tbuckley/cabot-search huggingface dataset:
Abstract 15765: Echocardiographic Pulmonary Arterial Pressure Estimates and Mortality: Evidence of Increased Risk at "Normal" Values
Authors: Jessica H Huston, Shi Huang, Tufik R Assad, John French, Eric H Farber-Eger, Quinn S Wells, Evan L Brittain
Journal: Circulation (2017)

Introduction: Echocardiographic estimation of right ventricular systolic pressure (RVSP) based on tricuspid regurgitant velocity (TRV) is a screening test for pulmonary hypertension (PH). Current guidelines recommend further evaluation for RVSP greater than 40mmHg; however, this recommendation is largely empiric and based on expert opinion. We hypothesized that the adjusted risk of mortality is increased at RVSP and TRV values below 40mmHg or 3m/sec, respectively. Methods: We used Vanderbilt’s de-identified medical record (Synthetic Derivative) to identify patients referred for transthoracic echocardiography between 1997 to 2014 with a recorded RVSP or TRV value. We used Cox proportional hazard models with restricted cubic splines to measure the association between RVSP/TRV and mortality after adjusting for confounders. We analyzed RVSP and TRV separately given the subjectivity in estimating right atrial pressure to calculate RVSP. Results: We identified 54,233 individuals with a TRV value and 48,296 with...
Electronic versus Combustible Cigarette Effects on Inflammasome Component Release into Human Lung
Authors: MuChun Tsai, Min-Ae Song, Christian McAndrew, Theodore M. Brasky, Jo L. Freudenheim, Ewy Mathé, Joseph McElroy, Sarah A. Reisinger, Peter G. Shields, Mark D. Wewers
Journal: American Journal of Respiratory and Critical Care Medicine (2019)
Current use of ROS1 testing in clinical practice in the United States, France, Germany, Italy, and Japan.
Authors: Pieter De Richter
Journal: Journal of Clinical Oncology (2014)

e22108 Background: ROS1 gene rearrangements have been identified as a potential predictive marker for crizotinib response in NSCLC. Currently, ROS1 testing is not part of clinical guidelines or drug labels. Despite this, some oncologists and pathologists are testing for ROS1 rearrangements in the clinical setting. Here, we investigate the current levels of usage and impact on treatment choice of ROS-1 testing in 5 different countries. Methods: A panel of oncologists/cancer-treating physicians and pathologists in the US (N=90), France, Germany, Italy and Japan were asked to complete a perceptual questionnaire and then report on de-identified NSCLC patients and cancer tissues that had recently been tested for any markers. The physicians were asked to complete details on the molecular diagnostics tests conducted for each patient / tissue, the reasons for testing and not testing, the methodologies used for testing, the location of testing, the testing sequence, and the impact on treatment choice. All data was collected through an online survey between August 2013 and January 2014. Results: 35% of drug-treating physicians in the US stated they had tested for ROS1 for any of their patients in the past 6 months, compared to 19% in Italy, 18% in France, 12% in Germany, and 3% in Japan. 10% (29/300) of US MDx-tested NSCLC patients/tissues were tested for ROS1, compared to 2% in Italy (4/196), 5% in France (8/167), 3% in German (5/167) and 0% (0/243) in Japan. The stated impact on treatment choice was high for 83% (15/18) out of ROS1-tested patients in the US, despite the majority of them testing negative for ROS1 rearrangements. Conclusions: ROS1 testing is part of the current clinical practice of a significant subset of US oncologists and pathologists, whereas it is less common in EU3 and currently virtually non-existent in Japan.
Histone H3.3 K27M Accelerates Spontaneous Brainstem Glioma and Drives Restricted Changes in Bivalent Gene Expression
Authors: Jon D. Larson, Lawryn H. Kasper, Barbara S. Paugh, Hongjian Jin, Gang Wu, Chang-Hyuk Kwon, Yiping Fan, Timothy I. Shaw, André B. Silveira, Chunxu Qu, Raymond Xu, Xiaoyan Zhu, Junyuan Zhang, Helen R. Russell, Jennifer L. Peters, David Finkelstein, Beisi Xu, Tong Lin, Christopher L. Tinkle, Zoltan Patay, Arzu Onar-Thomas, Stanley B. Pounds, Peter J. McKinnon, David W. Ellison, Jinghui Zhang, Suzanne J. Baker
Journal: Cancer Cell (2018)
Treatment anxiety in breast cancer patients and their partners.
Authors: Constanze Banz-Jansen, Julian Wagner, Achim Rody
Journal: Journal of Clinical Oncology (2014)

