tbuckley/cabot-search huggingface dataset:
Systemic chemotherapy (SC) before cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) in patients with peritoneal mucinous carcinomatosis of appendiceal origin (PMCA).
Authors: Vladimir Milovanov, Armando Sardi, Panayotis Ledakis, Nail Aydin, William Andres Jimenez, Michelle Sittig, Ryan Macdonald, Vadim Gushchin
Journal: Journal of Clinical Oncology (2014)

e15179 Background: The role of SC before and after CRS/HIPEC for patients with PMCA is unclear. This study aims to explore the effect of SC prior to CRS/HIPEC on overall survival (OS) in patients with PMCA treated at a medical center specializing in peritoneal surface malignancies. Methods: A retrospective analysis of the prospective database of 344 CRS/HIPEC patients identified 102 patients with PMCA underwent only one CRS/HIPEC between February 1998 - June 2013. Forty-six patients (45%) had SC before CRS/HIPEC (Group 1) and the remaining 56 did not (Group 2). OS was estimated by Kaplan-Meier survival curves and the Log-Rank Test. Other known risk factors were analyzed. Results: Thirty-five men and 67 women, mean age of 52 years (range 25–78), had mean follow-up of 31 months. The groups were similar regarding peritoneal carcinomatosis index, completeness of cytoreduction, lymph node positivity and postoperative SC. In Group 1, all patients received 5-FU based chemotherapy and 16 received Bevacizumab as part of their regimen. Mean number of prior SC cycles was 6 (range 2-16). Median time from diagnosis to CRS/HIPEC was 170 days (Group 1) and 74 days (Group 2). Mean delay of CRS/HIPEC due to SC was 117 (range 28-428) days. OS from diagnosis/HIPEC at 1, 3, and 5 years was 95, 59, 34%/83, 37, 21% in the Group 1 and 96, 78, 67%/86, 72, 62% in the Group 2, respectively (p=0.007). Twenty four (52%) patients in the Group 1 and 13 (23%) patients in Group 2 had signet ring cell histology (SRCH) (p=0,002). Due to the different number of SRCH among the groups, two separate analyses were performed: one with only SRCH patients and another with all other. Among SRCH patients 3-year survival was 54% in both: SC and no prior SC groups (p=0.569). 5-year OS for patients without SRCH was 43% in the SC group vs. 77% in the group with no prior SC (p=0.007). Conclusions: Currently used preoperative SC did not improve OS in PMCA patients with SRCH, and associated with poor OS in patients without SRCH. This may be due to aggressive tumor biology in the SC group or the delay of CRS/HIPEC. Prospective studies are necessary in order to delineate the role of SC in appendiceal cancer.
Abstract 10962: Temporal Patterns of Self-Weighing Behavior and Weight Loss in the Health eHeart Study
Authors: Yaguang Zheng, Geoffrey H Tison, Susan M Sereika, Lora E Burke, Jeffrey Olgin, Gregory M Marcus, Kirstin Aschbacher, Mark J Pletcher
Journal: Circulation (2018)

Introduction: Self-weighing may promote attainment and maintenance of healthy weight that is important for cardiovascular health; however, the natural temporal patterns of self-weighing are unclear...
Abstract 19052: Preoperative Non-invasive RVSP Correlates Poorly with Invasively Measured Pulmonary Artery Systolic Pressure During General Anesthesia
Authors: Sonia Jain, Arun Subramanian
Journal: Circulation (2012)

