tbuckley/cabot-search huggingface dataset:
Clinical characteristics and outcome of cancer patients with tuberculosis.
Authors: Anupama Dutt Mane, Sanjay P Deshmukh, Abhijit Babasaheb Gotkhinde, Minish Mahendra Jain
Journal: Journal of Clinical Oncology (2015)

e22219 Background: Tuberculosis infection in cancer patients is thought to increase immunity and possible better survival. The aim of this study is to compare the clinical characteristics and outcome of patients with cancer and tuberculosis (test group) and cancer only without tuberculosis (control group). Methods: This is a retrospective case control study of cancer patients with tuberculosis and without tuberculosis. A review of the data base of Cancer Centre at Ruby Hall Clinic, Pune, India was performed from 2006 till end of 2014. Cases were matched according to age and stage with randomly selected controls. The inclusion criterion for test group was cancer patients who were detected with tuberculosis either concurrent with cancer or during or after the treatment of cancer. Results: Out of total 32,400 cancer patients registered for treatment during the last 9 years, only 20 (0.006%) were diagnosed with tuberculosis. These 20 cases were matched with 20 randomly selected controls according to gender, age, stage and type of cancer. Majority (90%) of the patients in test group had extrapulmonary tuberculosis. Imaging was ambiguous with tuberculous lesions mimicking cancer metastases. All patients received complete cancer treatment according to standard guidelines. One patient was lost to follow up in test group and 5 patients were lost to follow up in control group. These 6 patients and their matches were excluded from final survival analysis. Out of 14 matched cases, 11 from test group were doing well as on the last visit of follow up as compared to 6 from the control group. There were no recurrences in the test group as compared to 3 cases of recurrence in control group. There were 3 deaths in test group as compared to 5 deaths in control group. Conclusions: The presence of tuberculosis with cancer causes clinical and radiological diagnostic difficulties. The survival of cancer patients with tuberculosis appears to be better than cancer patients without tuberculosis, however larger studies are required for confirmation of this finding.
Association Between Opioid Dose Variability and Opioid Overdose Among Adults Prescribed Long-term Opioid Therapy
Authors: Jason M. Glanz, Ingrid A. Binswanger, Susan M. Shetterly, Komal J. Narwaney, Stan Xu
Journal: JAMA Network Open (2019)

<h3>Importance</h3> Attempts to discontinue opioid therapy to reduce the risk of overdose and adhere to prescribing guidelines may lead patients to be exposed to variability in opioid dosing. Such dose variability may increase the risk of opioid overdose even if therapy discontinuation is associated with a reduction in risk. <h3>Objective</h3> To examine the association between opioid dose variability and opioid overdose. <h3>Design, Setting, and Participants</h3> A nested case-control study was conducted in a large Colorado integrated health plan and delivery system from January 1, 2006, through June 30, 2018. Cohort members were individuals prescribed long-term opioid therapy. <h3>Exposures</h3> Dose variability was defined as the SD of the milligrams of morphine equivalents across each patient's follow-up and categorized based on the quintile distribution of the SD in the cohort (0-5.3, 5.4-9.1, 9.2-14.6, 14.7-27.2, and &gt;27.2 mg of morphine equivalents). <h3>Main Outcomes and Measures</h3> Opioid overdose cases were identified using<i>International Classification of Diseases, Ninth Revision</i>and<i>International Statistical Classification of Diseases and Related Health Problems, Tenth Revision </i>codes. Each case patient with overdose was matched to up to 20 control patients using risk set sampling. Conditional logistic regression models were used to generate matched odds ratios and 95% CIs, adjusted for age, sex, race/ethnicity, drug or alcohol use disorder, tobacco use, benzodiazepine dispensings, medical comorbidities, mental health disorder, opioid dose, and opioid formulation. <h3>Results</h3> In a cohort of 14 898 patients (mean [SD] age, 56.3 [16.0] years; 8988 [60.3%] female) prescribed long-term opioid therapy, 228 case patients with incident opioid overdose were matched to 3547 control patients. The mean (SD) duration of opioid therapy was 36.7 (33.7) months in case patients and 33.0 (30.9) months in control patients. High-dose variability (SD &gt;27.2 mg of morphine equivalents) was associated with a significantly increased risk of overdose compared with low-dose variability (matched odds ratio, 3.32; 95% CI, 1.63-6.77) independent of opioid dose. <h3>Conclusions and Relevance</h3> Variability in opioid dose may be a risk factor for opioid overdose, suggesting that practitioners should seek to minimize dose variability when managing long-term opioid therapy.
Abstract 15299: Short-Term Vagal Nerve Stimulation Exerts Powerful Anti-Inflammatory Effects Without Noticeable Hemodynamic Impact in Rats With Pulmonary Arterial Hypertension
Authors: Keimei Yoshida, Keita Saku, Kazuhiko Kamada, Mariko Tanaka, Takuya Akashi, Kohtaro Abe, Takuya Kishi, Kenji Sunagawa, Hiroyuki Tsutsui
Journal: Circulation (2017)

