tbuckley/cabot-search huggingface dataset:
Pneumocystis and glucocorticoid use: to prophylax or not to prophylax (and when?); that is the question
Authors: Kevin L Winthrop, John W Baddley
Journal: Annals of the Rheumatic Diseases (2018)

Pneumocystis jiroveci is an opportunistic fungus with the ability to cause lethal pneumonia in those with advanced immunosuppression.1 Fortunately, this outcome is preventable with prophylaxis. Unfortunately, however, deciding who is immunosuppressed enough to justify prophylaxis can be a confusing subject, particularly among rheumatology patients where immunosuppression waxes and wanes based on the use of immunosuppressive therapies and the contribution of the underlying inflammatory disease. Foggy notions persist regarding who is at risk, the level of absolute risk where the risk-benefit of using trimethoprim/sulfamethoxazole (TMP/SMX) or other prophylaxis is worthwhile, and when can prophylaxis be safely stopped.2 The article by Park et al published in the Annals of Rheumatic Diseases 3 sheds light on these important questions, such that a picture of how to approach this issue clinically might finally be more clear for the practicing rheumatologist.

Given the difficulty studying these questions in a randomised controlled trial fashion, comparative effectiveness studies such as this one might provide the next best thing. In the article, the authors address the following questions: in patients starting high-dose glucocorticoids and taking them greater than 4 weeks, what is the risk of pneumocystic jiroveci pneumonia (PJP) (and the risk factors for it) and how does risk relate to dose? Further, they evaluate the efficacy of TMP/SMX prophylaxis. To answer these questions, they retrospectively identified an institutional cohort of rheumatology patients in Korea treated with ‘high-dose’ glucocorticoids (>30 mg/day) for 4 or more weeks. Within this cohort, they selected patients offered TMP/SMX prophylaxis and compared their incidence of PJP with the remainder of the group that did not receive prophylaxis. There were important underlying differences between the groups, as one might expect, and it was clear that the treating physicians had generally chosen to give TMP/SMX to those they had perceived at higher risk for …
Formation of TIAR/TIA-1-containing stress granules depends on the kinetics of oxygen partial pressure decline and may suppress angiogenesis by HIF pathway
Authors: Oana Domnisoru, Gabriela Krasteva, Friedrich Grimminger, Werner Seeger, Frank Rose, Jorg Hanze
Journal: Cancer Research (2008)

1763  Rationale: T-cell intracellular antigen 1 (TIA-1) and TIA-1 related protein (TIAR) are ubiquitously expressed RNA binding proteins that contribute to the formation of stress granules. They inhibit the translation of mRNA under stress conditions. Both global and specific translation of mRNA is affected. Stress granules assembly has been observed after heat shock, ultraviolet radiation, oxidative stress and other disturbances to cellular homeostasis. Our aim was to characterize stress granules formation under defined hypoxic conditions, and to analyze how TIAR and TIA1 influence hypoxia-inducible factor (HIF)-dependent gene regulation and angiogenesis. Methods:  Oxygen partial pressure was measured with a sensor equipped sonde placed in the medium of the cells, stress granules were visualised by immuocytofluorescence, protein level of TIAR/TIA1 and HIF1α was analyzed by Western Blot, the activity of HIF pathway was analyzed using luciferase reporter gene assay, that measures HIF target activation by hypoxia-responsive element (HRE). Angiogenesis was assessed by plating human umbilical vein endothelial cells (HUVEC) on Matrigel and quantifying the total length of tube-like structures which are spontaneously forming (tube formation assay).  Results: When either human A549 lung adenocarcinoma cells, or HUVEC were cultured in a hypoxic gas incubator (10 mmHg oxygen), the formation of stress granules was not observed. However, when employing Oxyrase (Oxyrase, Inc.), an enzyme that consumes oxygen from the medium, stress granules formation was observed. Oxyrase also caused pronounced HIF1α accumulation, and induction of HIF-dependent gene regulation as measured by reporter gene assay. Interestingly, the oxygen partial pressure decreased from 130 mmHg to 10 mmHg in the hypoxic chamber after about 1.5 hours, whereas in the case of Oxyrase, the oxygen concentration decreased to 10 mmHg within 10 minutes. A strong increase in HRE activation after inhibition of TIAR by small interfering RNA (siRNA) was observed using a reporter gene assay. Interestingly, also an increase of angiogenesis as analysed by tube formation assay was observed when HUVEC were transfected with siRNA TIAR Conclusion: We conclude that apart from the absolute oxygen concentration, the kinetics of oxygen partial pressure decline was also critical for stress granules formation. Furthermore, there is a particular suppression of HIF signalling and of angiogenesis by TIAR.
Abstract 14775: Current Results of Open Repair of Descending Thoracic and Thoracoabdominal Aortic Aneurysms
Authors: Mario Gaudino, Christopher Lau, Monica Munjal, Mohamed Elsayed, Umberto Benedetto, Leonard N Girardi
Journal: Circulation (2015)

