tbuckley/cabot-search huggingface dataset:
Association of Optimal Implementation of Sodium-Glucose Cotransporter 2 Inhibitor Therapy With Outcome for Patients With Heart Failure
Authors: Nikhil S. Bassi, Boback Ziaeian, Clyde W. Yancy, Gregg C. Fonarow
Journal: JAMA Cardiology (2020)

<h3>Importance</h3> Sodium-glucose cotransporter 2 inhibitor (SGLT2-i) therapy provided incremental survival benefit to patients with heart failure and reduced ejection fraction (HFrEF) who received guideline-directed medical therapy regardless of type 2 diabetes status in a recent clinical trial. To date, estimation of the potential benefits that could be gained from optimal implementation of SGLT2-i therapy at the population level has not been quantified. <h3>Objective</h3> To quantify the projected gains for deaths prevented or postponed with comprehensive implementation of SGLT2-i therapy for patients with HFrEF in the United States. <h3>Design, Setting, and Participants</h3> This decision analytical model, performed from September 25 to October 20, 2019, used published sources to estimate the US population of patients with HFrEF eligible for SGLT2-i therapy and the numbers needed to treat to prevent or postpone overt death. Sensitivity analyses were performed to account for the range of potential benefits. <h3>Main Outcomes and Measures</h3> All-cause mortality. <h3>Results</h3> Of the 3.1 million patients with HFrEF in the United States, 2 132 800 (69%) were projected to be candidates for SGLT2-i therapy. Optimal implementation of SGLT2-i therapy was empirically estimated to prevent up to 34 125 deaths per year (range 21 840-49 140 deaths per year). A secondary analysis excluding patients on the basis of N-terminal–pro brain natriuretic peptide levels and other trial entry criteria would yield a potential benefit of 25 594 deaths per year prevented (range, 16 380-36 855 deaths per year prevented). <h3>Conclusions and Relevance</h3> This study suggests that a substantial number of deaths in the United States could be prevented by optimal implementation of SGLT2-i therapy. These data support implementation of the current evidence into practice in a timely manner to achieve important public health benefits and to reduce the mortality burden of HFrEF.
Covid-19: South Korea relaxes social distancing after the number of new cases drops below 10 a day
Authors: Elisabeth Mahase
Journal: BMJ (2020)

Covid-19: South Korea relaxes social distancing after the number of new cases drops below 10 a day Elisabeth MahaseThe BMJ South Korea has announced it will begin easing social distancing measures from 6 May, as the number of new confirmed cases dropped to very low levels.Prime Minister Chung Sye-kyun told the public that the government will allow businesses to reopen in phases and gatherings and events can place as long as they follow disinfection guidelines.Parks, libraries, schools, and other public facilities could also start to reopen in phases.
Transjugular intrahepatic portal-systemic shunt in the treatment of refractory ascites: Effect on clinical, renal, humoral, and hemodynamic parameters*1
Authors: J QUIROGA
Journal: Hepatology (1995)

Seventeen cirrhotics with refractory ascites were treated with transjugular intrahepatic portosystemic shunt (TIPS) and followed for 15.5 ± 3.4 months. Five patients died, four within 3 months after TIPS (hepatocellular failure) and one after 22 months (cholangiocarcinoma). Six patients received transplants 1 to 10 months after the procedure. Actuarial survival at 6, 12, and 24 months was 75%, 75%, and 63%, respectively. Portosystemic venous pressure gradient decreased by 46% at 1 month and by 38% at 7 to 12 months. Eight patients presented 18 stenoses 1 to 18 months after TIPS. Twelve stenoses required balloon dilatation. Tense ascites was present before TIPS in 100% of the patients, whereas it was mild or absent in 56% at 1 month, in 66% at 3 to 6 months, in 57% at 7 to 12 months, and in 100% at 24 months after TIPS. Requirements for diuretics and paracentesis decreased after TIPS (P < .001, both). One month after TIPS, urinary and fractional sodium excretion increased (P < .001, both), plasma renin activity, plasma aldosterone (P < .005, both), and plasma norepinephrine (P < .05) decreased and cardiac output (P < .01) increased, systemic vascular resistances (P < .005) decreased, and arterial pressure did not change. Acute hepatic encephalopathy was frequent early after TIPS but was responsive to treatment and caused no long-term disability. In conclusion, TIPS is useful in the treatment of refractory ascites through lowering portal pressure and improving renal sodium excretion. This effect could be attributable to an increase in effective blood volume causing deactivation of vasopressor systems.
Emergency departments must not return to pre-covid days of overcrowding and lack of safety, says college
Authors: Adrian O’Dowd
Journal: BMJ (2020)

UK emergency departments must never return to their previous state of being overcrowded, as well as being sources of hospital acquired infection and unsafe for staff to work in, experts have said.

