tbuckley/cabot-search huggingface dataset:
P072 MEFV/miR-326 axis involvement in human macrophage polarization
Authors: M Robin, G Sarrabay, B Peynircioglu, S Ozen, I Touitou, I Duroux-Richard, F Apparailly
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Career situation of first and presenting author</h3> Young investigator. <h3>Introduction</h3> Familial Mediterranean fever (FMF) is an inherited autoinflammatory disease, characterized by acute self-resolving attacks of fever and serositis, which mainly prevails in populations around the Mediterranean sea. It is caused by mutations in the <i>MEFV</i> gene, which encodes the pyrin protein. The alteration of <i>MEFV</i> mRNA expression in monocytes is related to both genotype and phenotype of the disease, suggesting that the pathophysiology of FMF can be regulated on a quantitative defect of <i>MEFV</i> mRNA. <h3>Objectives</h3> Since microRNAs (miRNAs) are implicated in a number of diseases including FMF, the present study aimed at identifying miRNA regulators of <i>MEFV</i> expression involved in monocyte inflammatory response. <h3>Methods</h3> MiRWalk2.0 database was used to identify putative miRNA target sequences within the 3'-UTR mRNA of <i>MEFV</i>. Human primary CD14<sup>+</sup> monocytes were sorted from peripheral blood of healthy donors using magnetic microbeads and differentiated into M1 or M2 macrophages following IFNγ/LPS or IL4/IL13 stimulation, respectively. Using RT-qPCR, M1/M2 polarization was validated by measuring the expression of prototypic M1 and M2 markers: the chemokine <i>CXCL10</i> and the macrophage mannose receptor 1 (<i>MRC1</i> also known as CD206), respectively, as well as the <i>MEFV</i> mRNA. We used loss-of-function method to evaluate the effect of candidate miRNA on CD14<sup>+</sup> monocytes, i.e. its role on macrophages classical versus alternative polarization. IL-10 expression was quantified using ELISA. <h3>Results</h3> <i>In silico</i> analyses revealed that miR-326 targets putatively the 3'UTR mRNA of <i>MEFV</i>. miRNAs and mRNAs quantification in polarized macrophages showed that miR-326 is mainly expressed by the M2-type macrophages, and <i>MEFV</i> by the M1-type macrophages. Loss-of-function studies showed that neutralization of miR-326 in M2 macrophages induced the expression of <i>MEFV</i> and <i>CXCL10</i> while reducing <i>MRC1</i> expression level. Furthermore, enforced expression of miR-326 in M1 macrophages significantly repressed <i>MEFV</i> expression and induced the production of IL-10. <h3>Conclusions</h3> A miR-326/<i>MEFV</i> axis seems to be implicated in macrophage polarization and might explain the observed monocyte versatility in FMF. <h3>Disclosure of Interest</h3> None declared.
GP recruitment in Scotland is “challenging,” warns auditor
Authors: Bryan Christie
Journal: BMJ (2019)

Ambitious plans to recruit an extra 800 family doctors to work in Scotland by 2027 will be hard to meet, says a critical report on GP recruitment from Audit Scotland.1

It accuses the Scottish government of making bold commitments without having a reliable basis for implementation and calls for much more detailed work to be completed on workforce planning.

Expanding the GP workforce and changing how primary care services are delivered are central to the plan to move …
Glutamate Signaling in Hepatic Stellate Cells Drives Alcoholic Steatosis
Authors: Won-Mook Choi, Hee-Hoon Kim, Myung-Ho Kim, Resat Cinar, Hyon-Seung Yi, Hyuk Soo Eun, Seok-Hwan Kim, Young Jae Choi, Young-Sun Lee, So Yeon Kim, Wonhyo Seo, Jun-Hee Lee, Young-Ri Shim, Ye Eun Kim, Keungmo Yang, Tom Ryu, Jung Hwan Hwang, Chul-Ho Lee, Hueng-Sik Choi, Bin Gao, Won Kim, Sang Kyum Kim, George Kunos, Won-Il Jeong
Journal: Cell Metabolism (2019)
Abstract 17493: Enhanced Expression of Neopterin is Associated With Aortic Valve Stenosis in Patients With Bicuspid Aortic Valve
Authors: Shunsuke Kagawa, Masashi Nakagawa, Kenji Shimeno, Ryo Matsumoto, Yoshiki Matsumura, Yukio Abe, Kazuo Haze, Takahiko Naruko, Minoru Yoshiyama, Makiko Ueda
Journal: Circulation (2017)