Introduction: Pulmonary hypertension (PH) is an independent marker of surgical morbidity. Right ventricular systolic pressure (RVSP) measured by transthoracic echocardiography (TTE), correlates poorly with pulmonary artery systolic pressure (PASP) measured by right heart catheterization, especially in PH. The correlation between TTE derived RVSP and intraoperative PASP, while under general anesthesia, is not known. In this study, the association between preoperative RVSP and intraoperative PASP was tested. Methods: All consenting adult surgical patients requiring intraoperative pulmonary pressure monitoring in a 2 year period were retrospectively identified. Patients who had TTE estimated RVSP ≥ 40 mmHg, measured within a week prior to the index surgery, were included. RVSP was calculated from tricuspid regurgitant velocity using the modified Bernoulli equation. For intraoperative PASP, the median of the first 10 minutes after PAC placement was used. CVP, arterial systolic pressure, minimum alveolar concentration of anesthetic (MAC) and basic demographic data were also collected. Agreement between RVSP and PASP was tested using the concordance correlation coefficient. Multivariate linear regression and Bland-Altman plot were used to further refine the analysis. Results: 129 patients met inclusion criteria. Median age (IQR) was 73 (62 - 79) years; TTE was performed a median (IQR) of 2 (1 - 3) days prior to surgery; mean (SD) RVSP was 56.1 (±12.4) mmHg and mean (SD) PASP was 42.1 (±14.9) mmHg. Concordance correlation coefficient between RVSP and PASP was only 0.13 (95% CI 0.02 - 0.24). On multivariate linear regression, PASP was significantly associated with RVSP and CVP (p &lt; 0.01), but not anesthetic MAC, age or proximity of measurements. Bland-Altman bias was -13.9 mmHg; 95% limits of agreement were -48.0 to +20.1 mmHg. Conclusion: Preoperative RVSP measured by TTE correlates poorly with intraoperative PASP measured by PAC during general anesthesia.
Abstract MP74: It's Not Too Late to Improve Adherence: Association Between All-Cause Mortality and Statin Adherence Change After Acute Myocardial Infarction
Authors: Ryan P Hickson, Jennifer G Robinson, Izabela E Annis, Ley A Killeya-Jones, Gang Fang
Journal: Circulation (2018)

Introduction: Hospitalization for acute myocardial infarction (AMI) affects medication adherence in prevalent statin users. Our objective was to estimate the association between changes in statin adherence and all-cause mortality after AMI discharge. Hypothesis: Patients who are adherent both pre- and post-AMI have the lowest risk of all-cause mortality. Methods: Medicare administrative claims were used to identify AMI hospitalizations in 2008-2010. Patients were ≥66 years old, continuously enrolled ≥360 days pre-AMI with a statin prescription claim, discharged to home/self-care, and survived ≥180 days post-AMI with continuous enrollment. Statin adherence was measured in the 180 days pre- and post-AMI hospitalization using proportion of days covered and categorized as severely nonadherent, moderately nonadherent, and adherent. The exposure was categorical change in statin adherence from pre- to post-AMI (9 categories, see Figure); adherent/adherent was the reference group. Patients were followed for all-cause mortality from 180 days post-discharge for up to 18 months. A multivariable Cox proportional hazards model estimated hazard ratios (HRs). Results: Of 101,011 eligible patients, 15% decreased, 20% increased, and 64% did not change statin adherence categories. Compared to patients who were adherent pre- and post-AMI, the adjusted HR (95% confidence intervals [CIs]) for patients who increased from severely nonadherent to adherent was 0.93 (95% CI: 0.85-1.02); other increases in adherence had similar HRs (see Figure). Compared to patients who were adherent pre- and post-AMI, the adjusted HR for patients who decreased from adherent to severely nonadherent was 1.22 (95% CI: 1.13-1.33); other decreases in adherence had similar HRs. Conclusions: Although patients with decreased statin adherence had the worst mortality outcomes, those with increased adherence had similar or better outcomes than continuously adherent patients, showing that, even after an AMI, it is not too late to improve statin adherence.
Monitoring the T cell response to spontaneous mammary tumors using a novel transgenic mouse model
Authors: Erika M. Wall, Katy Milne, Brad H. Nelson
Journal: Cancer Research (2005)

