Publications by authors named "Daniel Sellers"

12 Publications

  • Page 1 of 1

Protective efficacy of Ad26.COV2.S against SARS-CoV-2 B.1.351 in macaques.

Nature 2021 08 23;596(7872):423-427. Epub 2021 Jun 23.

Bioqual, Rockville, MD, USA.

The emergence of SARS-CoV-2 variants that partially evade neutralizing antibodies poses a threat to the efficacy of current COVID-19 vaccines. The Ad26.COV2.S vaccine expresses a stabilized spike protein from the WA1/2020 strain of SARS-CoV-2, and has recently demonstrated protective efficacy against symptomatic COVID-19 in humans in several geographical regions-including in South Africa, where 95% of sequenced viruses in cases of COVID-19 were the B.1.351 variant. Here we show that Ad26.COV2.S elicits humoral and cellular immune responses that cross-react with the B.1.351 variant and protects against B.1.351 challenge in rhesus macaques. Ad26.COV2.S induced lower binding and neutralizing antibodies against B.1.351 as compared to WA1/2020, but elicited comparable CD8 and CD4 T cell responses against the WA1/2020, B.1.351, B.1.1.7, P.1 and CAL.20C variants. B.1.351 infection of control rhesus macaques resulted in higher levels of virus replication in bronchoalveolar lavage and nasal swabs than did WA1/2020 infection. Ad26.COV2.S provided robust protection against both WA1/2020 and B.1.351, although we observed higher levels of virus in vaccinated macaques after B.1.351 challenge. These data demonstrate that Ad26.COV2.S provided robust protection against B.1.351 challenge in rhesus macaques. Our findings have important implications for vaccine control of SARS-CoV-2 variants of concern.
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http://dx.doi.org/10.1038/s41586-021-03732-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8373608PMC
August 2021

Immunogenicity of COVID-19 mRNA Vaccines in Pregnant and Lactating Women.

JAMA 2021 06;325(23):2370-2380

Harvard Medical School, Boston, Massachusetts.

Importance: Pregnant women are at increased risk of morbidity and mortality from COVID-19 but have been excluded from the phase 3 COVID-19 vaccine trials. Data on vaccine safety and immunogenicity in these populations are therefore limited.

Objective: To evaluate the immunogenicity of COVID-19 messenger RNA (mRNA) vaccines in pregnant and lactating women, including against emerging SARS-CoV-2 variants of concern.

Design, Setting, And Participants: An exploratory, descriptive, prospective cohort study enrolled 103 women who received a COVID-19 vaccine from December 2020 through March 2021 and 28 women who had confirmed SARS-CoV-2 infection from April 2020 through March 2021 (the last follow-up date was March 26, 2021). This study enrolled 30 pregnant, 16 lactating, and 57 neither pregnant nor lactating women who received either the mRNA-1273 (Moderna) or BNT162b2 (Pfizer-BioNTech) COVID-19 vaccines and 22 pregnant and 6 nonpregnant unvaccinated women with SARS-CoV-2 infection.

Main Outcomes And Measures: SARS-CoV-2 receptor binding domain binding, neutralizing, and functional nonneutralizing antibody responses from pregnant, lactating, and nonpregnant women were assessed following vaccination. Spike-specific T-cell responses were evaluated using IFN-γ enzyme-linked immunospot and multiparameter intracellular cytokine-staining assays. Humoral and cellular immune responses were determined against the original SARS-CoV-2 USA-WA1/2020 strain as well as against the B.1.1.7 and B.1.351 variants.

Results: This study enrolled 103 women aged 18 to 45 years (66% non-Hispanic White) who received a COVID-19 mRNA vaccine. After the second vaccine dose, fever was reported in 4 pregnant women (14%; SD, 6%), 7 lactating women (44%; SD, 12%), and 27 nonpregnant women (52%; SD, 7%). Binding, neutralizing, and functional nonneutralizing antibody responses as well as CD4 and CD8 T-cell responses were present in pregnant, lactating, and nonpregnant women following vaccination. Binding and neutralizing antibodies were also observed in infant cord blood and breast milk. Binding and neutralizing antibody titers against the SARS-CoV-2 B.1.1.7 and B.1.351 variants of concern were reduced, but T-cell responses were preserved against viral variants.

