tbuckley/cabot-search huggingface dataset:
Yield of Surveillance Colonoscopies 1 Year After Curative Surgical Colorectal Cancer Resections
Authors: Meta C.J. van Lanschot, Monique E. van Leerdam, Iris Lansdorp-Vogelaar, Sharon Doets, Iris D. Nagtegaal, Hermien W. Schreurs, René W.M. van der Hulst, Beatriz Carvalho, Evelien Dekker, Anne-Marie van Berkel
Journal: Clinical Gastroenterology and Hepatology (2019)
The Challenges and Opportunities of Small Effects
Authors: Martin P. Paulus, Wesley K. Thompson
Journal: JAMA Psychiatry (2019)

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Reexamining the Open-Vein Hypothesis for Acute Deep Venous Thrombosis
Authors: Ashwin S. Nathan, Jay Giri
Journal: Circulation (2019)

The advent of catheter-based therapies and synthetic thrombolytics has allowed physicians to assume a more active role in the treatment of DVT.Proponents of thrombolytic and catheter-based therapies are adherents of the open-vein hypothesis, whereby early and active removal of thrombus may improve deep venous
Abstract 17908: Changes in Gut Microbiome Early After Fontan Operation
Authors: Jyoti K Patel, Ceylan E Tanes, Kyle Bittinger, Kathryn Dodds, David J Goldberg, Frederic D Bushman, Gary D Wu, Jack Rychik
Journal: Circulation (2016)

Introduction: A growing body of evidence supports the role of the gut microbiome in human health and well-being. The unique physiological conditions imposed by the Fontan operation (FO) may influen...
Radiofrequency ablation (RFA) combined with chemotherapy for unresectable colorectal liver metastases (CRC LM): Interim results of a randomised phase II study of the EORTC-NCRI CCSG-ALM Intergroup 40004 (CLOCC)
Authors: T. Ruers, F. van Coevorden, J. Pierie, I. Borel Rinkes, C. Punt, J. Ledermann, G. J. Poston, W. Bechstein, M. Lentz, L. Collette, B. Nordlinger
Journal: Journal of Clinical Oncology (2008)

4012 Background: In patients with a limited number of unresectable CRC LM there is an increasing tendency to combine systemic chemotherapy (CT) with local tumour destruction by RFA. However, the benefit of this combined treatment has not been proven. Methods: This study evaluated the addition of RFA to systemic CT in patients with unresectable CRC LM up to 9 lesions and without extrahepatic disease. Between April 2002 and June 2007, 119 pts were randomised between CT alone or CT plus RFA (alone or combined with surgical resection). In both arms, CT consisted of 6 months FOLFOX (oxaliplatin 85mg/m2 and LV5FU2) plus, since October 2005, bevacizumab. Primary endpoint was overall survival at 30 months. Safety and feasibility were secondary endpoints. Results: Treatment data are available for 101 of 113 patients recruited before 2007. Two of 56 allocated to CT never started treatment due to progression, while 7 of 57 allocated to RFA never started CT, three due to postoperative complications; toxicity data are available for 92 patients (45 RFA, 47 CT arm) having received at least one cycle of CT. Baseline characteristics were similar between arms: 60% had ≥ 4 LM. Twenty-four in each arm completed the full CT (53.3% RFA, 51.0% CT arm). CT was discontinued for toxicity and progression in 23% and 7.5% of patients in the RFA arm versus 16% and 17% in the CT arm. Toxicity profiles were identical between arms. Grade ≥ 3 haematological toxicity (ANC) was 24% in the RFA arm and 23% in the CT arm. Grade ≥ 3 diarrhoea, nausea, neurotoxicity and fatigue were reported in 18%, 13%, 20% and 11% of patients in the RFA arm and 15%, 11%, 11% and 0% in the CT arm, respectively. Complications after RFA were observed in 22% of patients: fever 11%, fatigue 6.6% and wound infection 4.4%. There was one post-operative death (2.2%). Conclusion: This is the first study that prospectively investigates the efficacy of RFA in combination with CT. Combined treatment of RFA plus CT was safely performed. Data on time to progression will become available in Spring 2008. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Boston Scientific, sanofi-aventis
Interim 2018/19 influenza vaccine effectiveness: six European studies, October 2018 to January 2019
Authors: Esther Kissling, Angela Rose, Hanne-Dorthe Emborg, Alin Gherasim, Richard Pebody, Francisco Pozo, Ramona Trebbien, Clara Mazagatos, Heather Whitaker, Marta Valenciano
Journal: Eurosurveillance (2019)

