tbuckley/cabot-search huggingface dataset:
Abstract 9197: Lesion Size and Adverse Event Profile of the TactiFlex™ Ablation Catheter, Sensor Enabled™ in a Porcine Thigh Model
Authors: Jed Overmann, Greg Ginn, Nicholas Ambrosius, Christopher Geurkink, Zada Thamavong, Jeffrey Fish
Journal: Circulation (2021)

Background: Advanced irrigated catheters, such as the FlexAbility™ Ablation Catheter, Sensor Enabled™ (FlexAbility SE), improve safety during RF ablation. Integration of contact force sensing technology with FlexAbility SE is clinically desirable to further enhance procedural efficacy and safety. Objective: To compare lesion size and adverse events in a perfused porcine thigh model for the TactiFlex™ Ablation Catheter, Sensor Enabled™ (TactiFlex SE) and its market-released predecessor, FlexAbility SE. Methods: Power controlled RF ablations were performed in 5 swine at either a nominal (30W, 60s; N=88) or maximum (50W, 10s; N=74) setting (20 g, 13 ml/min irrigation rate for all). Trials were balanced between parallel and perpendicular tip orientations. Coagulum formation, steam pops, char and lesion depth and width were documented. At each setting, lesion depth and width were assessed for equivalence between catheters (linear mixed model). Results for both orientations were pooled and adverse events were evaluated for non-inferiority of TactiFlex SE compared to FlexAbility SE (logistic regression). Results: Lesion depth and width were equivalent between TactiFlex SE and FlexAbility SE for all conditions (pre-specified- equivalence interval = ±1.67mm). TactiFlex SE was non-inferior to FlexAbility SE for rate of coagulum and char (pre-specified upper -non-inferiority margin = 20% ). No steam pops occurred with either catheter. Conclusion: The TactiFlex™ Ablation Catheter, Sensor Enabled™ produced equivalent lesion sizes and a favorable adverse event profile when compared to the FlexAbility™ Ablation Catheter, Sensor Enabled™ in a perfused porcine thigh model.
COVID-19 in Patients with Monoclonal Gammopathy of Undetermined Significance (MGUS): An Observational Retrospective Study
Authors: Nicola Sgherza, Paola Curci, Rita Rizzi, Silvio Tafuri, Pasquale Stefanizzi, Vanda Strafella, Daniela Di Gennaro, Angelantonio Vitucci, Antonio Palma, Antonella Vita Russo Rossi, Luigi Vimercati, Francesco Albano, Pellegrino Musto
Journal: Blood (2021)
Safety of Anti-NKG2A Blocking Antibody Monalizumab As Maintenance Therapy after Allogeneic Hematopoietic Stem Cell Transplantation: A Phase I Study
Authors: Raynier Devillier, Sabine Furst, Agnes boyer Chammard, Thomas Pagliardini, Samia Harbi, Valerio Maisano, Angela Granata, Faezeh Legrand, Jihane Pakradouni, jean Marie Boher, Cyril Fauriat, Anne-Sophie Chretien, Christian Chabannon, Norbert Vey, Eric Vivier, Daniel Olive, Didier Blaise
Journal: Blood (2021)
The Mucosally-Adherent Rectal Microbiota Contains Features Unique to Alcohol-Related Cirrhosis
Authors: Ting-Chin David Shen, Scott G. Daniel, Shivali Patel, Emily Kaplan, Lillian Phung, Kaylin Lemelle-Thomas, Lillian Chau, Lindsay Herman, Calvin Trisolini, Aimee Stonelake, Emily Toal, Vandana Khungar, Kyle Bittinger, K. Rajender Reddy, Gary D. Wu
Journal: Gut Microbes (2021)

Most studies examining correlations between the gut microbiota and disease states focus on fecal samples due to ease of collection, yet there are distinct differences when compared to samples collected from the colonic mucosa. Although fecal microbiota has been reported to be altered in cirrhosis, correlation with mucosal microbiota characterized via rectal swab has not been previously described in this patient population. We conducted a cross-sectional analysis using 39 stool and 39 rectal swabs from adult patients with cirrhosis of different etiologies and performed shotgun metagenomic sequencing. Bacterial growth studies were performed with Escherichia coli. Two asaccharolytic bacterial taxa, Finegoldia magna and Porphyromonas asaccharolytica, were increased in rectal swabs relative to stool (FDR < 0.01). Genomic analysis of the microbiome revealed 58 genes and 16 pathways that differed between stool and rectal swabs (FDR < 0.05), where rectal swabs were enriched for pathways associated with protein synthesis and cellular proliferation but decreased in carbohydrate metabolism. Although no features in the fecal microbiome differentiated cirrhosis etiologies, the mucosal microbiome revealed decreased abundances of E. coli and Enterobacteriaceae in alcohol-related cirrhosis relative to non-alcohol related cirrhosis (FDR < 0.05). In vitro bacterial culture studies showed that physiological concentrations of ethanol and its oxidative metabolites inhibited E. coli growth in a pH- and concentration-dependent manner. Characterization of the mucosally associated gut microbiome via rectal swab revealed findings consistent with amino acid/nitrogen abundance versus carbohydrate limitation in the mucosal microenvironment as well as unique features of alcohol-related cirrhosis possibly consistent with the influence of host-derived metabolites on the composition of mucosally adherent microbiota.
