tbuckley/cabot-search huggingface dataset:
HIV-1 viremia not suppressible by antiretroviral therapy can originate from large T cell clones producing infectious virus
Authors: Elias K. Halvas, Kevin W. Joseph, Leah D. Brandt, Shuang Guo, Michele D. Sobolewski, Jana L. Jacobs, Camille Tumiotto, John K. Bui, Joshua C. Cyktor, Brandon F. Keele, Gene D. Morse, Michael J. Bale, Wei Shao, Mary F. Kearney, John M. Coffin, Jason W. Rausch, Xiaolin Wu, Stephen H. Hughes, John W. Mellors
Journal: Journal of Clinical Investigation (2020)

BACKGROUNDHIV-1 viremia that is not suppressed by combination antiretroviral therapy (ART) is generally attributed to incomplete medication adherence and/or drug resistance. We evaluated individuals referred by clinicians for nonsuppressible viremia (plasma HIV-1 RNA above 40 copies/mL) despite reported adherence to ART and the absence of drug resistance to the current ART regimen.METHODSSamples were collected from at least 2 time points from 8 donors who had nonsuppressible viremia for more than 6 months. Single templates of HIV-1 RNA obtained from plasma and viral outgrowth of cultured cells and from proviral DNA were amplified by PCR and sequenced for evidence of clones of cells that produced infectious viruses. Clones were confirmed by host-proviral integration site analysis.RESULTSHIV-1 genomic RNA with identical sequences were identified in plasma samples from all 8 donors. The identical viral RNA sequences did not change over time and did not evolve resistance to the ART regimen. In 4 of the donors, viral RNA sequences obtained from plasma matched those sequences from viral outgrowth cultures, indicating that the viruses were replication competent. Integration sites for infectious proviruses from those 4 donors were mapped to the introns of the MATR3, ZNF268, ZNF721/ABCA11P, and ABCA11P genes. The sizes of the clones were estimated to be from 50 million to 350 million cells.CONCLUSIONThese findings show that clones of HIV-1-infected cells producing virus can cause failure of ART to suppress viremia. The mechanisms involved in clonal expansion and persistence need to be defined to effectively target viremia and the HIV-1 reservoir.FUNDINGNational Cancer Institute, NIH; Howard Hughes Medical Research Fellows Program, Howard Hughes Medical Institute; Bill and Melinda Gates Foundation; Office of AIDS Research; American Cancer Society; National Cancer Institute through a Leidos subcontract; National Institute for Allergy and Infectious Diseases, NIH, to the I4C Martin Delaney Collaboratory; University of Rochester Center for AIDS Research and University of Rochester HIV/AIDS Clinical Trials Unit.
Outcomes of Percutaneous Trans–Right Atrial Access to the Left Ventricle for Catheter Ablation of Ventricular Tachycardia in Patients With Mechanical Aortic and Mitral Valves
Authors: Pasquale Santangeli, Matthew C. Hyman, Daniele Muser, David J. Callans, Kalyanam Shivkumar, Francis E. Marchlinski
Journal: JAMA Cardiology (2020)

