tbuckley/cabot-search huggingface dataset:
Letter to the Editor: Proton Pump Inhibitors Are Associated With Minimal and Overt Hepatic Encephalopathy and Increased Mortality in Patients With Cirrhosis
Authors: Yu‐Jen Chen, Chia‐Fen Tsai, Yen‐Po Wang, Ching‐Liang Lu
Journal: Hepatology (2019)

Potential conflict of interest: Nothing to report. To the Editor: We read the paper by Nardelli et al. with great interest.1 The study tried to establish the correlation between the use of proton pump inhibitors (PPIs) and the occurrence of minimal/overt hepatic encephalopathy (HE) among patients with cirrhosis. In accordance with our previous retrospective population study,2 Nardelli et al. confirmed that patients with cirrhosis using PPIs were at higher risk of developing overt HE in their prospective cohort. They further provided evidence to support that PPI use was also an independent factor in determining minimal HE occurrence. In addition, PPI users were found to have significantly lower survival than PPI nonusers (41% vs. 81%; P < 0.001), and PPIs were identified as one of the independent factors in association with mortality. We are concerned about the connection between increased mortality and PPI use because the comorbidities associated with PPI use were not considered in the analysis. Although the mechanism is unclear, previous studies do demonstrate increased mortality among PPI users in patients with cirrhosis,3 myocardial infarction,4 and cancer.5 Nardelli et al.1 have separated PPI users into the patients with appropriate and inappropriate use. A considerably high number of inappropriate PPI users (73 out of 125, 58%) was identified. It would then be interesting to know whether the appropriate use of PPIs will have any impact on survival. If both inappropriate and appropriate PPI users showed lower survival than the PPI nonusers, there may exist a cause–effect relationship between mortality and PPI use. Therefore, we should be careful in prescribing PPIs to patients with cirrhosis. On the contrary, if lower survival can only be identified in the appropriate PPI users, it might be the comorbidities associated with increased PPI use that contributed to the higher mortality. In this situation, the PPIs could just be innocent bystanders. PPIs are widely used in daily clinical practice. Concerns have recently been raised about the side effects and overuse. We suggest that the authors take advantage of their data to clarify the role of PPIs in contributing to potentially increased mortality among patients with cirrhosis. With this knowledge, we may establish a basis inviting further studies to understand the potentially important clinical relationship and to remind clinicians to act as a responsible prescriber for adequate PPI use.
Fungi participate in the dysbiosis of gut microbiota in patients with primary sclerosing cholangitis
Authors: Sara Lemoinne, Astrid Kemgang, Karima Ben Belkacem, Marjolène Straube, Sarah Jegou, Christophe Corpechot, Olivier Chazouillères, Chantal Housset, Harry Sokol
Journal: Gut (2019)

Objective Patients with primary sclerosing cholangitis (PSC) were previously shown to display a bacterial gut dysbiosis but fungal microbiota has never been examined in these patients. The aim of this study was to assess the fungal gut microbiota in patients with PSC. Design We analysed the faecal microbiota of patients with PSC and concomitant IBD (n=27), patients with PSC and no IBD (n=22), patients with IBD and no PSC (n=33) and healthy subjects (n=30). Bacterial and fungal composition of the faecal microbiota was determined using 16S and ITS2 sequencing, respectively. Results We found that patients with PSC harboured bacterial dysbiosis characterised by a decreased biodiversity, an altered composition and a decreased correlation network density. These alterations of the microbiota were associated with PSC, independently of IBD status. For the first time, we showed that patients with PSC displayed a fungal gut dysbiosis, characterised by a relative increase in biodiversity and an altered composition. Notably, we observed an increased proportion of Exophiala and a decreased proportion of Saccharomyces cerevisiae . Compared with patients with IBD and healthy subjects, the gut microbiota of patients with PSC exhibited a strong disruption in bacteria-fungi correlation network, suggesting an alteration in the interkingdom crosstalk. Conclusion This study demonstrates that bacteria and fungi contribute to gut dysbiosis in PSC.
The concomitant use of milk thistle in pediatric acute lymphoblastic leukemia for the prevention and treatment chemotherapy related hepatotoxicities.
Authors: Sule Unal, Turan Bayhan, Betul Tavil, Fatma Gumruk, Mualla Cetin
Journal: Journal of Clinical Oncology (2015)