Introduction: We have previously reported that chronic vagal nerve stimulation (VNS) improved survival of pulmonary arterial hypertension (PAH) in rats (Fig. 1). Since the excessive inflammatory re...
Estimated Number of Cases of High-Grade Cervical Lesions Diagnosed Among Women — United States, 2008 and 2016
Authors: Nancy M. McClung, Julia W. Gargano, Ina U. Park, Erin Whitney, Nasreen Abdullah, Sara Ehlers, Nancy M. Bennett, Mary Scahill, Linda M. Niccolai, Monica Brackney, Marie R. Griffin, Manideepthi Pemmaraju, Troy D. Querec, Angela A. Cleveland, Elizabeth R. Unger, Lauri E. Markowitz, Sheelah Blankenship, Stephanie Allen, James Meek, Kyle Higgins, James Hadler, Lynn Sosa, Kayla Saadeh, Deana Fink, Michael Silverberg, Melissa E. Powell, Shannon Q. Allain, Christina Felsen, RaeAnne Bogart, Marina Oktapodas Feiler, Rebecca M. Dahl
Journal: MMWR Morbidity and Mortality Weekly Report (2019)

Human papillomavirus (HPV) causes approximately 30,000 cancers in the United States annually (1). HPV vaccination was introduced in 2006 to prevent HPV-associated cancers and diseases (1). Cervical cancer is the most common HPV-associated cancer in women (1). Whereas HPV-associated cancers typically take decades to develop, screen-detected high-grade cervical lesions (cervical intraepithelial neoplasia grades 2 [CIN2], 3 [CIN3], and adenocarcinoma in situ, collectively CIN2+) develop within a few years after infection and have been used to monitor HPV vaccine impact (1-3). CDC analyzed data from the Human Papillomavirus Vaccine Impact Monitoring Project (HPV-IMPACT), a population-based CIN2+ surveillance system, to describe rates of CIN2+ among women aged ≥18 years during 2008-2016. Age-specific rates were applied to U.S. population data to estimate the total number of CIN2+ cases diagnosed in the United States in 2008* and in 2016. From 2008 to 2016, the rate of CIN2+ per 100,000 women declined significantly in women aged 18-19 years and 20-24 years and increased significantly in women aged 40-64 years. In the United States in 2008, an estimated 216,000 (95% confidence interval [CI] = 194,000-241,000) CIN2+ cases were diagnosed, 55% of which were in women aged 18-29 years; in 2016, an estimated 196,000 (95% CI = 176,000-221,000) CIN2+ cases were diagnosed, 36% of which were in women aged 18-29 years. During 2008 and 2016, an estimated 76% of CIN2+ cases were attributable to HPV types targeted by the vaccine currently used in the United States. These estimates of CIN2+ cases likely reflect changes in CIN2+ detection resulting from updated cervical cancer screening and management recommendations, as well as primary prevention through HPV vaccination. Increasing coverage of HPV vaccination in females at the routine age of 11 or 12 years and catch-up vaccination through age 26 years will contribute to further reduction in cervical precancers.
Minerva: September 1999
Authors: Yasmin Drabu, Selma Mehdi, Janet Migliozzi, Tracey Miller
Journal: BMJ (1999)

Doctors practising in Florida are outraged by orders from the state's medical board to submit fingerprints to the Federal Bureau of Investigation or face a fine or jail (American Medical News 1999 August 2). Their fingerprints will be kept on file and used to identify bogus doctors practising without credentials. To add to the humiliation, the state's doctors have to present to a police station to submit their prints, which will be a novel experience for most of them. Strangely, chiropractors and chiropodists are also being targeted.

