tbuckley/cabot-search huggingface dataset:
Community-acquired pneumonia in the emergency department: an algorithm to facilitate diagnosis and guide chest CT scan indication
Authors: P. Loubet, S. Tubiana, Y.E. Claessens, L. Epelboin, C. Ficko, J. Le Bel, B. Rammaert, N. Garin, V. Prendki, J. Stirnemann, C. Leport, Y. Yazdanpanah, E. Varon, X. Duval, Y.E. Claessens, X. Duval, E. Bouvard, M.F. Carette, M.P. Debray, C. Mayaud, C. Leport, N. Houhou, S. Tubiana, M. Benjoar, F.X. Blanc, A.L. Brun, L. Epelboin, C. Ficko, A. Khalil, H. Lefloch, J.M. Naccache, B. Rammaert, A. Abry, J.C. Allo, S. Andre, C. Andreotti, N. Baarir, M. Bendahou, L. Benlafia, J. Bernard, A. Berthoumieu, M.E. Billemont, J. Bokobza, A.L. Brun, E. Burggraff, P. Canavaggio, M.F. Carette, E. Casalino, S. Castro, C. Choquet, H. Clément, L. Colosi, A. Dabreteau, S. Damelincourt, S. Dautheville, M.P. Debray, M. Delay, S. Delerme, L. Depierre, F. Djamouri, F. Dumas, M.R.S. Fadel, A. Feydey, Y. Freund, L. Garcia, H. Goulet, P. Hausfater, E. Ilic-Habensus, M.O. Josse, J. Kansao, Y. Kieffer, F. Lecomte, K. Lemkarane, P. Madonna, O. Meyniard, L. Mzabi, D. Pariente, J. Pernet, F. Perruche, J.M. Piquet, R. Ranerison, P. Ray, F. Renai, E. Rouff, D. Saget, K. Saïdi, G. Sauvin, E. Trabattoni, N. Trimech, C. Auger, B. Pasquet, S. Tamazirt, J.M. Treluyer, F. Tubach, J. Wang, O. Chassany, C. Misse
Journal: Clinical Microbiology and Infection (2019)
BMA votes to poll members on its assisted dying stance
Authors: Richard Hurley
Journal: BMJ (2019)

The BMA has voted to poll its members to ascertain their views on whether the association should adopt a neutral position on assisted dying rather than one against.

After a lively debate, representatives passed this part of the motion by 149 votes to 115, at their annual meeting in Belfast on 25 June.

The association’s current policy,1 reaffirmed at the 2016 annual meeting, is to oppose legalised physician assisted suicide for terminally ill people.

Jacky Davis, a consultant radiologist, proposing the 2019 motion on behalf of the Islington division, said that even if everyone had access to the best hospice care at least 5000 people a year would die suffering in unrelieved pain.

Davis, who works …
The unforeseen business and medical consequences of EHR data collection for a real-world data multiple myeloma registry.
Authors: Kevin M. Keogh, Andrew J. Belli, Monica M. Matta, Kathryn A. Tanenbaum, Kaeleigh Farrish, Michael Mulcahy, Shivam Mathura, Christopher Williams, Shaadi Mehr, Daniel Auclair, Andrew David Norden, Steven E. Labkoff
Journal: Journal of Clinical Oncology (2019)

