tbuckley/cabot-search huggingface dataset:
Improving the quality of oral cancer drug delivery across a health system.
Authors: Katherine Enright, Rosemary Ku, Daniela Gallo-Hershberg, Aliya Pardhan, Leta Marie Forbes
Journal: Journal of Clinical Oncology (2020)

184 Background: Oral systemic therapy (ST) presents unique care delivery challenges. Gaps in patient education and monitoring for patients on oral ST delivery are well documented and can result in decreased adherence or increased toxicity. Within Ontario, cancer care is provincially coordinated through Ontario Health- Cancer Care Ontario (OH-CCO), but locally implemented by 14 Regional Cancer Programs (RCPs). Using a centrally coordinated, but regionally implemented quality improvement (QI) approach, we aimed to improve the quality of oral ST delivery across Ontario by enabling the use of patient specific monitoring plans to optimize treatment adherence and toxicity management. Methods: Between 2018 and 2020 a 2 year focused QI project was undertaken. A suite of 19 quality measures were developed to measure different quality domains for oral ST delivery including treatment plan documentation, patient education, toxicity/adherence monitoring and toxicity outcomes. In year 1, all regions used the suite of quality measures to establish baseline performance and develop a QI plan using rapid cycle improvement methodology to improve performance in at least 1 domain based on regional gaps and priorities. Projects were implemented and evaluated during year 2. OH-CCO provided QI coaching through dissemination of standardized QI tools, a monthly discussion forum and project specific feedback. At the end of year 2, a post-implementation evaluation was performed for each region. Results: 15 centers participated, representing all RCPs across Ontario. The participating centers implemented QI projects focused on treatment plan documentation (N = 3), patient education (N = 10) and toxicity/adherence management (N = 5), with some focusing on multiple domains. All centers reported an improvement in at least 1 domain (see Table). Key enablers identified include engagement with a multi-disciplinary team and the use of technology, while barriers include lack of onsite dispensing pharmacy. Future work will continue to focus on quality of oral ST delivery and better pharmacy integration. Conclusions: Through a centrally coordinated, locally implemented QI project, improvement in quality of oral ST care was achieved across Ontario. This model of QI focus has the potential to be adaptable across health systems. [Table: see text]
Relapsing Mitral Involvement in Antineutrophil Cytoplasmic Antibody–Associated Vasculitis
Authors: Aurélie Briane, Bastien Jamet, Antoine Mugniot, Antoine Néel, Christian Agard
Journal: Clinical Nuclear Medicine (2020)

Abstract Cardiac valvular involvement in antineutrophil cytoplasmic antibody (ANCA)–associated vasculitis is very rare. We report the case of a patient seen in 2019, followed for ANCA-associated vasculitis for 15 years, who had a first relapse with cardiac valvular involvement in 2012, and who underwent a second histologically proven vasculitis relapse involving mitral periprosthetic endocardium. PET/CT imaging showed an intense and focal FDG activity of paramitral bioprosthesis leak site. Mitral bioprosthesis was replaced, and the patient improved with steroids and rituximab. Through this exceptional case, we suggest that FDG PET/CT could be of interest in the follow-up of ANCA-associated vasculitis with cardiac valvular involvement.
Exome Sequencing for Prenatal Diagnosis in Nonimmune Hydrops Fetalis
Authors: Teresa N. Sparks, Billie R. Lianoglou, Rebecca R. Adami, Ilina D. Pluym, Kerry Holliman, Jennifer Duffy, Sarah L. Downum, Sachi Patel, Amanda Faubel, Nina M. Boe, Nancy T. Field, Aisling Murphy, Louise C. Laurent, Jennifer Jolley, Cherry Uy, Anne M. Slavotinek, Patrick Devine, Ugur Hodoglugil, Jessica Van Ziffle, Stephan J. Sanders, Tippi C. MacKenzie, Mary E. Norton
Journal: New England Journal of Medicine (2020)