Introduction: Open repair of thoracic and thoracoabdominal aortic aneurysms (DTA and TAAA respectively) constitutes a benchmark for comparison with endovascular techniques. Hypothesis. To evaluate the current results of the open repair of DTA and TAAA. Methods. Open DTA and TAAA repair was performed on 675 consecutive patients (210 TAA and 465 TAAA). Three surgical techniques were used based on the type of the aneurysm and the risk profile of the patient: clamp and saw, partial bypass or hypothermic circulatory arrest. Spinal drain was used in 82.7% of patients. Regression analysis was performed to identify independent determinants of in-hospital and late outcomes and individual major postoperative complications. Propensity matching (PPM) was used to compare results of the different surgical techniques Results. Operative mortality was 5.6% (38/675); incidence of postoperative spinal cord injury, stroke, need for tracheostomy, myocardial infarction and dialysis were 2.8%, 0.7%, 7.7%, 0.6% and 5.2% respectively. Kaplan Mayer survival at five-year was 57.8%. Female gender, urgent operation and preoperative dialysis were independent predictors of adverse in-hospital adverse events. Preoperative renal and respiratory failure were associated with follow-up death. Female gender and preoperative chronic pulmonary disease were associated with postoperative need for tracheostomy, whereas preoperative renal failure, urgent operation and peripheral vascular disease predicted the need for postoperative dialysis. Due to the low number of events, logistic regression analysis was not possible for predictors of spinal cord injury. In the PPM groups no difference was found in the early and late outcome between patients treated with different techniques (see table). Conclusion: In the current era open TAA and TAAA repair allows excellent outcomes.
Colors Beyond the Visible
Authors: Dana Saade, Mayra B. C. Maymone, Neelam A. Vashi
Journal: JAMA Dermatology (2018)

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 Dermatology 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 Dermatology journal
Effect of Exenatide Once-Weekly on Clinical Outcomes in Patients With Type 2 Diabetes Mellitus and Cardiovascular Disease: Insights From the EXSCEL Trial
Authors: R J Mentz, M A Bethel, V P Thompson, Y Lokhnygina, J B Buse, J C Chan, J Choi, S M Gustavson, N Iqbal, A P Maggioni, S P Marso, P Ohman, N J Pagidipati, N Poulter, A Ramachandran, B Zinman, R R Holman, A F Hernandez, Grp Exscels.
Journal: Circulation (2017)
CAD-CAP: une base de données française à vocation internationale, pour le développement et la validation d'outils de diagnostic assisté par ordinateur en vidéocapsule endoscopique du grêle
Authors: X Dray, C Li, JC Saurin, F Cholet, G Rahmi, JP Le Mouel, C Leandri, S Lecleire, X Amiot, JM Delvaux, C Duburque, R Gérard, R Leenhardt, F Mesli, G Vanbiervliet, I Nion Larmurier, S Sacher-Huvelin, C Simon-Chane, R Olivier, A Histace
Journal: Endoscopy (2018)

La vidéocapsule endoscopique du grêle (VCE-G) est un examen de première ligne dans l'exploration non-invasive de l'intestin grêle. Avec un nombre moyen de 50000 images du grêle par examen, l'interprétation d'un enregistrement reste fastidieux et chronophage (en moyenne 30 à 40 minutes par vidéo), et source potentielle de lésions manquées. Aussi, le développement de programmes de détection assisté par ordinateur (DAO) est un enjeu majeur de recherche en VCE-G. La création d'une banque d'images et de vidéo de VCE-G, ouvertes à la communauté des chercheurs dans ce domaine, est indispensable d'une part aux processus d'apprentissage par ordinateur (machine learning) et d'autre part aux comparaisons valides de différents algorithmes.
Pathogen Inactivation Strategies to Improve Blood Safety
Authors: Dana V. Devine
Journal: JAMA Oncology (2018)

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 Oncology 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 Oncology journal
Fitting mSMART Into the Current Clinical Management of Waldenström Macroglobulinemia—Reply
Authors: Prashant Kapoor, Morie A. Gertz, Stephen M. Ansell
Journal: JAMA Oncology (2018)