4252  Many human cancers elicit immune recognition but are nevertheless able to persist and disseminate in immunocompetent individuals. Our goal is to characterize the immune response to spontaneously developing mammary tumors and define the mechanisms by which tumors evade rejection by tumor-specific T cells. We have developed a novel transgenic mouse mammary tumor model in which tumor formation is driven by expression of a modified version of HER2/neu. The modified oncogene, designated neuOTI/OTII, was created by addition of CD8+ (OT-I) and CD4+ (OT-II) T cell epitopes from ovalbumin to the C-terminus of HER2/neu. These epitope tags allow neuOTI/OTII to be recognized by T cell receptor (TCR) transgenic CD8+ and CD4+ T cells specific for these epitopes. Such T cells can be labeled and infused into mice expressing neuOTI/OTII, thereby allowing precise monitoring of CD4+ and CD8+ T cell responses to both established and developing mammary tumors. Transgenic mice expressing neuOTI/OTII together with a dominant-negative p53 transgene (DNp53) develop spontaneous mammary carcinomas at 7-10 months of age with an average latency of 8 months. NeuOTI/OTII is strongly expressed in tumors but not in any other tissues examined. Tumors and derived cell lines are positive for MHC Class I and negative for MHC Class II, Fas, FasL and the costimulatory molecules, B7-1 and B7-2. As expected, CD8+ (OT-I) and CD4+ (OT-II) T cells become activated in vitro when exposed to cells expressing neuOTI/OTII. To study the T cell response to spontaneously arising tumors, naive OT-I or OT-II TCR-transgenic T cells were labeled with the fluorescent dye CFSE and adoptively transferred into tumor-bearing neuOTI/OTII x DNp53 mice. At serial time points, T cell proliferation was evaluated by monitoring reduction in CFSE intensity. T cells were also analyzed for expression of cell surface activation markers. In 5/5 mice that received OT-II cells, little or no proliferation was observed in response to neuOTI/OTII x DNp53 tumors, even as late as 13 days post transfer. In 1/1 mouse that received OT-I and OT-II T cells together, OT-I cells began proliferating within 3 days while OT-II cells remained unresponsive. Unexpectedly, tumor progression stabilized within 4 days of T cell infusion and complete tumor regression had occurred by day 10. These preliminary results suggest that established tumors are capable of triggering a strong, potentially curative, CD8+ response, but appear to selectively evade CD4+ cells. We are currently investigating why OT-II T cells fail to respond to spontaneous neuOTI/OTII x DNp53 tumors as well as the requirements for successful tumor eradication by OT-I T cells.
In-hospital outcomes following thrombolysis for acute ischemic stroke in patients with primary brain tumors.
Authors: Aditi Shastri, Yogesh Moradiya, Santosh Murthy
Journal: Journal of Clinical Oncology (2014)

e13021 Background: Data on the thrombolysis outcomes in patients with primary brain tumors is limited. We aimed to study stroke outcomes following thrombolysis in these patients at a population level. Methods: Patients with acute ischemic stroke who received thrombolysis, were identified from the 2002-2011 Nationwide Inpatient Sample. Patients with primary brain tumor-associated strokes (BTS) and non-brain tumor associated strokes (NBTS) were compared based on demographics, comorbidities, and outcomes. Wilcoxon-Mann-Whitney and Pearson Chi-square tests were used for comparison of continuous and categorical variables respectively. Cochran-Mantel-Haenszel test was used to calculate unadjusted odds ratios. Logistic regression was used to assess stroke outcomes following thrombolysis. The main outcomes were inpatient mortality, home discharge and ICH rate. Results: Of the 124,083 thrombolysis-treated stroke patients, 416 had brain tumors. BTS had higher age quartiles (p=0.005), more females (66.9% vs. 49.0%, p<0.001), and more White patients (65% vs. 59.9%, p<0.006). In the univariate analysis, home discharge was significantly lower in BTS (OR: 0.77, CI: 0.61-0.96, p=0.022), while there was no difference in mortality or ICH rates. In the regression model, BTS were not associated with mortality, home discharge (OR: 1.15, CI: 0.87-1.53, p=0.40) or ICH rate (OR: 0.94, CI: 0.62-1.44, p=0.801). Subgroup analysis on brain tumor subtype showed that malignant BTS were independently associated with higher in-hospital mortality (OR: 2.51, CI: 1.66-3.79, p<0.001) and lower home discharge rates (OR: 0.36, CI: 0.18-0.72, p=0.004). Brain tumor subtype was not independently associated with ICH. Conclusions: Thrombolytic therapy for acute stroke appears to be safe in patients with primary brain tumors, with similar rates of ICH. Malignant BTS have worse outcomes, while benign BTS have outcomes comparable to NBTS. Careful consideration of tumor pathology may aid in selection of patients with poor thrombolysis outcomes.
Prognostic value of peroxisome proliferator-activated receptor gamma expression on clinical outcome of myxoid liposarcoma.
Authors: Akihiko Takeuchi, Norio Yamamoto, Toshiharu Shirai, Katsuhiro Hayashi, Hideji Nishida, Yoshikazu Tanzawa, Hiroaki Kimura, Shinji Miwa, Kentaro Igarashi, Shingo Shimozaki, Takashi Kato, Yu Aoki, Takashi Higuchi, Hiroyuki Tsuchiya
Journal: Journal of Clinical Oncology (2014)

