tbuckley/cabot-search huggingface dataset:
Annals Story Slam - The Medicine Man
Authors: Michael Schull
Journal: Annals of Internal Medicine (2017)

Web Exclusives19 September 2017Annals Story Slam - The Medicine ManFREEMichael Schull, MD, MScMichael Schull, MD, MScFrom Institute for Clinical Evaluative Sciences, Toronto, Ontario, Canada.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/W17-0054 SectionsAboutVisual Abstract ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail Video. Annals Story Slam - The Medicine Man "The Medicine Man," by Dr. Michael Schull (Duration 05:44)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: From Institute for Clinical Evaluative Sciences, Toronto, Ontario, Canada.Current Author Address: Michael Schull, MD, MSc, Institute for Clinical Evaluative Sciences, Toronto, Ontario, Canada; e-mail, [email protected]on.ca. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 19 September 2017Volume 167, Issue 6Page: SS1 ePublished: 19 September 2017 Issue Published: 19 September 2017 Copyright & PermissionsCopyright © 2017 by American College of Physicians. All Rights Reserved.Loading ...
Physiology of Mucus Secretion
Journal: JNCI Journal of the National Cancer Institute (1945)

Physiology of Mucus Secretion Get access Franklin Hollander Franklin Hollander Gastroenterological Research Laboratory, Mount Sinai Hospital, New York Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 5, Issue 5, April 1945, Page 367, https://doi.org/10.1093/jnci/5.5.367 Published: 01 April 1945
AB1184 Educational needs of patients with rheumatic diseases receiving biologics
Authors: AT Kotulska, EJ Kucharz, P Wiland, M Olesinska, A Felis-Giemza, M Kopec-Medrek, W Romanowski, L Szymczak-Bartz, M Tlustochowicz, J Lewandowicz, J Kowalska-Majka, J Bucka, M Majdan, Z Kielbik, M Korkosz, A Bielinska, P Leszczynski, K Pawlak-Bus, M Puszczewicz, M Majewski, K Smolik, T Migas-Kukla, M Sochocka-Bykowska, M Szarecka, B Luberda, M Falenta-Hitnarowicz, J Swikszcz-Gniadek, W Lepiarz-Rusek, G Rozwadowski, B Chara, J Zajdel, Z Zdrojewski, I Rosmus-Kuczia
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> Biologics are still considered by patients as a new and partially enigmatic tool for management of rheumatic diseases. <h3>Objectives</h3> The study was designed to evaluate educational needs and sources of knowledge in patients with rheumatic diseases treated with biologics. <h3>Methods</h3> Anonymous questionnaires were distributed in 23 Polish rheumatological centers involved in the treatment, 1231 questionnaires were used for analysis. Responses were received from 606 patients with rheumatoid arthritis, 427 with ankylosing spondylitis, 117 psoriatic arthritis, and 62 adult patients with juvenile idiopathic arthritis (in whom administration of the drugs had been introduced before they were 18-year-old), as well as 19 ones receiving the drugs due to other musculoskeletal disorders. The investigated group constituted about one-fifth of all rheumatic patients on biologics in Poland. <h3>Results</h3> Almost all the patients had learnt for the first time on biologics from their rheumatologist (93%). Few only patients had got such data from internet or from other patients. Likewise, most of the patients got majority of educational data on treatment with biologics from rheumatologist who was supervising the therapy (82%). Remaining sources included internet (8%) and other patients (5%). Relative low number of patients was educated by nurses (2%). Most of the patients (87%) were looking for more details on biological treatment. The patients with rheumatic disease lasting less than 10 yrs. were more interested in the management than those suffering longer. Most of the patients (94%) considered their rheumatologist as the main person responsible for their education on biologics. There was no difference between patients with various rheumatic diseases as well as no difference was found between female and male patients. Biological treatment attracted more interest in younger than older patients. <h3>Conclusions</h3> Education is still a challenge in patients receiving biologics. Most of the patients represented traditional attitude to health education, expecting almost all educational data to be provided by their physician. We were surprised that role of the nurses was found to be rather low. An increase in role of nurses seems to be the future aim of the educational efforts in Polish rheumatology. <h3>Disclosure of Interest</h3> None declared
SAT0126 Mental health benefits associated with reduction in disease activity among rheumatoid arthritis patients: a systematic review of the literature
Authors: V Strand, R Rendas-Baum, M Kosinski, D Brooks, R Ganguly
