tbuckley/cabot-search huggingface dataset:
A DROP-IN Gamma Probe for Robot-assisted Radioguided Surgery of Lymph Nodes During Radical Prostatectomy
Authors: Paolo Dell’Oglio, Philippa Meershoek, Tobias Maurer, Esther M.K. Wit, Pim J. van Leeuwen, Henk G. van der Poel, Fijs W.B. van Leeuwen, Matthias N. van Oosterom
Journal: European Urology (2020)

The DROP-IN gamma probe was introduced to overcome the restricted manoeuvrability of traditional laparoscopic gamma probes. Through enhanced manoeuvrability and surgical autonomy, the DROP-IN promotes the implementation of radioguided surgery in the robotic setting. To confirm the utility and safety profile of the DROP-IN gamma probe and to perform a comparison with the traditional laparoscopic gamma probe and fluorescence guidance. Twenty-five prostate cancer patients were scheduled for a robot-assisted sentinel lymph node (SN) procedure, extended pelvic lymph node dissection, and prostatectomy at a single European centre. After intraprostatic injection of indocyanine green (ICG)-99mTc-nanocolloid (n = 12) or 99mTc-nanocolloid + ICG (n = 13), SN locations were defined using preoperative imaging. Surgical excision of SNs was performed under image guidance using the DROP-IN gamma probe, the traditional laparoscopic gamma probe, and fluorescence imaging. Intraoperative SN detection was assessed for the different modalities and related to anatomical locations. Patient follow-up was included (a median of 18 mo). Overall, 47 SNs were pursued in vivo by the DROP-IN gamma probe, of which 100% were identified. No adverse events related to its use were observed. In vivo fluorescence imaging identified 91% of these SNs. The laparoscopic gamma probe identified only 76% of these SNs, where the detection inaccuracies appeared to be related to specific anatomical regions. Owing to improved manoeuvrability, the DROP-IN probe yielded improved SN detection rates compared with the traditional gamma probe and fluorescence imaging. These findings underline that the DROP-IN technology provides a valuable tool for radioguided surgery in the robotic setting. Radioguided robot-assisted surgery with the novel DROP-IN gamma probe is feasible and safe. It enables more efficient intraoperative identification of sentinel lymph nodes than can be achieved with a traditional laparoscopic gamma probe. The use of the DROP-IN probe in combination with fluorescence imaging allows for a complementary optical confirmation of node localisations.
Abstract 13752: Impact of Pre-ablation Weight Changes on Freedom From Atrial Fibrillation
Authors: Graham Peigh, Kelly Vogel, Rachel M Kaplan, Jeremiah Wasserlauf, Anna Pfenniger, Alexandru B Chicos, Rishi Arora, Susan Kim, Albert Lin, Nishant Verma, Kaustubha Patil, Bradley P Knight, Rod S Passman
Journal: Circulation (2020)

Introduction: Obesity is an established risk factor for recurrent atrial fibrillation (AF) after ablation. The impact of pre-procedure weight changes on freedom from AF (FFAF) post-ablation in both obese and non-obese patients is unknown. Hypothesis: Weight gain over the year prior to AF ablation is associated with reduced FFAF. Methods: A single-center retrospective cohort study of patients undergoing AF ablation using cryoballoon (CBA) was performed. Prior to ablation, all candidates were encouraged to adopt healthy lifestyle habits according to AHA guidelines, including weight loss, by their treating physician. Inclusion criteria included availability of weight measurements 1-year prior to and at the time of CBA, and post-CBA follow up &gt; 90 days. The primary endpoint was FFAF through 1-year after the 3-month blanking period. Results: Among 747 CBA performed from 2011-2017, 720 patients (49% male; average age 61.3 ± 10.3 years) met inclusion criteria. Of these, 241 patients (33.5%) were obese (body mass index ≥ 30) and 337 (46.8%) had non-paroxysmal AF. There were 9.5 ± 2.8 freezes per patient and 99 patients had additional ablation lesion sets delivered. Overall, FFAF was observed in 506 (70.3%) patients at 15 months. Multivariate analysis revealed that weight loss (p&lt;0.001), paroxysmal AF (p=0.036), shorter duration of AF diagnosis (p=0.022) and absence of AF during the 90-day blanking period (p&lt;0.001) were associated with FFAF. Kaplan-Meier estimates of FFAF by pre-ablation weight changes in obese and non-obese patients are shown in Figure 1a-b. In obese and non-obese patients, weight loss was associated with FFAF in a dose- dependent and binary manner, respectively. Conclusions: Weight gain in the year prior to AF ablation was associated with lower rates of FFAF regardless of baseline BMI. Patient directed weight loss should be encouraged prior to AF ablation.