<h3>Importance</h3> In patients with mechanical valves in the aortic and mitral positions, percutaneous access to the left ventricle (LV) via a transfemoral approach for catheter ablation of ventricular tachycardia (VT) has been considered infeasible. <h3>Objective</h3> To describe the outcomes of a novel percutaneous trans–right atrial (RA) access to the LV via a femoral venous approach for catheter ablation of VT in patients with mechanical aortic and mitral valves. <h3>Design, Setting, and Participants</h3> This observational study included consecutive patients with mechanical valves in the aortic and mitral positions and recurrent monomorphic drug-refractory VT associated with an LV substrate. Percutaneous LV access was performed from a transfemoral venous route with the aid of a deflectable sheath and a radiofrequency wire by creating an iatrogenic Gerbode defect with direct puncture of the inferior and medial aspect of the RA, adjacent to the inferior-septal process of the LV (ISP-LV), under intracardiac echography guidance. Once the wire crossed to the LV, balloon dilatation of the ventriculotomy site (with a noncompliant balloon; diameter, 8 to 10 mm) was performed to facilitate passage of the sheath within the LV. <h3>Exposures</h3> Percutaneous trans-RA access to the LV via puncture of the ISP-LV to perform catheter ablation of VT in patients with mechanical aortic and mitral valves. <h3>Main Outcomes and Measures</h3> Feasibility and safety of a trans-RA access to the LV for catheter ablation of VT. <h3>Results</h3> A total of 4 patients (mean [SD] age, 60 [7] years; mean [SD] LV ejection fraction, 31% [9%]) with recurrent VT associated with an LV substrate (ischemic cardiomyopathy, 3 patients; nonischemic cardiomyopathy, 1 patient) and mechanical valves in the aortic and mitral position underwent trans-RA access through the ISP-LV for catheter ablation of VT. The time to obtain LV access ranged from 60 minutes (first case) to 22 minutes (last case) (mean [SD], 36 [15] minutes). No complications associated with the access occurred. In particular, in the 3 patients with preserved atrioventricular conduction at baseline, no new conduction abnormalities were observed after the access. Complete VT noninducibility at programmed ventricular stimulation was achieved in 3 cases, and no patient had VT recurrence at a median follow-up of 14 months (range, 6-21 months). <h3>Conclusions and Relevance</h3> A percutaneous trans-RA access to the LV via a femoral venous approach for catheter ablation of VT in patients with mechanical aortic and mitral valves is feasible and appears safe. This novel technique may allow for catheter ablation of VT in a population of patients in whom conventional LV access via retrograde aortic or atrial transseptal routes is not possible.
Liver Stiffness by Magnetic Resonance Elastography Predicts Future Cirrhosis, Decompensation, and Death in NAFLD
Authors: Tolga Gidener, Omar T Ahmed, Joseph J Larson, Kristin C Mara, Terry M Therneau, Sudhakar K Venkatesh, Richard L Ehman, Meng Yin, Alina M Allen
Journal: Clinical Gastroenterology and Hepatology (2020)
Benign biliary strictures: utility of novel biodegradable biliary stents in surgically altered anatomy
Authors: Sreelakshmi Kotha, Philip Berry, Usman Raja, Terry Wong
Journal: Endoscopy (2020)

Benign biliary strictures are traditionally managed by placement of either plastic stents or, more recently, fully covered self-expandable metal stents (FcSEMs) [1] [2]. Though effective, plastic stents need replacement every 2 – 3 months, whereas FcSEMs need removal in 6 – 9 months, both requiring repeat endoscopic retrograde cholangiopancreatography (ERCP). Surgically altered anatomy makes ERCP challenging, and these patients require either a percutaneous approach or balloon-assisted endoscopy with specially designed biliary instruments.
Telemedicine in Oncology and Reimbursement Policy During COVID-19 and Beyond
Authors: Sheetal M. Kircher, Mary Mulcahy, Aparna Kalyan, Christine B. Weldon, Julia R. Trosman, Al B. Benson
Journal: Journal of the National Comprehensive Cancer Network (2021)

The first confirmed case of coronavirus disease 2019 (COVID-19) in the United States was reported on January 20, 2020. As of September 17, 2020, there were more than 6.6 million confirmed cases and 196,277 deaths. Limited data are available on outcomes of immunocompromised patients, but early published reports from China indicate that those with cancer have a 3.5 times higher risk of ICU admission, mechanical ventilation, or death than those without cancer. Because of the uncertain behavior of COVID-19, it has become imperative for practices to limit exposure to vulnerable patients. Telemedicine has been one of the cornerstones of caring for patients with cancer during the COVID-19 pandemic. This review provides an overview of reimbursement policy by public and private payers before and during the COVID-19 pandemic, describes implications in cancer care, and offers considerations for future reimbursement policy.
External Validation of a Multiparametric Magnetic Resonance Imaging–based Nomogram for the Prediction of Extracapsular Extension and Seminal Vesicle Invasion in Prostate Cancer Patients Undergoing Radical Prostatectomy
Authors: Romain Diamand, Guillaume Ploussard, Mathieu Roumiguié, Marco Oderda, Daniel Benamran, Gaelle Fiard, Thierry Quackels, Grégoire Assenmacher, Giuseppe Simone, Julien Van Damme, Bernard Malavaud, Christophe Iselin, Jean-Luc Descotes, Jean-Baptiste Roche, Alexandre Peltier, Thierry Roumeguère, Simone Albisinni
Journal: European Urology (2020)
Pre- and Postoperative Capecitabine Without or With Oxaliplatin in Locally Advanced Rectal Cancer: PETACC 6 Trial by EORTC GITCG and ROG, AIO, AGITG, BGDO, and FFCD
Authors: Hans-Joachim Schmoll, Alexander Stein, Eric Van Cutsem, Timothy Price, Ralf D. Hofheinz, Bernard Nordlinger, Jean-François Daisne, Jos Janssens, Baruch Brenner, Hans Reinel, Stephan Hollerbach, Karel Caca, Florian Fauth, Carla V. Hannig, John Zalcberg, Niall Tebbutt, Murielle E. Mauer, Sandrine Marreaud, Manfred P. Lutz, Karin Haustermans
Journal: Journal of Clinical Oncology (2020)