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> The association between physical functioning and rheumatoid arthritis (RA) disease activity is well established. In randomized controlled trials (RCTs) of RA treatment, reductions in disease activity result in improved physical functioning. The mental health benefits associated with reductions in disease activity are less well recognized. <h3>Objectives</h3> Investigate the association between reductions in RA disease activity and measures of mental health status. <h3>Methods</h3> A systematic review of the published literature of RCTs in RA was conducted. The search was limited to those published in the last 10 years that included the Short-Form (SF)-36 Health Survey as an outcome measure. <h3>Results</h3> The search strategy yielded 77 articles of which 38 were excluded for the following reasons: not RCT (23); focus exclusively on early RA (9); psychometric evaluation (4); review study (1); and off topic (1). Of the 39 articles reporting mean changes in scores on the SF-36 mental health (MH) and role emotional (RE) domains by treatment group, 3 articles also presented these changes in association with reductions in RA disease activity measures.<sup>1–3</sup> In relation to American College of Rheumatology (ACR) response criteria, small to moderate (0.2–0.5 standard deviation [SD]) effect size changes in RE and MH domain scores were observed among RA patients whose ACR responses ranged from 20–49%. Moderate to large effect sizes (0.5–0.8 SD) were reported in RE and MH domain change scores among ACR50 responders. Similar changes in RE and MH domain scores were reported by patients with reductions in Simplified Disease Activity Index (SDAI) of ≥10 points. <h3>Conclusions</h3> The benefits of clinically meaningful reductions in disease activity among RA patients not only include improved physical functioning but also meaningful improvements in overall mental health status. The improvement in mental health is positively associated with reduction in disease activity, with only small to moderate improvements associated with less than ACR50 responses. Additional work is needed to investigate the incremental effects of RA therapies on mental health beyond the effects related to improvements in disease activity. <h3>References</h3> Emery P, et al. J Rheumatol. 2006;33(4):681–689. Russell AS, et al. Ann Rheum Dis. 2007;66(2):189–194. Strand V, et al. Health Qual Life Outcomes. 2014;12:31. <h3>Disclosure of Interest</h3> V. Strand Consultant for: Abbvie, Amgen, AstraZeneca, BiogenIdec, Boehringer Ingelheim, Celltrion, Crescendo, Genentech/Roche, GSK, Janssen, Lilly, Merck, Novartis, Pfizer, Regeneron, Samsung, Sanofi and UCB, R. Rendas-Baum Employee of: Optum, M. Kosinski Employee of: Optum, D. Brooks Shareholder of: GlaxoSmithKline, Employee of: GlaxoSmithKline, R. Ganguly Shareholder of: GlaxoSmithKline, Employee of: GlaxoSmithKline
THU0326 Short and long-term follow-up with adalimumad in refractory uveitis associated to behÇet's disease. multicenter study of 74 patients
Authors: L Domínguez-Casas, V Calvo-Río, E Beltrán, J S-Bursόn, M Mesquida, A Adán, M Hernandez, M H-Grafella, E V-Pascual, L M-Costa, A Sellas, M Cordero-Coma, M Díaz-Llopis, R Gallego, D Salom, J G-Serrano, N Ortego, J Herreras, A G-Aparicio, O Maíz, A Blanco, I Torre, D Díaz-Valle, E Pato, E Aurrecoechea, M Caracuel, F Gamero, E Minguez, C Carrasco, A Olive, J Vázquez, O R-Moreno, J Manero, S Muñoz, M Gandia, E Rubio-Romero, F Toyos-SMiera, F Lόpez-Longo, J Nolla, M Revenga, N Vegas-Revenga, C Fernández-Díaz, R Demetrio-Pablo, M González-Gay, R Blanco
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Objectives</h3> To evaluate the efficacy of adalimumab (ADA) in short and long term follow-up in refractory uveitis of Behçet9s disease (BD) <h3>Methods</h3> Multicenter study. Ocular inflammation was evaluated according to “SUN working Group” (Am J Ophthalmol 2005;140:509–516), and the macular thickening with OCT. A comparison was carried out between baseline, and follow-up visits. Results are expressed as mean±SD or median [IQR]. Continuous variables were compared with Wilcoxon test. <h3>Results</h3> We studied 74 patients/132 affected eyes (39M/35W); mean age 38.7±11.3. The ocular pattern was panuveitis (n=45), posterior uveitis (n=14), anterior uveitis (n=14) and intermediate uveitis (n=1). Before ADA, systemic treatment with corticosteroids, iv metilprednisolone (n=23), Cyclosporin A (58), azathioprine (33), metotrexate (31) and other drugs (28) was used. The dose of ADA was 40 mg/2 weeks/ sc in monotherapy (n=22) or combined (n=52). Most patients showed a rapid and progressive improvement (TABLE). The 24 patients (37 affected eyes) with CME showed a significant improvement. ADA was optimized in 23 (31.1%) that were in remission for 15.3±9 months. Interval of administration was increased to 3 (n=6), 4 (13), 5 (1), 6 (1) and 8 weeks. After a mean follow-up of 13.0±9.7 months after optimization, 21 patients were stable and 2 had a severe flare. In 4 patients ADA was stopped after 35.2±9.3 months in remission. The main adverse effects observed were lymphoma (n=1), pneumonia (1), and 2° bacteriemia by E. Coli (1) <h3>Conclusions</h3> ADA was effective in short and long-term follow-up in refractory uveitis associated to BD. Optimization or even suspension of ADA is possible. <h3>Disclosure of Interest</h3> None declared