Influenza A(H1N1)pdm09 and A(H3N2) viruses both circulated in Europe in October 2018-January 2019. Interim results from six studies indicate that 2018/19 influenza vaccine effectiveness (VE) estimates among all ages in primary care was 32-43% against influenza A; higher against A(H1N1)pdm09 and lower against A(H3N2). Among hospitalised older adults, VE estimates were 34-38% against influenza A and slightly lower against A(H1N1)pdm09. Influenza vaccination is of continued benefit during the ongoing 2018/19 influenza season.
Nilotinib Deregulates Cell Cycle Checkpoints, ABC Transporters Genes and JAK-STAT Signaling Pathway of CD34+/Lin- Cells in Chronic-Phase Chronic Myeloid Leukemia (CP-CML) Patients after 12 Months of Treatment
Authors: Alessandra Trojani, Ester Pungolino, Giuseppe Rossi, Mariella D'adda, Milena Lodola, Alessandra Dal Molin, Giacomo Baruzzo, Alessandra Perego, Mauro Turrini, Chiara Elena, Lorenza Maria Borin, Alessandra Iurlo, Simona Malato, Francesco Spina, Maria Luisa Latargia, Pierangelo Spedini, Salvatore Artale, Michela Anghilieri, Carraro Maria Cristina, Cristina Bucelli, Gabriella De Canal, Enrica Morra, Roberto Cairoli
Journal: Blood (2018)
Relative Prognostic Importance and Optimal Levels of Risk Factors for Mortality and Cardiovascular Outcomes in Type 1 Diabetes Mellitus
Authors: Aidin Rawshani, Araz Rawshani, Naveed Sattar, Stefan Franzén, Darren K. McGuire, Björn Eliasson, Ann-Marie Svensson, Björn Zethelius, Mervete Miftaraj, Annika Rosengren, Soffia Gudbjörnsdottir
Journal: Circulation (2019)

Background: The strength of association and optimal levels for risk factors related to excess risk of death and cardiovascular outcomes in type 1 diabetes mellitus have been sparsely studied. Methods: In a national observational cohort study from the Swedish National Diabetes Register from 1998 to 2014, we assessed relative prognostic importance of 17 risk factors for death and cardiovascular outcomes in individuals with type 1 diabetes mellitus. We used Cox regression and machine learning analyses. In addition, we examined optimal cut point levels for glycohemoglobin, systolic blood pressure, and low-density lipoprotein cholesterol. Patients with type 1 diabetes mellitus were followed up until death or study end on December 31, 2013. The primary outcomes were death resulting from all causes, fatal/nonfatal acute myocardial infarction, fatal/nonfatal stroke, and hospitalization for heart failure. Results: Of 32 611 patients with type 1 diabetes mellitus, 1809 (5.5%) died during follow-up over 10.4 years. The strongest predictors for death and cardiovascular outcomes were glycohemoglobin, albuminuria, duration of diabetes mellitus, systolic blood pressure, and low-density lipoprotein cholesterol. Glycohemoglobin displayed ≈2% higher risk for each 1-mmol/mol increase (equating to ≈22% per 1% glycohemoglobin difference), whereas low-density lipoprotein cholesterol was associated with 35% to 50% greater risk for each 1-mmol/L increase. Microalbuminuria or macroalbuminuria was associated with 2 to 4 times greater risk for cardiovascular complications and death. Glycohemoglobin &lt;53 mmol/mol (7.0%), systolic blood pressure &lt;140 mm Hg, and low-density lipoprotein cholesterol &lt;2.5 mmol/L were associated with significantly lower risk for outcomes observed. Conclusions: Glycohemoglobin, albuminuria, duration of diabetes mellitus, systolic blood pressure, and low-density lipoprotein cholesterol appear to be the most important predictors for mortality and cardiovascular outcomes in patients with type 1 diabetes mellitus. Lower levels for glycohemoglobin, systolic blood pressure, and low-density lipoprotein cholesterol than contemporary guideline target levels appear to be associated with significantly lower risk for outcomes.
Chlamydial infections. Pt. 1.
Authors: Schachter J
Journal: New England Journal of Medicine (1978)

