tbuckley/cabot-search huggingface dataset:
Polyclonal serum free light chain elevation is associated with increased risk of monoclonal gammopathies
Authors: Shaji Kumar, Dirk R. Larson, Angela Dispenzieri, Terry M. Therneau, David L. Murray, P. Leif Bergsagel, Robert A. Kyle, S. Vincent Rajkumar
Journal: Blood Cancer Journal (2019)

Abstract Monoclonal gammopathies (MG) constitute a spectrum of disorders starting from a monoclonal gammopathy of undetermined significance (MGUS) to active disease requiring therapy such as multiple myeloma. MG are characterized by proliferation of clonal plasma cells (PC) secreting a monoclonal protein either as intact immunoglobulin or free kappa or lambda free light chains (FLC). We hypothesized that a polyclonal elevation of serum FLC may indicate an inflammatory state that precedes development of MG. We studied 15,630 individuals from Olmsted county, who did not have MGUS based on baseline screening studies. At a median follow-up of 18.1 years, 264 patients had developed a clonal PC disorder; 252 with MGUS, 1 with SMM, 8 with MM, and 3 with amyloidosis, translating to an annual incidence of development of a MG of 0.1%. We examined the baseline polyclonal ΣFLC (kappa + lambda FLC) from the initial screening and grouped them into deciles. The highest decile group had a 2.6-fold (95% CI; 1.8, 3.7) increase in the risk of developing a MG, P &lt; 0.001. We demonstrate for the first time, the increased risk of developing MG in patients with elevated serum FLC, suggesting that an underlying inflammatory state may play an etiologic role.
EFFECTIVENESS AND TOLERABILITY OF VERY LOW VOLUME PREPARATION FOR COLONOSCOPY: A PROSPECTIVE, MULTICENTER STUDY
Authors: M Maida, G Morreale, E Sinagra, M Manganaro, D Schillaci, A Cirrone Cipolla, S Garufi, S Camilleri
Journal: Endoscopy (2019)

Effectiveness and tolerability of bowel cleansing is essential for a quality colonoscopy. The aims of this study were to assess the effectiveness and tolerability of novel 1L PEG preparation compared to 4L and 2L PEG solutions and to evaluate factors associated with a bowel cleansing success.
Evaluation of pathological complete response as a trial-level surrogate for long-term survival outcomes among triple-negative breast cancer patients receiving neoadjuvant therapy
Authors: M. Huang, C.Z. Qi, S. Ramsey, A. Briggs, J. Zhao, A. Haiderali, V. Karantza, J. Xie, C. Gu, P.A. Fasching
Journal: Annals of Oncology (2019)

Background: Pathological complete response (pCR) is a commonly used endpoint in neoadjuvant trials for breast cancer (BC). A pooled analysis sponsored by FDA (Cortazar et al, 2014) showed pCR is a significant predictor of survival outcomes; however, it found little association between magnitude of difference in pCR rates and difference in survival between treatment arms in general BC or triple negative BC (TNBC). To reflect more recent evidence, this study aimed to update and focus the evaluation on the trial-level association between pCR and survival outcomes in TNBC. Methods: Randomized controlled trials (RCTs) of neoadjuvant treatments for TNBC were identified through a targeted literature review (TLR) of publications all years through October 2018. RCTs that reported outcomes for both pCR and event-free survival (EFS) or overall survival (OS) in TNBC were included. Similarly as in Cortazar 2014, a weighted linear regression analysis on a logarithmic scale was performed based on odds ratios for pCR and hazard ratios for EFS/OS within each RCT. The coefficient of determination (R²) was used to measure the trial-level association between the treatment effects on pCR and survival. Scenario analyses were conducted to assess the impact of divergent study designs and pCR definitions across the RCTs. Results: Ten comparisons from 8 RCTs were identified by the TLR, which were all published after the Cortazar study. The primary analysis reported a moderate association between the improvement in pCR and EFS (R²=0.79). The R² between the improvement in pCR and OS was 0.42. Similar association was found in all scenario analyses. Conclusions: Although uncertainty remains as to the validity of the trial-level surrogate, with availability of more TNBC-focused trials, this study demonstrated substantially stronger trial-level association between pCR and survival outcomes in TNBC compared with the findings in previous studies. With the increasing trend of TNBC-focused drug development, more robust evidence and sufficient amount of data may be available in the near future to address the uncertainty with respect to the association between pCR and long-term survival. Legal entity responsible for the study: Merck & Co., Inc. Funding: Merck & Co., Inc. Disclosure: M. Huang, J. Zhao, A. Haiderali, V. Karantza: Employee: Merck & CO., Inc. C.Z. Qi, J. Xie, C. Gu: Employee: Analysis Group, which received funding from Merck & CO., Inc. to conduct this work. S. Ramsey: Consultant: Merck, AstraZeneca, Bayer, BMS, Genentech; Board of directors: LabKey A. Briggs, P.A. Fasching: Consultant of Merck & Co., Inc.
Breast cancer in young women: A multi-center 10-year experience
Authors: I.F. Eiriz, N.G. Pereira, M.T. Neves, M.V. Batista, T.C. Tomás, S. Braga
Journal: Annals of Oncology (2019)

