tbuckley/cabot-search huggingface dataset:
Effect of a Fracture Liaison Service on the Rate of Subsequent Fracture Among Patients With a Fragility Fracture in the Norwegian Capture the Fracture Initiative (NoFRACT)
Authors: Camilla Andreasen, Lene B. Solberg, Trude Basso, Tove T. Borgen, Cecilie Dahl, Torbjørn Wisløff, Gunhild Hagen, Ellen M. Apalset, Jan-Erik Gjertsen, Wender Figved, Lars M. Hübschle, Jens M. Stutzer, Jan Elvenes, Ragnar M. Joakimsen, Unni Syversen, Erik F. Eriksen, Lars Nordsletten, Frede Frihagen, Tone K. Omsland, Åshild Bjørnerem
Journal: JAMA Network Open (2018)

<h3>Importance</h3> Fragility fracture is a major health issue because of the accompanying morbidity, mortality, and financial cost. Despite the high cost to society and personal cost to affected individuals, secondary fracture prevention is suboptimal in Norway, mainly because most patients with osteoporotic fractures do not receive treatment with antiosteoporotic drugs after fracture repair. <h3>Objectives</h3> To improve secondary fracture prevention by introducing a standardized intervention program and to investigate the effect of the program on the rate of subsequent fractures. <h3>Design, Setting, and Participants</h3> Trial protocol of the Norwegian Capture the Fracture Initiative (NoFRACT), an ongoing, stepped wedge cluster randomized clinical trial in 7 hospitals in Norway. The participating hospitals were cluster randomized to an intervention starting date: May 1, 2015; September 1, 2015; and January 1, 2016. Follow-up is through December 31, 2019. The outcome data were merged from national registries of women and men 50 years and older with a recent fragility fracture treated at 1 of the 7 hospitals. <h3>Discussion</h3> The NoFRACT trial is intended to enroll 82 000 patients (intervention period, 26 000 patients; control period, 56 000 patients), of whom 23 578 are currently enrolled by January 2018. Interventions include a standardized program for identification, assessment, and treatment of osteoporosis in patients with a fragility fracture that is led by a trained coordinating nurse. The primary outcome is rate of subsequent fracture (per 10 000 person-years) based on national registry data. Outcomes before (2008-2015; control period) and after (2015-2019; intervention period) the intervention will be compared, and each hospital will act as its own control. Use of outcomes from national registry data means that all patients are included in the analysis regardless of whether they are exposed to the intervention (intention to treat). A sensitivity analysis with a transition window will be performed to mitigate possible within-cluster contamination. <h3>Results</h3> Results are planned to be disseminated through publications in peer-reviewed journals and presented at local, national, and international conferences. <h3>Conclusions</h3> By introducing a standardized intervention program for assessment and treatment of osteoporosis in patients with fragility fractures, we expect to document reduced rates of subsequent fractures and fracture-related mortality. <h3>Trial Registration</h3> ClinicalTrials.gov Identifier:NCT02536898
Induction of Oxidative Stress Through Inhibition of Thioredoxin Reductase 1 Is an Effective Therapeutic Approach for Hepatocellular Carcinoma
Authors: Derek Lee, Iris Ming‐Jing Xu, David Kung‐Chun Chiu, Josef Leibold, Aki Pui‐Wah Tse, Macus Hao‐Ran Bao, Vincent Wai‐Hin Yuen, Cerise Yuen‐Ki Chan, Robin Kit‐Ho Lai, Don Wai‐Ching Chin, Daniel For‐Fan Chan, Tan‐To Cheung, Siu‐Ho Chok, Chun‐Ming Wong, Scott W. Lowe, Irene Oi‐Lin Ng, Carmen Chak‐Lui Wong
Journal: Hepatology (2018)

