tbuckley/cabot-search huggingface dataset:
Annals Story Slam - Checking Boxes
Authors: Riddhi S. Shah
Journal: Annals of Internal Medicine (2019)

Web Exclusives7 May 2019Annals Story Slam - Checking BoxesFREERiddhi S. Shah, MDRiddhi S. Shah, MDSearch for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/W19-0009 SectionsAboutVisual Abstract ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail Video. Annals Story Slam - Checking Boxes "Checking Boxes," by Dr. Riddhi S. Shah (Duration 5:35)Building on the popular Annals feature “On Being a Doctor,” storytellers share stories about the experience of doctoring on video.For more videos from and information on Annals Story Slam, visit go.annals.org/StorySlam. Comments0 CommentsSign In to Submit A Comment Author, Article, and Disclosure InformationAffiliations: This article was published at Annals.org on 12 April 2019. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 7 May 2019Volume 170, Issue 9Page: SS1 ePublished: 12 April 2019 Issue Published: 7 May 2019 Copyright & PermissionsCopyright © 2019 by American College of Physicians. All Rights Reserved.Loading ...
Impact of chest imaging quality on the diagnosis of the usual interstitial pneumonia pattern: a hub and spoke study
Authors: Giacomo Sgalla, Anna Rita Larici, Antonina Re, Alessandra Farchione, Giuseppe Cicchetti, Lucio Calandriello, Alessia Comes, Nicoletta Golfi, Bruno Iovene, Francesco Varone, Riccardo Manfredi, Luca Richeldi
Journal: European Respiratory Journal (2019)

<b>CT technical quality affects the recognition of the UIP pattern by thoracic radiologists. Optimal CT scanning protocols should be implemented in spoke centres to speed up the diagnostic work-up of IPF, reducing costs and further radiation exposure.</b>http://bit.ly/2Jo4EqQ
PI3K/AKT/mTOR pathway and androgen receptor expression as potential therapeutic targets for triple-negative breast cancer.
Authors: Mirco Pistelli, Zelmira Ballatore, Mariagrazia De Lisa, Arianna Della Mora, Tommasina Biscotti, Alfredo Santinelli, Alessandra Pagliacci, Nicola Battelli, Elena Maccaroni, Raffaella Bracci, Rossana Berardi, Stefano Cascinu
Journal: Journal of Clinical Oncology (2015)

e12069 Background: The activation of the PI3K/Akt/mTOR pathway plays a role in several types of cancers including triple-negative breast cancer (TNBC). In addition, a high activation level of the PI3K/Akt/mTOR pathway has been related to worse prognosis and resistance to conventional chemotherapy. Moreover the activated form phosphorylated mTOR (p-mTOR) expression was found frequently in TNBC. Our aims were to assess expression of the activated form p-mTOR in early TNBC and to evaluate possible correlations between clinical-pathological features, AR expression and disease outcome (disease-free survival, DFS and overall survival, OS). Methods: Between January 2009 and December 2013, all consecutive patients diagnosed and treated of invasive TNBC at our institution were eligible. Patients with stage IV of disease were excluded. The evaluation of p-mTOR immunohistochemical staining considered either the percentage of positive tumor cells (range 0-100%) and staining intensity (range 0-3+); then a global score was performed and patients were further divided into two groups (p-mTOR positive vs negative). Results: 98 TNBC patients were included. The median age at diagnosis was 52 years (range 26-83). 32.6% of cases were p-mTOR positive. p-mTOR expression did not correlate with age, histological type, grade, lymph node status, lympho-vascular invasion and necrosis. Interestingly, p-mTOR positivity was associated with smaller tumor size (p = 0.03) and positive AR expression (p = 0.04). Univariate survival analysis revealed that positive immunostaining for p-mTOR was not associated with DFS (p = 0.74) and OS (p = 0.81). Conclusions: Our preliminary results revealed that almost one third of TNBC showed a high activation level of the PI3K/Akt/mTOR, without any prognostic impact on survival. However, mTOR activation has been associated with tumour size and AR expression, confirming pre-clinical microarray analysis (Lehman BD et al 2014) and suggesting that combination of AR antagonism and PI3K inhibition may have a synergistic effect as potential therapeutic targets for this selected subgroup of TNBC.
Outcomes of hypertonic saline inhalation as a treatment modality in nontuberculous mycobacterial pulmonary disease
Authors: Anne Huiberts, Sanne M.H. Zweijpfenning, Lian J. Pennings, Martin J. Boeree, Jakko van Ingen, Cecile Magis-Escurra, Wouter Hoefsloot
Journal: European Respiratory Journal (2019)

