tbuckley/cabot-search huggingface dataset:
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Authors: Neil Mehta, Jennifer L. Dodge, Francis Y. Yao
Journal: Hepatology (2019)

Potential conflict of interest: Nothing to report. We thank Jiang et al. for their letter to the editor on our study,1 which analyzed patients with hepatocellular carcinoma (HCC) in the United Network for Organ Sharing (UNOS) database with at least one pre–liver transplant (LT) alpha‐fetoprotein (AFP) >1,000 ng/mL. We demonstrated significantly improved posttransplant survival and decreased HCC recurrence among patients with a reduction in AFP to <500 ng/mL with local‐regional therapy (LRT), validating the recently approved national policy. Impressively, those with AFP reduction pre‐LT to <100 ng/mL demonstrated nearly 90% survival 5 years post‐LT. Jiang et al. raised the concern that we did not investigate the effectiveness of LRT modalities in achieving this AFP reduction. They also pointed out that patterns of posttransplant tumor recurrence were not provided, though unfortunately these data are unavailable in the UNOS database. Our article emphasized the importance of LRT in this population. Not surprisingly, LRT was reported in only 55% with AFP >1,000 at LT versus nearly 90% of those with an AFP reduction to <500. We also showed that a period of observation is required for evaluating changes in AFP due to LRT pre‐LT, providing additional justification for the 6‐month mandatory delay in awarding HCC exception points. However, assessing the efficacy of the LRT modality is challenging in the UNOS due to limited LRT data. Among patients receiving LRT, transarterial chemoembolization (TACE) use was similar to AFP at LT category (P = 0.81). Importantly, on univariate Cox proportional hazards regression, we found no association between LRT type and post‐LT death or recurrence. In the literature, comparisons regarding the relative efficacy of LRT modalities are lacking, especially among LT candidates with an AFP >1,000 ng/mL. The PREMIERE trial,2 a small, single‐center phase 2 prospective randomized study, compared conventional TACE with Y90 in Barcelona Clinic Liver Cancer stage A/B patients. The authors found significantly longer time to progression with Y90 >2 at 6 months compared to 7 months with TACE. However, only 56% were ever listed for LT, and only 10% had a pretreatment AFP >200. At this time, we are unable to make specific recommendations on the most effective LRT modality in those presenting with an AFP >1,000. However, applying repeated LRT with AFP reduction to at least <500 with partial or complete response on imaging is associated with improved post‐LT outcome. These results provide further evidence that biomarkers and LRT response are still the main factors in improving selection criteria.3
Extending the phenotype of midface toddler excoriation syndrome (MiTES): Five new cases in three families with PR domain containing protein 12 (PRDM12) mutations
Authors: Arun C. Inamadar, Keshavmurthy Vinay, Bayanne Olabi, Nivedita Sarveswaran, Anuradha Bishnoi, Christopher G. Woods, Celia Moss
Journal: Journal of the American Academy of Dermatology (2019)
OTU-07 Near focus narrow and imaging driven artificial intelligence for the diagnosis of gastro-oesophageal reflux disease
Authors: Shraddha Gulati, Julius Bernth, Junkai Liao, Dmytro Poliyivets, Sukhdev Chatu, Andrew Emmanuel, Amyn Haji, Hongbin Liu, Bu’Hussain Hayee
Journal: Endoscopy (2019)

