tbuckley/cabot-search huggingface dataset:
Uremic Solute-Aryl Hydrocarbon Receptor-Tissue Factor Axis Associates with Thrombosis after Vascular Injury in Humans
Authors: Vijaya B. Kolachalama, Moshe Shashar, Faisal Alousi, Sowmya Shivanna, Keshab Rijal, Mostafa E. Belghasem, Joshua Walker, Shinobu Matsuura, Gary H. Chang, C. Michael Gibson, Laura M. Dember, Jean M. Francis, Katya Ravid, Vipul C. Chitalia
Journal: Journal of the American Society of Nephrology (2018)

Individuals with CKD are particularly predisposed to thrombosis after vascular injury. Using mouse models, we recently described indoxyl sulfate, a tryptophan metabolite retained in CKD and an activator of tissue factor (TF) through aryl hydrocarbon receptor (AHR) signaling, as an inducer of thrombosis across the CKD spectrum. However, the translation of findings from animal models to humans is often challenging. Here, we investigated the uremic solute–AHR–TF thrombosis axis in two human cohorts, using a targeted metabolomics approach to probe a set of tryptophan products and high-throughput assays to measure AHR and TF activity. Analysis of baseline serum samples was performed from 473 participants with advanced CKD from the Dialysis Access Consortium Clopidogrel Prevention of Early AV Fistula Thrombosis trial. Participants with subsequent arteriovenous thrombosis had significantly higher levels of indoxyl sulfate and kynurenine, another uremic solute, and greater activity of AHR and TF, than those without thrombosis. Pattern recognition analysis using the components of the thrombosis axis facilitated clustering of the thrombotic and nonthrombotic groups. We further validated these findings using 377 baseline samples from participants in the Thrombolysis in Myocardial Infarction II trial, many of whom had CKD stage 2–3. Mechanistic probing revealed that kynurenine enhances thrombosis after vascular injury in an animal model and regulates thrombosis in an AHR-dependent manner. This human validation of the solute-AHR-TF axis supports further studies probing its utility in risk stratification of patients with CKD and exploring its role in other diseases with heightened risk of thrombosis.
Comparison of the diagnostic performances of ultrasonography, CT and fine needle aspiration cytology for the prediction of lymph node metastasis in patients with lymph node dissection of papillary thyroid carcinoma: A retrospective cohort study
Authors: Na Lae Eun, Eun Ju Son, Jeong-Ah Kim, Hye Mi Gweon, Jung-Hyun Kang, Ji Hyun Youk
Journal: International Journal of Surgery (2018)
Infographic: Trends in paediatric and adolescent ACL injuries
Authors: Louise Shaw, Caroline F Finch, Sheree Bekker
Journal: British Journal of Sports Medicine (2018)

Media attention and parental concern have recently brought a higher awareness to ACL injuries in children and adolescents,1 2 given their potential for unfavourable healthcare costs and outcomes in the long term.3 4 Greater demands being placed on youth athletes through increased training, younger sports specialisation and emphasis on year-round competitive play have led to an increase in the diagnosis of sports-specific knee injuries.3 However, there is little research into the trends of ACL injuries in this population. …
Ibrutinib Inhibits cGVHD Pathogenic Pre-Germinal Center B-Cells and Follicular Helper Cells While Preserving Immune Memory and Th1 T-Cells
Authors: Bita Sahaf, Dmitry Tebaykin, Melissa Hopper, Patricia Cheung, Fabiola Bittencourt, Corey S. Cutler, Mukta Arora, Edmund K. Waller, Madan Jagasia, Iskra Pusic, Mary E. Flowers, Aaron C. Logan, Samantha Jaglowski, Jason Lih, Isabelle Solman, Indu D. Lal, Lori Styles, John S. Hill, Danelle F. James, Sean Bendall, David B. Miklos, Jason Dubovsky
Journal: Blood (2017)
Association of Oral Microbiome With Risk for Incident Head and Neck Squamous Cell Cancer
Authors: Richard B. Hayes, Jiyoung Ahn, Xiaozhou Fan, Brandilyn A. Peters, Yingfei Ma, Liying Yang, Ilir Agalliu, Robert D. Burk, Ian Ganly, Mark P. Purdue, Neal D. Freedman, Susan M. Gapstur, Zhiheng Pei
Journal: JAMA Oncology (2018)

