tbuckley/cabot-search huggingface dataset:
Abstract 19724: Utility of High Risk Patients Detected by Cardiac Magnetic Resonance Adding on Risk Score Improves the Predictive Value of Future Coronary Event in Subjects Without Coronary Artery Disease
Authors: Kazuhiro Nakao, Teruo Noguchi, Yasuhide Asaumi, Yoshiaki Morita, Kunihiro Nishimura, Michikazu Nakai, Yoshihiro Miyamoto, Tomohiro Kawasaki, Satohi Yasuda
Journal: Circulation (2017)

Background: Coronary high-intensity plaque (HIP) with a high plaque-to-myocardial signal intensity ratio (PMR) detected by non-contrast T1-weighted imaging has emerged as a novel predicting factor ...
Coronavirus Disease 2019 Hangover: A Rising Tide of Alcohol Use Disorder and Alcohol‐Associated Liver Disease
Authors: Ben L. Da, Gene Y. Im, Thomas D. Schiano
Journal: Hepatology (2020)

The coronavirus disease 2019 (COVID‐19) pandemic has had a tremendous global impact since it began in November of 2019. However, there are concerns that the COVID‐19 pandemic will not affect all equally and that some populations will be particularly vulnerable. Relevant to liver disease, patients with alcohol use disorder (AUD) and alcohol‐associated liver disease (ALD) may be among the populations that are the most severely impacted. The reasons for this include being at a higher risk of severe COVID‐19 infection due to a depressed immune system and high‐risk underlying comorbidities, the injurious effect of COVID‐19 on the liver, the inability to attend regular visits with providers, diversion of hospital resources, and social isolation leading to psychological decompensation and increased drinking or relapse. As a result, we fear that there will be a dramatic rising tide of alcohol relapse, admissions for decompensated ALD, and an increase in newly diagnosed patients with AUD/ALD post–COVID‐19 pandemic. Providers and their institutions should implement preemptive strategies such as telehealth and aggressive patient outreach programs now to curb this anticipated problem. Liver transplantation (LT) centers should adapt to the pandemic by considering leniency to some LT candidates with ALD who cannot access appropriate alcohol treatment due to the current situation. In conclusion, the COVID‐19 pandemic will likely be especially detrimental to patients with AUD/ALD, and actions need to be taken now to limit the scope of this anticipated problem.
Barrier-protective effects of activated protein C in human alveolar epithelial cells
Authors: Ferranda Puig, Jéssica Tijero, Ramon Farre, Lluís Blanch, Daniel Navajas, Antonio Artigas
Journal: European Respiratory Journal (2013)

RATIONALE: The structural integrity of the alveolar epithelial monolayer depends on the balance between inward tension forces and outward adhesive tethering forces at cell-cell contacts. During the early stages of acute lung injury, this balance might be affected by alterations in the coagulation cascade. We aimed to study the effects of activated protein C (APC) on barrier integrity in cultured human lung epithelial cells exposed to thrombin (Thr). METHODS: The dynamics of barrier function were evaluated by measurements of transepithelial impedance (TI). Cell lines A549 and H441 and primary culture of human alveolar epithelial cells (HAECs) grown to confluence on gold microelectrodes, were pretreated with APC (50μg/ml) or culture medium (vehicle) for 3h. Subsequently, 50nM Thr or medium was added to the cell culture. TI was measured every minute up to 70 minutes. Cells pretreated with vehicle for 3h and challenged with medium instead of Thr were defined as control group. RESULTS: The acute response to Thr produced a significant decline in TI in all three cell types: 12.6% in A549, 13.5% in HAECs, and 5.8% in H441, reflecting increased permeability. This decline in TI was rapid, reaching a low point between 1 and 10 min after Thr challenge. Then, the pattern of the response to Thr in the three human lung epithelial cell types differed. The Thr-induced acute decline in TI was significantly attenuated by pretreatment with APC in all three cell types (4.6% in A549, 5.9% in HAECs, and 1.4% in H441 cells), suggesting a barrier-protective response. No significant changes in TI values were found between with APC pretreated cells and control cells. ACKNOWLEDGEMENT: FIS-PI08/0646 and Fundacio Parc Tauli.
Evaluating the Risk of Macrovascular Events and Mortality Among People With Multiple Sclerosis in England
Authors: Raffaele Palladino, Ruth Ann Marrie, Azeem Majeed, Jeremy Chataway
Journal: JAMA Neurology (2020)