<h3>Introduction</h3> Gastro-oesophageal reflux disease(GORD) is a common condition carrying an arduous process for diagnosis. Symptom questionnaires and proton-pump inhibitor challenge lack reliability and white light endoscopy (WLE) is often normal. Objective measurement of oesophageal acid exposure time (AET) require invasive testing. Changes in intrapapillary capillary loops (IPCLs) identified using narrow band imaging(NBI) have been proposed as a marker for reflux. We evaluated a near focus (NF-NBI) driven artificial intelligence(AI) model for the diagnosis of GORD. <h3>Methods</h3> Patients with symptoms of GORD (recorded using the Reflux Disease Questionnaire(RDQ)) were prospectively recruited over 10 months. Upper endoscopy recorded multiple NF-NBI images, video and biopsies of the lower oesophagus. If endoscopy using High-Definition WLE was normal, a pH-recording capsule was placed. Patients were defined according to Lyon criteria; Erosive oesophagitis(EO);non-erosive reflux disease(NERD);functional heartburn(FH). Two forms of AI were developed and evaluated to automate regions of interest (ROI) and detect IPCLs and morphology: computer vision (CV) and deep convoluted neural network(DCNN) using Resnet50. DCNN was evaluated using training: unseen testing dataset ratios of 50:50 (3872:4280 images) and 75:25 (6484:1668 images). For the purposes of training the AI models, EO and NERD cases were combined as 'GORD'. A novel combined classifier (CC) of both AI methods was evaluated. <h3>Results</h3> 78 consecutive patients were recruited. n=68 (46 Female, 44.41±12.91 years): GORD n=27 (EO n=6, NERD n=21) and FH n=41 were analysed. The mean IPCL per ROI count was greater in GORD vs FH: 33.2 ± 5.19 vs 28.1 ± 5.42 p=0.0003 and was used as the primary diagnostic tool. IPCL morphology for GERD vs FH: length 16.29 vs 16.98, p=0.19; width 7.8 vs 7.8, p=0.98; red 118.8 vs 120.6, p=0.44; green 114.3 vs 118, p0.004; blue 94.24 vs 97.54 p=0.07. With CV: mean IPCLs/ROI (threshold 27.6) had sensitivity, specificity, AUC: 88.9, 58.5, 0.76 (p=0.0003) for GORD. With DCNN 50:50 these results were 58%, 86% and 76% respectively. DCNN 75:25 produced 67%, 92%, 83% respectively. CC improved overall specificity(89.1%) and accuracy(78.1%) but not sensitivity(63%). <h3>Conclusion</h3> AI using NF-NBI is a novel method for the diagnosis of GORD. With increased data, improvements in diagnostic accuracy is achieved further improved using a CC. This model has the potential to provide a reliable safe single-test diagnosis of GORD.
Abnormal collagen type V deposition in lung fibroblast ins correlated with a worse pulmonary function in systemic sclerosis
Authors: R. Souza, W. Teodora, Solange Carrasco, Ronaldo Adib Kairalla, C. Borges, C. Goldenstein Schainberg, E. Parra, E. Carvalho, Eloísa Silva Dutra de Oliveira Bonfá, Natalino Hajime Yoshinari, Vera Luiza Capelozzi
Journal: European Respiratory Journal (2007)
Standardized Outcomes in Nephrology—Glomerular Disease (SONG-GD): establishing a core outcome set for trials in patients with glomerular disease
Authors: Simon A. Carter, Liz Lightstone, Daniel Cattran, Arvind Bagga, Sean J. Barbour, Jonathan Barratt, John Boletis, Dawn Caster, Rosanna Coppo, Fernando C. Fervenza, Jürgen Floege, Michelle Hladunewich, Jonathan J. Hogan, A. Richard Kitching, Richard Lafayette, Ana Malvar, Jai Radhakrishnan, Brad H. Rovin, Hong Zhang, Talia Gutman, Martin Howell, Charlotte Logeman, Jenny I. Shen, Armando Teixeira-Pinto, Stephen I. Alexander, Yeoungjee Cho, Jonathan C. Craig, David Harris, David W. Johnson, Peter G. Kerr, Jessica Ryan, Andrea K. Viecelli, Angela Yee-Moon Wang, Martin Wilkie, Nicole Scholes-Robertson, Allison Tong
Journal: Kidney International (2019)
Gaussian Mixture Models for Probabilistic Classification of Breast Cancer
Authors: Indira Prabakaran, Zhengdong Wu, Changgun Lee, Brian Tong, Samantha Steeman, Gabriel Koo, Paul J. Zhang, Marina A. Guvakova
Journal: Cancer Research (2019)