Case-control studies show a possible relationship between oral bacteria and head and neck squamous cell cancer (HNSCC). Prospective studies are needed to examine the temporal relationship between oral microbiome and subsequent risk of HNSCC.To prospectively examine associations between the oral microbiome and incident HNSCC.This nested case-control study was carried out in 2 prospective cohort studies: the American Cancer Society Cancer Prevention Study II Nutrition Cohort (CPS-II) and the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial (PLCO). Among 122 004 participants, 129 incident patient cases of HNSCC were identified during an average 3.9 years of follow-up. Two controls per patient case (n = 254) were selected through incidence density sampling, matched on age, sex, race/ethnicity, and time since mouthwash collection. All participants provided mouthwash samples and were cancer-free at baseline.Oral microbiome composition and specific bacterial abundances were determined through bacterial 16S rRNA gene sequencing. Overall oral microbiome composition and specific taxa abundances were compared for the case group and the control group, using PERMANOVA and negative binomial generalized linear models, respectively, controlling for age, sex, race, cohort, smoking, alcohol, and oral human papillomavirus-16 status. Taxa with a 2-sided false discovery rate (FDR)-adjusted P-value (q-value) <.10 were considered significant.Incident HNSCC.The study included 58 patient cases from CPS-II (mean [SD] age, 71.0 [6.4] years; 16 [27.6%] women) and 71 patient cases from PLCO (mean [SD] age, 62.7 [4.8] years; 13 [18.3%] women). Two controls per patient case (n = 254) were selected through incidence density sampling, matched on age, sex, race/ethnicity, and time since mouthwash collection. Head and neck squamous cell cancer cases and controls were similar with respect to age, sex, and race. Patients in the case group were more often current tobacco smokers, tended to have greater alcohol consumption (among drinkers), and to be positive for oral carriage of papillomavirus-16. Overall microbiome composition was not associated with risk of HNSCC. Greater abundance of genera Corynebacterium (fold change [FC], 0.58; 95% confidence interval [CI], 0.41-0.80; q = .06) and Kingella (FC, 0.63; 95% CI, 0.46-0.86; q = .08) were associated with decreased risk of HNSCC, potentially owing to carcinogen metabolism capacity. These findings were consistent for both cohorts and by cohort follow-up time. The observed relationships tended to be stronger for larynx cancer and for individuals with a history of tobacco use.This study demonstrates that greater oral abundance of commensal Corynebacterium and Kingella is associated with decreased risk of HNSCC, with potential implications for cancer prevention.
Beta-blocker use in acute myocardial infarction patients with congestive heart failure
Authors: Stephanie W Lui, Carolyn Harper, Rita Redberg
Journal: Circulation (2001)

P49     Background: Beta-blockers have been shown to improve outcomes  for patients with acute myocardial infarction (AMI), but have been used  reluctantly in AMI patients with congestive heart failure (CHF).  However, recent studies have shown that the benefits of beta-blockers  outweigh the risks in AMI patients with CHF, and that beta-blockers are  a safe and effective treatment for these patients. The purpose of this  study is to evaluate the use of beta-blockers in AMI patients with CHF.  Methods: A random sample of 4,478 patients aged 65 and older was  selected from all fee-for-service Medicare beneficiaries discharged  from California hospitals between January to June, 1998 with a  principal diagnosis of AMI. After unconfirmed AMI cases and those with  unknown discharge status were excluded, there were 2,680 cases for  analysis. Results: In this study, 48.2% (1,291) of all AMI patients,  and 66.2% (290/438) of those with no contraindications received a  beta-blocker. Overall, 40.1% (1,074) had CHF plus other  contraindications, and 11.6% (312) had CHF but had no other  contraindications. Controlling for age, race, and gender, and compared  to those with no contraindications, beta-blocker prescription rates  were significantly lower among patients who had CHF as the only  documented reason for not prescribing a beta-blocker (OR=0.3, 95%  CI=0.3-0.5). Conclusions: Beta-blockers are underutilized in this  sample of AMI patients. CHF is an independent predictor for  non-prescription of a beta-blocker. Despite evidence from recent  studies suggesting its benefit, beta-blocker use is still suboptimal in  AMI patients, particularly those with CHF.
Bisphosphonates: Mechanisms of Action
Authors: Herbert Fleisch
Journal: Endocrine Reviews (1998)