Mechanism of Action and Clinical Impact of Ribociclib—Response
Authors: Debu Tripathy, Aditya Bardia, William R. Sellers
Journal: Clinical Cancer Research (2017)

We would like to thank Dr. Sorscher for the clarification provided. We would also like to point out that cyclin/CDK complexes, in addition to being a convergence point for multiple nutrition and growth factor signals, can also be oncogenically activated by way of amplification of CDKs and cyclins (cyclin D in particular is frequently amplified in ER+ breast cancer) as well as upstream driver genomic alterations such as HER2 amplification and BRAF mutations. Therefore, CDK4/6 inhibitors do represent a novel approach that affects Rb tumor suppressor gene (TSG) function, but Rb must be intact for this therapeutic effect. Replacement of TSG function would indeed be an important and quite a challenging milestone. Still, there are some cases of cancers with intact Rb function that are intrinsically resistant to CDK inhibitors, reflecting other mechanisms of resistance or bypass pathways that require further investigation.See the original Letter to the Editor, p. 5657D. Tripathy is a consultant/advisory board member for Novartis and Pfizer. A. Bardia is a consultant/advisory board member for Novartis. W.R. Sellers is an employee of and a consultant/advisory board member for Novartis.The content is solely the responsibility of the authors and does not necessarily represent the official views of the NCI or the NIH.The project described was supported in part by award number P30CA014089 from the NCI (to D. Tripathy). A. Bardia is supported by the NIH (4K12CA087723-14). Financial support for medical editorial assistance was provided by Novartis Pharmaceuticals Corporation.
SAT0080 Clinical significance of soluble CD163 in refractory systemic-onset idiopathic arthritis
Authors: Y Cui, H Zeng
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Objectives</h3> The present study explored the correlation of soluble CD163 with refractory systemic-onset juvenile idiopathic arthritis (refractory So-JIA) as well as the clinical significanceof soluble CD163 in (refractory So-JIA). <h3>Methods</h3> A total of 33 young patients diagnosed with So-JIA in the active period and 30 young patients diagnosed with So-JIA in the inactive period at Guangzhou Women and Children9s Medical Center (Guangzhou, China) from January 2010 to January 2012 as well as 40 age-matched healthy individuals, who had visited the hospital for medical examination in the same time-period were enrolled in the present study. Flow cytometry was used to determine the lymphocyte count and ELISA was adopted for determining the levels of soluble CD163 in serum <h3>Results</h3> The levels of soluble CD163 and their correlation with indexes of disease activity were observed. In patients with So-JIA in the active period, the levels of soluble CD163 and the Tcell count were significantly higher than those in the inactive So-JIA and healthy individuals (P&lt;0.05). Furthermore, the levels of soluble CD163 were positively correlated with C-reactive protein, ferritin, erythrocyte sedimentation rate, white blood cell count and immunoglobulin E as indexes of disease activity (P&lt;0.05). <h3>Conclusions</h3> Soluble CD163 is a more valuable index for early recognise refractory active So-JIA, which can provide a basis for active period development and clinical observation. <h3>Disclosure of Interest</h3> None declared
Modes of Rapid Polygenic Adaptation
Authors: Kavita Jain, Wolfgang Stephan
Journal: Molecular Biology and Evolution (2017)

Many experimental and field studies have shown that adaptation can occur very rapidly. Two qualitatively different modes of fast adaptation have been proposed: selective sweeps wherein large shifts in the allele frequencies occur at a few loci and evolution via small changes in the allele frequencies at many loci. Although the first process has been thoroughly investigated within the framework of population genetics, the latter is based on quantitative genetics and is much less understood. Here we summarize results from our recent theoretical studies of a quantitative genetic model of polygenic adaptation that makes explicit reference to population genetics to bridge the gap between the two frameworks. Our key results are that polygenic adaptation may be a rapid process and can proceed via subtle or dramatic changes in the allele frequency depending on the sizes of the phenotypic effects relative to a threshold value. We also discuss how the signals of polygenic selection may be detected in the genome. Although powerful methods are available to identify signatures of selective sweeps at loci controlling quantitative traits, the development of statistical tests for detecting small shifts of allele frequencies at quantitative trait loci is still in its infancy.