e20560 Background: The diagnosis of breast cancer and its treatment mean a significant challenge for the patient and her partner. We evaluated anxiety during the various phases of therapy and fear of certain procedures of breast cancer patients and their partners. Methods: 148 patients with primary diagnosis of breast cancer and 57 partners completed the State Trait Anxiety Inventory (STAI) and a subjective questionnaire about fear of certain procedures of breast cancer treatment during several phases of breast cancer treatment like examination for diagnosis, surgery and tumor board decision. Statistical evaluation was performed with the SPSS Statistic program and statistical testing with the Mann-Whitney U-test and the Kruskal-Wallis test. Results: The State Anxiety Inventory showed highest level of anxiety for patients at tumor board decision and surgery, for the partners at examination and tumor board decision. Patients older than 66 years were more anxious than younger patients while partners between 18 and 45 years of age had the highest State Anxiety levels. Patients were most worried about chemotherapy and mastectomy while the partners were most fearful about the necessity of a second operation and pain after surgery for their wives. Patients were significantly more worried about losing hair (p<0,001), gaining weight (p<0,001) and getting scars than their partners (p=0,027). The partners were significantly more worried about the patients not waking up after surgery (p<0,001) or having pain (p<0,001). Conclusions: Managing anxiety during breast cancer treatment is a major challenge. Supporting programs should take into consideration the different perspectives of the patients and of their partners.
Reduction of heart volume during neoadjuvant chemoradiation in patients with resectable esophageal cancer.
Authors: Nadia Haj Mohammad, Martijn Kamphuis, Maarten Hulshof, Mark van Berge Henegouwen, Jacques Bergman, Rianne de Bruin-Bon, Matthijs Boekholdt, Hanneke van Laarhoven
Journal: Journal of Clinical Oncology (2014)

4044 Background: Neoadjuvant chemoradiation (nCRT) followed by surgery based on the Dutch CROSS scheme is considered curative intent treatment for patients with resectable esophageal cancer. Ideally the high dose region of the radiotherapy treatment would only include the esophagus as target organ. However, inevitably the heart will receive a part of the chemoradiation dose. Recently, decreases in heart volume have been reported during nCRT. This change in heart volume can be of great importance because it could result in inaccurate dose delivery to the tumor and organs at risk. The aim of the study was to establish hemodynamic aspects and predictors of changes in heart volume during nCRT. Methods: A prospective pilot study was conducted in patients who were treated with 5 weeks nCRT consisting of carboplatin AUC 2 and paclitaxel 50 mg/m2 concomitant with radiotherapy (41.4 Gy/1.8 Gy per fraction) followed by resection. Physical parameters, cardiac volume on CT, cardiac blood markers (troponin, NT-proBNP, CK, CK-MB) and cardiac ultrasound including 2D strain analysis were obtained at baseline and at the end of treatment. Results: 23 patients were included. A significant mean decrease of 55.3 ml (6.1%) in heart volume was detected (95% CI 36.7-73.8 ml p=0.000). Blood pressure (BP) significantly decreased (systolic BP mean decrease of 18 mmHg (95% CI 11-26 mmHg p=0.000) and diastolic BP mean decrease of 8 mmHg (95% CI 2-14 mmHg p=0.008) and heart rate during cardiac ultrasound significantly increased with 6 beats/min (95% CI 1-11 beats/min p=0.021). An evident trend of an increased vena cava inferior collaps index of 5.1 % (95 % CI -0.8-11 % p=0.086) was observed, all suggesting dehydration in the course of treatment. Left ventricle ejection fraction, 2D strain and cardiac blood markers showed no significant changes. Independent predictors for reduced heart volume were low baseline creatinin (p= 0.001) and low left ventricle endsystolic volume (p= 0.012). Conclusions: The heart volume is significantly reduced after 5 weeks of nCRT and is not accompanied by overt cardiac dysfunction. Patients with low baseline creatinin and low left ventricle endsystolic volume are more at risk for heart volume reduction. Clinical trial information: NL42999.018.12.
Polygenic risk scores: a biased prediction?
Authors: Francisco M. De La Vega, Carlos D. Bustamante
Journal: Genome Medicine (2018)