Effectiveness of Capsule Endoscopy and Double-Balloon Enteroscopy in Suspected Complicated Celiac Disease
Authors: Francesca Ferretti, Federica Branchi, Stefania Orlando, Leda Roncoroni, Giulio Barigelletti, Sabrina Fabiano, Maurizio Vecchi, Roberto Penagini, Luisa Doneda, Luca Elli
Journal: Clinical Gastroenterology and Hepatology (2020)
Generation of uniform liver spheroids from human pluripotent stem cells for imaging-based drug toxicity analysis
Authors: Gyunggyu Lee, Hyemin Kim, Ji Young Park, Gyeongmin Kim, Jiyou Han, Seok Chung, Ji Hun Yang, Jang Su Jeon, Dong-Hun Woo, Choongseong Han, Sang Kyum Kim, Han-Jin Park, Jong-Hoon Kim
Journal: Biomaterials (2020)
Abstract 15324: Mavacamten Favorably Impacts Key Pathophysiologic Processes in Obstructive Hypertrophic Cardiomyopathy: Results From the EXPLORER-HCM Study
Authors: Sheila M Hegde, Theodore P Abraham, Daniel Jacoby, Andrew Wang, Carolyn Ho, Wanying Li, Amy J Sehnert, Scott D Solomon, iacopo olivotto, Steven J Lester
Journal: Circulation (2020)

Introduction: Obstructive hypertrophic cardiomyopathy (oHCM) is characterized by dynamic LV outflow tract (LVOT) obstruction resulting from ventricular hypertrophy and mitral valve systolic anterior motion (SAM), and by elevated left ventricular (LV) filling pressures, all of which result in a significant morbidity despite medical therapy. Mavacamten (Mava) is a novel inhibitor of cardiac myosin that significantly reduces LVOT gradients in oHCM, noted initially in the phase 2 PIONEER and more recently in the phase 3 EXPLORER-HCM studies. Additional echocardiographic analyses were performed to investigate the effect of Mava on focused measures of cardiac structure and function in oHCM. Methods: EXPLORER-HCM (NCT03470545) was a multicenter, double-blind, placebo-controlled, phase 3 study that randomized symptomatic oHCM patients (LV ejection fraction ≥55% and resting and/or provoked LVOT gradient ≥50 mmHg) 1:1 to Mava vs placebo for 30 weeks. Echocardiograms were performed serially every 2-4 weeks over 30 weeks. Results: In total, 251 patients with oHCM were enrolled and 244 patients completed the study (mean age 58.5; 40.6% female). Compared to placebo, 30-week treatment with Mava led to significant reductions in LA volume index (-7.5 ml/m 2 , p&lt;0.0001), lateral E/e’ (-3.8, p&lt;0.0001), septal E/e’ (-3.4, p&lt;0.0001), and LV mass index (-15.5 g/m 2 , p&lt;0.0001) ( Table ). Significantly more Mava-treated patients achieved resolution of mitral valve SAM compared to placebo (80.9% vs 34.0% of patients; difference of 46.8%; p&lt;0.0001) and mitral regurgitation (MR) (9.0% vs 0.0% of patients; difference of 9.0%; p=0.0006). Conclusions: Treatment with Mava for 30 weeks led to improvement in LV hypertrophy and markers of left-sided filling pressures (LA volume and E/e’). Furthermore, Mava treatment was associated with reduction of SAM and MR. These findings suggest that Mava has beneficial effects on several adverse pathophysiologic processes that are hallmarks of oHCM.
