tbuckley/cabot-search huggingface dataset:
Effects of Lumacaftor–Ivacaftor Therapy on Cystic Fibrosis Transmembrane Conductance Regulator Function in Phe508del Homozygous Patients with Cystic Fibrosis
Authors: Simon Y. Graeber, Christian Dopfer, Lutz Naehrlich, Lena Gyulumyan, Heike Scheuermann, Stephanie Hirtz, Sabine Wege, Heimo Mairbäurl, Marie Dorda, Rebecca Hyde, Azadeh Bagheri-Hanson, Claudia Rueckes-Nilges, Sebastian Fischer, Marcus A. Mall, Burkhard Tümmler
Journal: American Journal of Respiratory and Critical Care Medicine (2018)

The combination of the CFTR (cystic fibrosis transmembrane conductance regulator) corrector lumacaftor with the potentiator ivacaftor has been approved for the treatment of patients with cystic fibrosis homozygous for the Phe508del CFTR mutation. The phase 3 trials examined clinical outcomes but did not evaluate CFTR function in patients.To examine the effect of lumacaftor-ivacaftor on biomarkers of CFTR function in Phe508del homozygous patients with cystic fibrosis aged 12 years and older.This prospective observational study assessed clinical outcomes including FEV1% predicted and body mass index, and CFTR biomarkers including sweat chloride concentration, nasal potential difference, and intestinal current measurement before and 8-16 weeks after initiation of lumacaftor-ivacaftor.A total of 53 patients were enrolled in the study, and 52 patients had baseline and follow-up measurements. After initiation of lumacaftor-ivacaftor sweat chloride concentrations were reduced by 17.8 mmol/L (interquartile range [IQR], -25.9 to -6.1; P < 0.001), nasal potential difference showed partial rescue of CFTR function in nasal epithelia to a level of 10.2% (IQR, 0.0-26.1; P < 0.011), and intestinal current measurement showed functional improvement in rectal epithelia to a level of 17.7% of normal (IQR, 10.8-29.0; P < 0.001). All patients improved in at least one CFTR biomarker, but no correlations were found between CFTR biomarker responses and clinical outcomes.Lumacaftor-ivacaftor results in partial rescue of Phe508del CFTR function to levels comparable to the lower range of CFTR activity found in patients with residual function mutations. Functional improvement was detected even in the absence of short-term improvement of FEV1% predicted and body mass index. Clinical trial registered with www.clinicaltrials.gov (NCT02807415).
Abstract 16: A Clinical Study Of Older Children With Kawasaki Disease
Authors: Yukako Nagamori, Yoshihito Ogihara, Kayoko Sato, Takasuke Ebato, Kiyotaka Otani, Shinya Nakamura, Kastunori Minoura, Shohei Ogata, Masahiro Ishii
Journal: Circulation (2015)

Background: Kawasaki disease(KD) patients exhibiting a disease onset past infancy are likely to receive a delayed diagnosis, as it takes time for all major symptoms to manifest and the disease also includes many non-typical features. Most general pediatricians and infectious disease specialists may not consider KD in the differential diagnosis among schoolchildren. Objective: To examine the clinical features of KD in patients with school-age onset. Methods: Among a total of 650 patients who received a diagnosis of KD in groups Department of pediatrics, Kitasato University School of Medicine , Sagamihara Cooperation Hospital and Ebina General Hospital over the seven-year period from April 2007 to March 2014, we investigated schoolchildren 7 years of age or older. Using the patients’ medical records, we retrospectively assessed data for sex, age, duration of illness, symptoms, treatment effectiveness and coronary artery lesions. Results: Fourteen (2.2%) schoolchildren were identified (male: n=7, 50%). The median age was 8 years (oldest age: 12 years). The incomplete type was diagnosed in 4 cases (29%), and the typical type was diagnosed in 10 cases (71%). The median duration of illness was 5 days (range: 3-12 days). Five patients (36%) were diagnosed with lymphadenitis at the initial diagnosis. Two patients with Mycoplasma pneumonia and acute appendicitis received a delayed diagnosis of KD. Their symptoms included gastrointestinal symptoms, joint pain with headaches and muscle pain. Nine patients (64%) exhibited membranous desquamation. Two of these patients displayed swelling of the hands and feet at diagnosis. All 14 patients were first treated with intravenous immunoglobulin therapy (IVIG: 2 g/kg); only one patient was resistant. Two patients (14%) were diagnosed with transient coronary artery dilatation; however, no patients had coronary aneurysms. Conclusions: KD with a school-age onset is rare; however, the incidence of cardiovascular complications in such cases has been reported to be high. Therefore, providing an early diagnosis and appropriate therapy is necessary. Physicians should consider the possibility of KD in school-age children who present with a persistent fever.
Radiofrequency Ablation Versus Stereotactic Body Radiotherapy for Localized Hepatocellular Carcinoma in Nonsurgically Managed Patients: Analysis of the National Cancer Database
Authors: Devalkumar J. Rajyaguru, Andrew J. Borgert, Angela L. Smith, Reggie M. Thomes, Patrick D. Conway, Thorvardur R. Halfdanarson, Mark J. Truty, A. Nicholas Kurup, Ronald S. Go
Journal: Journal of Clinical Oncology (2018)

