tbuckley/cabot-search huggingface dataset:
The Epidemiology of Antineutrophil Cytoplasmic Autoantibody–Associated Vasculitis in Olmsted County, Minnesota
Authors: Alvise Berti, Divi Cornec, Cynthia S. Crowson, Ulrich Specks, Eric L. Matteson
Journal: Arthritis & Rheumatology (2017)

Objective To estimate the annual incidence, prevalence, and mortality of antineutrophil cytoplasmic autoantibody ( ANCA )–associated vasculitis ( AAV ) and its subsets, granulomatosis with polyangiitis (Wegener's) ( GPA ), microscopic polyangiitis ( MPA ), and eosinophilic granulomatosis with polyangiitis (Churg‐Strauss) ( EGPA ), in a US ‐based adult population. Methods All medical records of patients with a diagnosis of, or suspicion of having, AAV in Olmsted County, Minnesota from January 1, 1996 to December 31, 2015 were reviewed. AAV incidence rates were age‐ and sex‐adjusted to the 2010 US white population. Age‐ and sex‐adjusted prevalence of AAV was calculated on January 1, 2015. Survival rates observed in the study cohort were compared with expected rates in the Minnesota population. Results Of the 58 incident cases of AAV in Olmsted County during the study period, 23 (40%) were cases of GPA , 28 (48%) were cases of MPA , and 7 (12%) were cases of EGPA . Overall, 28 (48%) of the patients with AAV were women and 57 (98%) were white. The mean ± SD age at diagnosis was 61.1 ± 16.5 years. Thirty‐four patients (61%) had myeloperoxidase ( MPO )– ANCA s, and 17 (30%) were positive for proteinase 3 ( PR 3)– ANCA s; 5 (9%) were ANCA ‐negative. The annual incidence of AAV was 3.3 per 100,000 population (95% confidence interval [95% CI ] 2.4–4.1). The incidence rates of GPA , MPA , and EGPA were 1.3 (95% CI 0.8–1.8), 1.6 (95% CI 1.0–2.2), and 0.4 (95% CI 0.1–0.6), respectively. The overall prevalence of AAV was 42.1 per 100,000 (95% CI 29.6–54.6). The mortality rate among AAV patients overall, and among patients with EGPA , those with MPA , and those with MPO ‐ ANCA s, was increased in comparison to the Minnesota general population (each P &lt; 0.05), whereas mortality rates among patients with GPA , those with PR 3‐ ANCA s, and ANCA ‐negative patients did not differ from that in the general population. Conclusion The annual incidence of AAV in Olmsted County, Minnesota over the 20 years of the study was 3.3 per 100,000, with a prevalence of 42.1 per 100,000, which is substantially higher than the rates reported in other areas worldwide. The incidence of GPA was similar to that of MPA . Patients with MPA and those with EGPA , but not patients with GPA , experienced higher rates of mortality than that in the Minnesota general population. MPO ‐ ANCA s were a marker of poor survival in this population of patients with AAV .
Phase I trial of temsirolimus (TEM) and perifosine (PER) for recurrent or progressive malignant glioma (MG).
Authors: Thomas Joseph Kaley, Elena Pentsova, Antonio Marcilio Padula Omuro, Ingo K. Mellinghoff, Craig Nolan, Igor T. Gavrilovic, Lisa Marie DeAngelis, Mario E. Lacouture, Eric C. Holland, Andrew B. Lassman
Journal: Journal of Clinical Oncology (2013)