e19528 Background: Record retrieval on behalf of a consenting patient within the context of real-world data is not well understood. As the need for real-world data continues to expand, methods for the efficient transfer of information across consenting parties will be critical to enable research collaborations. This need was highlighted through a partnership between COTA and the Multiple Myeloma Research Foundation (MMRF). As one component of the pilot study, COTA managed the record retrieval of consenting patients before going on to abstract the data for use in a registry. Methods: The pilot study identified 23 patients that consented to the release of medical records at 54 institutions across 20 states. COTA partnered with a retrieval vendor and employed its own outreach efforts for acquisition. Outreach and retrieval techniques were similar across COTA and the vendor, including targeted calls, delivery of IRB-approved consent materials, and on-site requests. The 30-day release parameter for a covered entity under 45 CFR 164.524(b)(2) of HIPAA’s Privacy Rule was used to evaluate the observed return rates. Results: A total of 56 medical records were requested, and 48 records were retrieved. The mean (±SD) retrieval time across all sites was 33 (±58) days. We found that 54% of records were released in &lt; = 30 days, and 32% of records &gt; 30 days. 14% of requested records were never released, despite a median of 19 outreach attempts (range 10 to 43). Cited issues for delay or non-release consisted of 22 institutions questioning the validity of the certified electronic patient signature, 6 requiring a physical signature, and 5 requiring their own authorization forms. In no cases did the records contain structured metadata, such as LOINC, MedDRA, and RxNorm. Conclusions: This pilot showed an unpredictable variance associated with the release of records in the context of real-world data. This variance contributed to barriers and delays in broader research efforts. The lack of accompanying metadata with released records resulted in additional required data processing. Future studies should be conducted to establish best practices in the release and retrieval of medical records used to support real-world data research.
Abstract 12278: Mitochondrial Ca2+ Influx Contributes to Arrhythmic Risk in Nonischemic Cardiomyopathy
Authors: An Xie, Hong Liu, Anyu Zhou, Guangbin Shi, Samuel C Dudley
Journal: Circulation (2017)

Introduction: Heart failure (HF) is associated with increased arrhythmic risk and triggered activity. Abnormal Ca2+ handling is thought to underlie triggered activity, and mitochondria participate ...
The role of frailty and comorbidity in treatment (tx) of elderly patients with Hodgkin lymphoma (HL).
Authors: Angie Mae Rodday, Theresa Hahn, Peter K Lindenauer, Jonathan W. Friedberg, Andrew M. Evens, Susan K. Parsons
Journal: Journal of Clinical Oncology (2019)

e19011 Background: While HL is highly curable in younger patients, older patients have higher rates of tx failure and death, which may reflect age-related factors, tx decisions, or disease biology. We described first-line tx in elderly patients with HL by frailty, comorbidity, and age. Methods: We analyzed Surveillance, Epidemiology and End Results (SEER)-Medicare data from 1999-2014. Patients with incident classical HL and Medicare Part A and B fee for service were included. First-line tx within 4 months of diagnosis (dx) was determined from inpatient, outpatient, and physician/supplier claims using chemotherapy J-codes, HCPCS codes, and DRG codes and was categorized as standard regimen, any other tx, and no tx. Pre-existing frailty and comorbidity ≤6 months prior to dx were separately defined using validated claims-based algorithms. Multinomial logistic regression estimated adjusted odds ratios (aOR) and 95% confidence intervals (CI) to identify whether frailty, comorbidity, or age at dx were associated with first-line tx; their 3- and 2-way interactions were tested and removed if p &lt; 0.1. We adjusted for race/ethnicity, Medicaid dual enrollment, population density, histology, stage, B symptoms, year (yr) of dx, and SEER registry. Results: Analyses included 2789 patients: median age was 76 yrs. 65% were frail, 79% of patients had ≥1 comorbidity, and 61% were frail and had comorbidity. 41% received a standard regimen, 32% received other tx, and 27% received no tx. No interactions were significant. Frailty, comorbidity, and older age were associated more use of other tx or no tx then standard regimens (Table). Conclusions: Frailty, comorbidity, and age were associated with first-line tx in elderly patients with HL. This may reflect physician tx decision, end-of-life care, or unique disease biology in older patients. Future research will study the relationships between first-line tx and outcomes. [Table: see text]
Abstract 41: A novel high-throughput microfluidic drug screening platform using pancreatic ductal adenocarcinoma derived organoids
Authors: Bart Kramer, Wijnand van Paassen, Luuk de Haan, Henriette Lanz, Jos Joore
Journal: Cancer Research (2019)

