tbuckley/cabot-search huggingface dataset:
TCT-417 Outcomes of Successful Versus Failed Contemporary Chronic Total Occlusion Percutaneous Coronary Intervention
Authors: Michael Megaly, Mahmoud Khalil, Mir Basir, Margaret McEntegart, James Spratt, Bo Xu, Khaldoon Alaswad, Emmanouil Brilakis
Journal: Journal of the American College of Cardiology (2021)
Disparities in CKD Risks: Data from the CURE-CKD COVID-19 Sub-Registry
Authors: Susanne B. Nicholas, Robert W. Follett, Theona T. Tacorda, Xiaoyan Wang, Dennis Ruenger, Panayiotis Petousis, Bing Zhu, Tyler A. Davis, Davina J. Zamanzadeh, Kenn B. Daratha, Cami R. Jones, Keith C. Norris, Katherine R. Tuttle, Alex Bui
Journal: Journal of the American Society of Nephrology (2021)

Background: The SARS-CoV-2 pandemic accelerated health disparities in chronic kidney disease (CKD). Here, we describe risk factors and access to care surrogates (area deprivation index-ADI) for clinical outcomes among SARS-CoV-2-tested patients in the CURE-CKD Registry. Methods: We formed a COVID-19 Sub-Registry within CURE-CKD (1/1-6/30/2021;N=171,988) of patients with CKD, diabetes (DM)/pre-DM, or hypertension (HTN) with SARS-CoV-2 testing at UCLA Health (UCLA;N=17,884) and Providence St. Joseph Health (PSJH;N=154,104). Statistical analyses and fitted multivariable logistic regression models were adjusted for age and sex. The UCLA cohort included analyses for acute kidney injury (AKI), ADI (for poor housing, education, income), Charlson Comorbidity Index (CCI), and severe COVID-19 disease. Results: Odds ratios (OR) of COVID-19 positivity for the combined UCLA + PSJH population, as well as OR of having severe COVID-19 disease in the UCLA cohort are presented (Table). OR[95%CI] for AKI were higher for ages ≥80 years (1.77[1.14-2.46]), ADI by state (1.12[1.06-1.18]), CKD (12.20[8.46-17.58]) and pre-existing DM (3.65[2.62-5.08]), p<0.001. In the UCLA CURE-CKD population, AKI was associated with severe COVID-19 (r=0.26) and ICU admissions (r=0.29). Mortality was associated with severe COVID-19 disease (r=0.5). Conclusions: Non-White and/or LatinX race/ethnicity, ADI, CKD, DM, and older age were associated with higher risks of COVID-19 positivity, disease severity, and mortality in CURE-CKD. Efforts on viral screening, timely COVID-19 diagnosis, and optimal care delivery for patients with or at-risk for CKD are needed.
PD-L1<sup>high</sup> AT2 cells: a new player for alveoli regeneration
Authors: Charles Fouillade, Arturo Londoño-Vallejo
Journal: European Respiratory Journal (2021)

The lung is a notoriously quiescent organ with a very limited proportion of detectable proliferative cells in normal conditions. However, in response to injury, facultative progenitor cells have the capabilities to proliferate and differentiate. Over the past decades, several lung progenitor populations have been identified following their location ( i.e. proximal versus distal airways and alveolar region) [1]. In both humans and mice, several epithelial lineages are found in the trachea and upper airways, such as secretory (club), goblet, ciliated and neuroendocrine cells, along with the basal cells that line the epithelia. These basal cells have the capacity to self-renew and, when necessary, differentiate into other epithelial cells, such as ciliated, secretory or goblet cells [2–4]. In mice, basal cells are restricted to the trachea and main large bronchi, so additional epithelial populations with facultative progenitor abilities exist. For instance, lineage-tracing experiments have demonstrated that, after injury, secretory Scgb1a1+ cells, but not ciliated cells, may give rise to goblet cells [5]. Also, after proximal airways damage, some rare neuroendocrine cells, embedded in clusters called neuroendocrine bodies, proliferate and differentiate to repair the surrounding epithelium [6]. Variant club-secretory cells, located near neuroendocrine bodies, expressing Upk3a and resistant to naphthalene injury, are also able to differentiate into secretory and ciliated cells [7, 8]. A novel AT2 subset with Sftpclow and PD-L1high expression is capable of producing mature AT2 cells upon injury <https://bit.ly/2TDTQeS>
Recommendations were made for diagnosis and management of allergic reactions to COVID-19 vaccines
Authors: Dennis G. Maki
Journal: Annals of Internal Medicine (2021)