Abstract 16186: Intravascular Ultrasound-guided Surgical Unroofing in Symptomatic Patients With Myocardial Bridging of the Left Anterior Descending Artery
Authors: Takehiro Hashikata, Yasuhiro Honda, Hanjay Wang, Vedant S Pargaonkar, M Brooke Hollak, Ian S Rogers, Paul G Yock, Peter Fitzgerald, Ingela Schnittger, Jack Boyd, Jennifer A Tremmel
Journal: Circulation (2020)

Introduction: Myocardial bridging (MB) has been shown to cause significant clinical symptoms or adverse cardiac events in patients with no obstructive coronary artery disease. In contrast to medical therapy or stent placement with controversial efficacy, surgical unroofing (supra-arterial myotomy) of MB is considered to directly address the pathology with durable normalization of the altered hemodynamics. In this context, preoperative IVUS assessment can provide a precise map of the MB to guide the unroofing procedure, but it remains unclear if any IVUS parameter is related to the efficacy of this treatment. Methods: We evaluated 94 consecutive patients who underwent MB unroofing with serial (preoperative and 6-month follow-up) angina assessments using the Seattle Angina Questionnaire (SAQ). The primary outcome was the SAQ summary score, obtained by averaging the scores of physical limitation, angina frequency, and quality of life. Preoperative IVUS determined total MB length, halo thickness, arterial compression rate, maximal plaque burden upstream of MB, and septal branches originating in the tunneled LAD segment. Results: In all cases, preoperative IVUS successfully offered a geographic MB map with quantitative characteristics: MB length = 27.5 (20.2 to 40.3) mm, halo thickness = 0.54 (0.41 to 0.75) mm, arterial compression rate = 34 (26 to 43)%, and plaque burden = 34 (20 to 46)% [median (range) for all]. MB unroofing resulted in significant symptomatic improvements across all scales of SAQ (p&lt;0.001 for all) as well as the SAQ summary score (Figure), without any death or major complications. No significant correlation was observed between the preoperative IVUS parameters and the change in SAQ summary score after the surgery. Conclusions: IVUS-guided surgical unroofing safely and effectively achieved significant symptomatic improvements in patients with MB, regardless of the morphologic or morphometric MB characteristics assessed by preoperative IVUS.
Abstract 14885: E/e’ Does Not Consistently Track Left Atrial Pressure When Venous Return is Altered
Authors: James P Macnamara, Vivek Koshti, Erin Howden, JUstin Lawley, Christopher Hearon, Katrin Dias, Satyam Sarma, Benjamin D LEVINE
Journal: Circulation (2020)

Introduction: The E/e’ ratio is often used as a surrogate for left atrial pressure (LAP) despite concerns about reliability and accuracy when LAP is sequentially changed within individuals. This study tested how E/e’ tracks linearly with LAP with the aim of determining if invasive markers of diastolic function are associated with better tracking. Methods: Healthy subjects (n = 61, age 52±5 years) underwent manipulation of LAP with 2 levels of lower body negative pressure (LBNP -15 mm Hg, -30mm Hg) and 2 levels of rapid normal saline infusion (NS +15 mL/kg/min, +30 mL/kg/min) with a right heart catheter and echocardiography to define the LV end-diastolic pressure-volume relationship. E/e’ and pulmonary capillary wedge pressure (PCWP) were measured at each condition. Myocardial stiffness was calculated by the slope of the LV pressure-volume curve. LV relaxation was assessed with Tau: (Isovolumetric relaxation time/(ln(Systolic Blood Pressure x 0.9)-ln(PCWP)). R 2 of individual regressions of E/e’ and PCWP for each subject was used to determine quality of tracking across loading conditions. Results: PCWP ranged from 5 mm Hg to 20 mm Hg across loading conditions (p &lt;0.001). As a group, E wave velocity demonstrated a consistent linear relationship with PCWP while e’ was more variable (Figure) . The mean r 2 of individual regressions was 0.50 ± 0.29 with a high coefficient of variation of 57.1%. Higher baseline PCWP, myocardial stiffness or longer LV relaxation were not associated with improved tracking (p = 0.96, p = 0.55, p = 0.62 respectively). Conclusion: This study, the largest cohort to date with experimental altered LAP, highlights the difficulty assessing E/e’: As a cohort, E/e’ tracked with PCWP moderately well, but there was significant variation on an individual level which was independent of baseline LV filling pressure, stiffness and relaxation. Caution should be used when interpreting E/e’ as LAP in healthy individuals even with abnormalities in diastolic filling.