At this time what might be termed the 5th epidemic of interest in the chlamydiae a diverse group of microorganisms containing a number of pathogens that are important in both human and animal diseases is occurring.  Focus in this discussion of chlamydial infections is on taxonomy microbiology and latency.  The chlamydiae due to a unique developmental cycle that differentiates them from all other microorganisms have been placed in their own order--the chlamydiales.  There is 1 genus chlamydia and 2 species--Chlamydia psittaci and C. trachomatis.  All members of the genus share a common antigen.  The species can be differentiated on the basis of inclusion type.  C. trachomatis inclusions stain with iodine; C. psittaci inclusions do not.  Additionally C. trachomatis is sensitive to sulfonamides and C. psittaci is resistant.  A table lists the human diseases caused by chlamydia.  C. psittaci includes the organisms responsible for human psittacosis and for the avian infections that may ultimately cause the human disease.  Additionally different strains of C. psittaci cause a wide variety of diseases of animals.  Economically prominent among these are abortions arthritis and other systemic infections in sheep and cattle.  C. trachomatis includes the organisms responsible for trachoma inclusion conjunctivitis genital-tract infections and lymphogranuloma venereum.  With the exception of a few strains of rodent pneumonitis the C. trachomatis strains are human pathogens with the human as the sole natural host whereas C. psittaci strains appear to involve human diseases only as zoonoses.  C. trachomatis strains of human origin are more homogeneous.  The chlamydiae are obligatory intracellular parasites once considered to be large viruses sensitive to the action of some antimicrobials or antibiotics but a more sophisticated definition of viruses and bacteria has permitted the recognition that the chlamydiae are bacteria like and definitely not viruses.  They differ from the viruses in having 2 nucleic acids and in having a discrete cell wall quite analagous in structure and content to those of the gram negative bacteria.  The chlamydiae have a restricted metabolic capability and multiply within the host cell by binary fission.  They undergo no eclipse phase.  They are susceptible to antibiotics.  Careful study of any natural chlamydial host shows a substantial degree of latent or inapparent infections.  There is no convincing evidence that chlamydiae persist in the intact host in a nonreplicating form.  It is more likely that latent or subclinical infections represent persistent low levels of multiplication held in check by host defense mechanisms.  C. trachomatis infections of the genital tract represent the major focus of current interest in the chlamydia.  Chlamydia recovery has been associated with nongonococcal urethritis at a statistically significant level.  The implications of the double infection with chlamydiae in gonorrhea are clear; chlamydiae are responsible for approximately 70% of postgonococcal urethritis.
A Phase I Study of Pegylated Arginine Deiminase (Pegargiminase), Cisplatin, and Pemetrexed in Argininosuccinate Synthetase 1-Deficient Recurrent High-grade Glioma
Authors: Peter E. Hall, Rachel Lewis, Nelofer Syed, Richard Shaffer, Jane Evanson, Stephen Ellis, Matthew Williams, Xiaoxing Feng, Amanda Johnston, Jim A. Thomson, Fiona P. Harris, Raj Jena, Tomasz Matys, Sarah Jefferies, Kate Smith, Bor-Wen Wu, John S. Bomalaski, Timothy Crook, Kevin O'Neill, Dimitris Paraskevopoulos, Ramsay S. Khadeir, Michael Sheaff, Simon Pacey, Piers N. Plowman, Peter W. Szlosarek
Journal: Clinical Cancer Research (2019)