<h3>Importance</h3> People with multiple sclerosis (MS) are associated with an increased risk of cardiovascular disease and mortality; however, evidence from population-based studies is sparse. <h3>Objective</h3> To assess whether the risk of macrovascular events and mortality differs among people with MS compared with a matched population without MS in England. <h3>Design, Setting, and Participants</h3> A population-based retrospective matched cohort study was conducted in general practices registered with the Clinical Practice Research Datalink in England between January 1, 1987, and September 30, 2018, with a mean (SD) follow-up of 11.3 (6.5) years. A total of 12 251 patients with MS were matched with up to 6 people without MS (n = 72 572) by age, sex, and general practice. People with 3 or more diagnoses of MS recorded during the study period were included. The first MS diagnosis was considered as index date. <h3>Exposures</h3> Multiple sclerosis status. Analyses were also stratified by sex. <h3>Main Outcomes and Measures</h3> Main outcomes were acute coronary syndrome, cerebrovascular disease, any macrovascular disease (including peripheral arterial disease), and mortality (all-cause mortality and cardiovascular disease–specific mortality). Cox proportional hazards regression and Fine and Gray proportional subhazard regression models were used to assess differences in rates. <h3>Results</h3> A total of 12 251 people with MS (66.9% women; mean [SD] age, 44.9 [13.3] years) were matched with 72 572 people without MS (69.8% women; mean [SD] age, 44.9 [13.3] years). As compared with people without MS, people with MS were associated with a 28% increased hazard of acute coronary syndrome (hazard ratio [HR], 1.28; 95% CI, 1.09-1.51), 59% increased hazard of cerebrovascular disease (HR, 1.59; 95% CI, 1.32-1.92), 32% increased hazard of any macrovascular disease (HR, 1.32; 95% CI, 1.15-1.52), 3.5-fold increased hazard of all-cause mortality (HR, 3.46; 95% CI, 3.28-3.65), and 1.5-fold increased hazard in cardiovascular disease mortality (HR, 1.47; 95% CI, 1.27-1.71). Differences in macrovascular events were more pronounced among women than men. Mortality risk was also higher for women than men. Treatment with lipid-lowering medications (mainly statins) was associated with lower mortality rates among people with MS. <h3>Conclusions and Relevance</h3> This study suggests that MS is associated with an increased risk of cardiovascular and cerebrovascular disease that is not completely accounted for by traditional vascular risk factors. Given the adverse effects of these comorbidities on outcomes in patients with MS, further investigation is needed.
Nuclear Medicine Imaging Techniques of the Gastrointestinal System
Authors: Harvey A. Ziessman
Journal: Clinical Nuclear Medicine (2020)

Gastrointestinal scintigraphy takes advantage of the physiologic basis of radionuclide imaging and makes effective use of its quantitative potential. This chapter discusses the importance and clinical use of older, tried, and true scintigraphic studies of the gastrointestinal system, as well as newer techniques that are increasing in clinical importance. They are discussed not in the more common aboral order, from mouth to rectum, but according to a logical progression. All topics will be covered, beginning with solid gastric emptying, then liquid gastric emptying, gastric accommodation, small and large bowel intestinal transit, esophageal transit, gastroesophageal reflux, gastrointestinal bleeding, and the Meckel's scan.
Pre-transplant MRD negativity predicts favorable outcomes of CAR-T therapy followed by haploidentical HSCT for relapsed/refractory acute lymphoblastic leukemia: a multi-center retrospective study
Authors: Houli Zhao, Jieping Wei, Guoqing Wei, Yi Luo, Jimin Shi, Qu Cui, Mingfeng Zhao, Aibin Liang, Qing Zhang, Jianmin Yang, Xin Li, Jing Chen, Xianmin Song, Hongmei Jing, Yuhua Li, Siguo Hao, Wenjun Wu, Yamin Tan, Jian Yu, Yanmin Zhao, Xiaoyu Lai, Elaine Tan Su Yin, Yunxiong Wei, Ping Li, Jing Huang, Tao Wang, Didier Blaise, Lei Xiao, Alex H. Chang, Arnon Nagler, Mohamad Mohty, He Huang, Yongxian Hu
Journal: Journal of Hematology & Oncology (2020)