Treatment of nontuberculous mycobacterial pulmonary disease (NTM-PD) poses a challenge for clinicians and patients. Treatment involves 18–24 months of multidrug antibiotic therapy and has a cure rate of 50–70% [1]. Cure rates depend on the causative NTM species, drug susceptibility and disease manifestation; macrolide resistance and fibro-cavitary disease are risk factors for treatment failure. Even when treatment is considered successful, there is a high risk of recurrence, either by relapse or re-infection. Furthermore, adverse events, like gastrointestinal discomfort, are frequently seen and occasionally necessitate treatment discontinuation [1]. Management of underlying pulmonary disease is essential for successful NTM-PD treatment [1]. Since hypertonic saline (HS) inhalation is safe and has shown a clinical effect in bronchiectasis patients [2–4] we have included HS inhalation in our local NTM treatment protocol. In clinical practice, we advise patients with nodular-bronchiectatic disease to start with HS inhalation two times daily as the only therapy for the first 3 months. When patients tolerate HS and when there are no clinical signs of disease deterioration, we continue HS as the only treatment with close observation of possible disease progression. This clinical observation includes a high-resolution chest tomography, sputum or bronchoalveolar lavage mycobacterial cultures and pulmonary function tests. Patients with nontuberculous mycobacterial lung disease benefit from hypertonic saline inhalation <http://bit.ly/2WQpYMz>
<i>Mycobacterium avium</i> Complex Diversity within Lung Disease, as Revealed by Whole-Genome Sequencing
Authors: Darwin J. Operario, Suporn Pholwat, Alex F. Koeppel, Alyson Prorock, Yongde Bao, Katia Sol-Church, Michele Scheurenbrand, Melinda Poulter, Stephen Turner, Hardik I. Parikh, Amy Mathers, Eric R. Houpt
Journal: American Journal of Respiratory and Critical Care Medicine (2019)
Prospective assessment of quality of life in patients with advanced NSCLC treated in real world community oncology settings: Effects of initial treatment regimen and disease progression.
Authors: Mark S. Walker, Hans-Peter Goertz, Arliene Ravelo, Sebastien Hazard, Paul J. E. Miller, Lee Steven Schwartzberg
Journal: Journal of Clinical Oncology (2015)