e21039 Background: Milk thistle (MT) is being widely used for the prevention and treatment hepatotoxicities related to chemotherapy, although there is scarce data on use with this indication among pediatric patients. We aimed to test the safety and efficacy of MT use in pediatric patients with acute lymphoblastic leukemia (ALL). Methods: Of the 156 patients diagnosed with ALL at pediatric age group who were on St Jude Total XV, those who developed serum ALT > 200 IU/L and/or direct bilirubin (DB) 1.5-2.5 mg/dl for at least 3 times (prophylactic group, n = 9) and those who had serum ALT > 500 IU/L and/or DB > 2.5 mg/dl (treatment group, n = 5) were initiated MT at a dose of 80 mg/d for patients 15-20 kg, 160 mg/d for 21-40 kg, 240 mg/d for 41-60 kg and 320 mg/d for 61-70 kg. The patients in treatment group were continued prophylaxis with MT. The maximum course of MT use was pre-determined as 7 months. Results: Of the 156 patients, 14 (9%) were initiated MT. Median MT use was 5 months (0.5-7). Median age was 12 years (1.5-19). TPMT polymorphism was analyzed in 8 patients and 7 were wild type. Seven of the patients were on decreased dosage of 6-MP and/or methotrexate when MT was initiated and all were on ursodeoxycolic acid. Of the 14 patients 4 (28%) had less serum ALT increases > 200 IU/L/month after MT, compared to before MT period and 6 (43%) had less ALT increases > 500 IU/L/month after MT, compared to before MT period. The most dramatic benefit was observed in 2 of the patients with severe cholestatic hepatitis (DB at MT initiation: 23 mg/dl and 11 mg/dl, respectively). One patient developed urticaria and MT was ceased. Conclusions: Hepatotoxicity is a common complication of pediatric ALL treatments and may interrupt the regular treatment schedule. These interruptions of treatment in more than 10% of the whole protocol have been reported to increase the risk of bone marrow relapse, previously. Our study, indicates that MT has been effective in some of the patients to prevent and treat the hepatotoxicities among pediatric ALL patients. Our study exhibits the longest use of MT for this indication in pediatric ALL. However, further studies for the safety of concomitant use in terms of chemotherapy efficacy are mandatory.
Radiogenomic signatures of NSCLC brain metastases: A potential non-invasive imaging marker for ALK mutation
Authors: S. Wadhwa, G. Krishnab, M. Malhotra, K. Prabhash, V. Noronha, A. Joshi, V. Patil, A. Mahajan
Journal: Annals of Oncology (2019)

Background: NSCLC harbouring ALK rearrangement has a higher risk of developing brain metastases. Literature on MR Imaging radiogenomics (MRI-R) as predictors of ALK mutation is limited and less investigated. The aim of our study was to evaluate the semantic MRI-R parameters of NSCLC brain metastases and their correlation with ALK status. Methods: We analyzed clinical data on 75 patients who were tested for ALK mutation and underwent MR imaging at diagnosis. Multiparametric MRI was performed in all cases. The associations between ALK mutation status and clinical features specifically age, sex, smoking, histology, TNM stage and imaging variables of brain metastasis, were analyzed using descriptive analysis (chi-square test) and univariate logistic regression analysis. Results: There were 46 ALK positive and 29 ALK negative cases that were subjected to MRI-R analysis. ALK positive were predominantly young (83%) and non-smokers (87%) (p < 0.001). Statistically significant difference (p < 0.001) was observed in lesion morphology and its T2W border, fuzzy and infiltrative border with hypointense peripheral solid rim in ALK positive while well defined border and no solid rim in ALK negative. Predominant signal on T1W imaging was hypointense (p < 0.001) in ALK negative, whereas heterogeneity was marker of ALK positive status on T1W (p < 0.001). Lesions in ALK negative group showed central restriction on DW images (p-0.001) and peripheral restriction of the solid rim was characteristic of ALK positive (p < 0.001). ALK positive showed thick ring enhancement while patchy enhancement favoured ALK negative. Incidence of meningeal involvement was significantly higher in ALK positive and was absent in 80% of ALK negative (p-0.02). On univariate logistic regression analysis, statistically significant association was found between age, smoking history, T2W lesion morphology, T2W border, restricted diffusion, enhancement and meningeal positivity (p < 0.05). Conclusions: ALK positive brain metastases have peculiar MR imaging features that can be non-invasive diagnostic and predictive imaging biomarkers. MR radiogenomics have potential role in individualised management of ALK positive NSCLC brain metastasis. Legal entity responsible for the study: IEC TMH. Funding: Has not received any funding. Disclosure: All authors have declared no conflicts of interest.
Primary Resistance to Immune Checkpoint Inhibitors in Metastatic Colorectal Cancer—Beyond the Misdiagnosis
Authors: Vassiliki Kotoula, Florentia Fostira, Elena Fountzilas
Journal: JAMA Oncology (2019)

