tbuckley/cabot-search huggingface dataset:
Assessment of Anastomotic Biliary Complications in Adult Patients Undergoing High-Acuity Liver Transplant
Authors: Fady M. Kaldas, Islam M. Korayem, Tara A. Russell, Vatche G. Agopian, Antony Aziz, Joseph DiNorcia, Douglas G. Farmer, Hasan Yersiz, Jonathan R. Hiatt, Ronald W. Busuttil
Journal: JAMA Surgery (2019)

Anastomotic biliary complications (ABCs) constitute the most common technical complications in liver transplant (LT). Given the ever-increasing acuity of LT, identification of factors contributing to ABCs is essential to minimize morbidity and optimize outcomes. A detailed analysis in a patient population undergoing high-acuity LT is lacking.To evaluate the rate of, risk factors for, and outcomes of ABCs and acuity level in LT recipients.This retrospective cohort study included adult LT recipients from January 1, 2013, through June 30, 2016, at a single large urban transplant center. Patients were followed up for at least 12 months after LT until June 30, 2017. Of 520 consecutive adult patients undergoing LT, 509 LTs in 503 patients were included. Data were analyzed from May 1 through September 13, 2017.Liver transplant.Any complications occurring at the level of the biliary reconstruction.Among the 503 transplant recipients undergoing 509 LTs included in the analysis (62.3% male; median age, 58 years [interquartile range {IQR}, 50-63 years), median follow-up was 24 months (IQR, 16-34 months). Overall patient and graft survival at 1 year were 91.1% and 90.3%, respectively. The median Model for End-stage Liver Disease (MELD) score was 35 (IQR, 15-40) for the entire cohort. T tubes were used in 199 LTs (39.1%) during initial bile duct reconstruction. Overall incidence of ABCs included 103 LTs (20.2%). Anastomotic leak occurred in 25 LTs (4.9%) and stricture, 77 (15.1%). Exit-site leak in T tubes occurred in 36 (7.1%) and T tube obstruction in 16 (3.1%). Seventeen patients with ABCs required surgical revision of bile duct reconstruction. Multivariate analysis revealed the following 7 independent risk factors for ABCs: recipient hepatic artery thrombosis (odds ratio [OR], 12.41; 95% CI, 2.37-64.87; P = .003), second LT (OR, 4.05; 95% CI, 1.13-14.50; P = .03), recipient hepatic artery stenosis (OR, 3.81; 95% CI, 1.30-11.17; P = .02), donor hypertension (OR, 2.79; 95% CI, 1.27-6.11; P = .01), recipients with hepatocellular carcinoma (OR, 2.66; 95% CI, 1.23-5.74; P = .01), donor death due to anoxia (OR, 2.61; 95% CI, 1.13-6.03; P = .03), and use of nonabsorbable suture material for biliary reconstruction (OR, 2.45; 95% CI, 1.09-5.54; P = .03).This large, single-center series identified physiologic and anatomical independent risk factors contributing to ABCs after high-acuity LT. Careful consideration of these factors could guide perioperative management and mitigate potentially preventable ABCs.
Leukemogenesis in Seven Donor Cell Derived Myeloid Neoplasms Patients. Whole Exome Sequencing Reveals Clonal Dynamics
Authors: Julia Suárez González, Juan Carlos Triviño, Mi Kwon, Angela Figuera Alvarez, Guiomar Bautista, Jose Garcia-Marco, Antonio Balas, Jose Luis Vicario, Francisco José Ortuño, Raul Teruel Montoya, Jose María Álamo, Pascual Balsalobre, José Luís Díez Martín, Carolina Martínez-Laperche, Ismael Buño
Journal: Blood (2018)
Abstract P5-11-09: Feasibility of tracking plasma DNA mutation kinetics in estrogen receptor positive metastatic breast cancer using a novel digital PCR amplicon sequencing assay
Authors: S Kumar, D Lindsay, B Chen, AL Garrett, XM Tan, CK Anders, LA Carey, GP Gupta
Journal: Cancer Research (2019)