In the era of omics-driven research, it remains a common dilemma to stratify individual patients based on the molecular characteristics of their tumors. To improve molecular stratification of patients with breast cancer, we developed the Gaussian mixture model (GMM)-based classifier. This probabilistic classifier was built on mRNA expression data from more than 300 clinical samples of breast cancer and healthy tissue and was validated on datasets of ESR1, PGR, and ERBB2, which encode standard clinical markers and therapeutic targets. To demonstrate how a GMM approach could be exploited for multiclass classification using data from a candidate marker, we analyzed the insulin-like growth factor I receptor (IGF1R), a promising target, but a marker of uncertain importance in breast cancer. The GMM defined subclasses with downregulated (40%), unchanged (39%), upregulated (19%), and overexpressed (2%) IGF1R levels; inter- and intrapatient analyses of IGF1R transcript and protein levels supported these predictions. Overexpressed IGF1R was observed in a small percentage of tumors. Samples with unchanged and upregulated IGF1R were differentiated tumors, and downregulation of IGF1R correlated with poorly differentiated, high-risk hormone receptor-negative and HER2-positive tumors. A similar correlation was found in the independent cohort of carcinoma in situ, suggesting that loss or low expression of IGF1R is a marker of aggressiveness in subsets of preinvasive and invasive breast cancer. These results demonstrate the importance of probabilistic modeling that delves deeper into molecular data and aims to improve diagnostic classification, prognostic assessment, and treatment selection. SIGNIFICANCE: A GMM classifier demonstrates potential use for clinical validation of markers and determination of target populations, particularly when availability of specimens for marker development is low.
Police launch probe into “horrific” abuse of patients by staff at care facility
Authors: Gareth Iacobucci
Journal: BMJ (2019)

A police investigation has been launched after an undercover investigation by BBC Panorama 1 showed adults with learning disabilities and autism being abused by staff at a specialist hospital in the north east of England.

The footage screened on 22 May showed patients being mocked, intimidated, and restrained by staff at Whorlton Hall, a private secure hospital in County Durham that provides NHS funded care.

Sixteen care workers at the facility have subsequently been suspended and police are now investigating the abuse, which received widespread condemnation from government, medical leaders, and others.

The Care Quality Commission (CQC), which rated …
Acute exanthemas: a prospective study of 98 adult patients with an emphasis on cytokinic and metagenomic investigation
Authors: O. Deschamps, N. Ortonne, S. Hüe, C. Rodriguez, C. Deschodt, G. Hirsch, A. Colin, L. Grégoire, M.‐H. Delfau‐Larue, O. Chosidow, P. Wolkenstein, S. Ingen‐Housz‐Oro
Journal: British Journal of Dermatology (2019)

Acute exanthemas (AEs) are frequently seen; they can be caused by drugs or viruses but often the cause is unknown. To describe the clinical, virological and histological aspects of AEs and explore their cytokinic and metagenomic profiles. This prospective study examined 98 patients with AE, from February to July 2014. Clinical data were recorded in a standardized chart. Virological investigation and skin biopsies were performed. In addition, blood and skin samples were analysed for cytokines and then by a shotgun metagenomic approach. We identified five groups of patients: those with maculopapular exanthemas (MPEs) that were virally induced (group 1); those with drug‐induced MPEs (group 2), those with MPEs that were both viral and drug induced (group 3), those with idiopathic MPEs (group 4) and those with pityriasis rosea (group 5). A virus was identified in 29 cases (human herpesvirus 6, 72%). Cytokinic analysis of the skin (n = 23 MPEs) showed higher levels of interferon‐γ and interleukin‐1 receptor‐α in viral MPEs, higher interleukin‐33 levels in idiopathic MPEs, and higher macrophage inflammatory protein 1α levels in drug‐induced MPEs. By metagenomics analysis (n = 10 MPEs), viruses identified with routine practice methods were not found in group 1 (n = 4 MPEs). However, Enterovirus A was detected in two cases, especially in a group 1 patient for whom metagenomic analysis rectified the diagnosis of the culprit agent. Human herpesvirus 6 was the virus most frequently identified, and histology did not discriminate MPEs. In addition, the level of interleukin‐33 seen in idiopathic MPEs suggests that an environmental factor may be the trigger for these. The results bring into question the utility of routine polymerase chain reaction analysis and viral serology for determining cause in AE. What's already known about this topic? Acute exanthemas, especially maculopapular exanthemas, are a frequent reason for patients consulting emergency and dermatology departments. It is difficult to evaluate the aetiology of acute exanthema based on the clinical aspects. Few data are available on the investigations needed in routine practice, and no prospective series have been published. What does this study add? Our study provides a global and prospective description of acute exanthemas. Cytokine analysis could help to investigate the pathophysiology of idiopathic eruptions. Metagenomic analysis provides new insights about the value of routine practice virological investigations. We show for the first time the feasibility of metagenomics analysis in the skin, which results question the interest of routine PCR and viral sérologies for the exploration of such acute exanthemas.
Existe t-il des facteurs prédictifs de la présence d'anomalies aux biopsies coliques systématiques pratiquées dans le cadre d'exploration des diarrhées chroniques
Authors: R Baklouti, A Guediche, M Ben Abdelwahed, F Aissaoui, M Zakhama, W Bouhlel, W Ben Mansour, HL Mohamed, BC Nabil, L Safer
Journal: Endoscopy (2019)