Abstract 11138: Impact of Heart Rate Reduction on Recurrence After Catheter Ablation of Persistent Atrial Fibrillation
Authors: Masato Okada, Koichi Inoue, Nobuaki Tanaka, Koji Tanaka, Yuko Hirao, Takafumi Oka, Masaharu Masuda, Yoshio Furukawa, Akio Hirata, Yasuyuki Egami, Tetsuya Watanabe, Hitoshi Minamiguchi, Miwa Miyoshi, Akihiro Sunaga, Yohei Sotomi, Tomoharu Dohi, Shungo Hikoso, Yasushi Sakata
Journal: Circulation (2021)

Introduction: Predicting heart rate (HR) after restoration of sinus rhythm (SR) remains one of the challenges when performing catheter ablation (CA) of persistent atrial fibrillation (AF). Objectives: To evaluate the association between pre-ablation HR during AF and post-ablation HR during SR, and whether the HR reduction is associated with AF recurrence. Methods: The analysis was performed from the EARNEST-PVI trial, a randomized controlled trial designed to assess a CA strategy for persistent AF, which was conducted in the Osaka region of Japan. After excluding patients with beta-blocker prescription, a total of 216 patients (median age, 67 years; 20% female; 23% long-standing persistent AF) with AF rhythm at baseline and SR at discharge were enrolled in this study. Baseline HR during AF and post-ablation HR during SR was measured on admission and at discharge using the 12-lead electrocardiograms, respectively. Results: There was a mild correlation between baseline HR (median 82 [interquartile range 72-95] bpm) and post-ablation HR (78 [48-117] bpm) (r = 0.27, p &lt;0.001). Reduction in HR was positively associated with baseline HR (r = 0.79, p &lt;0.001) and was negatively associated with post-ablation HR (r = - 0.37, p &lt;0.001). During the follow-up of 1 year, 56 patients (25.9%) experienced AF recurrence. HR reduction had the higher diagnostic accuracy in predicting AF recurrence than HR at baseline and HR after CA (area under the curve, 0.625; 95% confidence interval, 0.557-0.690; p = 0.003). AF recurrence rate was significantly higher in 141 patients with smaller HR reduction (cut-off, &lt;14bpm) than those with larger HR reduction (31.9% vs. 14.7%, p = 0.009). After adjustment of age, gender, long-standing persistent AF, and CA strategy, HR reduction of &amp;lt;14 bpm was a significant predictor of AF recurrence (hazard ratio, 2.32; 95% confidence interval, 1.20-4.51; p = 0.013). Conclusions: There was a mild correlation between HR during AF and HR after restoration of SR in patients underwent CA of persistent AF. HR reduction after restoration of SR predicted AF recurrence.
