tbuckley/cabot-search huggingface dataset:
Time to Implement the Kidney Failure Risk Equation Into Pediatric Practice
Authors: Allison Dart, Paul Komenda, Navdeep Tangri
Journal: JAMA Pediatrics (2017)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Pediatrics HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Pediatrics journal
Living with breathlessness: a systematic literature review and qualitative synthesis
Authors: Ann Hutchinson, Natalie Barclay-Klingle, Kathleen Galvin, Miriam J. Johnson
Journal: European Respiratory Journal (2018)

What is the experience of people living with breathlessness due to medical conditions, those caring for them and those treating them, with regard to quality of life and the nature of clinical interactions?Electronic databases (Ovid MEDLINE, Embase, CINAHL Plus and PsycINFO) were searched (January 1987 to October 2017; English language), for qualitative studies exploring the experience of chronic breathlessness (patients, carers and clinicians). Two independent reviewers screened titles, abstracts and papers retrieved against inclusion criteria. Disagreements were resolved with a third reviewer. Primary qualitative data were extracted and synthesised using thematic synthesis.Inclusion and synthesis of 101 out of 2303 international papers produced four descriptive themes: 1) widespread effects of breathlessness; 2) coping; 3) help-seeking behaviour; and 4) clinicians' responsiveness to the symptom of breathlessness. The themes were combined to form the concept of "breathing space", to show how engaged coping and appropriate help-seeking (patient) and attention to symptom (clinician) helps maximise the patient's quality of living with breathlessness.Breathlessness has widespread impact on both patient and carer and affects breathing space. The degree of breathing space is influenced by interaction between the patient's coping style, their help-seeking behaviour and their clinician's responsiveness to breathlessness itself, in addition to managing the underlying disease.
Broadening response rates to PD-1 therapy in advanced lung adenocarcinoma: Viagenpumatucel-l (HS-110) in combination with nivolumab in the ongoing DURGA trial.
Authors: Daniel Morgensztern, Wael A. Harb, Kurt Alex Schalper, Melissa Leigh Price, Brandon Early, Taylor Houghton Schreiber
Journal: Journal of Clinical Oncology (2016)

TPS9102 Background: Viagenpumatucel-L (HS-110) is an allogeneic whole-cell vaccine, selected for high expression of adenocarcinoma tumor antigens, transfected to secrete gp96-Ig. Cell-secreted gp96-Ig delivers these cell-derived antigens directly to a recipient's own antigen presenting cells, resulting in highly selective activation of CD8+ cytotoxic T cells. Prior studies with viagenpumatucel-L (and related gp96-Ig vaccines) have shown a correlation between increases in CD8+ tumor infiltrating lymphocytes (TIL) and tumor response. Since the presence of TILs is one of the predictors for response to checkpoint inhibitors, the DURGA trial combining HS-110 with nivolumab was designed to explore the preclinical synergy between the two types of immunotherapy in an attempt to increase tumor inflammation and improve the response rates. Methods: Patients with advanced lung adenocarcinoma treated with at least one prior therapy are assigned to two cohorts based on baseline levels of TIL in patient biopsies: low TIL ( ≤ 10% CD8+ T cells) or high TIL ( > 10% CD8+ T cells). All patients receive standard of care nivolumab 3 mg/kg every 2 weeks and weekly HS-110 for 18 weeks or until disease progression or death. The 9-patient Phase 1b cohorts can be expanded to 30 patients in Phase 2 based on exhibited efficacy (Overall Response Rate (ORR)). The primary endpoint of the Phase 1b is safety and tolerability; the primary endpoint of the Phase 2 is ORR. Mandatory biopsies at baseline and Week 10 were used to track changes in TIL and PD-L1 staining. Peripheral blood mononuclear cells are evaluated by flow cytometry for detection of circulating leukocyte subsets, regulatory T cells, myeloid derived suppressor cells, activated T cells, and expression of immune checkpoint molecules on T cells. Cytokine and chemokine arrays from patient serum samples were also evaluated. Clinical trial information: NCT02439450 Clinical trial information: NCT02439450.
Abstract 15591: Mechanical Dyssynchrony of the Left Atrium During Sinus Rhythm is Associated With Stroke in Patients With History of Atrial Fibrillation
Authors: Luisa Ciuffo, Yuko Inoue, Susumu Tao, Esra G Ipek, Joao A Lima, Saman Nazarian, David D Spragg, Joseph Marine, Ronald D Berger, Hugh Calkins, Hiroshi Ashikaga
Journal: Circulation (2016)