Abstract Purpose: Patients with recurrent high-grade gliomas (HGG) are usually managed with alkylating chemotherapy ± bevacizumab. However, prognosis remains very poor. Preclinically, we showed that HGGs are a target for arginine depletion with pegargiminase (ADI-PEG20) due to epimutations of argininosuccinate synthetase (ASS1) and/or argininosuccinate lyase (ASL). Moreover, ADI-PEG20 disrupts pyrimidine pools in ASS1-deficient HGGs, thereby impacting sensitivity to the antifolate, pemetrexed. Patients and Methods: We expanded a phase I trial of ADI-PEG20 with pemetrexed and cisplatin (ADIPEMCIS) to patients with ASS1-deficient recurrent HGGs (NCT02029690). Patients were enrolled (01/16–06/17) to receive weekly ADI-PEG20 36 mg/m2 intramuscularly plus pemetrexed 500 mg/m2 and cisplatin 75 mg/m2 intravenously once every 3 weeks for up to 6 cycles. Patients with disease control were allowed ADI-PEG20 maintenance. The primary endpoints were safety, tolerability, and preliminary estimates of efficacy. Results: Ten ASS1-deficient heavily pretreated patients were treated with ADIPEMCIS therapy. Treatment was well tolerated with the majority of adverse events being Common Terminology Criteria for Adverse Events v4.03 grade 1-2. The best overall response was stable disease in 8 patients (80%). Plasma arginine was suppressed significantly below baseline with a reciprocal increase in citrulline during the sampling period. The anti–ADI-PEG20 antibody titer rose during the first 4 weeks of treatment before reaching a plateau. Median progression-free survival (PFS) was 5.2 months (95% confidence interval (CI), 2.5–20.8) and overall survival was 6.3 months (95% CI, 1.8–9.7). Conclusions: In this recurrent HGG study, ADIPEMCIS was well tolerated and compares favorably to historical controls. Additional trials of ADI-PEG20 in HGG are planned.
P080 The effect of activin a and follistatin on the interaction of endothelial cells and rheumatoid arthritis synovial fibroblasts
Authors: I Aykara, M Diller, S Rehart, U Müller-Ladner, E Neumann
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Career situation of first and presenting author</h3> Student for a master or a PhD. <h3>Introduction</h3> The autoregulatory cycle of activin A and its antagonist follistatin is well known in the hypothalamic-pituitary-gonadal axis, but activins also play an important role in autoimmune diseases, such as rheumatoid arthritis (RA). Due to inflammation, activin A is released, then inducing its antagonist follistatin. This negative feedback mechanism has been primarily described in hepatocytes, but is inactive in synovial fibroblasts from patients with rheumatoid arthritis (RASF). Synovial fibroblasts are mediators of cartilage destruction in RA. In inflamed synovium, there is an interaction of RASF with endothelial cells. Due to tissue hyperplasia and inflammation, neoangiogenesis, mediated in part by local fibroblasts, is increased in RA synovium. The effect of activin and follistatin on the interaction of RASF and endothelial cells is still unknown. <h3>Objectives</h3> This study focuses on the effect of the activin A and follistatin on the interaction of RASF and endothelial cells. <h3>Methods</h3> RASF were isolated from synovial tissue of patients with RA undergoing joint replacement surgery. Endothelial cells (HUVEC) were commercially obtained. RASF and HUVEC were stimulated in mono-, or coculture with activin A (15 ng/ml), follistatin (500 ng/ml) or IL-1β (1 ng/ml). After 18 hour the supernatants were collected and the concentrations of activin A, VEGF and IL-6 were measured by ELISA. <h3>Results</h3> IL-1β induced activin A release in RASF and HUVECs alone as well as in direct coculture. The stimulation with follistatin and IL-1β at the same time reduced the activin A concentration in HUVECs as well as in cocultures in comparison to stimulation with IL-1β alone (p&lt;0.05; n=4). In monocultures of RASF this reduction could not be detected. With respect to HUVECs, a significant reduction (p&lt;0.05) of the proinflammatory cytokine IL-6 after stimulation with activin A and IL-1β in comparison to the stimulation with IL-1β alone could be observed. The release of VEGF, which plays an important role in inflammation-induced neoangiogenesis, was induced in RASF with IL-1β (89%), activin A (55%), activin A and IL-1β (148%), follistatin and IL-1β (84%). In coculture with HUVECs, the induction was less pronounced as in monoculture (IL-1β (75%), activin A (22%), activin A and IL-1β (101%), follistatin and IL-1β (67%)). <h3>Conclusions</h3> The autoregulatory cycle of activin A and follistatin is active in HUVECs, but not in RASF. In direct coculture of HUVECs and RASF, the effects of HUVECs appear to overweigh resulting in a significant reduction of IL-1β in the presence of follistatin. <h3>Disclosure of Interest</h3> None declared.
Risk Factors for Hospital-Acquired Venous Thromboembolism in Children: Findings from the Children's Hospital-Acquired Thrombosis (CHAT) Registry
Authors: Brian R. Branchford, Julie Jaffray, Stacy E. Croteau, Michael Silvey, Nihal Bakeer, James D. Cooper, John H. Fargo, Lingyun Ji, Richard Sposto, Jemily Malvar, Emily Krava, Amy Stillings, Neil A Goldenberg, Guy Young, Arash Mahajerin
Journal: Blood (2018)
Clinical Outcomes of Escalation vs Early Intensive Disease-Modifying Therapy in Patients With Multiple Sclerosis
Authors: Katharine Harding, Owain Williams, Mark Willis, James Hrastelj, Anthony Rimmer, Fady Joseph, Valentina Tomassini, Mark Wardle, Trevor Pickersgill, Neil Robertson, Emma Tallantyre
Journal: JAMA Neurology (2019)