Background: The mechanisms responsible for the more rapid progression of aortic stenosis (AS) in patients with bicuspid aortic valve (BAV) than in those with tricuspid aortic valve (TAV) are unknow...
Effect of nutritional status and support on survival in esophageal cancer patients undergoing combined modality therapy
Authors: J. P. Plastaras, J. C. Haynes, R. Mick, L. M. Hertan, A. I. Urdaneta, J. M. Metz
Journal: Journal of Clinical Oncology (2009)

e20641 Background: Baseline nutritional status is associated with clinical outcomes in esophageal cancer. Moreover, nutritional support during chemoradiation has been shown to improve outcomes in other disease sites. This retrospective study evaluated the impact of nutritional interventions and baseline nutritional status on outcomes in patients (pts) with locally advanced esophageal cancer. Methods: A retrospective review was performed of 132 pts treated with curative intent using radiation (RT) between 1986 and 2007 at the Hospital of the University of Pennsylvania. The median age of the population was 60 years (range: 33–86). Esophagectomy was performed in 70%, with adjuvant RT in 60% and neoadjuvant RT in 40%. Concurrent chemotherapy was given to 85% of the group. Nutritional counseling was provided to 83% of pts. During RT, oral or enteral nutritional supplements were provided to 77% of pts and intravenous fluids (IVF) were given to 38%. Median follow-up was 14.1 months. Results: Median survival from end of radiation was 1.5 yrs. Median absolute and percentage weight loss during RT were 6.2 lbs and 3.8%, respectively. Median percentage decrease in hemoglobin and albumin were 5.7% and 9.1%, respectively. Univariable Cox regression analysis demonstrated a statistically significant association between weight loss of ≥5 lbs during RT and worse survival (HR 1.74, 95% CI 1.09 - 2.79, p=0.02). Decrease in hemoglobin of 5% or more (HR 1.22, 95% CI 0.59 - 2.54) and decrease in albumin of 10% or more (HR 1.09, 95% CI 0.48 - 2.48) were not associated with survival. Patients who received only nutritional supplements during RT survived significantly longer (p=0.03) than pts who received IVF regardless of nutritional supplementation (HR 2.12, 95% CI 1.12 - 4.01) or pts who received neither nutritional supplements nor IVF (HR 1.8, 95% CI 1.03 - 3.14). Conclusions: Weight loss during RT predicted for worse survival. Nutritional factors before and during RT may be important in outcomes in patients with esophageal cancer and may be modifiable. The use of IVF may be a potential indicator of worse prognosis. Future prospective studies should consider these factors in trial design. No significant financial relationships to disclose.
Epidermal growth factor receptor mutations and gene amplification in Japanese non-small cell lung cancer patients treated with gefitinib
Authors: T. Kawaguchi, H. Sasaki, M. Kawahara, H. Takeuchi, K. Iuchi, A. Matsumura, S. Isa, A. Kubo, M. Kitaichi, K. Kasai, M. Takada
Journal: Journal of Clinical Oncology (2006)

17063 Background: To evaluate relationship between epidermal growth factor receptor (EGFR) gene status and clinical outcome in patients with non-small-cell lung cancer (NSCLC) treated with gefitinib. Also, to examine an involvement of human papilloma virus (HPV) in EGFR status of these patients. Methods: Twenty seven patients with NSCLC who had relapsed after surgery and received gefitinib were included. Genomic DNA was extracted from the 12 paraffin and the 15 frozen surgical specimens. PCR and sequencing for genotyping were done for EGFR (exon 18–21) and ERBB2 (exon 19–22) and KRAS (exon 1). Gene amplification for EGFR was analyzed by quantitative real-time PCR. HPV was detected by PCR and in-situ PCR. Results: Nine patients (33%) had EGFR mutations; seven patients had deletion mutations in exon 19, one patient had missense mutations (L858R) in exon 21. Two patients had missense mutations (G719S, exon 18 and L838P, exon 21) No mutations were identified in ERBB2 and KRAS. EGFR copy number in the tumor cells ranged from 1.1 to 9.7, and increased EGFR copy numbers (≥3) were observed in six patients ( 22.2%). Two patients (7%) had HPV, and had no mutation and no amplification. Response rate (67% {six of nine patients} v 18% {three of 17 patients}; p = 0.012) was significantly better in patients with EGFR mutations than in patients with wild-type EGFR. Overall survival (median 17 v 9 months) was better in patients with EGFR mutations than in patients with wild-type EGFR. EGFR copy number and presence of HPV were not associated with clinical outcome. Conclusions: EGFR mutations were significantly associated with better clinical outcome in gefitinib treated NSCLC patients. No significant financial relationships to disclose.
Return to play after surgery for isolated unstable syndesmotic ankle injuries (West Point grade IIB and III) in 110 male professional football players: a retrospective cohort study
Authors: Pieter D'Hooghe, Alberto Grassi, Khalid Alkhelaifi, James Calder, Thomas PA Baltes, Stefano Zaffagnini, Jan Ekstrand
Journal: British Journal of Sports Medicine (2019)

