tbuckley/cabot-search huggingface dataset:
Endoscopic Management Of Individuals At High-Risk Of Gastrointestinal Cancer: A Multicentre Survey In Spain
Authors: J López-Vicente, D Rodriguez Alcalde, L Hernández Villalba, M López-Cerón Pinilla, E Ulloa Márquez
Journal: Endoscopy (2021)

Aims Population at increased lifetime risk of gastrointestinal cancer, due to hereditary factors as Lynch syndrome (LS), familial adenomatous polyposis (FAP), hereditary diffuse gastric cancer (HDGC), or due to self-conditions as serrated polyposis syndrome (SPS) or inflammatory bowel disease (IBD), need specific endoscopic surveillance. Recently several European and American Endoscopy Societies have published guidelines concerning the endoscopic management of these high-risk cancer syndromes. The aim of our study was to determine how these patients are handled in our endoscopy units and if guidelines recommendations are followed.
TCTAP C-097 Patience is Virtue: Thrombectomy, Watchful Waiting Followed by Intravascular Ultrasound (IVUS) Guided Percutaneous Coronary Intervention in a Case of High Thrombus Burden
Authors: Quah Wy Jin, Afrah Yousif Adam Haroon, Rhuban Sundran, Balachandran Kandasamy
Journal: Journal of the American College of Cardiology (2021)
Lubiprostone for Pediatric Functional Constipation: Randomized, Controlled, Double-Blind Study With Long-term Extension
Authors: Marc A. Benninga, Sunny Z. Hussain, Manu R. Sood, Samuel Nurko, Paul Hyman, Robert A. Clifford, Molly O’Gorman, Taryn Losch-Beridon, Shadreck Mareya, Peter Lichtlen, Carlo Di Lorenzo
Journal: Clinical Gastroenterology and Hepatology (2021)

Background & AimsPediatric functional constipation (PFC) is a common problem in children that causes distress and presents treatment challenges to health care professionals. We conducted a randomized, placebo-controlled trial (study 1) in patients with PFC (6–17 years of age) to evaluate the efficacy and safety of lubiprostone, followed by an open-label extension for those who completed the placebo-controlled phase (study 2).MethodsStudy 1 (NCT02042183) was a phase 3, multicenter, randomized, double-blind, placebo-controlled, 12-week study evaluating the efficacy and safety of lubiprostone 12 μg twice daily (BID) and 24 μg BID. Study 2 (NCT02138136) was a phase 3, long-term, open-label extension of study 1. In both studies, lubiprostone doses were based on patients' weight. Efficacy was assessed solely based on study 1, with a primary endpoint of overall spontaneous bowel movement (SBM) response (increase of ≥1 SBM/wk vs baseline and ≥3 SBMs/wk for ≥9 weeks, including 3 of the final 4 weeks).Results606 patients were randomized to treatment (placebo: n = 202; lubiprostone: n = 404) in study 1. No statistically significant difference in overall SBM response rate was observed between the lubiprostone and placebo groups (18.5% vs 14.4%; P = .2245). Both the 12-μg BID and 24-μg BID doses of lubiprostone were well tolerated in the double-blind and extension phases, with a safety profile consistent with that seen in adult studies.ConclusionsLubiprostone did not demonstrate statistically significant effectiveness over placebo in children and adolescents with PFC but did demonstrate a safety profile similar to that in adults. (ClinicalTrials.gov: Number: NCT02042183; Number: NCT02138136).
A Systematic Review and Meta-analysis of the Effectiveness and Toxicities of Lutetium-177–labeled Prostate-specific Membrane Antigen–targeted Radioligand Therapy in Metastatic Castration-Resistant Prostate Cancer
Authors: Mohammad S Sadaghiani, Sara Sheikhbahaei, Rudolf A Werner, Kenneth J Pienta, Martin G Pomper, Lilja B Solnes, Michael A Gorin, Nae-Yuh Wang, Steven P Rowe
Journal: European Urology (2021)
Evaluation of relationship between myocardial contractile state and left ventricular function in patients with aortic regurgitation.
Authors: W FShen, G SRoubin, C YChoong, B FHutton, P JHarris, P JFletcher, D TKelly
Journal: Circulation (1985)