Un bilan endoscopique et radiologique normal est une situation relativement fréquente dans l'exploration d'une diarrhée chronique. Des biopsies grêliques et coliques sont ainsi souvent réalisées afin de rechercher des lésions microscopiques pouvant expliquer la diarrhée. Le but de notre travail est de préciser l'apport des biopsies systématiques lors des coloscopies normales réalisées dans le cadre d'exploration de diarrhée chronique et de rechercher des facteurs prédictifs de la présence d'anomalies microscopiques.
Intrahepatic bile duct stone treatment combining electrohydraulic lithotripsy and peroral cholangioscopy through a choledochoduodenal fistula
Authors: Ryuichi Yamamoto, Toshiyuki Abe, Shosuke Hosaka, Takayoshi Akase, Ayasa Ito, Mikio Kawayama, Kazunao Watanabe
Journal: Endoscopy (2019)

A 62-year-old woman with intrahepatic bile duct stones ([Fig. 1]) and cholangitis symptoms was admitted to the hospital. She had undergone cholecystectomy 12 years previously for cholelithiasis. We performed endoscopic retrograde cholangiopancreatography (ERCP) to relieve her symptoms and reduce inflammation. Duodenoscopy showed an approximately 2-mm fistula in the duodenal bulb; guidewire placement and radiography confirmed a choledochoduodenal fistula. We performed balloon dilation of the choledochoduodenal fistula using a 6-mm balloon catheter (REN; Kaneka Medical Products, Tokyo, Japan). A single-operator fiberoptic cholangioscope direct visualization device (SpyGlass DS; Boston Scientific Corporation, Marlborough, Massachusetts, USA) was inserted over the guidewire into the intrahepatic bile duct under radiographic guidance, and all intrahepatic bile duct stones and debris were crushed via electrohydraulic lithotripsy (EHL). Finally, a 7-Fr plastic stent was inserted into the choledochoduodenal fistula ([Fig. 2] and [Fig. 3]; [Video 1]). Postoperative recovery was quick.
Effect of prophylaxis to toxoplasma gondii and pneumocistis carinii after bone marrow transplantation (bmt)
Authors: R S Medeiros, M Ostronoff, C M Machado, R L Silva, M. C. M. A. Macedo, C M Massumoto, E Zambon, H A Loterio, I F Rocha, Pedro Enrique Dorlhiac Llacer, Dalton de Alencar Fischer Chamone, Frederico Luiz Dulley
Journal: Blood (1995)
CtIP is essential for early B cell proliferation and development in mice
Authors: Xiangyu Liu, Xiaobin S. Wang, Brian J. Lee, Foon K. Wu-Baer, Xiaohui Lin, Zhengping Shao, Verna M. Estes, Jean Gautier, Richard Baer, Shan Zha
Journal: The Journal of Experimental Medicine (2019)

