tbuckley/cabot-search huggingface dataset:
Total Car-T Cost of Care Beyond the Price of Car-T Cell Therapy in Patients with Multiple Myeloma
Authors: Sundar Jagannath, Nedra Joseph, Concetta Crivera, Carolyn C. Jackson, Satish Valluri, Patricia Cost, Hilary Phelps, Rafal Slowik, Timothy Klein, Xueting Yu, Lee Smolen, Adam D Cohen
Journal: Blood (2021)
Liposome-encapsulated anthraquinone improves efficacy and safety in triple negative breast cancer
Authors: Thomashire A. George, Max M. Chen, Andreas Czosseck, Hsiang-Pei Chen, Hsu-Shan Huang, David J. Lundy
Journal: Journal of Controlled Release (2021)

Breast cancer is the most common cancer among women and a leading cause of death worldwide. Triple negative breast cancer (TNBC) is a highly aggressive subtype which is the most challenging to treat. Due to heterogeneity and a lack of specific molecular targets, small molecule-based chemotherapy is the preferred course of treatment. However, these drugs have high toxicity due to off-target effects on healthy tissues, and tumors may develop resistance. Here, we present a polyethylene glycol-modified nanoscale liposomal formulation (LipoRV) of a new anthraquinone derivative which has potent effects on multiple TNBC cell lines. LipoRV readily inhibited the cell cycle, induced cell apoptosis, and reduced long-term proliferative potential of TNBC cells. In a xenograft animal model, LipoRV successfully cleared tumors and demonstrated a good safety profile, without detrimental effects on biochemical markers. Finally, RNA sequencing of LipoRV-treated TNBC cells was carried out, indicating that LipoRV may have immunomodulatory properties. These findings demonstrate that a liposomal anthraquinone-based molecule has excellent promise for TNBC therapy in the future.
How common is palmoplantar pustulosis in Sweden?
Journal: British Journal of Dermatology (2021)

Palmoplantar (palmo meaning palm of the hand, plantar meaning sole of the foot) pustulosis (PPP) is a persistent (chronic) condition that causes blisters filled with fluid on the palms and the soles of the feet. The skin of the palms and soles can be very itchy and painful, particularly if there are deep cracks in the skin. The condition is persistent, but the symptoms can vary, becoming better and worse over time, often with no obvious cause.
Increased blood viscosity and red blood cell aggregation in patients with COVID‐19
Authors: Elie Nader, Christophe Nougier, Camille Boisson, Solene Poutrel, Judith Catella, Fiona Martin, Juliette Charvet, Sandrine Girard, Salomé Havard‐Guibert, Marie Martin, Hamdi Rezigue, Helene Desmurs‐Clavel, Céline Renoux, Philippe Joly, Nicolas Guillot, Yves Bertrand, Arnaud Hot, Yesim Dargaud, Philippe Connes
Journal: American Journal of Hematology (2021)