Abstract Estrogen Receptor 1 (ESR1) gene mutations in estrogen receptor positive (ER+) metastatic breast cancer (MBC) are associated with clinical resistance to endocrine therapy. A highly sensitive digital PCR (dPCR) assay was developed to evaluate the baseline abundance and kinetics of hotspot ESR1 mutations in plasma circulating tumor DNA (ctDNA) from 58 ER+ MBC patients who had progressed on at least one line of prior endocrine therapy. Consistent with prior reports, we demonstrate that detection of hotspot ESR1 mutations in plasma ctDNA is associated with shorter progression-free survival. However, after patients initiated a new course of systemic therapy, changes in plasma ESR1 mutation abundance did not correlate with the duration of disease control. To investigate whether mutational heterogeneity may account for this lack of correlation, we developed a customized dPCR multiplexed amplicon next-generation sequencing (NGS) assay to detect plasma ctDNA mutations in the complete coding sequence of ESR1 and TP53, as well as hotspot regions in PIK3CA. Assay validation revealed a 79% sensitivity and 100% specificity for detecting plasma ctDNA mutations with a lower limit of detecting a 1.6% mutant allele fraction. The NGS assay revealed non-hotspot ESR1 mutations in plasma DNA from 14 of 31 (45%) patients. We also observed dynamic changes in plasma ctDNA mutant allele fraction of PIK3CA and TP53 during systemic therapy. Changes in the cumulative mutant allele fraction of ESR1, PIK3CA, and TP53 in plasma ctDNA correlated with duration of clinical treatment response in a limited subset of patients (n=8) for whom NGS was performed at two or more time points. Thus, mutational heterogeneity limits the clinical utility of monitoring individual hotspot mutations in ESR1 over time in ER+ MBC patients. However, a plasma ctDNA NGS assay targeting ESR1, PIK3CA, and TP53 may be useful as an early predictor of response to systemic therapy. Citation Format: Kumar S, Lindsay D, Chen B, Garrett AL, Tan XM, Anders CK, Carey LA, Gupta GP. Feasibility of tracking plasma DNA mutation kinetics in estrogen receptor positive metastatic breast cancer using a novel digital PCR amplicon sequencing assay [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P5-11-09.
Abstract 16274: Prehospital Titration of Oxygen Post Resuscitation From Shockable Cardiac Arrest: Results From the Exact Pilot Study
Authors: Janet Bray, Stephen Bernard, Cindy Hein, Karen Smith, Michael Stephenson, Judith Finn, Hugh Grantham, Dion Stub, Teresa Williams, Peter Cameron
Journal: Circulation (2017)

Introduction: Hyperoxemia post-return of spontaneous circulation (post-ROSC) has been found to be harmful in animal and observational clinical studies. Previous bench-tests have suggested that oxyg...
Abstract P186: Gender Dependent Association Between Asthma and Hypertension in Nationally Representative Young Korean Adults
Authors: Hong Seok Lee, Kyong-Do Han, Gerald Pekler, Yong-Moon Park
Journal: Circulation (2016)

