tbuckley/cabot-search huggingface dataset:
MSI-low is an intermediate type between MSI-high and MSS in esophagogastric junction adenocarcinoma.
Authors: Yu Imamura, Tasuku Toihata, Manabu Takamatsu, Norio Tanaka, Shinji Mine, Seiichi Mori, Eiji Oki, Masaru Morita, Hideo Baba, Takeshi Sano, Masayuki Watanabe
Journal: Journal of Clinical Oncology (2019)

44 Background: High level of microsatellite instability (MSI-high) is an actionable molecular status in oncology, informing tumor response to immune checkpoint inhibitor. However, little is known about MSI-low. The aim of this study is to unveil the characteristics of MSI-low tumor in esophagogastric junction (EGJ) adenocarcinoma. Methods: Using 372 cases with chemo-naive EGJ adenocarcinoma tissue, MSI testing and Epstein Barr Virus (EBV)-DNA detection were performed by DNA fragment analysis (BAT25, BAT26, BAT40, D2S123, D5S346, and D17S250) and real-time PCR, respectively. MSI-high was defined as having two or more unstable markers, MSI-low as one, and microsatellite stable (MSS) as none. MSI status was compared with clinicopathological and molecular status including epigenetic alteration in MLH-1, LINE-1, and CpG methylator phenotype (CIMP), TP53 status (sequencing and immunohistological expression), Ki-67 index, intra-/peri-tumoral lymphocyte counts (CD8+ or FOXP3+), combined positive score (CPS) of PD-L1 expression. Results: MSI-low was detected in 29, MSI-high in 28, and EBV (+) in 9 cases. Three cases with MSI-low showed EBV (+), but MSI-high and EBV (+) were mutually exclusive. In 363 EBV (-) cases, MSI-low was associated with younger age (MSI-high 71.7 ± 11.3, MSI-low 61.3 ± 12.5, and MSS, 65.0 ± 12.3 years old, P = 0.003). Notably, MSI-low exhibited an intermediate type between MSI-high and MSS, in terms of no. of lymph node metastasis, and tumor immune microenvironment [no. of intra-/peri-tumoral CD8+ cells, no. of intra-/peri-tumoral FOXP3+ cells, and CPS of PD-L1 (all P among the 3 groups &lt; 0.05)]. In contrast to MSI-high tumors, MSI-low tumor was not associated with epigenetic alteration in any of MLH-1, LINE-1, or CIMP status. In survival analysis, 3-year disease-specific survival rate of MSI-low was better than that of MSS tumors, and similar to MSI-high (92.2% for MSI-low, 92.2% for MSI-high, and 69.6% for MSI-low). This trend was also observed in time to recurrence (P = 0.01). Conclusions: MSI-low cases exhibited an intermediate immune microenvironment between MSI-high and MSS, and favorable outcome. Our results may implicate MSI-low as a predictive biomarker for immune checkpoint inhibitor.
Impact of preoperative treatment with chemoradiotherapy or chemotherapy in patients with locally advanced or irresecable gastric cancer (LAGC).
Authors: C Diaz Romero, G Calderillo Ruiz, Marytere Herrera, E Ruiz Garcia, H Lopez Basave, A Leon Takahashi
Journal: Journal of Clinical Oncology (2019)

167 Background: The only curative treatment for gastric cancer remains surgery neoadjuvant chemoradiotherapy (NACRT) has shown decrease of staging and improve survival. La NACRT has been studied in esophagus cancer and Gastroesophagic Junction cancer but this trials did not include advanced gastric disease. The aim of our study was to investigate the role of Chemoradiotherapy (CTR) and chemotherapy (CT) in the treatment of LAGC. Methods: We retrospectively reviewed the medical records of 108 patients who were treated between December 2010 and January 2015, with preoperatory CRT or chemotherapy preoperatory (CT). Evaluating parameters of resectability, pathological response complete, prognostic with a 3-year follow-up. Results: 108 patients were analyzed, 61 man and 47 women, with median age 55 years, 83 (76.8%) with diffuse, 25 (23.2%) intestinal histology, however 83 patients (76.8%) had component of signet ring cells. Of the 108 patients, 41 (38%) received chemotherapy and 67 (62%) received CRT preoperative. R0 radical surgery was possible in 41 patients of which 24.3% (10/41) were in the group of CT and 46% (31/67) CRT group. Radiological progression was documented in 8 (19.5%) patients with CT and 11 (16.4%) with CRT. 7 patients were considered inoperable and 17 unresectable at the end of the preoperative treatment. The carcinomatosis was documented during the surgery in 11 and 12 patients in the CT or CRT group respectively. 10 patients developed complications gastrointestinal and hematologic to the treatment with CT and 23 patients with CRT, which 4 patients in CRT needed reoperation post-surgery. Any patient in the chemotherapy group reached complete pathologic response while of the CRT group achieved 5 complete pathological responses. Medium-3 years follow-up survival rate was 11% in the group treated with CT and 23% with CRT. Conclusions: Our revision showed a high rate of pathologic response and survival in patients with LAGC that received CRT preoperative followed by gastrectomy. On the other hand R0 resection has been reported to be a predictive factor for survival in this study were found more patients with resectable tumor after CRT preoperative.
Abstract 11132: Post-traumatic Stress Disorder is a Marker of Worse Endothelial Function
Authors: Marlene Grenon, Christopher Owens, Warren Gasper, Hugh Alley, Sandra Perez, Mary Whooley, Thomas Neylan, Beth Cohen
Journal: Circulation (2015)