e19027 Background: Overall objectives are to examine symptom burden and quality of life in prospectively accrued patients (pts) with advanced non-small cell lung cancer (NSCLC), treated in real world settings. The present report examines longitudinal quality of life (QOL) endpoints of the first 93 pts to complete one year of follow-up. Methods: Pts starting first line treatment of stage IIIB/IV NSCLC were prospectively accrued and consented at 34 US-based community oncology settings. Eligible pts received one of the following regimens: A: bevacizumab with chemotherapy doublet or with pemetrexed and carboplatin; B: chemotherapy doublet without bevacizumab; C: pemetrexed with cisplatin or carboplatin. Site staff collected baseline demographic and clinical information, and patient-reported outcome and symptom measures at baseline and each office visit. Total study sample is 156. Results: Of 156 pts, 71 (45.5%) were accrued in Regimen A, 25 (16.0%) in Regimen B, and 60 (38.4%) in Regimen C. Pts were 57.7% male, 85.9% Caucasian, with mean age 65.2 (±11.1). 13.5% had impaired performance status (ECOG 2+ or equivalent). Regimen varied by region, with more Southern pts receiving C and fewer receiving B than expected, p = 0.0013. Follow-up QOL data (634 surveys) were available for 93 pts: Regimen A: N = 38, B: N = 18, C: N = 37. Mixed models showed pts in Arm A to have significantly better symptoms, status, and functioning compared to Arm C on the EORTC: QLQ-C30 Physical Functioning scale (p = 0.001), MDASI Symptom Severity and Core Symptom scales (p < 0.0001, p = 0.0006), and the Rotterdam Activity Level Scale (p = 0.0155), with trends toward better outcomes on the QLQ-C30 Emotional and Cognitive Functioning scales (p = 0.0194, p = 0.0225). Outcomes tended to be poorer after disease progression, while on chemotherapy, and among pts with impaired performance status. Conclusions: Bevacizumab-containing regimens were associated with lower symptom burden and better QOL over one year follow-up in pts receiving treatment for advanced NSCLC in real world settings, with effects that exceeded the minimum important difference for most measures.
FRI-054-Immune-related hepatitis as an independent entity from autoimmune hepatitis: clinical, prognostic and therapeutic differences
Authors: Mar Riveiro-Barciela, Judit Vidal-González, Ana Barreira-Díaz, Eva Muñoz-Couselo, Lluís Viladomiu, Carolina Ortiz Velez, Fernando Martínez-Valle, Lluís Castells, Rafael Esteban, Maria Buti
Journal: Journal of Hepatology (2019)
Endobronchial surgery and photodynamic therapy for early central lung cancer treatment
Authors: S.S. Pirogov, L. Telegina, V. Sokolov, T. Karmakova, E. Filonenko, O. Pikin, A. Kaprin
Journal: Annals of Oncology (2019)

Background: Development of endoscopic therapeutic methods for early central lung cancer. Methods: During the period from 1984 to 2019 in P.A.Hertsen Moscow Research Oncologic Institute has accumulated clinical experience in endoscopic diagnostics and treatment of early central lung cancer in 129 patients (176 tumors). X-Ray negative ECLC was observed in 86% of cases. As a treatment approach - electrocoagulation was in used from 1984 to 1993 in 73 patients (91 tumors) with ECLC, PDT and argon plasma coagulation (APC) were used from 1992 to 2019 in 56 patients (85 tumors). The following agents for used for PDT: radachlorine, photohem, photosense photolon. Endoscopic methods in 90% of cases was selected due to unfeasibility of the conventional surgery. Results: In the group of patients with ECLC treated by electrocoagulation the complete tumor regression was observed in 89% of cases. The tumor recurrence observed only in 17% of cases. In the patients who received PDT and APC the results were determined by the tumor size. When the tumor size was not greater than 1 cm, complete regression was achieved in 100% of cases. When the tumor size ranged from 1 to 1.5 cm complete resorption was achieved in 75% of cases. and with the tumor size up to 2.5 cm complete regression was achieved in 29% of cases. In 9% of cases the recurrences were diagnosed. Follow-up period lasted up to 15 years. Median survival was 5.05 years. Five year survival rate was 50±12 %. Conclusions: Intraluminal endoscopic treatment methods - photodynamic therapy and argon-plasma coagulation in early central lung cancer patients, declined of conventional surgery, provides complete tumor regression in most of cases. 5-year disease-free survival achieved in half of patients group. Legal entity responsible for the study: The authors. Funding: Has not received any funding. Disclosure: All authors have declared no conflicts of interest.
Induction of nuclear protein-1 by thyroid hormone enhances platelet-derived growth factor A mediated angiogenesis in liver cancer
Authors: Ching-Ying Chen, Sheng-Ming Wu, Yang-Hsiang Lin, Hsiang-Cheng Chi, Syuan-Ling Lin, Chau-Ting Yeh, Wen-Yu Chuang, Kwang-Huei Lin
Journal: Theranostics (2019)