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Patient-reported experience combining complementary and alternative medicine (CAM) with conventional oncology treatment (COT).
Authors: Alvaro G. Menendez, Abdul Saied, N. Joseph Espat
Journal: Journal of Clinical Oncology (2015)

9625 Background: CAM encompasses a diverse group of interventions not generally considered to be part of COT. The objective of this study is to describe the characteristics, factors and patient reported experiences associated with the use of CAM by patients (pts) receiving COT. Methods: An IRB approved, 14 item questionnaire was offered to all pts receiving COT at a single institution cancer center over a defined 2 mo interval. Demographics, prevalence and type of CAM used; as well as specific questions to define oncologist endorsement of CAM in combination with COT were collected. Results: 198/215 (92%) questionnaires were completed and analyzed. Utilization of CAM before the diagnosis (dx) of cancer was seen in 21/198(11%) pts. Following a cancer dx, 114/198(58%) reported the use of CAM. Dietary supplements were the most commonly used 57/108(52%); 41/108(38%) used massage and other mind-body techniques; while 10/108(9%) used multiple types of CAM. The source of CAM information was the oncologist in 42/138(30%), TV in 26/138(19%) and friends/family in 23/138(17%). Analysis demonstrated no significant difference in the use of CAM by gender, age, level of education or family income; however Hispanic ethnicity was a statistically significant variable (p = 0.027) in reported quality of life improvement with CAM. 141/198(71%) of pts reported a desire to discuss CAM integration into their COT, however only 95/198(48%) did so. After discussion with their oncologist, 30/45(66%) of pts reported receiving additional information about CAM, 11/45(24%) reported that CAM use was acceptable but did not receive additional information and 4/45(9%) were discouraged from CAM use. Conclusions: This study reveals that routine CAM use is not uncommon, but is four times more frequent after a dx of cancer. The majority of pts do not address CAM with their oncologist, despite a reported interest in doing so. About 1/3 of oncologists were reported not to provide additional information and actually discouraged CAM. This study identifies that the majority of pts with cancer use CAM, however potential barriers between patients and oncologists exist for the effective integration of CAM with COT.
SAT-389-Obeticholic acid reduces matrix metalloproteinases activity via iNOS modulation in hepatic ischemia/reperfusion injury
Authors: Laura Giuseppina Di Pasqua, Giuseppina Palladini, Clarissa Berardo, Veronica Siciliano, Luciano Adorini, Plinio Richelmi, Massimiliano Cadamuro, Luca Fabris, Stefano Perlini, Mariapia Vairetti, Andrea Ferrigno
Journal: Journal of Hepatology (2019)
Investigating the correlation between disease burden and symptoms in patients with advanced stage lung cancer.
Authors: Christopher Geiger, Zhengjia Chen, Chao Zhang, Madhusmita Behera, Conor Ernst Steuer, Rathi Narayana Pillai, Suresh S. Ramalingam
Journal: Journal of Clinical Oncology (2015)