Introduction: Current knowledge supports significant associations between stressful life events including post-traumatic stress disorder (PTSD) and increases in cardiovascular disease (CVD) and mortality. Despite strong evidence supporting the association of PTSD and CVD, the underlying mechanisms remain poorly understood. Hypothesis: We hypothesized that patients with PTSD would demonstrate endothelial dysfunction, a key factor in the development and progression of CVD. Methods: Two hundred sixty one outpatients treated at the Veterans Affairs Medical Center (VAMC) underwent endothelial function (EF) testing as part of the OMEGA-PAD Study or the Mind Your Heart Study. Flow-mediated brachial artery vasodilation (FMD) was performed to assess EF and current PTSD symptoms were assessed with the PTSD Checklist for DSM-IV. Multivariate linear regression models were used to determine the association between PTSD and FMD. Results: Patients with PTSD (n=69) had a significantly lower brachial artery FMD (6.2 ± 3.4% vs 7.4 ± 3.8%; p=0.03). They also had higher systolic blood pressure (p=0.04), diastolic blood pressure (p=0.01) but were also less likely to be on an ace inhibitor (p=0.04) or a beta-blocker (p=0.05) (See Table). Furthermore, patients with PTSD were more likely to have depressive symptoms (p=&lt;0.0001). Univariate analysis demonstrated that PTSD (p=0.02), age (p=0.04), renal function as measured by eGFR (p=0.02), and hypertension (p=0.009) were associated with FMD. After adjusting for these factors, PTSD remained significantly associated with worse EF (coefficient -1.62, CI -2.93, -0.31, p=0.02). Conclusions: PTSD is associated with worse EF in an outpatient population treated at the VAMC San Francisco. Since current literature supports a heightened risk of CVD with a decrease in FMD, our data suggest that treatment of mental health issues has the potential to improve vascular function and subsequently the morbid burden of CVD.
OBESITY DYSREGULATES IMMUNOMETABOLIC STATUS IN ASTHMA AND IMPACTS VACCINE RESPONSES
Authors: Sarah E. Henrickson, Bertram Bengsch, Kaitlin C. O'Boyle, Sasikanth Manne, Ramin S. Herati, Laura A. Vella, Scott E. Hensley, Josh R. Rabinowitz, Susan E. Coffin, E. John Wherry
Journal: Journal of Allergy and Clinical Immunology (2019)
Descriptive study of the function of the small airway in healthy and asthmatic children
Authors: Blanca Barroso García, Diana Betancor Pérez, Rosialzira Natasha Vera, Victoria Villalobos Violan, Maria Del Mar Fernández Nieto
Journal: Journal of Allergy and Clinical Immunology (2019)

