tbuckley/cabot-search huggingface dataset:
Abstract 16689: Smartphone-enabled Device for the Monitoring of Blood Volume Variations Using Magnetohydrodynamic Voltages
Authors: Kevin J Wu, T. Stan Gregory, Charles Reeder, Bobby Leitmann, Augustus Huffines, Sheila Donovan, Luke Mosteller, Jonathan R Murrow, Zion Tsz Ho Tse
Journal: Circulation (2015)

Background: Blood volume assessment is a valuable clinical metric, which can diagnostically be used to assess tissue health, monitor patient rehabilitation, and track the progression of wound healing. Currently there exists several methods to assess flow (MRI, US), but are either limited in cost or portability, and may require injection of contrast agents. Magnetohydrodynamic voltages (VMHD) are induced through blood flow interactions with an external magnetic field, and have been successfully measured using a modified ECG recorder and software package [1]. We hypothesize that a portable device capable of measuring induced VMHD could be used to rapidly quantify changes in blood flow. Objectives: Develop a portable device capable of monitoring of variations in blood volumes using induced VMHD. Methods: A portable smartphone-based ECG monitor was developed to use methods proposed in [1] to extract a metric proportional to blood flow from acquired ECGs (Fig. 1a). ECGs were acquired in two healthy volunteers, the second being a trained athlete. VMHD was induced in the carotid artery while in the presence of 0.4T static magnetic field generated by a neodymium magnet embedded in the monitor (Fig. 1b). VMHD signal extraction was performed to isolate the voltage induced by the magnet. Integrating over the VMHD yielded a metric proportional to blood volume [1,2]. Trials were performed at rest and at an elevated heart rate (HR) from exercise stress. Results: Induced VMHD was shown to increase from the baseline during exercise by 59% and 106% for the healthy subject and the athlete, respectively; resulting in a 47% difference in VMHD variations between the trained athlete and the healthy subject (Fig. 1c). Conclusions: A stand-alone device capable of quickly assessing blood volumes in the field using custom hardware and smartphone technology was developed. The ability of the device to quantify VMHD-derived blood flow was demonstrated. Ref: [1] Tse, MRM, 2013. [2] Gregory, JCMR, 2015.
Ultrasound-guided or landmark techniques for central venous catheter placement in critically ill children
Authors: Ignacio Oulego-Erroz, Rafael González-Cortes, Patricia García-Soler, Mónica Balaguer-Gargallo, Manuel Frías-Pérez, Juan Mayordomo-Colunga, Ana Llorente-de-la-Fuente, Paula Santos-Herraiz, Juan José Menéndez-Suso, María Sánchez-Porras, Daniel Palanca-Arias, Carmen Clavero-Rubio, Mª Soledad Holanda-Peña, Luis Renter-Valdovinos, Sira Fernández-De-Miguel, Antonio Rodríguez-Núñez
Journal: Intensive Care Medicine (2017)
A Commitment to Open Source in Neuroscience
Authors: Padraig Gleeson, Andrew P. Davison, R. Angus Silver, Giorgio A. Ascoli
Journal: Neuron (2017)

Modern neuroscience increasingly relies on custom-developed software, but much of this is not being made available to the wider community. A group of researchers are pledging to make code they produce for data analysis and modeling open source, and are actively encouraging their colleagues to follow suit.
Abstract 11829: Improvement in Care and Outcomes for Ambulance-Transported ST-Elevation Myocardial Infarction Patients With and Without Out-of-Hospital Cardiac Arrest: A Mission: Lifeline STEMI ACCELERATOR Study
Authors: Kristian Kragholm, Di Lu, Karen Chiswell, Hussein Al-Khalidi, Mayme L Roettig, Matthew Roe, James Jollis, Christopher B Granger
Journal: Circulation (2016)