Background & Aims: Hepatocellular carcinoma (HCC) is among the leading causes of cancer deaths worldwide. Many studies indicate that disruption of cellular thyroid hormone signaling promotes HCC progression. However, the mechanisms underlying the regulation of genes downstream of thyroid hormone actions in HCC have remained elusive. In the current study, we identified NUPR1 (nuclear protein-1), a stress-induced protein that overexpresses in various neoplasia, is upregulated by triiodothyronine/thyroid hormone receptor (T3/TR) signaling and aimed to elucidate its role in angiogenesis in cancer progression. Methods: Quantitative reverse transcription-PCR, luciferase promoter and chromatin immunoprecipitation assays were performed to identify the NUPR1 regulatory mechanism by T3/TR. In vitro and In vivo vascular formations were performed to detect the angiogenic function of NUPR1. Human angiogenesis arrays were performed to identify the downstream angiogenic pathway. The sorafenib resistant ability of TR/NUPR1 was further examined in vitro and in vivo. Clinical relevance of TR, NUPR1 and platelet-derived growth factor A (PDGFA) were investigate in HCC samples using qRT-PCR and western blot. Results: Our experiments disclosed positive regulation of NUPR1 expression by T3/TR through direct binding to the -2066 to -1910 region of the NUPR1 promoter. Elevated NUPR1 and TR expression link to poor survival in clinical HCC specimens. An analysis of clinicopathological parameters showed that expression of NUPR1 is associated with vascular invasion and pathology stage. Functional studies revealed that NUPR1 induced endothelial cell angiogenesis in vitro and in vivo. Using a human angiogenesis array, we identified PDGFA as a target of NUPR1 in the downstream angiogenic pathway. NUPR1 induced transcription of PDGFA through direct binding to the corresponding promoter region, and inhibition of the PDGFA signaling pathway impaired angiogenesis in human umbilical vein endothelial cells (HUVECs). Notably, the angiogenic effects of NUPR1/PDGFA were mediated by the MEK/ERK signaling pathway. TR/NUPR1 expression increased cell viability and resistance to sorafenib treatment. Moreover NUPR1 expression was positively correlated with TRα, TRβ, and PDGFA expression. Conclusions: We propose that the T3/TR/NUPR1/PDGFA/MEK/ERK axis has a vital role in hepatocarcinogenesis and suggest NUPR1 as a potential therapeutic target in HCC.
Comparison of three different gene panels for determination of tumor mutational burden by next generation sequencing
Authors: R. Pappesch, C. Heydt, J. Rehker, S. Merkelbach-Bruse
Journal: Annals of Oncology (2019)