PURPOSE The PETACC 6 trial investigates whether the addition of oxaliplatin to preoperative capecitabine-based chemoradiation and postoperative capecitabine improves disease-free survival (DFS) in locally advanced rectal cancer. METHODS Between November 2008 and September 2011, patients with rectal adenocarcinoma within 12 cm from the anal verge, T3/4 and/or node positive, were randomly assigned to 5 weeks preoperative capecitabine-based chemoradiation (45-50.4 Gy) followed by six cycles of adjuvant capecitabine, both without (control arm, 1) or with (experimental arm, 2) oxaliplatin. The primary end point was improvement of 3-year DFS by oxaliplatin from 65% to 72% (hazard ratio [HR], 0.763). RESULTS A total of 1,094 patients were randomly assigned (intention to treat), and 1,068 eligible patients started their allocated treatment (arm 1, 543; arm 2, 525), with completion of protocol treatment in 68% (arm 1) v 54% (arm 2). A higher rate of grade 3/4 adverse events was reported in the experimental arm (14.4% v 37.3% and 23.4% v 46.6% for neoadjuvant and adjuvant treatment, respectively). At a median follow-up of 68 months (interquartile range, 58-74 months), 157 and 156 DFS events were observed in arms 1 and 2, respectively (adjusted HR, 1.02; 95% CI, 0.82 to 1.28; P = .835). Three-year DFS rate was not different, with 76.5% (95% CI, 72.7% to 79.9%) in arm 1, which is higher than anticipated, and 75.8% (95% CI, 71.9% to 79.3%) in arm 2. The 7-year DFS and overall survival (OS) rates were not different as well, with DFS of 66.1% v 65.5% (HR, 1.02) and OS of 73.5% v 73.7% (HR, 1.19) in arms 1 and 2, respectively. Subgroup analyses revealed heterogeneity in treatment effect according to German versus non-German site location, without detectable confounding factors in multivariable analysis. CONCLUSION The addition of oxaliplatin to preoperative capecitabine-based chemoradiation and postoperative adjuvant chemotherapy impairs tolerability and feasibility and does not improve efficacy.
Second-line regimens for HIV infection: outcomes after 144 weeks’ treatment using the public health approach in a randomised controlled trial in sub-Saharan Africa
Authors: J G Hakim, J A Thompson, C Kityo, A Hoppe, A Kambugu, J J van Oosterhout, A Lugemwa, A Siika, R Mwebaze, A Mweemba, G Abongomera, M J Thomason, P J Easterbrook, P Mugyenyi, A S Walker, N I Paton
Journal: The Lancet Infectious Diseases (2017)
Pleural Fluids Collected During The Second Multicenter Intrapleural Sepsis Trial (mist2) Demonstrate Highly Variable Fibrinolytic Potential Prior To The Treatment And Endogenous Fibrinolytic Activity Depletion During Intrapleural Fibrinolytic Therapy
Authors: A A Komissarov, G Florova, C Schaefer, N M Rahman, Lee Ycg., S Idell
Journal: American Journal of Respiratory and Critical Care Medicine (2013)
Abstract B25: Demographic characteristics and peripheral blood clinical laboratory variables predict irAE occurrence in patients with advanced melanoma receiving anti-PD-1 monotherapy
Authors: Xue Bai, Michelle S. Kim, Gyulnara Kasumova, Justine Cohen, Donald Lawrence, Christine Freedman, Riley Fadden, Krista Rubin, Tatyana Sharova, Keith Flaherty, Ryan Sullivan, Genevieve Boland
Journal: Cancer Research (2020)