Source CitationGreenhawt M, Abrams EM, Shaker M, et al. The risk of allergic reaction to SARS-CoV-2 vaccines and recommended evaluation and management: a systematic review, meta-analysis, GRADE assessment, and international consensus approach. J Allergy Clin Immunol Pract. 2021;9:3546-67. https://pubmed.ncbi.nlm.nih.gov/34153517/AbstractClinical Impact RatingsGIM/FP/GP: Allerg & Immunol: Public Health:
Synaptic dysfunction of Aldh1a1 neurons in the ventral tegmental area causes impulsive behaviors
Authors: Xinyan Li, Wenting Chen, Xian Huang, Wei Jing, Tongmei Zhang, Quntao Yu, Hongyan Yu, Hao Li, Qing Tian, Yumei Ding, Youming Lu
Journal: Molecular Neurodegeneration (2021)

Abstract Background Aldh1a1 neurons are a subtype of gamma-aminobutyric acid (GABA) inhibitory neurons that use Aldh1a1 rather than glutamate decarboxylase (GAD) as an enzyme for synthesizing GABA transmitters. However, the behaviors and circuits of this newly identified subtype of inhibitory interneurons remain unknown. Methods We generated a mutant mouse line in which cyclization recombination enzyme (CRE) was expressed under the control of the Aldh1a1 promotor (Aldh1a1-CRE mice). Using this mutant strain of mice together with the heterozygous male Alzheimer’s disease (AD) related model mice (APPswe/PSEN1dE9, or AD mice) and a genetically modified retrograde and anterograde synaptic tracing strategy, we have studied a specific synaptic circuit of Aldh1a1 neurons with system-level function and disease progression in AD mice. Results We demonstrate that Aldh1a1 neurons encode delay of gratification that measures self-control skills in decision making by projecting inhibitory synapses directly onto excitatory glutamate neurons in the intermediate lateral septum (EGNIS) and receiving synaptic inputs from layer 5b pyramidal neurons in the medial prefrontal cortex (L5PN). L5PN → Aldh1a1 synaptic transmission undergoes long-term potentiation (LTP). Pathway specific inhibition by either genetic silencing presynaptic terminals or antagonizing postsynaptic receptors impairs delay of gratification, resulting in the impulsive behaviors. Further studies show that reconstitution of Aldh1a1-deficient neurons with the expression of exogenous Aldh1a1 (eAldh1a1) restores Aldh1a1 → EGNIS synaptic transmission and rescues the impulsive behaviors in AD mice. Conclusions These results not only identify a specific function and circuit of Aldh1a1 neurons but also provide a cellular point of entry to an important but understudied synaptic mechanism for the induction of impulsive behaviors at an early stage of AD.
Whole genome sequencing helps pinpoint a genetic diagnosis for patients
Authors: Katherine Schon
Journal: BMJ (2021)

Whole genome sequencing helps pinpoint a genetic diagnosis for patients Katherine Schon clinical research fellow and clinical genetics specialist registrarWhen I started as a specialty registrar in clinical genetics in 2013, genetic testing for rare disorders in the NHS involved single gene tests.These were performed at different specialist laboratories, by the labour-intensive process of Sanger sequencing.Due to the financial cost, sequencing was only ordered through clinical genetics departments, and requests were scrutinised at a departmental meeting.This approach could be successful for patients whose clinical features were highly specific for a single disorder, but for patients whose clinical features could be caused by mutations in many different genes (such as intellectual disability or mitochondrial disorders), finding a diagnosis by Sanger sequencing was extremely challenging.
Plasma proteins elevated in severe asthma despite oral steroid use and unrelated to Type-2 inflammation
Authors: Maria Sparreman Mikus, Johan Kolmert, Lars I. Andersson, Jörgen Östling, Richard G. Knowles, Cristina Gómez, Magnus Ericsson, John-Olof Thörngren, Payam Emami Khoonsari, Barbro Dahlén, Maciej Kupczyk, Bertrand De Meulder, Charles Auffray, Per S. Bakke, Bianca Beghe, Elisabeth H. Bel, Massimo Caruso, Pascal Chanez, Bo Chawes, Stephen J. Fowler, Mina Gaga, Thomas Geiser, Mark Gjomarkaj, Ildikó Horváth, Peter H. Howarth, Sebastian L. Johnston, Guy Joos, Norbert Krug, Paolo Montuschi, Jacek Musial, Ewa Niżankowska-Mogilnicka, Henric K. Olsson, Alberto Papi, Klaus F. Rabe, Thomas Sandström, Dominick E. Shaw, Nikolaos M. Siafakas, Mathias Uhlén, John H. Riley, Stewart Bates, Roelinde J.M. Middelveld, Craig E. Wheelock, Kian Fan Chung, Ian M. Adcock, Peter J. Sterk, Ratko Djukanovic, Peter Nilsson, Sven-Erik Dahlén, Anna James
Journal: European Respiratory Journal (2021)