The Royal College of Emergency Medicine issued a position statement on 6 May1 in which it warned that, if the NHS allowed hospitals to return to the old model of emergency care as covid-19 cases start to fall, patients’ lives would be put at risk.

The need for a “reset” in how care is delivered in emergency departments is vital to prevent a resurgence of covid-19 cases and to leave a permanent improvement in the care provided overall, it said.

Since the covid-19 pandemic began, emergency departments have …
Gene Therapy for Severe Combined Immunodeficiency X1.
Authors: S. Hacein-Bey-Abina, M. Schmidt, F. Le Deist, A. Garrigue, A. Borkhardt, N. Wulffraat, I.E. Alexander, U. Wintergerst, L.E. Leiva, E. Delabesse, E. Macintyre, M.L. Gougeon, G. Gyapay, J. Weinssenbach, C. Fraser, G. de Saint-Basile, J.L. Casanova, C. Von Kalle, A. Fischer, M. Cavazzana-Calvo
Journal: Blood (2005)
Hdac3 is an epigenetic inhibitor of the cytotoxicity program in CD8 T cells
Authors: Rong En Tay, Olamide Olawoyin, Paloma Cejas, Yingtian Xie, Clifford A. Meyer, Yoshinaga Ito, Qing Yu Weng, David E. Fisher, Henry W. Long, Myles Brown, Hye-Jung Kim, Kai W. Wucherpfennig
Journal: The Journal of Experimental Medicine (2020)

Cytotoxic T cells play a key role in adaptive immunity by killing infected or cancerous cells. While the transcriptional control of CD8 T cell differentiation and effector function following T cell activation has been extensively studied, little is known about epigenetic regulation of these processes. Here we show that the histone deacetylase HDAC3 inhibits CD8 T cell cytotoxicity early during activation and is required for persistence of activated CD8 T cells following resolution of an acute infection. Mechanistically, HDAC3 inhibits gene programs associated with cytotoxicity and effector differentiation of CD8 T cells including genes encoding essential cytotoxicity proteins and key transcription factors. These data identify HDAC3 as an epigenetic regulator of the CD8 T cell cytotoxicity program.
Ecarin based coagulation testing
Authors: Robert C. Gosselin, Jonathan Douxfils
Journal: American Journal of Hematology (2020)

Ecarin is derived from venom of Echis carinatus, and will activate prothrombin into meizothrombin which will then cleave fibrinogen to result in clot formation. Ecarin based testing has been described for decades, but these assays were typically restricted to reference or speciality coagulation laboratories. This test was initially described for the assessment of direct thrombin inhibitors (eg, bivalirudin lepirudin, or argatroban) and was not affected by heparins or heparinoids. Ecarin based assays were rarely used for anticoagulation monitoring until the emergence of the direct oral thrombin inhibitor dabigatran etexilate in 2010. As this test was mentioned in the prescribing information for dabigatran etexilate, there was increased interest for use by clinical laboratories as the preferred method for assessing the anticoagulant effect of this drug. The purpose of this document is to review the current status of ecarin based assays for assessing dabigatran. This is with the understanding that these methods can also be exploited for determining the anticoagulation effect of parenteral direct thrombin inhibitors, such as argatroban and bivalirudin.
COVID-19: a case for inhibiting IL-17?
Authors: Omar Pacha, Mary Alice Sallman, Scott E. Evans
Journal: Nature reviews. Immunology (2020)

IL-17 and IL-17 receptor inhibitors boast an impressive safety history and are widely available. Here, we argue that targeting IL-17 is immunologically plausible as a strategy to prevent acute respiratory distress syndrome (ARDS) in coronavirus disease 2019 (COVID-19) and discuss why we think that a clinical trial of a drug in this class could be a logical addition to the effort to find effective therapies. Levels of the cytokine IL-17 positively correlate with disease severity in COVID-19. Here, the authors argue that existing anti-IL-17 therapies should be considered for the treatment of severe COVID-19.
Defending Dolly
Authors: Steven Rose
Journal: The Lancet (2006)

Dolly, the world's best known sheep, was cloned at Roslin, near Edinburgh, in 1996. The Nature paper that made her and one of her creators, Ian Wilmut, overnight stars, came out in 1997. 3 years later, the science writer Colin Tudge collaborated with Wilmut and another key figure in the saga, Keith Campbell, in The Second Creation, a racy account of the achievement and the science behind it. Now Wilmut has teamed up with another science writer, Roger Highfield, to tell essentially the same story.
Paraneoplastic Encephalomyelitis With Glutamic Acid Decarboxylase Antibodies Presenting as Longitudinal Pyramidal Tract Hyperintensity
Authors: Oriol Miralles, Núria Caballol, Roser Velasco
Journal: JAMA Neurology (2020)

