tbuckley/cabot-search huggingface dataset:
Intravenous Thrombolysis Before Endovascular Thrombectomy for Acute Ischemic Stroke
Authors: Jeffrey L. Saver, Opeolu Adeoye
Journal: JAMA (2021)

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
Asxl1 C-terminal mutation perturbs neutrophil differentiation in zebrafish
Authors: Xiao Fang, Song’en Xu, Yiyue Zhang, Jin Xu, Zhibin Huang, Wei Liu, Shunqing Wang, Kuangyu Yen, Wenqing Zhang
Journal: Leukemia (2021)

Abstract ASXL1 is one of the most frequently mutated genes in malignant myeloid diseases. In patients with myeloid malignancies, ASXL1 mutations are usually heterozygous frameshift or nonsense mutations leading to C-terminal truncation. Current disease models have predominantly total loss of ASXL1 or overexpressed C-terminal truncations. These models cannot fully recapitulate leukemogenesis and disease progression. We generated an endogenous C-terminal-truncated Asxl1 mutant in zebrafish that mimics human myeloid malignancies. At the embryonic stage, neutrophil differentiation was explicitly blocked. At 6 months, mutants initially exhibited a myelodysplastic syndrome-like phenotype with neutrophilic dysplasia. At 1 year, about 13% of mutants further acquired the phenotype of monocytosis, which mimics chronic myelomonocytic leukemia, or increased progenitors, which mimics acute myeloid leukemia. These features are comparable to myeloid malignancy progression in humans. Furthermore, transcriptome analysis, inhibitor treatment, and rescue assays indicated that asxl1 -induced neutrophilic dysplasia was associated with reduced expression of bmi1a , a subunit of polycomb repressive complex 1 and a reported myeloid leukemia-associated gene. Our model demonstrated that neutrophilic dysplasia caused by asxl1 mutation is a foundation for the progression of myeloid malignancies, and illustrated a possible effect of the Asxl1-Bmi1a axis on regulating neutrophil development.
OP0144 Development of a prospective, longitudinal, inception cohort to evaluate the outcome of rheumatoid arthritis in african-americans
Authors: R Brasington
Journal: Annals of the Rheumatic Diseases (2001)

<h3></h3> It has been established that the prevalence of rheumatoid arthritis (RA) in African-Americans (AA) in the United States is comparable to that of the white population. However, data comparing the clinical manifestations and outcome of RA in AA and other ethnic groups is limited. Approximately 90% of the AA population of St. Louis, MO. lives within an area of twelve contiguous zip codes, within which is the Washington University School of Medicine (WUSM). Almost 60% of the individuals within these zip codes have incomes below the poverty level, and the vast majority of such patients receive their medical care at WUSM Rheumatology Clinic. In addition, our clinic provides care for patients from the surrounding geographic area who have a more diverse distribution of income and insurance status. We propose to develop an inception cohort of AA patients with RA by ACR criteria to be entered within one year of diagnosis, and follow this cohort prospectively in a longitudinal fashion. The primary comparison group will be white patients with early RA seen at the same outpatient clinic; Russian immigrants, Hispanics, and Asian-Pacific rim patients will serve as additional comparison groups if numbers of patients are sufficient. Demographic data will be collected on zip code, income, education, medical insurance status, and literacy. Treatment for each patient will be non-randomised, and determined by the patient's treating rheumatologist. Outcome measures will include the ACR core data set (tender and swollen joint count, MD and patient global assessment, pain VAS by patient, HAQ, and ESR), to be collected at baseline and every six months. Sharp scores will be obtained on radiographs of hands in all patients at baseline and at yearly intervals. Data will be analysed to compare ACR 50, ACR 70, mean ACR (N), HAQ scores, and Sharp scores for each group. We will also compare use of Disease Modifying Antirheumatic Drugs (DMARDs), specifically with regard to initiation in the first year, use of combinations of DMARDs, and use of biologic agents. Multivariate regression analysis will be performed to adjust for confounding variables which might influence outcome, such as income, education, duration of symptoms before seeking medical treatment, duration of symptoms before the introduction of DMARDs, and specific DMARDs used.
AB1050 CLINICAL IMPLICATIONS OF ULTRASONOGRAPHY (US) IN DIAGNOSIS AND MONITORING DISEASE ACTIVITY OF RELAPSING POLYCHONDRITIS (RP) AND COMPARATIVE INVESTIGATION BY US BETWEEN AURICLE OF RP, REPEATED TRAUMA, CELLULITIS AND HEALTHY SUBJECT
Authors: H. Nishikawa, Y. Taniguchi, M. Ogasawara, S. Inotani, E. Amano, T. Matsumoto, K. Hamada-Ode, Y. Shimamura, T. Horino, S. Fujimoto, Y. Terada
Journal: Annals of the Rheumatic Diseases (2020)