We studied the relationship between myocardial contractile state and left ventricular functional response to exercise in 14 asymptomatic patients with isolated moderate-to-severe aortic regurgitation and six control subjects. The slope of the systolic blood pressure-left ventricular end-systolic volume (pressure-volume) relationship determined by radionuclide ventriculography during angiotensin infusion was used as an indirect measure of myocardial contractility and was compared with left ventricular ejection fraction at rest and during both isometric handgrip and dynamic bicycle exercise. The slope of the pressure-volume relationship was significantly lower in patients with aortic regurgitation than in the control subjects (1.75 +/- 0.57 vs 2.78 +/- 0.42, p less than 0.01). The slope correlated exponentially with resting ejection fraction and was linearly related to changes in left ventricular ejection fraction during both handgrip and bicycle exercise. In patients with aortic regurgitation, resting ejec...
Rapid classification of positive blood cultures
Authors: J. R. Johnson
Journal: JAMA (1992)

<h3>To the Editor.</h3> —The authors of a recent study<sup>1</sup>evaluating the interpretation of positive blood cultures are to be commended for publicizing the unglamorous but important truth that infectious disease specialists commonly categorize positive blood cultures as reflecting true bacteremia as opposed to contamination, based on a few simple clinical and laboratory parameters. Whether it was really necessary to perform complex statistical analyses on an extensive data set to reach the study's conclusions is arguable, since the same conclusions probably could have been arrived at equally well through brief conversations with the participating infectious diseases specialists. The important point is that infectious disease specialists do indeed use time to culture positivity, number of cultures positive, organism type, and the pretest clinical likelihood of bacteremia to assess the validity of a positive blood culture. Infection at a different site caused by the same organism is also an important consideration; this
Functional and neurochemical evidence for partial cardiac sympathetic reinnervation after cardiac transplantation in humans.
Authors: D MKaye, MEsler, BKingwell, GMcPherson, DEsmore, GJennings
Journal: Circulation (1993)

BACKGROUNDThe presence of cardiac reinnervation in humans after cardiac transplantation has been widely debated, based on the application of differing methods for the assessment of neuronal function. Some of these techniques have been rather indirect; consequently, the time course and extent of cardiac reinnervation remains uncertain.METHODS AND RESULTSTo test for the presence of cardiac reinnervation after transplantation, we examined neurochemical (radiolabeled norepinephrine [NE] kinetics) and functional markers (power spectral analysis, heart rate response to exercise) of cardiac sympathetic nerve integrity in 15 cardiac transplantation recipients and 25 healthy control subjects of similar age. Cardiac transplantation subjects were studied 9 weeks to 8 years after cardiac transplantation (10  patients   2 years after cardiac transplantation). At rest, cardiac NE spillover was markedly attenuated early after transplantation (11.2 +/- 18.3 pmol/min) compared with...
Randomized Clinical Comparison of the Dual-Therapy CD34 Antibody-Covered Sirolimus-Eluting Combo Stent With the Sirolimus-Eluting Orsiro Stent in Patients Treated With Percutaneous Coronary Intervention: The SORT OUT X Trial
Authors: Lars Jakobsen, Evald H. Christiansen, Phillip Freeman, Johnny Kahlert, Karsten Veien, Michael Maeng, Bent Raungaard, Julia Ellert, Anton B. Villadsen, Steen D. Kristensen, Ole Ahlehoff, Martin K. Christensen, Christian J. Terkelsen, Hans Erik Bøtker, Jens Aaroe, Troels Thim, Leif Thuesen, Ahmed Aziz, Ashkan Eftekhari, Rebekka V. Jensen, Nicolaj B. Støttrup, Jeppe G. Rasmussen, Anders Junker, Svend E. Jensen, Henrik S. Hansen, Lisette O. Jensen
Journal: Circulation (2021)

