tbuckley/cabot-search huggingface dataset:
Abstract 326: Prehospital Use of Nasal Cannula End-Tidal CO <sub>2</sub> Monitoring in Non-Intubated Major Traumatic Brain Injury Patients
Authors: Daniel W Spaite, Bruce J Barnhart, Eric Helfenbein, Dawn Jorgenson, Saeed Babaeizadeh, Joshua B Gaither, Amber D Rice, Samuel M Keim, Chengcheng Hu
Journal: Circulation (2019)

Objective: Little is known about End-Tidal CO 2 monitoring using nasal cannula sensors (NC-CO 2 ) in non-intubated patients. Objective: To describe the patterns of NC-CO 2 seen during the EMS care of spontaneously breathing major Traumatic Brain Injury (TBI) patients. Methods: Continuous NC-CO 2 data (Philips MRx™ monitors) were evaluated from non-intubated, major (moderate, severe, critical) TBI cases (4/13-5/17) in the EPIC TBI Study (NIH 1R01NS071049). Descriptive statistics were used to evaluate case and NC-CO 2 attributes. Results: Included were 92 cases [median age = 50 (range 10-91; 66% male)]. Median respiratory rate (RR) was &gt;15/min in 87% of cases and &gt;20/min in 53%. The highest median RR was 39. Sixteen cases (17%) had a median NC-CO 2 &lt;20 mmHg, 37% (34) were 20-29, 18% (17) were 30-34, 25% (23) were 35-45. Two cases (2%) were 45-50, which has not been noted in this population previously. No case had a median NC-CO 2 &gt;50. Several common NC-CO 2 patterns emerged: 1) while the final level varied among patients, the vast majority of cases (79, 86%) attained a stable “plateau” with relatively small variation after that point; 2) ETCO 2 often “ramped up” from &lt;10mmHg to the plateau during the initial few seconds of monitoring (36; 39%); 3) many patients (40; 43%) had near-normal (30-34 mmHg) or even normal (35-45) ETCO 2 plateaus. In 78% of the cases with normal CO 2 plateaus (35-45mmHg), these levels were maintained despite high RR and/or dramatic variations in RR. Conclusions: This initial work identifies that NC-CO 2 monitoring may provide useful information in non-intubated EMS patients. After initial “ramp up,” the vast majority achieved stable readings despite dramatic RR variations. Most patients (53%) were spontaneously hyperventilating at rates more than twice “normal.” Despite this, almost half of them (43%) had ETCO 2 plateaus that were normal/near normal throughout their course. It is unclear whether the “very low” readings (&lt;30mmHg) represent true physiological hypocapnia or simply “washout” due to the sensors being in an open ventilatory space (the naris) with continuous ambient O 2 flow. Future studies comparing NC-CO 2 to measured arterial pCO 2 are needed to identify the correlation and accuracy of NC-CO 2 as a tool for evaluating ventilatory physiology.
Outcome of patients younger than 50 years old diagnosed with myelodysplastic syndromes (MDS): Single institution experience.
Authors: Aref Al-Kali, Rong He, Mrinal Patnaik, Karen Hanna, David Viswanatha, Patricia T. Greipp, Darci Zblewski, Michelle A. Elliott, Mark Robert Litzow, Phuong L. Nguyen
Journal: Journal of Clinical Oncology (2017)