The aim of this study was to (1) analyze blood viscosity, red blood cell (RBC) deformability, and aggregation in hospitalized patients with Coronavirus disease 19 (COVID-19); (2) test the associations between impaired blood rheology and blood coagulation; and (3) test the associations between impaired blood rheology and several indicators of clinical severity. A total of 172 patients with COVID-19, hospitalized in COVID-unit of the Internal Medicine Department (Lyon, France) participated in this study between January and May 2021. Clinical parameters were collected for each patient. Routine hematological/biochemical parameters, blood viscosity, RBC deformability and aggregation, and RBC senescence markers were measured on the first day of hospitalization. A control group of 38 healthy individuals was constituted to compare the blood rheological and RBC profile. Rotational thromboelastography was performed in 76 patients to study clot formation dynamics. Our study demonstrated that patients with COVID-19 had increased blood viscosity despite lower hematocrit than healthy individuals, as well as increased RBC aggregation. In-vitro experiments demonstrated a strong contribution of plasma fibrinogen in this RBC hyper-aggregation. RBC aggregation correlated positively with clot firmness, negatively with clot formation time, and positively with the length of hospitalization. Patients with oxygen supplementation had higher RBC aggregation and blood viscosity than those without, and patients with pulmonary lesions had higher RBC aggregation and enhanced coagulation than those without. This study is the first to demonstrate blood hyper-viscosity and RBC hyper-aggregation in a large cohort of patients with COVID-19 and describe associations with enhanced coagulation and clinical outcomes.
Table of Contents
Authors: Philippe Joubert, William Travis, Ramila Shilpakar, Dutta Paudel, Rajeev Sharma, Raj Silwal, Ranjan Sapkota, Prajowl Shrestha, Soniya Dulal, Kumar Piya, Man Tuladhar, Prakash Neupane, Meghnath Dhimal, Abesh Niroula, Dipesh Uprety
Journal: Journal of Thoracic Oncology (2021)
CD19 CAR-T Cell Therapy in Children with Relapsed and Refractory B-ALL
Authors: Olga Molostova, Larisa Shelikhova, Yakov Muzalevsky, Alexey Kazachenok, Rimma Khismatullina, Julia Abugova, Elena Kurnikova, Pavel Trakhtman, Dmitry Pershin, Viktoria Zubachenko, Maria Fadeeva, Alexander M Popov, Olga Illarionova, Natalia Miakova, Dmitry Litvinov, Galina Novichkova, Alexey Maschan, Michael Maschan
Journal: Blood (2021)
Screening and Interventions to Prevent Dental Caries in Children Younger Than 5 Years
Authors: Roger Chou, Miranda Pappas, Tracy Dana, Shelley Selph, Erica Hart, Rongwei F. Fu, Eli Schwarz
Journal: JAMA (2021)

A 2014 review for the US Preventive Services Task Force (USPSTF) found that oral fluoride supplementation and topical fluoride use were associated with reduced caries incidence in children younger than 5 years.To update the 2014 review on dental caries screening and preventive interventions to inform the USPSTF.Ovid MEDLINE, the Cochrane Central Register of Controlled Trials, and the Cochrane Database of Systematic Reviews (to September 2020); surveillance through July 23, 2021.Randomized clinical trials (RCTs) on screening, preventive interventions, referral to dental care; cohort studies on screening and referral; studies on diagnostic accuracy of primary care oral examination or risk assessment; and a systematic review on risk of fluorosis included in prior USPSTF reviews.One investigator abstracted data; a second checked accuracy. Two investigators independently rated study quality.Thirty-two studies (19 trials, 9 observational studies, and 4 nonrandomized clinical intervention studies [total 106 694 participants] and 1 systematic review [19 studies]) were included. No study evaluated effects of primary care screening on clinical outcomes. One study (n = 258) found primary care pediatrician examination associated with a sensitivity of 0.76 (95% CI, 0.55 to 0.91) and specificity of 0.95 (95% CI, 0.92 to 0.98) for identifying a child with cavities, and 1 study found a risk assessment tool associated with sensitivity of 0.53 and specificity of 0.77 (n = 697, CIs not reported) for a child with future caries. No new trials of dietary fluoride supplementation were identified. For prevention, topical fluoride compared with placebo or no topical fluoride was associated with decreased caries burden (13 trials, n = 5733; mean caries increment [difference in decayed, missing, and filled teeth or surfaces], -0.94 [95% CI, -1.74 to -0.34]) and likelihood of incident caries (12 trials, n = 8177; RR, 0.80 [95% CI, 0.66 to 0.95]; absolute risk difference, -7%) in higher-risk populations or settings, with no increased fluorosis risk. Evidence on other preventive interventions was limited (education, xylitol) or unavailable (silver diamine fluoride), and no study directly evaluated primary care dentistry referral vs no referral.There was no direct evidence on benefits and harms of primary care oral health screening or referral to dentist. Dietary fluoride supplementation and fluoride varnish were associated with improved caries outcomes in higher-risk children and settings.
Transfusion strategies in bleeding critically ill adults: a clinical practice guideline from the European Society of Intensive Care Medicine
Authors: Alexander P. J. Vlaar, Joanna C. Dionne, Sanne de Bruin, Marije Wijnberge, S. Jorinde Raasveld, Frank E. H. P. van Baarle, Massimo Antonelli, Cecile Aubron, Jacques Duranteau, Nicole P. Juffermans, Jens Meier, Gavin J. Murphy, Riccardo Abbasciano, Marcella C. A. Müller, Marcus Lance, Nathan D. Nielsen, Herbert Schöchl, Beverley J. Hunt, Maurizio Cecconi, Simon Oczkowski
Journal: Intensive Care Medicine (2021)