Hepatocellular carcinoma (HCC) is one of the most prevalent and lethal cancers worldwide which lacks effective treatment. Cancer cells experience high levels of oxidative stress due to increased generation of reactive oxygen species (ROS). Increased antioxidant‐producing capacity is therefore found in cancer cells to counteract oxidative stress. The thioredoxin system is a ubiquitous mammalian antioxidant system which scavenges ROS, and we demonstrate that it is vital for HCC growth as it maintains intracellular reduction‐oxidation (redox) homeostasis. Transcriptome sequencing in human HCC samples revealed significant overexpression of thioredoxin reductase 1 (TXNRD1), the cytosolic subunit and key enzyme of the thioredoxin system, with significant correlations to poorer clinicopathological features and patient survival. Driven by the transcriptional activation of nuclear factor (erythroid‐derived 2)–like 2, the master protector against oxidative stress, TXNRD1 counteracts intracellular ROS produced in human HCC. Inhibition of TXNRD1 through genetic inhibition hindered the proliferation of HCC cells and induced apoptosis in vitro . Administration of the pharmacological TXNRD1 inhibitor auranofin (AUR) effectively suppressed the growth of HCC tumors induced using the hydrodynamic tail vein injection and orthotopic implantation models in vivo. Furthermore, AUR sensitized HCC cells toward the conventional therapeutic sorafenib. Conclusion: Our study highlights the reliance of HCC cells on antioxidants for redox homeostasis and growth advantage; targeting TXNRD1 resulted in dramatic accumulation of ROS, which was found to be an effective approach for the suppression of HCC tumor growth.
A year of small heartbreaks (or, a physician writes her first death note)
Authors: Katharine Lawrence
Journal: Annals of Internal Medicine (2018)

Ad Libitum18 December 2018A year of small heartbreaks (or, a physician writes her first death note)Katharine Lawrence, MDKatharine Lawrence, MDNew York University School of Medicine, New York, New York (K.L.)Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/M18-1399 Audio Reading - “A year of small heartbreaks (or, a physician writes her first death note)” Audio. Virginia Hood, MD, reads "A year of small heartbreaks (or, a physician writes her first death note)," by K. Lawrence. Your browser does not support the audio element. Audio player progress bar Step backward in current audio track Play current audio trackPause current audio track Step forward in current audio track Mute current audio trackUnmute current audio track 00:00/ SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail For her, it had been,among other things,a year of small heartbreaks.She, unfamiliar with the ways of parting,had not yet learned to say goodbye.After thirty years.It started slowly,a creeping, where before there had been none.No warnings, either.Brittle shells, sprinkled, and ground to powder.The broken trappings of all her strife,of those she fell to love, to keepdespite their anonymity,their insistence on the leaving.Ghosts.Their swollen veins, broken skin; their eyeswhen they saw deathin the roomover her shoulder.On those first nights, when they passed, she was so alone.She, the harbinger.and, for once,... Author, Article, and Disclosure InformationAffiliations: New York University School of Medicine, New York, New York (K.L.)Current Author Address: Katharine Lawrence, MD; e-mail, katharine.[email protected]org. PreviousarticleNextarticle Advertisement Audio Reading - “A year of small heartbreaks (or, a physician writes her first death note)” Audio. Virginia Hood, MD, reads "A year of small heartbreaks (or, a physician writes her first death note)," by K. Lawrence. Your browser does not support the audio element. Audio player progress bar Step backward in current audio track Play current audio trackPause current audio track Step forward in current audio track Mute current audio trackUnmute current audio track 00:00/ FiguresReferencesRelatedDetails Metrics 18 December 2018Volume 169, Issue 12Page: 889KeywordsShouldersVeinsVentilators ePublished: 18 December 2018 Issue Published: 18 December 2018 Copyright & PermissionsCopyright © 2018 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
Pathology and pathobiology of pulmonary hypertension: state of the art and research perspectives
Authors: Marc Humbert, Christophe Guignabert, Sébastien Bonnet, Peter Dorfmüller, James R. Klinger, Mark R. Nicolls, Andrea J. Olschewski, Soni S. Pullamsetti, Ralph T. Schermuly, Kurt R. Stenmark, Marlene Rabinovitch
Journal: European Respiratory Journal (2018)