Abstract PO-076: Murine adapted FOLFIRINOX for standard-of-care in KPC mice
Authors: Martin C. Whittle, Aditi Palkar, Rachael Fasnacht, James Yan, Borith Kheng, Kianna Sinfuego, Shelley Thorsen, Sunil R. Hingorani
Journal: Cancer Research (2021)

Abstract Until relatively recently, the standard-of-care (SOC) treatment for pancreas cancer was not appreciably superior to best supportive care in prolonging life, and potentially new treatment strategies had a relatively modest bar to surmount. New combination regimens have emerged and novel therapies should therefore be compared against the current SOC. However, in preclinical development of novel agents, efficacy is frequently compared against vehicle control and less commonly against cytotoxic chemotherapy. Furthermore, virtually all studies of cytotoxic chemotherapy for PDA in mice have used gemcitabine (gem) monotherapy as standard-of-care, although this is no longer the standard for this disease. One of the current standard regimens, gem+nab-paclitaxel, cannot be given in mice without inducing immune responses because of the incorporation of human albumin in developing the taxol nanoparticles. The other new standard, FOLFIRINOX, is a complex 4-agent regimen that includes a 46-hour continuous infusion component that has been prohibitively challenging to deliver to animals. We have now built an appropriate dosing regimen incorporating these 4 agents that required a deliberate, step-by-step, program of empiric testing of the drugs, first, one at a time, then in various doublets and triplets, and, finally, as a whole regimen. The studies included close clinical evaluations and serial blood tests to follow complete blood counts (CBC). We have incorporated this regimen as the new SOC in our Murine Clinical Trials Program (MCTP). We propose that this mur-FOLIFIRINOX regimen should represent the new standard for murine studies. Citation Format: Martin C. Whittle, Aditi Palkar, Rachael Fasnacht, James Yan, Borith Kheng, Kianna Sinfuego, Shelley Thorsen, Sunil R. Hingorani. Murine adapted FOLFIRINOX for standard-of-care in KPC mice [abstract]. In: Proceedings of the AACR Virtual Special Conference on Pancreatic Cancer; 2021 Sep 29-30. Philadelphia (PA): AACR; Cancer Res 2021;81(22 Suppl):Abstract nr PO-076.
Pediatric Hydroxyurea Treatment Patterns, Sickle Cell Disease-Related Complication Rates, and Costs in a Large US Administrative Claims Database: A Retrospective Analysis
Authors: Deepa Manwani, Arthur Burnett, Jincy Paulose, Glorian P. Yen, Tanya Burton, Amy Anderson, Sara Wang, Soyon Lee, Santosh L. Saraf
Journal: Blood (2021)
Abstract 8931: The Role of Preoperative Hypertension on Neurocognitive Decline After Cardiac Surgery
Authors: Ronald K Phillips, Jun Feng, Guangbin Shi, Nicholas C Sellke, Laura A Scrimgeour, Afshin Ehsan, Frank W Sellke
Journal: Circulation (2021)

Introduction: Up to 80% of patients experience postoperative neurocognitive decline (pNCD) after cardiac surgery with cardiopulmonary bypass. Objective: We sought to identify the role of pre-op blood pressure (BP) control in pNCD and describe potential contributing mechanisms. Methods: Eligible patients undergoing cardiac surgery with the use of CPB were administered the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) preoperatively and at post-op day 4. We examined 31 patients in this pilot study, of whom 13 experienced pNCD. The highest systolic BP measured within 3 months (maxBP), and the average BP (aBP) taken at clinic visits within 1 year of surgery were used as metrics for BP. T-tests, chi-squared tests, and regression analyses were used. Blood samples were collected 6 hours preoperatively and at postop day 4 to assess cytokine levels (TNFa, C3a, CRP, IL-6) and mRNA expression using Applied Biosystems™ Clariom™ D Pico Assay. Results: Patients who maintained an aBP of ≥130mmHg had greater RBANS deficit than their counterparts (n=19, n=12 respectively; p&lt;0.005). There was also a linear relationship between aBP and RBANS score deficit (F&lt;0.04, adjusted R=11%). These relationships persisted within the younger half patients (n=16, p&lt;0.01) vs. older (n=15, p=0.16). Of patients with stage 2 hypertension or above (≥140mmHg, N=12) 67% experienced pNCD vs. 26% (p=0.02). Within hypertensive patients postoperatively, C3a was upregulated in patients who experienced pNCD (p&lt;0.04). Upon genomic analysis, macrophage markers were uniquely upregulated preoperatively, and genes involved in heme biosynthesis, glutathione synthesis, IL-10 inflammatory attenuation, and oxidative stress attenuation were downregulated postoperatively among patients who maintained an aBP of ≥130mmHg. Conclusions: BP control prior to surgery may play a role in pNCD. Genomic analysis explains a mechanism: upregulated immune response markers preoperatively and a weaker attenuation of oxidative stress and inflammation postoperatively. These effects are more robust among younger patients. The stage of preoperative hypertension may also influence the frequency of pNCD.