To develop evidence-based clinical practice recommendations regarding transfusion practices and transfusion in bleeding critically ill adults. A taskforce involving 15 international experts and 2 methodologists used the GRADE approach to guideline development. The taskforce addressed three main topics: transfusion support in massively and non-massively bleeding critically ill patients (transfusion ratios, blood products, and point of care testing) and the use of tranexamic acid. The panel developed and answered structured guideline questions using population, intervention, comparison, and outcomes (PICO) format. The taskforce generated 26 clinical practice recommendations (2 strong recommendations, 13 conditional recommendations, 11 no recommendation), and identified 10 PICOs with insufficient evidence to make a recommendation. This clinical practice guideline provides evidence-based recommendations for the management of massively and non-massively bleeding critically ill adult patients and identifies areas where further research is needed.
Estimation of the Timing and Intensity of Reemergence of Respiratory Syncytial Virus Following the COVID-19 Pandemic in the US
Authors: Zhe Zheng, Virginia E. Pitzer, Eugene D. Shapiro, Louis J. Bont, Daniel M. Weinberger
Journal: JAMA Network Open (2021)

<h3>Importance</h3> Respiratory syncytial virus (RSV) is a leading cause of hospitalizations in young children. RSV largely disappeared in 2020 owing to precautions taken because of the COVID-19 pandemic. Estimating the timing and intensity of the reemergence of RSV and the age groups affected is crucial for planning for the administration of prophylactic antibodies and anticipating hospital capacity. <h3>Objective</h3> To examine the association of different factors, including mitigation strategies, duration of maternal-derived immunity, and importation of external infections, with the dynamics of reemergent RSV epidemics. <h3>Design, Setting, and Participants</h3> This simulation modeling study used mathematical models to reproduce the annual epidemics of RSV before the COVID-19 pandemic in New York and California. These models were modified to project the trajectory of RSV epidemics from 2020 to 2025 under different scenarios with varying stringency of mitigation measures for SARS-CoV-2. Simulations also evaluated factors likely to affect the reemergence of RSV epidemics, including introduction of the virus from out-of-state sources and decreased transplacentally acquired immunity in infants. Models using parameters fitted to similar inpatient data sets from Colorado and Florida were used to illustrate these associations in populations with biennial RSV epidemics and year-round RSV circulation, respectively. Statistical analysis was performed from February to October 2021. <h3>Main Outcomes and Measures</h3> The primary outcome of this study was defined as the estimated number of RSV hospitalizations each month in the entire population. Secondary outcomes included the age distribution of hospitalizations among children less than 5 years of age, incidence of any RSV infection, and incidence of RSV lower respiratory tract infection. <h3>Results</h3> Among a simulated population of 19.45 million people, virus introduction from external sources was associated with the emergence of the spring and summer epidemic in 2021. There was a tradeoff between the intensity of the spring and summer epidemic in 2021 and the intensity of the epidemic in the subsequent winter. Among children 1 year of age, the estimated incidence of RSV hospitalizations was 707 per 100 000 children per year in the 2021 and 2022 RSV season, compared with 355 per 100 000 children per year in a typical RSV season. <h3>Conclusions and Relevance</h3> This simulation modeling study found that virus introduction from external sources was associated with the spring and summer epidemics in 2021. These findings suggest that pediatric departments should be alert to large RSV outbreaks in the coming seasons, the intensity of which could depend on the size of the spring and summer epidemic in that location. Enhanced surveillance is recommended for both prophylaxis administration and hospital capacity management.
Smoking Cessation
Authors: Manish S. Patel, Sheetal B. Patel, Michael B. Steinberg
Journal: Annals of Internal Medicine (2021)