Clinical and translational research has played a major role in advancing our understanding of pulmonary hypertension (PH), including pulmonary arterial hypertension and other forms of PH with severe vascular remodelling (e.g. chronic thromboembolic PH and pulmonary veno-occlusive disease). However, PH remains an incurable condition with a high mortality rate, underscoring the need for a better transfer of novel scientific knowledge into healthcare interventions. Herein, we review recent findings in pathology (with the questioning of the strict morphological categorisation of various forms of PH into pre- or post-capillary involvement of pulmonary vessels) and cellular mechanisms contributing to the onset and progression of pulmonary vascular remodelling associated with various forms of PH. We also discuss ways to improve management and to support and optimise drug development in this research field.
Functionality of patients with Chronic Obstructive Pulmonary Disease at 3 months follow-up after elastic resistance training: a randomized clinical trial
Authors: Isis Grigoletto Silva, Bruna Spolador de Alencar Silva, Ana Paula Coelho Figueira Freire, Ana Paula Soares dos Santos, Fabiano Francisco de Lima, Dionei Ramos, Ercy Mara Cipulo Ramos
Journal: Pulmonology (2018)
Iron Regulator Hepcidin Impairs Macrophage-Dependent Cardiac Repair After Injury
Authors: Ivana Zlatanova, Cristina Pinto, Philippe Bonnin, Jacques R.R. Mathieu, Wineke Bakker, Jose Vilar, Mathilde Lemitre, David Voehringer, Sophie Vaulont, Carole Peyssonnaux, Jean-Sébastien Silvestre
Journal: Circulation (2019)

Defective systemic and local iron metabolism correlates with cardiac disorders. Hepcidin, a master iron sensor, actively tunes iron trafficking. We hypothesized that hepcidin could play a key role to locally regulate cardiac homeostasis after acute myocardial infarction.Cardiac repair was analyzed in mice harboring specific cardiomyocyte or myeloid cell deficiency of hepcidin and challenged with acute myocardial infarction.We found that the expression of hepcidin was elevated after acute myocardial infarction and the specific deletion of hepcidin in cardiomyocytes failed to improve cardiac repair and function. However, transplantation of bone marrow-derived cells from hepcidin-deficient mice ( Hamp-/-) or from mice with specific deletion of hepcidin in myeloid cells (LysMCRE/+/ Hampf/f) improved cardiac function. This effect was associated with a robust reduction in the infarct size and tissue fibrosis in addition to favoring cardiomyocyte renewal. Macrophages lacking hepcidin promoted cardiomyocyte proliferation in a prototypic model of apical resection-induced cardiac regeneration in neonatal mice. Interleukin (IL)-6 increased hepcidin levels in inflammatory macrophages. Hepcidin deficiency enhanced the number of CD45+/CD11b+/F4/80+/CD64+/MHCIILow/chemokine (C-C motif) receptor 2 (CCR2)+ inflammatory macrophages and fostered signal transducer and activator of transcription factor-3 (STAT3) phosphorylation, an instrumental step in the release of IL-4 and IL-13. The combined genetic suppression of hepcidin and IL-4/IL-13 in macrophages failed to improve cardiac function in both adult and neonatal injured hearts.Hepcidin refrains macrophage-induced cardiac repair and regeneration through modulation of IL-4/IL-13 pathways.
Nilotinib Vs Nilotinib Plus Pegylated Interferon-alpha2b Induction and Nilotinib or Pegylated Interferon-alpha2b Maintenance Therapy for Newly Diagnosed BCR-ABL+ Chronic Myeloid Leukemia Patients in Chronic Phase: Interim Analysis of the Tiger (CML V)-Study
Authors: Andreas Hochhaus, Susanne Saussele, Gabriela M Baerlocher, Tim H Brümmendorf, Andreas Burchert, Paul La Rosée, Joerg Hasford, Rüdiger Hehlmann, Dominik Heim, Stefan W Krause, Philipp le Coutre, Dietger Niederwieser, Jiří Mayer, Thoralf Lange, Mathias Haenel, Frank Stegelmann, Arthur Gil, Thomas Ernst, Christian Fabisch, Markus Pfirrmann
Journal: Blood (2018)
Flush technique to minimize adverse reactions from syringe lubricant (silicone oil)
Authors: Carlos Gustavo Wambier, Evelyn Assis de Andrade, Luiza Stolz Cruz, Bruna Mikulis Lemes, Wayne D. Carey, Bárbara de Paula Silveira Moura, Alessandro Soares Both, Sarah Perillo de Farias Wambier, Flávio Luís Beltrame
Journal: Journal of the American Academy of Dermatology (2018)
Discovery of a series of dimethoxybenzene FGFR inhibitors with 5H-pyrrolo[2,3-b]pyrazine scaffold: structure–activity relationship, crystal structural characterization and in vivo study
Authors: Peng Wei, Bo Liu, Ruifeng Wang, Yinglei Gao, Lanlan Li, Yuchi Ma, Zhiwei Qian, Yuelei Chen, Maosheng Cheng, Meiyu Geng, Jingkang Shen, Dongmei Zhao, Jing Ai, Bing Xiong
Journal: Acta Pharmaceutica Sinica B (2018)