Purpose Data that guide selection of optimal local ablative therapy for the management localized hepatocellular carcinoma (HCC) are lacking. Because there are limited prospective comparative data for these treatment modalities, we aimed to compare the effectiveness of radiofrequency ablation (RFA) versus stereotactic body radiotherapy (SBRT) by using the National Cancer Database. Methods We conducted an observational study to compare the effectiveness of RFA versus SBRT in nonsurgically managed patients with stage I or II HCC. Overall survival was compared by using propensity score–weighted and propensity score–matched analyses based on patient-, facility-, and tumor-level characteristics. A sensitivity analysis was performed to evaluate the effect of severe fibrosis/cirrhosis. In addition, we performed exploratory analyses to determine the effectiveness of RFA and SBRT in clinically relevant patient subsets. Results Overall, 3,684 (92.6%) and 296 (7.4%) nonsurgically managed patients with stage I or II HCC received RFA or SBRT, respectively. After propensity matching, 5-year overall survival was 29.8% (95% CI, 24.5% to 35.3%) in the RFA group versus 19.3% (95% CI, 13.5% to 25.9%) in the SBRT group ( P &lt; .001). Inverse probability–weighted analysis yielded similar results. The benefit of RFA was consistent across all subgroups examined and was robust to the effects of severe fibrosis/cirrhosis. Conclusion Our study suggests that treatment with RFA yields superior survival compared with SBRT for nonsurgically managed patients with stage I or II HCC. Even though our results are limited by the biases related to the retrospective study design, we believe that, in the absence of a randomized clinical trial, our findings should be considered when recommending local ablative therapy for localized unresectable HCC.
Two Doctors Meet
Authors: Sarah Parker
Journal: Annals of Internal Medicine (2018)

Ad Libitum16 January 2018Two Doctors MeetSarah ParkerSarah ParkerFrom Knoxville, Tennessee.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/M17-1284 Audio Reading - “Two Doctors Meet” Audio. Virginia L. Hood, MD, Annals Associate Editor, reads "Two Doctors Meet," by S. Parker. 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 The doctor walked out of one of his clinic rooms and told his nurse he thought he was having a stroke. By the time I saw him, he was nonverbal, globally aphasic, unable to move his right side, his brain filling with rapidly expanding hemorrhage. He didn't understand what I was asking him to do. He couldn't tell me what he was feeling, but he recognized my white coat. He recognized the tone in my voice. He recognized the expression on my face. He took my hand in his left hand and repeatedly squeezed it and looked me right in ... Author, Article, and Disclosure InformationAffiliations: From Knoxville, Tennessee.Current Author Address: Sarah Parker, MD; e-mail, [email protected]edu. PreviousarticleNextarticle Advertisement Audio Reading - “Two Doctors Meet” Audio. Virginia L. Hood, MD, Annals Associate Editor, reads "Two Doctors Meet," by S. Parker. 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 Cited byLncRNA RGMB-AS1 facilitates pancreatic cancer cell proliferation and migration but inhibits cell apoptosis via miR-574-3p/PIM3 axis 16 January 2018Volume 168, Issue 2Page: 160KeywordsBrainEmotionsHemorrhageMemoryNursesStroke ePublished: 16 January 2018 Issue Published: 16 January 2018 Copyright & PermissionsCopyright © 2018 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
Cardioventilatory Control in Preterm-born Children and the Risk of Obstructive Sleep Apnea
Authors: Keren Armoni Domany, Md Monir Hossain, Leonardo Nava-Guerra, Michael C. Khoo, Keith McConnell, John L. Carroll, Yuanfang Xu, Mark DiFrancesco, Raouf S. Amin
Journal: American Journal of Respiratory and Critical Care Medicine (2018)