Exosomes derived from <i>Fusobacterium nucleatum</i>-infected colorectal cancer cells facilitate tumour metastasis by selectively carrying miR-1246/92b-3p/27a-3p and CXCL16
Authors: Songhe Guo, Jun Chen, Fangfang Chen, Qiuyao Zeng, Wan-Li Liu, Ge Zhang
Journal: Gut (2020)

Objective Exosomes released from tumour cells are packed with unique RNA and protein cargo, and they are emerging as an important mediator in the communication network that promotes tumour progression. The facultative intracellular bacterium Fusobacterium nucleatum (Fn) is an important colorectal cancer (CRC)-associated bacterium. To date, the function of exosomes from Fn-infected CRC cells has not been explored. Design Exosomes were isolated by sequential differential centrifugation and verified by transmission electron microscopy, NanoSight analysis and Western blotting. Given that exosomes have been shown to transport miRNAs and proteins to alter cellular functions, we performed miRNA sequencing and proteome analysis of exosomes from Fn-infected and non-infected cells. The biological role and mechanism of exosomes from Fn-infected cells in CRC tumour growth and liver metastasis were determined in vitro and in vivo. Results We demonstrated that exosomes delivered miR-1246/92b-3p/27a-3p and CXCL16/RhoA/IL-8 from Fn-infected cells into non-infected cells to increase cell migration ability in vitro and promote tumour metastasis in vivo. Finally, both circulating exosomal miR-1246/92b-3p/27a-3p and CXCL16 levels were closely associated with Fn abundance and tumour stage in patients with CRC. Conclusion This study suggests that Fn infection may stimulate tumour cells to generate miR-1246/92b-3p/27a-3p-rich and CXCL16/RhoA/IL-8 exosomes that are delivered to uninfected cells to promote prometastatic behaviours.
Abstract 15805: Longitudinal Changes in Univentricular Patients Pre-Bidirectional Cavopulmonary Connection and Pre-Fontan
Authors: Safwat Aly, Christopher Lam, Shi-Joon Yoo, Mike Seed, Rajiv Chaturvedi
Journal: Circulation (2020)

Background: Little is known about serial changes in the physiology of single ventricle (SV) patients during staged palliation and if HLHS patients differ from the rest. Methods: We analyzed SV patients who had a combined cath with CMR at both the preBCPC and preFontan studies from 2016-2019. Flow contrast mapping used to calculate pulmonary arterial (Qpa) and venous (Qpv) flow. Systemic blood flow (Qs) calculated using [superior vena cava (SVC) flow + descending aortic flow at the level diaphragm]. Cerebral vascular resistance (CVRi) calculated using [ascending aortic pressure (AoP)-right atrial pressure (RAP)/SVC flow]. Systemic vascular resistance (SVR) calculated using [(AoP-RaP)/Qs]. Pulmonary vascular resistance (PVR) was calculated using [(mean PAP - LAP)/Qpv]. Results: 30 patients were found, 10 with HLHS. The BCPC unloaded the heart, EDVi fell from preBCPC to preFontan. From preBCPC to preFontan(Table1): PA flow fell, but was compensated by increased APC flow to keep QpQs~1, PApressure and PVRi fell. Compared to others, the HLHS patients had larger hearts (EDVi) and lower PA but higher APC flow at both preBCPC(Table2)and preFontan(Table3). By preFontan, HLHS patients had worse function: higher ESVi, lower EF. Conclusion: QpQs ~1 is maintained by increase in APC flow. HLHS hearts are larger and deteriorate progressively.
