedback may improve compression depth.
ABCB1 (MDR1) genotype in relation to doxorubicin and docetaxel pharmacokinetics in patients with breast cancer
Authors: Joseph Gligorov, Frederic Selle, Eric Levy, Karine Beerblock, Pierre Saintigny, Daniele Avenin, Jean-Pierre Lotz, Keyvan Rezai, Jean-Francois Bernaudin, Serge Uzan, Pierre Levy, Francois Lokiec, Anne Fajac
Journal: Cancer Research (2007)

729  Interindividual variations in response to anticancer agents might be due to inherited variations in genes encoding proteins involved in drug transport. ABCB1 (MDR1) gene encodes an efflux transporter expressed in organs responsible for drug metabolism and polymorphisms of this gene have been reported which appear to be functional. Doxorubicin and docetaxel are substrates for ABCB1 and main drugs used in breast cancer treatment. We therefore investigated in patients treated with doxorubicin and docetaxel for breast cancer whether polymorphisms of ABCB1 gene could account for variations in pharmacokinetics of these drugs. The single nucleotide polymorphisms A61G, C1236T, G2677T/A, G2995A and C3435T were analysed using TaqManMGB probes for allelic discrimination. Plasma concentrations of doxorubicin and docetaxel were determined in patients during the first course of doxorubicin (n=64) and the first course of docetaxel (n=51). Mean values (+ SEM) of area under the concentration-time curve (AUC) of doxorubicin were lower for patients with 1236TT genotype than for patients with 1236CC or 1236CT genotype (2134 + 171 μg.h/L, n=11 and 2701 + 223 μg.h/L, n=53, respectively ; p=0.02, Mann-Whitney U two sample-test). No such difference in pharmacokinetics of docetaxel when considering C1236T polymorphism was found nor in pharmacokinetics of either doxorubicin or docetaxel when considering other polymorphisms. Mean values (+ SEM) of AUC of docetaxel were higher for patients with (61-1236-2677-2995-3435 AA-CT-GT-GG-CT) haplotype than for patients with other haplotypes (5553 + 607 µg.h/L, n=9 and 4906 µg.h/L + 896 µg.h/L, n= 42, respectively ; p=0.015). In addition, a preliminary study investigating pharmacokinetics and pathological response shows that mean values (+ SEM) of doxorubicin clearance were lower for pathological complete responders than for patients who were not (37 + 3 L/h, n=7 and 46 + 2 L/h, n= 17, respectively ; p=0.03, Mann-Whitney U two sample-test). In conclusion, these results suggest that ABCB1 polymorphisms play a role in pharmacokinetics of doxorubicin and docetaxel and that pharmacokinetics of doxorubicin might be involved in the pathological response of patients with breast cancer.
The natural history of veterans with colorectal cancer (CRC) over a period of 10 years.
Authors: Fengming Zhong, Neal Patel, Ying Margie Tang, Victor Tsu-Shih Chang, Nneoma Olivia Okoronkwo, Trent P Wang, Tanganyika Barnes, Basil Kasimis
Journal: Journal of Clinical Oncology (2014)