10574 Background: Myxoid liposarcoma (MLS) is considered as low-to-intermediate grade malignancy. However, it also have been reported that MLS metastases to extrapulmonary sites and the biomarker of prognosis has not fully discussed. Peroxisome proliferator-activated receptor gamma (PPARγ) is a ligand-activated transcription factor that belongs to the nuclear hormone receptor superfamily. PPARγ plays a central role in the differentiation of adipocytes from precursor cells and is also reported to exhibit anti-tumorigenic effects on a certain malignancy. It has been reported that PPARγ is expressed in liposarcoma and the activation of PPARγ induced apoptosis and promote the terminal differentiation in liposarcoma cells. The purpose of this study is to evaluate the expression of PPARγ in MLS and correlation between PPARγ expression and clinical outcome. Methods: Forty-three patients were enrolled in this study. The median age was 45.5 years (range, 14-90 years) and the mean follow-up period was 91 months (range, 13-344 months). The expression of PPARγ was investigated by immunohisochemistry. Results: Ten cases showed the high expression of PPARγ (labeling index: LI ≥ 50%) and 33 cases were the low expression (LI < 50%). Local recurrence was detected in 9 of 43 (20.9%) patients. Six of 43 (14.0%) patients developed extrapulmonary metastasis. The sites of metastasis were spine in 2 patients. Another 4 sites were femur, retroperitoneum, axilla, and lung, respectively. The metastasis-free survival was significantly higher in the patients with the low expression of PPARγ than those of the high expression (p=0.011). The overall cumulative 5 and 10-year survival of all patients was 97.4% and 92.3%. Conclusions: The low expression of PPARγ was a prognostic factor of the metastasis-free survival. It had been reported that FUS-CHOP, specific fusion protein confirmed in MLS, blocked the PPARγ pathways. So, we speculated the high expression of PPARγ might reflect the inhibition of the PPARγ pathways by FUS-CHOP fusion protein. Although the further analysis is necessary, the expression of PPARγ might be a novel prognostic marker of MLS.
Metabolic syndrome and risk of psoriasis
Authors: I. Snekvik, T.I.L. Nilsen, P.R. Romundstad, M. Saunes
Journal: British Journal of Dermatology (2019)

Psoriasis is a common chronic skin disease, which is associated with metabolic syndrome, but few have studied what comes first – the psoriasis or the metabolic syndrome. Metabolic syndrome is abdominal obesity, unfavourable levels of blood lipids, raised blood pressure and insulin resistance, and is associated with a substantially increased risk of cardiovascular disease. The researchers of this study are based in Norway, and they have followed 35 000 men and women over a period of 11 years. They aimed to find out if having metabolic syndrome would increase the risk of getting psoriasis. At the start of the study, a clinical examination of all participants was performed, where height, weight, waist circumference and blood pressure were measured. A blood sample was taken, and the participants answered a questionnaire. During this period, 374 individuals developed psoriasis. The researchers found that individuals with metabolic syndrome had 66% increased risk of developing psoriasis for the first time, compared to individuals without metabolic syndrome. When studying the different components of metabolic syndrome, they found that abdominal obesity was the most important factor in this association. The study shows that having a normal weight and avoiding a clustering of cardiovascular risk factors could help to prevent psoriasis.
Stage at diagnosis as a prognostic marker for patients with KRAS-mutant metastatic lung adenocarcinomas.
Authors: Helena Alexandra Yu, Matthew David Hellmann, Camelia S. Sima, Natalie Busby, Katherine Rodriguez, Gregory J. Riely, Mark G. Kris
Journal: Journal of Clinical Oncology (2014)

8111 Background: Stage at diagnosis, age, gender, mutation status, and performance status are recognized prognostic factors in lung cancers. These variables are independently associated with survival, and are fundamental to clinical trial design and data interpretation. Stage at the time of initial diagnosis has not previously been evaluated as a prognostic factor in patients (pts) with metastatic lung cancers, and is not controlled for in prospective trials. In order to adjust for the potential impact of tumor histology and presence of a driver oncogene, we evaluated the impact of stage at initial diagnosis on survival using a cohort of patients with KRAS-mutant, metastatic lung adenocarcinomas. Methods: We identified all pts with KRAS-mutant metastatic lung adenocarcinomas from Feb 2005 to Aug 2011. Stage at diagnosis, age, gender, smoking history, and Karnofsky performance status (KPS) were obtained from the medical record. Overall survival (OS) from date of diagnosis of recurrent/metastatic disease was estimated using Kaplan-Meier method and compared across groups in a multivariable Cox proportional hazards model. Results: 635 pts with KRAS-mutant lung adenocarcinomas and known stage at diagnosis were identified. Median age: 66 (range 31-89), women: 61%, never smokers: 7%. KPS was available in 471 pts, median KPS: 80%. When compared to pts with stage IV lung cancers at initial diagnosis, patients with early stage lung cancers that later recurred/metastasized had a longer OS from date of advanced disease (18 vs 13 mo, p=0.003). Advanced stage at diagnosis (4 vs 1-3, HR 1.5 [1.2-1.8], P<0.001) and lower KPS (≤70% vs ≥80%, HR 2.5 [2.0-3.2], P<0.001) were independently associated with shorter overall survival after adjusting for gender and smoking history in a multivariable analysis. Conclusions: In KRAS-mutant lung adenocarcinomas, stage at initial diagnosis was strongly associated with OS from diagnosis of recurrent/metastatic disease, with a 5 month difference in overall survival in patients with recurrent versus de novo stage IV lung cancers. Stage at diagnosis is a prognostic variable that should be accounted for in prospective randomized studies of new therapies in pts with metastatic lung cancers.
First-in-Human Mitochondrial Augmentation of Hematopoietic Stem Cells in Pearson Syndrome
Authors: Elad Jacoby, Moriya Blumkin, Yair Anikster, Nira Varda-Bloom, Julia Pansheen, Omer Bar Yoseph, Noah Gruber, Einat Lahav, Michal J Besser, Jacob Schachter, Noa Sher, Natalie Yivgi Ohana, Amos Toren
Journal: Blood (2018)
Survival differences by race/ethnicity in adolescents and young adults diagnosed with non-Hodgkin lymphoma.
Authors: Chun Chao, Vicki Y Chiu, Lanfang Xu, Robert Michael Cooper
Journal: Journal of Clinical Oncology (2014)