Introduction: ST-elevation myocardial infarction (STEMI) patients with out-of-hospital cardiac arrest (OHCA) may not only benefit from timely intervention (PCI) but also from temperature management and other critical care that often is offered at a PCI-center. Relative to non-OHCA STEMI patients, those with OHCA have previously been less likely to bypass the nearest hospital to reach a cardiac center. Methods: We reported time trends in emergency medical service (EMS) transport pattern and care of STEMI patients with and without OHCA included from ACTION®-GWTG™ hospitals (484 hospitals and 1253 EMS agencies in 16 US regions) with participation in the STEMI ACCELERATOR Mission: Lifeline (MLL) initiative between July 1 st 2012 (2012Q3) and March 31 st 2014 (2014Q1). Time trends by quarter were assessed using logistic regression with Generalized Estimating Equations to account for hospital clustering. Results: Of 13,189 EMS-transported patients, 88.7% (N=11,703) were direct presenters and 10.5% (N=1,227) of these had OHCA. Among 1,486 transfer-in patients, 21.7% (N=322) had OHCA. The proportion with OHCA taken directly to a PCI-center increased from 74.7% to 83.6% between 2012Q3-2014Q1 (OR per quarter= 1.07; 95% CI=1.02-1.14), compared to an increase of 89.0% to 91.0% for non-OHCA patients (OR=1.03; 95% CI=0.99-1.07; interaction p=0.23). Proportions examined with a prehospital ECG increased in both direct presenter groups (53.9% to 61.9% for OHCA; and 73.9% to 81.9% for non-OHCA; interaction p=0.12). Of 997 direct OHCA patients treated with primary PCI, a first medical contact(FMC-)-to-device time ≤90 minutes was met for 34.5% in 2012Q3 vs. 41.8% in 2014Q1 (51.6% and 56.1% for 9352 non-OHCA direct presenters treated with primary PCI; interaction p=0.72). In-hospital mortality for primary PCI-treated patients was 29.8% for direct OHCA presenters vs. 35.9% for transfer-in OHCA patients (OR=0.76; 95% CI=0.56-1.02), compared to 4.1% vs. 5.3% for non-OHCA direct vs. transfer-in patients (OR=0.86; 95% CI=0.64-1.16; interaction p=0.49). Conclusion: Increases in proportions with prehospital ECG, with direct transport to a PCI-center, and meeting FMC-to-device guideline-recommended goals were seen for STEMI patients with and without OHCA.
Effectiveness <i>versus</i> efficacy trials in COPD: how study design influences outcomes and applicability
Authors: Ashley Woodcock, Isabelle Boucot, David A. Leather, Jodie Crawford, Susan Collier, Nawar Diar Bakerly, Emma Hilton, Jørgen Vestbo
Journal: European Respiratory Journal (2018)

Guidelines for chronic obstructive pulmonary disease (COPD) management are based largely on results from double-blind randomised controlled trials (RCTs) of efficacy. These trials have high internal validity and test whether a drug is efficacious, but they are conducted in highly selected populations that may differ significantly from patients with COPD seen in routine practice.We compared the baseline characteristics, healthcare use and outcomes between the Salford Lung Study (SLS), an open-label effectiveness RCT, with six recent large-scale efficacy RCTs. We also calculated the proportion of SLS patients who would have been eligible for inclusion in an efficacy RCT by applying the inclusion criteria used in efficacy trials of combination treatments.SLS patients were older, included more females and more current smokers, had more comorbidities (including asthma), and had more often experienced exacerbations prior to inclusion. In the SLS, rates of moderate or severe exacerbations, incidence of overall serious adverse events (SAEs), and SAEs of pneumonia were more frequent. A maximum of 30% of patients enrolled in the SLS would have been eligible for a phase IIIa regulatory exacerbation study.Patients in large COPD efficacy RCTs have limited representativeness compared with an effectiveness trial. This should be considered when interpreting efficacy RCT outcomes and their inclusion into guidelines.
Four week target for children to access mental health services proposed
Authors: Jacqui Wise
Journal: BMJ (2017)

Children and young people in England should be able to access NHS funded mental health services within four weeks as part of a pilot scheme the government has proposed.

