tbuckley/cabot-search huggingface dataset:
A non-opioid analgesic implant for sustained post-operative intraperitoneal delivery of lidocaine, characterized using an ovine model
Authors: Darren Svirskis, Georgina Procter, Manisha Sharma, Prabhat Bhusal, Anusha Dravid, Wiremu MacFater, Ahmed Barazanchi, Laura Bennet, Kaushik Chandramouli, Sree Sreebhavan, Priyanka Agarwal, Satya Amirapu, Jacqueline A. Hannam, Gavin P. Andrews, Andrew Hill, David S. Jones
Journal: Biomaterials (2020)
Comment on Misra et al. Homozygous Hypomorphic <i>HNF1A</i> Alleles Are a Novel Cause of Young-Onset Diabetes and Result in Sulfonylurea-Sensitive Diabetes. Diabetes Care 2020;43:909–912
Authors: Hui-Xuan Wu, Long Li, Hou-De Zhou
Journal: Diabetes Care (2020)

With great interest, we have read the article by Misra et al. (1), which reported a family that suffered from young-onset and sulfonylurea-sensitive diabetes resulting from the homozygous hypomorphic HNF1A mutation. We appreciate the considerable achievement of new insights in diagnosis and pathogenicity of HNF1A germline mutation–induced diabetes, but we would like to make some comments about the interpretation of the results and discussion.

Misra et al. reported that the proband’s father met the criteria of prediabetes and the mother developed diabetes during pregnancy at the age of 29 years. The authors also concluded that two reported studies (2,3) featured heterozygous p.A251T HNF1A variant carriers …
Response to Comment on Flory et al. Reports of Lactic Acidosis Attributed to Metformin, 2015–2018. Diabetes Care 2020;43:244–246
Authors: James H. Flory, Sean Hennessy, Clifford J. Bailey, Silvio E. Inzucchi
Journal: Diabetes Care (2020)

We appreciate Dr. Brand’s commentary (1) on our brief report (2) and substantively agree with her points about the role of “duplication and latency” in distorting reporting rates for metformin-associated lactic acidosis (MALA). Her closing recommendation that analyses of adverse event reporting systems should be replicated across multiple databases is reasonable in many circumstances, but we argue that it would not be helpful in all cases.

With respect to duplication and latency, one of the major findings of our report was that crude analysis of MALA reporting rates in the U.S. Food and Drug Administration’s Adverse Event Reporting System (FAERS) is indeed distorted by the same major events that Dr. Brand …
European Registry on <i>Helicobacter pylori</i> management (Hp-EuReg): patterns and trends in first-line empirical eradication prescription and outcomes of 5 years and 21 533 patients
Authors: Olga P Nyssen, Dmitry Bordin, Bojan Tepes, Ángeles Pérez-Aisa, Dino Vaira, Maria Caldas, Luis Bujanda, Manuel Castro-Fernandez, Frode Lerang, Marcis Leja, Luís Rodrigo, Theodore Rokkas, Limas Kupcinskas, Jorge Pérez-Lasala, Laimas Jonaitis, Oleg Shvets, Antonio Gasbarrini, Halis Simsek, Anthony T R Axon, György Buzás, Jose Carlos Machado, Yaron Niv, Lyudmila Boyanova, Adrian Goldis, Vincent Lamy, Ante Tonkic, Krzysztof Przytulski, Christoph Beglinger, Marino Venerito, Peter Bytzer, Lisette Capelle, Tomica Milosavljević, Vladimir Milivojevic, Lea Veijola, Javier Molina-Infante, Liudmila Vologzhanina, Galina Fadeenko, Ines Ariño, Giulia Fiorini, Ana Garre, Jesús Garrido, Cristina F Pérez, Ignasi Puig, Frederic Heluwaert, Francis Megraud, Colm O'Morain, Javier P Gisbert
Journal: Gut (2020)