This case report describes a man with paraneoplastic neurological syndrome with paraneoplastic encephalomyelitis and small cell lung cancer who also had unusual pathophysiological features visible on magnetic resonance imaging.
Abstract 918: Glucuronidation genotypes and nicotine metabolic phenotypes: Importance of UGT2B10 and UGT2B17 knock-out polymorphisms
Authors: Gang Chen, Nino E. Giambrone, Doug Dluzen, Andrea S. Blevins-Primeau, Carla Gallagher, Diane McCloskey, Philip Lazarus
Journal: Cancer Research (2010)

Abstract Glucuronidation is an important pathway in the metabolism of nicotine, with ∼28% of urinary nicotine metabolites in the form of glucuronidated compounds. Recent in vitro studies have suggested that the UGTs 2B10 and 2B17 play major roles in nicotine glucuronidation with polymorphisms in both enzymes shown to significantly alter the levels of nicotine-, cotinine-, and trans-3-hydroxy-cotinine (3HC)-glucuronides in human liver microsomes in vitro. In the present study, the relationship between the levels of urinary nicotine metabolites and functional polymorphisms in UGTs 2B10 and 2B17 were analyzed in urine specimens from 104 Caucasian smokers. The levels of nicotine-glucuronide and cotinine-glucuronide were 47 (p&amp;lt;0.0005) and 47% (p&amp;lt;0.0001) lower, respectively, in urine from smokers exhibiting the UGT2B10 (*1/*2) genotype, and 98 (p&amp;lt;0.0001) and 99 (p&amp;lt;0.0001), respectively, in urine from smokers with the UGT2B10 (*2/*2) genotype, as compared to the urinary levels in wild-type UGT2B10 smokers. The levels of 3HC-glucuronide was 64% (p&amp;lt;0.0001) lower in the urine from smokers exhibiting the homozygous UGT2B17 (*2/*2) deletion genotype as compared to the levels in urine from wild-type UGT2B17 subjects. These data are consistent with previous in vitro studies and demonstrate that UGTs 2B10 and 2B17 play important roles in the glucuronidation of nicotine, cotinine and 3HC in vivo, and suggest the UGT2B10 codon 67 SNP and the UGT2B17 deletion significantly reduce overall glucuronidation rates of nicotine and its major metabolites in smokers. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 918.
PTH-023 Barrett’s surveillance in a district general hospital: do we follow guidelines for non-dysplastic barrett’s?
Authors: K Christodoulou, AR Farooqi, KT Shaw, IR Sargeant, DL Morris
Journal: Endoscopy (2018)

<h3>Introduction</h3> BSG 2013 guidelines for diagnosis and management of Barrett's oesophagus (BE) recommend surveillance intervals based on the length of BE, histology, and presence of intestinal metaplasia. Practice for BE surveillance varies nationally. East and North Hertfordshire NHS Trust is a district general hospital with a population of approx. 6 00 000. Since the 2013 guidelines most BE surveillance is done by 2 consultants and a specialist nurse. <h3>Methods</h3> A retrospective review of all gastroscopies performed for the indication of BE surveillance from 1/1/16 – 31/12/16. These were audited against BSG 2013 guidelines specifically looking at use of Prague criteria (PC), histology and selection of surveillance intervals. All endoscopies were performed using high definition video-endoscopes. <h3>Results</h3> 207 OGDs for BE surveillance were reviewed (median age 68 [29–90], 75% males). 144 (70%) recorded BE length using the PC. 23 (11%) had either no or minimal Barrett's (&lt;1 cm), of whom 15 (65%) were discharged. In the remaining 40 OGDs (19%) length of BE was unclear in 11 reports, able to be partially deduced from the free text in 20 cases, and fully deduced in 9 cases. Analysis of surveillance intervals was performed only on the 144 OGDs where length of BE was documented fully using PC. Amongst these were 17 cases of dysplasia (12%: 6 indefinite for dysplasia, 7 low grade dysplasia, 4 high grade dysplasia). The remaining 127 cases (88%) were non-dysplastic. Distribution of length of BE is displayed in figure 1. Of the non-dysplastic cases, 46 (36%) had a BE length of &lt;3 cm of whom 20 (43%) had surveillance interval of 3–5 years, 18 (40%) were discharged and 8 (17%) had a surveillance interval of 2 years. 81 (64%) had a BE length of ≥3 cm, of whom 74 (92%) had surveillance interval of 2–3 years, 1 (1%) for 1 year, 4 (5%) for 4–5 years, 1 (1%) was discharged and 1 (1%) died. <h3>Conclusions</h3> Whilst we reported 70% of our BE length using PC, a measure now recommended as a quality standard, a further 19% could have been reported this way. Our data show that only 10% (13) of our 127 non-dysplastic BE cases had an incorrect surveillance interval chosen, less than the figures suggested by JAG who estimate that 30% of patients undergo surveillance at incorrect intervals or where not indicated at all. Of the 207 OGDs analysed, 135 (65%) were carried out by one of our 2 consultants with specialist interest in BE or our BE specialist nurse endoscopist. We therefore support the advice that BE surveillance should be performed on dedicated lists in order to improve endoscopic quality reporting and choice of correct surveillance interval.
Grading of cellular rejection after orthotopic liver transplantation
Authors: S GUPTA
Journal: Hepatology (1995)