Objectives: To assess the clinical implications of ultrasonography (US) in monitoring disease activity and diagnosis of relapsing polychondritis (RP). Methods: Firstly, auricular (n=5) and nasal (n=1) chondritis of six patients with RP were assessed by US before and after treatments. The relationship between US findings and serum markers were evaluated. Moreover, the comparisons of US findings between the auricle of patients with RP (n=5), repeated trauma (n=5), cellulitis (n=2) and healthy subjects (n=5) were also assessed. Results: US finding before treatment showed low-echoic swollen auricular and nasal cartilage with increased power Doppler signals (PDS) in all cases of RP. US findings corresponded to biopsy findings. After treatment, the swollen ear and nose completely resolved. Then, US findings also showed dramatic reductions in swollen cartilage with the decrease in PDS. Although serum markers completely improved, US finding remained in 1 of 6 cases, and this case showed flare due to PSL tapering. Finally, RP could be differentiated from the damage of repeated trauma and cellulitis by the presence or absence of PDS and subperichondrial serous effusion. Conclusion: US of auricular and nasal cartilage in RP possibly facilitates evaluation of auricular lesions and monitoring of disease activity, especially when we consider the treatment response and the timing of drug tapering. Disclosure of Interests: None declared
FRI0193 Gastric and gallbladder motility in patients with systemic sclerosis: simultaneous real-time ultrasound study
Authors: PJ Kotyla, EJ Kucharz, L Brzezinska-Wcislo, B Sliwinska-Kotyla
Journal: Annals of the Rheumatic Diseases (2001)

<h3>Background</h3> Progressive systemic sclerosis (SSc) is a connective tissue disease where fibrosis of skin and internal organ is a hallmark of disease activity. One of the most affected system in the patients is the alimentary tract. <h3>Objectives</h3> The aim of the study was to determine self-related contraction and motor activity between stomach and gallbladder. <h3>Methods</h3> Study was performed in a group of twelve patients with SSc. Twelve sex- and age-matched healthy volunteers served as the controls. Gallbladder volume and emptying was assessed after ingestion of fat-rich 300 ml semi-liquid fluid. Changing cross section antrum diameter was measured in the same time. <h3>Results</h3> Delayed gastric emptying in patients with SSc was shown. Impaired gastric activity was especially seen in early and late phases of gastric emptying (p. &lt; 0,05) Gallbladder function was not altered, although compared to controls bile ejection fraction was slightly but statistically non-significant diminished. <h3>Conclusion</h3> Gastric motility disturbances observed in patients with SSc are mainly due to its involvement in the course of disease. We postulate that slightly impaired gallbladder function did not augment gastric contraction impairment.
Explore: A Prospective, Multinational Natural History Study of Patients with Acute Hepatic Porphyrias (AHP) with Recurrent Attacks
Authors: Eliane Sardh, Laurent Gouya, Joseph Bloomer, Manisha Balwani, Dwight Bissell, David C Rees, Ulrich Stolzel, John D. Phillips, Raili Kauppinen, Janneke Langendonk, Robert J. Desnick, Jean-Charles Deybach, Herbert L. Bonkovsky, Charles J. Parker, H Naik, Michael Badminton, Penny Stein, Elizabeth Minder, Jerzy Windyga, Pavel Martasek, Maria Domenica Cappellini, Paolo Ventura, Pauline Harper, Sverre Sandberg, Aasne Aarsand, Felix Alegre, Aneta Ivanova, Neila Talbi, Stephanie Rock, Amy Chan, Chang Heok Soh, Katherine A. McCarthy, W Querbes, Craig Penz, Amy Simon, Karl Anderson
Journal: Blood (2017)
Authors’ reply to Soljak, Robson and colleagues, and Kelly
Authors: Andrew Moscrop, Sue Ziebland, Gary Bloch, Janet Rodriguez Iraola
Journal: BMJ (2021)

We are grateful for the interest shown in our paper and for the responses on The BMJ website and on social media.1