The best approach for Helicobacter pylori management remains unclear. An audit process is essential to ensure clinical practice is aligned with best standards of care.International multicentre prospective non-interventional registry starting in 2013 aimed to evaluate the decisions and outcomes in H. pylori management by European gastroenterologists. Patients were registered in an e-CRF by AEG-REDCap. Variables included demographics, previous eradication attempts, prescribed treatment, adverse events and outcomes. Data monitoring was performed to ensure data quality. Time-trend and geographical analyses were performed.30 394 patients from 27 European countries were evaluated and 21 533 (78%) first-line empirical H. pylori treatments were included for analysis. Pretreatment resistance rates were 23% to clarithromycin, 32% to metronidazole and 13% to both. Triple therapy with amoxicillin and clarithromycin was most commonly prescribed (39%), achieving 81.5% modified intention-to-treat eradication rate. Over 90% eradication was obtained only with 10-day bismuth quadruple or 14-day concomitant treatments. Longer treatment duration, higher acid inhibition and compliance were associated with higher eradication rates. Time-trend analysis showed a region-dependent shift in prescriptions including abandoning triple therapies, using higher acid-inhibition and longer treatments, which was associated with an overall effectiveness increase (84%-90%).Management of H. pylori infection by European gastroenterologists is heterogeneous, suboptimal and discrepant with current recommendations. Only quadruple therapies lasting at least 10 days are able to achieve over 90% eradication rates. European recommendations are being slowly and heterogeneously incorporated into routine clinical practice, which was associated with a corresponding increase in effectiveness.
The role of endoscopic ultrasound guidance for biliary and pancreatic duct access and drainage to overcome the limitations of ERCP: a retrospective evaluation
Authors: Francisco Javier García-Alonso, Irene Peñas-Herrero, Ramon Sanchez-Ocana, Mariano Villarroel, Marta Cimavilla, Sergio Bazaga, Marina De Benito Sanz, Paula Gil-Simon, Carlos de la Serna-Higuera, Manuel Perez-Miranda
Journal: Endoscopy (2020)

Abstract Background Endoscopic ultrasound (EUS)-guided ductal access and drainage (EUS-DAD) of biliary/pancreatic ducts after failed endoscopic retrograde cholangiopancreatography (ERCP) is less invasive than percutaneous transhepatic biliary drainage (PTBD). The actual need for EUS-DAD remains unknown. We aimed to determine how often EUS-DAD is needed to overcome ERCP failure. Methods Consecutive duct access procedures (n = 2205; 95 % biliary) performed between June 2013 and November 2015 at a tertiary-care center were reviewed. ERCP was used first line, EUS-DAD as salvage after ERCP, and PTBD when both had failed. Procedures were defined as “index” in patients without prior endoscopic duct access and “combined” when EUS-DAD followed successful ERCP. The main outcomes were the EUS-DAD and PTBD rates. Results EUS-DAD was performed in 7.7 % (170/2205) of overall procedures: 9.1 % (116/1274) index and 5.8 % (54/931) follow-up. Most index EUS-DADs were performed following (46 %) or anticipating (39 %) ERCP failure, whereas 15 % followed successful ERCP (combined procedures). Among index procedures, the EUS-DAD rate was higher in surgically altered anatomy (58.2 % [39 /67)] vs. 6.4 % [77/1207]); PTBD was required in 0.2 % (3/1274). Among follow-up procedures, ERCP represented 85.7 %, cholangiopancreatography through mature transmural fistulas 8.5 %, and EUS-DAD 5.8 %; no patient required PTBD. The secondary PTBD rate was 0.1 % (3/2205). Six primary PTBDs were performed (overall PTBD rate 0.4 % [9/2205]). Conclusions EUS-DAD was required in 7.7 % of ERCPs for benign and malignant biliary/pancreatic duct indications. Salvage PTBD was required in 0.1 %. This high EUS-DAD rate reflects disease complexity, a wide definition of ERCP failure, and restrictive PTBD use, not poor ERCP skills. EUS-DAD effectively overcomes the limitations of ERCP eliminating the need for primary and salvage PTBD in most cases.
Development of methods for detecting the fate of mesenchymal stem cells regulated by bone bioactive materials
Authors: Jiang Le, Liu Zhongqun, Wang Zhaoyan, Su Yijun, Wang Yingjin, Wei Yaojie, Jiang Yanan, Jia Zhanrong, Ma Chunyang, Gang Fangli, Xu Nan, Zhao Lingyun, Wang Xiumei, Wu Qiong, Lu Xiong, Sun Xiaodan
Journal: Bioactive Materials (2020)