Abstract Background Consolidative allogeneic hematopoietic stem cell transplantation is a controversial option for patients with relapsed/refractory acute lymphoblastic leukemia after chimeric antigen receptor T cell (CAR-T) therapy. We performed a multicenter retrospective study to assess whether patients can benefit from haploidentical hematopoietic stem cell transplantation after CAR-T therapy. Methods A total of 122 patients after CAR-T therapy were enrolled, including 67 patients without subsequent transplantation (non-transplant group) and 55 patients with subsequent haploidentical hematopoietic stem cell transplantation (transplant group). Long-term outcome was assessed, as was its association with baseline patient characteristics. Results Compared with the non-transplant group, transplantation recipients had a higher 2-year overall survival (OS; 77.0% versus 36.4%; P &lt; 0.001) and leukemia-free survival (LFS; 65.6% versus 32.8%; P &lt; 0.001). Multivariate analysis showed that minimal residual disease (MRD) positivity at transplantation is an independent factor associated with poor LFS ( P = 0.005), OS ( P = 0.035), and high cumulative incidence rate of relapse ( P = 0.045). Pre-transplant MRD-negative recipients (MRD− group) had a lower cumulative incidence of relapse (17.3%) than those in the non-transplant group (67.2%; P &lt; 0.001) and pre-transplant MRD-positive recipients (MRD+ group) (65.8%; P = 0.006). The cumulative incidence of relapse in MRD+ and non-transplant groups did not differ significantly ( P = 0.139). The 2-year LFS in the non-transplant, MRD+, and MRD− groups was 32.8%, 27.6%, and 76.1%, respectively. The MRD− group had a higher LFS than the non-transplantation group ( P &lt; 0.001) and MRD+ group ( P = 0.007), whereas the LFS in the MRD+ and non-transplant groups did not differ significantly ( P = 0.305). The 2-year OS of the MRD− group was higher than that of the non-transplant group (83.3% versus 36.4%; P &lt; 0.001) but did not differ from that of the MRD+ group (83.3% versus 62.7%; P = 0.069). The OS in the non-transplant and MRD+ groups did not differ significantly ( P = 0.231). Conclusion Haploidentical hematopoietic stem cell transplantation with pre-transplant MRD negativity after CAR-T therapy could greatly improve LFS and OS in patients with relapsed/refractory acute lymphoblastic leukemia. Trial registration The study was registered in the Chinese clinical trial registry ( ChiCTR1900023957 ).
Identification of Human Single-Domain Antibodies against SARS-CoV-2
Authors: Yanling Wu, Cheng Li, Shuai Xia, Xiaolong Tian, Yu Kong, Zhi Wang, Chenjian Gu, Rong Zhang, Chao Tu, Youhua Xie, Zhenlin Yang, Lu Lu, Shibo Jiang, Tianlei Ying
Journal: Cell Host & Microbe (2020)
Incomplete Freund’s adjuvant reduces arginase and enhances Th1 dominance, TLR signaling and CD40 ligand expression in the vaccine site microenvironment
Authors: Karlyn E Pollack, Max O Meneveau, Marit M Melssen, Kevin T Lynch, Alexander F Koeppel, Samuel J Young, Stephen Turner, Pankaj Kumar, Katia Sol-Church, Ileana S Mauldin, Craig L Slingluff Jr
Journal: Journal for ImmunoTherapy of Cancer (2020)