Abstract Background: Although immune-related adverse effects (irAEs) are commonly seen in anti-PD-1 monotherapy-treated patients, their predictive biomarkers are still lacking. Methods: In this retrospective analysis, clinical data were collected from 141 advanced melanoma patients treated with anti-PD-1 monotherapy at Massachusetts General Hospital from Sept. 2009 to Dec. 2017. Demographic characteristics, baseline, and early-on-treatment (median 3 weeks after anti-PD-1 monotherapy initiation) routine laboratory variables were collected and correlated with occurrence of irAEs in both univariate and multivariate analyses. Results: 80/141 (56.7%) patients developed irAEs after anti-PD-1 monotherapy initiation. Significant independent predictive variables (P &amp;lt; 0.05) in favor of the occurrence of irAEs included the following: with no distant metastasis (Stage M0) before treatment initiation, high baseline neutrophils, and high early-on-treatment neutrophil-to-lymphocyte ratio (NLR). High baseline monocytes, high baseline basophils, and high early-on-treatment WBCs were of borderline significance (P &amp;lt; 0.1) in multivariate analyses. An irAE risk scoring model (total scale: 0-6) comprising these 6 factors (all as dichotomous variables) was established (HR 1.781, 95% CI 1.450 – 2.187, P &amp;lt; 0.001). Risks of developing at least one irAE within 12 weeks after anti-PD-1 monotherapy initiation were 0%, 21%, 21%, 39%, 30%, and 63%; within 48 weeks were 0%, 41%, 57%, 68%, 77%, and 100%, for patients with scores of 0 to 5 (no patient scored 6 within this cohort), respectively. Conclusions: Scoring system based on simple, easily accessible, and routinely tested biomarkers could be used to help predict the risk of irAEs occurrence in anti-PD-1 monotherapy-treated advanced melanoma patients. Citation Format: Xue Bai, Michelle S. Kim, Gyulnara Kasumova, Justine Cohen, Donald Lawrence, Christine Freedman, Riley Fadden, Krista Rubin, Tatyana Sharova, Keith Flaherty, Ryan Sullivan, Genevieve Boland. Demographic characteristics and peripheral blood clinical laboratory variables predict irAE occurrence in patients with advanced melanoma receiving anti-PD-1 monotherapy [abstract]. In: Proceedings of the AACR Special Conference on Melanoma: From Biology to Target; 2019 Jan 15-18; Houston, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(19 Suppl):Abstract nr B25.
Improving patient retention by optimizing appointment scheduling in an underserved oncology population within a public safety-net health system.
Authors: Jessica Meshman, Nirav Patel, David Asher, Erudye Muniz, Mario Hidalgo, Maria-Ana Abad, Marla Rodriguez, Kevin Alayon, Isabel Truglio, Stuart Samuels, Raphael Yechieli
Journal: Journal of Clinical Oncology (2020)

193 Background: Cancer patients in underserved populations are at high risk for patient attrition and treatment delay. We theorized that decreased appointment scheduling was contributing to a high no-show rate within an urban safety-net hospital. Clinic appointments were being scheduled in the department-specific record and verify system rather than the hospital-wide electronic health record (EHR). We sought to adopt EHR scheduling with the long-term goal of decreasing the no-show rate. Our aim was to utilize the Lean Six Sigma (LSS) methodologies to increase EHR scheduling of follow-up and rescheduling of no-show appointments to 50%. Methods: While involving the entire clinic staff, we utilized the Lean Six Sigma DMAIC model: define, measure, analyze, improve and control, to improve EHR appointment scheduling. Appointment data was collected for the 3 months prior to and during the intervention time period. We determined the root causes for delinquent scheduling, including lack of staff availability to schedule patients into two electronic systems and to call no-show patients. Interventions included implementation of an electronic order for follow-up scheduling and blocked time for personnel to contact no-show patients and verify scheduling. After the formation of a novel process map, control plan, and Failure Modes Effects Analysis (FMEA), the pilot study ran for 2 months. Results: Follow-up appointment scheduling into the EHR improved from 2% to 98% (p &lt; 0.01). After the first intervention month, the no-show rescheduling rate improved from 0% to 43% (p &lt; 0.01): below goal. The team revised the process map by substituting a no-show EHR order in place of the calendar intervention. This constituted the beginning of month 2 and no-show appointment rescheduling subsequently improved from 43% to 87% (p &lt; 0.01). The patient no-show rate was 19% during the pre-intervention period, 17% for the first intervention cycle and 15% for the second intervention cycle (p = 0.3). Conclusions: Utilization of LSS allowed for successful adoption of EHR appointment scheduling within our department. While not yet significant, the no-show rate appears to be trending downward as a result of improved scheduling, and we expect the no-show rate to continue to decline as the study matures. These findings suggest that optimized appointment scheduling may decrease patient retention in an at-risk population. Future directions include evaluating cancer outcomes and decreased healthcare costs as a result of higher patient retention.
Comparison of perspectives and practices to mitigate financial toxicity between advance practice providers and attending oncologists.
Authors: Meera Vimala Ragavan, Divya Ahuja Parikh, Manali I. Patel
Journal: Journal of Clinical Oncology (2020)