Background: Target lesion failure remains an issue with contemporary drug-eluting stents. Thus, the dual-therapy sirolimus-eluting and CD34+ antibody–coated Combo stent (DTS) was designed to further improve early healing. This study aimed to investigate whether the DTS is noninferior to the sirolimus-eluting Orsiro stent (SES) in an all-comers patient population. Methods: The SORT OUT X (Combo Stent Versus Orsiro Stent) trial, was a large-scale, randomized, multicenter, single-blind, 2-arm, noninferiority trial with registry-based follow-up. The primary end point target lesion failure was a composite of cardiac death, myocardial infarction, or target lesion revascularization within 12 months, analyzed using intention-to-treat. The trial was powered for assessing target lesion failure noninferiority of the DTS compared with the SES with a predetermined noninferiority margin of 0.021. Results: A total of 3146 patients were randomized to treatment with the DTS (1578 patients; 2008 lesions) or SES (1568 patients; 1982 lesions). At 12 months, intention-to-treat analysis showed that 100 patients (6.3%) assigned the DTS and 58 patients (3.7%) assigned the SES met the primary end point (absolute risk difference, 2.6% [upper limit of 1-sided 95% CI, 4.1%]; P (noninferiority)=0.76). The SES was superior to the DTS (incidence rate ratios for target lesion failure, 1.74 [95% CI, 1.26–2.41]; P =0.00086). The difference was explained mainly by a higher incidence of target lesion revascularization in the DTS group compared with the SES group (53 [3.4%] vs. 24 [1.5%]; incidence rate ratio, 2.22 [95% CI, 1.37–3.61]; P =0.0012). Conclusions: The DTS did not confirm noninferiority to the SES for target lesion failure at 12 months in an all-comer population. The SES was superior to the DTS mainly because the DTS was associated with an increased risk of target lesion revascularization. However, rates of death, cardiac death, and myocardial infarction at 12 months did not differ significantly between the 2 stent groups. Registration: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT03216733.
Werner Helicase Is a Synthetic-Lethal Vulnerability in Mismatch Repair–Deficient Colorectal Cancer Refractory to Targeted Therapies, Chemotherapy, and Immunotherapy
Authors: Gabriele Picco, Chiara M. Cattaneo, Esmée J. van Vliet, Giovanni Crisafulli, Giuseppe Rospo, Sarah Consonni, Sara F. Vieira, Iñigo Sánchez Rodríguez, Carlotta Cancelliere, Ruby Banerjee, Luuk J. Schipper, Daniele Oddo, Krijn K. Dijkstra, Jindrich Cinatl, Martin Michaelis, Fengtang Yang, Federica Di Nicolantonio, Andrea Sartore-Bianchi, Salvatore Siena, Sabrina Arena, Emile E. Voest, Alberto Bardelli, Mathew J. Garnett
Journal: Cancer Discovery (2021)