Asthma is characterized by edema, inflammation and increased mucus throughout the bronchial tree, also affecting distal airway less than 2 mm (the "small airway"). Its affectation is related to increase in the number of exacerbations and worse prognosis so its evaluation must be taken into account by a relevant therapeutic target. A retrospective observational study comparing the values of the small airway function (FEF 75/25, FEF75, FEF50, FEF25) of 84 patients with symptoms of suspicion of asthma: 20 healthy and 64 asthmatic children diagnosed by methacholine challenge test, using Student's t-test. Other variables are studied: sex, age, BMI, data of spirometric, bronchodilator test and fractional exhaled nitric oxide (FeNO). The sample consists of 40 boys and 44 girls, aged between 5 and 17 years (average age of 11.7 years). Average BMI is 19.5 Kg/m2. The values of FEV1/FVC, FEV1 and FVC are normal and the bronchodilator test negative in all patients. FeNO is over 25 ppb in 22 patients. The mean value of FEF75/25, FEF75, FEF50 and FEF25 is 3.6L (88.1%), 4.3L (90.9%), 4.2L (89.8%) and 1.5L (84.2%), respectively, in the asthmatic group, and 3.6L (101.2%), 5.7L (101.7%), 4.1L (103.5%) and 1.9L (96.1%) in the healthy group. We found significant difference in the values measured in percentage (adjusted to patient weight and size) of FEF75/25, FEF75 and FEF50 between the healthy and the asthmatic group (p=0.0165, p=0.0364 and p=0.0085, respectively). In our series, significant difference exists between FEF75/25, FEF75 and FEF50 between healthy and asthmatic children.
Neutrophil-to-lymphocyte ratio as a prognostic marker in patients with metastatic gallbladder cancer.
Authors: Mohamed Mady, Kritika Prasai, Siddhartha Yadav, Mohamed Abdelrahim Muddathir Hassan, Lewis R. Roberts, Mitesh J. Borad, Amit Mahipal
Journal: Journal of Clinical Oncology (2019)

442 Background: Neutrophil to lymphocyte ratio (NLR) has been used as an inflammation-based prognostic marker for various malignancies. The aim of our study was to determine whether NLR can independently predict the overall survival in patients with metastatic gallbladder cancer (GBC). Methods: We identified patients diagnosed with GBC who were treated at Mayo Clinic between the years 2000 and 2016. Patients who had nonmetastatic GBC were excluded along with the patients who did not have data for neutrophils and lymphocytes. Optimal cutoff point for NLR was identified by plotting martingale residuals against NLR and patients were divided into two groups, ≥ 5 or &lt; 5. Demographic, follow-up data and outcomes were collected by retrospective review of electronic medical records. Fisher’s exact test was used to compare categorical variables, while The Mann- Whitney U test was used to compare continuous variables. Kaplan-Meier curves were plotted for NLR ≥ 5 and NLR &lt; 5 and overall survival (OS) between the two groups were compared using log rank test. Multivariate survival analysis was performed using Cox-proportional hazard regression. Results: A total of 231 patients met our inclusion criteria, of which, 138 (60%) had NLR &lt; 5 and 93 (40%) had NLR ≥ 5. Patients with NLR ≥ 5 were more likely to be older and have poor performance score, lower albumin level, higher alkaline phosphatase level, and higher platelet count. There were no significant differences noted in gender, race and administration of chemotherapy between the two groups. In univariate analysis, patients with NLR ≥ 5 at presentation had a significantly worse OS compared to those with NLR &lt; 5 (Median survival: 3.6 vs. 8.8 months, p &lt; 0.001). In multivariate analysis, adjusting for age, ECOG status, albumin, ALP, AST, ALT, bilirubin, platelet count and administration of chemotherapy, NLR of ≥ 5 was associated with a worse OS compared to NLR &lt; 5 (HR: 1.70, 95% CI:1.20 – 2.39. p &lt; 0.05). Conclusions: Our study demonstrates that NLR ≥ 5 is an independent predictor of poor prognosis in patients with metastatic gallbladder cancer.
Triple Degradation of BTK, IKZF1 and IKZF3 in B-Cell Malignancies
Authors: Sara Morrow, Dennis Dobrovolsky, Eric Wang, Radosław P. Nowak, Katherine Donovan, Tyler Faust, Guang Yang, Zhengnian Li, Eric Fischer, Steven P Treon, David M Weinstock, Nathanael S. Gray
Journal: Blood (2018)
Inverse radiotherapy planning in reconstructive surgery for breast cancer
Authors: Ana Alicia Tejera Hernández, Víctor Manuel Vega Benítez, Juan Carlos Rocca Cardenas, Neith Ortega Pérez, Nieves Rodríguez Ibarria, María Isabel Gutiérrez Giner, Pedro Pérez Correa, Juan Carlos Díaz Chico, Juan Ramón Hernández Hernández
Journal: International Journal of Surgery (2019)
Prognostic value of nutritional status for esophageal cancer patients undergoing neoadjuvant therapy and resection.
Authors: Sabrina D Saeed, Jacques Fontaine, Luis Pena, Sarah E. Hoffe, Jessica Frakes, Rutika Metha, Erin Gurd, Jose Mario Pimiento
Journal: Journal of Clinical Oncology (2019)

