tbuckley/cabot-search huggingface dataset:
Development and clinical validation of an adeno/squamous multiplexed diagnostic assay for NSCLC.
Authors: Todd A. Hembrough, Wei-Li Liao, Sheeno Thyparambil, Heidi S. Erickson, George Carey, Thomas Guiel, Robert B. Heaton, David Krizman, Ignacio Ivan Wistuba, Ravi Salgia, Jon Burrows
Journal: Journal of Clinical Oncology (2013)

e19057 Background: The diagnosis of adenocarcinoma (ADC) vs. squamous cell carcinoma (SCC) in NSCLC is critical since new therapies (e.g. pemetrexed) are restricted to non-squamous NSCLC. Most diagnoses are made based on histopathology, though IHC is often performed as well. Since IHC is not quantitative, interpretation of intensity is subjective, and reproducibility can be problematic. Using the Liquid Tissue-SRM mass spectrometry (MS) platform, we have developed a quantitative, multiplexed clinical diagnostic assay to measure the adeno/squamous markers TTF-1/CK7 (ADC) and K5 and p63/40 (SCC) in FFPE tissue. This proteomic assay is epitope independent, and highly reproducible. Methods: Recombinant K5, K7, TTF-1 and p63/p40, were subjected to trypsin digestion mapping to identify peptides for MS analysis. Heavy isotope labeled peptides were synthesized as positive control peptides for quantitation. The multiplexed assay was technically validated on cell lines, and human tumor tissues. Results: ADC/SCC proteomic analysis was performed on a training set of 39 NSCLC tissues from U. of Chicago (20 ADC and 19 SCC). Principal Component Analysis was used to define optimal quantitative cutoffs for each of the four markers for the two tumor subtypes. The ADC diagnosis was unequivocal for all 20 ADC samples, however within the 19 SCC’s, one sample appeared to be ADC and two samples had markers for both ADC and SCC. Proteomic analysis of a test set of 194 NSCLC tumors (98 ADC and 98 SCC based on pathology reports) from MD Anderson Cancer Center was consistent with the observations in the training set. 93/98 ADC cases were confirmed by proteomic analysis, four ADC cases showed mixed or SCC phenotypes. Proteomic analysis confirmed 58/98 SCC cases but identified 27 cases as mixed ADC SCC or ADC based on TTF1/K5 expression. Further studies are ongoing to determine the clinical utility of these findings. Conclusions: These data demonstrate that quantitative proteomic analysis can define cut offs for ADC and SCC Biomarkers profiles in NSCLC tumors. These profiles can determine ADC, SCC and mixed phenotypes and provide physicians with accurate information to help them stratify their patients to the right evidence based treatment therapy.
Re: Zhengzheng Xu, Guangzhe Ge, Bao Guan, et al. Noninvasive Detection and Localization of Genitourinary Cancers Using Urinary Sediment DNA Methylomes and Copy Number Profiles. Eur Urol 2020;77:288–90
Authors: Yejinpeng Wang, Yaoyi Xiong, Xinghuan Wang
Journal: European Urology (2019)
A COMPARISON OF OUTCOMES OF PATIENTS WITH SEVERE TRICUSPID REGURGITATION UNDERGOING ISOLATED SURGICAL REPAIR VS. REPLACEMENT: A META-ANALYSIS AND META-REGRESSION
Authors: Mohammed Makkiya, Muhammad Farooq, Faraj Kargoli, Mohammed Algodi, Pedro Villablanca, Dee Dee Wang, Azeem Latib
Journal: Journal of the American College of Cardiology (2020)
COMPARISON OF OUTCOMES OF PATIENTS WITH CARDIOMYOPATHY UNDERGOING TRANSCATHETER AORTIC VALVE REPLACEMENT: ISCHEMIC VS. NON-ISCHEMIC
Authors: Mohammad Al-Akchar, Abdisamad M. Ibrahim, Nitin Tandan, Khalid Sawalha, Vivek Prakash, Mohsin Salih, Sachin Goel, Nilesh Goswami, Zaher Fanari
Journal: Journal of the American College of Cardiology (2020)
A chromosomal connectome for psychiatric and metabolic risk variants in adult dopaminergic neurons
Authors: Sergio Espeso-Gil, Tobias Halene, Jaroslav Bendl, Bibi Kassim, Gabriella Ben Hutta, Marina Iskhakova, Neda Shokrian, Pavan Auluck, Behnam Javidfar, Prashanth Rajarajan, Sandhya Chandrasekaran, Cyril J. Peter, Alanna Cote, Rebecca Birnbaum, Will Liao, Tyler Borrman, Jennifer Wiseman, Aaron Bell, Michael J. Bannon, Panagiotis Roussos, John F. Crary, Zhiping Weng, Stefano Marenco, Barbara Lipska, Nadejda M. Tsankova, Laura Huckins, Yan Jiang, Schahram Akbarian
Journal: Genome Medicine (2020)