Introduction: Depressed left atrial (LA) function during sinus rhythm is associated with stroke or transient ischemic attack (TIA) in patients with a history of atrial fibrillation (AF), independen...
Memantine prevents acute radiation-induced toxicities at hippocampal excitatory synapses
Authors: Joseph G Duman, Jeffrey Dinh, Wei Zhou, Henry Cham, Vasilis C Mavratsas, Matea Pavešković, Shalaka Mulherkar, Susan L McGovern, Kimberley F Tolias, David R Grosshans
Journal: Neuro-Oncology (2017)

Memantine has shown clinical utility in preventing radiation-induced cognitive impairment, but the mechanisms underlying its protective effects remain unknown. We hypothesized that abnormal glutamate signaling causes radiation-induced abnormalities in neuronal structure and that memantine prevents synaptic toxicity. Hippocampal cultures expressing enhanced green fluorescent protein were irradiated or sham-treated and their dendritic spine morphology assessed at acute (minutes) and later (days) times using high-resolution confocal microscopy. Excitatory synapses, defined by co-localization of the pre- and postsynaptic markers vesicular glutamate transporter 1 and postsynaptic density protein 95, were also analyzed. Neurons were pretreated with vehicle, the N-methyl-d-aspartate–type glutamate receptor antagonist memantine, or the glutamate scavenger glutamate pyruvate transaminase to assess glutamate signaling. For animal studies, Thy-1-YFP mice were treated with whole-brain radiotherapy or sham with or without memantine. Unlike previously reported long-term losses of dendritic spines, we found that the acute response to radiation is an initial increase in spines and excitatory synapses followed by a decrease in spine/synapse density with altered spine dynamics. Memantine pre-administration prevented this radiation-induced synaptic remodeling. These results demonstrate that radiation causes rapid, dynamic changes in synaptic structural plasticity, implicate abnormal glutamate signaling in cognitive dysfunction following brain irradiation, and describe a protective mechanism of memantine.
Importance of Complete Remission on Predicting Overall Survival in Patients with Lower-Risk Myelodysplastic Syndromes (MDS)
Authors: Aziz Nazha, Rami S. Komrokji, John Barnard, Najla H Al Ali, Gail J. Roboz, David P. Steensma, Amy E. DeZern, Jaime Fensterl, Guillermo Garcia-Manero, Alan F List, Jaroslaw P Maciejewski, Mikkael A. Sekeres
Journal: Blood (2016)
Precursor Frequency and Affinity Determine B Cell Competitive Fitness in Germinal Centers, Tested with Germline-Targeting HIV Vaccine Immunogens
Authors: Robert K. Abbott, Jeong Hyun Lee, Sergey Menis, Patrick Skog, Meghan Rossi, Takayuki Ota, Daniel W. Kulp, Deepika Bhullar, Oleksandr Kalyuzhniy, Colin Havenar-Daughton, William R. Schief, David Nemazee, Shane Crotty
Journal: Immunity (2017)
Case 40-2017
Authors: David B. Sykes, Rachel P. Rosovsky, Aneesh B. Singhal, R. Gilberto Gonzalez, Andrea P. Moy
Journal: New England Journal of Medicine (2017)

A 32-year-old woman was admitted to the hospital because of headache and loss of peripheral vision. One week earlier, she had presented with abdominal pain, anemia, thrombocytopenia, and splenic-vein thrombosis. A diagnostic test was performed, and management decisions were made.
Abstract 20228: Functional Contribution of the Fast Transient Outward Potassium Current to Repolarization in Non-Failing Human Ventricular Myocytes; A Dynamic Clamp Study
Authors: Steven Springer, Eric Johnson, Wei Wang, Anna Zhang, Evelyn Kanter, Kathryn Yamada, Jeanne Nerbonne
Journal: Circulation (2016)

The Ca2+-independent transient outward potassium current (Ito) contributes to the early phase of action potential repolarization in many species, but the functional contribution of the current to r...
Reconstituted high-density lipoproteins: novel biomimetic nanocarriers for drug delivery
Authors: Xinyi Ma, Qingxiang Song, Xiaoling Gao
Journal: Acta Pharmaceutica Sinica B (2017)