Abstract Targeted therapies, chemotherapy, and immunotherapy are used to treat patients with mismatch repair–deficient (dMMR)/microsatellite instability-high (MSI-H) colorectal cancer. The clinical effectiveness of targeted therapy and chemotherapy is limited by resistance and drug toxicities, and about half of patients receiving immunotherapy have disease that is refractory to immune checkpoint inhibitors. Loss of Werner syndrome ATP-dependent helicase (WRN) is a synthetic lethality in dMMR/MSI-H cells. To inform the development of WRN as a therapeutic target, we performed WRN knockout or knockdown in 60 heterogeneous dMMR colorectal cancer preclinical models, demonstrating that WRN dependency is an almost universal feature and a robust marker for patient selection. Furthermore, models of resistance to clinically relevant targeted therapy, chemotherapy, and immunotherapy retain WRN dependency. These data show the potential of therapeutically targeting WRN in patients with dMMR/MSI-H colorectal cancer and support WRN as a therapeutic option for patients with dMMR/MSI-H cancers refractory to current treatment strategies. Significance: We found that a large, diverse set of dMMR/MSI-H colorectal cancer preclinical models, including models of treatment-refractory disease, are WRN-dependent. Our results support WRN as a promising synthetic-lethal target in dMMR/MSI-H colorectal cancer tumors as a monotherapy or in combination with targeted agents, chemotherapy, or immunotherapy. This article is highlighted in the In This Issue feature, p. 1861
Role of high-risk antibiotic use in incidence of health-care-associated Clostridioides difficile infection in Quebec, Canada: a population-level ecological study
Authors: Elise Fortin, Daniel J G Thirion, Manale Ouakki, Christophe Garenc, Cindy Lalancette, Luc Bergeron, Danielle Moisan, Jasmin Villeneuve, Yves Longtin, Daniel Bolduc, Charles Frenette, Lise-Andrée Galarneau, Christophe Garenc, Cindy Lalancette, Yves Longtin, Vivian Loo, Muleka Ngenda Muadi, Natasha Parisien, Isabelle Rouleau, Noémie Savard, Josée Vachon, Jasmin Villeneuve
Journal: The Lancet Microbe (2021)

The incidence of health-care-associated Clostridioides difficile infections has been declining in the Canadian province of Quebec since 2015. We examined whether changes in high-risk antibiotic use could account for this decrease, as reported in other jurisdictions.We did a retrospective interrupted time-series analysis of 12 hospitals in the Canadian province of Quebec, representing a quarter of all health-care-associated C difficile infections in this region between April 1, 2012, and March 31, 2017. Data for high-risk antibiotic use (eg, amoxicillin-clavulanate, cephalosporins, fluoroquinolones, and clindamycin) in defined daily doses (DDDs) were extracted from local surveillance databases, and incidences of health-care-associated C difficile infections were extracted from provincial surveillance databases. We used hierarchical segmented Poisson regression to assess whether variations in rates of health-care-associated C difficile infections followed variations in antibiotic use.Overall, 4455 health-care-associated C difficile infections and 6 281 960 patient-days were reported in the 12 participating hospitals, representing around a quarter of the provincial data. A 50% decrease in the annual incidence of health-care-associated C difficile infections was recorded between 2012-13 and 2016-17 (9·4 infections per 10 000 patient-days vs 4·7 infections per 10 000 patient-days), and a 67% decrease in the proportion of these infections due to the NAP1/027 strain of C difficile was seen (64% in 2013 vs 21% in 2017). In total, 1 266 960 DDDs of high-risk antibiotics were distributed during the study period. An increasing time trend was noted in high-risk antibiotic use, reaching a total of 223 DDDs per 1000 patient-days in 2016-17. An increase of one DDD per 1000 patient-days was associated with a 0·2% increase in the rate of health-care-associated C difficile infections in the following 4-week period. A significant change in incidence of health-care-associated C difficile infections persisted despite adjustment for high-risk antibiotic use, as shown by a significant residual step change (0·825, 95% CI 0·731-0·932) and change in trend (0·987, 0·980-0·994).Changes in use of high-risk antibiotics do not entirely account for the sudden decrease in health-care-associated C difficile infections in the Canadian province of Quebec since 2015. Further studies are needed to understand factors implicated in the change in epidemiology of health-care-associated C difficile infections.Institut National de Santé Publique du Québec.
Pathophysiology of coronary artery spasm.
Authors: BFreedman, D RRichmond, D TKelly
Journal: Circulation (1982)