The green paper, Transforming Children and Young People’s Mental Health Provision ,1 sets out a number of measures to improve mental health support for children and adolescents. The government says that over £300 million (€340m; $402m) have been made available to fund the proposals. Consultation on the green paper, which builds on the vision set out in 2015’s Future in Mind ,2 will run for 13 weeks until 2 March 2018.

The government proposes incentivising every school and college to have a designated senior mental health lead by 2025. The lead will be a trained member of staff who will oversee the approach to mental health and wellbeing, help staff spot pupils who show …
Response by Yamagata et al to Letter Regarding Article, “Genotype-Phenotype Correlation of <i>SCN5A</i> Mutation for the Clinical and Electrocardiographic Characteristics of Probands With Brugada Syndrome: A Japanese Multicenter Registry”
Authors: Kenichiro Yamagata, Takeshi Aiba, Wataru Shimizu
Journal: Circulation (2017)
Primary care-led weight management for remission of type 2 diabetes (DiRECT): an open-label, cluster-randomised trial
Authors: Michael EJ Lean, Wilma S Leslie, Alison C Barnes, Naomi Brosnahan, George Thom, Louise McCombie, Carl Peters, Sviatlana Zhyzhneuskaya, Ahmad Al-Mrabeh, Kieren G Hollingsworth, Angela M Rodrigues, Lucia Rehackova, Ashley J Adamson, Falko F Sniehotta, John C Mathers, Hazel M Ross, Yvonne McIlvenna, Renae Stefanetti, Michael Trenell, Paul Welsh, Sharon Kean, Ian Ford, Alex McConnachie, Naveed Sattar, Roy Taylor
Journal: The Lancet (2017)
Predictors of sleepiness in obstructive sleep apnoea at baseline and after 6 months of continuous positive airway pressure therapy
Authors: Rohit Budhiraja, Clete A. Kushida, Deborah A. Nichols, James K. Walsh, Richard D. Simon, Daniel J. Gottlieb, Stuart F. Quan
Journal: European Respiratory Journal (2017)

We evaluated factors associated with subjective and objective sleepiness at baseline and after 6 months of continuous positive airway pressure (CPAP) therapy in patients with obstructive sleep apnoea (OSA). We analysed data from the Apnoea Positive Pressure Long-term Efficacy Study (APPLES), a prospective 6-month multicentre randomised controlled trial with 1105 subjects with OSA, 558 of who were randomised to active CPAP. Epworth sleepiness scale (ESS) scores and the mean sleep latency (MSL) on the maintenance of wakefulness test at baseline and after 6 months of CPAP therapy were recorded. Excessive sleepiness (ESS score &gt;10) was present in 543 (49.1%) participants. Younger age, presence of depression and higher apnoea–hypopnoea index were all associated with higher ESS scores and lower MSL. Randomisation to the CPAP group was associated with lower odds of sleepiness at 6 months. The prevalence of sleepiness was significantly lower in those using CPAP &gt;4 h·night −1 versus using CPAP ≤4 h·night −1 . Among those with good CPAP adherence, those with ESS &gt;10 at baseline had significantly higher odds (OR 8.2, p&lt;0.001) of persistent subjective sleepiness. Lower average nightly CPAP use and presence of sleepiness at baseline were independently associated with excessive subjective and objective sleepiness after 6 months of CPAP therapy.
Abstract 15474: Differential Proteoglycan Expression Contributes to the Pathogenesis of Heritable Aortic Aneurysm Formation
Authors: Morvarid Emami, Jasha W Trompf, Elizabeth Robertson, Stefanie S Portelli, Yaxin Lu, Sanaz Maleki, Craig McLachlan, Murat Kekic, Shisan Bao, Brett D Hambly, Richmond Jeremy
Journal: Circulation (2016)