Abstract 14066: <i>O</i> -GlcNAc Levels Stimulation is a New Potential Therapeutic Strategy at the Early Phase of Septic Shock in the Young
Authors: Thomas DUPAS, Manon DENIS, Justine Dontaine, Laurent Bultot, Antoine Persello, Angelique Erraud, Edith Bigot, Didier Vertommen, Jacques Lebreton, Arnaud tessier, Michel De Waard, Chantal Gauthier, Luc Bertrand, Bertrand R Rozec, Benjamin Lauzier
Journal: Circulation (2020)

Background: We have shown that increase in O -GlcNAc levels, a post-translational modification involved in the stress response, at the early phase of septic shock in adult (84 days old rats) is a potential new therapeutic strategy. Most studies focus in adults while the population most affected by septic shock, young children, is rarely studied. Considering that O- GlcNAc levels are higher in the young, the impact of O- GlcNAc on septic shock in the young should be tested. Purpose: Evaluate if O- GlcNAc stimulation could improve sepsis outcomes in young. Methods: Endotoxemic shock was induced in 28 days old rats with an i.v. injection of saline (CTRL, n=10) or LPS (O111:B4, 20mg.kg -1 - LPS, n=9). 1 hour after LPS rats were randomly assigned to no therapy (LPS), fluidotherapy (saline, 10ml.kg -1 - LPS+R, n=10) ± NButGT (10 mg.kg -1 - NButGT, n=11) to increase O- GlcNAc levels. 2 hours later, physiological functions and markers of severity were measured and used in adapted Pediatric RISk of Mortality score (PRISM score). The impact of treatment on survival was evaluated on n=16 per group. Mass spectrometry (MS) study was performed to identify O -GlcNAcylated proteins. Results: LPS induce a shock (mean arterial pressure (MAP): CTRL: 67.2 ± 1.9; LPS: 50.7 ± 2.1; mmHg; p&lt;0.05), alter biological parameters (lactates: CTRL: 3.92 ± 0.26; LPS: 6.42 ± 0.45; mmol.l -1 ; pH: CTRL: 7.27 ± 0.02; LPS: 7.15 ± 0.02; p&lt;0.05), PRISM score (p&lt;0.05) and is associated with multi organs dysfunction (troponin T: CTRL: 19.7 ± 4.0; LPS: 45.4 ± 11.4; ng.l -1 ; creatinine: CTRL: 15.9 ± 1.5; LPS: 25.3 ± 2.6; μmol.l -1 ; p&lt;0.05). LPS+R has no beneficial effect while NButGT improves MAP (p&lt;0.05), PRISM score (p&lt;0.05) and the median survival (NButGT: 36.0; LPS+R: 13.65; hours; p&lt;0.001) compared to LPS+R treatment. MS highlight important variations of O- GlcNAcylation particularly that of mitochondrial proteins. Conclusions: Despite higher O- GlcNAc levels, we demonstrate that O- GlcNAc stimulation is also a potential new therapeutic strategy for septic shock in young. Our results show that it is the difference between the basal levels and the post-stimulation levels which induces a protection against sepsis. Proteins identify by MS will need to be specifically studied to decipher their impact in septic shock.