On the face of it, prescribing exercise for patients seems like a good idea. Most people need to do more exercise and the health benefits are well established. Not everyone is fit enough to take exercise, however, and many general practitioners feel ill equipped to assess their patients' suitability for the prescription (British Journal of Sports Medicine 1999;33:387-8). The UK's Medical Defence Union suggests that doctors recommend exercise rather than prescribe it, unless they are happy to take responsibility for any mishap. Thankfully, there is as yet no case law in this area.

Doctors may feel uncomfortable with the idea of ageism in medicine, but a survey of older Italians …
FRI-199-First in Human, single ascending dose clinical trial of AIC649 in patients with chronic hepatitis
Authors: Ibironke Addy, Alen Jambrecina, Thomas Berg, Florian van Bömmel, Dirk Kropeit, Christiane Vank, Alexandra Bigge, Katja Nedoschinsky, Hans-Peter Stobernack, Manickam Rangaraju, Silke Kummer, Urte Matschl, Adam Gehring, Johanna Eberhard, Marcus Altfeld, Julian Schulze zur Wiesch, Holger Zimmermann, Daniela Paulsen
Journal: Journal of Hepatology (2019)
SAT-159-Genetic determinants in critical domains of NS5A are associated with genotype 1b HCV-induced hepatocellular carcinoma
Authors: Romina Salpini, Mohammad Alkhatib, Velia Chiara Di Maio, Valentina De Murtas, Marianna Aragri, Rossana Scutari, Angelica Sacco, Ennio Polilli, Chiara Masetti, Silvia Barbaliscia, Ada Bertoli, Valeria Cento, Vincenza Calvaruso, Filomena Morisco, Valeria Pace Palitti, Caterina Pasquazzi, Simona Francioso, Federica Sozio, Alessandro Pieri, Pierluigi Cacciatore, Sergio Babudieri, Elisabetta Teti, Cristina Mussini, Giustino Parruti, Vanni Borghi, Ilaria Lenci, Antonio Craxi, Massimo Andreoni, Angelico Mario, Ivana Rita Maida, Maria Santoro, Valentina Svicher, Carlo-federico Perno, Francesca Ceccherini Silberstein
Journal: Journal of Hepatology (2019)
THU-218-Immune reconstitution inflammatory syndrome and CD4 lymphocyte count as predictive factors for HBsAg seroclearance in HBV/HIV patients treated with antiretroviral therapy
Authors: Yasuharu Kawamoto, Satoshi Tanaka, Akio Ishihara, Dai Watanabe, Tomoko Uehira, Hisashi Ishida, Takuma Shirasaka, Eiji Mita
Journal: Journal of Hepatology (2019)
A Frizzled‐Like Cysteine‐Rich Domain in Glypican‐3 Mediates Wnt Binding and Regulates Hepatocellular Carcinoma Tumor Growth in Mice
Authors: Na Li, Liwen Wei, Xiaoyu Liu, Hongjun Bai, Yvonne Ye, Dan Li, Nan Li, Ulrich Baxa, Qun Wang, Ling Lv, Yun Chen, Mingqian Feng, Byungkook Lee, Wei Gao, Mitchell Ho
Journal: Hepatology (2019)

Wnt signaling is one of the key regulators of hepatocellular carcinoma (HCC) tumor progression. In addition to the classical receptor frizzled (FZD), various coreceptors including heparan sulfate proteoglycans (HSPGs) are involved in Wnt activation. Glypican‐3 (GPC3) is an HSPG that is overexpressed in HCC and functions as a Wnt coreceptor that modulates HCC cell proliferation. These features make GPC3 an attractive target for liver cancer therapy. However, the precise interaction of GPC3 and Wnt and how GPC3, Wnt, and FZD cooperate with each other are poorly understood. In this study, we established a structural model of GPC3 containing a putative FZD‐like cysteine‐rich domain at its N‐terminal lobe. We found that F41 and its surrounding residues in GPC3 formed a Wnt‐binding groove that interacted with the middle region located between the lipid thumb domain and the index finger domain of Wnt3a. Mutating residues in this groove significantly inhibited Wnt3a binding, β‐catenin activation, and the transcriptional activation of Wnt‐dependent genes. In contrast with the heparan sulfate chains, the Wnt‐binding groove that we identified in the protein core of GPC3 seemed to promote Wnt signaling in conditions when FZD was not abundant. Specifically, blocking this domain using an antibody inhibited Wnt activation. In HCC cells, mutating residue F41 on GPC3 inhibited activation of β‐catenin in vitro and reduced xenograft tumor growth in nude mice compared with cells expressing wild‐type GPC3. Conclusion : Our investigation demonstrates a detailed interaction of GPC3 and Wnt3a, reveals the precise mechanism of GPC3 acting as a Wnt coreceptor, and provides a potential target site on GPC3 for Wnt blocking and HCC therapy.
Asthma: traffic pollution is blamed for one in eight new cases in children
Authors: Nigel Hawkes
Journal: BMJ (2019)