Background Immunogenicity of cancer vaccines is impacted by adjuvants and schedule, but systematic assessments of their effects have not been performed. Montanide ISA-51, an incomplete Freund’s adjuvant (IFA), is used in many vaccine trials, but concerns have been raised about negative effects in murine studies. We found in humans that IFA enhances systemic immune responses and that repeat vaccination at one site (same site vaccination (SSV)) creates tertiary lymphoid structures (TLS) in the vaccine site microenvironment (VSME). We hypothesized that vaccination with peptides+IFA+pICLC or SSV×3 with peptides in IFA would create an immunogenic milieu locally at the VSME, with activated dendritic cells (DC), TLS-associated chemokines and a Th1-dominant VSME. Methods Biopsies of the VSME were obtained from participants on two clinical trials who were immunized with multiple melanoma peptides (MELITAC 12.1) in adjuvants comprising IFA and/or the TLR3-agonist pICLC. Biopsies were obtained either a week after one vaccine or a week after SSV×3. Controls included normal skin and skin injected with IFA without peptides. Gene expression analysis was performed by RNAseq. Results VSME samples were evaluated from 27 patients. One vaccine with peptides in pICLC+IFA enhanced expression of CD80, CD83, CD86 (p&lt;0.01), CD40 and CD40L (p&lt;0.0001) over normal skin; these effects were significantly enhanced for SSV with peptides+IFA. Vaccines containing pICLC increased expression of TBX21 (T-bet) but did not decrease GATA3 over normal skin, whereas SSV with peptides in IFA dramatically enhanced TBX21 and decreased GATA3, with high expression of IFNγ and STAT1. SSV with peptides in IFA also reduced arginase-1 (ARG1) expression and enhanced expression of TLR adapter molecules TICAM-1 (TRIF) and MYD88. Furthermore, SSV with IFA and peptides also enhanced expression of chemokines associated with TLS formation. Conclusions These findings suggest that SSV with peptides in IFA enhances CD40L expression by CD4 T cells, supports a Th1 microenvironment, with accumulation of activated and mature DC. Increased expression of TLR adaptor proteins after SSV with peptides in IFA might implicate effects of the skin microbiome. Reduced ARG1 may reflect diminished suppressive myeloid activity in the VSME. Trial registration number ( NCT00705640 , NCT01585350 ).
Hepatic stellate cell autophagy inhibits extracellular vesicle release to attenuate liver fibrosis
Authors: Jinhang Gao, Bo Wei, Thiago M. de Assuncao, Zhikui Liu, Xiao Hu, Samar Ibrahim, Shawna A. Cooper, Sheng Cao, Vijay H. Shah, Enis Kostallari
Journal: Journal of Hepatology (2020)
PTH-014 Post-polypectomy surveillance in the english bowel cancer screening programme: a prospective cohort study, preliminary results
Authors: Stewart Bonnington, Linda Sharp, Matt Rutter
Journal: Endoscopy (2018)