Background: It has been reported that those with asthma have increased risk of hypertension due to spastic nature of their smooth muscle as well as high cardiac burden of delivering the oxygenated air to the whole body. The prevalence of hypertension tended to increase concurrently with the prevalence of asthma. However, little is known about the relationship between asthma and hypertension in young adults. Method: Among subjects who participated in the Korea National Health and Nutrition Examination Survey conducted in 2008-2013, a total of 10,138 young adults (4,226 men and 5,912 women), aged 19[[Unable to Display Character: &amp;#8211;]]39 years were analyzed. Asthma was defined by self-report of ever receiving a diagnosis. Hypertension was defined as a systolic blood pressure (SBP) ≥140 mm Hg, a diastolic blood pressure (DBP) ≥90 mm Hg, or a self-reported current use of antihypertensive medications. Results: The prevalence of asthma was 10.7%(451/4226) in males and 7.8%(459/5912) in females. The prevalence of hypertension was 7.7%(325/4226) in males and 16.6%(981/5912) in females. Mean SBP and DBP were lower in males with asthma than males without asthma (114.4±0.6 vs. 115.5±0.2 (P=0.087), 76.6±0.5 vs. 77.6±0.2 (P=0.033) mmHg, respectively), whereas mean SBP and DBP were higher in females with asthma than females without asthma (106.2±0.7 vs. 104.9±0.2 (P=0.080), 70.9±0.6 vs. 69.6±0.2 (P=0.041) mmHg, respectively). In multiple logistic regression analyses, females with asthma were more likely to have hypertension compared to females without asthma [odds ratio (OR): 2.46, 95 % confidence interval (CI): 1.40-4.35], on the other hands, males with asthma were less likely to have hypertension [OR: 0.54, CI: 0.35-0.81] compared to males without asthma, after adjusting for age, smoking, drinking alcohol, exercise, income status, vitamin D concentration, metabolic risk factors, and co-existing allergic conditions, respectively. Conclusion: Asthma was positively associated with hypertension in female; inversely associated with hypertension in male. This result implies that asthma pathophysiology might be differentially associated with hypertension by gender in young adults. Furthermore, gender specific management of hypertension may be required in young asthmatic patients. Our findings need to be confirmed in prospective cohort and experimental studies to provide further explanation. Key words: Asthma ;hypertension; Prevalence;Blood pressure; KNHANES
Complete Response to the Combination Therapy with Androgen Blockade and Somatostatin Analogue in a Patient with Advanced Prostate Cancer: Magnetic Resonance Imaging with 1H-Spectroscopy: Part 2
Authors: Alessandro Sciarra, Valeria Panebianco, Mauro Ciccariello, Stefano Salciccia, Alessandro Gentilucci, Danilo Lisi, Roberto Passariello, Vincenzo Gentile, Franco Di Silverio
Journal: European Urology (2007)
Abstract B07: Characterization of branched-chain aminotransferase 1 as a novel therapeutic target for small cell lung cancer
Authors: Napoleon B. Butler, Keebeom Kim, Dong-wook Kim, Kwon Park
Journal: Clinical Cancer Research (2018)

Abstract Few studies have explored tumor metabolism to target small cell lung cancer (SCLC), for which treatment options are limited and eventually fail with resistance. The objective of this study is to identify novel biomarkers and therapeutic targets among molecular changes specific to the cancer cells relative to precancerous precursor cells. In our previous study, comparative profiling of precancerous cells with SCLC cells revealed branched-chain aminotransferase1 (Bcat1) as one of the most upregulated genes in the cancer cells relative to their precursors as well as normal lung. Based on this result, we hypothesize that the elevated Bcat1 plays a role in promoting SCLC. Here, we confirmed elevated Bcat1 protein expression in mouse SCLC cells relative to precancerous cells and in human SCLC lines. Targeting Bcat1 in mouse and human SCLC cells with shRNA or small-molecule inhibitors significantly reduced colony expansion in soft agar and formation of subcutaneous tumors in athymic nude mice. Inhibition of Bcat1 also reduced protein synthesis rate as measured by puromycin incorporation into protein. Additionally, we found Bcat1 plays a significant role in leucine catabolism in mouse SCLC using a coupled enzymatic assay. Taken together, these novel findings suggest that elevated Bcat1 promotes SCLC growth by supporting protein synthesis, which is necessary for proliferating cells. Given the proven safety profile of existing inhibitors of Bcat1, our findings are significant in supporting the concept of targeting Bcat1 as a novel and particularly valuable therapeutic strategy for SCLC. Citation Format: Napoleon B. Butler, Keebeom Kim, Dong-wook Kim, Kwon Park. Characterization of branched-chain aminotransferase 1 as a novel therapeutic target for small cell lung cancer [abstract]. In: Proceedings of the Fifth AACR-IASLC International Joint Conference: Lung Cancer Translational Science from the Bench to the Clinic; Jan 8-11, 2018; San Diego, CA. Philadelphia (PA): AACR; Clin Cancer Res 2018;24(17_Suppl):Abstract nr B07.
Mutations of the LKB1/STK11 gene in non-small cell lung cancer with loss of heterozygosity
Authors: Sei-Hoon Yang, Hyang-Jeong Jo, Hyeok Shim, Kang Kyoo Lee, Eun Jung Kim, Hye Yeon Jang, Eun-Taik Jeong, Raekil Park, Rajbir Gill, Tatiana Dracheva, Jin Jen
Journal: Cancer Research (2007)