Background: Breast cancer is the most frequent cancer diagnosed in adult young women in Europe. Although rare (<5% before 35 years), it is one of the leading causes of death in this age group. The aim of this study is to characterize a cohort of young women regarding incidence, tumor stage, biology, treatment and survival. Methods: We present a retrospective multi-center study of women less than 35 years old, diagnosed with breast cancer between 2008 and 2017. A total of 207 patients from 5 centers were included. Thirty five were excluded: 27 due to lack of data, 1 due to two different synchronous tumors and 7 had ductal in situ carcinoma. Data was analyzed using IBM SPPS statistics. Results: Median age was 31 years and ductal invasive carcinoma was the most frequent histologic subtype (91%). In the analysis of tumor subtype: 4% of tumors were luminal A, 20% luminal B HER2 positive, 47% luminal B HER2 negative, 8% HER2 positive (hormone receptor negative) and 20% triple negative. Forty eight percent of patients were diagnosed with early breast cancer, 45% were locally advanced and 6% had de novo metastatic cancer. Thirty nine percent of patients were treated with neoadjuvant chemotherapy (CT) and pathological complete response was obtained in 12%. Eighty three percent of patients were treated with adjuvant systemic therapy (CT or endocrine therapy), 18% exclusively with endocrine therapy. The median follow-up time was 53,5 months. Metastatic disease developed in 37 patients: 7 patients with bone metastasis only, 17 with both bone and visceral metastasis and 14 patients with central nervous system in addition to bone and visceral disease. The median survival of metastatic patients was 16,5 months. Local recurrence occurred in 3 patients with a median time of 27 months. Eighty five percent of these women are alive. Conclusions: As expected, frequency of HER2 positive and triple negative tumors is increased in this age group, and the frequency of locally advanced and de novo metastatic disease is more prevalent. The median survival of metastatic patients is low in this age group as is the median survival. Due to more aggressive biology, initial staging and survival, the group of very young women with breast cancer deserves special treatment approaches. Legal entity responsible for the study: Inês Fernandes Eiriz. Funding: Has not received any funding. Disclosure: All authors have declared no conflicts of interest.
Ancestral Admixture Is the Main Determinant of Global Biodiversity in Fission Yeast
Authors: Sergio Tusso, Bart P S Nieuwenhuis, Fritz J Sedlazeck, John W Davey, Daniel C Jeffares, Jochen B W Wolf
Journal: Molecular Biology and Evolution (2019)

Mutation and recombination are key evolutionary processes governing phenotypic variation and reproductive isolation. We here demonstrate that biodiversity within all globally known strains of Schizosaccharomyces pombe arose through admixture between two divergent ancestral lineages. Initial hybridization was inferred to have occurred ∼20-60 sexual outcrossing generations ago consistent with recent, human-induced migration at the onset of intensified transcontinental trade. Species-wide heritable phenotypic variation was explained near-exclusively by strain-specific arrangements of alternating ancestry components with evidence for transgressive segregation. Reproductive compatibility between strains was likewise predicted by the degree of shared ancestry. To assess the genetic determinants of ancestry block distribution across the genome, we characterized the type, frequency, and position of structural genomic variation using nanopore and single-molecule real-time sequencing. Despite being associated with double-strand break initiation points, over 800 segregating structural variants exerted overall little influence on the introgression landscape or on reproductive compatibility between strains. In contrast, we found strong ancestry disequilibrium consistent with negative epistatic selection shaping genomic ancestry combinations during the course of hybridization. This study provides a detailed, experimentally tractable example that genomes of natural populations are mosaics reflecting different evolutionary histories. Exploiting genome-wide heterogeneity in the history of ancestral recombination and lineage-specific mutations sheds new light on the population history of S. pombe and highlights the importance of hybridization as a creative force in generating biodiversity.
IRRIGATION OF THE INCOMPLETE SILVER SALT OF POLYACRYLIC ACID CONTAINING SILVER NANOPARTICLES IN HEMOSTASIS FOR INTRA-BIOPSY/POLYPECTOMY COLONIC BLEEDING
Authors: V Viktor, S Sergey, O Olga
Journal: Endoscopy (2019)