Soljak emphasises the importance of occupation, both as a marker of social class and as a determinant of occupational hazards.2 He points to workers at higher risk in the current context of covid-19. The lack of socioeconomic data …
Biomimetic Tympanic Membrane Replacement Made by Melt Electrowriting
Authors: Max von Witzleben, Thomas Stoppe, Tilman Ahlfeld, Anne Bernhardt, Marie‐Luise Polk, Matthias Bornitz, Marcus Neudert, Michael Gelinsky
Journal: Advanced Healthcare Materials (2021)

Abstract The tympanic membrane (TM) transfers sound waves from the air into mechanical motion for the ossicular chain. This requires a high sensitivity to small dynamic pressure changes and resistance to large quasi‐static pressure differences. The TM achieves this by providing a layered structure of about 100µm in thickness, a low flexural stiffness, and a high tensile strength. Chronically infected middle ears require reconstruction of a large area of the TM. However, current clinical treatment can cause a reduction in hearing. With the novel additive manufacturing technique of melt electrowriting (MEW), it is for the first time possible to fabricate highly organized and biodegradable membranes within the dimensions of the TM. Scaffold designs of various fiber composition are analyzed mechanically and acoustically. It can be demonstrated that by customizing fiber orientation, fiber diameter, and number of layers the desired properties of the TM can be met. An applied thin collagen layer seals the micropores of the MEW‐printed membrane while keeping the favorable mechanical and acoustical characteristics. The determined properties are beneficial for implantation, closely match those of the human TM, and support the growth of a neo‐epithelial layer. This proves the possibilities to create a biomimimetic TM replacement using MEW.
Gut CD4+ T cell phenotypes are a continuum molded by microbes, not by TH archetypes
Authors: Evgeny Kiner, Elijah Willie, Brinda Vijaykumar, Kaitavjeet Chowdhary, Hugo Schmutz, Jodie Chandler, Alexandra Schnell, Pratiksha I. Thakore, Graham LeGros, Sara Mostafavi, Diane Mathis, Christophe Benoist, Oscar Aguilar, Rhys Allan, Jilian Astarita, K. Frank Austen, Nora Barrett, Alev Baysoy, Christophe Benoist, Brian D. Brown, Matthew Buechler, Jason Buenrostro, Maria Acebes Casanova, Kyunghee Choi, Kaitavjeet Chowdhary, Marco Colonna, Ty Crowl, Tianda Deng, Jigar V. Desai, Fiona Desland, Maxime Dhainaut, Jiarui Ding, Claudia Dominguez, Daniel Dwyer, Michela Frascoli, Shani Gal-Oz, Ananda Goldrath, Ricardo Grieshaber-Bouyer, Baosen Jia, Tim Johanson, Stefan Jordan, Joonsoo Kang, Varun Kapoor, Ephraim Kenigsberg, Joel Kim, Ki wook Kim, Evgeny Kiner, Mitchell Kronenberg, Lewis Lanier, Catherine Laplace, Caleb Lareau, Andrew Leader, Jisu Lee, Assaf Magen, Barbara Maier, Alexandra Maslova, Diane Mathis, Adelle McFarland, Miriam Merad, Etienne Meunier, Paul Monach, Sara Mostafavi, Soren Muller, Christoph Muus, Hadas Ner-Gaon, Quyhn Nguyen, Peter A. Nigrovic, German Novakovsky, Stephen Nutt, Kayla Omilusik, Adriana Ortiz-Lopez, Mallory Paynich, Vincent Peng, Marc Potempa, Rachana Pradhan, Sara Quon, Ricardo Ramirez, Deepshika Ramanan, Gwendalyn Randolph, Aviv Regev, Samuel A. Rose, Kumba Seddu, Tal Shay, Avishai Shemesh, Justin Shyer, Christopher Smilie, Nick Spidale, Ayshwarya Subramanian, Katelyn Sylvia, Julie Tellier, Shannon Turley, Brinda Vijaykumar, Amy Wagers, Chendi Wang, Peter L. Wang, Aleksandra Wroblewska, Liang Yang, Aldrin Yim, Hideyuki Yoshida
Journal: Nature Immunology (2021)
THU0130 Systemic aa amyloidosis in rheumatoid arthritis – the influence of septic infection, tuberculosis or associated malignant tumours. a retrospective study
Authors: AJ Apathy, M Bely
Journal: Annals of the Rheumatic Diseases (2001)