High-density lipoproteins (HDL) are naturally-occurring nanoparticles that are biocompatible, non-immunogenic and completely biodegradable. These endogenous particles can circulate for an extended period of time and transport lipids, proteins and microRNA from donor cells to recipient cells. Based on their intrinsic targeting properties, HDL are regarded as promising drug delivery systems. In order to produce on a large scale and to avoid blood borne pollution, reconstituted high-density lipoproteins (rHDL) possessing the biological properties of HDL have been developed. This review summarizes the biological properties and biomedical applications of rHDL as drug delivery platforms. It focuses on the emerging approaches that have been developed for the generation of biomimetic nanoparticles rHDL to overcome the biological barriers to drug delivery, aiming to provide an alternative, promising avenue for efficient targeting transport of nanomedicine.
Prevalence and predictors of severe grief reactions and desire for support following a death in the intensive care unit: a multicentre observational study
Authors: James Downar, Ellen Koo, Amanda Roze des Ordons, Orla Smith, Deborah Cook, Eyal Golan, Sarah Hales, George Tomlinson, Csilla Kalocsai, Derek Strachan, Christopher MacKinnon, Tasnim Sinuff
Journal: Intensive Care Medicine (2017)
Growth and nutritional status, and their association with lung function: a study from the international Primary Ciliary Dyskinesia Cohort
Authors: Myrofora Goutaki, Florian S. Halbeisen, Ben D. Spycher, Elisabeth Maurer, Fabiën Belle, Israel Amirav, Laura Behan, Mieke Boon, Siobhan Carr, Carmen Casaulta, Annick Clement, Suzanne Crowley, Sharon Dell, Thomas Ferkol, Eric G. Haarman, Bulent Karadag, Michael Knowles, Cordula Koerner-Rettberg, Margaret W. Leigh, Michael R. Loebinger, Henryk Mazurek, Lucy Morgan, Kim G. Nielsen, Maria Phillipsen, Scott D. Sagel, Francesca Santamaria, Nicolaus Schwerk, Panayiotis Yiallouros, Jane S. Lucas, Claudia E. Kuehni
Journal: European Respiratory Journal (2017)

Chronic respiratory disease can affect growth and nutrition, which can influence lung function. We investigated height, body mass index (BMI), and lung function in patients with primary ciliary dyskinesia (PCD). In this study, based on the international PCD (iPCD) Cohort, we calculated z-scores for height and BMI using World Health Organization (WHO) and national growth references, and assessed associations with age, sex, country, diagnostic certainty, age at diagnosis, organ laterality and lung function in multilevel regression models that accounted for repeated measurements. We analysed 6402 measurements from 1609 iPCD Cohort patients. Height was reduced compared to WHO (z-score −0.12, 95% CI −0.17 to −0.06) and national references (z-score −0.27, 95% CI −0.33 to −0.21) in male and female patients in all age groups, with variation between countries. Height and BMI were higher in patients diagnosed earlier in life (p=0.026 and p&lt;0.001, respectively) and closely associated with forced expiratory volume in 1 s and forced vital capacity z-scores (p&lt;0.001). Our study indicates that both growth and nutrition are affected adversely in PCD patients from early life and are both strongly associated with lung function. If supported by longitudinal studies, these findings suggest that early diagnosis with multidisciplinary management and nutritional advice could improve growth and delay disease progression and lung function impairment in PCD.
Aptamer-guided siRNA-loaded nanomedicines for systemic gene silencing in CD-44 expressing murine triple-negative breast cancer model
Authors: Walhan Alshaer, Hervé Hillaireau, Juliette Vergnaud, Simona Mura, Claudine Deloménie, Félix Sauvage, Said Ismail, Elias Fattal
Journal: Journal of Controlled Release (2017)
DIAGNOSTIC PERFORMANCE OF DIFFERENT METHODS FOR DETECTION OF SENSITIZATION TO PRU P 3 IN SPAIN
Authors: Carmen M. D'Amelio, Marta M. Ferrer, Rubén M. Martínez-Aranguren, Jorge Martín-Cuesta, María J. Goikoetxea, Gabriel Gastaminza
Journal: Journal of Allergy and Clinical Immunology (2018)
Phase I pharmacokinetic study of single agent trametinib in advanced cancer patients with hepatic dysfunction: An NCI Organ Dysfunction Working Group (ODWG) study.
Authors: Anna Spreafico, Eric Chen, Solmaz Sahebjam, Daniel John Renouf, Karen Kelly, Albert C. Lockhart, Ulka N. Vaishampayan, Sebastien J. Hotte, Albiruni R. Razak, Lisa Wang, Lee-Anne Stayner, Alanna Bougie, Helen X. Chen, S. Percy Ivy, Lillian L. Siu
Journal: Journal of Clinical Oncology (2016)