<h3>Introduction</h3> The English Bowel Cancer Screening Programme (BCSP) offers individuals aged 60 to 74 years guaiac FOB testing (gFOBt), with an invitation for colonoscopy if positive. Of more than 3 00 000 individuals who have attended for colonoscopy, over 45 000 attended post-polypectomy surveillance (PPS) after having intermediate (IR) or high risk (HR) adenomas detected and resected at screening. It is established that screening reduces mortality from colorectal cancer (CRC). However, robust evidence to support PPS is lacking. <h3>Methods</h3> Details were extracted from the BSCP database for individuals who attended PPS from the start of the BCSP in 2006 until 3/1/2017. Data were analysed using Stata 14. <h3>Results</h3> 67,435 PPS episodes were performed in 45 151 individuals. 60% of individuals had attended only 1 PPS episode, 34% attended 2, 5% attended 3, and 0.4% attended 4 or 5. PPS episodes per year greatly increased over the study period. In 2008, 453 episodes were attended, rising to 13 698 in 2016 (figure 1). 70% of those attending PPS were male. 44% were aged 60–64 at the time of index screening, 43% aged 65–69, and 10% aged 70–74. The oldest age group had a higher proportion (68%) of HR individuals than in the younger groups. Screening risk category varied with gender. Overall, 40% of females and 51% of males were HR (figure 2). Overall, the findings at first PPS demonstrate a high proportion of individuals with no further adenoma found (table 1). <h3>Conclusions</h3> PPS accounts for an increasing proportion of endoscopy workload in the BCSP and more broadly in the UK and internationally. These results demonstrate a low proportion of CRC or IR or HR adenomas diagnosed at PPS in the BCSP. Individuals with HR adenomas at screening more often had further adenomas detected at first PPS when compared to those with IR adenomas at screening. HR individuals also had a higher probability of IR or HR adenomas at first PPS. CRC diagnosis at first PPS was low in both groups (≤0.5%). Further evaluation of the BCSP database is ongoing in order to identify subgroups most likely to benefit from PPS.
Genetic Variants in Arachidonic Acid Pathway Genes Associated with Nsaids-Exacerbated Respiratory Disease
Authors: Pedro Ayuso, Maria del Carmen Plaza-Serón, Natalia Blanca-López, Inmaculada Doña, Paloma Campo, Jose Julio Laguna, Joan Bartra, Victor Soriano-Gomis, María José Torres, Miguel Blanca, Jose A Cornejo-Garcia, James R. Perkins
Journal: Journal of Allergy and Clinical Immunology (2015)
Outcomes of triple-negative versus non-triple-negative breast cancers managed with breast-conservative therapy.
Authors: Abu Bakar Hafeez Bhatti, Amina Iqbal Khan, Neelam Siddiqui, Narjis Muzaffar, Mazhar Ali Shah
Journal: Journal of Clinical Oncology (2013)

70 Background: Triple-negative breast cancer represents a subgroup of breast cancer associated with aggressive behavior and high risk of local and regional failure. Aggressive surgical intervention is considered optimal for this cancer which has made role of Breast conservative therapy (BCT) debatable in these patients. The objective of this study was to compare outcome of BCT for triple negative versus non-triple–negative breast cancers. Methods: Data of patients who underwent breast conservative therapy between 1997-2009 at Shaukat Khanum Cancer Hospital and had complete receptor status information were extracted. Patients were divided into triple-negative breast cancer (TNBC) and non-TNBC. Patient characteristics, medical treatment modalities and adverse events between two groups were compared. Five year locoregional recurrence free, disease free and overall survival was calculated. Univariate and multivariate analysis was done to identify independent predictors of outcome. Results: A total of 194 patients with TNBC and 443 with non-TNBC were compared. Significant differences was present for age at presentation (p&lt;0.0001), family history (p=0.005), grade (p&lt;0.0001) and use of hormonal therapy (p&lt;0.0001). The actual number of locoregional failures, distant failures, and mortalities were not significantly different. No significant difference was present in 5-year locoregional recurrence free (96% vs. 92%, p=0.3), disease free (75% vs. 74%, p=0.7) and overall survival (78% vs. 83%, p=0.2). Tumor size, nodal involvement and hormonal treatment were independent predictors of survival on multivariate analysis. Conclusions: Breast-conservative therapy has comparable outcomes for triple-negative and non-triple–negative breast cancers.
Partnering With Patients to Bridge Gaps in Consent for Acute Care Research
Authors: Neal W. Dickert, Amanda Michelle Bernard, JoAnne M. Brabson, Rodney J. Hunter, Regina McLemore, Andrea R. Mitchell, Stephen Palmer, Barbara Reed, Michele Riedford, Raymond T. Simpson, Candace D. Speight, Tracie Steadman, Rebecca D. Pentz
Journal: The American Journal of Bioethics (2020)