3657  Inactivating germ-line mutations of the putative tumor-suppressor gene LKB1/STK11 at 19p13.3 has been shown to cause Peutz-Jeghers syndrome (PJS), an autosomal dominantly inherited disease characterized by a predisposition to mucocutaneous pigmentations, as well as various benign and malignant neoplasms including lung tumor. To identify the extent of chromosome 19p loss in primary human lung cancers, a total of 123 tumors were analyzed for allelic imbalance (AI) with eight microsatellite markers on ch. 19p. Over all, 54% (66/123) of the tested tumors showed AI suggestive of loss of heterozygosity (LOH). There was a trend towards higher LOH at 19p in African Americans (87%), stage I (75%), and current smokers (83%), In contrast, LOH for D19S883, a marker closest to LKB1/STK11, was only 38.8% and the lowest among tested microsatellite markers. This apparent retention of heterozyosity suggests the presence of homozygous deletion in this gene. Sequencing analysis was performed for the complete coding region of the LKB1/STK11 gene in 52 tumors having LOH at microsatellite markers immediately adjacent to the gene. In this present study, 11.5% of tumors (6/52) had mutations in the LKB1 gene. Most cases occurred in women, smoker, adenocarcinoma, and half of the cases were African Americans. Three missense and two nonsense mutations were detected as well as one tumor with a frameshift mutation that would result in a truncated protein. All mutations were tumor specific and five out of the six mutations occurred at novel mutation sites except one nonsense case at codon 120(E120X). In addition, we observed germ-line polymorphisms in 44/52 patients (84.6%) and found that African American patients had a significantly higher frequency of SNPs at the LKB/STK11 gene than the Caucasian group. Based on these findings, our data further supports the finding that loss of chromosome 19p and mutation of the LKB1/STK11 gene may play a role in the development of lung cancers and is associated with smoking, race and histological subtype.
Tiotropium Provides Greater Improvements In FEV1 Than An LTRA As Add-On To ICS In Children And Adolescents With Asthma: A Systematic Review
Authors: Stanley Goldstein, Christian Vogelberg, LeRoy Graham, Alberto de la Hoz, Kimberley Kallsen, Eckard H. Hamelmann
Journal: Journal of Allergy and Clinical Immunology (2019)
Abstract 20829: Galectin-3 Promoter Hypomethylation Drives Gene Expression in Hypertensive PASMC
Authors: Shirley Li, David Stepp, David Fulton, Scott Barman
Journal: Circulation (2017)