B cell development requires efficient proliferation and successful assembly and modifications of the immunoglobulin gene products. CtIP is an essential gene implicated in end resection and DNA repair. Here, we show that CtIP is essential for early B cell development but dispensable in naive B cells. CtIP loss is well tolerated in G1-arrested B cells and during V(D)J recombination, but in proliferating B cells, CtIP loss leads to a progressive cell death characterized by ATM hyperactivation, G2/M arrest, genomic instability, and 53BP1 nuclear body formation, indicating that the essential role of CtIP during proliferation underscores its stage-specific requirement in B cells. B cell proliferation requires phosphorylation of CtIP at T847 presumably by CDK, but not its interaction with CtBP or Rb or its nuclease activity. CtIP phosphorylation by ATM/ATR at T859 (T855 in mice) promotes end resection in G1-arrested cells but is dispensable for B cell development and class switch recombination, suggesting distinct roles for T859 and T847 phosphorylation in B cell development.
Ablation of Hepatocyte Smad1, Smad5, and Smad8 Causes Severe Tissue Iron Loading and Liver Fibrosis in Mice
Authors: Chia‐Yu Wang, Xia Xiao, Abraham Bayer, Yang Xu, Som Dev, Susanna Canali, Anil V. Nair, Ricard Masia, Jodie L. Babitt
Journal: Hepatology (2019)

A failure of iron to appropriately regulate liver hepcidin production is central to the pathogenesis of hereditary hemochromatosis. SMAD1/5 transcription factors, activated by bone morphogenetic protein (BMP) signaling, are major regulators of hepcidin production in response to iron; however, the role of SMAD8 and the contribution of SMADs to hepcidin production by other systemic cues remain uncertain. Here, we generated hepatocyte Smad8 single ( Smad8fl/fl;Alb‐Cre+ ), Smad1/5/8 triple ( Smad158;Alb‐Cre+ ), and littermate Smad1/5 double ( Smad15;Alb‐Cre+ ) knockout mice to investigate the role of SMAD8 in hepcidin and iron homeostasis regulation and liver injury. We found that Smad8;Alb‐Cre+ mice exhibited no iron phenotype, whereas Smad158;Alb‐Cre+ mice had greater iron overload than Smad15;Alb‐Cre+ mice. In contrast to the sexual dimorphism reported for wild‐type mice and other hemochromatosis models, hepcidin deficiency and extrahepatic iron loading were similarly severe in Smad15;Alb‐Cre+ and Smad158;Alb‐Cre+ female compared with male mice. Moreover, epidermal growth factor (EGF) failed to suppress hepcidin in Smad15;Alb‐Cre+ hepatocytes. Conversely, hepcidin was still increased by lipopolysaccharide in Smad158;Alb‐Cre+ mice, although lower basal hepcidin resulted in lower maximal hepcidin. Finally, unlike most mouse hemochromatosis models, Smad158;Alb‐Cre+ developed liver injury and fibrosis at 8 weeks. Liver injury and fibrosis were prevented in Smad158;Alb‐Cre+ mice by a low‐iron diet and were minimal in iron‐loaded Cre– mice. Conclusion : Hepatocyte Smad1/5/8 knockout mice are a model of hemochromatosis that encompasses liver injury and fibrosis seen in human disease. These mice reveal the redundant but critical role of SMAD8 in hepcidin and iron homeostasis regulation, establish a requirement for SMAD1/5/8 in hepcidin regulation by testosterone and EGF but not inflammation, and suggest a pathogenic role for both iron loading and SMAD1/5/8 deficiency in liver injury and fibrosis.
GASTRIC POLYPS: A RETROSPECTIVE COHORT ANALYSIS OF EPIDEMIOLOGICAL AND PHENOTYPIC CHARACTERISTICS
Authors: C Kapizioni, P Kourkoulis, P Giannelis, A Mellos, G Koutoufaris, K Milioni, E Xourgia, K Makris, V Ntouli, G Michalopoulos, S Vrakas, V Xourgias
Journal: Endoscopy (2019)