e14626 Background: We studied demographics, comorbidity, treatment, and other predictors of survival for patients (pts) with CRC to define the natural history Methods: In an IRB-approved protocol, we reviewed the records of pts diagnosed with CRC at a VA medical center from 01/01/2003 to 12/31/2012. Demographics, grade, stage, ECOG performance status (PS), CEA, Hemoglobin (HGB), and Albumin (ALB) at diagnosis, diagnosis by screening, cause of death, recurrence, survival, and treatment were studied. Comorbidity was assessed with the Charlson Comorbidity Index (CCI). Statistical analyses were performed with SAS 9.2 and Stata v11.0. Results: There were 296 pts with 294 men and 2 women. The median (M) age was 69 years (44-90). There were 4 (1.4%) pts with stage 0, 95 (33%) with stage I, 72(25%) stage II, 56(20%) with stage III, 57(20%) with stage IV CRC. The percentage of pts diagnosed by screening varied inversely with stage, from 43% (41 pts) for stage I, 22% (16 pts) for stage II, 20% (11 pts) for stage III, to 2% (1 pt) for stage IV (p<.001). M survival (MS) was 1,126 days (4-4004) with 143 pts (48%) deceased. Survival varied inversely with stage, with median survivals of 1,548 days for stage I, 1,557 days for stage II, 1011 days for stage III, and 413 days stage IV CRC pts (p<.001). Surgery was done in 232 pts (78%), chemotherapy in 102 pts (33%). Median ECOG PS was 1(0-4) and Charlson 4.1 (0.8-13.9). Death from CRC occurred in 5 (5%) pts with stage I, 17 (24%) pts with stage II, 15 (27%) pts with stage III, and 37(65%) pts with stage IV CRC (p<.001). Recurrence was experienced by 22 early stage pts (9%). For all stages, M HGB was 12.4 (6.5-16.7) gm/dl, CEA 2.5 (0.2-2071) ng/ml, and albumin 4.0 (2.1-4.8) gm/dl at diagnosis. By univariate analysis, stage (p<.001), HGB (p<.001), grade (p<.001), ECOG PS (p<.001), CCI (p<.001), CEA (p<.001), surgery (p<.001), chemotherapy (.049), and diagnosis by screening (p<.001) were predictive. In multivariate model, stage, Charlson, chemotherapy, ECOG PS, and albumin levels were predictive. Conclusions: In this study population, screening colonoscopy and chemotherapy are showing an effect on survival. Confirmation in large patient samples is planned. Supported by NJCCR
Phase 1 study of VX15/2503, a humanized IgG4 anti-SEMA4D antibody, in advanced cancer patients (pts).
Authors: Amita Patnaik, Ramesh K. Ramanathan, Drew Warren Rasco, Glen J. Weiss, Valerie Campello-Iddison, Cynthia Eddington, Terrence L. Fisher, Danielle Mutz, Lisa Blaydorn, Anthony W. Tolcher, John E. Leonard
Journal: Journal of Clinical Oncology (2014)

3052^ Background: Semaphorin 4D (SEMA4D) regulates cellular adhesion, motility and activation of cells of the nervous, vascular and immune systems; it also promotes tumor progression and metastasis. SEMA4D and its receptor plexin B1 are widely expressed in human tumors; the interaction of plexin B1 with MET and ERBB2 leads to SEMA4D-mediated transactivation of these membrane receptor kinases promoting tumor cell migration and invasive growth. The murine progenitor of VX15/2503 suppressed tumor growth in syngeneic and transgenic tumors. No toxicologic effects were noted in studies of VX15/2503 using rats and primates and PK/PD profiles were generally predictive of data from clinical trial subjects. Methods: A multiple ascending dose trial was initiated in adult pts with advanced refractory solid tumors; pts were administered weekly IV doses of VX15/2503 until progression. Dose levels were 0.3 to 20 mg/kg. Tumors were assessed by RECIST 1.1 after each 8 dose cycle. Biomarkers assessed were SEMA4D, VEGF, HGF, PLGF, and MET. Results: Enrollment has been concluded (n=42 Pts); sex 40.5%M/59.5%F. Mean age (yrs) 64.8; ECOG 0/1/2 are 28.6% /69%/4%. No MTD was found. One DLT (grade 3 GGT elevation; 15 mg/kg) was reported in a pancreatic cancer pt with disease progression. As of 12/16/2013 the most frequent treatment-related AE’s (n=42 pts) included grade 1/2 nausea (11.7%), arthralgia (7.3%), decreased appetite (7.3%), and fatigue (7.3%); 15 drug unrelated SAE’s were reported in 11 pts. No CR/PR were observed. Thirteen of 42 pts at all dose levels exhibited stable disease for at least 8 weeks. Pts with the longest duration of treatment included: 48-55 weeks (colorectal; 9 mg/kg) (breast; 15 mg/kg) (papillary thyroid; 20 mg/kg); these pts had relatively high T or B cell levels. VX15/2503 serum concentrations of ≥ 0.3 µg/mL produced complete T cell SEMA4D saturation. HAHA responses (titer > 100) with possible effects on PK were observed in 4 of 41 pts (10%); in only 1 pt (2%) was an effect of HAHA on PD observed. VX15/2503 half-life was roughly 4-5 days at doses ≥1.0 mg/kg. Conclusions: VX15/2503 was well tolerated at dose levels up to 20 mg/kg, with 450 doses administered to 42 pts. Future studies will be combination trials in selected tumor types. Clinical trial information: NCT01313065.
HIV and cancer: The 8-year experience of the reference center of infectious diseases in Portugal.
Authors: Diogo D'Agoretta D'Alpium Santos Costa, Rita Salvado, Jose Silva, Diana Ferreira, Ana Claudia Miranda, Kamal Mansinho
Journal: Journal of Clinical Oncology (2014)