The contribution of ventilatory control to the pathogenesis of obstructive sleep apnea (OSA) in preterm-born children is unknown.
Transmyocardial olmium-laser left ventricular revascularisation: clinical and perfusion evaluation
Authors: R. Baglini, G. Paterni, A Petronio, G. Amoroso, U. Limbruno, G. Boni, S. Pratali, R. Mariotti, U. Bortolotti, M. Mariani
Journal: Journal of the American College of Cardiology (1998)
Wider effects of the Bawa-Garba case on medical practice and public safety
Authors: Andrew L Spooner
Journal: BMJ (2018)

Most of us don’t know, and will never know, whether Hadiza Bawa-Garba was concentrating on the day or lacked specific knowledge.1 The same is true for other cases that have come to court or the General Medical Council. But comments imply that at least some people think that this was not malicious and was affected by the pressures of work and making decisions. Medical staff failures seem to become public when it is a child or an emotive issue such as sepsis. Errors occur every day. No action occurs for a single error if a problem does not arise. …
Increased risk of ischemic heart disease, hypertension, and type 2 diabetes in women with previous gestational diabetes mellitus, a target group in general practice for preventive interventions: A population-based cohort study
Authors: Barbara Daly, Konstantinos A. Toulis, Neil Thomas, Krishna Gokhale, James Martin, Jonathan Webber, Deepi Keerthy, Kate Jolly, Ponnusamy Saravanan, Krishnarajah Nirantharakumar
Journal: PLoS Medicine (2018)

Background Gestational diabetes mellitus (GDM) is associated with developing type 2 diabetes, but very few studies have examined its effect on developing cardiovascular disease. Methods and findings We conducted a retrospective cohort study utilizing a large primary care database in the United Kingdom. From 1 February 1990 to 15 May 2016, 9,118 women diagnosed with GDM were identified and randomly matched with 37,281 control women by age and timing of pregnancy (up to 3 months). Adjusted incidence rate ratios (IRRs) with 95% confidence intervals (CIs) were calculated for cardiovascular risk factors and cardiovascular disease. Women with GDM were more likely to develop type 2 diabetes (IRR = 21.96; 95% CI 18.31–26.34) and hypertension (IRR = 1.85; 95% CI 1.59–2.16) after adjusting for age, Townsend (deprivation) quintile, body mass index, and smoking. For ischemic heart disease (IHD), the IRR was 2.78 (95% CI 1.37–5.66), and for cerebrovascular disease 0.95 (95% CI 0.51–1.77; p-value = 0.87), after adjusting for the above covariates and lipid-lowering medication and hypertension at baseline. Follow-up screening for type 2 diabetes and cardiovascular risk factors was poor. Limitations include potential selective documentation of severe GDM for women in primary care, higher surveillance for outcomes in women diagnosed with GDM than control women, and a short median follow-up postpartum period, with a small number of outcomes for IHD and cerebrovascular disease. Conclusions Women diagnosed with GDM were at very high risk of developing type 2 diabetes and had a significantly increased incidence of hypertension and IHD. Identifying this group of women in general practice and targeting cardiovascular risk factors could improve long-term outcomes.
Abstract 15116: A Simplified Risk Score for the Prediction of Contrast-Induced Nephropathy in Patients Undergoing Percutaneous Coronary Interventions After Acute Myocardial Infarction
Authors: Georgios Lazaros, Theodoros Zografos, Evangelos Oikonomou, Gerasimos Siasos, Georgios Georgiopoulos, Emmanouil Vavouranakis, Alexios Antonopoulos, Konstantinos Kalogeras, Sotirios Tsalamandris, Georgia Vogiatzi, Dimitrios Tousoulis
Journal: Circulation (2016)