Gastric polyps are usually benign lesions incidentally found during upper gastrointestinal endoscopy. Aim of this study was to identify the frequency and topography of different types of gastric polyps as well as their epidemiologic characteristics.
Echoendoscopie et cytoponction: Quel apport dans les masses pancréatiques
Authors: Z Bouhnoun, S Bahja, H Abid, M Elyoussfi, N Aqodad, DA Benajah, M Elabkari, A Ibrahimi, N Lahmidani
Journal: Endoscopy (2019)

La ponction biopsie écho-endoscopique des masses pancréatiques, est une technique permettant par aspiration à l'aiguille fine l'obtention de matériel pour analyse cytohistologique. Elle est indiquée chaque fois qu'un examen histologique peut avoir un intérêt diagnostique et/ou thérapeutique. Nous avons analysé les caractéristiques épidémiologiques, cliniques, radiologiques et écho-endoscopiques des masses pancréatiques dont la décision de l'EE avec cytoponction a été posée en réunion de concertation multidisciplinaire (RCP) ainsi que la rentabilité diagnostique de cette technique.
Cholesterol-lowering medication: Impact on the clinical effect of adjuvant endocrine treatment in postmenopausal breast cancer
Authors: K.S. Harborg, U. Heide-Jørgensen, T.P. Ahern, M. Ewertz, D. Cronin Fenton, S. Borgquist
Journal: Annals of Oncology (2019)

Background: Observational studies suggest that cholesterol-lowering medication (CLM) use is associated with longer recurrence-free survival in breast cancer patients. Since 2007, aromatase inhibitors (AIs) have been guideline treatment for estrogen receptor positive (ER+) postmenopausal breast cancer. AI therapy is associated with increased cholesterol levels. We investigated the association of CLM use and breast cancer recurrence rate in patients treated with AIs. Methods: This cohort included all women diagnosed with stage I-III ER+ breast cancer from 2007-2016, treated with AI in the adjuvant setting, and registered in the Danish Breast Cancer Group database. We ascertained incident CLM exposure (≥1 prescription post-diagnosis) from the Danish National Prescription Registry and modelled CLM as a time-varying exposure lagged by 6 months. Follow-up began 6 months after diagnosis and continued to the first event of recurrence, death, emigration, 10 years or 25th September 2018. We estimated recurrence rates, and crude and adjusted hazard ratios (HRs) with 95% confidence intervals (95% CI), comparing CLM exposure with non-exposure. Results: We enrolled 12,947 eligible patients. Median follow-up was 4.6 years. During follow-up, the total person-years of the unexposed group was 56,171 (incidence rate per 1,000 person-years: 11.50 [95% CI: 10.63–12.42]) and 5,246 in the CLM exposed group (incidence rate per 1,000 person-years: 12.20 [95% CI: 9.40–15.58]). There was little evidence of a protective effect of CLM on breast cancer recurrence during total follow-up but some evidence during the first 5 years (Table). Conclusions: CLM use was not associated with a substantially reduced risk of breast cancer recurrence among AI users. Legal entity responsible for the study: Aarhus University Hospital. Funding: Jeppe Juhl Stiftelsen. Disclosure: All authors have declared no conflicts of interest. Table94PNo. of recurrences (person-years)Incidence rate per 1,000 person-years (95% CI)Crude HR (95% CI)Adjusted HR (95% CI)Recurrence during total follow-upNot CLM exposed646 (56,171)11.50 (10.63 - 12.42)(ref)(ref)CLM exposed64 (5,246)12.20 (9.40 - 15.58)0.84 (0.46 - 1.55)0.90 (0.68 - 1.20)Recurrence during the first 5 years of follow-upNot CLM exposed525 (46,590)11.27 (10.33 - 12.28)(ref)(ref)CLM exposed35 (3,290)10.64 (7.41 - 14.80)0.85 (0.60 - 1.20)0.76 (0.52 - 1.12) Open table in a new tab