Abstract Pancreatic cancer is one of the deadliest tumors due to the limited treatment options and late diagnosis. Here, we describe a novel high throughput drug screening platform combining a microfluidic based 3D-culture plate, and the recently described pancreatic ductal adenocarcinoma (PDAC) derived organoids. The microfluidic plate is a high throughput microfluidic 3D cell culture platform, supporting physiologically relevant models with a minimal requirement of cell material and enabling a wide range of flow and co-culture options (e.g. with blood vessels). Organoids were derived from human PDAC xenografts and seeded in the microfluidic plate. The low amount of tissue material required (4000 cells per chip) and the high number of replicates on one plate (n=96 on a standard microtiter format plate) renders the microfluidic plate an efficient and cost-effective platform for drug screening and toxicity assays on complex, 3D models. Organoids were exposed to various chemotherapeutic drugs for 72 hours. The viability of the organoids before and after drug treatment is monitored with standard viability assays and subsequently used to generate dose response curves. In conclusion, we showed that the microfluidic plate can be used for high throughput drug screening assays and toxicity screening, and demonstrated its compatibility with human pancreatic PDAC derived organoids. Citation Format: Bart Kramer, Wijnand van Paassen, Luuk de Haan, Henriette Lanz, Jos Joore. A novel high-throughput microfluidic drug screening platform using pancreatic ductal adenocarcinoma derived organoids [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 41.
Abstract 1092: V-ATPase family regulates lysosomal exocytosis and neutralizes with tumor-infiltrating lymphocytes for glioblastoma cells
Authors: Yu-Chan Chang, Michael Hsiao
Journal: Cancer Research (2019)

Abstract Immunotherapy based on checkpoint inhibitors provides substantial clinical benefit, but only to a minority of cancer patients. Targeted immunological checkpoint pathways have demonstrated anti-tumor cytotoxicity in the treatment of refractory cancers. However, cancer cells release specific “drones”, such as small vesicles, which increase their ability in the blood and released the proteins such as PD-L1 to block the attack from T cells then they have a change to reach the tumor forming. To characterization of exosomes forming, trafficking and secretion can be a novel therapeutic approach to improve immunotherapy in cancer patients. The ATPase H+ Transporting V0 and V1 subunits (V-ATPase, also called ATP6 family) are critical for acidifying a variety of intracellular compartments and lysosomal exocytosis. Nevertheless, the dysfunctional roles of V-ATPases in glioblastoma has not yet been elucidated. For this purposed, we investigated V-ATPase members in lysosomal vesicles and found several candidates are key factors in regulating lysosomal exocytosis in glioblastoma cells. We established transcriptomics datasets by various glioblastoma cell lines, the results showed V-ATPases are highly expressed in malignant cell lines compared to benign or normal immortalized cells. Immunohistochemistry also performed a trend of consistency that increased of V-ATPase expression in tumor parts than normal adjacent tissues. The expression level of several V-ATPase subunits is also associated with clinical parameters and survival rate. Moreover, we observed the number of tumor infiltrating lymphocyte (TILs) was decreased in clinical cohorts and two-way cell models. Therefore, we established V-ATPases related proteomics datasets and found some interaction partners could stabilized protein structure of V-ATPase. Specific peptide can compete between V-ATPase and the interacting partners and further modulate TILs in glioblastoma. This approach can be a novel therapeutic strategy that combines immunotherapy to against glioblastoma in clinical patients. Citation Format: Yu-Chan Chang, Michael Hsiao. V-ATPase family regulates lysosomal exocytosis and neutralizes with tumor-infiltrating lymphocytes for glioblastoma cells [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 1092.
Abstract MP28: Filtration Markers, Cardiovascular Disease and All-cause Mortality in Kidney Transplant Recipients: The FAVORIT Trial
Authors: Meredith C Foster, Daniel E Weiner, Andrew G Bostom, Myra A Carpenter, Lesley A Inker, Petr Jarolim, John W Kusek, Marc A Pfeffer, Madhumathi Rao, Andrew S Levey
Journal: Circulation (2016)