Asthma phenotyping requires novel biomarker discovery.To identify plasma biomarkers associated with asthma phenotypes by application of a new proteomic panel to samples from two well-characterised cohorts of severe (SA) and mild-to-moderate (MMA) asthmatics, COPD subjects and healthy controls (HCs).An antibody-based array targeting 177 proteins predominantly involved in pathways relevant to inflammation, lipid metabolism, signal transduction and extracellular matrix was applied to plasma from 525 asthmatics and HCs in the U-BIOPRED cohort, and 142 subjects with asthma and COPD from the validation cohort BIOAIR. Effects of oral corticosteroids (OCS) were determined by a 2-week, placebo-controlled OCS trial in BIOAIR, and confirmed by relation to objective OCS measures in U-BIOPRED.In U-BIOPRED, 110 proteins were significantly different, mostly elevated, in SA compared to MMA and HCs. 10 proteins were elevated in SA versus MMA in both U-BIOPRED and BIOAIR (alpha-1-antichymotrypsin, apolipoprotein-E, complement component 9, complement factor I, macrophage inflammatory protein-3, interleukin-6, sphingomyelin phosphodiesterase 3, TNF receptor superfamily member 11a, transforming growth factor-β and glutathione S-transferase). OCS treatment decreased most proteins, yet differences between SA and MMA remained following correction for OCS use. Consensus clustering of U-BIOPRED protein data yielded six clusters associated with asthma control, quality of life, blood neutrophils, high-sensitivity C-reactive protein and body mass index, but not Type-2 inflammatory biomarkers. The mast cell specific enzyme carboxypeptidase A3 was one major contributor to cluster differentiation.The plasma proteomic panel revealed previously unexplored yet potentially useful Type-2-independent biomarkers and validated several proteins with established involvement in the pathophysiology of SA.
GPs may help people at risk of self-harm by asking open questions and acknowledging distress
Authors: Helen Saul, Deniz Gursul
Journal: BMJ (2021)

The studyFord J, Thomas F, Byng R, McCabe R. Asking about self-harm and suicide in primary care: moral and practical dimensions. Patient Educ Couns 2020;104:4.To read the full NIHR Alert go to: https://evidence.nihr.ac.uk/alert/open-questions-improve-gp-conversations-self-harm/.
Correction: Expected changes in obesity after reformulation to reduce added sugars in beverages: A modeling study
Authors: Ana Basto-Abreu, Ariela Braverman-Bronstein, Dalia Camacho-García-Formentí, Rodrigo Zepeda-Tello, Barry M. Popkin, Juan Rivera-Dommarco, Mauricio Hernández-Ávila, Tonatiuh Barrientos-Gutiérrez
Journal: PLoS Medicine (2019)

There is an error in the reference for the source of the mathematical model used in this manuscript.The authors cited Chow&Hall 2008 instead
Disruption of HIV-1 co-receptors CCR5 and CXCR4 in primary human T cells and hematopoietic stem and progenitor cells using base editing
Authors: Friederike Knipping, Gregory A. Newby, Cindy R. Eide, Amber N. McElroy, Sarah C. Nielsen, Kyle Smith, Yongxing Fang, Tatjana I. Cornu, Caroline Costa, Alejandra Gutierrez-Guerrero, Samuel P. Bingea, Colby J. Feser, Benjamin Steinbeck, Keli L. Hippen, Bruce R. Blazar, Anton McCaffrey, Claudio Mussolino, Els Verhoeyen, Jakub Tolar, David R. Liu, Mark J. Osborn
Journal: Molecular Therapy (2021)