All 684 post-orthotopic liver transplantation (OLT) liver biopsies performed at the Royal Free Hospital (RFH) between 1988 and 1993, from 120 patients, were reviewed in order to try to define the relative importance of the histological features of immunosuppressionresponsive cellular rejection. Twenty histological features considered to be possible contributors to the diagnosis of cellular rejection were documented in a binary (presentlabsent) fashion. These features in 106 biopsy specimens obtained 1 to 8 days after OLT were analyzed using stepwise logistic discriminant analysis. All clinical and treatment records were reviewed, and each biopsy specimen was assigned to a diagnostic category depending on these records and follow-up information. Important determinants of the histological diagnosis of cellular rejection (which occurred in 84 of the 106 cases) were moderate/severe mixed portal inflammation, eosinophils, endotheliitis, and bile duct damage. When these all occurred together, the odds of rejection increased 3.6-fold. The original histological diagnosis was recorded, and each biopsy specimen showing cellular rejection was regraded according to the specific criteria of Snover et al., Demetris et al., and a novel RFH scoring system. The latter consists of evaluating portal inflammation, endotheliitis, eosinophils, and bile duct damage, each on a 0 to 3 scale (none, mild, moderate, or severe, respectively) and summation. The resulting cellular rejection score thus can range from 0 to 12. The agreement between the different scoring systems was analyzed using K statistics, and there was good concordance (K, 0.64 to 0.78), despite different histological criteria being used to derive each score. Each system showed a similar degree of sensitivity (87% to 96%). The specificity ranged from 59% to 77%. We conclude that the histological diagnosis of cellular rejection relies mainly on the previously described features of mixed portal inflammation, endotheliitis, eosinophils, and duct damage. There is scope for unification and simplification of the existing grading systems, which depend on differing criteria, and we suggest one such scheme.
Dilated Cardiomyopathies of the Adult
Authors: Robert Arnold Johnson, Igor Palacios
Journal: New England Journal of Medicine (1982)

(Second of Two Parts)Causes (continued)Acute Infectious Myopericarditis and Acute Inflammatory MyocarditisIn North America and Europe, acute infectious myopericarditis is most commonly caused by coxsackievirus B, Types 1 through 5. Other enteroviruses (coxsackievirus A, Types 4 and 16; echovirus, Types 9, 11 and 22; and poliovirus) are also relatively common causes of the disease.49, 110 111 112 113 These agents are each capable of causing dilated cardiomyopathy of abrupt onset; each sometimes produces an epidemic.41,42, 114 115 116 Toxoplasma gondii may produce sporadic cases of acute dilated cardiomyopathy, perhaps fairly commonly.117 Approximately 1 per cent of patients infected with Trypanosoma cruzi have an acute phase . . .
Abstract A32: Identifying actionable pathway malfunction scores with ML algorithm for omics data
Authors: Dmitrii Chebanov, Nadezhda Tatevosova, Irina Mikhaylova
Journal: Cancer Research (2020)