2095 Background: PI3K/AKT/mTOR signaling is important in MG biology, and therefore a potential therapeutic target. The mTOR inhibitor TEM and the AKT inhibitor PER are well tolerated as single agents but have limited activity. Preclinical data demonstrate synergistic anti-tumor effects during combined therapy including extensive tumor apoptosis, cell-cycle arrest among surviving cells, and inhibition of both AKT and mTOR. Therefore, we initiated a phase I trial of combined therapy in recurrent MGs. Methods: Adults with recurrent MG, KPS≥60, and not taking enzyme inducing AEDs were enrolled. There was no limitation on prior therapies except prior RT and temozolomide were mandatory. The dose of TEM was escalated in each cohort using standard 3 + 3 design from 15 mg to 170 mg administered once weekly. The dose of PER was fixed as a 600 mg load on day 1 followed by 100 mg nightly (the single dose MTD) until dose level 7 when the load increased to 900mg. Results: Thirty-four patients (24 men) with median age 52 (range, 21-71) and median KPS 80 (range, 60-100) participated. Diagnoses included GBM (18), AA (7), AO (7) or transformed LGG (2). Twenty-one received bevacizumab previously. There were a total of 5 DLTs: 1 at dose level 3 (50mg TEM), then 2 at dose level 7 expansion (170mg TEM), and then 2 at dose level 6 expansion (170mg TEM). DLTs included thrombocytopenia (n=3), intracerebral hemorrhage (n=1) and lung infection (n=1). Two uPR were seen at 170mg TEM. Grade 3 non-dose limiting toxicities per patient included lymphopenia (7), hyperglycemia (4), anemia (2), neutropenia (1), transaminitis (3), hypophosphatemia (3), hypercholesterolemia (3), thrombocytopenia (2), and mucositis (2). The MTD is defined as 115mg TEM (dose level 5). Conclusions: Combination therapy with TEM 115 mg weekly and PER 100 mg daily (following 600 mg load) is tolerable in heavily pre-treated adults with recurrent MGs. Clinical trial information: NCT01051557.
Practical considerations for choosing a mouse model of Alzheimer’s disease
Authors: Joanna L. Jankowsky, Hui Zheng
Journal: Molecular Neurodegeneration (2017)

Alzheimer's disease (AD) is behaviorally identified by progressive memory impairment and pathologically characterized by the triad of β-amyloid plaques, neurofibrillary tangles, and neurodegeneration. Genetic mutations and risk factors have been identified that are either causal or modify the disease progression. These genetic and pathological features serve as basis for the creation and validation of mouse models of AD. Efforts made in the past quarter-century have produced over 100 genetically engineered mouse lines that recapitulate some aspects of AD clinicopathology. These models have been valuable resources for understanding genetic interactions that contribute to disease and cellular reactions that are engaged in response. Here we focus on mouse models that have been widely used stalwarts of the field or that are recently developed bellwethers of the future. Rather than providing a summary of each model, we endeavor to compare and contrast the genetic approaches employed and to discuss their respective advantages and limitations. We offer a critical account of the variables which may contribute to inconsistent findings and the factors that should be considered when choosing a model and interpreting the results. We hope to present an insightful review of current AD mouse models and to provide a practical guide for selecting models best matched to the experimental question at hand.
Abstract 12659: Relationship Between Cardiac Structure and Function With Neurocognition in the Hispanic Community Health Study/ Study of Latinos (HCHS/SOL) Echocardiographic Study of Latinos (Echo-SOL) Ancillary Study
Authors: Mohamed Faher Almahmoud, Hector M Gonzalez, Wassim Tarraf, Neil Schneiderman, Mayank M Kansal, Melissa Lamar, Gregory A Talavera, Carlos J Rodriguez
Journal: Circulation (2016)

Background: Neurocognitive impairment is an important challenge facing the growing elderly population. The heart’s effect on the brain with regard to neurocognition is less well-studied. We evaluated the association between cardiac structure and function with neurocognition measurements in a population-based cohort. Methods: The Echo-SOL Ancillary Study of Hispanic adults aged 45-74 years provided comprehensive neurocognitive and echocardiography assessments for cross-sectional analysis. Neurocognitive measures included the Word Fluency (WF) Test, the Brief-Spanish English Verbal Learning Test (SEVLT), and the Digit Symbol Substitution Test (DSST); lower WF, SEVLT, and DSST scores signifying worse neurocognitive function. Multivariable linear and logistic regression models were fit using survey statistics and accounted for sampling probabilities, age, sex, diabetes, hypertension, and BMI. Results: 1818 participants were included in the analysis: mean age 56-years, and 56% women. Higher left ventricular mass index was associated with lower SEVLT and DSST scores, whereas lower Ejection Fraction and lower peak systolic velocity were associated with lower WF scores. Lower SEVLT scores were seen with a higher prevalence of abnormal left ventricular geometry and higher relative wall thickness. Mitral annular relaxation velocities (e’) were significantly associated with lower SEVLT and WF scores. Additionally, a higher ratio of mitral inflow velocity with mitral annular early diastolic velocity (E/e’) and more prevalent left ventricular diastolic dysfunction were significantly associated with lower SEVLT scores. Conclusion: Abnormalities in cardiac structure and function are associated with alterations in neurocognitive function in Hispanics/Latinos. Further study is needed to determine the mechanisms (e.g., impairment of cerebral flow, silent brain infarctions) mediating these potentially important heart-brain associations.
The effect of smoking on exacerbation risk in eosinophilic patients with COPD
Authors: Christian R. Osadnik, Martin I. MacDonald, Philip G. Bardin
Journal: European Respiratory Journal (2017)