9580 Background: Adolescents and young adults (AYAs) with cancer have not experienced the same degree of survival improvements as in younger children and older adults. Several barriers have been identified in delivering optimal oncology care in AYAs, including lack of knowledge on the biology and factors affecting survival in AYA cancer. Here we evaluated if survival differs by race/ethnicity in AYAs diagnosed with non-Hodgkin lymphoma (NHL). Methods: AYAs (ages 15-39) diagnosed with incident NHL in 1990-2010 were identified at Kaiser Permanente Southern California (KPSC), a large managed care organization. KPSC members have relatively equal health care access, which minimizes confounding due to access variations. Information on demographic and cancer characteristics was obtained from KPSC’s Surveillance, Epidemiology and End Results-affiliated cancer registry. Mortality data were obtained from California and national death registries. Patients were followed from NHL diagnosis to 5 year after or 12/31/2012, whichever came first. Multivariable Cox model was used to evaluate the association between race/ethnicity and mortality, adjusting for age, sex, cancer stage and year of diagnosis. Results: A total of 724 AYAs with NHL were included (mean age at diagnosis: 31), of whom 60% were male, 45% were non-Hispanic white, 10% were African American, 36% were Hispanic, and 8% were Asians. The distribution of stages at diagnosis was 18% stage I, 17% stage II, 16% stage III, and 40% stage IV. Overall 5-year survival was 70% (number of deaths =218). Compared to non-Hispanic whites, all minorities were associated with increased 5-year mortality: hazard ratio for African American = 1.74, 95% confidence interval (1.10-2.74), for Hispanic =1.31 (0.95-1.82), and for Asians =1.84 (1.03-3.28). Male sex, increasing age and advanced cancer stage were all significantly associated with elevated mortality. A significant survival improvement was observed over calendar years. Conclusions: A survival disparity for race/ethnicity was observed in AYAs with NHL despite relatively equal access to care. These results call for studies to further understand mechanisms underlying the inferior survival among minority subgroups.
Outcome of Patients with Aggressive B Cell Lymphomas Who Receive Second-Line Salvage Immunochemotherapy Following Treatment Failure of Intensive First-Line Immunochemotherapy
Authors: Emily C. Ayers, Shaoying Li, Jeffrey Medeiros, David A. Bond, Kami J. Maddocks, Pallawi Torka, Angel Mier Hicks, Madeira Curry, Nina D. Wagner-Johnston, Reem Karmali, Amir Behdad, Bita Fakhri, Brad S Kahl, Michael C Churnetski, Jonathon B. Cohen, Nishitha Reddy, Dipenkumar Modi, Radhakrishnan Ramchandren, Christina Howlett, Lori A. Leslie, Samuel Cytryn, Catherine Diefenbach, Rawan Faramand, Julio C. Chavez, Adam J Olszewski, Yang Liu, Stefan Klaus Barta, Dhruvika Mukhija, Brian T. Hill, Helen Ma, Jennifer E Amengual, Sunita Nathan, Sarit Assouline, Victor M. Orellana-Noia, Craig A. Portell, Ashwin Chandar, Kevin A. David, Anshu Giri, Brian T. Hess, Daniel J. Landsburg
Journal: Blood (2018)