tbuckley/cabot-search huggingface dataset:
Correspondence on ‘Five-year treat-to-target outcomes after methotrexate induction therapy with or without other csDMARDs and temporary glucocorticoids for rheumatoid arthritis in the CareRA trial’
Authors: Siddharth Jain, Varun Dhir
Journal: Annals of the Rheumatic Diseases (2021)

Correspondence on 'Five-year treat-to-target outcomes after methotrexate induction therapy with or without other csDMARDs and temporary glucocorticoids for rheumatoid arthritis in the CareRA trial'The 5-year follow-up data of the Care-RA cohort are interesting. 1However, a few points merit consideration and clarification.Findings in the high-risk group reaffirm the fact that upfront combination disease-modifying antirheumatic drugs (DMARDs) are not needed even in patients of rheumatoid arthritis (RA) with poor prognostic factors, provided a treat-to-target strategy is followed.However, we wish to draw attention to the lowrisk group which compared initial methotrexate (MTX) monotherapy to MTX+prednisolone bridging (COBRA-Slim).The results in the low-risk group seem counterintuitive to previous landmark trials (including the BeSt and the TEAR) that found long-term outcomes to be essentially determined by treating-totarget, with the intensity of initial treatment only guiding the rapidity of response achieved. 2 3However, in the CareRA-plus, the initial difference in disease activity between MTX monotherapy vs MTX+prednisolone bridging (COBRA-Slim) in the low-risk group persisted for up to 5 years-this could reignite interest in the concept of 'a time-limited window of opportunity' in early RA. 4 However, it must be stressed that any conclusions in the lowrisk group should be guarded, as the numbers included in this group (n=49 at the start of this long-term extension study; 38 by the end of follow-up at 5 years) were too few to draw any reliable conclusions.Unfortunately, there was no MTX monotherapy arm in the high-risk group which had more patients, and thus could have better answered the question whether addition of bridging glucocorticoids to initial MTX monotherapy improves long-term outcomes in early RA, when followed by a tight step-up approach to treatment target.Considering the little incremental response in any treatment arm after the first year, more details regarding the treatment escalation strategies followed after the protocol-specified two step escalation (step 1 and step 2) would be insightful.We would be interested in knowing the treatment changes (switches or additions) after the protocolised first year till year 5 (in the ~50% of patients who required such changes) and the final treatment patients were taking at the end of 5 years.Nevertheless, the authors must be congratulated for their study which has reaffirmed the fact that excellent results are possible with conventional synthetic DMARDs+prednisolone in a majority of cases and biological DMARDs are required in only a minority of patients (one-fourth) with RA.
Orphan CpG islands amplify poised enhancer regulatory activity and determine target gene responsiveness
Authors: Tomas Pachano, Víctor Sánchez-Gaya, Thais Ealo, Maria Mariner-Faulí, Tore Bleckwehl, Helena G. Asenjo, Patricia Respuela, Sara Cruz-Molina, María Muñoz-San Martín, Endika Haro, Wilfred F. J. van IJcken, David Landeira, Alvaro Rada-Iglesias
Journal: Nature Genetics (2021)
International multicentre observational study to assess the efficacy and safety of a 0·5 mg kg <sup>−1</sup> per day starting dose of oral corticosteroids to treat bullous pemphigoid
Authors: V. Hébert, S. Bastos, K. Drenovska, J. Meijer, S. Ingen‐Housz‐Oro, C. Bedane, L. Lunardon, S. Debarbieux, H. Jedlickova, F. Caux, G. Chaby, M. D’Incan, C. Feliciani, C. Boulard, N. Schumacher, E. Schmidt, A. Roussel, M.A. Richard, J. Gottlieb, V. Ferranti, O. Guérin, J. Bénichou, P. Joly
Journal: British Journal of Dermatology (2021)