We read with interest the findings of Kerkhof et al. [1], demonstrating an increased exacerbation risk in eosinophilic patients (eosinophil counts ≥0.45×109·L–1) with chronic obstructive pulmonary disease (COPD). When compared to a normal reference group (eosinophil counts of between 0.05 and 0.45×109·L–1), the rate ratios (RR) for exacerbations in the following year were lower in current smokers (RR=0.86) than in ex-smokers (RR=1.32). This finding is counter-intuitive and contrasts with data from large studies that demonstrate exacerbation reductions in COPD patients who cease smoking [2, 3]. A suppressive effect of active tobacco smoke on eosinophils is proposed as an explanatory mechanism by the authors; however, we feel the impact of potential confounders on this study finding should first be excluded prior to accepting this rationale. Higher exacerbation risk in COPD ex-smokers could reflect higher prior exacerbation history <http://ow.ly/TbwP30fJNGj>
Larissa Heart Failure Risk Score: a proposed simple score for risk stratification in chronic heart failure
Authors: Andrew Xanthopoulos, Konstantinos Tryposkiadis, Gregory Giamouzis, Dimitrios Konstantinou, George Giannakoulas, Haralambos Karvounis, Michael W. Kattan, John Skoularigis, John Parissis, Randall C. Starling, Filippos Triposkiadis
Journal: European Journal of Heart Failure (2017)
Use of Advanced Imaging Tests and the Not-So-Incidental Harms of Incidental Findings
Authors: Rebecca Smith-Bindman
Journal: JAMA Internal Medicine (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 Internal Medicine 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 Internal Medicine journal
Biomarker-related risk for myocardial infarction and serious infections in patients with rheumatoid arthritis: a population-based study
Authors: Jeffrey R Curtis, Fenglong Xie, Lang Chen, Kenneth G Saag, Huifeng Yun, Paul Muntner
Journal: Annals of the Rheumatic Diseases (2017)

Rheumatoid arthritis (RA) disease activity and associated systemic inflammation has been associated with serious infection (SIEs), myocardial infarction (MI) and coronary heart disease (CHD) events based on a few registry studies or clinical trials. There are few data from large-scale population-based studies given feasibility challenges in conducting such investigations.Multibiomarker disease activity (MBDA) test scores (n=77 641) were linked to Medicare for US patients with RA. Outcomes of interest were hospitalised pneumonia/sepsis (SIE), MI and a composite CHD outcome. The MBDA score ranges from 1 to 100 and was analysed as time-varying. Cox proportional hazards models evaluated the association between MBDA score and SIEs, MI and CHD events, controlling for potential confounders. A sensitivity analysis excluded C reactive protein (CRP) from the MBDA score.There were 17 433 and 16 796 patients eligible for the SIE and MI/CHD analyses, respectively. Mean (SD) age was 69 (11) years, 79% were women, 81% were white and 38% were disabled. Over 16 424 person-years of follow-up, there were 452 SIE events, 132 MIs and 181 CHD events. Higher MBDA scores were associated with SIEs (HR=1.32, 95% CI 1.23 to 1.41 per 10 unit MBDA score change). For MI/CHD events, a threshold effect was present; higher disease activity by MBDA score was associated with increased MI (HR=1.52, 95% CI 0.92 to 2.49) and CHD rates (HR=1.54, 95% CI 1.01 to 2.34, comparing scores ≥30 vs <30). Analyses of the MBDA score without CRP yielded similar results.Higher MBDA scores were associated with hospitalised infection, MI and CHD events in a large, predominantly older, US RA population.
Clinical practice guideline on diagnosis and treatment of hyponatraemia (vol 40, pg 320, 2014)
Authors: Goce Spasovski, Raymond Vanholder, Bruno Allolio, Djillali Annane, Steve Ball, Daniel Bichet, Guy Decaux, Wiebke Fenske, Ewout Hoorn, Carole Ichai, Michael Joannidis, Alain Soupart, Robert Zietse, Maria Haller, Sabine van der Veer, Wim van Biesen, Evi Nagler
Journal: Intensive Care Medicine (2014)
Tumor Side as Model of Integrative Molecular Classification of Colorectal Cancer
Authors: Rodrigo Dienstmann
Journal: Clinical Cancer Research (2017)