Air pollution from traffic is responsible for four million new cases of childhood asthma worldwide every year, says a study that links local measures of air pollution to incidence rates of the disease.1

On average around one in eight new cases of the disease in children is attributable to traffic pollution, but in Shanghai, one of the worst affected cities, the proportion rises to nearly half. Of the 10 areas with the highest numbers of cases attributable to traffic pollution, eight are in China; the other two are Moscow and Seoul.

London ranks lower down the list, in 35th place, with 29% of new cases …
SAT-074-Prevalence and risk factors of colonization by multidrug resistant bacteria in cirrhotic patients admitted to the intensive care unit in a Spanish tertiary hospital
Authors: Daniel Abad, Beatriz Dendariena, Trinidad Serrano, Pilar Luque, Javier Castillo, Alberto Lué, Claudia Mendoza, Jose Ramón Paño, Luis Cortés, Sandra García, Sara Lorente
Journal: Journal of Hepatology (2019)
Estimating the potential impact of the UK government’s sugar reduction programme on child and adult health: modelling study
Authors: Ben Amies-Cull, Adam D M Briggs, Peter Scarborough
Journal: BMJ (2019)

Abstract Objective To estimate the impact of the UK government’s sugar reduction programme on child and adult obesity, adult disease burden, and healthcare costs. Design Modelling study. Setting Simulated scenario based on National Diet and Nutrition Survey waves 5 and 6, England. Participants 1508 survey respondents were used to model weight change among the population of England aged 4-80 years. Main outcome measures Calorie change, weight change, and body mass index change were estimated for children and adults. Impact on non-communicable disease incidence, quality adjusted life years, and healthcare costs were estimated for adults. Changes to disease burden were modelled with the PRIMEtime-CE Model, based on the 2014 population in England aged 18-80. Results If the sugar reduction programme was achieved in its entirety and resulted in the planned sugar reduction, then the calorie reduction was estimated to be 25 kcal/day (1 kcal=4.18 kJ=0.00418 MJ) for 4-10 year olds (95% confidence interval 23 to 26), 25 kcal/day (24 to 28) for 11-18 year olds, and 19 kcal/day (17 to 20) for adults. The reduction in obesity could represent 5.5% of the baseline obese population of 4-10 year olds, 2.2% of obese 11-18 year olds, and 5.5% of obese 19-80 year olds. A modelled 51 729 quality adjusted life years (95% uncertainty interval 45 768 to 57 242) were saved over 10 years, including 154 550 (132 623 to 174 604) cases of diabetes and relating to a net healthcare saving of £285.8m (€332.5m, $373.5m; £249.7m to £319.8m). Conclusions The UK government’s sugar reduction programme could reduce the burden of obesity and obesity related disease, provided that reductions in sugar levels and portion sizes do not prompt unanticipated changes in eating patterns or product formulation.
Abstract 20294: Longer Time to VT Ablation Correlates With More Complex Ventricular Substrate
Authors: Asad Aboud, Sushan Yang, Jay Montgomery, Ricardo M Lugo, Pablo Saavedra, Juan Carlos Estrada, Sharon Shen, Walter Clair, Robert Abraham, George Crossley, Christopher Ellis, Quinn Wells, Yan R Su, Benjamin Shoemaker, Arvindh Kanagasundram
Journal: Circulation (2017)