e12520 Background: Combination antiretroviral therapy (cART) has turned HIV infection into a complex chronic disease. There has been a progressive shift in the cancer spectrum from AIDS-defining cancers (ADC) to non-ADC (NADC). Methods: 8-year (2006-2013) retrospective, observational and non-controlled cohort analysis was performed in inpatients with concomitant diagnosis of HIV infection and cancer at the Infectious Diseases Department of the Hospital Egas Moniz. The aim of the study was to investigate the prevalence of NADC in HIV-infected patients (pts) and to assess the risk factors associated with these malignancies. We studied demographic data, substance abuse history, time of diagnosis and type of cancer, HIV staging and treatment and presence of HBV/HCV co-infection. We performed a multivariable logistic regression to identify factors associated with NADC. Results: 116 pts were evaluated with a median age of 44 years (range 24-84), mostly male (74.14%), 43.1% current smokers, 25% and 32% with a history of alcohol and injectable drugs abuse, respectively. 96.6% with HIV-1 and 4.3% with both HIV-1/2 serotypes. 68 pts (58.6%) with ADC, including 45 (66.6%) with Kaposi´s sarcoma, 14 (20.6%) with non-Hodgkin lymphoma and 9 (8%) with cervical cancer. Among the NADC (48; 41.4%), the most frequent localizations were digestive tract (14; 29.1%) and lung (8; 16.7%). Comparatively with ADC, the NADC presented higher prevalence of older (in medium 10 years) and male gender as well as higher TCD4+ counts at the time of the cancer diagnosis (147 ± 168 vs 368±280, p <0,001), inferior TCD4+ nadir (101 ± 127 vs 192±179, p<0,001) and higher viral load (314562 ± 705445 vs 237412±823064, p<0,001). cART was more prevalent in the group of NADC (70.97% vs 30.23%). No significant differences in which concerns the co-infection HBV (13.43% vs 10.42%) and HCV (37.3% vs 39.58%). Age (Odds Ratio (OR)= 1.09, p<0.00), male gender (OR= 7.07, p=0.00) and cART (OR= 5.35, p=0.00) were significantly associated with NADC. Conclusions: In this population, ADC were the most prevalent. The development of NADC was associated with increasing age, male gender and cART. There are several questions to be addressed in the future to understand why this is happening.
Abstract #2198: p27 (Kip1) gene dosage plays a role in cell cycle progression and tumor suppression in Shh-mediated medulloblastoma
Authors: Bobby Bhatia, David Liu, Andrew Koff, Anna Kenney
Journal: Cancer Research (2009)

Medulloblastoma, a brain tumor arising in the cerebellum, is the most common solid childhood malignancy. Gaining insight into mechanisms regulating transformation of medulloblastoma cells-of-origin will lead to development of better treatments and new mouse models in which to test those treatments. Cerebellar granule neuron precursors (CGNPs) are proposed cells-of-origin for certain classes of medulloblastoma. These cells require signaling by the secreted factor Sonic hedgehog (Shh) for their proliferation during brain development. Mutations causing aberrant activation of the Shh signaling pathway are implicated in human and mouse medulloblastomas. To promote proliferation and oncogenic transformation, Shh alone is not sufficient; cooperative interactions with other signaling pathways are required. We previously showed that loss or inactivation of the tumor suppressor Tuberous Sclerosis Complex (TSC), composed of the proteins TSC1 and TSC2, leads to cyclin dependent kinase inhibitor p27 (Kip1) loss or mislocalization in CGNPs and in Shh-mediated medulloblastoma. Using mice that express an activated mutant allele of the Shh receptor component Smoothened (SmoA1), we find that SmoA1 mice with p27 heterozygosity have a decreased survival compared to mice having two wild-type p27 alleles. Also, these mice maintain wild-type p27 protein, which is aberrantly localized to the cytoplasm. Interestingly, SmoA1 mice with complete loss of p27 do not show enhanced medulloblastoma incidence, resembling instead tumor latency of SmoA1 +/+ p27 +/+  mice. This may reflect the requirement for p27 in recruiting cyclin D/cdk4/6 to promote cell cycle progression. Together, our data indicate that the dosage of p27 plays a role in cell cycle progression and tumor suppression in Shh-mediated medulloblastoma expansion. We are currently investigating how proteins interacting with p27 play roles in cell cycle progression/regulation in medulloblastoma.   Citation Information:  In: Proc Am Assoc Cancer Res; 2009 Apr 18-22; Denver, CO. Philadelphia (PA): AACR; 2009. Abstract nr 2198.
Functional Analysis of the FOXO3 Gene on the Induction of Fetal Hemoglobin in K562 Cells
Authors: Flávia Peixoto Albuquerque, Pedro Luis Franca-Neto, Rafael de Oliveira Franca, Aderson da Silva Araujo, Fernando F. Costa, Marcos Bezerra, Antonio R. Lucena-Araujo
Journal: Blood (2018)
Abstract 19033: Incidence of Left Bundle Branch Block - Associated Cardiomyopathy
Authors: Sunita Sharma, Harsh Barot, Andrew Schwartzman, Richard D Patten
Journal: Circulation (2017)