Clinical trials for acute conditions such as myocardial infarction and stroke pose challenges related to informed consent due to time limitations, stress, and severe illness. Consent processes should be sensitive to the context in which trials are conducted and to needs of patients and surrogate decision-makers. This manuscript describes a collaborative effort between ethicists, researchers, patients, and surrogates to develop patient-driven, patient-centered approaches to consent for clinical trials in acute myocardial infarction and stroke.Our group identified important ways in which existing consent processes and forms for clinical trials fail to meet patients' and surrogates' needs in the acute context. We collaborated to create model forms and consent processes that are substantially shorter and, hopefully, better-matched to patients' and surrogates' needs and expectations from the perspective of content, structure, and tone. These changes, however, challenge some common conventions regarding consent.
PTH-005 Dyspepsia in 2017: are we adhering to guidelines?
Authors: Fiza Ahmed, Kalpesh Besherdas
Journal: Endoscopy (2018)

Dyspepsia in 2017: are we adhering to guidelines? <h3>Introduction</h3> Recent NICE guidance advocates a test-and-treat strategy for H. pylori in the management of dyspepsia without red-flag features (simple dyspepsia). In addition, NICE recommends trialling symptomatic management with proton pump inhibitors (PPI) or histamine receptor antagonists (H2RA). Upper gastrointestinal (UGI) endoscopy is recommended only if symptoms persist despite these strategies. The aim of this study was to assess degrees of adherence to current guidelines across various UGI endoscopy referral pathways (for example, GP direct access and gastroenterology clinics). <h3>Methods</h3> A single-centre, retrospective analysis was performed for patients who underwent endoscopy from 2016–2017, at a large district general hospital in North London. Data was obtained from Unisoft Endoscopy Reporting Tool software, alongside electronic patient records. Patient data was scrutinised for the following features prior to endoscopy: Presence of red–flag symptoms Endoscopy referral pathway type H. pylori investigations and treatment Management with PPI or H2RA <h3>Results</h3> Data was collected for 250 patients who underwent UGI endoscopy for dyspepsia. 53% were simple dyspepsia cases. 15% had clear red-flag symptoms warranting urgent endoscopy. 4% had symptoms warranting non-urgent endoscopy. 28% had no data available regarding red-flag symptoms. The majority of patients were referred for endoscopy either from gastroenterology clinics (47%) or GP direct access (43%). Other sources included surgical clinics and 1-stop clinics (10%). 60% of patients underwent H. pylori investigations prior to endoscopy. 35% had not been tested by the time of endoscopy. 5% had no data available regarding investigations. 33% of patients did not trial management prior to endoscopy. Of simple dyspepsia cases, 21/133 had not trialled management (11 had been referred from gastroenterology clinics, 6 from general surgery clinics, and 4 by GP direct access). Additionally, 51/133 of simple dyspepsia cases had not undergone H. pylori stool testing prior to endoscopy. The majority of these patients had been referred from gastroenterology clinics or GP direct access. <h3>Conclusions</h3> The majority of patients (53%) included in the study had no symptoms warranting urgent endoscopy. However, over 33% of patients had no H. pylori testing prior to endoscopy – furthermore, 15% had no trial of treatment. Lack of adherence to guidelines was present across all referral pathways. For an endoscopy service to function effectively, it must not be overloaded with inappropriate referrals; failure to follow guidelines increases this burden. Despite widespread availability of these guidelines, implementation remains poorly practised. Thus, NICE endoscopy referral guidance requires better implementation, by means such as increasing awareness in both primary and secondary care.
The Authors Reply:
Authors: Simon Winther, My Svensson, Hanne Skou Jørgensen, Kirsten Bouchelouche, Lars Christian Gormsen, Birgitte Bang Pedersen, Niels Ramsing Holm, Hans Erik Bøtker, Per Ivarsen, Morten Bøttcher
Journal: JACC. Cardiovascular imaging (2016)