Early application of airway pressure release ventilation may reduce the duration of mechanical ventilation in acute respiratory distress syndrome
Authors: Yongfang Zhou, Xiaodong Jin, Yinxia Lv, Peng Wang, Yunqing Yang, Guopeng Liang, Bo Wang, Yan Kang
Journal: Intensive Care Medicine (2017)

Experimental animal models of acute respiratory distress syndrome (ARDS) have shown that the updated airway pressure release ventilation (APRV) methodologies may significantly improve oxygenation, maximize lung recruitment, and attenuate lung injury, without circulatory depression. This led us to hypothesize that early application of APRV in patients with ARDS would allow pulmonary function to recover faster and would reduce the duration of mechanical ventilation as compared with low tidal volume lung protective ventilation (LTV).A total of 138 patients with ARDS who received mechanical ventilation for <48 h between May 2015 to October 2016 while in the critical care medicine unit (ICU) of the West China Hospital of Sichuan University were enrolled in the study. Patients were randomly assigned to receive APRV (n = 71) or LTV (n = 67). The settings for APRV were: high airway pressure (Phigh) set at the last plateau airway pressure (Pplat), not to exceed 30 cmH2O) and low airway pressure ( Plow) set at 5 cmH2O; the release phase (Tlow) setting adjusted to terminate the peak expiratory flow rate to ≥ 50%; release frequency of 10-14 cycles/min. The settings for LTV were: target tidal volume of 6 mL/kg of predicted body weight; Pplat not exceeding 30 cmH2O; positive end-expiratory pressure (PEEP) guided by the PEEP-FiO2 table according to the ARDSnet protocol. The primary outcome was the number of days without mechanical ventilation from enrollment to day 28. The secondary endpoints included oxygenation, Pplat, respiratory system compliance, and patient outcomes.Compared with the LTV group, patients in the APRV group had a higher median number of ventilator-free days {19 [interquartile range (IQR) 8-22] vs. 2 (IQR 0-15); P < 0.001}. This finding was independent of the coexisting differences in chronic disease. The APRV group had a shorter stay in the ICU (P = 0.003). The ICU mortality rate was 19.7% in the APRV group versus 34.3% in the LTV group (P = 0.053) and was associated with better oxygenation and respiratory system compliance, lower Pplat, and less sedation requirement during the first week following enrollment (P < 0.05, repeated-measures analysis of variance).Compared with LTV, early application of APRV in patients with ARDS improved oxygenation and respiratory system compliance, decreased Pplat and reduced the duration of both mechanical ventilation and ICU stay.