Introduction: The presence of left bundle branch block (LBBB) is often an indicator of structural heart disease. Accordingly, patients who develop LBBB are at increased risk of heart failure and su...
Comparative outcomes of patients with intraductal papillary mucinous neoplasm associated cancer (IPMN-Ca) to those with pancreatic ductal carcinoma (PDAC) following resection.
Authors: Kavya Krishna, Mark Bloomston, Peter Muscarella, Somashekar Krishna, Lai Wei, Darwin Conwell, Tanios S. Bekaii-Saab
Journal: Journal of Clinical Oncology (2014)

e15227 Background: IPMN-Ca is thought to have a better prognosis vs. PDAC. There is limited data comparing outcomes following surgical resection for IPMN-Ca vs. PDAC. Methods: Retrospective review of pancreatic cancer resections between 2000 and 2012 at a single tertiary care center. Results: A total of 225 pancreatic resections (IPMN-Ca: 39, PDAC: 186) were included. By univariate analysis (Table 1), median overall survival was significantly higher in patients with IPMN-Ca vs. PDAC. PDAC patients were younger, more head of pancreas lesions, more advanced T, N stage, lymphovascular invasion, perineural invasion, poor degree of differentiation and higher rates of recurrence. Following multivariate analysis, which included variables in univariate analysis with p <0.05, there was no significant difference in survival or recurrence with PDACs vs. IPMN-Ca. Conclusions: When controlling for known prognostic factors in our multivariate analysis, we found no significant differences in outcome between PDAC and IPMN-Ca, although PDAC had more adverse features. These findings may have implications on future considerations in prospective adjuvant trial inclusion for pancreas cancer. Univariate analysis comparing pancreatic ductal adenocarcinoma (PDAC) and intraductal papillary mucinous neoplasm associated cancer (IPMN-Ca). Categorical variables IPMN-Ca; n= 39 PDAC; n=186 p-value Jaundice No Yes 21 13 37 112 <0.001 Location Head/uncinate/neck Body Tail Entire pancreas 23 6 7 2 166 4 15 1 <0.001 Degree of differentiation Well/moderate Poor 26 5 122 64 0.043 Margin Negative Positive 27 12 138 48 0.52 Lymphovascular invasion No Yes 24 13 62 118 <0.001 Perineural invasion No Yes 14 23 14 168 <0.001 T stage Early (T1-T2) Advanced (T3-T4) 15 23 15 171 <0.001 N stage N0 N1 20 19 42 144 <0.001 Recurrence No Yes Unknown 12 11 16 34 91 61 0.046 CA 19-9 >1000 IU No Yes 24 5 156 0 <0.001 Continuous variables; median (range) Age (years) 73.4 (46.8- 85.3) 65.8 (19.9-88.9) 0.002 Total bilirubin (mg/dL) 1 (0.1-24.9) 4.6 (0.2-30.3) 0.03 Size of lesion (cm) 4.5 (1-11.8) 3.3 (0.20 – 8.0) 0.003 Time to recurrence (months) 15.5 10.6 0.23 Overall survival (months) 25.6 13.9 0.014
Clinical utility of the 12-gene DCIS score assay: Impact on treatment (Tx) recommendations.
Authors: Michael Alvarado, Dennis Carter, J. Michael Guenther, James Hagans, Rachel Lei, Charles E. Leonard, Jennifer Manders, Amy P. Sing, Michael S. Broder, Eunice Chang, Dasha Cherepanov, Wendy C. Hsiao, Michael Schultz
Journal: Journal of Clinical Oncology (2014)