2578 Background: Trametinib (T), an orally available MEK 1/2 inhibitor, is FDA approved for BRAFV600E/K mutant advanced melanoma, at the single agent RP2D of 2 mg QD. Its clinical development has involved a variety of refractory cancers. A phase I study was conducted to establish the maximum tolerated dose (MTD), dose-limiting toxicity (DLT) and pharmacokinetic (PK) profile of T in advanced solid tumor patients (pts) with varying degrees of hepatic dysfunction (HD). Methods: Advanced cancer pts with ECOG ≤2, adequate renal and bone marrow functions, were stratified (NCI ODWG Criteria) into 4 HD groups: normal (NO), mild (ML), moderate (MD), severe (SV). T was given QD on a 28-days cycle, with dose escalation occurring in sequential cohorts of pts within each HD group (starting dose: NO, ML: 2mg; MD: 1.5 mg; SV: 1mg). PK samples were collected at days 15-16 in cycle 1. Results: Between Mar '14-Nov '15, 30 (17 NO, 7 ML, 3 MD, 3SV) pts were treated. Median age 60, male 43%, ECOG≤1: 97%. Common tumor types: GI non-CRC 17%, NSCLC 17%, uveal melanoma 13%. All cohorts drug-related AEs (All Grades/Grade 3-4): skin rash 73%/7%, increased transaminases 43%/7%, fatigue 40%/7%. No DLTs so far occurred in ML, MD and SV groups. Dose delay and dose reduction occurred in 47% and 20% of all pts respectively. PK data were available in 10 NO and 6 ML HD cohort pts (Table). Of 23 pts evaluable for response, 13 (56%) had stable disease and 2 (9%) pts partial response (NSCLC; ovarian). Median duration of response was 3.6 months (range 1-13.7+). Conclusions: The RP2D for trametinib in ML group, which has completed accrual, is 2 mg QD. The PK profile in NO and ML groups is comparable. Thus far, T appeared to be tolerated within all groups. Accrual in MD and SV groups is ongoing at 1.5 mg QD and 1 mg QD respectively. Clinical trial information: NCT02070549.PK analysis for NO and ML groups. NO: 2mg QD (n=10) 90% CI ML: 2 mg QD (n=6) 90% CI AUC (ng*hr/ml) (SD) 507.5 ± 189.0 (397.9 – 617.0) 387.7 ± 201.3 (222.2 – 553.3) Cmax (ng/ml) (SD) 30.37 ± 12.15 (23.3 – 37.4) 29.53 ± 15.88 (16.5 – 42.6) Cmin (ng/ml) (SD) 16.30 ± 6.47 (12.6 – 20.1) 12.14 ± 6.95 (6.4 – 17.9) CL/F (L/hr) 4.51 ± 1.85 (3.44 – 5.57) 6.20 ± 2.82 (3.88 – 8.52) Tmax (hr) (range) median: 2 (1-4) median: 1 (0-2)
Annals Story Slam - There's No Place Like Home
Authors: Lisa Bellini
Journal: Annals of Internal Medicine (2017)

Web Exclusives19 December 2017Annals Story Slam - There's No Place Like HomeFREELisa Bellini, MDLisa Bellini, MDUniversity of Pennsylvania, Philadelphia, Pennsylvania (L.B.)Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/W17-0070 SectionsAboutVisual Abstract ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail Video. Annals Story Slam - There's No Place Like Home "There's No Place Like Home," by Dr. Lisa Bellini (Duration 6:56)Building on the popular Annals feature “On Being a Doctor,” storytellers share stories about the experience of doctoring on video.For more videos from and information on Annals Story Slam, visit go.annals.org/StorySlam. Comments0 CommentsSign In to Submit A Comment Author, Article, and Disclosure InformationAffiliations: University of Pennsylvania, Philadelphia, Pennsylvania (L.B.)Current Author Address: Lisa Bellini, MD; e-mail, lisa.[email protected]upenn.edu. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 19 December 2017Volume 167, Issue 12Page: SS1 ePublished: 19 December 2017 Issue Published: 19 December 2017 Copyright & PermissionsCopyright © 2017 by American College of Physicians. All Rights Reserved.Loading ...
Improved method for synthesis of low molecular weight protamine–siRNA conjugate
Authors: Zhili Yu, Junxiao Ye, Xing Pei, Lu Sun, Ergang Liu, Jianxin Wang, Yongzhuo Huang, Seung Jin Lee, Huining He
Journal: Acta Pharmaceutica Sinica B (2017)