e19057 Background: Previous studies have shown that lung cancer patients (pts) with higher baseline quality of life (QOL) scores on the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC-QLQ) had significantly improved overall survival. Patients with more severe symptoms on the Lung Cancer Symptom Scale (LCSS) had worse QOL and overall outcomes. However, no studies have focused on the relationship between lung cancer tumor burden and patient symptoms or QOL. We hypothesized that patients with larger tumor burden will experience worse symptoms and decreased QOL compared to patients with smaller tumor burden. Methods: 89 pts with newly diagnosed advanced stage lung cancer within the three months prior to study enrollment rated their symptoms and QOL using the LCSS and EORTC. Tumor burden was calculated as the sum total of the dimensions of each target lesion meeting RECIST criteria, summed both with and without restricting the total number of lesions. The relationship between tumor burden or metastatic sites, patient QOL and symptom severity was determined using univariate and multivariate analyses. Results: 84% of pts were diagnosed with non-small cell carcinoma and 71% had metastatic disease at enrollment. 47% were Caucasian, 89% were prior or current smokers, and the median ECOG performance status was 1. Pts had a median of 4 measurable lesions with a median total tumor burden of 16.4 cm. The median QOL score was 58/100 and median LCSS symptom score was 37/100. There was a significant negative correlation between patient QOL and both total tumor burden (p = .028) and total number of cancerous lesions (p = .045). Additionally, patient symptom severity was positively associated with both total tumor burden (p = .047) and total number of cancer sites (p = .034). Patients’ QOL was negatively associated with pleural effusions (p = .022) and liver/adrenal involvement (p = .044). Finally, pts with bony involvement had increased pain (p = .018). Conclusions: Patients with larger tumor burden have worse subjective QOL and increased severity of symptoms. Tumor burden may best be assessed in QOL studies without restricting total number of lesions to five as defined in the RECIST criteria.
THU-160-Outcomes of the national strategy on hepatitis C treatment with direct acting antivirals in a real-life setting: Results from a national survey in Slovenia
Authors: Mojca Maticic, Zala Pirnat, Jelka Meglic Volkar, Sergeja Gregorcic, Mojca Rajter, Janja Prah, Tadeja Kotar, Zvonko Baklan, Ksenija Ekart Koren, Tanja Selic Kurincic, Tatjana Remec, Anica Kurent, Emil Pal, Matjaz Hafner, Katja Novak, Mojca Ribnikar, Mario Poljak, Jerneja Videcnik Zorman
Journal: Journal of Hepatology (2019)
FRI-209-Exploring TH1/TH2 adjuvants to improve the efficacy of the therapeutic vaccination against chronic hepatitis B
Authors: Jinpeng Su, Anna Kosinska, Livia Brunner, Julia Sacherl, Géraldine Frank, Katrin Singethan, Julia Hasreiter, Frank Thiele, Nicolas Collin, Ulrike Portzer
Journal: Journal of Hepatology (2019)
PS-041-Intense angiocrine crosstalk between liver endothelial cell subtypes leads to liver capillarization and recruitment of myeloid progenitors
Authors: Stefan Thomann, Sofia Weiler, Simone Marquard, Martin Dittmer, Daniel Kazdal, Marcell Tóth, Teng Wei, Stephanie Roessler, Carsten Sticht, Norbert Gretz, Carolin Mogler, Claudia Ball, Hanno Glimm, Eduard Ryschich, Peter Schirmacher, Kai Breuhahn
Journal: Journal of Hepatology (2019)
TCTAP A-028 Prognostic Significance of Reperfusion Delays in Patients Presenting for ST-elevation Myocardial Infarction in the Tunisian Context
Authors: Walid Jomaa, Ouday Ben Abdeljelil, Mohamed Ali Ben Tekaya, Ikram Chamtouri, Khaldoun Ben Hamda, Faouzi Maatouk
Journal: Journal of the American College of Cardiology (2019)
Hyperspectral cell sociology reveals spatial tumor-immune cell interactions associated with lung cancer recurrence
Authors: Katey S. S. Enfield, Spencer D. Martin, Erin A. Marshall, Sonia H. Y. Kung, Paul Gallagher, Katy Milne, Zhaoyang Chen, Brad H. Nelson, Stephen Lam, John C. English, Calum E. MacAulay, Wan L. Lam, Martial Guillaud
Journal: Journal for ImmunoTherapy of Cancer (2019)