<h3>Background</h3> Systemic secondary (reactive) AA amyloidosis (AAa) is one of the most important complications of rheumatoid arthritis (RA). The AA amyloid precursors are produced by the liver, basically determined by the chronic relapsing inflammation of RA. The disease may be complicated by other inflammatory phenomena, such as generalised septic infection, chronic active tuberculosis, or may be accompanied by malignant tumours and consequent inflammation. <h3>Objectives</h3> The aim of this study was to determine the role of lethal, generalised septic infection, or associated diseases like tuberculosis, and malignant tumours on the development and course of amyloidosis. <h3>Methods</h3> A randomised autopsy population of 161 in-patients (female 116, average age of 64.9 years; male 45, average age of 66.2 years at death) with rheumatoid arthritis (RA) was studied.<sup>1</sup> AA amyloidosis (AAa), lethal septic infection (SI), inactive post-primary tuberculosis (Tb), or active miliary tuberculosis (mTb), and malignant tumours (mTu) was post mortem diagnosed histologically. The links between AAa and coexisting complications (SI, Tb, mT, and mTu) were analysed by chi<sup>2</sup>-test. <h3>Results</h3> AAa was observed in 34 (21.1%), SI in 22 (13.7%), Tb in 13 (8.1%), mTb in 6 (3.7%) and mTu in 13 (8.1%) of 161 RA patients. AAa was associated with SI in 1, with Tb in 2, with mTb in 2, with mTu in 3 of 34 cases. There was a negative association between AAa and SI (value of association coefficient was negative: -0.7346). There was no significant correlation between AAa and SI (chi² = 3.1279, p &lt; 0.07), Tb (chi² = 0.0302, p &lt; 0.86), mTb (chi² = 0.05638, p &lt; 0.81), or mTu (chi² = 0.0302, p &lt; 0.86). <h3>Conclusion</h3> AAa may be considered a direct consequence of RA. Coexistent inflammatory complications (SI, Tb, or mTb, mTu) did not influence statistically the frequency of AAa in our autopsied RA patients. Post-primary tuberculotic scars did not represent an active inflammation, and did not have a statistically significant influence on amyloidosis. Miliary dissemination of tuberculosis (endogenous reactivation of post-primary tuberculosis) must be considered a terminal pre-mortem phenomenon, which ? because of its terminal onset – did not have a statistically significant effect on prevalence of AAa. Based on the negative value of association coefficient between AAa an SI may guess a diminished reactivity of the vessels and tissues infiltrated by amyloid. This effect is nearly significant (chi² = 3.1279, p &lt; 0.07). <h3>Reference</h3> Bély M. Krankheitsmodifizierende Faktoren bei chronischer Polyarthritis. D. Sc. Acad. Sci. Hung. Thesis. Budapest, 1993
Abstract 19468: Pharmacological Inhibition of Plasminogen Activator Inhibitor-1 Decreases Atherosclerosis Formation in a Murine Model of Obesity and Metabolic Syndrome
Authors: Yan Ji, Tammy L Strawn, William P Fay
Journal: Circulation (2016)

Introduction: Metabolic syndrome (MetS=abdominal obesity, dyslipidemia, hyperglycemia, and hypertension) is strongly associated with increased risk of atherosclerosis (athero) and increased express...
Imaging Drug for Prostate Cancer
Authors: Mary Chris Jaklevic
Journal: JAMA (2021)

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
HP0012 The discriminatory validity of the new zealand score for hip and knee surgery in a uk population
Authors: FM Toye, SE Lamb, JH Barlow, CC Wright
Journal: Annals of the Rheumatic Diseases (2001)