e18560 Background: Myelodysplastic syndromes (MDS) are rare hematological neoplasms typically seen in the elderly. Young MDS (yMDS) patients ( &lt; 50 years old) have been reported to comprise between 3-6% in the Surveillance, Epidemiology and End Results (Ma X et al, Cancer 2007; Rollison R et al, Blood 2008) with a better overall survival (OS). Methods: 1012 MDS patients from 1993 to 2015 were found after IRB approval was obtained. All cases had their bone marrow slides reviewed at our institution. yMDS Patients were included as cohort 1, while the rest as cohort 2. Survival estimates were calculated using Kaplan-Meier curves and univariate and multivariate analyses was based on log-rank testing using JMP software version 10. Results: We found 68 (7%) yMDS patients with a median age of 42 years (range, 18-49). Female gender was more common (43% vs 31%, p = 0.05) while platelets were lower in yMDS (61 vs 102, p &lt; 0.0001). Therapy related MDS (t-MDS) was more frequent (33% vs 17%, p = 0.005), as was transformation to acute myeloid leukemia (AML) in yMDS (28 % vs 11%, p = 0.0004). Allogenic hematopoietic cell transplantation (HCT) was more frequent in yMDS (42% vs 4%, p &lt; 0.0001). Survival outcome: Median OS was longer for cohort 1 vs cohort 2 but did not reach statistical significance (43 vs 21 months, p = 0.1). Median progression free survival (PFS) was shorter for cohort 1 vs cohort 2 but also did not reach statistical significance (8 vs 12 months, p = 0.3). Median OS for cohort 1 based on R-IPSS was 44, 105, 40, 18, and 12 months for very low, low, intermediate, high and very high risk groups, respectively (p = 0.09). Median OS was shorter in t-MDS vs de novo MDS in yMDS (13 vs 47 months, p = 0.04). yMDS patients who transformed to AML had worse median OS (18 vs 93 months, p = 0.001). On multivariate analysis neither t-MDS nor R-IPSS had a statistically significant impact on OS. Conclusions: MDS is rarely diagnosed under the age of 50 with IPSS-R being less powerful in detecting mOS. Among yMDS patients, there was a higher proportion of t-MDS compared to older patients with subsequent higher rates of AML transformation and higher rates of allogeneic HCT. In our study, we did not find an improved OS for yMDS patients compared to older patients.
A phase 1/2A trial of synthetic DNA vaccine immunotherapy targeting HPV-16 and -18 after chemoradiation for cervical cancer.
Authors: Yasmin Hasan, Michael T. Spiotto, Larissa V Furtado, Ana Isabel Tergas, Nita Karnik Lee, Rebecca A. Brooks, Anne Ritke McCall, Daniel William Golden, Shruti Jolly, Gini F. Fleming, Matthew P Morrow, Jeffrey Skolnik, Mark Esser, Rakesh Kumar, Ralph R. Weichselbaum
Journal: Journal of Clinical Oncology (2018)

5525 Background: DNA immunotherapies targeting HPV oncogenes, E6 and E7, have demonstrated clinical efficacy in pre-invasive cervical lesions. Here, we assessed the feasibility of chemoradiation and adjuvant MEDI0457 (INO-3112), a DNA-based immunotherapy targeting HPV-16 and HPV-18 E6 and E7 oncogenes, followed by electroporation (EP) with the CELLECTRA device, in locally advanced and recurrent cervical cancer patients. Methods: Safety and immunogenicity of MEDI0457 were assessed in HPV-16- or HPV-18-positive newly-diagnosed inoperable (Cohort 1, C1) or persistent and/or recurrent disease (Cohort 2, C2) cervical cancer patients treated with standard therapy. MEDI0457 was delivered with EP on day 0, weeks 4, 8, and 12. The primary endpoint was to evaluate safety and tolerability. Secondary objectives included clinical response (PET-CT, clinical exam) and immune responses against HPV antigens as measured by Interferon-g (IFNg) secretion by peripheral blood mononuclear cells and anti-E6/E7 antibody titers. Results: As of Jan 23, 2018, 10 patients (7 C1, 3 C2) with stage IB1-IV HPV 16 (n = 7) or 18 (n = 3) cervical cancers received MEDI0457 after conventional therapy. Treatment-related adverse events were all Grade 1, primarily injection site related. At up to 60 weeks of follow-up, all C1 patients remain alive with no evidence of disease clinically and on PET/CT. Of 3 C2 patients, 1 died, 1 had persistent disease and one remains free of disease. Antibody responses against HPV oncoproteins were detected in up to 60% of patients (anti-HPV16 E6 response: 5/10 patients, anti-HPV18 E6 response: 3/10 patients, anti-HPV16 E7 response: 4/10 patients, anti-HPV18 E7 response 6/10 patients). IFN-g responses were detected in 4/7 C1 patients while no IFN-g response was detected in C2 patients. Conclusions: Adjuvant MEDI0457 is feasible after chemoradiation for locally advanced and/or recurrent cervical cancer. More than half of the patients developed detectable immune responses to HPV antigens after treatment. These results support further study into the efficacy of adding DNA therapy with CELLECTRA EP to chemoradiation for HPV-related cancers. Clinical trial information: NCT02172911.
TCT-681 Culprit Vessel Only versus Multivessel Percutaneous Coronary Intervention in Acute ST Elevation Myocardial Infarction with Cardiogenic Shock: A Comprehensive Updated Meta-Analysis
Authors: Muhammad Khalid, Abdul Khan, Muhammad Ayub, Furqan Khattak, Ghulam Murtaza, Timir Paul
Journal: Journal of the American College of Cardiology (2018)
Association of Hospital Length of Stay and Complications With Readmission After Open Pancreaticoduodenectomy
Authors: Jerry Jiang, Alex Upfill-Brown, Amanda M. Dann, Stephanie S. Kim, Mark D. Girgis, Jonathan C. King, Timothy R. Donahue
Journal: JAMA Surgery (2018)