A new study highlights the biases and inaccuracies of polygenic risk scores (PRS) when predicting disease risk in individuals from populations other than those used in their derivation. The design bias of workhorse tools used for research, particularly genotyping arrays, contributes to these distortions. To avoid further inequities in health outcomes, the inclusion of diverse populations in research, unbiased genotyping, and methods of bias reduction in PRS are critical.
Abstract 17852: Epinephrine Does Not Impact Survival and May Worsen Neurological Outcomes in Out-of-hospital Cardiac Arrest: Meta-analysis of Randomized Control Trials
Authors: Sayf Altabaqchali, Shashi Kumar, Emad Aziz, Eyal Herzog, Cody William, Salim Kanaan, Marcos Molina, Walter Pierce, Segio Timmerman, Rina Kumari, Christos Maniotis, Klio Chantziara, Erdal Gursoy, Cezar Benjo, Alex Benjo
Journal: Circulation (2015)

Background: Advanced cardiac life support is a corner stone in the management of cardiac arrest and epinephrine is an important part of its armamentarium. Randomized controlled trials and observational studies have demonstrated inconsistent results regarding the benefits of epinephrine in out-of-hospital cardiac arrest. We conducted a meta-analysis to evaluate mortality and neurological outcomes. Methods: All randomized controlled trials regarding out of hospital cardiac resuscitation were sought using PubMed and Scopus databases from 1963 until June 2015. We calculated the chances of patients surviving to hospital admission and through discharge as well as having a good neurological outcome. Data was analyzed with RevMan 5.2 software. Results: Epinephrine was found to be associated with a higher rate of hospital arrival but not survival to discharge. Epinephrine also had numerically less favorable neurologic outcomes neurological but despite that this was seen in all trials this did not reach statistical significance (OR 0.71, CI95% 0.45-1.12, p 0.14). Conclusion: There is no data to support the use of epinephrine in out-of-hospital cardiac arrest patients. Increased unjustified financial and perhaps social costs seem to be present. Larger randomized controlled trials are needed.
Small interfering RNA delivery to the neurons near the amyloid plaques for improved treatment of Alzheimer׳s disease
Authors: Qian Guo, Xiaoyao Zheng, Peng Yang, Xiaoying Pang, Kang Qian, Pengzhen Wang, Shuting Xu, Dongyu Sheng, Liuchang Wang, Jinxu Cao, Wei Lu, Qizhi Zhang, Xinguo Jiang
Journal: Acta Pharmaceutica Sinica B (2018)