Abstract Background: Driver mutations are traditionally considered as actionable biomarkers for targeted drugs, but the resistance and relapse effects often occur even when these events are precisely discovered. At the same time, primary DNA mutations can be only the triggers for cell malignancy and further development of the tumor occurs due to following pathways imbalance, which may be reflected in gene expression. The goal is to detect preaffected pathways that are most close to the oncogenic affected state, so during the treatment strategy planning we could consider these pathways as the next potential targets after nonresponse or relapse. Methods: We took the data from TCGA Pan-Cancer Atlas on whole-exome sequencing and RNA expression for 33 cancers. Mutations were filtered based on their pathogenicity (1,2). The training set included data on mutations and corresponded RNA levels of 1821 cancer pathways-related genes (3). ML method-logistic regression, with 5-fold cross-validation with a test set, was realized on Python 3.7. Results: Using gene expression data, 9 most common actionable events were predicted: oncogenic mutations affecting Ras, Raf, Ras/Raf/MEK, PI3K, CDK protein families, amplifications of EGFR, ERBB2, CDK4 genes, with an accuracy of 80% - 93%. Results were the probabilities of events: range 10-30% occurrence is shown. Discussion: We considered the obtained molecular events probabilities as the scores of corresponding pathways’ malfunctions. For some molecular events, more than one-third of patients has &amp;gt;10% affected (unbalanced) pathway state. This approach after validation can be used in clinical research practice for patient cohorts risk stratification, or as additional reinforcement for drug companion tests. References: 1. COSMIC; 2. Chakravarty et al., 2017a; 3. KEGG. Citation Format: Dmitrii Chebanov, Nadezhda Tatevosova, Irina Mikhaylova. Identifying actionable pathway malfunction scores with ML algorithm for omics data [abstract]. In: Proceedings of the AACR Special Conference on the Microbiome, Viruses, and Cancer; 2020 Feb 21-24; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2020;80(8 Suppl):Abstract nr A32.
AB0313 Short-Term Effects of Tnf Inhibitors on Bone Turnover Markers and Bone Mineral Density in Rheumatoid Arthritis:
Authors: G. Orsolini, G. Adami, O. Viapiana, L. Idolazzi, A. Fassio, M. Vitiello, D. Gatti, M. Rossini
Journal: Annals of the Rheumatic Diseases (2016)

<h3>Background</h3> TNFα inhibitors (TNFαI) exert positive effects on disease activity in rheumatoid arthritis (RA). Bone involvement is a major determinant of functional impairment in this disease. <h3>Objectives</h3> Here we investigated the short-term effects of TNFαI therapy on bone metabolism and density. <h3>Methods</h3> We studied 54 patients with RA starting a TNFI biologic drug, in whom any factor known to interfere with bone metabolism was excluded or rigorously accounted for. We measured at baseline and after 6 month therapy bone turnover markers (BTM): N-propeptide of type I collagen (P1NP), and bone alkaline phosphates (bAP) for bone formation and serum C-terminal telopeptide of type I collagen (CTX) for bone resorption. We also evaluated bone mineral density (BMD) at hip and lumbar by dual energy X ray absorptiometry (DEXA). <h3>Results</h3> All bone markers rose significantly and these changes were not dependent on steroids dosage; a significant decrease in femoral neck BMD was also observed (see Table). <h3>Conclusions</h3> These results indicate that TNFαI therapy in RA over 6 months is associated with an early increase in bone turnover and a decline in hip BMD. <h3>Disclosure of Interest</h3> None declared
Covid-19: adverse mental health outcomes for healthcare workers
Authors: Jessica A Gold
Journal: BMJ (2020)

Frontline medical workers are at risk of not just adverse physical outcomes from coronavirus disease 2019 (covid-19) but psychological ones too. 1 Data from previous pandemics, particularly after quarantine, suggest that healthcare workers might develop symptoms of post-traumatic stress disorder, depression, and substance use disorders. 2Preliminary data from China and Italy during the covid-19 pandemic offer further evidence; healthcare workers in China reported depression (in 50.3%), anxiety (44.6%), and insomnia (34.0%). 3 4 Concerns about these data are compounded by high rates of pre-existing mental health and substance use disorders in this population, 5 with physicians having rates of suicide among the highest of any profession. 68][9] Less is known about interventions for the mental health of healthcare workers during pandemics.
Abstract 20300: Microvascular Obstruction in Non Infarct Related Coronary Arteries in an Independent Predictor of Major Adverse Cardiovascular Events in ST Segment Elevation Myocardial Infarction Patients
Authors: Reza Khorramirouz, Michel T Corban, Shi-Wei Yang, John P Bois, Thomas A Foley, Lilach O Lerman, Amir Lerman
Journal: Circulation (2017)

Background: Coronary microvascular disease has been associated with increased myocardial ischemia and adverse cardiovascular events (MACE). The prognostic value of non-infarct-related coronary arte...
Abstract 15158: Ultrasound Guided Microbore Vascular Access for Pacemakers is Associated With the Lowest Rate of Venous Access Related Complications
Authors: Patrick Hayle, Daniel Garner, Dylmitr Rittoo, Nick Newall
Journal: Circulation (2018)

Introduction: We have innovated ultrasound (US) guided vascular access for pacemaker implantation through two iterations. Hypothesis: We sought to determine success rates and complications arising ...