It has long since been recognized that colorectal cancer is molecularly heterogeneous and its clinical behavior differs if the primary tumor was located in the right or left side of the colon. Recent studies have shown that part of this heterogeneity is captured by the anatomic location of the tumor. Clin Cancer Res; 24(5); 989-90. ©2017 AACRSee related article by Loree et al., p. 1062.
Lymph node ratio (LNR) in sentinel lymph node biopsy (SLNB) era: Are we losing prognostic information?
Authors: Keith Ian Quintyne, Bernie Woulfe, John Calvin Coffey, Rajnish K. Gupta
Journal: Journal of Clinical Oncology (2015)

e12634 Background: The number of involved axillary lymph nodes (LNs) found on pathological assessment is regarded as a significant prognostic factor for patients with early-stage breast cancer (EBC). Recent reports have suggested that LNR may be a better surrogate at predicting cancer-specific outcome than the number of involved LN. This retrospective study investigated the prognostic value of LNR, using earlier published cut-off values, before the introduction of SLNB. Methods: A population-based study was performed, using data from UHL Oncology Database, including all women diagnosed with node-positive EBC between 01/01/2001 and 31/12/2010 (N = 553). Records were retrospectively evaluated for clinical, demographic and pathologic data. Majority had axillary node clearance (ANC) (548/553; 99.1%). Patients were divided into 3 LNR risk groups (Low: ≤ 0.20; Intermediate: 0.21 – 0.65; and High: > 0.65). Kaplan-Meier survival analysis was performed. Proportional hazard modelling was undertaken to evaluate whether LNR was associated with overall survival (OS). Results: Median follow-up: 59.8 months (IQR: 37.1 – 88.9). LNR distribution: Low: 303/553 (54.8%), Intermediate: 160/553 (28.9%) and, High: 90/553 (16.3%). Kaplan-Meier estimates for OS stratified by LNR risk group, showed Low risk group had better outcome for OS (p < 0.001). 5- and 10-year OS survival rates were 63% and 58%, respectively. The number of positive LNs correlated with 10-year OS (66%, 48% and, 48% for patients with N1, N2 and N3 stage respectively; p < 0.001). LNR also correlated with 5-year OS (69%, 48% and, 41% for Low-, Intermediate-, and High-risk groups respectively; p < 0.001). Significantly, LNR on multivariate analysis also formed a prognostic model when combined with age, ER status, PgR status and, HER2 status (p < 0.001). Conclusions: Our findings support the use LNR as a predictor for OS for patients with EBC in Mid-Western Ireland. LNR should be considered as an independent prognostic variable to the current prognostic instruments already in use. In a SLNB and Z0011 era, are we losing potential prognostic information?
Functional analysis of novel TBX5 T-box mutations associated with Holt-Oram syndrome (vol 88, pg 130, 2010)
Authors: Cornelis J. J. Boogerd, Dennis Dooijes, Aho Ilgun, Inge B. Mathijssen, Roel Hordijk, Ingrid M. B. H. van de Laar, Patrick Rump, Hermine E. Veenstra-Knol, Antoon F. M. Moorman, Phil Barnett, Alex V. Postma
Journal: Cardiovascular Research (2011)
La strategia della Comunità Europea contro la resistenza antimicrobica
Authors: S Bronzwaer, A Lönnroth, R Haigh
Journal: Eurosurveillance (2004)

Nel 2001 la Commissione Europea ha presentato una strategia contro la resistenza antimicrobica. Negli anni precedenti, il problema e stato affrontato con un crescente numero di misure isolate, ma in questa strategia la Commissione delinea un approccio generale della Comunita Europea in tutti i settori. La strategia consiste di quindici azioni in quattro aree chiave: sorveglianza, prevenzione, ricerca e sviluppo di prodotti, cooperazione internazionale. Una parte importante di questa strategia e la Council Recommendation sull'uso prudente degli agenti antimicrobici in medicina umana. La raccomandazione fornisce un set dettagliato di azioni di sanita pubblica per contenere la resistenza antimicrobica. Questo articolo presenta gli undici punti di azione della strategia che sono direttamente correlati con la medicina umana, e discute le relative attivita della Commissione Europea. Nel nuovo programma di sanita pubblica come pure nel programma di ricerca dell'Unione Europea, la resistenza antimicrobica e una priorita chiave.
Sustained Release of Immunosuppressant by Nanoparticle-anchoring Hydrogel Scaffold Improved the Survival of Transplanted Stem Cells and Tissue Regeneration
Authors: Ruixiang Li, Jianming Liang, Yuwei He, Jing Qin, Huining He, Seungjin Lee, Zhiqing Pang, Jianxin Wang
Journal: Theranostics (2017)