Gene therapy represents a promising treatment for the Alzheimer׳s disease (AD). However, gene delivery specific to brain lesions through systemic administration remains big challenge. In our previous work, we have developed an siRNA nanocomplex able to be specifically delivered to the amyloid plaques through surface modification with both CGN peptide for the blood–brain barrier (BBB) penetration and QSH peptide for β-amyloid binding. But, whether the as-designed nanocomplex could indeed improve the gene accumulation in the impaired neuron cells and ameliorate AD-associated symptoms remains further study. Herein, we prepared the nanocomplexes with an siRNA against β-site amyloid precursor protein-cleaving enzyme 1 (BACE1), the rate-limiting enzyme of Aβ production, as the therapeutic siRNA of AD. The nanocomplexes exhibited high distribution in the Aβ deposits-enriched hippocampus, especially in the neurons near the amyloid plaques after intravenous administration. In APP/PS1 transgenic mice, the nanocomplexes down-regulated BACE1 in both mRNA and protein levels, as well as Aβ and amyloid plaques to the level of wild-type mice. Moreover, the nanocomplexes significantly increased the level of synaptophysin and rescued memory loss of the AD transgenic mice without hematological or histological toxicity. Taken together, this work presented direct evidences that the design of precise gene delivery to the AD lesions markedly improves the therapeutic outcome.
The ACCROBAT I study: Three-year follow-up of a prospective phase II study with neoadjuvant TPF before bioradiotherapy for stage III-IV unresectable squamous cell head and neck cancer.
Authors: Clas Mercke, Helena Sjödin, Hedda Haugen, Gun Wickart-Johansson, Fernanda Costa-Svedman, Gabriella von Dobeln, Gregori Margolin, Mats Hellstrom, Jan Nyman
Journal: Journal of Clinical Oncology (2014)

e17004 Background: Concomittant cisplatinbased chemoradiotherapy increases tumour control compared to radiation alone. However, both acute and late toxicity can be important and the influence on rate of distant metastases is small. We exchanged cisplatin (P) for cetuximab (E) to reduce locoregional toxicity of external, mostly IMRT based radiotherapy, when possible boosted with brachytherapy (BT), and added neoadjuvant TPF to impact risk of peripheral metastases Methods: Patients (pts) with untreated stage III-IV , WHO 0-1, unresectable squamous cell carcinoma of the oral cavity, oropharynx, larynx and hypopharynx had 2 cycles of TPF (docetaxel and cisplatin 75mg/m2 day 1, 5-FU 1000/m2 96 hours CI) every 3 weeks followed by RT (68Gy/4.5 weeks) with E given one week before (400mg/m2) and weekly during RT (250mg/m2). BT of 8-15 Gy completed RT for oral and oropharyngeal tumors (not tonsillar T1-2). Neck dissection was considered for N2-3 disease. Tumor response was evaluated according to RECIST with CT, MRI or PET/CT before RT and 6 weeks FU. Toxicity (CTC 3.0) and QL (EORTC QLQ 30) were registered during and after treatment. Results: From 070401 to 090731 90 pts were enrolled in the study and were analysed 3 year FU. Median age 58, males 72, oral cavity 9, oropharynx 58, larynx 10, hypopharynx 13, stage IV disease 76 , (T4 22, T4N+ 15). Remission after TPF: CR 8, PR 44, SD 26 and PD 1, not evaluated 11 (off study 2) Toxicity(acute): TPF cycles delayed 3, reduced 25, toxicity grade 5= 1 /90 pts (sepsis); E-cycles delayed 18, reduced 10, grade 3 hypersensitivity reaction 3/90, grade 3 neck dermatitis 3/90 pts. Alive NED 3 year FU 68/90pts (76%), DOD 7 (8%), dead intercurrent 6 (1 treatment related sepsis), alive with disease 7, lost FU 2. Toxicity (3 year): 3 pts; grade 3 dysphagia 2 (1 PEG), fatigue 1. Conclusions: Neoadjuvant TPF can be given before aggressive radiotherapy with cetuximab exchanged for cisplatin with manageable, mostly acute toxicities. Antitumor effects are promising with 3-year survival rate of 76%
Primary bone marrow DLBCL, a unique biology of a very rare presentation.
Authors: Omar Salah Aljitawi, Wei Cui, Abdulraheem Yacoub
Journal: Journal of Clinical Oncology (2014)