The endoscopic hemostasis techniques and tools growth in parallel with the new techniques of endoscopic surgery. Clinical endoscopist must be aware of all available hemostatic tool to optimize the management of bleeding in daily practice. This study aims to assess usefulness of the new irrigation technique for intraprocedural colonic bleeding.
Développement de critères cholangioscopiques pour le diagnostic des sténoses biliaires indéterminées
Authors: H Elbacha, H Rafik, S Leblanc, S Grabar, B Vedrenne, B Napoléon, F Fumex, K Barange, R Laugier, F Prat
Journal: Endoscopy (2019)

La cholangioscopie permet une exploration endoscopique des voies biliaires et améliore les performances diagnostiques lors de l'exploration des sténoses biliaires par rapport aux autres techniques d'imagerie. Cependant, l'interprétation des images cholangioscopiques reste subjective en l'absence d'une classification de référence. L'objectif de notre étude est d'établir des critères d'analyse visuelle permettant de distinguer les lésions bénignes et malignes.
ENDOSCOPIC SUBMUCOSAL DISSECTION OF GASTRIC TUMOURS: EXPERIENCE FROM THREE LARGE EUROPEAN TERTIARY CENTRES
Authors: M Abdelrahim, K Kandiah, P Bhandari, A Repici, S Seewald, R Masseli, M Invernizzi, A Alkandari, E Hossain, S Arndtz
Journal: Endoscopy (2019)

We aim to review the efficacy and safety of ESD for early gastric neoplasia from three large European referral centres.
Estimated Ages of JUUL Twitter Followers
Authors: Annice E. Kim, Robert Chew, Michael Wenger, Margaret Cress, Thomas Bukowski, Matthew Farrelly, Elizabeth Hair
Journal: JAMA Pediatrics (2019)

Discussion | This study should be interpreted in the context of its limitations; like other survey studies, there is potential for recall bias and possible selection bias for more technologysavvy parents, given that the survey was administered online.Millennial parents had higher DDS scores than older parents, demonstrating riskier behavior that is associated with the motor vehicle crash rate.However, texting while driving was common among millennial and older parents.A low proportion of parents said their pediatrician had spoken to them about distracted driving, and few parents used an app to restrict texting while driving; both are areas for potential intervention.
Focal Peritoneal Mesothelioma Demonstrated on FDG PET/CT
Authors: Jie Xiao, Hongyan Yin, Dengfeng Cheng, Hongcheng Shi, Yan Xiu
Journal: Clinical Nuclear Medicine (2019)

Abstract A 48-year-old woman was experiencing abdominal pain and melena for 3 months. Because of these symptoms combined with increased level of tumor marker CA125, possible abdominal malignancy was considered, and an FDG PET/CT was performed to assess occult tumor. The images revealed multiple hypermetabolic lesions along the peritoneal surface. Pathological examination after biopsy demonstrated low-grade epithelioid peritoneal mesothelioma.
Abstract 19291: Iron Deprivation Inhibits mTOR Activity by Regulating Amino Acid Homeostasis
Authors: Jason S Shapiro, Hsiang-Chun Chang, Tatsuya Sato, Konrad T Sawicki, Meng Shang, Marina Bayeva, Gary Lopaschuk, Perry J Blackshear, Hossein Ardehali
Journal: Circulation (2017)