I. Introduction II. Chemistry III. Effects in Vivo A. Inhibition of calcification B. Inhibition of bone resorption C. Effects on bone formation D. Effects on noncalcified tissues IV. Mechanisms of Action A. Calcification B. Bone resorption C. Other effects V. Pharmacokinetics VI. Animal Toxicology and Human Adverse Events A. Animal toxicology B. Human adverse events VII. Conclusion
Prolonged Disease-Free Survival after One Course of Perioperative Adjuvant Chemotherapy for Node-Negative Breast Cancer
Journal: New England Journal of Medicine (1989)

We compared a single perioperative cycle of adjuvant combination chemotherapy with no adjuvant treatment in a randomized trial (Ludwig Trial V) including 1275 patients with breast cancer who had no axillary-node metastases. The chemotherapy was administered on days 1 and 8, beginning within 36 hours after mastectomy, and consisted of cyclophosphamide, methotrexate, fluorouracil, and leucovorin. At a median follow-up of 42 months, the mean four-year disease-free survival (+/- SE) was 77 +/- 2 percent among the patients who received chemotherapy perioperatively, as compared with 73 +/- 2 percent among the patients who received no adjuvant treatment (hazard ratio, 0.77; 95 percent confidence interval, 0.61 to 0.98; P = 0.04). An advantage was observed for both premenopausal and postmenopausal women. The magnitude of the treatment effect was largest among patients with no or low estrogen-receptor content in the primary tumor. We conclude that chemotherapy modifies the post-operative course of node-negative breast cancer. Further trials to investigate an optimal selection of patients and treatments should be regarded as the best available therapeutic approach.
Avoid stigmatising language for people who use drugs, global commission urges
Authors: Adrian O’Dowd
Journal: BMJ (2018)

People who use drugs are unfairly stigmatised by being described in derogatory terms by some clinicians, politicians, and the media, a global report has said.1

Terms such as “junkie,” “addict,” and “drug/substance abuser” should be avoided, said the Global Commission on Drug Policy—a body made up of political leaders, cultural figures, and personalities from the business sector, including Kofi Annan, former secretary general of the United Nations, and Richard Branson, founder of the Virgin Group.

In a report published on 9 January the commission said that it wanted to tackle worldwide problems in drug perception. “Prejudices …
Percutaneous Closure Versus Medical Treatment in Stroke Patients With Patent Foramen Ovale
Authors: Salvatore De Rosa, Horst Sievert, Jolanda Sabatino, Alberto Polimeni, Sabato Sorrentino, Ciro Indolfi
Journal: Annals of Internal Medicine (2018)