Tobacco smoking is the leading cause of preventable death in the United States, and its harms are well established. Physicians have more evidence-based resources than ever before to effectively treat smoking, including new uses and combinations of U.S. Food and Drug Administration–approved pharmacotherapies and expanded community programs. In addition, electronic nicotine delivery systems are potential treatment tools, but their safety and efficacy need to be established. Finally, high-priority groups, such as persons with cancer diagnoses or hospitalized patients, may benefit from particular attention to their tobacco use.
185P Effect of 17β-estradiol and prolactin in the cytotoxicity of NK cells on cervical cancer cells
Authors: A.L. Pereira-Suárez, A. Godoy-Pacheco, M. García-Chagollán, A. Ramírez-De-Arellano, C.D. Hernández-Silva, A.D.C. Aguilar-Lemarroy, J.C. Villegas-Pineda
Journal: Annals of Oncology (2021)
WHO provides 2 conditional recommendations for casirivimab–imdevimab combination therapy in COVID-19
Authors: Cody Dunne, Eddy Lang
Journal: Annals of Internal Medicine (2021)

Rochwerg B, Agarwal A, Siemieniuk RA, et al. Update to living WHO guideline on drugs for covid-19. BMJ. 2021;374:n2219. 34556469.
166TiP Pembrolizumab combined with neoadjuvant chemotherapy versus neoadjuvant chemoradiotherapy followed surgery for locally advanced esophageal squamous cell carcinoma: Protocol for a multi-center, prospective, randomized-controlled, phase III clinical study (Keystone-002)
Authors: H. Jiang, X. Shang, C. Zhang, J. Yue, X. Duan, Z. Ma, C. Chen, W. Zhang, Q. Pang, W. Zhang, L. Liu, X. Ren, B. Meng, G. Zhao, P. Zhang, Y. Wei, Y. Ma, L. Zhang, Y. Li
Journal: Annals of Oncology (2021)
Effect modification of greenness on PM<sub>2.5</sub>associated all-cause mortality in a multidrug-resistant tuberculosis cohort
Authors: Erjia Ge, Jianhui Gao, Xiaolin Wei, Zhoupeng Ren, Jing Wei, Xin Liu, Xiaomeng Wang, Jieming Zhong, Jingru Lu, Xiaomei Tian, Fangrong Fei, Bin Chen, Xiaolin Wang, Ying Peng, Ming Luo, Juan Lei
Journal: Thorax (2021)

Rationale Evidence for the association between fine particulate matter (PM 2.5 ) and mortality among patients with tuberculosis (TB) is limited. Whether greenness protects air pollution-related mortality among patients with multidrug-resistant tuberculosis (MDR-TB) is completely unknown. Methods 2305 patients reported in Zhejiang and Ningxia were followed up from MDR-TB diagnosis until death, loss to follow-up or end of the study (31 December 2019), with an average follow-up of 1724 days per patient. 16-day averages of contemporaneous Normalised Difference Vegetation Index (NDVI) in the 500 m buffer of patient’s residence, annual average PM 2.5 and estimated oxidant capacity O x were assigned to patients regarding their geocoded home addresses. Cox proportional hazards regression models were used to estimate HRs per 10 μg/m 3 exposure to PM 2.5 and all-cause mortality among the cohort and individuals across the three tertiles, adjusting for potential covariates. Results HRs of 1.702 (95% CI 1.680 to 1.725) and 1.169 (1.162 to 1.175) were observed for PM 2.5 associated with mortality for the full cohort and individuals with the greatest tertile of NDVI. Exposures to PM 2.5 were stronger in association with mortality for younger patients (HR 2.434 (2.432 to 2.435)), female (2.209 (1.874 to 2.845)), patients in rural (1.780 (1.731 to 1.829)) and from Ningxia (1.221 (1.078 to 1.385)). Cumulative exposures increased the HRs of PM 2.5 -related mortality, while greater greenness flattened the risk with HRs reduced in 0.188–0.194 on average. Conclusions Individuals with MDR-TB could benefit from greenness by having attenuated associations between PM 2.5 and mortality. Improving greener space and air quality may contribute to lower the risk of mortality from TB/MDR-TB and other diseases.
Cancer Induces a Stress Ileopathy Depending on β-Adrenergic Receptors and Promoting Dysbiosis that Contributes to Carcinogenesis
Authors: Satoru Yonekura, Safae Terrisse, Carolina Alves Costa Silva, Antoine Lafarge, Valerio Iebba, Gladys Ferrere, Anne-Gaëlle Goubet, Jean-Eudes Fahrner, Imran Lahmar, Kousuke Ueda, Gibrail Mansouri, Eugénie Pizzato, Pierre Ly, Marine Mazzenga, Cassandra Thelemaque, Marine Fidelle, Fanny Jaulin, Jérôme Cartry, Marc Deloger, Marine Aglave, Nathalie Droin, Paule Opolon, Angélique Puget, Fanny Mann, Michel Neunlist, Anne Bessard, Laetitia Aymeric, Tamara Matysiak-Budnik, Jacques Bosq, Paul Hofman, Connie P.M. Duong, Sophie Ugolini, Valentin Quiniou, Sylvie Berrard, Bernhard Ryffel, Oliver Kepp, Guido Kroemer, Bertrand Routy, Leonardo Lordello, Mohamed-Amine Bani, Nicola Segata, Fjodor Yousef Yengej, Hans Clevers, Jean-Yves Scoazec, Edoardo Pasolli, Lisa Derosa, Laurence Zitvogel
Journal: Cancer Discovery (2021)