82 Background: Characterizing the oncology provider’s role in addressing the growing epidemic of financial toxicity faced by cancer patients is of increasing importance. Advance practice providers (APPs) increasingly serve as primary providers for many cancer patients, but no studies to date have examined their perspectives and practices in addressing financial toxicity, nor compared them to that of attending physicians. Methods: We developed an 18-question electronic, anonymous survey informed by an extensive literature search regarding perspectives on the provider’s role and current practices in addressing financial toxicity. We emailed the survey to 75 attending physicians and 117 APPs at our institution’s cancer center. Responses during the study period 12/12/2018-1/31/2019 were analyzed. Results: 32 attending physicians and 28 APPs completed the survey. Response rates were higher among attending physicians (42%) compared to APPs (24%). Attending physicians were more likely than APPs to agree that providers should openly discuss cost (75% vs. 36%, p = 0.002). APPs were more likely to agree that providers should defer cost conversations to a third party (57% vs. 31%, p = 0.04) and make the same treatment recommendation regardless of cost (50% vs. 25%, p = 0.022). Use of cost-effectiveness (CE) guidelines was higher among APPs compared to attending physicians (71% vs. 31%, p = 0.0019). Awareness of out of pocket costs, frequency of referrals to financial counselors, and ranking of top barriers to cost conversations (price transparency, knowledge of resources, and time) were similar between attending physicians and APPs. Conclusions: While APPs and attending physicians differed considerably in their perspectives on the role oncology providers should take in mitigating financial toxicity, they were more consistent in current practices and identification of barriers to cost conversations. APPs were interestingly more likely to use CE guidelines than attending physicians. Higher response rates among attending physicians may reflect inherently stronger opinions regarding the provider’s role in addressing financial toxicity. Future studies should explore these differences to better inform provider-level interventions to reduce financial toxicity.
“When Offered to Participate”: A Systematic Review and Meta-Analysis of Patient Agreement to Participate in Cancer Clinical Trials
Authors: Joseph M Unger, Dawn L Hershman, Cathee Till, Lori M Minasian, Raymond U Osarogiagbon, Mark E Fleury, Riha Vaidya
Journal: JNCI Journal of the National Cancer Institute (2020)

Patient participation in clinical trials is vital for knowledge advancement and outcomes improvement. Few adult cancer patients participate in trials. Although patient.
Autoimmune Keratitis after Atezolizumab Treatment
Authors: Joo Youn Oh
Journal: New England Journal of Medicine (2020)

A 46-year-old woman receiving atezolizumab treatment had pain, redness, tearing, photophobia, and blurring of vision in both eyes. Slit-lamp examination showed evidence of corneal epithelial damage, and a diagnosis of autoimmune keratitis was made.
The aging mouse microbiome has obesogenic characteristics
Authors: Dana Binyamin, Nir Werbner, Meital Nuriel-Ohayon, Atara Uzan, Hadar Mor, Atallah Abbas, Oren Ziv, Raffaele Teperino, Roee Gutman, Omry Koren
Journal: Genome Medicine (2020)

Abstract Background During aging, there is a physiological decline, an increase of morbidity and mortality, and a natural change in the gut microbiome. In this study, we investigated the influence of the gut microbiome on different metabolic parameters in adult and aged mice. Methods Fecal and blood samples from adult ( n = 42, 100–300 days) and aging ( n = 32, 550–750 days) mice were collected. Microbiome analysis was done using QIIME2. Mouse weight and body composition were measured using NMR, and insulin and leptin levels in the blood were measured with Mouse Adipokine Magnetic Bead Panel kit. Fecal microbiota transplantation experiments from adult and aged mice into young germ-free mice were carried out in order to examine the effect of the gut microbiome of adult and aging mice on weight, body composition, insulin, and leptin. Results We demonstrate that the microbiomes from adult and aged mice are distinguishable. We also report changes in metabolic parameters as we observed significantly higher weight and fat mass and low lean mass in aged compared to adult mice along with high insulin and leptin levels in the blood. The transplanted gut microbiome from aged mice transferred part of the phenotypes seen in aged mice. Fat body mass and insulin levels were higher in the mice who received feces from aged mice than mice receiving feces from adult mice. In addition, they consumed more food and had a higher respiratory quotient compared to mice receiving adult feces. Conclusions We conclude that aged mice have a gut microbiota with obesogenic characteristics. In addition, the gut bacterial population itself is sufficient to induce some of the manifestations of obesity.