Objectives To evaluate time to return to play following surgical stabilisation of isolated unstable syndesmosis injuries in a cohort of professional male football players. Methods All professional football players undergoing surgery for isolated unstable syndesmosis injury (West Point grade ≥IIB) at a specialised Orthopaedic and Sports Medicine Hospital were followed up until return to play (minimum ≥6 months). Players with a stable syndesmosis, injuries older than 6 weeks, concomitant medial or lateral malleolar fracture or previous ankle surgery were excluded. During rehabilitation, time required to return to sports-specific rehabilitation, team training and first match play, were recorded. Results Between January 2012 and December 2017, a total of 110 male professional football players were included. The mean time required to begin on field rehabilitation was 37±12 days, while the mean time to return to team training was 72±28 days. The first official match was played on average 103±28 days postoperatively. Multivariable analysis revealed that the severity of injury, the concomitant presence of talar cartilage injury and the age of the player were significantly associated (p&lt;0.00001) with time to return to on field rehabilitation, team training and match play. Conclusion In this cohort of professional football players, surgical stabilisation of isolated unstable syndesmosis injuries (West Point grade ≥IIB) allowed for relatively quick return to play. High grade injury (West Point grade III), concomitant cartilage injury and greater age were associated with longer return to play times. Level of evidence Longitudinal observational cohort study (level II).
High Intake of Phenolic Acids Is Associated With Reduced Risk of Colorectal Adenomas Among Smokers
Authors: Naomi Fliss-Isakov, Giuseppe Grosso, Federico Salomone, Justyna Godos, Fabio Galvano, Dana Ivancovsky-Wajcman, Oren Shibolet, Revital Kariv, Shira Zelber-Sagi
Journal: Clinical Gastroenterology and Hepatology (2019)
ARST1321: Pazopanib neoadjuvant trial in non-rhabdomysarcoma soft tissue sarcomas: A report of major wound complications.
Authors: Thomas Scharschmidt, Yen-Lin Chen, Dian Wang, Yueh-Yun Chi, Mark Kayton, Joel Sorger, R. Lor Randall, Douglas S. Hawkins, Aaron R. Weiss
Journal: Journal of Clinical Oncology (2019)

11059 Background: The care of soft tissue sarcomas is complex and multidisciplinary in nature. Even without radiation or chemotherapy wound complications are common after surgical resection with a reported incidence of 6-42%. Wound complication rates with the use of neoadjuvant chemoradiation for high-grade soft tissue sarcomas has been reported and supported in the literature to be approximately 30%. Relevant to this study, a trial evaluating the use of a VEGF receptor inhibitor (bevacizumab) in combination with radiation pre-operatively in soft tissue sarcomas reported a wound complication rate of 25%. ARST 1321 is a phase II/III study evaluating the tyrosine kinase inhibitor Pazopanib +/- chemotherapy and radiation in select high-grade soft tissue sarcomas. The dose-finding phase has been completed and the objective of this report is to detail the major wound complications observed with this protocol. Methods: Patient enrolled on all arms of the study (Pre-operative radiation, +/- pazopanib, +/- doxorubicin and ifosphamide) were evaluated for wound complications (Grade I/II and Grade III). Patient demographics, tumor characteristics, and complication details were compiled and analyzed. Results: There were a total of 130 evaluable patients (100 patients on chemotherapy arm, 30 on non-chemotherapy arm). There were 38 overall wound complications reported (38/130, 29%). 23/38 (60%) occurred on the chemotherapy arm; therefore that cohort had 23/100 (23%) wound complication rate, while the non-chemotherapy cohort had an overall rate of 50% (15/30). Grade III wound complications represented 23/38 (66%) of all the complications. 30/38 (79%) of the complications were in the lower extremity. 23/38 (60%) patients were aged &gt; 18 years. Conclusions: The overall rate of wound complications observed was 29% (38/130) which remains within the accepted historical rate based upon literature review without the use of a tyrosine kinase inhibitor. The overall major wound complication (grade III) rate was 19% (25/130). Also consistent with the literature is the finding that a majority of the complications occurred in the lower extremity. In conclusion, the addition of a tyrosine kinase inhibitor (pazopanib) has a wound complication toxicity profile comparable to current and historical literature. Clinical trial information: NCT02180867.
Direct decompressive surgery with post-operative radiotherapy (S + RT) versus radiotherapy (RT) alone for the treatment of metastatic epidural spinal cord compression (MESCC): A cost-utility analysis using Ontario health economic data
Authors: K. K. Chan, J. Furlan, S. Guillermo, K. Lam, C. Klinger, M. G. Fehlings, R. A. Patchell, A. Laporte
Journal: Journal of Clinical Oncology (2006)