Gut dysbiosis has been associated with intestinal and extraintestinal malignancies, but whether and how carcinogenesis drives compositional shifts of the microbiome to its own benefit remains an open conundrum. Here, we show that malignant processes can cause ileal mucosa atrophy, with villous microvascular constriction associated with dominance of sympathetic over cholinergic signaling. The rapid onset of tumorigenesis induced a burst of REG3γ release by ileal cells, and transient epithelial barrier permeability that culminated in overt and long-lasting dysbiosis dominated by Gram-positive Clostridium species. Pharmacologic blockade of β-adrenergic receptors or genetic deficiency in Adrb2 gene, vancomycin, or cohousing of tumor bearers with tumor-free littermates prevented cancer-induced ileopathy, eventually slowing tumor growth kinetics. Patients with cancer harbor distinct hallmarks of this stress ileopathy dominated by Clostridium species. Hence, stress ileopathy is a corollary disease of extraintestinal malignancies requiring specific therapies. Whether gut dysbiosis promotes tumorigenesis and how it controls tumor progression remain open questions. We show that 50% of transplantable extraintestinal malignancies triggered a β-adrenergic receptor-dependent ileal mucosa atrophy, associated with increased gut permeability, sustained Clostridium spp.-related dysbiosis, and cancer growth. Vancomycin or propranolol prevented cancer-associated stress ileopathy. This article is highlighted in the In This Issue feature, p. 873.
m6A target microRNAs in serum for cancer detection
Authors: Bo Zhang, Zhenmei Chen, Baorui Tao, Chenhe Yi, Zhifei Lin, Yitong Li, Weiqing Shao, Jing Lin, Jinhong Chen
Journal: Molecular Cancer (2021)