Genomic alterations are commonly found in the signaling pathways of fibroblast growth factor receptors (FGFRs). Although there is no selective FGFR inhibitors in market, several promising inhibitors have been investigated in clinical trials, and showed encouraging efficacies in patients. By designing a hybrid between the FGFR-selectivity-enhancing motif dimethoxybenzene group and our previously identified novel scaffold, we discovered a new series of potent FGFR inhibitors, with the best one showing sub-nanomolar enzymatic activity. After several round of optimization and with the solved crystal structure, detailed structureactivity relationship was elaborated. Together with in vitro metabolic stability tests and in vivo pharmacokinetic profiling, a representative compound (35) was selected and tested in xenograft mouse model, and the result demonstrated that inhibitor 35 was effective against tumors with FGFR genetic alterations, exhibiting potential for further development.
Abstract 008: Casual and 24-hour Urinary Sodium-to-potassium Ratio and Intakes of Sodium and Potassium Among Men and Women From Multi-ethnic General Populations: The Intersalt Study
Authors: Toshiyuki Iwahori, Katsuyuki Miura, Hirotsugu Ueshima, Queenie Chan, Hisatomi Arima, Alan R Dyer, Paul Elliott, Jeremiah Stamler
Journal: Circulation (2018)

Background: Urinary sodium-to-potassium ratio may be more strongly related to blood pressure and cardiovascular disease than either urinary sodium or potassium alone. The casual urine sodium-to-potassium ratio is readily obtained, can provide prompt on-site feedback, and with repeated measurements may provide useful individual estimates of 24-hour urinary sodium-to-potassium ratio. The World Health Organization (WHO) has recently published guidelines for sodium and potassium intakes, but no generally accepted guideline prevails for favorable sodium-to-potassium ratio. Objective: Our primary aim was to compare the level of urinary Na/K ratio with the current recommended levels of Na and K intakes suggested in WHO guidelines. Methods: INTERSALT is an international study on associations of multiple urinary variables, with blood pressure (BP), based on standardized data on 24-hour and casual urinary electrolyte excretion in 10,065 individuals from 52 population samples in 32 countries. The associations between casual urinary sodium-to-potassium ratio and 24-hour urinary sodium and potassium excretion of individuals were assessed by correlation and stratification analysis. Results: Mean 24-hour sodium and potassium excretions were 156.0 mmol/24h and 55.2 mmol/24h; mean 24-hour urinary sodium-to-potassium ratio was 3.24. Pearson-r correlation coefficients of casual urinary sodium-to-potassium ratio with 24-hour sodium and potassium excretions were 0.42 and -0.34, respectively, and these were 0.57 and -0.48 for 24-hour urinary sodium-to-potassium ratio. The proportion of participants with estimated sodium chloride intake below the WHO recommended guideline of 85 mmol/day was 61.1% for those with casual urinary sodium-to-potassium ratio less than 1, and 96.3% where the 24-hour ratio was less than 1. For potassium, the proportion of people with potassium intake more than the WHO recommended guideline of 90 mmol/day was 21.3% where the casual urinary sodium-to-potassium ratio was less than 1 and 28.6% for the 24-hour urinary sodium-to-potassium ratio. Conclusions: Casual urinary sodium-to-potassium ratio less than 1 may be a useful indicator of adherence to the World Health Organization recommended levels of sodium intake, and to a lesser extent potassium intake in diverse different populations.
The hepatokine Tsukushi gates energy expenditure via brown fat sympathetic innervation
Authors: Qiuyu Wang, Vishal P. Sharma, Hong Shen, Yuanyuan Xiao, Qi Zhu, Xuelian Xiong, Liang Guo, Lin Jiang, Kunimasa Ohta, Siming Li, Haifei Shi, Liangyou Rui, Jiandie D. Lin
Journal: Nature Metabolism (2018)
A severe case of refractory esophageal stenosis induced by nivolumab and responding to tocilizumab therapy
Authors: Alice Horisberger, Stefano La Rosa, Jean-Philippe Zurcher, Stefan Zimmermann, Francois Spertini, George Coukos, Michel Obeid
Journal: Journal for ImmunoTherapy of Cancer (2018)