Background: New evidence emerged recently regarding the percutaneous closure of patent foramen ovale (PFO) to prevent recurrent stroke in patients with cryptogenic stroke. Purpose: To compare risks for recurrent cerebrovascular events in adults with PFO and cryptogenic stroke who underwent PFO closure versus those who received medical therapy alone. Data Sources: PubMed, Scopus, and Google Scholar from 1 December 2004 through 14 September 2017; references of eligible studies; relevant scientific session abstracts; and cardiology Web sites. Study Selection: Randomized controlled trials, published in English, that compared PFO closure using a currently available device with medical treatment alone and that reported, at minimum, the rates of stroke or transient ischemic attack (TIA) or of new-onset atrial fibrillation (AF) or atrial flutter (AFL). Data Extraction: 2 investigators independently extracted study data and assessed study quality. Data Synthesis: 4 of 5 trials comparing PFO closure with medical therapy used commercially available devices. These 4 trials, involving 2531 patients, found that PFO closure reduced the risk for the main outcome of stroke or TIA (risk difference [RD], −0.029 [95% CI, −0.050 to −0.007]) and increased the risk for new-onset AF or AFL (RD, 0.033 [CI, 0.012 to 0.054]). The beneficial effect of PFO closure was associated with larger interatrial shunts (P = 0.034). Limitation: Trials were not double-blind, and inclusion criteria were heterogeneous. Conclusion: Compared with medical treatment, PFO closure prevents recurrent stroke and TIA but increases the incidence of AF or AFL in PFO carriers with cryptogenic stroke. Primary Funding Source: Italian Ministry of Education, University and Research (MIUR). (PROSPERO: CRD42017074686)
Hypoxemia from sublingual nitroglycerin
Authors: Z. Danilevicius
Journal: JAMA (1979)

Kopman et al<sup>1</sup>accidentally discovered that after the administration of nitroglycerin in the course of induction of anesthesia for cardiac surgery, some patients had surprisingly low Pao<sub>2</sub>values. Therefore, these investigators undertook a special study of the effect of nitroglycerin on arterial blood gases and hemodynamics in a group of patients with coronary heart disease. They examined 21 patients. Thirteen of these patients received morphine and scopolamine as a premedication when sublingual nitroglycerin was given. Eight patients did not receive premedication. In the 13 patients who received premedication, the Pao<sub>2</sub>level decreased from a mean of 65+13 to 55+11 mm Hg following the administration of nitroglycerin. In the eight patients who did not receive premedication, the mean value of 78±10 mm Hg decreased to 64±8 mm Hg. In both groups pH and Pco<sub>2</sub>values did not change. The study provided conclusive evidence that sublingual nitroglycerin adversely
IgE sensitization profiles of adult patients with moderate and severe atopic dermatitis: is there a role for molecular-based allergy diagnosis?
Authors: Karine Boufleur, Janaina ML. Melo, Renata Nahas Cardili, Marcelo ABR. Amaral, Mariana PL. Ferriani, Thais N. Mendonça, Luana SM. Maia, LuisaKarla P. Arruda, Adriana S. Moreno
Journal: Journal of Allergy and Clinical Immunology (2018)
Growth and Rupture Risk of Small Unruptured Intracranial Aneurysms
Authors: Mark S. Roberts
Journal: Annals of Internal Medicine (2018)