European guidelines propose a 0·5 mg kg-1 per day dose of oral prednisone as initial treatment for bullous pemphigoid (BP). We assessed the safety and efficacy of this regimen depending on BP extent and general condition of the patients.In a prospective international study, we consecutively included all patients diagnosed with BP. Patients received a 0·5 mg kg-1 per day dose of prednisone, which was then gradually tapered 15 days after disease control, with the aim of stopping prednisone or maintaining minimal treatment (0·1 mg kg-1 per day) within 6 months after the start of treatment. The two coprimary endpoints were control of disease activity at day 21 and 1-year overall survival. Disease severity was assessed according to the Bullous Pemphigoid Disease Area Index (BPDAI) score.In total, 198 patients were included between 2015 and 2017. The final analysis comprised 190 patients with a mean age of 80·9 (SD 9·1) years. Control of disease activity was achieved at day 21 in 119 patients [62·6%, 95% confidence interval (CI) 55·3-69.5]; 18 of 24 patients (75%, 95% CI 53·3-90·2), 75 of 110 patients (68·8%, 95% CI 59·2-77·3) and 26 of 56 patients (46.4%, 95% CI 33·0-60·3) had mild, moderate and severe BP, respectively (P = 0·0218). A total of 30 patients died during the study. The overall Kaplan-Meier 1-year survival was 82·6% (95% CI 76·3-87·4) corresponding to 90·9%, 83·0% and 80·0% rates in patients with mild, moderate and severe BP, respectively (P = 0·5). Thresholds of 49 points for BPDAI score and 70 points for Karnofsky score yielded maximal Youden index values with respect to disease control at day 21 and 1-year survival, respectively.A 0·5 mg kg-1 per day dose of prednisone is a valuable therapeutic option in patients with mild or moderate BP whose general condition allows them to be autonomous.
Wnt5a Can Induce Activation of Rac1 and Proliferation in Mantle Cell Lymphoma Via a ROR1-Dependent, but BTK-Independent, Signaling Pathway
Authors: Jian Yu, Yun Chen, Liguang Chen, Ling Zhang, Laura Z. Rassenti, George F. Widhopf, Thomas J. Kipps
Journal: Blood (2017)
Changes in Physician Work Hours and Patterns During the COVID-19 Pandemic
Authors: Xiaochu Hu, Michael J. Dill
Journal: JAMA Network Open (2021)

2020were 47.8 (95% CI, 46.6-49.1 hours per week; P < .001),an approximate 6% decrease from January 2019.The percentage of physicians reporting full-time work status declined from 84.17% (95% CI, 83.13% to 85.22%) before COVID-19 to 80.65% (95% CI, 79.03%-82.27%)(P < .001)during the pandemic, and those who claimed to "still have the same activities" at work declined from 83.90% (95% CI, 82.65% to 85.14%) to 78.00% (95% CI, 76.01% to 79.98%) (P < .001)(Table ).Although rare, the percentage of physicians reporting being laid off increased from 0.05% (95% CI, -0.01% to 0.11%) to 0.45% (95% CI, 0.21% to 0.70%) during COVID-19 (P < .001).The percentage of parents of preschool-aged children among full-time, female physicians decreased from 17.98% (95% CI, 16.05% to 19.91%) to 14.10% (11.59% to 16.60%) (P = .009)and did not significantly change among male physicians. DiscussionThis study found that physicians' work hours have significantly decreased since the start of the COVID-19 pandemic in the US, accelerating an existing, gradual decline. 6There was also a decreased percentage of physicians working full-time, a rise in the percentage who were laid off, and increased changes in physicians' usual activities.These observed changes may reflect the decrease in health care utilization 1 and the increased flexibilities instigated by COVID-19-driven regulations. 4The decline in the percentage of parents with preschool-aged children among only female physicians may suggest a disproportionate uptake of childcare responsibilities among female physicians.This study leveraged the timely, longitudinal design of CPS data to provide early evidence of changes in physician work hours and patterns.However, this study also had limitations: the CPS Figure.
Abstract 59: Antimir Therapy Ameliorates HIF1-mediated Loss of SERCA2 and Cardiac Contractility
Authors: Allison L Williams, Chad Walton, Keith MacCannell, Abigail Avelar, Ralph Shohet
Journal: Circulation Research (2016)