This study uses data from the American College of Surgeons National Quality Improvement Program databases to evaluate associations between hospital length of stay and postoperative complications with hospital readmission among patients who underwent open pancreaticoduodenectomy.
Identification and functional characterization of long noncoding RNA NMR as biomarker for metastasis and prognosis in esophageal squamous cell carcinoma.
Authors: Yuan Li, Jiagen Li, Nan Sun, Mei Luo, Chengcheng Zhou, Xuejiao Shi, Wenhui Yang, Zhiliang Lu, Zhaoli Chen, Jie He
Journal: Journal of Clinical Oncology (2017)

e15587 Background: Long noncoding RNAs (lncRNA) have been implicated in cancer but most of them remain largely unstudied. Methods: In this study, we identified a NSUN2 methylated lncRNA (NMR), which is significantly upregulated in esophageal squamous cell carcinoma (ESCC), functions as a key regulator of ESCC tumor metastasis and drug resistance. Results: In microarray data of 119 paired ESCC and normal tissues, NMR was significantly overexpressed in ESCC (P &lt; 0.001), and overexpression of NMR indicated poor overall survival of ESCC patients (P = 0.003); in RNA sequencing data of 20 cancer types from TCGA, including 426 head and neck squamous cell carcinoma (HNSC) patients, NMR was significantly upregulated in HNSC tissues (P &lt; 0.01), and patients with higher T stage, N stage, and m stage had significantly higher NMR expression (P &lt; 0.05). Dysregulation of NMR was also validated in an independent cohort with 83 ESCC patients. Consistently, NMR was significantly overexpressed in ESCC (P &lt; 0.001), and high NMR expression was significantly associated with lymph node metastasis and poor overall survival (P &lt; 0.05). Functional experiments demonstrated that NMR could promote tumor cell migration and invasion, inhibit cisplatin-induced apoptosis and increase drug resistance in ESCC cells. Mechanistically, transcription of NMR could be upregulated by NF-κB activation after IL-1β and TNF-α treatment. RNA sequencing after interference highlighted alterations in collagen metabolic process and ERK1 and ERK2 cascade. Further validation proved that NMR could promote the expression of MMP3 and MMP10, at least partially by ERK1/2 pathway. Conclusions: Taken together, these findings suggest that NMR functions as an oncogenic gene in ESCC and may serve as novel biomarker and therapeutic target in ESCC.
Abstract P035: Accuracy of Self-Reported Weights Recorded Online: Results from the POWER Trial at Hopkins
Authors: Gerald J Jerome, Nae-Yuh Wang, Nowella Durkin, Jeanne Charleston, Stephanie Fitzpatrick, Gail L Daumit, Richard R Rubin, Jeanne M Clark, Arlene Dalcin, Janelle W Coughlin, Hsin-Chien Yeh, Thomas A Louis, Lawrence J Appel
Journal: Circulation (2013)