Coronary arterial measurements were made from cineangiograms in patients with positive and negative ergonovine tests. In those with positive tests, normal segments of arteries adjacent to the site of spasm and arteries without spasm showed no greater sensitivity to ergonovine than arteries from control patients (20 +/- 13% constriction vs 17 +/- 12%, NS). In patients with positive and negative ergonovine tests, constriction was measured at lesion sites after ergonovine and compared with values predicted from a geometric theory. The measured constriction was always greater than predicted in patients with a positive ergonovine test, and frequently less than predicted in patients with a negative test. The increased sensitivity of arteries that show localized vasospasm at lesion sites after ergonovine administration is not explained by geometry alone.
Sudden cardiac death in heart failure. The role of abnormal repolarization.
Authors: G FTomaselli, D JBeuckelmann, H GCalkins, R DBerger, P DKessler, J HLawrence, DKass, A MFeldman, EMarban
Journal: Circulation (1994)

Congestive heart failure is a common, highly lethal cardiovascular disorder claiming over 200,000 lives a year in the United States alone. Some 50% of the deaths in heart failure patients are sudden, and most of these are probably the result of ventricular tachyarrhythmias. Methods designed to identify patients at risk have been remarkably unrewarding, as have attempts to intervene and prevent sudden death in these patients. The failure to impact favorably on the incidence of sudden death in heart failure patients stems largely from a lack of understanding of the underlying mechanisms of arrhythmogenesis. This article explores the role of abnormalities of ventricular repolarization in heart failure patients. We will examine evidence for the hypothesis that alteration of repolarizing K+ channel expression in failing myocardium predisposes to abnormalities in repolarization that are arrhythmogenic. The possible utility of novel electrophysiological and ECG measures of altered ventricular repolarization will...
Homopolish: a method for the removal of systematic errors in nanopore sequencing by homologous polishing
Authors: Yao-Ting Huang, Po-Yu Liu, Pei-Wen Shih
Journal: Genome biology (2021)

Nanopore sequencing has been widely used for the reconstruction of microbial genomes. Owing to higher error rates, errors on the genome are corrected via neural networks trained by Nanopore reads. However, the systematic errors usually remain uncorrected. This paper designs a model that is trained by homologous sequences for the correction of Nanopore systematic errors. The developed program, Homopolish, outperforms Medaka and HELEN in bacteria, viruses, fungi, and metagenomic datasets. When combined with Medaka/HELEN, the genome quality can exceed Q50 on R9.4 flow cells. We show that Nanopore-only sequencing can produce high-quality microbial genomes sufficient for downstream analysis.
Coronary blood flow after the regression of pressure-overload left ventricular hypertrophy.
Authors: KIshihara, M RZile, MNagatsu, KNakano, MTomita, SKanazawa, LClamp, GDeFreyte, B ACarabello
Journal: Circulation Research (1992)

Abnormal coronary blood flow (CBF) in long-standing left ventricular (LV) pressure-overload hypertrophy has been associated with ischemia and LV dysfunction. Thus, goals of therapy in pressure overload are not only the relief of the overload itself but also regression in hypertrophy and subsequent improvement in CBF. However, little is known about CBF in humans or in large mammals after the relief of pressure overload, when the hypertrophy has regressed. This study was performed to test the hypothesis that, even 6 months after the relief of pressure overload in the dog, CBF would still be abnormal. Three groups of dogs were studied: 1) normal control dogs (NL group), 2) dogs with LV pressure-overload hypertrophy (LVH group), and 3) dogs that had developed LV pressure-overload hypertrophy but in whom the pressure overload was relieved 6 months before the final study (LVH Reg group). CBF was studied in conscious dogs by use of the radiolabeled microsphere technique at rest, during rapid atrial pacing, and d...
Comment on: Ekinci et al. Dietary Salt Intake and Mortality in Patients With Type 2 Diabetes. Diabetes Care 2011;34:703-709
Authors: Hiddo J. Lambers Heerspink, Arjan Kwakernaak, Dick de Zeeuw, Gerjan Navis
Journal: Diabetes Care (2011)

Ekinci et al. (1) report that lower 24-h urinary sodium excretion is paradoxically associated with an increased risk of all-cause and cardiovascular mortality in type 2 diabetes. They conclude, “Such data call into question universal recommendations that all adults should endeavor to reduce their salt intake.” The authors are to be commended for basing their prospective observational study on repeated 24-h urine excretions. However, we believe that their conclusions need to be treated with caution for several reasons.