Introduction: Contrast-induced nephropathy (CIN) following percutaneous coronary interventions (PCI) in patients with acute myocardial infarction (AMI) is associated with high morbidity and mortali...
Re: Zhangqun Ye, Guohua Zeng, Huan Yang, et al. Efficacy and Safety of Tamsulosin in Medical Expulsive Therapy for Distal Ureteral Stones with Renal Colic: A Multicenter, Randomized, Double-blind, Placebo-controlled Trial. Eur Urol 2018;73:385–91.
Authors: Christian Seitz
Journal: European Urology (2018)
Abstract 13165: Comparison of Strut Coverage at 2 Weeks After Second and Third Generation DES Implantation in Patients With STEMI
Authors: Masahiro Shimoda, Hirohiko Ando, Akihiro Suzuki, Shinichiro Sakurai, Akiyoshi Kurita, Katsuhisa Waseda, Hiroaki Takashima, Tetsuya Amano
Journal: Circulation (2016)

Background: Third generation drug-eluting stent (DES) is characterized by thinner strut and abluminal coating with bioabsorbable polymer, and in vitro studies has demonstrated earlier endothelialization than previous generation of DES. However, whether this holds true also in human coronary is unknown. Objective: Using optical coherence tomography (OCT), we compared strut coverage between 2 nd generation DES (XIENCE) and 3 rd generation DES (SYNERGY) at 2 weeks after stent implantation for ST-segment elevation myocardial infarction (STEMI). Methods: Twenty-four patients with STEMI who were underwent primary percutaneous coronary intervention with XIENCE (n=14) or SYNERGY (n=10) were enrolled in this study. Angiographic and OCT were conducted at just after and 2 weeks after stent implantation. Two independent analysts who were blind to the clinical and stent information analyzed all images. Results: A total of 4362 struts were analyzed in this OCT study. There was no difference between XIENCE and SYNERGY in percentage of malapposed struts (5.38% vs. 4.78%, p=0.81), percentage of residual thrombus (57.1% vs. 40.0%, p=0.43) and maximal thrombus area (0.20mm 2 vs. 0.15mm 2 , p=0.61). Percentage of strut coverage was significantly higher in SYNERGY than XIENCE (42.9% vs. 22.8%, p=0.0007). Conclusion: At 2 weeks after stent implantation for STEMI lesions, increased strut coverage was observed in SYNERGY than XIENCE, suggesting earlier vascular healing after SYNERGY implantation.
Prevalence of obesity, hypertension, and diabetes, and cascade of care in sub-Saharan Africa: a cross-sectional, population-based study in rural and urban Malawi
Authors: Alison J Price, Amelia C Crampin, Alemayehu Amberbir, Ndoliwe Kayuni-Chihana, Crispin Musicha, Terence Tafatatha, Keith Branson, Debbie A Lawlor, Elenaus Mwaiyeghele, Lawrence Nkhwazi, Liam Smeeth, Neil Pearce, Elizabeth Munthali, Beatrice M Mwagomba, Charles Mwansambo, Judith R Glynn, Shabbar Jaffar, Moffat Nyirenda
Journal: The Lancet Diabetes & Endocrinology (2018)