Introduction: Websites are increasingly used to track weights during weight loss interventions, yet the accuracy of these self-reported weights is unclear. Methods: This study examined the accuracy...
Lung tumorspheres as a platform for testing new therapeutic strategies in lung cancer.
Authors: Ester Munera-Maravilla, Alejandro Herreros-Pomares, Silvia Calabuig-Fariñas, Eva Escorihuela, Rut Lucas, Rosa Farras, Ana Blasco, Eloisa Jantus-Lewintre, Carlos Camps
Journal: Journal of Clinical Oncology (2016)

e23177 Background: Resistance to treatment is one of the causes influencing the high mortality of lung cancer. This feature seems to be dependent of a small subset of special characteristics of self-renewal, differentiation and ability to grow as spheroids in serum-free medium, which are known as Cancer Stem Cells (CSCs). The aim of our study is to obtain spheroids from lung cancer cell lines and to use them as an in vitro platform for drug screening. Methods: Monolayer cultures and lungspheroids from A549, H1650 and PC9 cell lines were plated at desired density in 200 µl of medium in 96-well plates. Drugs commonly used in clinical guidelines (Cisplatin, Paclitaxel, Gefitinib, Erlotinib, Afatinib, Pemetrexed and Vinorelbine) and specific inhibitors of Wnt and Hedgehog pathways (Iwp2, Xav939, LDE225 and Vismodegib and Salynomicin) were added in triplicates at 1 and 10µM. Cell viability was measured after 48 and 72 hours using MTS Assay and was normalized to the respective mock-treated control cells and presented as percentage of control. Results: Our previous results revealed that lungspheres have higher levels of expression of genes related to Wnt and Hedhehog pathways than cells grown in adherence. Wnt and Hedgehog inhibitors showed higher cytotoxic effects on spheroids than in cells grown in monolayers. Incubation of A549 cells with 10 μM of, Salynomicin, XAV939 and Iwp2 revealed the differential effect of these compounds on spheroids and cells cultured in monolayer (69,2% vs. 38%, 43,74% vs. 10,44 and 43,5 vs. 23,9, respectively) Remarkably, the cytotoxicities on spheroids of the specific inhibitors of “stemness” were higher than the observed with other drugs currently used in the treatment of lung cancer patients. Conclusions: Our data suggest that spheroids derived from lung cancer cell lines are a useful short-term culture platform for testing cytotoxic effects of new drugs in a simple and cost-effective way. The next step is the study of different combinations of Wnt/ Hedhehog inhibitors with classical drugs in order to increase the effectiveness against CSC, which could be a promising therapeutic strategy to eradicate tumour. This work was supported in part, by a grant [RD12/0036/0025] from RTICC, and PI12-02838 from ISCIII.
Last year of life of adolescent young adult (AYA) oncology patients: Inpatient utilization.
Authors: Emily E. Johnston, Elysia Marie Alvarez, Olga Saynina, Lee Sanders, Smita Bhatia, Lisa J Chamberlain
Journal: Journal of Clinical Oncology (2017)