Excessive proteoglycan (PG) accumulation is a distinct feature of heritable thoracic aortic aneurysms (TAA), damaging the elastic lamellar units. PGs have both mechanical and signaling roles. Versican, perlecan and decorin can be upregulated by TGFβ signaling in various disease states. Increased TGFβ signaling is implicated in the pathogenesis of Bicuspid Aortic Valve (BAV) and Marfan Syndrome (MFS) associated thoracic aortic aneurysms (TAA). Perlecan organizes the endothelial BM and elastic lamellae and inhibits VSMC proliferation. Versican forms a loose matrix and its degradation products can alter VSMC proliferation. Biglycan and decorin have overlapping roles in fibrillogenesis, collagen assembly and TGFβ sequestration. We hypothesized that in both BAV-TAA and MFS-TAA PG expression will be altered and may exacerbate TAA pathogenesis. Computational immunohistochemistry was used to quantify PG expression in aortic tissue from human BAV-TAA (n=8), human MFS-TAA (n=8) and controls (n=5). Perlecan expression was increased (p
Multilayer polyion complex nanoformulations of superoxide dismutase 1 for acute spinal cord injury
Authors: N.V. Nukolova, A.D. Aleksashkin, T.O. Abakumova, A.Y. Morozova, I.L. Gubskiy, Е.А. Kirzhanova, M.A. Abakumov, V.P. Chekhonin, N.L. Klyachko, A.V. Kabanov
Journal: Journal of Controlled Release (2017)
Efficacy and safety of tocilizumab in patients with refractory Takayasu arteritis: results from a randomised, double-blind, placebo-controlled, phase 3 trial in Japan (the TAKT study)
Authors: Yoshikazu Nakaoka, Mitsuaki Isobe, Syuji Takei, Yoshiya Tanaka, Tomonori Ishii, Shumpei Yokota, Akira Nomura, Seitaro Yoshida, Norihiro Nishimoto
Journal: Annals of the Rheumatic Diseases (2017)

To investigate the efficacy and safety of the interleukin-6 receptor antibody tocilizumab in patients with Takayasu arteritis (TAK).Patients with TAK who had relapsed within the previous 12 weeks were induced into remission with oral glucocorticoid therapy. In this double-blind, placebo-controlled trial, patients were randomly assigned 1:1 to receive weekly tocilizumab 162 mg or placebo subcutaneously, and oral glucocorticoids were tapered 10 %/week from week 4 to a minimum of 0.1 mg/kg/day until 19 patients relapsed. The primary endpoint was time to relapse of TAK, defined as ≥2 of the following: objective systemic symptoms, subjective systemic symptoms, elevated inflammation markers, vascular signs and symptoms or ischaemic symptoms.The intent-to-treat and safety populations included 18 tocilizumab-treated and 18 placebo-treated patients. The per-protocol set (PPS) included 16 tocilizumab-treated and 17 placebo-treated patients. HRs for time to relapse of TAK were 0.41 (95.41% CI 0.15 to 1.10; p=0.0596) in the intent-to-treat population (primary endpoint) based on relapse in eight tocilizumab-treated and 11 placebo-treated patients and 0.34 (95.41% CI 0.11 to 1.00; p=0.0345) in the PPS. The secondary endpoints, time to relapse assessed by Kerr's definition and clinical symptoms only, were consistent with the primary endpoint. Serious adverse events were reported in one tocilizumab-treated and two placebo-treated patients. There were no serious infections and no deaths.Although the primary endpoint was not met, the results suggest favour for tocilizumab over placebo for time to relapse of TAK without new safety concerns. Further investigation is warranted to confirm the efficacy of tocilizumab in patients with refractory TAK.JapicCTI-142616.
Axicabtagene Ciloleucel CAR T-Cell Therapy in Refractory Large B-Cell Lymphoma
Authors: Sattva S. Neelapu, Frederick L. Locke, Nancy L. Bartlett, Lazaros J. Lekakis, David B. Miklos, Caron A. Jacobson, Ira Braunschweig, Olalekan O. Oluwole, Tanya Siddiqi, Yi Lin, John M. Timmerman, Patrick J. Stiff, Jonathan W. Friedberg, Ian W. Flinn, Andre Goy, Brian T. Hill, Mitchell R. Smith, Abhinav Deol, Umar Farooq, Peter McSweeney, Javier Munoz, Irit Avivi, Januario E. Castro, Jason R. Westin, Julio C. Chavez, Armin Ghobadi, Krishna V. Komanduri, Ronald Levy, Eric D. Jacobsen, Thomas E. Witzig, Patrick Reagan, Adrian Bot, John Rossi, Lynn Navale, Yizhou Jiang, Jeff Aycock, Meg Elias, David Chang, Jeff Wiezorek, William Y. Go
Journal: New England Journal of Medicine (2017)