Sub-Saharan Africa is in rapid demographic transition, and non-communicable diseases are increasingly important causes of morbidity and mortality. We investigated the burden of diabetes, overweight and obesity, hypertension, and multimorbidity, their treatment, and their associations with lifestyle and other factors in Malawi, a very poor country with a predominantly rural-but rapidly growing urban-population, to identify high-risk populations and inform appropriate interventions.
Elevated Eosinophil Lineage-Committed Progenitors In Skin Lesions Of Patients With Moderate-To-Severe Atopic Dermatitis
Authors: Emma Price, Dhuha Al-Sajee, Sai Sakktee Krisna, Karen J. Howie, Caroline Munoz, Michelle Yee, Mathew Patel, Paul M. O'Byrne, Hermenio Lima, Roma Sehmi, Gail M. Gauvreau
Journal: Journal of Allergy and Clinical Immunology (2018)
In postmenopausal women with osteoporosis, romosozumab followed by alendronate reduced fractures vs alendronate alone
Authors: Calvin Hirsch
Journal: Annals of Internal Medicine (2018)

ACP Journal Club16 January 2018In postmenopausal women with osteoporosis, romosozumab followed by alendronate reduced fractures vs alendronate aloneCalvin Hirsch, MDCalvin Hirsch, MDUC Davis Medical Center, Sacramento, California, USA (C.H.)Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/ACPJC-2018-168-2-003 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail Source CitationSaag KG, Petersen J, Brandi ML, et al. Romosozumab or alendronate for fracture prevention in women with osteoporosis. N Engl J Med. 2017;377:1417-27. https://pubmed.ncbi.nlm.nih.gov/28892457Clinical Impact RatingsGIM/FP/GP: Endocrinology: Geriatrics: Rheumatology: References1 Langdahl BL, Libanati C, Crittenden DB, et al. Romosozumab (sclerostin monoclonal antibody) versus teriparatide in postmenopausal women with osteoporosis transitioning from oral bisphosphonate therapy: a randomised, open-label, phase 3 trial. Lancet. 2017;390:1585-94. [PMID: 28755782] Google Scholar2 Anagnostis P, Paschou SA, Mintziori G, et al. Drug holidays from bisphosphonates and denosumab in postmenopausal osteoporosis: EMAS position statement. Maturitas. 2017;101:23-30. [PMID: 28539165] Google Scholar3 He XW, Wang E, Bao YY, et al. High serum levels of sclerostin and Dickkopf-1 are associated with acute ischaemic stroke. Atherosclerosis. 2016;253:22-8. [PMID: 27573735] Google Scholar4 Matthijs Blankesteijn W, Hermans KC. Wnt signaling in atherosclerosis. Eur J Pharmacol. 2015;763:122-30. [PMID: 25987418] Google Scholar Author, Article, and Disclosure InformationAffiliations: UC Davis Medical Center, Sacramento, California, USA (C.H.)This article was published at Annals.org on 2 January 2018. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited byMiR-27a-3p promotes the osteogenic differentiation by activating CRY2/ERK1/2 axisShikonin mitigates ovariectomy-induced bone loss and RANKL-induced osteoclastogenesis via TRAF6-mediated signaling pathways 16 January 2018Volume 168, Issue 2Page: JC3KeywordsBone mineral densityHip fracturesOsteoporosisPopulation statisticsProteinsRheumatologyRisk ratioSerious adverse eventsStrokeSubcutaneous injections ePublished: 16 January 2018 Issue Published: 16 January 2018 Copyright & PermissionsCopyright © 2018 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
Abstracts 662 to 889
Journal: Hepatology (2007)