RNAi technology has aroused wide public interest due to its high efficiency and specificity to treat multiple types of diseases. However, the effective delivery of siRNA remains a challenge due to its large molecular weight and strong anionic charge. Considering their remarkable functions in vivo and features that are often desired in drug delivery carriers, biomimetic systems for siRNA delivery become an effective and promising strategy. Based on this, covalent attachment of synthetic cell penetrating peptides (CPP) to siRNA has become of great interest. We developed a monomeric covalent conjugate of low molecular weight protamine (LMWP, a well-established CPP) and siRNA via a cytosol-cleavable disulfide linkage using PEG as a crosslinker. Results showed that the conjugates didn't generate coagulation, and exhibited much better RNAi potency and intracellular delivery compared with the conventional charge-complexed CPP/siRNA aggregates. Three different synthetic and purification methods were compared in order to optimize synthesis efficiency and product yield. The methodology using hetero-bifunctional NHS-PEG-OPSS as a crosslinker to synthesize LMWP-siRNA simplified the synthesis and purification process and produced the highest yield. These results pave the way towards siRNA biomimetic delivery and future clinical translation.
Flow-cytometric vs. -morphologic assessment of remission in childhood acute lymphoblastic leukemia: a report from the Children’s Oncology Group (COG)
Authors: Sumit Gupta, Meenakshi Devidas, Mignon L. Loh, Elizabeth A. Raetz, Si Chen, Cindy Wang, Patrick Brown, Andrew J. Carroll, Nyla A. Heerema, Julie M. Gastier-Foster, Kimberly P. Dunsmore, Eric C. Larsen, Kelly W. Maloney, Leonard A. Mattano, Stuart S. Winter, Naomi J. Winick, William L. Carroll, Stephen P. Hunger, Michael J. Borowitz, Brent L. Wood
Journal: Leukemia (2018)
Association of Emergency-Only vs Standard Hemodialysis With Mortality and Health Care Use Among Undocumented Immigrants With End-stage Renal Disease
Authors: Lilia Cervantes, Delphine Tuot, Rajeev Raghavan, Stuart Linas, Jeff Zoucha, Lena Sweeney, Chandan Vangala, Madelyne Hull, Mario Camacho, Angela Keniston, Charles E. McCulloch, Vanessa Grubbs, Jessica Kendrick, Neil R. Powe
Journal: JAMA Internal Medicine (2017)

Undocumented immigrants with end-stage renal disease have variable access to hemodialysis in the United States despite evidence-based standards for frequency of dialysis care.To determine whether mortality and health care use differs among undocumented immigrants who receive emergency-only hemodialysis vs standard hemodialysis (3 times weekly at a health care center).A retrospective cohort study was conducted of undocumented immigrants with incident end-stage renal disease who initiated emergency-only hemodialysis (Denver Health, Denver, Colorado, and Harris Health, Houston, Texas) or standard (Zuckerberg San Francisco General Hospital, San Francisco, California) hemodialysis between January 1, 2007, and July 15, 2014.Access to emergency-only hemodialysis vs standard hemodialysis.The primary outcome was mortality. Secondary outcomes were health care use (acute care days and ambulatory care visits) and rates of bacteremia. Outcomes were adjusted for propensity to undergo emergency hemodialysis vs standard hemodialysis.A total of 211 undocumented patients (86 women and 125 men; mean [SD] age, 46.5 [14.6] years; 42 from the standard hemodialysis group and 169 from the emergency-only hemodialysis group) initiated hemodialysis during the study period. Patients receiving standard hemodialysis were more likely to initiate hemodialysis with an arteriovenous fistula or graft and had higher albumin and hemoglobin levels than patients receiving emergency-only hemodialysis. Adjusting for propensity score, the mean 3-year relative hazard of mortality among patients who received emergency-only hemodialysis was nearly 5-fold (hazard ratio, 4.96; 95% CI, 0.93-26.45; P = .06) greater compared with patients who received standard hemodialysis. Mean 5-year relative hazard of mortality for patients who received emergency-only hemodialysis was more than 14-fold (hazard ratio, 14.13; 95% CI, 1.24-161.00; P = .03) higher than for those who received standard hemodialysis after adjustment for propensity score. The number of acute care days for patients who received emergency-only hemodialysis was 9.81 times (95% CI, 6.27-15.35; P < .001) the expected number of days for patients who had standard hemodialysis after adjustment for propensity score. Ambulatory care visits for patients who received emergency-only hemodialysis were 0.31 (95% CI, 0.21-0.46; P < .001) times less than the expected number of days for patients who received standard hemodialysis.Undocumented immigrants with end-stage renal disease treated with emergency-only hemodialysis have higher mortality and spend more days in the hospital than those receiving standard hemodialysis. States and cities should consider offering standard hemodialysis to undocumented immigrants.