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 Oncology 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 Oncology journal
Impact de la cholangiopancréatoscopie rétrograde Spyglass™ sur la prise en charge des atteintes bilio-pancréatiques indéterminées: Résultats finaux d'une étude multicentrique française
Authors: S Leblanc, F Foissac, T Ponchon, R Laugier, F Maire, A Charachon, D Coumaros, B Vedrenne, P Bichard, I Boytchev, S Gaujoux, A Laquière, B Terris, N Kaddour, S Chaussade, F Prat
Journal: Endoscopy (2018)

La cholangiopancréatoscopie rétrograde utilisant le système Spyglass™ (Boston Scientific, USA), permet, au cours du cathétérisme bilio-pancréatique (CPRE) une étude visuelle des lésions et la réalisation de biopsies dirigées. Une étude française prospective, multicentrique, a étudié l'impact du Spyglass™ sur la prise en charge des atteintes bilio-pancréatiques indéterminées. Nous en présentons ici les résultats finaux.
Abstract 15084: Physiological and Hormonal Predictors for Blood Pressure Response after Percutaneous Transluminal Renal Angioplasty
Authors: Kentaro Jujo, Keisuke Nakabayashi, Issei Ishida, Yuki Suzuki, Katsumi Saito
Journal: Circulation (2012)

BACKGROUNDS: Percutaneous transluminal renal angioplasty (PTRA) improves patency in atherosclerotic renal artery stenosis (ARAS). However, blood pressure (BP) improvement as primary purpose was achieved in only 20-40% of patients performed PTRA.   METHODS AND RESULTS: This study included 29 consecutive patients with ARAS detected by aortography for etiological screening of hypertension and performed staged PTRA in a single cardiovascular center from June 2010 till March 2012. Patients were categorized as ‘responders’ depending on mean BP decrease more than 10 mmHg 2 days after PTRA compared to baseline. Ultrasonographic data, hormonal parameters and renal functions were also evaluated at the same time points. As results, although there was no significant difference in BP at baseline between responders and non-responders (systolic, 150±21 vs. 141±18, p=0.21; diastolic, 75±13 vs. 65±12, p=0.061; mean, 100±14 vs. 91±12 mmHg, p=0.070, respectively), 14 responders achieved 21±9.0 mmHg decrease in mean BP, did 15 non-responders only 0.5±8.5 mmHg (p>0.01). On clinical backgrounds and initial medication, there also was no statistical difference. In terms of echorenographic parameters, the average value of peak systolic velocity (PSV) was significantly higher (218±95 vs. 160±41 cm/sec., p=0.039) and resistive index was significantly lower (0.78±0.05 vs. 0.84±0.07, p>0.01) in responders. Interestingly, renal/aorta ratio or acceleration time did not reach statistical significance between the groups. Assessment of hormonal parameters revealed that the concentration of serum aldosterone at baseline was significantly higher in responders (111±66 vs. 65±42 ng/dL, p=0.032), yet other parameters including plasma renin activity and serum BNP did not differ statistically between the groups. Moreover, renal function evaluated by serum creatinine, estimated GFR and cystatin C did not exhibit any significant difference between responders and non-responders.   CONCLUSION: The present study demonstrated that one physiological (PSV) and one hormonal (aldosterone) parameters were preoperative predictors of favorable BP response to PTRA. These findings may help clinicians to optimize risk-benefit profile of PTRA and reduce unnecessary intervention.
Exploiting Nanobodies’ Singular Traits
Authors: Jessica R. Ingram, Florian I. Schmidt, Hidde L. Ploegh
Journal: Annual Review of Immunology (2018)