In a phase 1 trial, axicabtagene ciloleucel (axi-cel), an autologous anti-CD19 chimeric antigen receptor (CAR) T-cell therapy, showed efficacy in patients with refractory large B-cell lymphoma after the failure of conventional therapy.In this multicenter, phase 2 trial, we enrolled 111 patients with diffuse large B-cell lymphoma, primary mediastinal B-cell lymphoma, or transformed follicular lymphoma who had refractory disease despite undergoing recommended prior therapy. Patients received a target dose of 2×106 anti-CD19 CAR T cells per kilogram of body weight after receiving a conditioning regimen of low-dose cyclophosphamide and fludarabine. The primary end point was the rate of objective response (calculated as the combined rates of complete response and partial response). Secondary end points included overall survival, safety, and biomarker assessments.Among the 111 patients who were enrolled, axi-cel was successfully manufactured for 110 (99%) and administered to 101 (91%). The objective response rate was 82%, and the complete response rate was 54%.With a median follow-up of 15.4 months, 42% of the patients continued to have a response, with 40% continuing to have a complete response. The overall rate of survival at 18 months was 52%. The most common adverse events of grade 3 or higher during treatment were neutropenia (in 78% of the patients), anemia (in 43%), and thrombocytopenia (in 38%). Grade 3 or higher cytokine release syndrome and neurologic events occurred in 13% and 28% of the patients, respectively. Three of the patients died during treatment. Higher CAR T-cell levels in blood were associated with response.In this multicenter study, patients with refractory large B-cell lymphoma who received CAR T-cell therapy with axi-cel had high levels of durable response, with a safety profile that included myelosuppression, the cytokine release syndrome, and neurologic events. (Funded by Kite Pharma and the Leukemia and Lymphoma Society Therapy Acceleration Program; ZUMA-1 ClinicalTrials.gov number, NCT02348216 .).
Surveillance for hepatobiliary cancers in patients with primary sclerosing cholangitis
Authors: Ahmad Hassan Ali, James H. Tabibian, Navine Nasser‐Ghodsi, Ryan J. Lennon, Thomas DeLeon, Mitesh J. Borad, Moira Hilscher, Marina G. Silveira, Elizabeth J. Carey, Keith D. Lindor
Journal: Hepatology (2017)