Abstract 9507: Evening Dosing of Antihypertensive Treatment is Not Associated With a Better Prognosis
Authors: Alejandro De La Sierra, Luis M Ruilope, Pablo Martinez-Camblor, Ernest Vinyoles, Manuel Gorostidi, Julian Segura, Bryan Williams
Journal: Circulation (2021)

Introduction: Night BP is the most powerful estimate of cardiovascular prognosis. It has been suggested that bedtime administration of antihypertensive therapy may favour night BP reduction and prognosis. Hypothesis: We aimed to evaluate the mortality risk in treated hypertensives, depending on the schedule of treatment administration (entirely in the morning, entirely at bedtime, or combined morning and evening) at the time ABPM was performed. Methods: Vital status and cardiovascular death were obtained from death certificates in 26751 treated hypertensives (mean age 62, 60% males), enrolled in the Spanish ABPM Registry, and having a valid 24-h ABPM at entry. Cox-models adjusted for clinical confounders and 24-hour systolic BP were used for HR calculation in groups depending on treatment administration. Results: Among the 26751 evaluable patients, most (76.7%) received their medication exclusively in the morning; 13% exclusively in the evening, and 10.3% in a multiple schedule both in the morning and in the evening. Mortality incidence in these 3 groups were 13.7, 17.8 and 21.8 per 1000 patients/year, respectively. Compared to patients receiving their antihypertensive medication entirely in the morning (reference group), those receiving their medication entirely in the evening did not show a significant increase in the HR for total mortality (1.06; 95%CI: 0.93-1.21) or in cardiovascular mortality (1.15; 0.93-1.41) after adjustment for clinical confounders and 24-hour systolic BP. Patients receiving their antihypertensive medication both in the morning and at bedtime had an increased risk for mortality (1.29; 1.14-1.48) and for cardiovascular mortality (1.46; 1.18-1.80). Additional analyses using double-robust propensity score yielded similar results. Conclusions: Morning or bedtime dosing of the antihypertensive medication has no effect on prognosis. We have found that patients receiving their medication in a multiple schedule, including morning and evening dosing have an increased risk of mortality and cardiovascular mortality, even after adjustment for confounders. However, we cannot exclude other aspects, such as a poorer treatment adherence, being the responsible of this worse prognosis.
Community Versus Academic Practice in Essential Thrombocythemia and Myelofibrosis: Differences in Clinical Characteristics, Diagnosis, Treatment Patterns, and Symptom Burden (Analysis of Data from the MOST Study)
Authors: Roger Lyons, David Lessen, Salman Fazal, Robyn Scherber, Patricia Kalafut, Haobo Ren, Ellen Ritchie
Journal: Blood (2021)
Prediction of Early Onset Cytokine Release Syndrome and Neurologic Events after Axicabtagene Ciloleucel in Large B-Cell Lymphoma Based on Machine Learning Algorithms
Authors: Qinghua Song, Tao Hu, Sattva S. Neelapu, Frederick L. Locke, Caron Jacobson, David B. Miklos, Olalekan O. Oluwole, Marie José Kersten, Max Topp, Jenny J. Kim, Kanwarjit Singh, Jorge Andrade, Lei Huang, Allen Xue, Marco Schupp, Myrna Nahas, Rhine R. Shen, Adrian Bot
Journal: Blood (2021)
Safety and efficacy of erythropoietin for the treatment of patients with optic neuritis (TONE): a randomised, double-blind, multicentre, placebo-controlled study