e18047 Background: Studies of AYA oncology patients’ end-of-life care utilization are critical as cancer is the leading cause of non-accidental AYA death and end-of-life care contributes significantly to healthcare expenditures. We sought to determine the quantity of and disparities in inpatient utilization in the last year of life of AYAs with cancer. Methods: Using the California Office of Statewide Health Planning and Development administrative database linked to death certificates, we performed a retrospective population-based analysis of cancer patients aged 15-39 who died between 2000 and 2011. We determined the number of hospital days and inpatient costs for each patient in their last year of life. We determined clinical and socio-demographic factors associated with high inpatient utilization. We also evaluated admission patterns (frequency and location) as death approached. Results: The 12,883 patients were admitted an average of 40 days in their last year of life, resulting in $149,307 per patient in inpatient costs [non last year of life AYA oncology: 11.6 days (p &lt; 0.01) and $43,423 (p &lt; 0.01)]. As death approached, admission rates and the percent of admissions at non-specialty centers increased. Five percent of patients used 20% of bed-days in the last year (high-utilizers). Sociodemographic and clinical factors associated with high utilization included younger age (15-21y: OR = 2.85; 95% CI, 2.3-3.6, 22-30y: OR = 1.81; 95% CI, 1.5-2.2, reference: 31-39y), Hispanic ethnicity (OR = 1.51; 95% CI, 1.2-1.9, reference: Non-Hispanic White), non-HMO insurance (private: OR = 1.48; 95% CI, 1.1-2.0, public/self pay: OR = 1.84; 95% CI 1.3-2.5), and hematologic malignancies (OR = 3.11; 95% CI 2.6-3.8, reference: solid tumors). Conclusions: AYA oncology decedents spent 40 days in the hospital in their last year of life, with average costs approaching $150,000 per patient. Subgroup with high utilization had distinct sociodemographic and clinical characteristics and non-specialty center admissions increased as death approached. This demonstrates the need for availability of palliative care at non-specialty centers. Whether these disparities and admission patterns represent goal-concurrent care needs to be examined.
Impact of metformin use on pathologic response following chemoradiotherapy in rectal cancer.
Authors: Theodore Seth Thomas, Bindiya Patel, Suhong Luo, Chetan Vakkalagadda, Jesse W. Keller, Eric Marshall Knoche, Kristen Marie Sanfilippo, Kenneth Robert Carson
Journal: Journal of Clinical Oncology (2018)

e15642 Background: Locally advanced rectal cancer is commonly treated with chemoradiotherapy (CRT) followed by surgical resection. Response to preop CRT is assessed by surgical pathology findings at time of resection. Pathologic complete response (pCR) has been associated with locoregional control and overall survival. Metformin is an antidiabetic medication hypothesized to enhance the anti-neoplastic effects of radiation and synergize with CRT leading to improved response quality. Prior small studies suggest that metformin use during CRT increases the frequency of pCR. This study evaluated the association between metformin use during preop CRT on pathologic response in a Veterans Health Administration (VHA) cohort of diabetic rectal cancer patients. Methods: The VA Central Cancer Registry was used to identify patients diagnosed with rectal cancer using ICD-03 codes (C19.9, C20.9) from Oct 1st, 2001-Dec 31st, 2014. The analytic cohort included patients with type 2 diabetes mellitus (based on ICD-09 codes) receiving preop CRT who underwent surgical resection. All patients had a documented pathologic stage confirmed by chart review and pCR was defined as no residual tumor (pT0N0). Metformin use was determined using linked pharmacy data, defined as any prescription within 90 days of RT initiation. The primary outcome was incidence of pCR associated with metformin use, evaluated using multivariable logistic regression analysis. Results: The final cohort consisted of 597 diabetic patients, including 258 (43%) metformin users. Metformin users were older than non-users (median age 63 vs 62 years, p = 0.04) with no significant difference in race, stage, and chemotherapy agents administered. Response to CRT was similar among metformin users and non-users with 16.3% (42/258) vs 17.4% (59/339) (p = 0.72) achieving pCR, respectively. After controlling for potential confounding variables (age, stage, radiation dose,chemotherapy), logistic regression failed to demonstrate an association between metformin use and pCR (OR 0.80, 95% CI 0.51-1.24). Conclusions: Metformin use was not associated with a higher frequency of pCR when combined with preop CRT in this large VHA cohort of diabetic rectal cancer patients.
Risk of synchronous distant recurrence at time of local-regional recurrence in stage II and III breast cancer patients.
Authors: Heather B. Neuman, Jessica R. Schumacher, Amanda B. Francescatti, Taiwo Adesoye, Stephen B. Edge, Menggang Yu, Daniel McKellar, David P Winchester, Caprice Christian Greenberg
Journal: Journal of Clinical Oncology (2016)