133 Background: Malnutrition, linked to decreased patient tolerance to chemotherapy and increased rates of therapy-related toxicity, negatively affects cancer prognosis. Esophageal carcinomas (EC) frequently present with dysphagia and significant weight loss which may be exacerbated by neoadjuvant chemoradiation, placing EC patients at an increased risk of malnutrition. We therefore aim to assess the prognostic value of pre-operative malnutrition for esophageal cancer patients undergoing neoadjuvant therapy (NAT). Methods: Query of our institution’s IRB approved database of 1113 EC patients (pts) identified 725 individuals who underwent NAT followed by resection from 1994-2018. Seventy-six pts were considered to be at higher nutritional risk during NAT, as indicated by significant weight loss and enteral feeding tube requirement (ETF+), while 644 did not receive pre-operative feeding tube placement (ETF–). Clinicopathologic characteristics, post-operative outcomes, and survival were compared between ETF+ and ETF– using various statistical methods. Results: Of the included pts, 83% were male with a median age of 64.5 (28-86) years. Between ETF+ (n = 76) and ETF– (n = 644), pt characteristics were balanced in terms of initial stage, age, histology and tumor location. A higher percentage of ETF+ pts had &gt; 5% weight loss before NAT (32 vs. 6%; p &lt; .01). ETF+ was associated with a significantly worse median survival (27 vs. 77 m; p &lt; .01), but not with increased post-operative length of hospital stay (p = .69), complications (p = .20) or tumor recurrence (p = .89). Although completion of chemotherapy (p = .46) and radiation (p = .49) were comparable between ETF+ and ETF–, tumor response was worse in the ETF+ group (71 vs. 60% non-complete response; p = .02). Conclusions: Our results suggest that baseline malnutrition is a risk factor for poor survival and negatively impacts the efficacy of neoadjuvant therapy in EC patients. Poor response to NAT in malnourished patients may stem from impaired immune function. Future prospective studies should evaluate other parameters for nutritional assessment to further assess the impact of malnutrition on tumor regression and survival after NAT.
Utilizing cultural and ethnic variables in a survey to identify individuals at high risk for gastric cancer.
Authors: Ian Solsky, Michael Parides, Clyde Schechter, Bruce D. Rapkin, Haejin In
Journal: Journal of Clinical Oncology (2019)

23 Background: Absence of national US gastric cancer (GC) screening necessitates alternative methods like surveys to identify high-risk populations. Identification of high-risk persons may be enhanced by adding ethnic and cultural variables to more conventionally known risk factors for GC. Methods: Data from a prior case-control study of 40 GC cases and 100 controls were used. A "conventional" risk factor model (age, gender, family history of GC, body mass index, excessive salt intake, alcohol, smoking, blood type, H pylori) was compared to one incorporating ethnic and cultural variables (race, immigration, generation, cultural food at ages 15-18 years, acculturation and education) using model fit, sensitivity, specificity and expected positive predictive values (PPV). Stepwise regression was then used to create a model from this pool of variables. PPV was calculated using Bayes' Theorem applied to the baseline GC incidence in the US (7.2 per 100,000). Results: The "conventional" model required 14 questions and resulted in 25% sensitivity, 94% specificity, 28 per 100,000 PPV at the 70% probability cut-off, and AUC=0.871. The model incorporating ethnic and cultural variables required 38 questions and resulted in 48% sensitivity, 91% specificity, 38 per 100,000 PPV, and AUC =0.965. After eliminating items less predictive at p=0.2, age, gender, family history of GC, excessive salt intake, immigration, generation and race remained in the model. This model required 7 questions and resulted in 45% sensitivity, 96% specificity, 81 per 100,000 PPV and AUC=0.914. Conclusions: The model with the greatest ability to identify persons at risk of GC included ethnic and cultural variables. This model can be translated into a survey with few items that can serve as a highly scalable tool to identify high-risk individuals. Support: UG1CA189823 [Table: see text]
Abstract 16909: Heart Transplantation in Children With Turner Syndrome: Analysis of a Linked Dataset
Authors: Joshua D Chew, Jonathan H Soslow, Cary Thurm, Matt Hall, Debra A Dodd, Brian Feingold, Jill H Simmons, Justin Godown
Journal: Circulation (2017)

Introduction: Little is known about heart transplantation (HT) in patients with Turner syndrome (TS). Patients with TS and hypoplastic left heart syndrome (HLHS) have poor outcomes with single vent...
Partial Oral Therapy for Osteomyelitis and Endocarditis — Is It Time?
Authors: Helen W. Boucher
Journal: New England Journal of Medicine (2019)