Ischemic heart disease is a major precipitant of heart failure in the developed world. Hypoxia inducible factor 1 (HIF1) is a highly oxygen-sensitive protein and the principal regulator of hypoxia-related signaling including changes in metabolism and angiogenesis. To more fully understand the role of HIF1 in the heart, our lab has developed a transgenic mouse model in which a stable form of HIF-1alpha can be inducibly expressed under normoxic conditions in cardiomyocytes. Upon HIF1 induction, genes associated with calcium signaling are downregulated and metabolism is shifted toward glycolysis. Strikingly, these mice also show a rapid decrease in cardiac contractility and concurrent loss of SERCA2 protein expression (up to 90%) within one week. SERCA2a (sarcoplasmic/endoplasmic reticulum calcium ATPase 2) is the ATP-dependent calcium pump required for calcium re-uptake during excitation-contraction coupling in the heart and its dysfunction has been implicated in heart failure. To extend the physiological significance of these findings, we examined ischemic heart tissue from WT mice subjected to ligation of the left anterior descending (LAD) artery to mimic myocardial infarction. At one day and 3 days post-ligation, we observed an increase in transcripts needed for glycolysis and decreased abundance of transcripts from the genes for proteins that regulate excitation-contraction including the ryanodine receptor, phospholamban and SERCA2. We also observed that while SERCA2 transcript decreased in HIF1 transgenic hearts, it did not fully account for the observed protein loss. Microarray analysis found miR-29c to be substantially upregulated and a potential regulator of SERCA2 expression. Subsequent in vitro analysis confirmed miR-29c reduced SERCA2 expression by 20-30% and could be modulated with an anti-sense inhibitor. In vivo administration of the antimir to miR-29c also improved cardiac contractility and SERCA2 expression in HIF1 transgenic mice. These results suggest that a HIF1 regulated microRNA, miR-29c, contributes to loss of SERCA2 in hypoxia and can be therapeutically targeted to improve cardiac function.
Patients With Acute Myocarditis Following mRNA COVID-19 Vaccination
Authors: Han W. Kim, Elizabeth R. Jenista, David C. Wendell, Clerio F. Azevedo, Michael J. Campbell, Stephen N. Darty, Michele A. Parker, Raymond J. Kim
Journal: JAMA Cardiology (2021)

Vaccine-associated myocarditis is an unusual entity that has been described for the smallpox vaccine, but only anecdotal case reports have been described for other vaccines. Whether COVID-19 vaccination may be linked to the occurrence of myocarditis is unknown.To describe a group of 7 patients with acute myocarditis over 3 months, 4 of whom had recent messenger RNA (mRNA) COVID-19 vaccination.All patients referred for cardiovascular magnetic resonance imaging at Duke University Medical Center were asked to participate in a prospective outcomes registry. Two searches of the registry database were performed: first, to identify patients with acute myocarditis for the 3-month period between February 1 and April 30 for 2017 through 2021, and second, to identify all patients with possible vaccine-associated myocarditis for the past 20 years. Once patients with possible vaccine-associated myocarditis were identified, data available in the registry were supplemented by additional data collection from the electronic health record and a telephone interview.mRNA COVID-19 vaccine.Occurrence of acute myocarditis by cardiovascular magnetic resonance imaging.In the 3-month period between February 1 and April 30, 2021, 7 patients with acute myocarditis were identified, of which 4 occurred within 5 days of COVID-19 vaccination. Three were younger male individuals (age, 23-36 years) and 1 was a 70-year-old female individual. All 4 had received the second dose of an mRNA vaccine (2 received mRNA-1273 [Moderna], and 2 received BNT162b2 [Pfizer]). All presented with severe chest pain, had biomarker evidence of myocardial injury, and were hospitalized. Coincident testing for COVID-19 and respiratory viruses provided no alternative explanation. Cardiac magnetic resonance imaging findings were typical for myocarditis, including regional dysfunction, late gadolinium enhancement, and elevated native T1 and T2.In this study, magnetic resonance imaging findings were found to be consistent with acute myocarditis in 7 patients; 4 of whom had preceding COVID-19 vaccination. Further investigation is needed to determine associations of COVID-19 vaccination and myocarditis.
Abstract 125: Role of 14-3-3eta Protein in the Heart During Aging: Involvement of MAPK Mediated Endoplasmic Reticulum Signaling in Senescence-accelerated Prone Mice
Authors: Vijayasree V Giridharan, Remya Sreedhar, Somasundaram Arumugam, VengadeshPrabu Karuppagounder, Suresh S Palaniyandi, Prasanna Krishnamurthy, Joao L DeQuevedo, Kenichi Watanabe, Tetsuya Konishi, Rajarajan A Thandavarayan
Journal: Circulation Research (2016)

Heart failure is typically related to aging as there is a definite relationship between age-related changes in the heart and the pathogenesis of heart failure. We have previously reported the involvement of p38 mitogen-activated protein kinase protein in cardiac function using animal models of heart failure. To further understand its relationship with aging-induced heart failure, we have compared its expression in the hearts of senescence accelerated-prone (SAMP8) mice and their control (SAMR1) with normal aging behavior. We have identified its activation along with reduced expression of 14-3-3η protein in SAMP8 mice hearts than in SAMR1 mice. To reveal the downstream signaling, we have measured the endoplasmic reticulum stress marker proteins along with some inflammatory and apoptosis markers and identified a significant increase in SAMP8 mice hearts than that of SAMR1. In addition, we have performed comet assay and revealed a significant DNA damage in the cardiomyocytes of SAMP8 mice when compared with SAMR1 mice. All these results demonstrate the role of 14-3-3η protein and the downstream mitogen-activated protein kinase-mediated endoplasmic reticulum stress, and apoptosis and DNA damage in aging-induced cardiac malfunction in SAMP8 mice. Thus targeting this signaling might be effective in treating age-related cardiac dysfunction.
Trusts need support to help NHS meet net zero ambitions, say leaders
Authors: Matthew Limb
Journal: BMJ (2021)