The outcome of scaffold-based stem cell transplantation remains unsatisfied due to the poor survival of transplanted cells. One of the major hurdles associated with the stem cell survival is the immune rejection, which can be effectively reduced by the use of immunosuppressant. However, ideal localized and sustained release of immunosuppressant is difficult to be realized, because it is arduous to hold the drug delivery system within scaffold for a long period of time. In the present study, the sustained release of immunosuppressant for the purpose of improving the survival of stem cells was successfully realized by a nanoparticle-anchoring hydrogel scaffold we developed. Methods: Poly (lactic-co-glycolic acid) (PLGA) nanoparticles were modified with RADA16 (RNPs), a self-assembling peptide, and then anchored to a RADA16 hydrogel (RNPs + Gel). The immobilization of RNPs in hydrogel was measured in vitro and in vivo, including the Brownian motion and cumulative leakage of RNPs and the in vivo retention of injected RNPs with hydrogel. Tacrolimus, as a typical immunosuppressant, was encapsulated in RNPs (T-RNPs) that were anchored to the hydrogel and its release behavior were studied. Endothelial progenitor cells (EPCs), as model stem cells, were cultured in the T-RNPs-anchoring hydrogel to test the immune-suppressing effect. The cytotoxicity of the scaffold against EPCs was also measured compared with free tacrolimus-loaded hydrogel. The therapeutic efficacy of the scaffold laden with EPCs on the hind limb ischemia was further evaluated in mice. Results: The Brownian motion and cumulative leakage of RNPs were significantly decreased compared with the un-modified nanoparticles (NPs). The in vivo retention of injected RNPs with hydrogel was obviously longer than that of NPs with hydrogel. The release of tacrolimus from T-RNPs + Gel could be sustained for 28 days. Compared with free tacrolimus-loaded hydrogel, the immune responses were significantly reduced and the survival of EPCs was greatly improved both in vitro and in vivo. The results of histological evaluation, including accumulation of immune cells and deposition of anti-graft antibodies, further revealed significantly lessened immune rejection in T-RNPs-anchoring hydrogel group compared with other groups. In pharmacodynamics study, the scaffold laden with EPCs was applied to treat hind limb ischemia in mice and significantly promoted the blood perfusion (~91 % versus ~36 % in control group). Conclusion: The nanoparticle-anchoring hydrogel scaffold is promising for localized immunosuppressant release, thereby can enhance the survival of transplanted cells and finally lead to successful tissue regeneration.
Plasmacytoid dendritic cells protect from viral bronchiolitis and asthma through semaphorin 4a–mediated T reg expansion
Authors: Jason P. Lynch, Rhiannon B. Werder, Zhixuan Loh, Md. Al Amin Sikder, Bodie Curren, Vivian Zhang, Matthew J. Rogers, Katie Lane, Jennifer Simpson, Stuart B. Mazzone, Kirsten Spann, John Hayball, Kerrilyn Diener, Mark L. Everard, Christopher C. Blyth, Christian Forstner, Paul G. Dennis, Nida Murtaza, Mark Morrison, Páraic Ó Cuív, Ping Zhang, Ashraful Haque, Geoffrey R. Hill, Peter D. Sly, John W. Upham, Simon Phipps
Journal: The Journal of Experimental Medicine (2017)

Respiratory syncytial virus–bronchiolitis is a major independent risk factor for subsequent asthma, but the causal mechanisms remain obscure. We identified that transient plasmacytoid dendritic cell (pDC) depletion during primary Pneumovirus infection alone predisposed to severe bronchiolitis in early life and subsequent asthma in later life after reinfection. pDC depletion ablated interferon production and increased viral load; however, the heightened immunopathology and susceptibility to subsequent asthma stemmed from a failure to expand functional neuropilin-1+ regulatory T (T reg) cells in the absence of pDC-derived semaphorin 4a (Sema4a). In adult mice, pDC depletion predisposed to severe bronchiolitis only after antibiotic treatment. Consistent with a protective role for the microbiome, treatment of pDC-depleted neonates with the microbial-derived metabolite propionate promoted Sema4a-dependent T reg cell expansion, ameliorating both diseases. In children with viral bronchiolitis, nasal propionate levels were decreased and correlated with an IL-6high/IL-10low microenvironment. We highlight a common but age-related Sema4a-mediated pathway by which pDCs and microbial colonization induce T reg cell expansion to protect against severe bronchiolitis and subsequent asthma.