<h3>Background</h3> The tumor microenvironment (TME) is a complex mixture of tumor epithelium, stroma and immune cells, and the immune component of the TME is highly prognostic for tumor progression and patient outcome. In lung cancer, anti-PD-1 therapy significantly improves patient survival through activation of T cell cytotoxicity against tumor cells. Direct contact between CD8+ T cells and target cells is necessary for CD8+ T cell activity, indicating that spatial organization of immune cells within the TME reflects a critical process in anti-tumor immunity. Current immunohistochemistry (IHC) imaging techniques identify immune cell numbers and densities, but lack assessment of cell–cell spatial relationships (or "cell sociology"). Immune functionality, however, is often dictated by cell-to-cell contact and cannot be resolved by simple metrics of cell density (for example, number of cells per mm<sup>2</sup>). To address this issue, we developed a Hyperspectral Cell Sociology technology platform for the analysis of cell–cell interactions in multi-channel IHC-stained tissue. <h3>Methods</h3> Tissue sections of primary tumors from lung adenocarcinoma patients with known clinical outcome were stained using multiplex IHC for CD3, CD8, and CD79a, and hyperspectral image analysis determined the phenotype of all cells. A Voronoi diagram for each cell was used to approximate cell boundaries, and the cell type of all neighboring cells was identified and quantified. Monte Carlo analysis was used to assess whether cell sociology patterns were likely due to random distributions of the cells. <h3>Results</h3> High density of intra-tumoral CD8+ T cells was significantly associated with non-recurrence of tumors. A cell sociology pattern of CD8+ T cells surrounded by tumor cells was more significantly associated with non-recurrence compared to CD8+ T cell density alone. CD3+ CD8- T cells surrounded by tumor cells was also associated with non-recurrence, but at a similar significance as cell density alone. Cell sociology metrics improved recurrence classifications of 12 patients. Monte Carlo re-sampling analysis determined that these cell sociology patterns were non-random. <h3>Conclusion</h3> Hyperspectral Cell Sociology expands our understanding of the complex interplay between tumor cells and immune infiltrate. This technology could improve predictions of responses to immunotherapy and lead to a deeper understanding of anti-tumor immunity.
THU-037-Soluble MAdCAM-1 as a novel marker of hepatic endothelial dysfunction in acutely decompensated cirrhosis
Authors: Jonathon Graham, Francesca Trovato, Davide Erminelli, Xiaohong Huang, Rodrigo Liberal, Diego VERGANI, Giorgina Mieli-Vergani, Yun Ma, Bu Hayee, Mark J W McPhail
Journal: Journal of Hepatology (2019)
SAT-415-High levels of basement membrane remodelling (C4M) and low activity of wound healing (FPA) reflect fibrosis in alcoholic liver disease
Authors: Natasja Gudmann, Maja Thiele, Mette Juul Nielsen, Bjørn Stæhr Madsen, Sönke Detlefsen, Linda S. Moeller, Maria Kjærgaard, Diana Leeming, Morten Karsdal, Aleksander Krag
Journal: Journal of Hepatology (2019)
<i>Notes from the Field:</i> Acute Hepatitis A Virus Infection Among Previously Vaccinated Persons with HIV Infection — Tennessee, 2018
Authors: Julia Brennan, Kelly Moore, Lindsey Sizemore, Samantha A. Mathieson, Carolyn Wester, John R. Dunn, William Schaffner, Timothy F. Jones
Journal: MMWR Morbidity and Mortality Weekly Report (2019)

Complete immunization against hepatitis A requires 2 doses of a monovalent vaccine or 3 doses of a combined hepatitis A and hepatitis B vaccine; approximately 90% of vaccinated persons achieve protective antibody levels after a single dose of either product (1).However, persons living with human immunodeficiency virus (HIV) infection might not develop the same level of immunity after hepatitis A virus (HAV) vaccination as do immunocompetent persons (2,3).Compared with immunocompetent persons, seroconversion rates among persons with HIV infection are lower and are further affected by CD4 count and HIV viral load at the time of the first dose of vaccine (3).In addition, time to seroconversion is longer (3), and duration of protection wanes earlier (4) among persons with HIV infection.During an outbreak, evaluating predictors of a better vaccine response (CD4 count and HIV viral load at the time of first vaccination) is generally not feasible.Routine assessment of immune response after vaccination is not recommended for persons in general, nor for those with HIV infection (1); therefore, providers use a documented history of HAV vaccination to guide decisions regarding administration of HAV postexposure prophylaxis (PEP).However, compared with vaccination among the general population, a previous hepatitis A vaccination in persons with HIV infection after a high-risk exposure (e.g., household member or sexual contact) might not reliably protect against illness.The Tennessee Department of Health (TDH) sought to determine the frequency at which persons with HIV infection who were previously vaccinated for hepatitis A developed HAV infection during an HAV outbreak.Confirmed HAV cases reported to TDH during an ongoing HAV outbreak during December 1, 2017-September 20, 2018, were reviewed to identify patients with HIV coinfection.Data gathered from case report forms, surveillance databases, and medical records were used to evaluate HIV status and HAV vaccination history.Among 249 confirmed cases of HAV infection, 11 (4%) occurred among persons with HIV infection, six of whom had received a partial or complete vaccination series before acute HAV infection (Table ).All six patients were men.Among