<h3>Importance</h3> Uncertainty remains about how aggressively to treat early multiple sclerosis. High-efficacy disease-modifying therapies (DMTs) are often reserved for individuals expressing poor prognostic features at baseline. <h3>Objective</h3> To analyze long-term outcomes in a population-based cohort according to initial treatment strategy. <h3>Design, Setting and Participants</h3> In this cohort study, data were derived from January 1998 to December 2016, and analysis was performed in January 2017. From a total of 720 patients prescribed a DMT, 592 (82%) were included in analysis. Reasons for exclusion were first treated elsewhere or privately (n = 39), clinical trial participant (n = 25), and insufficient clinical data (n = 45). <h3>Exposures</h3> Patients were classified according to first-line treatment strategy: high-efficacy (early intensive treatment [EIT]) or moderate-efficacy DMT (escalation [ESC]). <h3>Main Outcomes and Measures</h3> Primary outcome was 5-year change in Expanded Disability Status Scale score. Secondary outcome was time to sustained accumulation of disability (SAD). Models were adjusted for sex, age at treatment, year of starting DMT, and escalation to high-efficacy treatment in the ESC group. <h3>Results</h3> Mean (SD) age of 592 patients at symptom onset was 27.0 (9.4) years. Mean (SD) 5-year change in Expanded Disability Status Scale score was lower in the EIT group than the ESC group (0.3 [1.5] vs 1.2 [1.5]); this remained significant after adjustment for relevant covariates (β = −0.85; 95% CI, −1.38 to −0.32;<i>P</i> = .002). Median (95% CI) time to SAD was 6.0 (3.17-9.16) years for EIT and 3.14 (2.77-4.00) years for ESC (<i>P</i> = .05). For those within the ESC group who escalated to high-efficacy DMT as second-line treatment, median (95% CI) time to SAD was 3.3 years (1.8-5.6; compared with EIT group log-rank test<i>P</i> = .08). After adjustment for relevant covariates, there was no difference in hazard of SAD between the groups. However, 60% of those who escalated to high-efficacy DMTs were observed to develop SAD while still receiving initial moderate-efficacy treatment before escalation. <h3>Conclusions and Relevance</h3> In a real-life setting, long-term outcomes were more favorable following early intensive therapy vs first-line moderate-efficacy DMT. Contemporary surveillance strategies and escalation protocols may be insufficiently responsive. This finding is particularly relevant as patients in real-world practice are typically selected for an EIT approach to therapy on the basis of clinical and radiological features predictive of a poor outcome. These data support the need for a prospective randomized clinical trial.
Abstract P6-07-01: Withdrawn
Authors: EM Jiagge, S Wong, R Gilani, T Luthur, J Bensenhaver, JK Oppong, I Kyei, E Adjei, B Awuah, J Li, J Carpten, M Wicha, L Newman, S Merajver
Journal: Cancer Research (2018)

Abstract This abstract was withdrawn by the authors.
Cystic fibrosis papers of the year 2008
Authors: Ian M Balfour-Lynn
Journal: Journal of the Royal Society of Medicine (2009)

The literature search was conducted using PubMed (www.ncbi.nlm.nih.gov/sites/entrez), entering the search term ‘cystic fibrosis’, for the period 13 November 2007 to 1 November 2008. There were 1380 papers identified, and when limits were set for ‘clinical trial’ and ‘randomized controlled trial’ this left 44 papers. In addition, three meta‐analyses and three practice guidelines were identified. The papers selected for this review are a personal choice of studies with important or interesting clinical messages.
CRANIOTOMY IN MICROCEPHALUS.Lecture delivered to the Post-Graduate Medical School, Chicago, 1898.
Authors: CARL BECK
Journal: JAMA (1894)

(<i>Concluded from page 646</i>). What has been done so far? I have been able to collect seventy cases of this operation, all being on record; all histories were not obtainable; many cases have not been published. Most of the reports come from France and America, only one each from Germany, Italy and Spain. This shows clearly that the German surgeons are conservative or reluctant in this question. They do not operate in these instances. Their standpoint is clearly shown in the discussion, which was held when Case 47 of our table was presented before the Medical Society of Vienna. The histories of all cases of Lannelongue, though I tried to get their details I could not obtain, and must only refer to his résumé before the Congress of French Surgeons in which he gives a detailed account of what he has done. I have purposely excluded all cases that have