533Alated by immobilized anti-CD3.Surface markers expression and cytokine production was evaluated by FACS.Data were analyzed using Student's test (paired two tailed) and results are means±SD.Results.VitD3 strongly reduced the production of IL-12 (4,4±5,3% vs 1,1±1,6%, p<0.05) and TNF-α (5,2± 3,8% vs 1,0± 1,2%, p<0.05) by CD40L-stimulated monocyte-macrophages. VitD3 also significantly reduced the expression of CD80 (74,9± 13,1% vs 31± 27,2%, p<0.05) but not that of CD40 (14,5±7,4% vs 14,6±7,4%, p>0,05).Finally, the addition of VitD3 in T lymphocytes cultured in the presence of immobilized anti-CD3 plus autologous CD40L-stimulated macrophages resulted in a marked decrease in the production of IFN-g (6,9± 7,1% vs 2,9± 2,8 %, p<0.05).Conclusion.VitD3 interferes with the co-stimulatory activity of macrophages and cytokines production induced by CD40L.Therefore this compound has a potential role in controlling rejection in liver transplanted patients.
Canonical Notch signaling is dispensable for adult steady-state and stress myelo-erythropoiesis
Authors: Sara Duarte, Petter S. Woll, Natalija Buza-Vidas, Desmond Wai Loon Chin, Hanane Boukarabila, Tiago C. Luís, Laura Stenson, Tiphaine Bouriez-Jones, Helen Ferry, Adam J. Mead, Deborah Atkinson, Shaobo Jin, Sally-Ann Clark, Bishan Wu, Emmanouela Repapi, Nicki Gray, Stephen Taylor, Anders P. Mutvei, Yat Long Tsoi, Claus Nerlov, Urban Lendahl, Sten Eirik W. Jacobsen
Journal: Blood (2018)
Safety and effectiveness of SGM-101, a fluorescent antibody targeting carcinoembryonic antigen, for intraoperative detection of colorectal cancer: a dose-escalation pilot study
Authors: Leonora S F Boogerd, Charlotte E S Hoogstins, Dennis P Schaap, Miranda Kusters, Henricus J M Handgraaf, Maxime J M van der Valk, Denise E Hilling, Fabian A Holman, Koen C M J Peeters, J Sven D Mieog, Cornelis J H van de Velde, Arantza Farina-Sarasqueta, Ineke van Lijnschoten, Bérénice Framery, André Pèlegrin, Marian Gutowski, Simon W Nienhuijs, Ignace H J T de Hingh, Grard A P Nieuwenhuijzen, Harm J T Rutten, Francoise Cailler, Jacobus Burggraaf, Alexander L Vahrmeijer
Journal: The Lancet. Gastroenterology & hepatology (2018)
Adoptive Cellular Therapy with Donor Lymphocyte Infusion Versus a Second Allogeneic Hematopoietic Cell Transplant for Post-Allograft Relapsed Acute Myeloid Leukemia: An Intent-to-Treat Analysis on Behalf of the Acute Leukemia Working Party of the European Society for Blood and Marrow Transplantation (EBMT)
Authors: Mohamed A Kharfan-Dabaja, Myriam Labopin, Emmanuelle Polge, Taiga Nishihori, Ali Bazarbachi, Jürgen Finke, Michael Stadler, Gerhard Ehninger, Bruno Lioure, Nicolaas Schaap, Boris V Afanasyev, Moshe Yeshurun, Cecilia Isaksson, Johan Maertens, Yves Chalandon, Christoph Schmid, Arnon Nagler, Mohamad Mohty
Journal: Blood (2017)
Identification of a relevant allergen in the induction of rhinoconjuntivitis in subjects sensitized to peach pollen
Authors: Elisa Haroun-Díaz, Laura Victorio-Puche, Natalia Blanca López, Damian lopez-Sanchez, Maria Luisa Somoza, Jose Alessandro Bastidas-Parlanti, Francisco Javier Ruano Pérez, María Gabriela Canto, Araceli Diaz Perales, Miguel Blanca
Journal: Journal of Allergy and Clinical Immunology (2018)
A double negative: inhibition of hepatic Gi signaling improves glucose homeostasis
Authors: Allen M. Spiegel
Journal: Journal of Clinical Investigation (2018)

Hepatic glucose production (HGP) is a key determinant of glucose homeostasis. Glucagon binding to its cognate seven-transmembrane Gs-coupled receptor in hepatocytes stimulates cAMP production, resulting in increased HGP. In this issue of the JCI, Rossi and colleagues tested the hypothesis that activation of hepatic Gi-coupled receptors, which should inhibit cAMP production, would oppose the cAMP-inducing action of glucagon and thereby decrease HGP. Surprisingly, however, the opposite occurred: activation of Gi signaling increased HGP via a novel mechanism, while inhibition of Gi signaling reduced HGP. These results define a new physiologic role for hepatic Gi signaling and identify a potential therapeutic target for HGP regulation.