The fate of mesenchymal stem cells (MSCs) is regulated by biological, physical and chemical signals. Developments in biotechnology and materials science promoted the occurrence of bioactive materials which can provide physical and chemical signals for MSCs to regulate their fate. In order to design and synthesize materials that can precisely regulate the fate of MSCs, the relationship between the properties of materials and the fate of mesenchymal stem cells need to be clarified, in which the detection of the fate of mesenchymal stem cells plays an important role. In the past 30 years, a series of detection technologies have been developed to detect the fate of MSCs regulated by bioactive materials, among which high-throughput technology has shown great advantages due to its ability to detect large amounts of data at one time. In this review, the latest research progresses of detecting the fate of MSCs regulated by bone bioactive materials (BBMs) are systematically reviewed from traditional technology to high-throughput technology which is emphasized especially. Moreover, current problems and the future development direction of detection technologies of the MSCs fate regulated by BBMs are prospected. The aim of this review is to provide a detection technical framework for researchers to establish the relationship between the properties of BMMs and the fate of MSCs, so as to help researchers to design and synthesize BBMs better which can precisely regulate the fate of MSCs.
Anakinra in COVID‐19—How to Interpret Elevations of Serum Liver Enzymes: Comment on the Article by Navarro‐Millán et al
Authors: Giulio Cavalli, Lorenzo Dagna
Journal: Arthritis & Rheumatology (2020)

To the Editor: We read with interest the article by Navarro-Millán and colleagues on the use of anakinra in patients with severe coronavirus disease 2019 (COVID-19) with acute respiratory syndrome coronavirus 2 and hyperinflammation (1). The authors tried to identify the clinical phenotype most likely to benefit from treatment with anakinra, in order to maximize utility and prevent exposure to unnecessary risks of immunosuppression. Indeed, administration of anakinra to 11 patients yielded promising results overall, although the lack of a control group and prior treatment with high-dose glucocorticoids in 8 patients limit interpretation of the findings. However, Navarro-Millán et al state that in previous studies of anakinra in COVID-19, severe respiratory failure was not a requisite for treatment initiation. This is incorrect, as a previous cohort study from our group in Milan, Italy, had remarkably similar eligibility criteria for administration of anakinra. Specifically, all patients had hyperinflammation, defined as elevated ferritin and/or C-reactive protein levels, and acute respiratory syndrome requiring noninvasive ventilation (2). The outcome measures were also similar, as was the ultimate aim to avoid mechanical ventilation. Similarities between these studies help in interpreting another finding from Navarro-Millán and colleagues—elevated serum liver transaminase levels in patients receiving anakinra. Both the study by Navarro-Millán et al and ours included this finding, which led to tapering or discontinuation of anakinra in some patients. However, our study also included a control population of patients who, despite not receiving anakinra, exhibited similar elevations of serum liver enzyme levels (2). This led us to hypothesize that elevations of liver enzyme levels reflect underlying disease severity, rather than treatment toxicity. Elevation of serum liver enzyme levels is uncommon in patients receiving anakinra for approved indications. Conversely, it is a hallmark of both viral infections and macrophage activation syndrome, a condition that shares similarities with the hyperinflammatory response observed in some COVID-19 patients and is commonly treated with high-dose anakinra (3, 4). Whether anakinra should be discontinued in patients with COVID-19 and elevated liver enzymes thereby remains debatable. Though perceived as the clinically responsible choice, discontinuation of anakinra in these patients may actually lead to detrimental hyperinflammation, of which elevated liver enzyme levels are merely an accompanying feature. Dr. Cavalli has received consulting fees, speaking fees, and/or honoraria from Novartis and Pfizer (less than $10,000 each). Dr. Dagna has received consulting fees, speaking fees, and/or honoraria from Novartis and Pfizer (less than $10,000 each).
Programming Multifaceted Pulmonary T Cell Immunity by Combination Adjuvants
Authors: Chandranaik B. Marinaik, Brock Kingstad-Bakke, Woojong Lee, Masato Hatta, Michelle Sonsalla, Autumn Larsen, Brandon Neldner, David J. Gasper, Ross M. Kedl, Yoshihiro Kawaoka, M. Suresh
Journal: Cell Reports Medicine (2020)