<h3>Background</h3> There is currently no standardised method for prioritising patients joint replacement surgery in the UK. The New Zealand (NZ) score could be used to assist prioritisation.<sup>1</sup> This approach has not been tested in the UK. <h3>Objectives</h3> To determine whether the NZ score is associated with measures of pain and function, in a sample of 176 people who were currently waiting for, or being considered for total knee replacement. <h3>Methods</h3> Patients completed the WOMAC scores, a Likert scale for distress (0–4), and a 100 mm VAS for pain. Leg power was tested using a leg extensor power rig. The number of sit to stands in one minute was recorded. In NZ a cut off point of between 55–65 is used. Those scoring below 55 are not recommended for surgery. Patients were stratified into 2 groups. The first group included all those scoring below 55, and the second group all those who scored 55 or above. Spearman's correlation was performed to identify correlation between the NZ score and other measures. Mann-Whitney tests were performed in order to test differences between groups. <h3>Results</h3> 44% were male, with a mean age of 69(SD9). Mean duration of symptoms was 10 years (SD12), and mean VAS score for pain was 57 (SD24). 68% were already listed for surgery. Significant correlations were found between the NZ score and all other measures p &lt; 0.01 (2-tailed). A higher NZ score was associated with more pain, less functional ability and reduced strength. The Rho values are shown in the table. Median scores for all measurements were significantly different between the two groups p &lt; 0.01 (2-tailed). 28% scored 55 or above, 85% of these were already listed for surgery, 67% were listed as "routine" cases and 33% were listed as "soon". Those scoring above 55 were weaker, had reduced function, and more pain than those scoring below 55. These differences were statistically and clinically significant. <h3>Conclusion</h3> The NZ score is associated with pain and function in a UK population of patients waiting for, or being considered for total knee replacement surgery. Further research is needed to identify whether a score of 55 is the optimal cut off point. This cut off point did not distinguish between patients who were already listed for surgery and those who were not. However, it did identify higher patient need. <h3>Reference</h3> Hadorn DC, Holmes AC. The New Zealand priority criteria project part1: overview. Br Med J. 1997;314:131–4
Pembrolizumab plus chemotherapy for previously untreated, HER2-negative unresectable or metastatic advanced gastric or gastroesophageal junction (G/GEJ) adenocarcinoma: KEYNOTE-859.
Authors: Josep Tabernero, Yung-Jue Bang, Eric Van Cutsem, Charles S. Fuchs, Yelena Y. Janjigian, Pooja Bhagia, Kan Li, David E. Adelberg, Shu Kui Qin
Journal: Journal of Clinical Oncology (2021)

TPS263 Background: For patients with unresectable, locally advanced recurrent or metastatic G/GEJ cancer, the standard of care includes a fluoropyrimidine plus a platinum-based agent as first-line therapy. The PD-1 inhibitor pembrolizumab has demonstrated durable antitumor activity in this patient population across lines of therapy. Herein, we describe the randomized, double-blind, phase 3 KEYNOTE-859 trial (NCT03675737) of first-line pembrolizumab plus chemotherapy in patients with advanced G/GEJ adenocarcinoma. Methods: Patients with histologically or cytologically confirmed, locally advanced unresectable or metastatic G/GEJ adenocarcinoma with known PD-L1 expression status, HER2-negative disease, measurable disease per RECIST v1.1, and ECOG performance status of 0 or 1 will be randomly assigned 1:1 to receive pembrolizumab plus chemotherapy or placebo plus chemotherapy. Randomization will be stratified by geographic region (Europe/Israel/North America/Australia vs Asia vs rest of world), PD-L1 tumor expression status (combined positive score &lt; 1 vs ≥1), and combination chemotherapy (FP vs CAPOX). Pembrolizumab or placebo will be administered at 200 mg IV every 3 weeks (Q3W). The chemotherapy regimen will be investigator’s choice of FP (continuous infusion of 5-fluorouracil [800 mg/m 2 /day on days 1-5 of each cycle] plus IV cisplatin [80 mg/m 2 ] Q3W) or CAPOX (oral capecitabine [1000 mg/m 2 twice daily on days 1-14 of each cycle] plus IV oxaliplatin [130 mg/m 2 on day 1 of each cycle] Q3W). Duration of cisplatin or oxaliplatin may be capped at 6 cycles per local country guidelines; treatment with 5-fluorouracil or capecitabine may continue per protocol. Treatment with pembrolizumab or placebo will continue for ≤35 administrations (~2 years) or until disease progression, unacceptable toxicity, intercurrent illness that prevents further administration of treatment, investigator decision, or noncompliance. Imaging will be performed at screening and subsequently every 6 weeks until disease progression, start of new anticancer treatment, withdrawal of consent, or death. Adverse events will be monitored throughout the study from the time of randomization to 30 days after the last dose of study treatment (90 days for serious adverse events). The dual primary end points are OS and PFS per RECIST v1.1 as assessed by blinded independent central review (BICR). Secondary end points include ORR and DOR per RECIST v1.1 as assessed by BICR, safety, and tolerability. Enrollment is ongoing. Clinical trial information: NCT03675737.