Abstract 16999: Utilization of Recommended Guidelines Across States for the Annual Preparticipation Physical Evaluation of Adolescent Athletes
Authors: Zane Blank, JEFFREY ROBINSON, Robert L Spicer
Journal: Circulation (2020)

Introduction: Annual preparticipation physical evaluation (PPE) is used to screen adolescents for potential causes of sudden cardiac death prior to competitive athletics. While screening varies by state, the AHA published 14 recommended screening criteria in 2014. This study sought to define utilization of the 14 screening elements for high school athletes in the 50 states. Methods: PPE forms were requested from the high school athletics governing body of each state. Forms were analyzed to identify which of the 14 elements were explicitly fulfilled. Comparisons were made to the prior 12-point screening criteria (2007). Additional forms from private organizations or other professional societies were excluded. Results: A total of 48 states (96%) had PPE forms posted online and publicly accessible. The remaining 2 states (4%) deferred the specific method of PPE documentation to individual school districts and provided no standardized form. Of the 48 states providing forms, 13 (27%) included all 14 AHA screening elements. The median criteria met by each state was 11 (range 3-14). The 2 elements added by the AHA in 2014 (“prior restriction from participation in sports” and “prior testing for the heart, ordered by a physician”) were included by 42 (88%) and 36 (75%) states, respectively, with 13 (27%) states missing at least 1 of these. The 3 criteria most commonly absent were 1) examination of femoral pulses to exclude coarctation (58%), 2) family history of “hypertrophic or dilated cardiomyopathy, long-QT syndrome, or other ion channelopathies, Marfan syndrome, or clinically significant arrhythmias, or specific knowledge of genetic cardiac conditions in family members” (31%), and 3) personal history of elevated systemic blood pressure (27%). There was no difference in the number of states fulfilling all current 14-point criteria (13, 27%) versus the prior 12-point criteria (13, 27%) ( p =NS). Conclusions: Annual preparticipation forms are intended to improve the health and safety of athletes; however, a minority of states currently include all 14 screening criteria from the AHA. As athlete wellness and the prevention of sudden cardiac death remain national priorities, interventions are needed to increase inclusion of recommended criteria across all states.
Results from the IRoc-GN international registry of patients with COVID-19 and glomerular disease suggest close monitoring
Authors: Meryl Waldman, Maria Jose Soler, Clara García-Carro, Liz Lightstone, Tabitha Turner-Stokes, Megan Griffith, Joan Torras, Laura Martinez Valenzuela, Oriol Bestard, Colin Geddes, Oliver Flossmann, Kelly L. Budge, Chiara Cantarelli, Enrico Fiaccadori, Marco Delsante, Enrique Morales, Eduardo Gutierrez, Jose A. Niño-Cruz, Armando J. Martinez-Rueda, Giorgia Comai, Claudia Bini, Gaetano La Manna, Maria F. Slon, Joaquin Manrique, Irene Agraz, Ninet Sinaii, Paolo Cravedi
Journal: Kidney International (2020)

The effects of SARS-CoV-2 infection on individuals with immune-mediated glomerulonephritis, who are often undergoing immunosuppressive treatments, are unknown. Therefore, we created the International Registry of COVID infection in glomerulonephritis (IRoc-GN) and identified 40 patients with glomerulonephritis and COVID-19 followed in centers in North America and Europe. Detailed information on glomerulonephritis diagnosis, kidney parameters, and baseline immunosuppression prior to infection were recorded, as well as clinical presentation, laboratory values, treatment, complications, and outcomes of COVID-19. This cohort was compared to 80 COVID-positive control cases from the general population without glomerulonephritis matched for the time of infection. The majority (70%) of the patients with glomerulonephritis and all the controls were hospitalized. Patients with glomerulonephritis had significantly higher mortality (15% vs. 5%, respectively) and acute kidney injury (39% vs. 14%) than controls, while the need for kidney replacement therapy was not statistically different between the two groups. Receiving immunosuppression or renin-angiotensin-aldosterone system inhibitors at presentation did not increase the risk of death or acute kidney injury in the glomerulonephritis cohort. In the cohort with glomerulonephritis, lower serum albumin at presentation and shorter duration of glomerular disease were associated with greater risk of acute kidney injury and need for kidney replacement therapy. No differences in outcomes occurred between patients with primary glomerulonephritis versus glomerulonephritis associated with a systemic autoimmune disease (lupus or vasculitis). Thus, due to the higher mortality and risk of acute kidney injury than in the general population without glomerulonephritis, patients with glomerulonephritis and COVID-19 should be carefully monitored, especially when they present with low serum albumin levels.