6576 Background: National Comprehensive Cancer Network (NCCN) guidelines recommend systemic imaging for local-regional recurrence after breast cancer treatment. Limited data exists to support this recommendation. Our objective was to determine the rate of synchronous distant recurrence at the time of local-regional recurrence in high-risk patients and identify clinical factors associated with increased risk of synchronous metastases. Methods: A stage-stratified random sample of 10,333 patients diagnosed with Stage II-III breast cancer in 2006-2007 was selected from the National Cancer Database for additional medical record abstraction of imaging and recurrence. Patients who experienced local-regional recurrence within five years of diagnosis were identified. Synchronous presentation of distant metastases (within 30 days) was determined. Patient factors associated with synchronous presentation were assessed with logistic regression. Results: Of 10,333 patients, 442 (4.3%) developed a local-regional recurrence. Synchronous distant metastases were identified in 27.1% (n = 120). These metastases were most commonly detected on cross-sectional imaging (55.8%) or patient-reported symptoms (31.7%). The proportion of synchronous metastases varied by local-regional recurrence type (p = 0.008) and was highest for women with lymph node (35.6%), followed by chest wall (31.0%), and in-breast (15.9%) recurrence, and for patients with stage III (37.4%) versus stage II (20.1%) disease (p = 0.009). Age, molecular tumor subtype, and race were not associated with the likelihood of synchronous metastases. Conclusions: Approximately 27% of high-risk patients with local-regional recurrence have synchronous distant metastases. This data provides support for the current NCCN recommendation for systemic imaging in this setting, particularly for patients with lymph node or chest wall recurrences.
Accounting for improved prostate cancer mortality outcomes in Haitian men: A histological analysis.
Authors: Nick Thoreson, Alexander Rand, Carmen Sarita-Reyes, Mahmoud Soliman, Lei Li, Muhammad M. Qureshi, Gretchen Gignac, Ariel Hirsch
Journal: Journal of Clinical Oncology (2017)

e16557 Background: In a previous wide-ranging study on the outcomes of prostate cancer patients at a safety-net hospital, we discovered significantly improved mortality outcomes for Haitian Creole prostate cancer patients compared to all other languages spoken, including black English speakers, with p = 0.017 [Rand, AE, et al., Clin Genitourin Cancer. (6):455-60 (2014)]. In order to assess any molecular indications that could be contributing to this finding, we performed a histological analysis of prostate cancer specimens, comparing black English-speaking patients to Haitian Creole patients. Methods: We sampled prostatectomies from 34 black English-speaking patients and 38 black Haitian Creole-speaking patients, taken between December 2011 and June 2015. In addition to primary and secondary Gleason scores, extraprostatic extension (EPE), seminal vesicle invasion (SVI), lymphovascular invasion (LVI), and perineural invasion (PNI), we observed any small amounts of grade 5 tissue present for the tertiary Gleason score. Finally, we analyzed the presence of acute and chronic inflammation and inflammatory severity. A chi square analysis was used to compare the categories between the Haitian and non-Haitian sets, with a probability less than 0.05 considered statistically significant. Results: While the null hypothesis was confirmed for primary, secondary, and total Gleason scores, 23.7% of the Haitian samples had a tertiary Gleason score of 5, compared to only 6.3% of non-Haitian samples (p = 0.046). The two populations exhibited similar rates of EPE (p = 0.719), SVI (p = 0.884), and PNI (p = 0.597), with no LVI apparent in any sample. No significant trends were noted in acute vs. chronic inflammation (p = 0.402) or severity of inflammation (p = 0.601). Conclusions: Samples taken from Haitian Creole-speaking patients had a significantly higher rate of grade 5 tertiary Gleason tissue than the non-Haitian patient samples. The presence of a tertiary Gleason score indicates a higher risk of metastasis, yet the Haitian samples do not reveal a greater rate of extraprostatic invasion. Further studies investigating underlying health factors among Haitian patients might be useful in accounting for improved patient outcomes.