<h3>Background</h3> The prevalence of esophageal stenosis caused by immune checkpoint inhibitors in the context of induced immune mucositis and esophagitis is extremely rare. <h3>Case presentation</h3> We report the case of a patient with stage IV pulmonary adenocarcinoma treated for 6 months with nivolumab who developed bilateral sterile conjunctivitis followed by oropharyngeal mucositis and esophagitis complicated by a severe esophageal stenosis. The laryngeal margin and hypopharyngeal mucosa appeared highly inflammatory with fibrinous deposits. Esophagogastroduodenoscopy revealed mucositis with a scar-like structure immediately below the upper esophageal sphincter with nonulcerative mucosa and an inflammatory aspect of the entire esophagus. No involvement of the stomach was observed. Oropharynx biopsies displayed marked lymphocytic T cell-infiltration with several foci of monocellular necrosis in the squamous epithelium. No morphologic evidence of adenocarcinoma and no signs of mycotic, bacterial or viral infection were noted. A blood sample revealed a discrete increase in the erythrocyte sedimentation rate (ESR) with no eosinophilia or leukocytosis. Liver and kidney function panel tests were normal. A thoracoabdominal CT scan reported no evidence of disease recurrence. Despite multiple boluses of methylprednisolone and high doses of prednisone continued for several months, the patient experienced very rapid symptomatological reappearance during three steroid tapering attempts and aggravation of his esophageal stenosis to an aphagic stage, requiring a nasogastric tube. This long course of high-dose corticosteroid treatment was complicated with osteoporosis-induced fractures with several spontaneous compressions of thoracolumbar vertebrae requiring an enlarged T10 to L5 cementoplasty. Anti-IL-6 blockade therapy with tocilizumab resulted in excellent clinical response, allowing the total resolution of the immune-related adverse events (irAEs) and leading to successful steroid tapering. <h3>Conclusions</h3> Herein, we describe the first case of a patient who developed autoimmune mucositis and esophagitis complicated by a severe refractory esophageal stenosis induced during treatment by nivolumab, which completely resolved after personalized treatment with tocilizumab, suggesting a role of IL-6 blockade in the management of severe steroid refractory esophageal stenosis and more broadly in refractory immune-related adverse events.
In-Flight Medical Emergencies
Authors: Christian Martin-Gill, Thomas J. Doyle, Donald M. Yealy
Journal: JAMA (2018)

<h3>Importance</h3> In-flight medical emergencies (IMEs) are common and occur in a complex environment with limited medical resources. Health care personnel are often asked to assist affected passengers and the flight team, and many have limited experience in this environment. <h3>Observations</h3> In-flight medical emergencies are estimated to occur in approximately 1 per 604 flights, or 24 to 130 IMEs per 1 million passengers. These events happen in a unique environment, with airplane cabin pressurization equivalent to an altitude of 5000 to 8000 ft during flight, exposing patients to a low partial pressure of oxygen and low humidity. Minimum requirements for emergency medical kit equipment in the United States include an automated external defibrillator; equipment to obtain a basic assessment, hemorrhage control, and initiation of an intravenous line; and medications to treat basic conditions. Other countries have different minimum medical kit standards, and individual airlines have expanded the contents of their medical kit. The most common IMEs involve syncope or near-syncope (32.7%) and gastrointestinal (14.8%), respiratory (10.1%), and cardiovascular (7.0%) symptoms. Diversion of the aircraft from landing at the scheduled destination to a different airport because of a medical emergency occurs in an estimated 4.4% (95% CI, 4.3%-4.6%) of IMEs. Protections for medical volunteers who respond to IMEs in the United States include a Good Samaritan provision of the Aviation Medical Assistance Act and components of the Montreal Convention, although the duty to respond and legal protections vary across countries. Medical volunteers should identify their background and skills, perform an assessment, and report findings to ground-based medical support personnel through the flight crew. Ground-based recommendations ultimately guide interventions on board. <h3>Conclusions and Relevance</h3> In-flight medical emergencies most commonly involve near-syncope and gastrointestinal, respiratory, and cardiovascular symptoms. Health care professionals can assist during these emergencies as part of a collaborative team involving the flight crew and ground-based physicians.
Providing Individual Research Results to Participants—Reply
Authors: Charlene A. Wong, Adrian F. Hernandez, Robert M. Califf
Journal: JAMA (2018)

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