Health bosses have welcomed progress towards reducing the NHS’s carbon footprint but say new government funding to help some hospitals save energy may not be enough to meet ambitions.

Under the national strategy, launched in October 2020, the NHS in England has committed itself to becoming “net zero” by 2040 for greenhouse gas emissions produced by its services, buildings, and vehicles.1

NHS England and NHS Improvement’s public board meeting on 24 June approved further steps to deliver this target, including the allocation of £260m (€302m; $360m) decarbonisation funding to around 30 trusts and a timetable for trusts and local health systems to deliver green targets.

At the board meeting, …
Abstract 291: Cardiopulmonary Resuscitation Prior to Arrival of Emergency Medical Services in Arizona Extended Care Facilities
Authors: Steven A Maher, Amber D Rice, Joshua B Gaither, Chengcheng Hu, Margaret Mullins, Daniel W Spaite, Bentley J Bobrow
Journal: Circulation (2019)

Background: Extended care facilities (ECFs) house unique patient populations with increased risk of out of hospital cardiac arrest (OHCA) and with unique, generally medically trained first responders initiating care prior to arrival of emergency medical services (EMS). However, little is known about bystander cardiopulmonary resuscitation (CPR) and resuscitation outcomes in this population. Our aim is to assess rate of CPR delivery prior to EMS arrival in cases of OHCA among residents ECFs across the state of Arizona. Methods: Cases of OHCA between 2016-2018, cared for by participating Arizona EMS agencies, were included if OHCA occurred at an ECF, age 18+, and was of presumed cardiac etiology. Association between survival status at discharge and bystander CPR was examined first by Chi-squared test then by logistic regression, which adjusted for important risk factors and potential confounders including: age, gender, witnessed arrest, shockable initial rhythm, and return of spontaneous circulation (ROSC) in EMS care. Results: There were 1,046 cases included in this study after excluding 32 cases with DNR and 11 with unknown bystander CPR status. Median patient age was 74 (interquartile range 64, 83). The overall rate of CPR prior to EMS arrival was 78.4% (95% CI, 75.8%, 80.9%). Survival to hospital discharge and survival with favorable neurologic outcome were not different between nursing home patients who received CPR prior to EMS arrival and those who did not [6.2% vs. 4.4% (p = 0.34) and 3.1% vs. 1.8% (p = 0.29)]. There was no statistically significant difference in the adjusted analysis. Conclusions: In this study population CPR was commonly delivered prior to EMS arrival. However, delivery of CPR prior to EMS arrival was not associated with survival to hospital discharge or favorable neurologic outcome. The lack of positive association between CPR prior to arrival and survival to hospital discharge may be related to comorbid factors present in ECF patients or differences in the time between collapse and initiation of CPR. Further study is needed to identify factors that might improve survival in this unique population.
Diffusing capacity of the lung for carbon monoxide: association with long-term outcomes after lung transplantation in a 20-year longitudinal study
Authors: David Ross Darley, Jin Ma, Ella Huszti, Rasheed Ghany, Michael Hutcheon, Chung-Wai Chow, Jussi Tikkanen, Shaf Keshavjee, Lianne Gail Singer, Tereza Martinu
Journal: European Respiratory Journal (2021)