Background: Cardiovascular disease (CVD) is common in kidney transplant recipients (KTRs). The level of kidney function (glomerular filtration rate [GFR]) estimated from serum creatinine has been shown to be independently associated with CVD outcomes in a wide range of populations, including KTRs. In other populations, CVD outcomes are more strongly associated with the alternative filtration markers serum cystatin C and beta-2-microglobulin (B2M) than creatinine, but this has not been evaluated in KTRs. Methods: We performed a case-cohort study of participants of the Folic Acid for Vascular Outcome Reduction in Transplantation (FAVORIT) Trial, a randomized, double blind clinical trial of homocysteine lowering with B vitamins in KTRs. Study participants were enrolled from 2002-07 from centers in the US, Canada &amp; Brazil; we studied a 15% random subcohort of eligible baseline participants (N=508; mean age 52 years, 38% women) and all additional eligible adjudicated CVD (CVD death, myocardial infarction, resuscitated sudden death, stroke, N=211) and all-cause mortality (N=314) events that occurred through June 2009. Filtration markers measured at baseline were expressed as estimated GFR using established CKD-EPI equations (eGFRcr, eGFRcys &amp; eGFRB2M). Associations of eGFRcr, eGFRcys &amp; eGFRB2M with CVD and mortality were evaluated with weighted Cox proportional hazard regression to account for the case-cohort design. Results: In multivariable adjusted models eGFRcr was not significantly associated with CVD or all-cause mortality. In contrast, both lower eGFRcys and eGFRB2M were associated with increased risk of CVD and all-cause mortality (Figure). Findings were similar when eGFR was treated as a continuous variable. Conclusion: Similar to non-transplant cohorts, cystatin C and B2M have stronger risk associations for CVD and all-cause mortality compared to creatinine in KTRs. These findings likely reflect differences in their non-GFR determinants; future work is needed to evaluate non-GFR determinants in KTRs.
Abstract 504: Acarbose enhances intratumoral CD8 T cell responses in a pre-clinical model of kidney cancer
Authors: Rachael M. Orlandella, Daniel L. Smith, Lyse A. Norian
Journal: Cancer Research (2019)

Abstract Metastatic renal cell carcinoma (RCC) exhibits high mortality rates and chemotherapeutic resistance. Treatment options include immune-stimulatory therapies, such as high-dose IL-2 and anti-PD-1; however, these agents only generate responses in 20-50% of patients. This illustrates the need to find ways to improve patient response rates. Long-term caloric restriction (CR) extends longevity and reduces cancer risk in animal studies. Caloric restriction mimetics (CRMs), which replicate the benefits of CR without reductions in calorie intake, were recently found to enhance chemotherapeutic efficacy by improving CD8 T cell mediated anti-tumor immunity. Here we examined acarbose, an FDA-approved anti-diabetic agent with CRM properties, in a preclinical model of kidney cancer. BALB/c mice were orthotopically tumor challenged with syngeneic luciferase-expressing Renca renal carcinoma cells, which spontaneously metastasize to the lungs. Mice were then randomized to either an acarbose-supplemented or control diet. Compared to mice on control diet, acarbose did not alter renal tumor progression at Day 28. Importantly, acarbose did not exacerbate weight loss associated with renal tumor growth. Flow cytometric analysis at Day 28 revealed increased frequencies of activated (CD44+CD62L-) intra-tumoral CD8 T cells in mice on acarbose (p=0.012). Additionally, renal tumors from mice on acarbose displayed increased frequencies of early effector (CD127-KLRG1-) CD8 T cells, in addition to heightened frequencies of PD-1+ CD8s. These findings suggest that acarbose exhibits immune-modulatory properties which could promote anti-tumor immunity. Future experiments will focus on elucidating mechanisms contributing to alterations in anti-tumor immunity. Importantly, these studies warrant investigating acarbose in combination with currently available treatments as a potentially novel therapeutic adjuvant. Citation Format: Rachael M. Orlandella, Daniel L. Smith, Lyse A. Norian. Acarbose enhances intratumoral CD8 T cell responses in a pre-clinical model of kidney cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 504.
Abstract 1706: High-quality whole-genome sequencing and analysis of FFPE samples from multiplecancer types
Authors: Shannon T. Bailey, James Lund, Muhammad Ekram, Wanfeng Yu, Richard T. Williams, Hongye Sun, Jeffrey R. Gulcher
Journal: Cancer Research (2019)