Background: The introduction of cancer immunotherapies has improved survival rates of certain groups of patients. According to first studies, that used whole exome sequencing, the accumulation of tumor neoantigens and therefore tumor mutational burden (TMB) could be used as molecular marker for prediction. In this study, large gene panel assays of different suppliers were tested on 28 DNA samples derived from formalin fixed, paraffin-embedded (FFPE) tumor tissue with regard to implementation in routine diagnostics. Methods: After DNA isolation the following kits of three different suppliers have been used for library preparation: A custom SureSelectXTHS Target Assay (Agilent Technologies, Santa Clara, CA, USA), the NEOplus v2 RUO assay (New Oncology, Cologne, Germany) and the TruSight Oncology 500 kit (Ilumina, San Diego, CA, USA, TSO500) following manufacturers' protocol. All assays were sequenced on the NextSeq 500 system (Illumina). For quality control the TapeStation 4200 System (Agilent Technologies) was used. Results: All kits tested showed different final concentration after library preparation. Fragment sizes were as expected and libraries were suitable for sequencing. In terms of time needed for library preparation the NEOplus v2 RUO assay was the most laborious kit. The resulting TMB-scores showed similar picture for all kits and samples tested. For all panels access to the results of the sequenced genes and detected variants is possible. Data access differs between the developers in terms of availability and manageability. Since not all kits use unique molecular identifiers (UMI) the filtering capabilities are different. Conclusions: In this study, three different gene panel assays for TMB-determination were tested. All panels provided a similar TMB-score for the analysed samples. In terms of usage and in respect of implementation in routine diagnostics, time and efficiency are the most important parameters. Here, the TSO500 kit and the SureSelectXTHS Target Assay showed the best potential for the use in routine diagnostics. Legal entity responsible for the study: The authors. Funding: Has not received any funding. Disclosure: C. Heydt: Honoraria: AstraZeneca, BMS, Illumina. S. Merkelbach-Bruse: Honoraria: AstraZeneca; Advisory role: AstraZeneca, Roche. All other authors have declared no conflicts of interest.
LBP-34-Effect of Resistance Associated Substitutions on Retreatment of HCV infected patients with prior failure to Direct Acting Antiviral Therapy
Authors: David Smith, Daniel Bradshaw, Jean Mbisa, Carmen Manso, David Bibby, Josh Singer, Emma Thomson, Ana Filipe, Elihu Aranday-Cortes, Azim Ansari, Anthony Brown, Emma Hudson, Jennifer Benselin, Brendan Healy, John Mclauchlan, Eleanor Barnes, William Irving
Journal: Journal of Hepatology (2019)
Monitoring treatment response in <i>EGFR</i> mutant non-small cell lung cancer patients using mutational load in circulating cell-free tumour DNA.
Authors: Alvaro Taus, Ainhoa Hernandez, Maria del Carmen Vela, Gemma Martinez, Gabriel Piquer, Roser Correa, Raquel Longaron, Joana Vidal, David Casadevall, Lara Pijuan, Clara Montagut, Sergi Serrano, Joan Albanell, Edurne Arriola, Beatriz Bellosillo
Journal: Journal of Clinical Oncology (2015)

e19089 Background: The identification of activating EGFR mutations is essential for deciding therapy of non-small cell lung cancer (NSCLC) patients. Although evaluation of tumour biopsy material is the gold standard for EGFRmutation testing, this approach remains challenging due to the invasiveness of the procedure and intra-tumour heterogeneity. Mutation detection in circulating cell-free tumour DNA can overcome these caveats and also be used for tracking tumour dynamics Methods: Fifty-six plasma samples from 19 EGFR mutant NSCLC patients treated with tyrosine kinase inhibitors (TKIs) were collected during the course of the disease. EGFRmutations were quantified by the BEAMing technology. The correlation with paired tumour biopsies in terms of mutation detection and with the radiological response evaluation during follow-up was analysed. Results: Paired plasma and tumoural samples were compared in 14 samples. EGFRmutations were detected in plasma in 10/14 patients (5 cases M1a/M0; 5 cases M1b) showing an association between plasma and tumour biopsy of 71.4%. The 4 cases negative for plasma analysis were all M1a. Plasma samples from 7 patients at radiological objective response to anti-EGFR TKIs were available for analysis: in 5 samples EGFR mutation disappeared from plasma at partial response, in 1 case a decrease in EGFR mutation load was observed. No correlation was seen in 1case, in which mutation load increased.In 2 of these cases, samples collected previously to the radiologic evaluation were available; in one case response could have been predicted by the disappearance of EGFR mutation in plasma Plasma samples from 7 patientswere available to analyse correlation with radiological progression; in 4 cases EGFRmutational load increased and in 3 it reemerged. Resistance mutation T790M was detected in 2 samples. In 4 cases with available plasma prior to the radiological progression, mutation reappeared in 2 and increased in the other 2 Conclusions: A good association (71.4%) in the detection of EGFR mutations was found between plasma and tumour biopsies by BEAMing technology. Moreover, BEAMing is a promising tool for tracking clonal dynamics in EGFR mutant NSCLC patients.
FRI-448-Correction of a metabolic liver disease after ex vivo gene editing of defective human primary hepatocytes
Authors: Stephen Strom, Mihaela Zabulica, Raghuraman chittoor srinivasan, Christina Hammarstedt, Tingting Wu, Olav Rooyackers, Beat Thöny, Gabriella Allegri, Johannes Häberle
Journal: Journal of Hepatology (2019)
SAT-266-High rates of early HCV reinfections after DAA therapy in active intravenous drug users attended at mobile harm reduction units
Authors: Jorge Valencia, Alejandro Alvaro-Meca, Guillermo Cuevas, Jesús Troya, Angela Morro, Jorge Gutiérrez, Ismael Escobar, Jorge Alvarez, Irene Cañamares, Pablo Ryan
Journal: Journal of Hepatology (2019)
FRI-487-A new prognosis prediction model in patients with hepatocellular carcinoma after Yttrium-90 radioembolization
Authors: Jae Seung Lee, Han Ah Lee, Mi Young Jeon, Tae Seop Lim, Beom Kyung Kim, Jun Yong Park, Do Young Kim, Sang Hoon Ahn, Kwang-Hyub Han, Yeon Seok Seo, Seung Up Kim
Journal: Journal of Hepatology (2019)
The Evolving Uses of “Real-World” Data
Authors: Ethan Basch, Deborah Schrag
Journal: JAMA (2019)