Induction of protective mucosal T cell memory remains a formidable challenge to vaccinologists. Using a combination adjuvant strategy that elicits potent CD8 and CD4 T cell responses, we define the tenets of vaccine-induced pulmonary T cell immunity. An acrylic-acid-based adjuvant (ADJ), in combination with Toll-like receptor (TLR) agonists glucopyranosyl lipid adjuvant (GLA) or CpG, promotes mucosal imprinting but engages distinct transcription programs to drive different degrees of terminal differentiation and disparate polarization of TH1/TC1/TH17/TC17 effector/memory T cells. Combination of ADJ with GLA, but not CpG, dampens T cell receptor (TCR) signaling, mitigates terminal differentiation of effectors, and enhances the development of CD4 and CD8 TRM cells that protect against H1N1 and H5N1 influenza viruses. Mechanistically, vaccine-elicited CD4 T cells play a vital role in optimal programming of CD8 TRM and viral control. Taken together, these findings provide further insights into vaccine-induced multifaceted mucosal T cell immunity with implications in the development of vaccines against respiratorypathogens, including influenza virus and SARS-CoV-2.
Ultrathin and Robust Hydrogel Coatings on Cardiovascular Medical Devices to Mitigate Thromboembolic and Infectious Complications
Authors: German Parada, Yan Yu, William Riley, Sarah Lojovich, Diane Tshikudi, Qing Ling, Yefang Zhang, Jiaxin Wang, Lei Ling, Yueying Yang, Seemantini Nadkarni, Christoph Nabzdyk, Xuanhe Zhao
Journal: Advanced Healthcare Materials (2020)

Abstract Thromboembolic and infectious complications stemming from the use of cardiovascular medical devices are still common and result in significant morbidity and mortality. There is no strategy to date that effectively addresses both challenges at the same time. Various surface modification strategies (e.g., silver, heparin, and liquid‐impregnated surfaces) are proposed yet each has several limitations and shortcomings. Here, it is shown that the incorporation of an ultrathin and mechanically robust hydrogel layer reduces bacterial adhesion to medical‐grade tubing by 95%. It is additionally demonstrated, through a combination of in vitro and in vivo tests, that the hydrogel layer significantly reduces the formation and adhesion of blood clots to the tubing without affecting the blood's intrinsic clotting ability. The adhesion of clots to the tubing walls is reduced by over 90% (in vitro model), which results in an ≈60% increase in the device occlusion time (time before closure due to clot formation) in an in vivo porcine model. The advantageous properties of this passive coating make it a promising surface material candidate for medical devices interfacing with blood.
Abstract 16453: Increased Activity of Tissue ACE Impairs Dilation of Coronary Arterioles in Obesity
Authors: Attila Feher, James Cassuto, Zsolt Bagi
Journal: Circulation (2011)

Angiotensin converting enzyme (ACE) inhibitors prevent cardiovascular complications independent from their blood pressure lowering effect. We hypothesized that vascular ACE activity is increased in...
Excess mortality due to COVID-19 in Germany
Authors: Andreas Stang, Fabian Standl, Bernd Kowall, Bastian Brune, Juliane Böttcher, Marcus Brinkmann, Ulf Dittmer, Karl-Heinz Jöckel
Journal: Journal of Infection (2020)

ObjectivesThe first wave of the SARS-CoV-2 pandemic in Germany lasted from week 10 to 23 in 2020. The aim is to provide estimates of excess mortality in Germany during this time.MethodsWe analyzed age-specific numbers of deaths per week from 2016 to week 26 in 2020. We used weekly mean numbers of deaths of 2016–2019 to estimate expected weekly numbers for 2020. We estimated standardized mortality ratios (SMR) and 95% confidence intervals.ResultsDuring the first wave observed numbers of deaths were higher than expected for age groups 60–69, 80–89, and 90+. The age group 70–79 years did not show excess mortality. The net excess number of deaths for weeks 10–23 was +8,071. The overall SMR was 1•03 (95%CI 1•03–1•04). The largest increase occurred among people aged 80–89 and 90+ (SMR=1•08 and SMR=1•09). A sensitivity analysis that accounts for demographic changes revealed an overall SMR of 0•98 (95%CI 0•98–0•99) and a deficit of 4,926 deaths for week 10–23, 2020.ConclusionsThe excess mortality existed for two months. The favorable course of the first wave may be explained by a younger age at infection at the beginning of the pandemic, lower contact rates, and a more efficient pandemic management.
Physicians and Social Determinants of Health
Authors: John Morgan
Journal: JAMA (2020)