First, as the authors also state, this is an observational study, prone to unmeasured and residual confounding that may have played a dominant role in eliciting these paradoxical results.

Second, and possibly a …
Relation between upper limit of vulnerability and defibrillation threshold in humans.
Authors: P SChen, G KFeld, J MKriett, M MMower, R YTarazi, R PFleck, C DSwerdlow, E SGang, R MKass
Journal: Circulation (1993)

BACKGROUNDIn the canine model, an  limit of shock strength exists that can induce ventricular fibrillation during the vulnerable period of the cardiac cycle. This shock strength (the  limit of vulnerability) closely correlates with the defibrillation threshold and supports the upper limit of  hypothesis of defibrillation. It is not known whether an  limit of vulnerability exists in humans or whether this limit correlates with the defibrillation threshold.METHODS AND RESULTSIn 13 patients undergoing implantable cardioverter-defibrillator implantation, the shock strengths associated with a 50% probability of reaching the  limit of vulnerability (ULV50) and a 50% probability of reaching the defibrillation threshold (DFT50) were determined by the up-down algorithm. The ULV50 was determined only for the mid-upslope of the positive T waves and for the mid-downslope of the negative T waves. No major complications occurred during surgery. An  limit of vulnerability was demo...
Coagulant activities of platelets in coronary artery disease.
Authors: A KRao, P DMintz, S JLavine, A ABove, M TMcDonough, J FSpann, P NWalsh
Journal: Circulation (1984)

Platelets have been implicated in the pathogenesis of coronary artery disease, and a number of studies have examined platelet function and coagulation parameters in such patients. We have examined platelet coagulant activities, volumes, and aggregate ratios in 23 patients with chest pain, seven of whom had normal coronary angiograms (group I) and 16 of whom had angiographically proven coronary artery disease (group II). There were no significant differences in the mean values for platelet volume or platelet aggregate ratios between the two groups. The platelet coagulant activities concerned with initiation and the early stages of intrinsic coagulation were significantly increased in patients in group II as compared with those in group I. No significant differences were noted between the two groups with respect to prothrombin time, partial thromboplastin time, and plasma levels of fibrinogen and coagulation factors V and VIII. However, the mean activity in plasma of antithrombin III (but not the level of a...
Dissolution of peripheral arterial thrombi by ultrasound.
Authors: MAriani, M CFishbein, J SChae, HSadeghi, A DMichael, S BDubin, R JSiegel
Journal: Circulation (1991)

BACKGROUNDWe have previously shown that continuous-wave ultrasound can rapidly dissolve human thrombi in vitro, with 99% of all residual particles measuring less than 10 microns in diameter. To assess the effects of pulsed-wave ultrasound energy on whole blood clots, 1) in vitro studies were preformed to assess precisely the rates of clot disruption and to quantify particulate size, and 2) in vivo studies were performed to assess the efficacy and safety of catheter-delivered ultrasound for intra-arterial thrombus dissolution.METHODS AND RESULTSIn vitro, we studied 50 samples of human whole blood clots and using an 89-cm-long wire probe, applied pulse-wave energies from 8 to 23 W. The corresponding peak-to-peak tip displacement range was 63.5 - 102 microns. We studied arterial thrombosis in vivo in 21 canine superficial femoral arteries. To produce an acute thrombosis, 200 units of thrombin followed by 2 ml of 72-hour-old autologous clot were injected into a 5-7-cm segment of femoral artery and left to coa...