8570 Background: For selected patients with MESCC, S + RT has recently been shown to improve patients’ ability to ambulate and reduce opioid and corticosteroid use when compared with RT alone, with a trend towards survival benefit. (Patchell et al Lancet 2005) The economic impact of adopting this intervention has not been assessed previously. Methods: An analytic decision model was constructed based on the results from Patchell et al. (2005) The perspective of the public health care insurer of Ontario was adopted for the analysis. Costing was performed by using Ontario data for the following items: surgery, radiotherapy, hospitalization, home care services, palliative hospice, and medications. Utilities were obtained from the Harvard University Catalogue of preference score (HUC) and the Health Outcomes Data Repository Data - Health Utility list (HODaR). The primary analysis is a cost-utility analysis comparing surgery and radiotherapy (S+RT) with radiotherapy alone (RT). A probabilistic sensitivity analysis with Monte-Carlo simulation was performed. Results: When comparing S+ RT with RT alone, the incremental cost-effectiveness ratio (ICER) is CAD$ 43,796 per QALY gained. The cost-utility of S + RT is CAD$ 509,084 per QALY and that of RT alone is CAD$ 2,381,246 per QALY. S + RT costs approximately CAD$ 33 more when compared with RT alone per ambulatory day gained. The cost of surgery is partially offset by the decreased cost of hospice palliative care since more patients remain ambulatory and stay at home. Monte-Carlo simulation showed that there is a 25% chance that S + RT may dominate RT alone. The results are sensitive but generally robust to changes in assumptions about the costs of surgery, home care and palliative hospice care. Conclusions: S+RT is likely cost-effective when compared with RT alone for the treatment of MESCC in selected patients, and should be considered by health care policy makers. No significant financial relationships to disclose.
Trends in the Mental Health Services. A Symposium of Original and Reprinted Papers.
Journal: JAMA (1963)

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 HomeNew OnlineCurrent IssueFor Authors 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) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More 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 journal
Airway morphometry in COPD with bronchiectasis: a view on all airway generations
Authors: Stephanie Everaerts, John E. McDonough, Stijn E. Verleden, Iván Josipovic, Matthieu Boone, Adriana Dubbeldam, Carolien Mathyssen, Jef Serré, Lieven J. Dupont, Ghislaine Gayan-Ramirez, Johny Verschakelen, James C. Hogg, Geert M. Verleden, Bart M. Vanaudenaerde, Wim Janssens
Journal: European Respiratory Journal (2019)

The pathophysiological processes underlying bronchiectasis in chronic obstructive pulmonary disease (COPD) are not understood. In COPD, both small and large airways are progressively lost. It is currently not known to what extent the different airway generations of patients with COPD and bronchiectasis are involved. COPD explant lungs with bronchiectasis were compared to COPD explant lungs without bronchiectasis and unused donor lungs as controls. In order to investigate all airway generations, a multimodal imaging approach using different resolutions was conducted. Per group, five lungs were frozen (n=15) and underwent computed tomography (CT) imaging for large airway evaluation, with four tissue cores per lung imaged for measurements of the terminal bronchioles. Two additional lungs per group (n=6) were air-dried for lobar microCT images that allow airway segmentation and three-dimensional quantification of the complete airway tree. COPD lungs with bronchiectasis had significantly more airways compared to COPD lungs without bronchiectasis (p&lt;0.001), with large airway numbers similar to control lungs. This difference was present in both upper and lower lobes. Lack of tapering was present (p=0.010) and larger diameters were demonstrated in lower lobes with bronchiectasis (p=0.010). MicroCT analysis of tissue cores showed similar reductions of tissue percentage, surface density and number of terminal bronchioles in both COPD groups compared to control lungs. Although terminal bronchioles were equally reduced in COPD lungs with and without bronchiectasis, significantly more large and small airways were found in COPD lungs with bronchiectasis.
Role of radiotherapy for elderly DLBCL patients in the rituximab (R) era: Final results of the RICOVER-60-no-rx study of the DSHNHL.
Authors: Gerhard Held, Niels Murawski, Marita Ziepert, Viola Poeschel, Carsten Zwick, Marcel Reiser, Sibylla Wilhelm, Tobias Gaska, Michael Heike, Joerg Schubert, Norbert Schmitz, Markus Loeffler, Christian Ruebe, Michael Pfreundschuh
Journal: Journal of Clinical Oncology (2012)