11050 Background: About 20% of breast cancers (BC) are DCIS. Local recurrence (LR) rates with surgery alone are 15-60%; about 50% are invasive. Radiation (XRT) reduces LR by 50% but has not impacted survival. Clinicians and patients (pts) must decide between multiple options including breast conserving surgery, mastectomy, partial or whole breast XRT, and hormonal manipulation. Traditional clinicopathologic (CP) factors provide an average LR risk derived from population studies. The validated Oncotype DX 12-gene assay for DCIS gives additional, independent, individual estimates of 10-year risk of any LR and invasive LR. We report the first study to assess the impact of the DCIS Score result on XRT recommendations for pts with DCIS. Baseline (BL) characteristics are described here; final results on change in Tx recommendations from pre- to post-assay will be presented at the meeting. Methods: 11 U.S. sites enrolled pts with DCIS from 9/2012-1/2014. Pts with LCIS but no DCIS, invasive BC, or planned mastectomy were excluded. Data were prospectively collected on CP factors, physician estimates of LR risk, DCIS score, and Tx recommendation before and after the assay result was known. The study received IRB approval. Results: 110 pts had a mean age of 60.1 yrs (SD: 9.9); 75.5% were postmenopausal. Mean DCIS size was 13.5mm (SD: 15.8); 20% had nuclear grade of 1, 46.4% grade 2, and 33.6% grade 3. Necrosis was noted in 63.6% (focal in 29.1%). Median distance from closest margin was 3mm. ER and PR IHC tests were positive in 85.5% and 78.2%. Mean physician-assessed 10-yr risk of LR was 20.8% (range 6-40%) for any LR and 10.9% (3-25%) for invasive LR. Anti-estrogen Tx was recommended in 72.7%, aromatase inhibitor in 20.9%, XRT in 72.7%, and additional surgery in 18.2%. Conclusions: The DCIS Score use may reduce both under- and overtreatment; establishing its impact on treatment decisions is critical to understanding the utility of this genomic assay in clinical practice.The BL characteristics of the cohort, the LR risk estimate and the pre-assay Tx recommendations are consistent with current practices, including 73% recommended XRT. The full analysis will assess the clinical utility of incorporating the DCIS Score result into clinical practice.
Use of thallium scintigraphy and bone scintigraphy for differentiating between chondrosarcoma and chondroblastic osteosarcoma.
Authors: Takashi Kato, Norio Yamamoto, Hideji Nishida, Hiroaki Kimura, Akihiko Takeuchi, Shingo Shimozaki, Yu Aoki, Takashi Higuchi, Hiroyuki Tsuchiya
Journal: Journal of Clinical Oncology (2014)

e21506 Background: Chondrosarcoma and chondroblastic osteosarcoma yield similar imaging and histological findings. Therefore, it is difficult to differentiate between the two conditions even on using needle biopsy. However, discrimination between the two is very important since their treatments differ as well. We examined whether the use of bone scintigraphy or thallium scintigraphy would be useful for differentiating between chondrosarcoma and chondroblastic osteosarcoma. Methods: Four cases of chondrosarcoma and seven cases of chondroblastic osteosarcoma were diagnosed histologically through biopsy and surgical excision. The patients underwent bone scintigraphy and thallium scintigraphy prior to treatment, and we compared the mean and maximum accumulation values of chondrosarcoma and chondroblastic osteosarcoma. Results: On bone scintigraphy, the mean accumulation value of chondrosarcoma was 1.95 (range, 1.08–2.81), while that of chondroblastic osteosarcoma was 7.28 (range, 3.28–23.70). The mean maximum accumulation value of chondrosarcoma was 2.12 (range, 0.98–3.94), while that of chondroblastic osteosarcoma was 6.45 (range, 2.31–18.47). On thallium scintigraphy, the mean accumulation value of chondrosarcoma was 1.83 (range, 0.91–3.33), while that of chondroblastic osteosarcoma was 3.03 (range, 0.89–4.27). The mean maximum accumulation value of chondrosarcoma was 1.80 (range, 1.00–2.56), while that of chondroblastic osteosarcoma was 2.39 (range, 1.04–6.17). On bone scintigraphy, the accumulation value in chondroblastic osteosarcoma tended to be higher than that of chondrosarcoma. Conclusions: Bone scintigraphy could be a useful test for differentiating between chondrosarcoma and chondroblastic osteosarcoma.
Cladribine Combined with Idarubicin and Ara-C (CLIA) As a Frontline and Salvage Treatment for Young Patients (≤65 yrs) with Acute Myeloid Leukemia
Authors: Preetesh Jain, Hagop M. Kantarjian, Farhad Ravandi, Elias Jabbour, Naval Daver, Naveen Pemmaraju, Courtney D DiNardo, Yesid Alvarado, Nitin Jain, Gautam Borthakur, Srdan Verstovsek, Alessandra Ferrajoli, Maro Ohanian, Marina Konopleva, Kiran Naqvi, Tina Fitch, Guillermo Garcia-Manero, Jorge E. Cortes, Zeev Estrov, Tapan M. Kadia
Journal: Blood (2016)