Authors: Wolf A Lagrèze, Sebastian Küchlin, Gabriele Ihorst, Birgit Grotejohann, Flemming Beisse, Martin Volkmann, Sven P Heinrich, Philipp Albrecht, Judith Ungewiss, Michael Wörner, Martin J Hug, Sebastian Wolf, Ricarda Diem, Philipp Albrecht, Orhan Aktas, Anna Beck, Anke Beckmann, Flemming Beisse, Achim Berthele, Lena Bönig, Ricarda Diem, Heike Elflein, Dirk Fitzner, Vinzenz Fleischer, Stefan Gingele, Birgit Grotejohann, Tanja Guthoff, Rainer Guthoff, Kathrin Hartmann, Andrea Hassenstein, Christoph Heesen, Katharina Hein, Sven P. Heinrich, Karsten Hufendiek, Martin J. Hug, Konstantin Huhn, Martin W. Hümmert, Gabriele Ihorst, Matthias Klopfer, Friedrich E. Kruse, Sebastian Küchlin, Tania Kümpfel, Wolf A. Lagrèze, Ralf A. Linker, Katrin Lorenz, Fanni E. Molnár, Elisabeth Mulazzani, Marcus Müller, Florian T. Nickel, Marion Noll, Amelie Pielen, Susanne Pitz, Sebastian Rauer, Michael Reich, Sina Rosenkranz, Philipp Schwenkenbecher, Nelly Siller, Thomas Skripuletz, Martin Stangel, Jan-Patrick Stellmann, Klarissa Stürner, Kurt-Wolfram Sühs, Judith Ungewiss, Timo Uphaus, Christian van Oterendorp, Martin Volkmann, Bettina Wabbels, Helmut Wilhelm, Sebastian Wolf, Michael Wörner, Ulf Ziemann, Frauke Zipp
Journal: The Lancet Neurology (2021)
When I use a word . . . . Examining the efficiency paradox
Authors: Jeffrey K Aronson
Journal: BMJ (2021)

Healthcare involves tackling patients’ problems using many different types of resources, both human and technological, and the spaces in which they operate. Variability in, on the one hand, human abilities, the performance of technologies, and the available facilities, and, on the other, the problems that patients present with distorts our ability to maximize the efficiency with which we use healthcare resources while minimizing the time a patient spends in the healthcare system and the inconvenience involved. Variability in demand and lack of resources also contribute. The efficiency paradox is that in healthcare efficient use of resources tends to increase the time a patient spends in the system and the inconvenience involved. But the efficiency paradox is not a paradox at all. It is a consequence of identifiable problems in the way that healthcare is delivered, albeit without identifiable solutions that can be simply implemented.
SEQUOIA: Results of a Phase 3 Randomized Study of Zanubrutinib versus Bendamustine + Rituximab (BR) in Patients with Treatment-Naïve (TN) Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma (CLL/SLL)
Authors: Constantine S. Tam, Krzysztof Giannopoulos, Wojciech Jurczak, Martin Šimkovič, Mazyar Shadman, Anders Österborg, Luca Laurenti, Patricia Walker, Stephen Opat, Henry Chan, Hanna Ciepluch, Richard Greil, Monica Tani, Marek Trněný, Danielle M. Brander, Ian W. Flinn, Sebastian Grosicki, Emma Verner, Jennifer R. Brown, Brad S. Kahl, Paolo Ghia, Tian Tian, Carol Marimpietri, Jason C. Paik, Aileen Cohen, Jane Huang, Tadeusz Robak, Peter Hillmen
Journal: Blood (2021)
MS4A3 promotes differentiation in chronic myeloid leukemia by enhancing common β-chain cytokine receptor endocytosis
Authors: Helong Zhao, Anthony D. Pomicter, Anna M. Eiring, Anca Franzini, Jonathan Ahmann, Jae-Yeon Hwang, Anna Senina, Bret Helton, Siddharth Iyer, Dongqing Yan, Jamshid S. Khorashad, Matthew S. Zabriskie, Anupriya Agarwal, Hannah M. Redwine, Amber D. Bowler, Phillip M. Clair, Shannon K. McWeeney, Brian J. Druker, Jeffrey W. Tyner, Derek L. Stirewalt, Vivian G. Oehler, Sooryanarayana Varambally, Kristofer C. Berrett, Jeffery M. Vahrenkamp, Jason Gertz, Katherine E. Varley, Jerald P. Radich, Michael W. Deininger
Journal: Blood (2021)