Abstract Background Midbrain dopaminergic neurons (MDN) represent 0.0005% of the brain’s neuronal population and mediate cognition, food intake, and metabolism. MDN are also posited to underlay the neurobiological dysfunction of schizophrenia (SCZ), a severe neuropsychiatric disorder that is characterized by psychosis as well as multifactorial medical co-morbidities, including metabolic disease, contributing to markedly increased morbidity and mortality. Paradoxically, however, the genetic risk sequences of psychosis and traits associated with metabolic disease, such as body mass, show very limited overlap. Methods We investigated the genomic interaction of SCZ with medical conditions and traits, including body mass index (BMI), by exploring the MDN’s “spatial genome,” including chromosomal contact landscapes as a critical layer of cell type-specific epigenomic regulation. Low-input Hi-C protocols were applied to 5–10 × 10 3 dopaminergic and other cell-specific nuclei collected by fluorescence-activated nuclei sorting from the adult human midbrain. Results The Hi-C-reconstructed MDN spatial genome revealed 11 “Euclidean hot spots” of clustered chromatin domains harboring risk sequences for SCZ and elevated BMI. Inter- and intra-chromosomal contacts interconnecting SCZ and BMI risk sequences showed massive enrichment for brain-specific expression quantitative trait loci (eQTL), with gene ontologies, regulatory motifs and proteomic interactions related to adipogenesis and lipid regulation, dopaminergic neurogenesis and neuronal connectivity, and reward- and addiction-related pathways. Conclusions We uncovered shared nuclear topographies of cognitive and metabolic risk variants. More broadly, our PsychENCODE sponsored Hi-C study offers a novel genomic approach for the study of psychiatric and medical co-morbidities constrained by limited overlap of their respective genetic risk architectures on the linear genome.
IMPAIRED REGENERATIVE CAPACITY PREDICTS OUTCOMES IN PATIENTS WITH CORONARY ARTERY DISEASE AND RENAL INSUFFICIENCY
Authors: Anurag Mehta, Ayman Samman Tahhan, Chang Liu, Devinder Dhindsa, Aditi Nayak, Ananya Hooda, Kasra Moazzami, Shabatun Islam, Steven Rogers, Zakaria Almuwaqqat, Iraj Hesaroieh, Ali Mokhtari, Yi-An Ko, Edmund Waller, Arshed A. Quyyumi
Journal: Journal of the American College of Cardiology (2020)
Faecal virome transplantation decreases symptoms of type 2 diabetes and obesity in a murine model
Authors: Torben Sølbeck Rasmussen, Caroline Märta Junker Mentzel, Witold Kot, Josué Leonardo Castro-Mejía, Simone Zuffa, Jonathan Richard Swann, Lars Hestbjerg Hansen, Finn Kvist Vogensen, Axel Kornerup Hansen, Dennis Sandris Nielsen
Journal: Gut (2020)

Development of obesity and type 2 diabetes (T2D) are associated with gut microbiota (GM) changes. The gut viral community is predominated by bacteriophages (phages), which are viruses that attack bacteria in a host-specific manner. The antagonistic behaviour of phages has the potential to alter the GM. As a proof-of-concept, we demonstrate the efficacy of faecal virome transplantation (FVT) from lean donors for shifting the phenotype of obese mice into closer resemblance of lean mice.The FVT consisted of viromes with distinct profiles extracted from the caecal content of mice from different vendors that were fed a low-fat (LF) diet for 14 weeks. Male C57BL/6NTac mice were divided into five groups: LF (as diet control), high-fat (HF) diet, HF+ampicillin (Amp), HF+Amp+FVT and HF+FVT. At weeks 6 and 7 of the study, the HF+FVT and HF+Amp+FVT mice were treated with FVT by oral gavage. The Amp groups were treated with Amp 24 hours prior to first FVT treatment.Six weeks after first FVT, the HF+FVT mice showed a significant decrease in weight gain compared with the HF group. Further, glucose tolerance was comparable between the LF and HF+FVT mice, while the other HF groups all had impaired glucose tolerance. These observations were supported by significant shifts in GM composition, blood plasma metabolome and expression levels of genes associated with obesity and T2D development.Transfer of caecal viral communities from mice with a lean phenotype into mice with an obese phenotype led to reduced weight gain and normalised blood glucose parameters relative to lean mice. We hypothesise that this effect is mediated via FVT-induced GM changes.