8022 Background: 117/306 (38%) of the total of 1,222 elderly (61-80 y) DLBCL pts. treated in RICOVER-60 with 6xR-CHOP-14+2R were assigned to receive additional radiotherapy (Rx) to bulky disease (Pfreundschuh et al., Lancet Oncol. 2008). To study the relevance of Rx to bulky disease (Bx), 166 pts. were prospectively treated without Rx in the R-CHOP-14-noRx amendment of RICOVER-60. Methods: The outcome of 166 R-CHOP-14-noRx patients was compared with the 306 patients who had received 6xR-CHOP-14+2R plus radiotherapy to Bx (≥7.5 cm) in RICOVER-60. Methods: The outcome of 166 R-CHOP-14-noRx patients was compared with the 306 patients who had received 6xR-CHOP-14+2R plus radiotherapy to Bx (≥7.5 cm) in RICOVER-60. Results: 164/166 R-CHOP-noRx patients are evaluable (median observation: 39 mos). Patients in R-CHOP-noRx were older (71 vs. 69 y.; median; p=0.018), more frequently in advanced stages (60% vs. 50%; p=0.037), and with extranodal involvement (63% vs. 53%; p=0.024), while Bx was more frequent in R-CHOP-14-Rx (38% vs. 29%; p=0.038). Overall response to therapy, EFS and OS were similar in the two studies adjusting for the prognostic imbalances between the cohorts. Patients with Bx who received received additional radiotherapy to Bx in R-CHOP-14-Rx had a better 3-year EFS (80% vs. 54%; p=0.001), a better PFS (88% vs. 62%; p&lt;0.001), and a better OS (90% vs. 65%; p=0.001) compared to R-CHOP-14-noRx. This was due the worse outcome of pts. with Bx in R-CHOP-14-noRx not achieving CR or CRu after 6xR-CHOP, since there was no difference in 3-year EFS in patients with Bx in CR or CRu after 6xR-CHOP-14 with and without additional radiotherapy (3-year EFS and PFS: 84% vs. 75%; p=0.430); OS 87% vs. 79%; p=0.839). Conclusions: In the R era, radiotherapy to bulky disease does not improve the outcome of elderly pts. in CR/CRu after completion of R-CHOP-14 immunochemotherapy, but appears to be beneficial for pts. with Bx not achieving CR/Cru. By restricting Bx radiotherapy to patients not achieving a CR/CRu, 43% of the patients with Bx could be spared radiotherapy. Supported by Deutsche Krebshilfe.
Comparative Efficacy of Treatment Options for Minimal Hepatic Encephalopathy: A Systematic Review and Network Meta-Analysis
Authors: Radha K. Dhiman, Kiran K. Thumburu, Nipun Verma, Madhu Chopra, Sahaj Rathi, Usha Dutta, Ashwani K. Singal, Sunil Taneja, Ajay Duseja, Meenu Singh
Journal: Clinical Gastroenterology and Hepatology (2019)
Doctor who falsely claimed she passed specialty certificate exam is struck off
Authors: Clare Dyer
Journal: BMJ (2019)

A doctor who took up a consultant endocrinologist post after falsely claiming to have passed her specialty certificate examination has been struck off the UK medical register.

Rasheeta Sivapackianathan twice took the diabetes and endocrinology specialist exam and received letters notifying her of her failing marks, but she altered one of the letters to suggest that she had passed, and uploaded it to her e-portfolio.

She first took the exam in June 2016 and learnt in July that she had failed. But later that month she told the training programme director in a penultimate year assessment that she had passed, and repeated the …