Abstract Next-generation sequencing analysis of formalin-fixed, paraffin-embedded (FFPE) samples has the potential to lead to major advances in cancer treatment and prevention. However, whole-genome sequencing (WGS) of these samples has remained challenging due to the difficult process of isolating high-quality DNA and distinguishing true variant calls from artifacts. As evidence of these challenges, only four WGS studies of FFPE samples have been published to date. Previous work has attempted to overcome these challenges by using whole-exome sequencing or smaller exon panels at high coverage depths with publications reporting success from less than half to most samples. Thus, there has not been widespread adoption of using FFPE samples for next-generation sequencing. We developed a novel DNA extraction and library prep protocol for whole-genome sequencing of FFPE tissue samples. This method produces larger DNA fragments that can be successfully used for WGS. We previously presented results of a large esophageal cancer cohort where we sequenced over 1,000 samples in tumor-normal pairs with data equivalent to that generated from fresh-frozen tissues. We recently expanded the tumor types, ages, and sources and achieved similar results. We have assayed FFPE tissues derived from breast cancer, colorectal cancer, non-small cell lung cancer, prostate cancer, and melanoma. These samples were sourced from several different labs, which have used variations on the standard fixation protocol. Some of these FFPE samples were over 15 years old. Variant calling provides excellent results without excessive C&amp;gt;T mutations. The coverage uniformity was very good, and CNV calls were made with results comparable to published TCGA data. These samples have been analyzed for MSI and TMB, and the results are comparable to those using fresh tissues. Our method makes new types of clinical studies possible utilizing FFPE samples that have been generated as part of standard hospital procedures. This method also facilitates performing studies comparing primary and recurrent cancers easier to establish and run as recurrent cancer cases can be enrolled and stored FFPE primary samples used to establish a cancer baseline. Citation Format: Shannon T. Bailey, James Lund, Muhammad Ekram, Wanfeng Yu, Richard T. Williams, Hongye Sun, Jeffrey R. Gulcher. High-quality whole-genome sequencing and analysis of FFPE samples from multiplecancer types [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 1706.
Cost-effectiveness of endoscopic ultrasound-directed transgastric ERCP compared with device-assisted and laparoscopic-assisted ERCP in patients with Roux-en-Y anatomy
Authors: Hailey J. James, Theodore W. James, Stephanie B. Wheeler, Jennifer C. Spencer, Todd H. Baron
Journal: Endoscopy (2019)

Roux-en-Y gastric bypass (RYGB) surgery is the second most common weight loss surgery in the United States. Treatment of pancreaticobiliary disease in this patient population is challenging due to the altered anatomy, which limits the use of standard instruments and techniques. Both nonoperative and operative modalities are available to overcome these limitations, including device-assisted (DAE) endoscopic retrograde cholangiopancreatography (ERCP), laparoscopic-assisted (LA) ERCP, and endoscopic ultrasound-directed transgastric ERCP (EDGE). The aim of this study was to compare the cost-effectiveness of ERCP-based modalities for treatment of pancreaticobiliary diseases in post-RYGB patients.A decision tree model with a 1-year time horizon was used to analyze the cost-effectiveness of EDGE, DAE-ERCP, and LA-ERCP in post-RYGB patients. Monte Carlo simulation was used to assess a plausible range of incremental cost-effectiveness ratios, net monetary benefit calculations, and a cost-effectiveness acceptability curve. One-way sensitivity analyses and probabilistic sensitivity analyses were also performed to assess how changes in key parameters affected model conclusions.EDGE resulted in the lowest total costs and highest total quality-adjusted life-years (QALY) for a total of $5188/QALY, making it the dominant alternative compared with DAE-ERCP and LA-ERCP. In probabilistic analyses, EDGE was the most cost-effective modality compared with LA-ERCP and DAE-ERCP in 94.4 % and 97.1 % of simulations, respectively.EDGE was the most cost-effective modality in post-RYGB anatomy for treatment of pancreaticobiliary diseases compared with DAE-ERCP and LA-ERCP. Sensitivity analysis demonstrated that this conclusion was robust to changes in important model parameters.