Influence of mild and moderate hepatic impairment on the pharmacokinetics (PK) of the pan-HER inhibitor dacomitinib.
Authors: Nagdeep Giri, Anna Plotka, Yali Liang, Tanya Boutros, Grace Ni, Joanna Masters, Michael DeMicco, Patricia Pardo, Carlo Bello, Joseph O'Connell
Journal: Journal of Clinical Oncology (2013)

2568 Background: Dacomitinib (D) is a highly selective irreversible small molecule inhibitor of the HER family of tyrosine kinases in clinical development for NSCLC.Prior clinical studies of D, which has minimal renal excretion (~3%), enrolled pts with protocol-defined adequate liver function. Liver metastases, leading to abnormal liver function tests, are common in pts with advanced cancer. This study evaluated the effect of hepatic impairment on PK and safety of D following a single oral dose in subjects with mild or moderate hepatic impairment. Methods: In this phase I, open-label, parallel group study, 25 subjects with either normal hepatic function (n=8) or mild (Child-Pugh A; n=8) or moderate (Child-Pugh B; n=9) hepatic impairment were administered a single, oral dose of D (30 mg). PK samples were collected at intervals up to 264 h post-dose and safety was assessed by laboratory abnormalities, physical examination, vital signs, ECGs, and AE monitoring. Analysis of variance was performed on natural log-transformed AUC and C max to estimate adjusted mean differences between groups and 90% CIs, which were exponentiated to produce the adjusted GMR and 90% CI of the ratios. Results: GMR and 90% CI for AUC inf and C max (preliminary analyses) are listed.Mean D exposure (AUC inf and C max ) was similar in subjects with normal hepatic function and those with mild impairment. Moderate hepatic impairment decreased D exposure by 15% and 20% for AUC inf and C max , respectively, vs normal hepatic function, but the 90% CI was relatively wide, and included 1. Plasma protein binding of D was similar in the 3 groups. No clinically significant treatment-related AEs were reported. Conclusions: Mean D exposure (AUC inf and C max ) was similar in subjects with normal hepatic function and those with mild impairment. Mean D exposure appeared slightly lower in subjects with moderate impairment. Dose reduction of D in subjects with mild or moderate hepatic impairment may not be necessary. A single 30 mg dose of D was well tolerated in subjects with mild or moderate hepatic impairment. Clinical trial information: NCT01571388. [Table: see text]
ELECTROPHYSIOLOGICAL MANIFESTATIONS OF SUPRA-VENTRICULAR TACHYCARDIAS WITH CONCEALED NODO-VENTRICULAR FIBERS
Authors: Wei Wei, Caihua Sang, Sulin Zheng, Roderick Tung, Xunzhang Wang, Deyong Long, Yumei Xue, Shulin Wu
Journal: Journal of the American College of Cardiology (2020)
Clinicopathologic features of KRAS-mutated colorectal tumors vary by site of mutation.