Introduction: Pulmonary Arterial Hypertension (PAH) is a progressive disease of the lung vasculature that is accompanied by excessive proliferation of pulmonary artery smooth muscle cells (PASMC). We have identified galectin-3 (Gal-3) as a pro-proliferative, pro-fibrotic and anti-apoptotic gene that is not only upregulated in PASMC from several models of PAH as well as in human PAH, but is functionally important as determined by the ability of Gal-3 inhibitors as well as a Gal-3 knockout rat to ameliorate altered hemodynamics and right ventricle remodeling in multiple models of PAH. Hypothesis: However, how Gal-3 is upregulated remains poorly understood. Results: PASMC isolated from PAH rats exhibited an enduring capacity for increased proliferation and expressed higher levels of Gal-3 suggesting an epigenetic mechanism of regulation. Treatment of PASMC with DNA methylation inhibitors robustly increased Gal-3 expression in both control human and rat PASMC but not in MCT-derived PASMC. Pyrosequencing analy...
Six-step Trimethoprim-Sulfamethoxazole Desensitization Protocol in non-HIV patients with Self-reported Sulfa Allergy: A Single Center Experience
Authors: Annamaria G. Mechtler, Natalia Chamorro-Pareja, Ismael Carrillo-Martin, Daniela Haehn, Alexei Gonzalez-Estrada
Journal: Journal of Allergy and Clinical Immunology (2019)
Survival with Parenchymal and Pleural Invasion of Non–Small Cell Lung Cancers Less than 30 mm
Authors: Rowena Yip, Teng Ma, Raja M. Flores, David Yankelevitz, Claudia I. Henschke, Claudia I. Henschke, David F. Yankelevitz, Rowena Yip, Mary Salvatore, Raja Flores, Andrea Wolf, Mildred Chen, Daniel M. Libby, James P. Smith, Mark Pasmantier, A.P. Reeves, Steven Markowitz, Albert Miller, Jose Cervera Deval, Heidi Roberts, Demetris Patsios, Shusuke Sone, Takaomi Hanaoka, Javier Zulueta, Juan P. de-Torres, Maria D. Lozano, Ralph Aye, Kristin Manning, Thomas Bauer, Stefano Canitano, Salvatore Giunta, Enser Cole, Karl Klingler, John H.M. Austin, Gregory D.N. Pearson, Dorith Shaham, Cheryl Aylesworth, Patrick Meyers, Shahriyour Andaz, Davood Vafai, David Naidich, Georgeann McGuinness, Barry Sheppard, Matthew Rifkin, M. Kristin Thorsen, Richard Hansen, Samuel Kopel, William Mayfield, Dan Luedke, Donald Klippenstein, Alan Litwin, Peter A. Loud, Leslie J. Kohman, Ernest M. Scalzetti, Richard Thurer, Nestor Villamizar, Arfa Khan, Rakesh Shah, Xueguo Liu, Gary Herzog, Diana Yeh, Ning Wu, Joseph Lowry, Mary Salvatore, Carmine Frumiento, David S. Mendelson, Michael V. Smith, Robert Korst, Jana Taylor, Michelle S. Ginsberg, Michaela Straznicka, Mark Widmann, Gary Cecchi, Terence A.S. Matalon, Paul Scheinberg, Shari-Lynn Odzer, David Olsen, Fred Grannis, Arnold Rotter, Daniel Ray, David Mullen, Peter H. Wiernik, Edson H. Cheung, Melissa Lim, Louis DeCunzo, Robert Glassberg, Harvey Pass, Carmen Endress, Mark Yoder, Palmi Shah, Laura Welch, Michael Kalafer, Jeremy Green, James Walsh, David Bertsch, Elmer Camacho, Cynthia Chin, James O’Brien, James C. Willey
Journal: Journal of Thoracic Oncology (2019)
Shoulder pain: physiotherapy patients who believe in their ability to move show better recovery
Authors: Susan Mayor
Journal: BMJ (2019)

Patients’ belief in their ability to move despite having shoulder pain and their expectation of a positive outcome are associated with recovery from musculoskeletal pain with physiotherapy, an observational study has shown.1

Rachel Chester, lead study author from the University of East Anglia in Norwich, said, “Physiotherapy management is effective for many people with shoulder pain, but not everyone. We wanted to find out what factors predict why some people do better than others.”

Persistent musculoskeletal shoulder pain accounts for around 3% of visits to GPs every year. The pain can be disabling …
Trifluridine/tipiracil (FTD/TPI) and regorafenib (REG) in patients with metastatic colorectal cancer (mCRC): A single institution retrospective study.
Authors: Anuj K. Patel, Kimmie Ng, Mei Sheng Duh, Victoria E. Barghout, Lynn Huynh, Mihran Ara Yenikomshian, Camara Sharperson, Lauren K. Brais, Charles S. Fuchs
Journal: Journal of Clinical Oncology (2019)