Conclusion And Relevance: In this exploratory analysis of a convenience sample, receipt of a COVID-19 mRNA vaccine was immunogenic in pregnant women, and vaccine-elicited antibodies were transported to infant cord blood and breast milk. Pregnant and nonpregnant women who were vaccinated developed cross-reactive antibody responses and T-cell responses against SARS-CoV-2 variants of concern.
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http://dx.doi.org/10.1001/jama.2021.7563DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8120446PMC
June 2021

Enhanced Recovery for Liver Transplantation: A First Step on a Long Road.

Transplantation 2021 May 6. Epub 2021 May 6.

Department of Anesthesiology and Pain Medicine, University of Toronto, Canada Multi-Organ Transplant and HPB Surgical Oncology, Division of General Surgery, Department of Surgery, University of Toronto, Canada Multi-Organ Transplant, Department of Medicine, University of Toronto, Canada Multi-Organ Transplant, Anesthesiology and Pain Medicine, University of Toronto, Canada.

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http://dx.doi.org/10.1097/TP.0000000000003809DOI Listing
May 2021

A Pragmatic Non-Randomized Trial of Prehabilitation Prior to Cancer Surgery: Study Protocol and COVID-19-Related Adaptations.

Front Oncol 2021 10;11:629207. Epub 2021 Mar 10.

Faculty of Medicine, University of Toronto, Toronto, ON, Canada.

Background: Experimental data highlight the potential benefits and health system cost savings related to surgical prehabilitation; however, adequately powered randomized controlled trial (RCT) data remain nascent. Emerging prehabilitation services may be informed by early RCT data but can be limited in informing real-world program development. Pragmatic trials emphasize external validity and generalizability to understand and advise intervention development and implementation in clinical settings. This paper presents the methodology of a pragmatic prehabilitation trial to complement emerging phase III clinical trials and inform implementation strategies.

Methods: This is a pilot pragmatic clinical trial conducted in a large academic hospital in Toronto, Ontario, Canada to assess feasibility of clinical implementation and derive estimates of effectiveness. Feasibility data include program referral rates, enrolment and attrition, intervention adherence and safety, participant satisfaction, and barriers and facilitators to programming. The study aims to receive 150 eligible referrals for adult, English-speaking, preoperative oncology patients with an identified indication for prehabilitation (., frailty, deconditioning, malnutrition, psychological distress). Study participants undergo a baseline assessment and shared-decision making regarding the intervention setting: either facility-based prehabilitation or home-based prehabilitation. In both scenarios, participants receive an individualized exercise prescription, stress-reduction psychological support, nutrition counseling, and protein supplementation, and if appropriate, smoking cessation program referrals. Secondary objectives include estimating intervention effects at the week prior to surgery and 30 and 90 days postoperatively. Outcomes include surgical complications, postoperative length of stay, mortality, hospital readmissions, physical fitness, psychological well-being, and quality of life. Data from participants who decline the intervention but consent for research-related access to health records will serve as comparators. The COVID-19 pandemic required the introduction of a 'virtual program' using only telephone or internet-based communication for screening, assessments, or intervention was introduced.

Conclusion: This pragmatic trial will provide evidence on the feasibility and viability of prehabilitation services delivered under usual clinical conditions. Study amendments due to the COVID-19 pandemic are presented as strategies to maintain prehabilitation research and services to potentially mitigate the consequences of extended surgery wait times.
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http://dx.doi.org/10.3389/fonc.2021.629207DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7987917PMC
March 2021

Myocardial Preconditioning With Volatile Anesthetics: Goodbye to All That?

J Cardiothorac Vasc Anesth 2020 12 20;34(12):3257-3258. Epub 2020 Aug 20.

Department of Anesthesia and Pain Management, Toronto General Hospital, University Health Network, University of Toronto, Toronto, Canada.

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http://dx.doi.org/10.1053/j.jvca.2020.08.032DOI Listing
December 2020

Massively parallel screening of synthetic microbial communities.

Proc Natl Acad Sci U S A 2019 06 11;116(26):12804-12809. Epub 2019 Jun 11.

Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139;

Microbial communities have numerous potential applications in biotechnology, agriculture, and medicine. Nevertheless, the limited accuracy with which we can predict interspecies interactions and environmental dependencies hinders efforts to rationally engineer beneficial consortia. Empirical screening is a complementary approach wherein synthetic communities are combinatorially constructed and assayed in high throughput. However, assembling many combinations of microbes is logistically complex and difficult to achieve on a timescale commensurate with microbial growth. Here, we introduce the kChip, a droplets-based platform that performs rapid, massively parallel, bottom-up construction and screening of synthetic microbial communities. We first show that the kChip enables phenotypic characterization of microbes across environmental conditions. Next, in a screen of ∼100,000 multispecies communities comprising up to 19 soil isolates, we identified sets that promote the growth of the model plant symbiont in a manner robust to carbon source variation and the presence of additional species. Broadly, kChip screening can identify multispecies consortia possessing any optically assayable function, including facilitation of biocontrol agents, suppression of pathogens, degradation of recalcitrant substrates, and robustness of these functions to perturbation, with many applications across basic and applied microbial ecology.
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http://dx.doi.org/10.1073/pnas.1900102116DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6600964PMC
June 2019

Response: The Evolution of Lung Transplant Anesthesia.

J Cardiothorac Vasc Anesth 2018 02 19;32(1):e1. Epub 2017 Apr 19.

Toronto Lung Transplant Program, Toronto General Hospital, Toronto, ON, Canada.

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http://dx.doi.org/10.1053/j.jvca.2017.04.028DOI Listing
February 2018

Anesthesia for Pulmonary Endarterectomy and Extracorporeal Membrane Oxygenation in a Patient With Achondroplasia.

J Cardiothorac Vasc Anesth 2017 10 8;31(5):1789-1794. Epub 2017 Feb 8.

Toronto General Hospital, Toronto, ON, Canada.

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http://dx.doi.org/10.1053/j.jvca.2017.02.038DOI Listing
October 2017

The Evolution of Anesthesia for Lung Transplantation.

J Cardiothorac Vasc Anesth 2017 06 22;31(3):1071-1079. Epub 2016 Nov 22.

Toronto General Hospital, Toronto, ON, Canada.

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http://dx.doi.org/10.1053/j.jvca.2016.11.034DOI Listing
June 2017

Dexmedetomidine: magic bullet or firing blanks?

J Thorac Dis 2016 Nov;8(11):3024-3027

Department of Anesthesia and Pain Management, Toronto General Hospital, University of Toronto, Toronto, Canada.

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http://dx.doi.org/10.21037/jtd.2016.11.34DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5179421PMC
November 2016

Introduction of microsurgery in Vietnam by a charitable organization: a 15-year experience.

Plast Reconstr Surg 2007 Apr;119(4):1267-1273

Hanoi, Vietnam; Springfield, Ill.; Toronto, Ontario, Canada; Taipei, Taiwan; and Boston, Mass. From Military Hospital 108; Southern Illinois University; Toronto General Hospital; Chang Gung Memorial Hospital; and Brigham and Women's Hospital, Harvard Medical School.

Background: Microsurgical procedures, although equipment- and labor-intensive, allow efficient treatment of selected soft-tissue, bone, and peripheral nerve defects. The precise surgical skills required and the high equipment and institutional costs have been deterrents to initiating programs in developing countries. The authors report their 15-year international effort in facilitating the development of microsurgical techniques in Vietnam.

Methods: The authors reviewed their educational, logistical, and operative experience from 11 Operation Smile International missions to Vietnam and the microsurgical procedures performed independently by Vietnamese surgeons at the Central Military Hospital 108 in Hanoi.

Results: Over 15 years, Operation Smile International missions to Vietnam performed 108 free tissue transfer operations with 15 peripheral nerve transfer procedures and 143 nonmicrosurgical reconstructive operations. Visiting surgeons with specialized expertise taught facial reanimation, flap prefabrication, and perforator flaps. During this same period, Vietnamese surgeons became facile with microsurgical techniques and independently performed a wide array of these procedures in the institutions visited. Vietnamese surgeons have organized microsurgery divisions within some hospital departments and now teach microsurgical techniques. Repeated missions allowed for patient follow-up, staged procedures, educational exchange, and quality control. Several Vietnamese surgeons have traveled abroad to obtain additional training and have set up training programs in other areas of Vietnam.

Conclusions: Charitable organizations can help surgeons in developing countries master complex microsurgical techniques through short-term medical missions, donation of equipment and supplies, and the encouragement of institutional support. A continuing education program, including local conferences, microsurgical laboratory training facilities, and study abroad, can aid this introduction.
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http://dx.doi.org/10.1097/01.prs.0000254544.65054.95DOI Listing
April 2007
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