The cause of most fetal anomalies is not determined prenatally. Exome sequencing has transformed genetic diagnosis after birth, but its usefulness for prenatal diagnosis is still emerging. Nonimmune hydrops fetalis (NIHF), a fetal abnormality that is often lethal, has numerous genetic causes; the extent to which exome sequencing can aid in its diagnosis is unclear.We evaluated a series of 127 consecutive unexplained cases of NIHF that were defined by the presence of fetal ascites, pleural or pericardial effusions, skin edema, cystic hygroma, increased nuchal translucency, or a combination of these conditions. The primary outcome was the diagnostic yield of exome sequencing for detecting genetic variants that were classified as either pathogenic or likely pathogenic according to the criteria of the American College of Medical Genetics and Genomics. Secondary outcomes were the percentage of cases associated with specific genetic disorders and the proportion of variants that were inherited.In 37 of the 127 cases (29%), we identified diagnostic genetic variants, including those for disorders affecting the RAS-MAPK cell-signaling pathway (known as RASopathies) (30% of the genetic diagnoses); inborn errors of metabolism and musculoskeletal disorders (11% each); lymphatic, neurodevelopmental, cardiovascular, and hematologic disorders (8% each); and others. Prognoses ranged from a relatively mild outcome to death during the perinatal period. Overall, 68% of the cases (25 of 37) with diagnostic variants were autosomal dominant (of which 12% were inherited and 88% were de novo), 27% (10 of 37) were autosomal recessive (of which 95% were inherited and 5% were de novo), 1 was inherited X-linked recessive, and 1 was of uncertain inheritance. We identified potentially diagnostic variants in an additional 12 cases.In this large case series of 127 fetuses with unexplained NIHF, we identified a diagnostic genetic variant in approximately one third of the cases. (Funded by the UCSF Center for Maternal-Fetal Precision Medicine and others; ClinicalTrials.gov number, NCT03412760.).
Achieving zero covid is not easy, but the alternative is far worse
Authors: Martin McKee
Journal: BMJ (2020)

Thornley and colleagues confuse eradication, permanent reduction to zero of the worldwide incidence of infection, with the reduction to zero of infection in a defined geographical area.12 New Zealand, and other countries, has shown that elimination of SARS-CoV-2 transmission can be achieved for periods of time, even though the virus might occasionally be imported either in infected individuals or on fomites, as seems likely to have been the case in Auckland. An elimination strategy accepts this and adopts measures to prevent further spread throughout the country. …
A compromised developmental trajectory of the infant gut microbiome and metabolome in atopic eczema
Authors: Le Duc Huy Ta, James Chun Yip Chan, Gaik Chin Yap, Rikky W. Purbojati, Daniela I. Drautz-Moses, Yanqing Michelle Koh, Carina Jing Xuan Tay, Chiung-Hui Huang, Dorinda Yan Qin Kioh, Jia Yun Woon, Elizabeth Huiwen Tham, Evelyn Xiu Ling Loo, Lynette P.C. Shek, Neerja Karnani, Anne Goh, Hugo P.S. Van Bever, Oon Hoe Teoh, Yiong Huak Chan, Christophe Lay, Jan Knol, Fabian Yap, Kok Hian Tan, Yap-Seng Chong, Keith M. Godfrey, Staffan Kjelleberg, Stephan C. Schuster, Eric Chun Yong Chan, Bee Wah Lee
Journal: Gut Microbes (2020)

Evidence is accumulating that the establishment of the gut microbiome in early life influences the development of atopic eczema. In this longitudinal study, we used integrated multi-omics analyses to infer functional mechanisms by which the microbiome modulates atopic eczema risk. We measured the functionality of the gut microbiome and metabolome of 63 infants between ages 3 weeks and 12 months with well-defined eczema cases and controls in a sub-cohort from the Growing Up in Singapore Toward healthy Outcomes (GUSTO) mother-offspring cohort. At 3 weeks, the microbiome and metabolome of allergen-sensitized atopic eczema infants were characterized by an enrichment of Escherichia coli and Klebsiella pneumoniae, associated with increased stool D-glucose concentration and increased gene expression of associated virulence factors. A delayed colonization by beneficial Bacteroides fragilis and subsequent delayed accumulation of butyrate and propionate producers after 3 months was also observed. Here, we describe an aberrant developmental trajectory of the gut microbiome and stool metabolome in allergen sensitized atopic eczema infants.The infographic describes an impaired developmental trajectory of the gut microbiome and metabolome in allergen-sensitized atopic eczema (AE) infants and infer its contribution in modulating allergy risk in the Singaporean mother-offspring GUSTO cohort. The key microbial signature of AE is characterized by (1) an enrichment of Escherichia coli and Klebsiella pneumoniae which are associated with accumulation of pre-glycolysis intermediates (D-glucose) via the trehalose metabolic pathway, increased gene expression of associated virulence factors (invasin, adhesin, flagellin and lipopolysaccharides) by utilizing ATP from oxidative phosphorylation and delayed production of butyrate and propionate, (2) depletion of Bacteroides fragilis which resulted in lower expression of immunostimulatory bacterial cell envelope structure and folate (vitamin B9) biosynthesis pathway, and (3) accompanied depletion of bacterial groups with the ability to derive butyrate and propionate through direct or indirect pathways which collectively resulted in reduced glycolysis, butyrate and propionate biosynthesis.
Pan-HLA prediction of SARS-CoV-2 epitopes
Authors: Katie M. Campbell, Gabriela Steiner, Daniel K. Wells, Antoni Ribas, Anusha Kalbasi
Journal: Clinical Cancer Research (2020)