Antimicrobial resistance threatens health and global security, with an estimated 162,000 deaths per year in the United States caused by multidrug-resistant infections.1 Surveillance and stewardship through the use of narrow-spectrum therapy, shorter durations of therapy, and oral rather than parenteral therapy, as well as the development of new medicines and diagnostics and improvements in infection prevention through a "One Health" approach — with connections among human patients, animals, and the environment taken into account — are key strategies for combating antimicrobial resistance.2,3 Osteomyelitis and infective endocarditis are heterogeneous infections, often involving prosthetic devices. Care provided by infectious-diseases physicians, orthopedic surgeons, . . .
Abstract 18796: Staging Reperfused Myocardial Infarctions With CMR Requires Both T2 and T2* Imaging
Authors: Guan Wang, Hsin-Jung Yang, Avinash Kali, Ivan Cokic, Joseph Franci, Songbai Li, Rohan Dharmakumar
Journal: Circulation (2017)

Introduction: CMR-based staging of myocardial infarction (MI) with or without contrast agents relies on the resolution of edema in the chronic phase, which is determined on the basis of T2-based im...
DYNAMO: A Phase II Study of Duvelisib (IPI-145) in Patients With Refractory Indolent Non-Hodgkin Lymphoma
Authors: Ian W. Flinn, Carole B. Miller, Kirit M. Ardeshna, Scott Tetreault, Sarit E. Assouline, Jiri Mayer, Michele Merli, Scott D. Lunin, Andrew R. Pettitt, Zoltan Nagy, Olivier Tournilhac, Karem-Etienne Abou-Nassar, Michael Crump, Eric D. Jacobsen, Sven de Vos, Virginia M. Kelly, Weiliang Shi, Lori Steelman, NgocDiep Le, David T. Weaver, Stephanie Lustgarten, Nina D. Wagner-Johnston, Pier Luigi Zinzani
Journal: Journal of Clinical Oncology (2019)

PURPOSE Indolent non-Hodgkin lymphoma (iNHL) remains largely incurable and often requires multiple lines of treatment after becoming refractory to standard therapies. Duvelisib was approved by the Food and Drug Administration for relapsed or refractory (RR) chronic lymphocytic leukemia or small lymphocytic lymphoma (SLL) and RR follicular lymphoma (FL) after two or more prior systemic therapies. On the basis of the activity of duvelisib, a first-in-class oral dual inhibitor of phosphoinositide 3-kinase-δ,-γ, in RR iNHL in a phase I study, the safety and efficacy of duvelisib monotherapy was evaluated in iNHL refractory to rituximab and either chemotherapy or radioimmunotherapy. PATIENTS AND METHODS Eligible patients had measurable iNHL (FL, SLL, or marginal zone B-cell lymphoma) double refractory to rituximab (monotherapy or in combination) and to either chemotherapy or radioimmunotherapy. All were treated with duvelisib 25 mg orally twice daily in 28-day cycles until progression, unacceptable toxicity, or death. The primary end point was overall response rate (ORR) using the revised International Working Group criteria for malignant lymphoma. RESULTS This open-label, global phase II trial enrolled 129 patients (median age, 65 years; median of three prior lines of therapy) with an ORR of 47.3% (SLL, 67.9%; FL, 42.2%; MZL, 38.9%). The estimated median duration of response was 10 months, and the estimated median progression-free survival was 9.5 months. The most frequent any-grade treatment-emergent adverse events (TEAEs) were diarrhea (48.8%), nausea (29.5%), neutropenia (28.7%), fatigue (27.9%), and cough (27.1%). Among the 88.4% of patients with at least one grade 3 or greater TEAE, the most common TEAEs were neutropenia (24.8%), diarrhea (14.7%), anemia (14.7%), and thrombocytopenia (11.6%). CONCLUSION In the DYNAMO study, oral duvelisib monotherapy demonstrated clinically meaningful activity and a manageable safety profile in heavily pretreated, double-refractory iNHL, consistent with previous observations. Duvelisib may provide a new oral treatment option for this patient population of which many are elderly and in need of additional therapies.
Routine monitoring with pleural manometry during therapeutic large-volume thoracentesis to prevent pleural-pressure-related complications: a multicentre, single-blind randomised controlled trial
Authors: Robert J Lentz, Andrew D Lerner, Jasleen K Pannu, Christopher M Merrick, Lance Roller, Charla Walston, Sarah Valenti, Tracey Goddard, Heidi Chen, John T Huggins, Otis B Rickman, Lonny Yarmus, Ioannis Psallidas, Najib M Rahman, Richard W Light, Fabien Maldonado
Journal: The Lancet Respiratory Medicine (2019)