Introduction: It is unknown if the functional characteristics of endocardial scar change over time from initial VT diagnosis. Hypothesis: Patients with longer duration from index VT have more compl...
Experience of detection of circulating tumor cells (CTCs) in patients with epithelial tumors.
Authors: Inna Arnoldovna Novikova, Oleg Ivanovich Kit, Andrey Vladimirovich Bakhtin, Aleksey Yurievich Maksimov, Elena N. Chernikova, Rukiyat Isaeva, Olesya N. Selyutina, Elena Petrovna Ulianova, Dmitry Aleksandrovich Shvyrev
Journal: Journal of Clinical Oncology (2015)

e22017 Background: The purpose of this study was to analyze the content and detection rate of CTCs in blood of patients with kidney, prostate, breast, lung and colon cancers. Methods: 187 patients were recruited, including 100 with colon cancer (42-82 y.o., mean age 63.7±1.9), stage III-IV; 25 - breast cancer (34-76 y.o., mean age 54.8±2.2), stage IIa-IIIa; 20 – lung cancer (50-61 y.o., mean age 52.3±4.8), stage IV; 30 - prostate cancer, (58-83 y.o., mean age 71.6±3.9), stage IV; 6 - pancreatic cancer (55-66 y.o., mean age 61.5±3.6), stage IV; 6 – kidney cancer (44-68 y.o., mean age 58.8±2.3), stage IV. G3 adenocarcinoma - 48.6%, G2 adenocarcinoma - 32%, infiltrating ductal carcinoma – 12.3%, clear cell carcinoma - 3.2%, other cancer – 3.9%. CellSearch System, Janssen Diagnostics, LLC was used to detect CTCs. Absolute CTCs content was calculated taking into account morphologic characteristics and expression of various surface markers (CK 8, 18, 19, CD 45). Results: CTCs were detected in 114 (61%) of 187 patients. CTCs were found in 28% of patients with breast cancer (1-4 CTCs); colon cancer - 69% (1-402 CTCs); prostate cancer – 60% (1-190 CTCs); lung cancer – 40% (1-3 CTCs); kidney cancer - 67% (2-5 CTCs); pancreatic cancer - 33% (1-2 CTCs). In G2 adenocarcinoma - 62%; G3 adenocarcinoma – 71.4%; infiltrating ductal carcinoma - 30.4%; clear cell carcinoma - 67%; undifferentiated carcinoma - 50%. Conclusions: Content and detection rate of CTCs vary widely in tumors of different localizations. Studying detection of CTCs in epithelial tumors of different localizations will be continued.
A Bayesian framework that integrates multi-omics data and gene networks predicts risk genes from schizophrenia GWAS data
Authors: Quan Wang, Rui Chen, Feixiong Cheng, Qiang Wei, Ying Ji, Hai Yang, Xue Zhong, Ran Tao, Zhexing Wen, James S. Sutcliffe, Chunyu Liu, Edwin H. Cook, Nancy J. Cox, Bingshan Li
Journal: Nature Neuroscience (2019)
Tumor-derived nanovesicles promote lung distribution of the therapeutic nanovector through repression of Kupffer cell-mediated phagocytosis
Authors: Xiaolan Qiu, Zhi Li, Xuedong Han, Linlin Zhen, Chao Luo, Minmin Liu, Kun Yu, Yi Ren
Journal: Theranostics (2019)