The unique class of heavy chain-only antibodies, present in Camelidae, can be shrunk to just the variable region of the heavy chain to yield VHHs, also called nanobodies. About one-tenth the size of their full-size counterparts, nanobodies can serve in applications similar to those for conventional antibodies, but they come with a number of signature advantages that find increasing application in biology. They not only function as crystallization chaperones but also can be expressed inside cells as such, or fused to other proteins to perturb the function of their targets, for example, by enforcing their localization or degradation. Their small size also affords advantages when applied in vivo, for example, in imaging applications. Here we review such applications, with particular emphasis on those areas where conventional antibodies would face a more challenging environment.
P020 Toll-like receptor 9 influences inflammatory arthritis and osteoclastogenesis
Authors: A Fischer, S Abdollahi-Rodsaz, ACY Yau, E Lonnblom, R Holmdahl, G Steiner
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Introduction</h3> Release and insufficient removal of endogenous nucleic acids may be involved in triggering autoimmune reactions important in the initiation of systemic autoimmune diseases including rheumatoid arthritis (RA). Nucleic acid sensing molecules, such as the endosomal Toll-like receptors (TLRs) 7 and 9, have been linked to pathogenic autoimmune processes, but their role in RA is less clear. <h3>Objectives</h3> To gain more insight into the role of TLR9 in autoimmune arthritis, TLR9 inhibition was investigated in rats with pristane-induced arthritis (PIA). To further investigate TLR9 involvement, streptococcal cell wall (SCW) arthritis was induced in TLR9<sup>-/-</sup> mice. <h3>Methods</h3> Arthritis was induced in mice with SCW lysates and in rats with the mineral oil pristane. Rats were treated with a TLR9 antagonist, starting before disease induction. Arthritis was scored using established scoring systems, inflammation and bone erosion was quantified by histological analysis of the paws. Levels of α−1-acid-glycoprotein (AGP), rheumatoid factor (RF) and IL-6 in sera were analysed. The role of TLR9 in osteoclast differentiation was investigated <i>in vitro</i>. <h3>Results</h3> In PIA, which is T cell-dependent, the TLR9 antagonist reduced arthritis severity by ~50%. This was accompanied by a reduction of AGP, IL-6 and RF in the sera of these animals. In addition, TLR9 inhibition led to reduced inflammation, bone erosion and cartilage degradation in the paws. Moreover, the T cell-dependent chronic phase of SCW arthritis was significantly suppressed in TLR9<sup>-/-</sup> mice. Remarkably, TLR7 and TLR9 mRNA levels strongly differed in the course of <i>in vitro</i> osteoclastogenesis. Whereas TLR7 expression did not change throughout osteoclastogenesis, expression of TLR9 was higher in precursor cells than in mature osteoclasts and stimulation with a TLR9 agonist (CpG) completely inhibited osteoclastogenesis. <h3>Conclusions</h3> The results suggest a crucial role for TLR9 in the T cell-dependent phases of PIA and SCW arthritis and thus an important involvement of the DNA (CpG) recognising TLR9 in the induction of arthritogenic autoimmune reactions. In addition, TLR9 also seems to play a role in the initiation of osteoclast differentiation which needs to be further elucidated in future experiments. <h3>Disclosure of interest</h3> None declared
Hypoxia-inducible factor (HIF) 1α and 2α as predictive markers of outcome to VEGFR tyrosine kinase inhibitors (TKI) in renal cell carcinoma (RCC).
Authors: M.I. Saez, Jose Manuel Trigo Perez, L.G. Perez-Rivas, L. Perez-Villa, R. Villatoro, A. Montesa, J.I. Cid, M. Leon, V. de Luque, C. Fernandez, C. Quero, B. Pajares, E. Alba
Journal: Journal of Clinical Oncology (2012)

4630 Background: Relevant biomarkers in RCC are needed to identify appropriate candidates for selected targeted therapies. Mutations in the von Hippel-Lindau (VHL) gene result in the accumulation of HIF and increased expression of proangiogenic factors, including VEGF. Methods: Metastatic clear RCC patients with available baseline tumor samples who received first-line oral VEGFR-TKI were included in this analysis. VHL mutation/hypermethylation status and HIF1α and HIF2α immunohistochemical staining were analyzed from paraffin-embedded tumors. Additionally, a panel of candidate VEGF and VEGFR2 genetic SNPs was determined from peripheral blood samples. HIF was scored as negative or positive based on staining intensity (0-10% and &gt; 10%, respectively). Results were evaluated for associations with clinical outcome. Results: 80 patients were included: 71 evaluable for HIF expression, 63 for VHL status and 52 for SNPs. 73% received treatment with sunitinib and median follow-up was 21.5 months. Unlike VHL status, HIF1 and HIF2 positive expression showed a significant correlation with PFS and OS. HIF1α was also predictive for response rate (RR). On multivariate analysis adjusting for other prognostic factors, HIF1α and HIF2α remained the most significant independent predictive factors for survival (adjusted HR 0.09, 95% CI 0.03-0.28, p &lt; 0.0001 and HR 0.13, 95% CI 0.04-0.37, p &lt; 0.0001; respectively). We did not find any statistically significant differences based on the VEGF and VEGFR2 SNPs analyzed. Conclusions: HIF1α and HIF2α levels represent the most important independent predictive factors of outcome for VEGFR-TKI therapy in metastatic RCC. These findings may contribute to optimize treatment with targeted agents. [Table: see text]