FRI0050 Type ii collagen secreted from articular chondrocytes is mainly destroyed by cathepsin s in ra mice
Authors: J Zhao, Q Huang, H Ren, M Yang
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> Mast cells have long been recognized to increase strikingly in number in the synovial membrane of rheumatoid arthritis (RA), accounting for 5% of the surface synovial membrane cells. Type II collagen has the longest half-life in cartilage matrix. The main cells which might affect articular cartilage in RA are synovial fibroblasts, synovial macrophages and mast cells. The latter two could express cathepsin S. <h3>Objectives</h3> We aimed to find the cells which have the biggest influence on type II collagen secreted from articular chondrocytes and the possible mechanisms in RA mice. <h3>Methods</h3> Four types of cells from collagen-induced arthritis model-established C57BL/6 mice were primary cultured, including synovial fibroblasts, peritoneal macrophages, bone marrow-derived mast cells and articular chondrocytes. The first three were co-cultured with articular chondrocytes separately. LHVS, a specific inhibitor of cathepsin S, and E64, a broad-spectrum inhibitor of cysteine protease, were added into the cocultures of macrophages and articular chondrocytes separately. Also, C48/80, an activator of mast cells, LHVS, and E64 were added into the cocultures of mast cells and articular chondrocytes separately. The culture supernatant fluid was collected. The concentration of cathepsin S and type II collagen were measured by ELISA. The expression of type II collagen mRNA in each group was detected with RTPCR. <h3>Results</h3> Macrophages and mast cells expressed cathepsin S, while synovial fibroblasts did not express cathepsin S. Synovial fibroblasts had little effect on the expression of type II collagen from articular chondrocytes. When articular chondrocytes were co-cultured with macrophages, the expression of type II collagen decreased (8.79±2.79ng/ml),compared with the control group (17.75±7.84ng/ml). The secretion of type II collagen could return to normal by the inhibitors of cathepsin S, both LHVS (16.15±8.05 ng/ml) and E64 (12.55±6.64 ng/ml). When articular chondrocytes were co-cultured with mast cells, the type II collagen could be restrained by C48/80 (9.82±0.42ng/ml), compared with the control group (26.09±9.34ng/ml). Similarly, the secretion of type II collagen could return to normal by LHVS and E64 (16.15±8.05 ng/ml, 12.55±6.64 ng/ml, respectively). There was no significant difference in the expression of type II collagen mRNA between different groups. It showed that the type II collagen was not suppressed at the transcription level, but was mainly destroyed by cathepsin S after secretion. <h3>Conclusions</h3> Macrophages and mast cells are the major sources of cathepsin S, which might be the main factor that destroys type II collagen secreted from articular chondrocytes in RA mice. <h3>Disclosure of Interest</h3> None declared
FRI0714 Lupus nephritis and prognosis. effect of membranous and other components of the histology
Authors: MU Martinez Martinez, C Vallín-Orozco, HE Esparza-Holguin, G Aguilera-Barragán Pickens, D Martínez-Galla, C Abud-Mendoza
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> In 1983 Austin et al. informed a series of prognostic factors (including histology) associated with the development of renal failure in patients with lupus nephritis (LN). Differences in actual therapies may have different hazard ratios of renal failure than the described by Austin et al.<sup>1</sup> <h3>Objectives</h3> To evaluate histological factors associated with a decline in kidney function (DKF) in patients with SLE. <h3>Methods</h3> We evaluated all the patients in whom a kidney biopsy was performed. DKF was defined as a glomerular filtration rate (GFR) of less than 60 ml/min/m<sup>2</sup> in two determinations in the follow-up. Histology was graded according to Austin et al.<sup>1</sup> (activity and chronicity) by a renal pathology specialist. Factors associated with the development of DKF were evaluated through Kaplan-Meier curves and Cox regression analysis (bivariate and multivariate). <h3>Results</h3> At this moment, we have followed 170 patients with LN and kidney biopsy, 130 (76.5%) women, mean age at kidney biopsy was 29.7±13.2 years; classes of LN were: 71 patients (41.8%) class IV, 30 (17.6%) class V, 22 (12.9%) class III/V, 19 (11.2%) class IV/V, 16 (9.4%) class III, and other classes 12 patients; 135 patients (79.5%) have a minimum follow-up of 12 months. There were statistically significant differences in four groups of LN: pure proliferative (classes III or IV), the combination with membranous (III/IV±V), pure membranous (V) or other classes (Figure1). In the bivariate analysis, factors statistically significant associated with the development of DKF were: glomerular sclerosis, fibrous crescents, interstitial cell infiltration and tubular atrophy; having membranous component resulted as a "protector" factor for the development of DKF. The Cox regression model included all the factors with a p-value less than 0.25 in the bivariate analysis; independent factors associated with increased HR of DKF were glomerular sclerosis and fibrous crescents; however, hyaline thrombi and presence of membranous nephritis were associated with a decreased HR of DKF. (Table 1). <h3>Conclusions</h3> We describe factors associated with a DKF. We found that the proliferative LN in combination with membranous have a better prognosis than pure proliferative LN. Our study could help to evaluate the effects of therapies in LN. <h3>References</h3> Austin HA, et al. Am J Med 1983;75:382–391. <h3>Disclosure of Interest</h3> None declared