Tumor-derived nanovesicles have been widely used as a biomarker or therapeutic target in various tumor types.However, these nanovesicles have limited use in therapy due to the risk of advancing tumor development.Methods: Exosome-like nanovesicles (ENVs) were developed from metastatic breast cancer 4T1 cells-derived exosomes.The distribution of ENVs and their impact on macrophage-mediated phagocytosis were evaluated.The effect of ENVs pretreatment on anti-lung metastasis therapeutic effects of chemotherapeutic drugs delivered by DOTAP/DOPE liposomes in breast cancer-bearing mice was also examined.Results: We demonstrated that, following intravenous injection in mice, ENVs were preferentially uptaken by Kupffer cells and repressed phagocytosis.The decreased uptake appeared to be due to the translocation of membrane nucleolin from the inner face of the plasma membrane to the cell surface and intercellular Ca 2+ fluxes, leading to altered expression of genes involved in phagocytosis by macrophages.Mice pretreated with 4T1-derived ENVs led to the decreased uptake of DOTAP: DOPE liposomes (DDL) in the liver.Consequently, doxorubicin-loaded DDL transported to the lungs instead of the liver, effectively inhibiting breast cancer lung metastasis.Importantly, 4T1 cells exosome-derived ENVs had no detectable toxicity in vivo and low-risk to promote tumor growth and metastasis compared to 4T1 cells exosomes.Conclusion: Our results suggested that pretreatment with 4T1 ENVs represents a strategy to escape Kupffer cell-mediated phagocytosis effectively targeting drug delivery vehicles to tumor metastasis, reducing the IC50 of the chemotherapeutic drugs, and avoiding adverse side effects.
THU-025-Pathway-analysis using datasets of GWAS and microarray identified IFNG as the most significant upstream-regulator in primary biliary cholangitis
Authors: Kazuko Ueno Ueno, Yoshihiro Aiba, Shinji Shimoda, Yuki Hitomi, Olivier Gervais, Yosuke Kawai, Minae Kawashima, Nao Nishida, Kaname Kojima, Seigo Abiru, Shinya Nagaoka, Atsumasa Komori, Hiroshi Yatsuhashi, Atsushi Tanaka, Masao Nagasaki, Katsushi Tokunaga, Minoru Nakamura
Journal: Journal of Hepatology (2019)
FRI-081-Characterisation of severe liver injury induced by immune checkpoint inhibitors
Authors: Yana Davidov, Afif Yaccob, Orit Pappo, Nora Balint-Lahat, Oranit Cohen-ezra, Maria Lihter, Itai Kalisky, Ziv Ben Ari, Ella Veitsman
Journal: Journal of Hepatology (2019)
Adverse fat depots, marrow adiposity, and skeletal deficits in long-term survivors of pediatric hematopoietic stem cell transplantation.
Authors: Sogol Mostoufi-Moab, Jeremy Magland, Elizabeth Isaacoff, Wenli Sun, Chamith S Rajapakse, Babette Zemel, Felix Wehrli, Karuna Shekdar, Joshua Baker, Jin Long, Mary B Leonard
Journal: Journal of Clinical Oncology (2015)

10073 Background: Allogeneic hematopoietic stem-cell transplantation (alloHSCT) survivors treated with total body irradiation (TBI) exhibit bone deficits and excess adiposity, potentially related to altered mesenchymal stem cell differentiation into osteoblasts or adipocytes. Methods: We examined associations among fat distribution, bone microarchitecture, and insulin resistance in alloHSCT survivors after TBI. This was a cross-sectional observational study of 25 alloHSCT survivors (aged 12-25 years) a median of 9.7 (4.3-19.3) years after alloHSCT compared to 25 age-, race-, and sex-matched healthy controls. Vertebral MR spectroscopic imaging and tibia micro-MRI were used to quantify marrow adipose tissue (MAT) and trabecular microarchitecture. Additional measures included DXA whole-body fat mass (WB-FM), leg lean mass (Leg-LM), trunk visceral adipose tissue (VAT), and CT calf muscle density. Insulin resistance in alloHSCT survivors was estimated by HOMA-IR. Results: AlloHSCT survivors had lower Leg-LM (p< 0.001), and greater VAT (p< 0.01), MAT (p< 0.001) and fat infiltration of muscle (p= 0.04) independent of WB-FM, vs. matched-controls; BMI did not differ. Survivors had lower bone volume fraction and abnormal microarchitecture including greater erosion and more rod-like structure vs. controls (all p= 0.04); 14 had vertebral deformities and two had compression fractures. Greater WB-FM, VAT, MAT and muscle fat infiltration were associated with abnormal trabecular microarchitecture (p< 0.04 for all). AlloHSCT HOMA-IR was elevated, associated with younger age at transplantation (p< 0.01), and positively correlated with WB-FM and VAT (both p< 0.01). Conclusions: Long-term survivors demonstrate sarcopenic obesity, insulin resistance, and vertebral deformities. The markedly increased marrow adiposity, abnormal bone microarchitecture, and abnormal fat distribution highlight the risks of long-term treatment-related morbidity and mortality in alloHSCT recipients after TBI. Future studies are needed to identify strategies to prevent and treat metabolic and skeletal complications in this growing population of childhood alloHSCT survivors.