Disruption of CCR5 or CXCR4, the main human immunodeficiency virus type 1 (HIV-1) co-receptors, has been shown to protect primary human CD4+ T cells from HIV-1 infection. Base editing can install targeted point mutations in cellular genomes, and can thus efficiently inactivate genes by introducing stop codons or eliminating start codons without double-stranded DNA break formation. Here, we applied base editors for individual and simultaneous disruption of both co-receptors in primary human CD4+ T cells. Using cytosine base editors we observed premature stop codon introduction in up to 89% of sequenced CCR5 or CXCR4 alleles. Using adenine base editors we eliminated the start codon in CCR5 in up to 95% of primary human CD4+ T cell and up to 88% of CD34+ hematopoietic stem and progenitor cell target alleles. Genome-wide specificity analysis revealed low numbers of off-target mutations that were introduced by base editing, located predominantly in intergenic or intronic regions. We show that our editing strategies prevent transduction with CCR5-tropic and CXCR4-tropic viral vectors in up to 79% and 88% of human CD4+ T cells, respectively. The engineered T cells maintained functionality and overall our results demonstrate the effectiveness of base-editing strategies for efficient and specific ablation of HIV co-receptors in clinically relevant cell types.
<i>Bifidobacterium</i> catabolism of human milk oligosaccharides overrides endogenous competitive exclusion driving colonization and protection
Authors: Britta E. Heiss, Amy M. Ehrlich, Maria X. Maldonado-Gomez, Diana H. Taft, Jules A. Larke, Michael L. Goodson, Carolyn M. Slupsky, Daniel J. Tancredi, Helen E. Raybould, David A. Mills
Journal: Gut Microbes (2021)

Understanding how exogenous microbes stably colonize the animal gut is essential to reveal mechanisms of action and tailor effective probiotic treatments. Bifidobacterium species are naturally enriched in the gastrointestinal tract of breast-fed infants. Human milk oligosaccharides (HMOs) are associated with this enrichment. However, direct mechanistic proof of the importance of HMOs in this colonization is lacking given milk contains additional factors that impact the gut microbiota. This study examined mice supplemented with the HMO 2ʹfucosyllactose (2ʹFL) together with a 2ʹFL-consuming strain, Bifidobacterium pseudocatenulatum MP80. 2ʹFL supplementation creates a niche for high levels of B.p. MP80 persistence, similar to Bifidobacterium levels seen in breast-fed infants. This synergism impacted gut microbiota composition, activated anti-inflammatory pathways and protected against chemically-induced colitis. These results demonstrate that bacterial-milk glycan interactions alone drive enrichment of beneficial Bifidobacterium and provide a model for tunable colonization thus facilitating insight into mechanisms of health promotion by bifidobacteriain neonates.
TCT-230 One-Year Results After Transcatheter Aortic Valve Replacement With Balloon-Expandable Valves: Comparison of SAPIEN 3 Ultra and SAPIEN 3
Authors: Tobias Rheude, Katharina Kornhuber, Costanza Pellegrini, Markus Freißmuth, Finn Syryca, Patrick Mayr, Hector Alvarez Covarrubias, Markus Kasel, Michael Joner, Erion Xhepa
Journal: Journal of the American College of Cardiology (2021)
<scp>Long‐Term</scp> Efficacy and Safety of Guselkumab, a Monoclonal Antibody Specific to the p19 Subunit of Interleukin‐23, Through Two Years: Results From a Phase <scp>III</scp>, Randomized, <scp>Double‐Blind</scp>, <scp>Placebo‐Controlled</scp> Study Conducted in <scp>Biologic‐Naive</scp> Patients With Active Psoriatic Arthritis
Authors: Iain B. McInnes, Proton Rahman, Alice B. Gottlieb, Elizabeth C. Hsia, Alexa P. Kollmeier, Xie L. Xu, Yusang Jiang, Shihong Sheng, May Shawi, Soumya D. Chakravarty, Désirée van der Heijde, Philip J. Mease
Journal: Arthritis & Rheumatology (2021)