Introduction: Delineating antiviral T-cell responses to SARS-CoV-2 may shed light on the heterogeneity of clinicaloutcomes and inform vaccine or therapeutic approaches  Viral antigens can be predicted using computational toolsthat calculate the binding affinity between viral peptides and antigen presentation machinery  However, in order toaccount for the role of host genetics in the diversity of responses, this analysis must be performed withconsideration of the global diversity of the human leukocyte antigen (HLA) proteins responsible for antigenpresentation  Methods: We deployed binding predictions across the SARS-CoV-2 peptidome for 9,360 Class I HLA alleles (2,987HLA-A;3,707 HLA-B;2,666 HLA-C;9-mers) using a consensus approach of 7 algorithms and 3,486 Class II HLAalleles (15-mers) using a consensus approach of 4 algorithms  All pMHC predictions were filtered to include onlythose with consensus binding less than 500 nM  Results: There were 368,145 unique combinations of peptides and HLA alleles (pMHCs) with a predicted bindingaffinity of less than 500nM, including 1,103 unique 9-mer and 2,547 15-mer peptides and 1,022 MHC Class I and8,075 MHC Class II HLA proteins  Of these pMHCs, 82% of 9-mers overlapped with 15-mers, suggesting cross-presentation to both CD4 and CD8 T cells in a subset of individuals  We evaluated this filtered dataset with respectto the population frequency of HLA haplotypes  While the predicted susceptibility of SARS-CoV-2 antigenpresentation differed greatly across countries, there was a subset of 21 Class I antigens shared by common HLAtypes across 30 or more countries (out of 79 countries with reported population frequency data)  Our database hasbeen made publicly available, and we have developed a user interface to explore the results based upon viralproteins, HLA alleles, or country populations of interest  Conclusions: With the ongoing SARS-CoV-2 pandemic, there are worldwide efforts to generate a successfulvaccine and to evaluate clinical samples to understand the viral pathogenesis and diverse outcomes in patients This application can serve as a guide to identify responses of putative SARS-CoV-2-specific T cells across patients with a broad range of HLA haplotypes internationally
Physical activity is good for older adults—but is programme implementation being overlooked? A systematic review of intervention studies that reported frameworks or measures of implementation
Authors: Samantha M Gray, Heather A McKay, Lindsay Nettlefold, Douglas Race, Heather M Macdonald, Patti-Jean Naylor, Joanie Sims-Gould
Journal: British Journal of Sports Medicine (2020)

To examine older adult physical activity (PA) intervention studies that evaluated implementation and/or scale-up. Research question 1: What implementation and/or scale-up indicators (specific, observable and measurable characteristics that show the progress of implementation) were reported? Research question 2: What implementation and/or scale-up frameworks were reported? Research question 3: Did studies evaluate the relationship between implementation or scale-up of the intervention and individual level health/behaviour outcomes? If yes, how?Systematic review.Publications from electronic databases and hand searches (2000 to December 2019).Any PA intervention studies with community-dwelling older adult participants (mean age ≥60 years). Required indicators: (a) Must report amount of PA as an outcome, with validated self-report or objective measures, and (b) Must have reported at least one implementation or scale-up framework and/or one implementation or scale-up indicator.137 studies were included for research question 1, 11 for question 2 and 22 for question 3. 137 studies reported an implementation indicator: 14 unique indicators. None were specified as indicators for scale-up evaluation. 11 studies were guided by an implementation or scale-up framework. 22 studies described a relationship between an implementation indicator and an individual-level health outcome.There is need for implementation research that extends beyond analysis at the individual level, includes clearly defined indicators and provides a guiding framework to support PA initiatives in older adults. Such implementation studies should evaluate factors in the broader context (eg,political, environmental) that influence scale-up.CRD42018091839.
Effects of COVID-19 on an academic breast oncology center in New York City.
Authors: Jake Prigoff, Grace Hillyer, Fletcher Bell, Melissa Kate Accordino
Journal: Journal of Clinical Oncology (2020)