The diffusing capacity of the lung for carbon monoxide corrected for haemoglobin (DLCOcor) measures gas movement across the alveolar-capillary interface. We hypothesised that DLCOcor is a sensitive measure of injurious allograft processes disrupting this interface.To determine the prognostic significance of the DLCOcor trajectory on chronic lung allograft dysfunction (CLAD) and survival.A retrospective analysis was conducted of all bilateral lung transplant recipients at a single centre, between January 1998 and January 2018, with one or more DLCOcor measurements. Low baseline DLCOcor was defined as the failure to achieve a DLCOcor >75% predicted. Drops in DLCOcor were defined as >15% below recent baseline.1259 out of 1492 lung transplant recipients were included. The median (range) time to peak DLCOcor was 354 (181-737) days and the mean±sd DLCOcor was 80.2±21.2% pred. Multivariable analysis demonstrated that low baseline DLCOcor was significantly associated with death (hazrd ratio (HR) 1.68, 95% CI 1.27-2.20; p<0.001). Low baseline DLCOcor was not independently associated with CLAD after adjustment for low baseline forced expiratory volume in 1 s or forced vital capacity. Any DLCOcor declines ≥15% were significantly associated with death, independent of concurrent spirometric decline. Lower percentage predicted DLCOcor values at CLAD onset were associated with shorter post-CLAD survival (HR 0.75 per 10%-unit change, p<0.01).Low baseline DLCOcor and post-transplant declines in DLCOcor were significantly associated with survival, independent of spirometric measurements. We propose that DLCOcor testing may allow identification of a subphenotype of baseline and chronic allograft dysfunction not captured by spirometry. There may be benefit in routine monitoring of DLCOcor after lung transplantation to identify patients at risk of poor outcomes.
Integrated genomic, epidemiologic investigation of Candida auris skin colonization in a skilled nursing facility
Authors: Diana M. Proctor, Thelma Dangana, D. Joseph Sexton, Christine Fukuda, Rachel D. Yelin, Mary Stanley, Pamela B. Bell, Sangeetha Baskaran, Clay Deming, Qiong Chen, Sean Conlan, Morgan Park, Jim Mullikin, Jim Thomas, Alice Young, Gerry Bouffard, Betty Barnabas, Shelise Brooks, Joel Han, Shi-ling Ho, Juyun Kim, Richelle Legaspi, Quino Maduro, Holly Marfani, Casandra Montemayor, Nancy Riebow, Karen Schandler, Brian Schmidt, Christina Sison, Mal Stantripop, Sean Black, Mila Dekhtyar, Cathy Masiello, Jenny McDowell, Pam Thomas, Meg Vemulapalli, Rory M. Welsh, Snigdha Vallabhaneni, Tom Chiller, Kaitlin Forsberg, Stephanie R. Black, Massimo Pacilli, Heidi H. Kong, Michael Y. Lin, Michael E. Schoeny, Anastasia P. Litvintseva, Julia A. Segre, Mary K. Hayden
Journal: Nature Medicine (2021)
Neuroinflammation: Design and Evaluation of an In Vitro Mild Traumatic Brain Injury Modeling System Using 3D Printed Mini Impact Device on the 3D Cultured Human iPSC Derived Neural Progenitor Cells (Adv. Healthcare Mater. 12/2021)
Authors: Wen Shi, Pengfei Dong, Mitchell A. Kuss, Linxia Gu, Forrest Kievit, Hyung Joon Kim, Bin Duan
Journal: Advanced Healthcare Materials (2021)

In article number 2100180 by Bin Duan and co-workers, a mini weight drop impact device is 3D printed, which can produce controlled and repeated impact injury to 3D cultured human iPSC derived neurospheres. This in vitro platform shows that both increased amount of impact injury and the existence of microglia enhance the astrocyte activation, which recapitulates several hallmarks of mild traumatic brain injury.
Systemic rheumatic disease flares after SARS-CoV-2 vaccination among rheumatology outpatients in New York City
Authors: Medha Barbhaiya, Jonah M. Levine, Vivian P. Bykerk, Deanna Jannat-Khah, Lisa A. Mandl
Journal: Annals of the Rheumatic Diseases (2021)

Early mobilisation initiatives within the critical care environment have been shown to improve outcomes for patients. Early mobilisation has been defined as occurring within the first two to five days of the intensive care stay, but in practice this can be difficult to deliver. We conducted a quality improvement (QI) project to deliver early mobilisation in a large general intensive care unit. Mechanically ventilated medical patients received an integrated package of care involving two additional daily sessions of mobility therapy, in combination with minimal sedation where possible. Prospective baseline data was collected from January to March 2012; the QI project commenced in April 2012. Improvement cycle 1 completed in March 2015 and improvement cycle 2 in March 2016. Results have suggested a reduction in time to first mobilisation for intensive care survivors from 16.3 days in 2012, to 4.3 days at the end of improvement cycle 2. This was associated with a decrease in mean intensive care length of stay from 20.8 days in 2012, to 11.2 days at the end of improvement cycle 2. This QI project enabled patients to mobilise out of bed within the first five days of their intensive care stay and to be discharged earlier from the ICU, on going analysis is required to verify these findings.