e19555 Background: Diffuse large B cell lymphoma (DLBCL) is the most common adult lymphoma. Bone marrow (BM) involvement at presentation is 8-10%, but can be up to 30% during the course of disease. Primary bone marrow DLBCL (PBML) is a very rare entity in which clinicobiological significance is not well defined, but perceived to represent a particularly poor-risk subclass. Criteria to diagnose PBML encompass isolated BM infiltration, and the exclusion of leukemia/lymphomas that are considered to primarily involve the BM. In a retrospectively review by IELSG from 12 institutions in over a 25-year period, only 15 cases met the criteria. The biology behind the exclusive confinement to the BM compartment remains elusive. Cadherins, on the other hand, are transmembrane proteins that play important roles in cell adhesion and might help explain PBML confinement to the BM microenvironment. Herein, we describe two cases of PBML in which we evaluated E -cadherin and N-cadherin expression Methods: The age, race, presenting symptoms, laboratory features, and radiographic findings are described. Bone marrow clot and biopsy sections were stained for N- and E-cadherin expression by immunohistochemistry. Results: Two patients, a 77-year-old Caucasian man and a 61 years old African American woman, presented with progressive and profound pancytopenia and transfusion dependence. BM biopsies showed hypercellular BM with 90% and 50% involvement by DLBCL, respectively. The malignant lymphocytes were positive for CD20, CD79a, Pax5, CD45 and MUM1. Both samples were EBER negative and showed no evidence of MYC, BCL2 and BCL6 rearrangement. PET-CT scan showed marked increase in metabolic activity diffusely involving the axial skeleton but no metabolically active lymphadenopathy or extramedullary disease. Peripheral blood did not show circulating malignant lymphocytes. Immunohistochemistry stains showed strong N-cadherin expression in the malignant cells in both patient samples. E-cadherin staining was negative. Conclusions: Expression of the adhesion molecule marker N-cadherin in lymphoma cells might help explain their confinement to the BM microenvironment. Future studies should focus on exploring the role of N-cadherin in this rare entity of DLBCL.
Association of recurrence patterns following resection of pancreatic adenocarcinoma with overall survival.
Authors: Jin He, Neda Rezaee, Wenchuan Wu, John L. Cameron, Nita Ahuja, Timothy M. Pawlik, Joseph M. Herman, Ralph H. Hruban, Matthew Weiss, Lei Zheng, Christopher Lee Wolfgang
Journal: Journal of Clinical Oncology (2014)