Authors: Van Karlyle Morris, Michael J. Overman, Cathy Eng, Eduardo Vilar Sanchez, Maria Morelli, Zhiqin Jiang, Rajyalakshmi Luthra, Dipen M. Maru, Funda Meric-Bernstam, Scott Kopetz
Journal: Journal of Clinical Oncology (2013)

3632 Background: KRAS mutations in codons 12 and 13 are present in approximately 40% of all colon cancers and predict a lack of response to monoclonal antibodies to the EGFR among patients with metastatic disease. Activating mutations in codons 61 and 146 occur less frequently, and the clinicopathologic features of this subpopulation of KRAS-mutant colorectal tumors have not been clearly defined. Methods: Records of patients treated at MD Anderson Cancer Center between December 2000 and August 2012 for metastatic colorectal cancer whose tumors underwent testing for a KRAS mutation were reviewed for clinical characteristics, concurrent mutations, and survival outcomes. Associations between mutation status and clinic features were measured by calculation of odds ratios, and survival was estimated according to the Kaplan-Meier method. Results: Among the 487 records reviewed, 225 KRAS 12/13 mutations (47.2%) and 14 KRAS 61/146 mutations (2.9%) were detected. Liver metastases were less common for patients with KRAS 61/146 mutations than for patients with KRAS 12/13 mutations (OR 0.26, p-value=0.02). No difference in lung metastases was identified for KRAS 61/146 mutated patients when compared to those with KRAS wild-type tumors (OR=2.1, p-value=0.26), even though lung metastases were more common for patients with KRAS 12/13 mutations (OR 2.86, p-value=0.001). There was no association between the presence of a KRAS 61/146 mutation and gender, stage at presentation, site of primary tumor, body mass index, tobacco history, or concurrent PIK3CA mutation. Whereas a worse survival difference from the time of metastasis detection was noted for KRAS 12/13 patients when compared to those with KRAS wild-type tumors (HR 1.74, p-value= 0.002), patients with KRAS 61/146 mutations demonstrated no change in survival outcome (HR 1.10, p-value=0.87). Conclusions: Patients with KRAS 61/146 mutations have different patterns of metastases compared to KRAS 12/13, but do not appear to share the poor prognosis associated with the more common KRAS 12/13. These results suggest that clinical phenotypes for patients afflicted with colorectal cancer may differ based on the specific codon mutated within the KRAS oncogene.
A RARE CASE OF BRONCHIAL VARICES CAUSING HEMOPTYSIS AS A RESULT OF PULMONARY VEIN STENOSIS FOLLOWING CATHETER ABLATION FOR ATRIAL FIBRILLATION
Authors: Binita Dahal, Ashraf Eldabh, Anita Dahal, Saurabh Sharma, Sudhakar Sattur, Pramod Deshmukh
Journal: Journal of the American College of Cardiology (2020)
BALLISTOCARDIOGRAPHY TO IDENTIFY HIGH LEFT ATRIAL PRESSURE IN PATIENTS WITH HEART FAILURE
Authors: Li Zhang, Bin Wang, Peiwei Cai, Shaochun Zhuang, Zhengpei Chu, Shi Qingfeng, Fei Ye, Junhao Hu, Chao Yang, Pengyang Li
Journal: Journal of the American College of Cardiology (2020)
DETERMINANTS OF ATRIAL FIBRILLATION PROGRESSION IN CHRONIC KIDNEY DISEASE PATIENTS WITH CARDIAC IMPLANTABLE ELECTRONIC DEVICES (DATA FROM THE MEDTRONIC CARELINK DATABASE)
Authors: Karolina Szummer, Krishna Pundi, Alexander Perino, Jun Fan, Mitra Kothari, Mintu Turakhia
Journal: Journal of the American College of Cardiology (2020)
YIA20-003: CD229 CAR T Cells Eliminate Multiple Myeloma and Tumor Propagating Cells but Show Limited Targeting of Normal T Cells
Authors: Tim Luetkens, Sabarinath Venniyil Radhakrishnan, Sandra D. Scherer, Patricia Davis, Erica R. Vander Mause, Michael L. Olson, Sara Yousef, Jens Panse, Yasmina Abdiche, K. David Li, Rodney R. Miles, William Matsui, Alana L. Welm, Djordje Atanackovic
Journal: Journal of the National Comprehensive Cancer Network (2020)
INTERVENTION TO REDUCE INAPPROPRIATE TELEMETRY MONITORING IN A UNIVERSITY HOSPITAL: A QUALITY INITIATIVE
Authors: Khagendra Dahal, Adil Yousuf, Priyanka Gill, Kendall Douglass, Munish Kumar Kannabhiran, Sampath Singireddy, Evan Devillier, Vihn Nguyen, Ricky Bass, Kalgi Modi
Journal: Journal of the American College of Cardiology (2020)
Breaking bad news: Comparison of perspectives of Middle Eastern cancer patients and their relatives.