Letters16 January 2018Growth and Rupture Risk of Small Unruptured Intracranial AneurysmsMark S. Roberts, MD, MPPMark S. Roberts, MD, MPPUniversity of Pittsburgh Graduate School of Public Health, Pittsburgh, Pennsylvania (M.S.R.)Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/L17-0523 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail TO THE EDITOR:As a survivor of the spontaneous rupture of an asymptomatic 3-mm aneurysm of the left posterior inferior cerebellar artery, I read Malhotra and colleagues' review (1) on the growth and rupture of small intracranial aneurysms with interest. Just as the textbooks report, I experienced a “thunderclap” headache while in the shower; was in the emergency department within 20 minutes; and, shortly after undergoing computed tomography, was intubated with a burr hole placed to relieve already developing hydrocephalus from a large subarachnoid hemorrhage. After 2 urgent surgeries, a few weeks of rehabilitation, and several months of recovery, I ...Reference1. Malhotra A, Wu X, Forman HP, Grossetta Nardini HK, Matouk CC, Gandhi D, et al. Growth and rtiture risk of small unruptured intracranial aneurysms: a systematic review. Ann Intern Med. 2017;167:26-33. [PMID: 28586893]. doi:10.7326/M17-0246 LinkGoogle Scholar Author, Article, and Disclosure InformationAffiliations: University of Pittsburgh Graduate School of Public Health, Pittsburgh, Pennsylvania (M.S.R.)Disclosures: The author has disclosed no conflicts of interest. The form can be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=L17-0523. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetailsSee AlsoGrowth and Rupture Risk of Small Unruptured Intracranial Aneurysms Ajay Malhotra , Xiao Wu , Howard P. Forman , Holly K. Grossetta Nardini , Charles C. Matouk , Dheeraj Gandhi , Christopher Moore , and Pina Sanelli Growth and Rupture Risk of Small Unruptured Intracranial Aneurysms Ajay Malhotra and Xiao Wu Metrics 16 January 2018Volume 168, Issue 2Page: 159KeywordsAneurysmsComputed axial tomographyConflicts of interestDisclosureEmergency departmentEvidence based medicineHeadachesHydrocephalusSubarachnoid hemorrhageSurgery ePublished: 16 January 2018 Issue Published: 16 January 2018 Copyright & PermissionsCopyright © 2018 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
Lack of penetration of amikacin into saliva of tuberculosis patients
Authors: Simone H.J. van den Elsen, Onno W. Akkerman, Justine R. Huisman, Daan J. Touw, Tjip S. van der Werf, Mathieu S. Bolhuis, Jan-Willem C. Alffenaar
Journal: European Respiratory Journal (2018)

In the 2016 update of the World Health Organization treatment guideline for drug-resistant tuberculosis (TB), a shorter multidrug-resistant TB regimen was proposed because of its higher treatment outcomes [1]. However, therapeutic drug monitoring (TDM) is an excellent method to improve clinical outcomes as well and its practice is on the rise [2]. A well-known side-effect of group B injectable anti-TB drugs ( e.g . amikacin) is ototoxicity [3]. TDM could also be a solution to minimise side-effects by lowering the drug exposure [4]. In the study by van Altena et al. [5] , TDM was practised using the ratio of peak concentration ( C max) to minimal inhibitory concentration (MIC) and this resulted in a reduction in patients with hearing loss. Saliva is considered as an alternative matrix for TDM because it is easy, noninvasive and more patient friendly to sample [6]. Studies found a limited penetration of gentamycin and tobramycin into saliva [7], while detectable levels of amikacin in saliva of neonates were reported [8]. Given the low penetration of aminoglycosides into saliva and interest in C max for TDM of amikacin, our objective was to study whether the salivary C max of amikacin is measurable and useful in salivary TDM. Salivary C max TDM of amikacin was not feasible in TB treatment due to the very low penetration into saliva <http://ow.ly/d6v230h0bWG>
pH‐Responsive PEG–Doxorubicin‐Encapsulated Aza‐BODIPY Nanotheranostic Agent for Imaging‐Guided Synergistic Cancer Therapy
Authors: Dapeng Chen, Qianyun Tang, Jianhua Zou, Xiaoyan Yang, Wei Huang, Qi Zhang, Jinjun Shao, Xiaochen Dong
Journal: Advanced Healthcare Materials (2018)