592 Background: FTD/TPI and REG have both demonstrated prolonged survival in refractory mCRC patients (pts) when compared to placebo but limited comparative effectiveness data are available. This study aims to compare outcomes following initiation of FTD/TPI or REG for mCRC at a single academic cancer center. Methods: Retrospective chart reviews were conducted in all pts with mCRC who initiated FTD/TPI or REG between 2012-2017. Analyses of time from index therapy initiation to discontinuation for any reason (TTD), real-world response rates (rwRR) and disease control rates (rwDCR) were performed. Cox proportional hazards models adjusting for demographic and clinical characteristics were performed for overall survival (OS). Results: 126 FTD/TPI and 95 REG pts were included. Baseline characteristics were similar in both groups, though more pts treated with FTD/TPI had right-sided primary tumors compared to REG (30.4% vs. 25.5%, p = 0.43). Treatment patterns pre- and post-index therapy were comparable in both groups. Median observation duration for FTD/TPI and REG was 7.1 and 6.3 months, respectively. Mean TTD was 88.4 days for FTD/TPI pts and 84.2 days for REG pts (p = 0.42). Fewer pts treated with FTD/TPI discontinued due to toxicities than pts treated with REG (8.2% vs. 24.2%, p = 0.001). A higher proportion of FTD/TPI pts had no dose modifications vs. REG pts (84.0% vs. 64.1%, p &lt; 0.001). OS was similar between the two groups (adjusted hazard ratio [HR] FTD/TPI vs. REG: 0.79, p = 0.13). FTD/TPI pts had higher rwRR (52.5% vs. 34.2%, p = 0.01) and rwDCR (64.2% vs. 46.1%, p = 0.01) than REG pts. In the subgroup of pts ≥ 65 years, mean TTD was higher in FTD/TPI pts (105.9 vs. 77.6 days, p = 0.004). Pts ≥ 65 years receiving FTD/TPI had better OS than REG pts (HR: 0.51, p = 0.03). Conclusions: In this single institution study, TTD and OS were similar between pts treated with FTD/TPI and REG. Fewer pts treated with FTD/TPI than REG discontinued due to toxicities or required dose modification. Reported responses rates were higher in FTD/TPI pts. Older pts (≥ 65 years) on FTD/TPI remained on treatment longer and had better OS than REG pts.
Leptomeningeal carcinomatosis in BRCA-mutated pancreatic cancer.
Authors: Jessica Anne Slostad, Christopher Leigh Hallemeier, William R Bamlet, Fergus Couch, Robert R. McWilliams
Journal: Journal of Clinical Oncology (2019)

239 Background: Pancreatic adenocarcinoma is a rapidly fatal cancer with 5-year overall survival &lt;5%. 5-10% of pancreatic cancers occur in patients with family history of disease, and 5-27% of these familial cancers are BRCA associated, with defects in Homologous Recombination Repair (HRR). In breast and ovarian cancer, BRCA mutations may be associated with increased risk for brain metastasis (BM). BM is rare in pancreatic cancer, but it is suggested HRR deficient pancreatic cancer patients may have an increased risk for BM/LC. Methods: We analyzed 3030 prospectively identified patients with pancreatic cancer and HHR mutation germline sequencing data (BRCA1/2, ATM, PALB2) from the Mayo Clinic Pancreatic Cancer SPORE Registry. We used clinical databases (2000-2018) to assess the presence of BM or leptomeningeal carcinomatosis (LC). Unconditional logistic regression analysis, with Odds Ratio (OR) and 95% Confidence Interval (CI), assessed the association between HRR gene germline mutation carrier status and any BM. Results: Of 3030 total pancreatic cancer patients, 8 were diagnosed with clinically evident BM/LC (0.26%), confirming the very low incidence of this metastasis site (Table). Of these, all had BM, and 4 also had LC present. No patients had LC diagnosed without BM present. 175/3030 (5.8%) patients had a germline HHR gene mutation. Of these, 1 patient was a BRCA2 carrier (0.57% of HRR deficient patients). 7 /2763 (0.25%) patients without germline HRR mutations had BM or LC (p = 0.44, OR 2.26; 95% CI: 0.27, 18.49). Conclusions: To our knowledge, this is the largest review of BRCA-associated pancreatic cancer patients with BM or LC. The incidence of BM is rare at 0.27%, with LC at 0.14%. Limitations include likely underdiagnosis given short clinical course and lack of availability of somatic HRR gene status. Our study suggests HRR germline carrier patients may have an increased risk of BM/LC development compared to non-carriers. Given rarity, larger studies should be explored. [Table: see text]
NOX2 Derived Superoxide Induces Pro-Tumoral p16INK4a Driven Senescence in the AML Bone Marrow Microenvironment
Authors: Charlotte Hellmich, Amina Abdul-Aziz, Yu Sun, Christopher Richard Marlein, Eoghan Forde, Rachel E Piddock, Manar Shafat, Adam Morfakis, Mehta Tarang, Federica Di Palma, Christopher Ingham, Angela Collins, Anna Haestier, Judith Campisi, Kristian Bowles, Stuart Rushworth
Journal: Blood (2018)