Authors: Jamal M Zekri, Syed Mustafa Karim, Sawsan Bassi, Bakr M Bin Sadiq, Ehab Esmat Fawzy, Yousseff Ibrahim Nauf
Journal: Journal of Clinical Oncology (2013)

9568 Background: It is believed in some Middle Eastern (ME) cultures that disclosure of bad news to cancer patients may cause loss of hope. On many occasions the relatives’ and patients’ wishes are opposed regarding this matter. This study investigates cancer patients’ and their relatives’ perspectives regarding communication of cancer-related bad news in a ME population. Methods: Nine close-ended questions were designed in a questionnaire format to obtain cancer patients’ (cohort I) and their relatives’ (cohort II) perspectives regarding communication of cancer related bad news from diagnosis to end-of-life. The questionnaire was answered by patients and relatives during out-patient visits. Chi-square test was used to test differences in responses between the two cohorts. Results: 203 participants (100 patients and 103 relatives) completed the questionnaire. In cohorts I and II, 28% and 58% of participants were males respectively (p&lt;0.001). In contrast to relatives’ views, majority of patients preferred to be informed of diagnosis and possible adverse outcome of their illness, as detailed in the Table. Conclusions: Our study indicates that there is significant discordance between the preferences of ME cancer patients and their relatives regarding disclosure of cancer related bad news to the patient. As opposed to relatives’ beliefs, most patients would prefer to know bad news throughout the course of their illness. Unless a patient indicates otherwise, physicians should strive to keep cancer patients informed of their health related events. [Table: see text]
CLINICAL CHARACTERISTICS OF PATIENTS CLASSIFIED AS VERY HIGH RISK AND NOT VERY HIGH RISK BASED ON THE 2018 AHA/ACC MULTI-SOCIETY CHOLESTEROL GUIDELINE
Authors: Aparna Sajja, Amir Ali, Hsin-Fang Li, Kateri Spinelli, Salim S. Virani, Seth Shay Martin, Tyler J. Gluckman
Journal: Journal of the American College of Cardiology (2020)
Phase II study of cetuximab plus FOLFIRI as first-line treatment in patients with unresectable/metastatic gastric or gastroesophageal junction (GEJ) adenocarcinoma (FOLCETUX study): Preliminary results
Authors: C. Pinto, F. Di Fabio, S. Siena, S. Cascinu, F. L. Rojas Llimpe, C. Ceccarelli, V. Mutri, S. Giaquinta, E. Piana, A. A. Martoni
Journal: Journal of Clinical Oncology (2006)

4031 Background: Aim of this study was to evaluate efficacy and safety of cetuximab plus FOLFIRI as first-line treatment for advanced gastric or GEJ cancer. Methods: Eligibility criteria: histological diagnosis of stomach or GEJ adenocarcinoma, unresectable/metastatic/recurrent disease, EGFR+ (Dako), measurable disease, no prior chemotherapy for advanced cancer. Pts received cetuximab weekly at 400 mg/m 2 iv loading dose, then at 250 mg/m 2 iv, CPT11 180 mg/m 2 iv d1, LFA 100 mg/m 2 iv followed by 5FU 400 mg/m 2 iv bolus and 600 mg/m 2 iv continuous infusion 22h d1–2 (FOLFIRI) every 2 weeks, for a maximum of 24 weeks, then cetuximab alone was allowed in pts with CR/PR/SD. Objective response (OR) activity was assessed by CT and PET at baseline and after 6 weeks, and further by CT± PET every 6 weeks. Results: From November 2004 to December 2005, 49/54 (90.7%) screened subjects were EGFR+, and 38 pts were enrolled. Pt characteristics: 26 (68.4%) males, 12 (31.6%) females; median age 63.5 years (39–82); median KPS 90 (70–100); 34 (89.4%) stomach, 4 (10.5%) GEJ; 18 (47.3%) gastrectomy; 13 (34.2%) adjuvant chemotherapy; 4 (10.5%) locally advanced disease, 34 (89.4%) metastatic disease; main metastatic sites: 19 (50%) lymphonodes, 12 (31.5%) liver, 4 (10.5%) lung, 8 (21.0%) peritoneal. Median number of treatment weeks was: 10 (1–46). Median dose intensity was: 5FU 100% (25–100), CPT11 100% (25–100) and cetuximab 100% (80–100). At the present time, 25 pts are assessable for response and 28 for toxicity. The OR (RECIST) were: 3 (12%) CR,11 (44%) PR, e.g. 56% CR + PR (95% CI: 37–75), 11 (44%) SD. The PFS at 3 months is 80% (95% CI: 64–96). Survival data are premature (73.6% of the pts are alive; median follow-up 3 months, range 1–12). Grade 3–4 toxicity (CTC v3.0) was: 15 (53.6%) neutropenia (1 pt died of febrile neutropenia), 1 (3.4%) thrombocytopenia, 2 (6.8%) hypertransaminasemia, 1 (3.4%) hyperbilirubinemia. Cutaneous toxicity was: 7 (25%) gr1, 11 (39.2%) gr2, 5 (17.8%) gr3. Conclusions: Combination of cetuximab and FOLFIRI appears to be active in gastric and GEJ adenocarcinoma, with a high response and disease control rate. This treatment has been well-tolerated; the major toxicity is neutropenia. No significant financial relationships to disclose.