Background: Cells require iron to carry out myriad enzymatic functions necessary for growth and metabolism. Derangements in cellular iron regulation have been linked to multiple forms of both genet...
LUMEN-APPOSING METAL STENT (LAMS) DISLODGMENT DURING POST-BARIATRIC ERCP: ENDOSCOPIC BRIDGING WITH A DOUBLE-CHANNEL ENDOSCOPE
Authors: S Bazaga, R Sánchez-Ocaña, A Yaiza Carbajo, FJ García-Alonso, M de Benito, C de la Serna Higuera, M Pérez-Miranda
Journal: Endoscopy (2019)

EUS directed trans-gastric ERCP allows access to the excluded stomach through a gastro-gastrostomy in Roux-en-Y gastric bypass. We similarly fashioned a jejuno-jejunal EUS-guided LAMS anastomosis to allow through-the-stent (TTS) ERCP in a patient with recurrent pancreatitis and duodenal switch (DS), a bariatrically altered anatomy distinctly precluding peroral ERCP. We present techniques for localizing the biliary limb in DS and for managing LAMS dislodgment.
2019 update of the EULAR recommendations for the management of SLE: don’t forget chloroquine
Authors: Gabriel Figueroa-Parra, Carmen Magdalena Gamboa-Alonso, Ana Laura De-Leon-Ibarra, Dionicio Angel Galarza-Delgado
Journal: Annals of the Rheumatic Diseases (2019)

2019 update of the EULAR recommendations for the management of SLE: don't forget chloroquineRecently, the journal published the 2019 update of the European League Against Rheumatism (EULAR) recommendations for the management of systemic lupus erythematosus (SLE) 1 that we reviewed with great interest.It drew our attention that the lack of mention of chloroquine as another option in the treatment of SLE within the antimalarials drugs, considering this an important omission that should be taken into consideration.3][4][5][6] We also agree that because of having a safer drug profile with less side effects, hydroxychloroquine should be preferred over chloroquine; nevertheless, the availability in other regions of the world could be variable and also, we should take into consideration the higher cost of hydroxychloroquine over chloroquine that in middle-income and low-income countries could be a bigger consideration.We understand that the recommendations are aimed mostly to the European community, and even when there have been major efforts to counteract the geographic differences with the developing of recommendations adapted to every region, 7-9 we believe from a global perspective that there are countries who continue supporting their clinical decisions on recommendations made by the most important associations in the world.This is the reason, we consider pertinent to highlight this observation.
Inferring the Evolution and Progression of Small-Cell Lung Cancer by Single-Cell Sequencing of Circulating Tumor Cells
Authors: Zhe Su, Zhijie Wang, Xiaohui Ni, Jianchun Duan, Yan Gao, Minglei Zhuo, Ruoyan Li, Jun Zhao, Qi Ma, Hua Bai, Hengyu Chen, Shuhang Wang, Xixi Chen, Tongtong An, Yuyan Wang, Yanhua Tian, Jiangyong Yu, Di Wang, Xiaoliang Sunney Xie, Fan Bai, Jie Wang
Journal: Clinical Cancer Research (2019)

Abstract Purpose: Genomic analyses of small-cell lung cancer (SCLC) are limited by the availability of tumor specimens. This study aimed to investigate the suitability of single-cell sequencing of circulating tumor cells (CTC) as a method of inferring the evolution and progression of SCLCs. Experimental Design: Between July 1, 2011, and July 28, 2014, 48 consecutively diagnosed patients with SCLC were recruited for this study. CTCs were captured from each patient with CellSearch system. Somatic mutations and copy number alterations (CNA) were monitored by single-cell sequencing of CTCs during chemotherapy. Results: Single-cell sequencing of CTCs can provide a mutational atlas for SCLC. A 10-CNA score based on single CTCs was established as a classifier for outcomes of initial chemotherapy in patients with SCLC. The survival analyses demonstrated that patients with low CNA scores (&amp;lt;0) had significantly prolonged progression-free survival (PFS) and overall survival (OS) after first-line chemotherapy in comparison with those with high scores (≥0; PFS: 212 days vs. 110.5 days, P = 0.0042; and OS: 223.5 days vs. 424 days, P = 0.0006). The positive predictive value and negative predictive value of the CNA score for clinical subtype (refractory vs. sensitive) were 80.0% and 93.7%, respectively. By tracing allele-specific CNAs in CTCs isolated at different time points during chemotherapy, we showed that CNA heterogeneity might result from allelic losses of initially consistent CNAs. Conclusions: Single CTC-based sequencing can be utilized to depict the genomic profiles and evolutionary history of SCLC, thus offering the potential for clinical stratification of patients with SCLC.
A Student Reflection on Doctoring With Confidence
Authors: John E. Coda
Journal: Annals of Internal Medicine (2019)