Primary sclerosing cholangitis (PSC) is a risk factor for cholangiocarcinoma (CCA) and gallbladder carcinoma (GBCa). Surveillance for GBCa is recommended, but the clinical utility of surveillance for other hepatobiliary cancers (HBCa) in PSC, namely CCA and hepatocellular carcinoma (HCC), remains unclear. We aimed to determine whether surveillance is associated with better survival after diagnosis of HBCa in patients with PSC. Medical records of PSC patients seen at the Mayo Clinic Rochester from 1995 to 2015 were reviewed. Patients were included if they had ≥1 year of follow‐up and developed HBCa. Patients were categorized according to their surveillance status (abdominal imaging, carbohydrate antigen 19‐9, and alpha‐fetoprotein). The primary endpoints were HBCa recurrence, HBCa‐related death, and all‐cause mortality. Overall survival was assessed by the Kaplan‐Meier survival method; HBCa‐related survival was assessed using competing risk regression. Tests of significance were two‐tailed, and a P value &lt;0.05 was considered statistically significant. From 1995 to 2015, a total of 79 of 830 PSC patients were diagnosed with HBCa. Cumulative follow‐up was 712 and 283 person‐years pre‐ and post‐HBCa diagnosis, respectively. Seventy‐eight percent of patients (54/79) developed CCA, 21% (17/79) HCC, 6% (5/79) GBCa, 3% (2/79) both CCA and HCC, and 1% (1/79) both HCC and GBCa. Fifty‐one percent (40/79) were under HBCa surveillance, and 49% (39/79) were not. Patients in the surveillance group had significantly higher 5‐year overall survival (68% versus 20%, respectively; P &lt; 0.001) and significantly lower 5‐year probability of experiencing an HBCa‐related adverse event (32% versus 75%, respectively; P &lt; 0.001) compared with the no‐surveillance group. Conclusion: This study demonstrates that HBCa surveillance significantly improves outcomes, including survival, in patients with PSC. (H epatology 2018;67:2338‐2351).
The need for longer time horizons for cost-utility evaluation in bullous pemphigoid: reply from the authors
Authors: J.M. Mason, H.C. Williams, F. Wojnarowska
Journal: British Journal of Dermatology (2017)

Linked Article:Liu et al. Br J Dermatol 2018; 178:809–810. Linked Article:Mason et al. Br J Dermatol 2018; 178:415–423.
A Randomized Trial of Bortezomib in Late Antibody-Mediated Kidney Transplant Rejection
Authors: Farsad Eskandary, Heinz Regele, Lukas Baumann, Gregor Bond, Nicolas Kozakowski, Markus Wahrmann, Luis G. Hidalgo, Helmuth Haslacher, Christopher C. Kaltenecker, Marie-Bernadette Aretin, Rainer Oberbauer, Martin Posch, Anton Staudenherz, Ammon Handisurya, Jeff Reeve, Philip F. Halloran, Georg A. Böhmig
Journal: Journal of the American Society of Nephrology (2017)

Export Late antibody-mediated rejection (ABMR) is a leading cause of kidney allograft failure. Uncontrolled studies have suggested efficacy of the proteasome inhibitor bortezomib, but no systematic trial has been undertaken to support its use in ABMR. In this randomized, placebo-controlled trial (the Bortezomib in Late Antibody-Mediated Kidney Transplant Rejection [BORTEJECT] Trial), we investigated whether two cycles of bortezomib (each cycle: 1.3 mg/m2 intravenously on days 1, 4, 8, and 11) prevent GFR decline by halting the progression of late donor-specific antibody (DSA)–positive ABMR. Forty-four DSA-positive kidney transplant recipients with characteristic ABMR morphology (median time after transplant, 5.0 years; pretransplant DSA documented in 19 recipients), who were identified on cross-sectional screening of 741 patients, were randomly assigned to receive bortezomib (n=21) or placebo (n=23). The 0.5-ml/min per 1.73 m2 per year (95% confidence interval, −4.8 to 5.8) difference detected between bortezomib and placebo in eGFR slope (primary end point) was not significant (P=0.86). We detected no significant differences between bortezomib- and placebo-treated groups in median measured GFR at 24 months (33 versus 42 ml/min per 1.73 m2; P=0.31), 2-year graft survival (81% versus 96%; P=0.12), urinary protein concentration, DSA levels, or morphologic or molecular rejection phenotypes in 24-month follow-up biopsy specimens. Bortezomib, however, associated with gastrointestinal and hematologic toxicity. In conclusion, our trial failed to show that bortezomib prevents GFR loss, improves histologic or molecular disease features, or reduces DSA, despite significant toxicity. Our results reinforce the need for systematic trials to dissect the efficiency and safety of new treatments for late ABMR.