Treatment with EGFR tyrosine kinase inhibitors beyond progression in long-term responders to erlotinib in advanced non-small cell lung cancer: A case-control study of overall survival.
Authors: Martin Faehling, Robert Eckert, Torsten G. Kamp, Sabine Kuom, Werner Spengler
Journal: Journal of Clinical Oncology (2012)

7572 Background: EGFR-tyrosine kinase inhibitor (TKI) such as erlotinib lead to prolonged disease stabilization in some patients with advanced NSCLC. It is so far not clear how to treat patients who progress after prolonged response to erlotinib. TKI therapy beyond progression with added chemotherapy, radiotherapy or best supportive care (BSC) may improve survival compared to chemotherapy, radiotherapy or BSC alone. Methods: We retrospectively analyzed all NSCLC patients treated with erlotinib at our institutions since 2004 who progressed after at least stable disease on erlotinib for at least six months (n=41). Twenty-seven patients were treated with TKI beyond progression (TKI patients), of whom 24 received erlotinib and 3 afatinib. Fourteen patients did not receive further TKI treatment after progression (controls). Overall survival (OS) from progression on TKI and OS from diagnosis of lung cancer was analyzed for the whole population and case-control subpopulations of pairs matched for gender, smoking status, and histology. Results: Treatment with TKI and chemotherapy was well tolerated with no increase in grade 3 and 4 toxicities. TKI-patients had a significantly longer OS from progression on TKI (case control: median 21.0 vs. 3.0 months, HR 0.175) and longer OS from diagnosis of lung cancer (case control: median 28.5 vs. 15.3 months, HR 0.335). Conclusions: In long-term erlotinib responders, treatment with TKI beyond progression in addition to chemotherapy or radiotherapy is feasible and well tolerated with limited toxicity. TKI-treatment beyond progression improved OS compared to treatment with TKI-free chemotherapy or radiotherapy.
GIANT SINUS OF VALSALVA PSEUDOANEURYSM WITH AN ANOMALOUS LEFT CIRCUMFLEX ARTERY IN A PATIENT WITH BICUSPID AORTIC VALVE
Authors: Kristin M. Stawiarski, Asiya Mahmut, Boris Sheynburg, Elenita Kanin, Michael Dewar, Stuart W. Zarich
Journal: Journal of the American College of Cardiology (2020)
2020 ACC Clinical Competencies for Nurse Practitioners and Physician Assistants in Adult Cardiovascular Medicine
Authors: George P. Rodgers, Jane A. Linderbaum, Dorothy D. Pearson, Susan M. Fernandes, Susan D. Housholder-Hughes, Lisa A. Mendes, Nancy C. Berg, Jennifer Day, David Drajpuch, Blair Erb, Marci Farquhar-Snow, Heather Johnson, Patricia Keegan, Christine Kindler, Rhonda Larsen, Viet T. Le, Michelle J. Nickolaus, Celeste M. Phillips, Laura Ross, Sherrie R. Webb, Erica S. Zado
Journal: Journal of the American College of Cardiology (2020)