Letters21 May 2019A Student Reflection on Doctoring With ConfidenceJohn E. Coda, BSJohn E. Coda, BSPenn State College of Medicine, Hershey, Pennsylvania (J.E.C.)Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/L19-0120 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail TO THE EDITOR:I read Treadway's (1) reflection on the confidence gap and her experiences of this phenomenon in her clinical training with interest. Early in my third year of medical school, as part of a primary care clerkship, I took part in a series of standardized patient encounters meant to evaluate our ability as effective communicators. After 1 encounter, I received feedback from an actor portraying a patient that I had voiced uncertainty too often when he challenged me. He also noted that I began my responses with modifiers, such as “I think.” Puzzled, I asked the actor how ...References1. Treadway N. A student reflection on doctoring with confidence: mind the gap. Ann Intern Med. 2018;169:564-5. [PMID: 30208402]. doi:10.7326/M18-0865 LinkGoogle Scholar2. Lee KB, Vaishnavi SN, Lau SK, Andriole DA, Jeffe DB. “Making the grade”: noncognitive predictors of medical students' clinical clerkship grades. J Natl Med Assoc. 2007;99:1138-50. [PMID: 17987918] MedlineGoogle Scholar Author, Article, and Disclosure InformationAffiliations: Penn State College of Medicine, Hershey, Pennsylvania (J.E.C.)Disclosures: The author has disclosed no conflicts of interest. The form can be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=L19-0120. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetailsSee AlsoA Student Reflection on Doctoring With Confidence: Mind the Gap Nicole Treadway A Student Reflection on Doctoring With Confidence Juan N. Lessing and Mary E. Lacy A Student Reflection on Doctoring With Confidence Nicole Treadway A Student Reflection on Doctoring With Confidence Richard L. Kravitz Metrics 21 May 2019Volume 170, Issue 10Page: 738KeywordsConflicts of interestDisclosurePopulation statisticsRacial and ethnic issuesSexual identity ePublished: 21 May 2019 Issue Published: 21 May 2019 Copyright & PermissionsCopyright © 2019 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
The Use of Radiation Therapy for the Treatment of Malignant Pleural Mesothelioma: Expert Opinion from the National Cancer Institute Thoracic Malignancy Steering Committee, International Association for the Study of Lung Cancer, and Mesothelioma Applied Research Foundation
Authors: Daniel R. Gomez, Andreas Rimner, Charles B. Simone, B.C. John Cho, Marc de Perrot, Alex A. Adjei, Raphael Bueno, Ritu R. Gill, David H. Harpole, Mary Hesdorffer, Fred R. Hirsch, Andrew A. Jackson, Harvey I. Pass, David C. Rice, Valerie W. Rusch, Anne S. Tsao, Ellen Yorke, Kenneth Rosenzweig
Journal: Journal of Thoracic Oncology (2019)

IntroductionDetailed guidelines regarding the use of radiation therapy for malignant pleural mesothelioma (MPM) are currently lacking because of the rarity of the disease, the wide spectrum of clinical presentations, and the paucity of high-level data on individual treatment approaches.MethodsIn March 2017, a multidisciplinary meeting of mesothelioma experts was cosponsored by the U.S. National Cancer Institute, International Association for the Study of Lung Cancer Research, and Mesothelioma Applied Research Foundation. Among the outcomes of this conference was the foundation of detailed, multidisciplinary consensus guidelines.ResultsHere we present consensus recommendations on the use of radiation therapy for MPM in three discrete scenarios: (1) hemithoracic radiation therapy to be used before or after extrapleural pneumonectomy; (2) hemithoracic radiation to be used as an adjuvant to lung-sparing procedures (i.e., without pneumonectomy); and (3) palliative radiation therapy for focal symptoms caused by the disease. We discuss appropriate simulation techniques, treatment volumes, dose fractionation regimens, and normal tissue constraints. We also assess the role of particle beam therapy, specifically, proton beam therapy, for MPM.ConclusionThe recommendations provided in this consensus statement should serve as important guidelines for developing future clinical trials of treatment approaches for MPM.