To assess long-term efficacy and safety of guselkumab, an interleukin-23 p19 subunit (IL-23p19) inhibitor, in patients with active psoriatic arthritis (PsA) from the phase III DISCOVER-2 trial.In the DISCOVER-2 trial, patients with active PsA (≥5 swollen joints and ≥5 tender joints; C-reactive protein level ≥0.6 mg/dl) despite prior nonbiologic therapy were randomized to receive the following: guselkumab 100 mg every 4 weeks; guselkumab 100 mg at weeks 0 and 4 and then every 8 weeks; or placebo with crossover to guselkumab 100 mg every 4 weeks, beginning at week 24. Efficacy assessments included American College of Rheumatology ≥20%/50%/70% improvement criteria (ACR20/50/70), Investigator's Global Assessment (IGA) of psoriasis score of 0 (indicating complete skin clearance), resolution of enthesitis (Leeds Enthesitis Index) and dactylitis (Dactylitis Severity Score), and changes in the Sharp/van der Heijde modified radiographic scores for PsA. Clinical data (imputed as no response/no change from baseline if missing) and observed radiographic data were summarized through week 100; safety assessments continued through week 112.Of the 739 randomized and treated patients, 652 (88%) completed treatment through week 100. Across groups of guselkumab-treated patients (including those in the placebo-guselkumab crossover group), the following findings at week 100 indicated that amelioration of arthritis signs/symptoms and extraarticular manifestations was durable through 2 years: ACR20 response (68-76%), ACR50 response (48-56%), ACR70 response (30-36%), IGA score of 0 (55-67%), enthesitis resolution (62-70%), and dactylitis resolution (72-83%). Mean changes in the Sharp/van der Heijde modified score for PsA from weeks 52 to week 100 (range 0.13-0.75) indicated that the low rates of radiographic progression observed among guselkumab-treated patients at earlier time points extended through week 100. Through week 112, 8% (5.8 per 100 patient-years) and 3% (1.9 per 100 patient-years) of the 731 guselkumab-treated patients had a serious adverse event or serious infection, respectively; 1 death occurred (road traffic accident).In biologic-naive PsA patients, guselkumab provided durable improvements in multiple disease domains with no unexpected safety findings through 2 years.
Effect of corticosteroid dosing on outcomes in high‐grade immune checkpoint inhibitor hepatitis
Authors: Michael Li, Danny Wong, Alexander S. Vogel, Jordan S. Sack, Osama E. Rahma, F. Stephen Hodi, Stephen D. Zucker, Shilpa Grover
Journal: Hepatology (2021)

Abstract Background and Aims Consensus guidelines recommend high‐dose corticosteroids (1–2 mg/kg/day methylprednisolone equivalents) for treating grade ≥3 immune checkpoint inhibitor (ICI) hepatitis. We examined the effect of corticosteroid dosing on time to alanine aminotransferase (ALT) normalization, need for additional immunosuppression, and steroid‐related complications. Approach and Results We conducted a retrospective cohort study of 215 ICI‐treated patients from 2010 to 2020 who developed grade ≥3 (ALT &gt; 200 U/L) ICI hepatitis. Patients were grouped by initial corticosteroid dose (≥1.5 mg/kg or &lt;1.5 mg/kg methylprednisolone equivalents). Propensity scores were calculated predicting the risk of receiving the higher steroid dose and used in inverse probability of treatment weighted (IPTW) logistic or Cox regression. The 87 patients in the ≥1.5 mg/kg group received higher initial (2.0 vs. 0.8 mg/kg/day, p &lt; 0.001) and maximum (2.0 vs. 1.0 mg/kg/day, p &lt; 0.001) steroid doses than the 128 patients in the &lt;1.5 mg/kg group. There was no difference between the higher versus lower‐dose groups in development of steroid‐refractory hepatitis (OR 1.22, 95% CI 0.79–1.89, p = 0.365) on IPTW‐logistic regression. In patients with steroid‐responsive disease, there was no difference between the two groups in time to ALT normalization using either standard Cox regression (HR 1.02, 95% CI 0.72–1.45, p = 0.903) or IPTW‐Cox regression (HR 1.09, 95% CI 0.78–1.51, p = 0.610). The ≥1.5 mg/kg group had longer exposure to corticosteroids (median 60 vs. 44 days, p = 0.005) and higher incidences of infection (18.4% vs. 7.0%, relative risk [RR] 2.6, 95% CI 1.2–5.6, p = 0.011) and hyperglycemia requiring treatment (23.3% vs. 7.8%, RR 3.0, 95% CI 1.5‐6.0, p = 0.001). Conclusions In patients with high‐grade ICI hepatitis, initial treatment with 1 mg/kg/day methylprednisolone equivalents provides similar hepatitis outcomes with reduced risk of steroid‐related complications when compared with higher‐dose regimens.
A painful swollen ankle after a fall
Authors: Timothy J Sadler, Philipp Riede
Journal: BMJ (2021)

A man in his 30s presented to the emergency department with a pronation twisting injury to his right ankle after falling down a step three days earlier. Within minutes of the injury he experienced pain and ankle swelling. The pain had subsided at the time of presentation, but the patient was still unable to bear weight on the affected foot. A large ankle joint effusion with generalised reduced range of movement was detected on examination. No specific area of focal tenderness was found on palpation. Radiography …
TCT-22 Single-Center Long-Term Experience With Carotid Artery Stenting in High-Risk Patients
Authors: Rafath Ullah, Blair Tilkens, Kevin Bodker, Aashish Katapadi, Khalil Odeh, James Adefisoye, Khawaja Afzal Ammar, Jayant Khitha, Suhail Q. Allaqaband, Tanvir Bajwa, Mark W. Mewissen
Journal: Journal of the American College of Cardiology (2021)