The terms real-world data (RWD) and real-world evidence (RWE) have entered the medical lexicon to refer to data sources and analyses characterizing routine health care delivery.1 RWD and RWE are most often defined by what they are not: information from experiments such as randomized clinical trials.
Experience of prophylactic cranial irradiation in extensive stage small cell lung cancer at a regional cancer center in India
Authors: R.R. Jat, R.K. Rai, S.L. Jakhar, S.K. Beniwal, N. Sharma, H.S. Kumar
Journal: Annals of Oncology (2019)

Background: We conducted this randomized trial at our center to assess benefits of prophylactic cranial irradiation (PCI) in cases of extensive stage small cell lung cancer (eSCLC), who showed complete or partial response to 4 cycles of cisplatin and etoposide chemotherapy-based regime. Methods: For the study, 71 patients of histology proven SCLC with extensive stage (with no symptomatic and radiological brain metastasis) on clinico-radiological examination were randomized into two arms (Arm A and Arm B). Patients in Arm A were treated with PCI whilw those in Arm B were kept on observation, patient in both arms were followed for 1 year. Primary endpoint of the study was to assess the time of onset of symptomatic brain metastasis in both arms. Computer Tomography (CT scan) or Magnetic Resonance Imaging (MRI) was performed in patients who had any symptom suggestive of brain metastasis. Results: Patients in both arms (36 in Arm A and 35 in Arm B) were comparable for baseline characteristics. Patients in Arm A had significantly low risk of symptomatic brain metastasis then Arm B (p value = <0.005). The risk of brain metastasis in Arm A was 19.4% and in Arm B it was 51.4%. Mean duration for freedom from symptomatic brain metastasis in Arm A was 8.36 months while it was 4.49 months for Arm B. Overall 1 year median survival rate in Arm A was significantly higher in Arm A then Arm B (8 months vs 4 months). Patients in Arm A had higher toxicities, but they were mostly manageable and were not associated with poor quality of life. Conclusions: PCI is associated with significantly low risk of symptomatic brain metastasis and higher overall survival without affecting quality of life in eSCLC. Legal entity responsible for the study: Aacharya Tulsi Regional Cancer Treatment and Research Center, Bikaner. Funding: Has not received any funding. Disclosure: All authors have declared no conflicts of interest.