4127 Background: Although recurrence is common after curative resection of pancreatic ductal adenocarcinoma (PDAC), little is known regarding the pattern of recurrence. Methods: We reviewed clinical data of 1,138 consecutive patients with PDAC who underwent pancreatectomy from 2000 to 2010 to document the pattern of recurrence based on CT and/or MRI and/or FDG-PET scan. Local recurrence (LR) was defined as cancer recurrence at the pancreatectomy site. Recurrence in the omentum, peritoneum, liver, lung, spine, pelvic or supraclavicular lymph nodes was considered as distal recurrence (DR). Results: The median follow up was 17 months (IQR 26 months). Of 845 patients with complete follow-up, 470 (55.6%) had recurrence with the following pattern: LR only in 111 (23.6%), liver recurrence only in 128 (27.2%), lung recurrence only in 55 (11.7%), local and DR in 84 (17.9%), and other recurrences in 92 (19.6%). 405 (86.2%) patients had only intra-abdominal recurrence. In the patients who recurred, 49.8% and 80.2% recurred within 1 year and 2 years from the resection respectively. The incidence of recurrence at different time after pancreatectomy was summarized in the Table. More patients with liver only recurrence occurred within 6 months after resection comparing to that with LR only (41% vs 9%, p<0.001). The median overall survival (OS) of the entire cohort is 22.6 month and varied significantly based on recurrence pattern (Table). The median OS of patients with lung only recurrence is longer than that with liver only recurrence (31.6 vs 16.7 months, p<0.001). Conclusions: The pattern of recurrence is associated with distinct survival and supports the observation that PDAC is genetically diverse. Our findings are important in selecting patients for personalized treatment combinations and laying the groundwork for defining the molecular basis behind the biological diversity of PDAC. The median OS and incidence of different recurrence pattern at different time after pancreatectomy. Time after pancreatectomy Median OS 6 mo 12 mo 24 mo 60 mo (m) Local only 10 9% 44 40% 82 74% 106 95% 25 Liver only 53 41% 86 67% 111 87% 126 98% 16 Lung only 7 13% 15 27% 35 64% 55 100% 32 LR and DR 17 20% 47 56% 72 86% 84 100% 20 Other 14 15% 42 46% 75 82% 90 98% 20
Expected Survival in Patients with Smoldering Multiple Myeloma and Multiple Myeloma
Authors: Moritz Binder, S. Vincent Rajkumar, Arjun Lakshman, Martha Q. Lacy, Morie A. Gertz, Francis K. Buadi, Angela Dispenzieri, Lisa Hwa, Amie Fonder, Miriam Hobbs, Suzanne R. Hayman, Steven Zeldenrust, John A. Lust, Stephen J. Russell, Nelson Leung, Prashant Kapoor, Ronald S. Go, Wilson I Gonsalves, Taxiarchis Kourelis, Rahma Warsame, Robert A. Kyle, Shaji K. Kumar
Journal: Blood (2018)
Predicting outcome of advanced head and neck cancer by measuring tumor blood perfusion in patients receiving neoadjuvant chemotherapy.
Authors: Kishore Singh, Rubu Sunku, Arun Rathi, Gaurav Shanker Pradhan
Journal: Journal of Clinical Oncology (2014)

e17006 Background: Computed Tomography measurements of perfusion have been done in advanced head and neck cancers, undergoing neo -adjuvant chemotherapy, to predict outcome. Methods: Forty patients with T3 and T4, (any nodal status) of carcinoma oropharynx, laryngo-pharynx was included in study. All received neo-adjuvant chemotherapy consisting of paclitaxel (175mg/m2 day 1), cisplatin (100mg/m2 day 2) and 5 fluorouracil (500mg/m2 day 2 to 6 CI) for 3 cycles every 21 days. Computed tomography was performed on 128 slice multidetector CT (MDCT). Parameters obtained were: tumor volume, blood flow, blood volume, permeability and time to peak enhancement, at baseline and after 3rd cycle of chemotherapy. Results: Post chemotherapy, 22 patients were responder (> 50% decrease in tumor volume), and 18 were non responder (< 50% decrease or increase in volume). Perfusion parameter for tumor was significantly different from normal tissue for blood flow p < 0.0001 [Tumor mass range 0.23 - 176 (Average 55.91), normal tissue range 0.68 - 28.59 (Average 10.15)]. Significant difference noted in blood volume between tumor and normal tissue, p < 0.001[Tumor mass range 0.4 - 21.17 (Average 10.43), normal tissue range 0.11 - 19 (Average 8.6)]. Also permeability of tumor mass was significantly higher than normal tissue P < 0.001[Tumor mass range 2.8 - 157.72 (Average 32.11), normal tissue range 0.58 - 32.74 (Average 10.11)]. Time to peak enhancement showed significant difference between tumor and normal tissue, p < 0.015 [Tumor mass range 4.16 - 28.57 (Average 15.04), normal tissue range 1.34 - 27.24 (Average 17.75)]. Tumor blood flow was significantly higher among responders (p <0.048) [Responder Range 61.03 – 5727.63 Mean 1287.29, Non responder Range (-92.09) – 1245.41 Mean 383.37]. Blood volume and permeability were increased insignificantly among responders (p <0.32 and p <0.07 respectively). Time to peak enhancement was shorter (insignificant) among responders, (p<0.058). Post chemotherapy changes in perfusion parameters among responders and non responders were not different. Conclusions: The perfusion measurement by MDCT appears to be promising for identifying responders.