Abstract Recent studies have revealed the significant dysregulation of m 6 A level in peripheral blood in several cancer types and its value in diagnosis. Nonetheless, a biomarker for accurate screening of multiple cancer types has not been established based on the perspective of m 6 A modification. In this study, we aimed to develop a serum diagnostic signature based on the m 6 A target miRNAs for the mass detection of cancer. A total of 14965 serum samples with 12 cancer types were included. Based on training cohort ( n =7299), we developed the m6A-miRNAs signature using a support vector machine algorithm for cancer detection. The m6A-miRNAs signature showed high accuracy, and its area under the curve (AUC) in the training, internal validation and external validation cohort reached 0.979 (95%CI 0.976 - 0.982), 0.976 (95%CI 0.973 - 0.979) and 0.936 (95%CI 0.922 - 0.951), respectively. In the performance of distinguishing cancer types, the m6A-miRNAs signature showed superior sensitivity in each cancer type and presented a satisfactory AUC in identifying lung cancer, gastric cancer and hepatocellular carcinoma. Additionally, the diagnostic performance of m6A-miRNAs was not interfered by the gender, age and benign disease. In short, this study revealed the value of serum circulating m 6 A miRNAs in cancer detection and provided a new direction and strategy for the development of novel biomarkers with high accuracy, low cost and less invasiveness for mass cancer screening, such as RNA modification.
Evaluation of a Case Series of Patients With Palmoplantar Pustulosis in the United States
Authors: Megan H. Noe, Marilyn T. Wan, Arash Mostaghimi, Joel M. Gelfand, Ritesh Agnihothri, April W. Armstrong, Tina Bhutani, Alina Bridges, Nicholas Brownstone, Melissa Butt, Kristina P. Callis Duffin, Christian Carr, Andrew Creadore, Katherine L. DeNiro, Sheena Desai, Arturo R. Dominguez, Emily K. Duffy, Janet A. Fairley, Alisa Femia, Johann E. Gudjonsson, Jessica A. Kaffenberger, Kimberly L. Katz, Joslyn S. Kirby, Stephanie T. Le, Edgar Martinez, Emanual Maverakis, Bridget Myers, Haley B. Naik, Caroline A. Nelson, Alex G. Ortega-Loayza, Molly E. Plovanich, Lauren K. Rangel, Vignesh Ravi, Vidhatha D. Reddy, Jamal Z. Saleh, Jeena K. Sandhu, Hadir Shakshouk, Bridget E. Shields, Zakariyah Sharif-Sidi, Jacob Smith, Amanda Steahr, Atrin Toussi, Karolyn A. Wanat, Bo Wang, Brian M. Wei, Annika Weinhammer, Scott D. Worswick, Alexander Yang
Journal: JAMA Dermatology (2021)

<h3>Importance</h3> Palmoplantar pustulosis (PPP) is a is a chronic, orphan disease with limited epidemiological data. <h3>Objective</h3> To describe the clinical characteristics, treatments, longitudinal disease course, and health care utilization in adults with PPP across the US. <h3>Design, Setting, and Participants</h3> This retrospective, longitudinal case series from 20 academic dermatology practices in the US included a consecutive sample of 197 adults who met the European Rare and Severe Psoriasis Expert Network consensus definition for PPP between January 1, 2007, and December 31, 2018. Data analysis was performed June 2020 to December 2020. <h3>Main Outcomes and Measures</h3> The primary outcome was to describe the patient characteristics, associated medical comorbidities, treatment patterns, complications, and PPP-specific health care utilization. <h3>Results</h3> Of 197 patients, 145 (73.6%) were female, and the mean (SD) age at presentation was 53.0 (12.6) years, with a mean (SD) follow-up time of 22.1 (28.0) months. On initial presentation, 95 (48.2%) patients reported skin pain, and 39 (19.8%) reported difficulty using hands and/or feet. Seventy patients (35.5%) were treated with systemic treatments, and use of more than 20 different systemic therapies was reported. In patients with at least 6 months of follow-up (n = 128), a median (IQR) of 3.7 (4-10) dermatology visits per year were reported; 24 (18.8%) patients had 5 or more visits during the study period. <h3>Conclusions and Relevance</h3> In this case series, PPP was associated with persistent symptoms, continued health care utilization, and a lack of consensus regarding effective treatments, emphasizing the unmet medical need in this population. Additional research is necessary to understand treatment response in these patients.
2021 ACC/AHA/SCAI Guideline for Coronary Artery Revascularization
Authors: Jennifer S. Lawton, Jacqueline E. Tamis-Holland, Sripal Bangalore, Eric R. Bates, Theresa M. Beckie, James M. Bischoff, John A. Bittl, Mauricio G. Cohen, J. Michael DiMaio, Creighton W. Don, Stephen E. Fremes, Mario F. Gaudino, Zachary D. Goldberger, Michael C. Grant, Jang B. Jaswal, Paul A. Kurlansky, Roxana Mehran, Thomas S. Metkus, Lorraine C. Nnacheta, Sunil V. Rao, Frank W. Sellke, Garima Sharma, Celina M. Yong, Brittany A. Zwischenberger
Journal: Journal of the American College of Cardiology (2021)