Abstract Synergistic cancer therapy is of great interest for multiple advantages, such as excellent targeting accuracy, low side effects, and enhanced therapeutic efficiency. Herein, a near‐infrared photosensitizer aza‐BODIPY (AB) with high singlet oxygen quantum yield (Φ Δ = 82%) is designed and synthesized. With Schiff's base obtained from condensation reaction between doxorubicin (DOX) and polyethylene glycol‐benzaldehyde (PEG–CHO) as the polymer matrix, aza‐BODIPY is encapsulated to afford hydrophilic nanoparticles (DAB NPs). The DAB NPs exhibit high reactive oxygen species (ROS) generation rate and outstanding photothermal conversion efficiency (η = 38.3%) under irradiation. In vivo fluorescence‐ and photothermal‐imaging (PTI) results demonstrate that DAB NPs can specifically accumulate at tumor sites and serve as dual‐modal imaging probe for cancer diagnosis. Particularly, triggered by acidic tumor microenvironment, the HCN bond of Schiff's base would be broken simultaneously, resulting in the efficient release of DOX from DAB NPs at tumor sites as well as enhancing the targeting performance of chemotherapeutics. Compared with free DOX and aza‐BODIPY nanoparticles, DAB NPs can inhibit tumor growth more effectively through pH‐responsive photodynamic/photothermal/chemo synergistic therapy. This report may also present a practicable strategy to develop a pH‐responsive nanotheranostic agent for tumor targeting, imaging, and therapy.
Macroporous Hydrogels: Structured Macroporous Hydrogels: Progress, Challenges, and Opportunities (Adv. Healthcare Mater. 1/2018)
Authors: Kevin J. De France, Fei Xu, Todd Hoare
Journal: Advanced Healthcare Materials (2018)

Structured macroporous hydrogels offer both the swelling and interfacial properties of bulk hydrogels as well as the transport properties of “hard” macroporous materials, making these networks intriguing for many biomedical applications. In article number 1700927, Todd Hoare and co-workers summarize conventional preparation methods of structured macroporous hydrogels and highlight the progress, opportunities and challenges associated with such hydrogels, with a particular emphasis on creating high strength networks, anisotropic pores, and using solvent-free preparation techniques. Pictured, a macroporous hydrogel with anisotropic pores is used for directing cell growth throughout the network. Cover image by Dr. Kevin Yager, Brookhaven National Laboratories.
Targeted Therapy for Advanced Solid Tumors on the Basis of Molecular Profiles: Results From MyPathway, an Open-Label, Phase IIa Multiple Basket Study
Authors: John D. Hainsworth, Funda Meric-Bernstam, Charles Swanton, Herbert Hurwitz, David R. Spigel, Christopher Sweeney, Howard A. Burris, Ron Bose, Bongin Yoo, Alisha Stein, Mary Beattie, Razelle Kurzrock
Journal: Journal of Clinical Oncology (2018)

Purpose Detection of specific molecular alterations in tumors guides the selection of effective targeted treatment of patients with several types of cancer. These molecular alterations may occur in other tumor types for which the efficacy of targeted therapy remains unclear. The MyPathway study evaluates the efficacy and safety of selected targeted therapies in tumor types that harbor relevant genetic alterations but are outside of current labeling for these treatments. Methods MyPathway ( ClinicalTrials.gov identifier: NCT02091141) is a multicenter, nonrandomized, phase IIa multiple basket study. Patients with advanced refractory solid tumors harboring molecular alterations in human epidermal growth factor receptor-2, epidermal growth factor receptor, v-raf murine sarcoma viral oncogene homolog B1, or the Hedgehog pathway are treated with pertuzumab plus trastuzumab, erlotinib, vemurafenib, or vismodegib, respectively. The primary end point is investigator-assessed objective response rate within each tumor-pathway cohort. Results Between April 1, 2014 and November 1, 2016, 251 patients with 35 different tumor types received study treatment. The efficacy population contains 230 treated patients who were evaluated for response or discontinued treatment before evaluation. Fifty-two patients (23%) with 14 different tumor types had objective responses (complete, n = 4; partial, n = 48). Tumor-pathway cohorts with notable objective response rates included human epidermal growth factor receptor-2-amplified/overexpressing colorectal (38% [14 of 37]; 95% CI, 23% to 55%) and v-raf murine sarcoma viral oncogene homolog B1 V600-mutated non-small-cell lung cancer (43% [six of 14]; 95% CI, 18% to 71%). Conclusion The four currently approved targeted therapy regimens in the MyPathway study produced meaningful responses when administered without chemotherapy in several refractory solid tumor types not currently labeled for these agents.