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
Near Infrared‐Activatable Platinum‐Decorated Gold Nanostars for Synergistic Photothermal/Ferroptotic Therapy in Combating Cancer Drug Resistance
Authors: Andrea C. del Valle, Chih‐Kuang Yeh, Yu‐Fen Huang
Journal: Advanced Healthcare Materials (2020)

Abstract Ferroptotic cell death results from glutathione peroxidase 4 (GPX4) inactivation and/or glutathione (GSH) depletion. Elevated GSH levels are often found in multidrug‐resistant (MDR) tumor cells, reducing their sensitivity to chemotherapeutic drugs and the efficacy of treatment. MDR cells also acquire a dependency on GPX4, reducing their oxidative stress and promoting their survival. Therefore, the depletion of GSH and inactivation of GPX4 has the potential to be a superior treatment strategy for MDR tumors. Platinum‐decorated gold nanostars (Pt‐AuNS) are presented as a novel metal nanoprodrug for ferroptotic therapy against MDR tumors. Under dark conditions, the synthesized Pt‐AuNS exhibit negligible levels of toxicity. Upon exposure of the Pt‐AuNS to near‐infrared (NIR) light, active metallic (Pt and Au) species are released, subsequently inducing cytotoxicity. The mechanism of action is attributed to GSH depletion and GPX4 inactivation, accumulating lipid hydroperoxides, which in turn leads to ferroptosis. In in vivo xenograft, the MDR cancer model confirmed the NIR light‐activation of Pt‐AuNS prodrugs, resulting in efficient ferroptotic therapeutic action against MDR tumors without long‐term side effects. The findings lay the groundwork for using Pt‐AuNS prodrugs responsive to NIR light as ferroptosis‐inducing agents in chemo‐resistant cancer cells and demonstrate their potential for use in future clinical applications.
MOLECULAR EPIDEMIOLOGICAL EVIDENCE THAT SOCIAL NETWORK RESEARCH CAN IDENTIFY HEPATITIS C TRANSMISSION PATHWAYS IN PEOPLE WHO INJECT DRUGS
Authors: Rachel Sacks-Davis, Galina Daraganova, Campbell Aitken, Peter Higgs, Rebecca Jenkinson, Samantha L Tracy, Scott Bowden, Garry Robins, Phillipa Pattison, Jason Grebely, Alyssa E Barry, Margaret Hellard
Journal: Hepatology (2011)
Development of Novel, Value-Based, Digital Endpoints for Clinical Trials: A Structured Approach Toward Fit-for-Purpose Validation
Authors: M. D. Kruizinga, F. E. Stuurman, V. Exadaktylos, R. J. Doll, D. T. Stephenson, G. J. Groeneveld, G. J. A. Driessen, A. F. Cohen
Journal: Pharmacological Reviews (2020)

Novel digital endpoints gathered via wearables, small devices, or algorithms hold great promise for clinical trials. However, implementation has been slow because of a lack of guidelines regarding the validation process of these new measurements. In this paper, we propose a pragmatic approach toward selection and fit-for-purpose validation of digital endpoints. Measurements should be value-based, meaning the measurements should directly measure or be associated with meaningful outcomes for patients. Devices should be assessed regarding technological validity. Most importantly, a rigorous clinical validation process should appraise the tolerability, difference between patients and controls, repeatability, detection of clinical events, and correlation with traditional endpoints. When technically and clinically fit-for-purpose, case building in interventional clinical trials starts to generate evidence regarding the response to new or existing health-care interventions. This process may lead to the digital endpoint replacing traditional endpoints, such as clinical rating scales or questionnaires in clinical trials. We recommend initiating more data-sharing collaborations to prevent unnecessary duplication of research and integration of value-based measurements in clinical care to enhance acceptance by health-care professionals. Finally, we invite researchers and regulators to adopt this approach to ensure a timely implementation of digital measurements and value-based thinking in clinical trial design and health care. <h3>Significance Statement</h3> Novel digital endpoints are often cited as promising for the clinical trial of the future. However, clear validation guidelines are lacking in the literature. This paper contains pragmatic criteria for the selection, technical validation, and clinical validation of novel digital endpoints and provides recommendations for future work and collaboration.