The chronic phase of chronic myeloid leukemia (CP-CML) is characterized by the excessive production of maturating myeloid cells. As CML stem/progenitor cells (LSPCs) are poised to cycle and differentiate, LSPCs must balance conservation and differentiation to avoid exhaustion, similar to normal hematopoiesis under stress. Since BCR-ABL1 tyrosine kinase inhibitors (TKIs) eliminate differentiating cells but spare BCR-ABL1-independent LSPCs, understanding the mechanisms that regulate LSPC differentiation may inform strategies to eliminate LSPCs. Upon performing a meta-analysis of published CML transcriptomes, we discovered that low expression of the MS4A3 transmembrane protein is a universal characteristic of LSPC quiescence, BCR-ABL1 independence, and transformation to blast phase (BP). Several mechanisms are involved in suppressing MS4A3, including aberrant methylation and a MECOM-C/EBPε axis. Contrary to previous reports, we find that MS4A3 does not function as a G1/S phase inhibitor but promotes endocytosis of common β-chain (βc) cytokine receptors upon GM-CSF/IL-3 stimulation, enhancing downstream signaling and cellular differentiation. This suggests that LSPCs downregulate MS4A3 to evade βc cytokine-induced differentiation and maintain a more primitive, TKI-insensitive state. Accordingly, knockdown (KD) or deletion of MS4A3/Ms4a3 promotes TKI resistance and survival of CML cells ex vivo and enhances leukemogenesis in vivo, while targeted delivery of exogenous MS4A3 protein promotes differentiation. These data support a model in which MS4A3 governs response to differentiating myeloid cytokines, providing a unifying mechanism for the differentiation block characteristic of CML quiescence and BP-CML. Promoting MS4A3 reexpression or delivery of ectopic MS4A3 may help eliminate LSPCs in vivo.
Abstract 13107: Effectiveness Of The Outpatient Pritikin Intensive Cardiac Rehabilitation Program In Patients With Heart Failure
Authors: Lauren K Park, Kristin McKenzie, Erin Mckenzie, Natalie Stranczek, Elena Deych, Susan B RACETTE, Linda R Peterson
Journal: Circulation (2021)

Introduction: The Pritikin intensive cardiac rehabilitation (ICR) program includes structured exercise sessions augmented by heart health education sessions for patients recovering from myocardial infarction, cardiac surgery, PCI, and stable angina. Medicare coverage for ICR expanded to include patients with heart failure (HF) with reduced ejection fraction (HFrEF, EF &lt;35%). However, the efficacy of outpatient ICR on improvement of cardiovascular disease (CVD) risk factors in all patients with HF, regardless of EF, is unknown. Hypothesis: Patients with HF who participate in the outpatient Pritikin ICR program will have improvements in several clinically significant CVD risk factors, including cardiorespiratory fitness, strength, body composition, and lipid profiles. Methods: We performed a prospective cohort study of patients with HF enrolled in the outpatient Pritikin ICR program at Barnes Jewish West County Hospital in St. Louis, MO. Patients referred for ICR since 1/1/2017 were invited to participate in assessments at baseline (BL) and after completing 24 ICR visits. Each visit included a monitored exercise session plus a Pritikin education session focusing on dietary changes (low-fat, low-sodium, high-fiber foods) and stress management through a series of videos, cooking classes, and workshops. We measured body composition using bioelectrical impedance, cardiorespiratory fitness using a 6-min walk test, hand grip strength by dynamometry, and lipids by venipuncture. Values are presented as median difference, and interquartile range (IQR) from BL to visit 24. Results: 84 patients with HF (68% HfrEF, 32% HfpEF; 70.2% also diagnosed with MI, CABG, or PCI; 40% women; mean age 69.9 [SD 9.6] y), completed BL and visit 24 assessments over an average of 9.9 weeks. Significant improvements (all P &lt;0.01) were observed for whole-body fat (-1.2%, IQR -2.4, 0.8), trunk fat (-1.3%, -3.2, 0.5), fat free mass (+0.6 kg, -0.3, 1.7), 6-min walk distance (+45.7 m, 17.9, 68.9), hand grip strength (+1.0 kg, -0.4, 2.9), and LDL cholesterol (-3 mg/dL, -14, 6). Conclusion: Outpatient Pritikin ICR results in significant cardiovascular benefits in patients with HF by enhancing exercise capacity and strength, reducing adiposity, and improving lipid profiles.