51 Background: The influx of patients to the healthcare system due to COVID-19 impacted healthcare practices including the care of breast cancer patients. Our aim is to describe the impact this pandemic had on breast cancer care delivery at an academic center in NYC to inform policy and procedure for future crises that limit patient access to on-site facilities. Methods: A survey was sent to physicians involved in the care of patients with breast cancer at Columbia University Irving Medical Center in May 2020. Participants were asked about practice structure and changes to breast cancer care. The primary outcome was the degree that providers believed breast oncology patients’ clinical outcomes were significantly impacted by COVID-19. Secondary outcomes included changes in diagnostic and management approaches and advice for future providers faced with a similar pandemic. Results: The response rate was 65.4% (17/26). This included physicians from medical oncology (n = 7), radiology (n = 4), breast surgery (n = 3), radiation oncology (n = 2), and plastic surgery (n = 1). Seventy-six percent of physicians somewhat agreed, agreed, or strongly agreed that oncologic outcomes may be significantly impacted by the COVID-19 pandemic. Nearly half (47%) of respondents reported delays in the workup of patients due to COVID-19 with 50.0% for mammograms, 47.5% for bone scans, 46.0% for ultrasounds, 43.8% for PET scans, and 43.3% for biopsies. Eighty-two percent reported delays in overall oncologic management. Delays to systemic therapy were: intravenous/targeted therapy (37.9%), intramuscular/subcutaneous endocrine therapy (28.3%), oral chemotherapy/targeted therapy (22.9%), and oral endocrine therapy (12.8%). Delays to local therapy were: surgery (64.4%) and radiation therapy (44.6%). Almost two-thirds (64.7%) reported it necessary to use alternative oncologic management strategies. The most common piece of advice our providers offered was to increase testing capacity to all patients, especially when coming to a healthcare facility. Conclusions: The COVID-19 pandemic has caused major disruption to breast cancer practices. Breast oncology physicians reported delays in management in over 80% of patients, and the need to use alternative management strategies in over 60% of patients. Effects of these disruptions on oncologic outcomes are unknown, but over 75% of our physicians believe this will significantly impact breast oncology patients’ outcomes. There's a need for policies and procedures to structure patient care should there be a future crisis that limits patient access to oncologic care.
A multicentered academic medical center experience of a simulated root cause analysis (RCA) for hematology/oncology fellows.
Authors: Danielle Wallace, Denise Cochran, Jennifer Michelle Duff, Julia Lee Close, Martina Cathryn Murphy, Arpan Patel
Journal: Journal of Clinical Oncology (2020)

188 Background: Quality improvement and patient safety education is an Accreditation Council for Graduate Medical Education (ACGME) common program requirement for hematology/oncology fellowships. Specifically, the ACGME requires trainee participation in interprofessional clinical patient safety activities, such as root cause analyses. These can be challenging to incorporate into busy schedules and are intimidating to some trainees, but simulated RCAs are a novel way to assure trainees gain important patient safety skills. We report on a multicentered experience utilizing a simulated RCA educational module in an attempt to provide fellows with the tools needed to participate in a live RCA and to increase awareness of the need to analyze patient safety events. Methods: The two-hour module included a didactic session explaining the basics of an RCA including common terminology, effective chart review, and personal interviews. The fellows assessed a patient safety event of a missed coagulopathy and created an event flow map and fishbone analysis. They then formed root cause/contributing factor statements and proposed a solution. Seventeen fellows from two institutions completed pre- and post-session surveys regarding the experience. Results: There was a 47% increase in both the percentage of fellows who felt comfortable participating in live RCAs in the future, and in the number of fellows who felt comfortable with using the tools typically utilized in an RCA. 70.59% of respondents felt that as a result of the mock RCA, they were more likely to report a near miss or adverse event. Conclusions: Mock RCAs are a feasible method of incorporating ACGME-required patient safety activities into hematology/oncology fellow education and are effective in increasing their comfort and understanding of important quality improvement skills
Olympic competition climbing: the beginning of a new era—a narrative review
Authors: Christoph Lutter, Thomas Tischer, Volker Rainer Schöffl
Journal: British Journal of Sports Medicine (2020)

Climbing as a competition sport has become increasingly popular in recent years, particularly the sub-discipline of bouldering. The sport will debut in the Tokyo Summer Olympic Games. National and international competitions have three disciplines: lead (climbing with rope protection), bouldering (climbing at lower heights with mattress floor protection) and speed (maximum speed climbing on a standardised route in 1-on-1 mode). There is also a ‘combined mode’ of all three disciplines ( combined ) which forms the Olympic competition format; all competition formats are held on artificial walls. Existing literature describes a predominantly low injury frequency and severity in elite climbing. In comparison to climbing on real rock, artificial climbing walls have recently been associated with higher injury rates. Finger injuries such as tenosynovitis, pulley lesions and growth plate injuries are the most common injuries. As finger injuries are sport-specific, medical supervision of climbing athletes requires specific medical knowledge for diagnosis and treatment. There is so far little evidence on effective injury prevention measures in top athletes, and antidoping measures, in general, requiring further work in this field. An improved data situation regarding high-performance climbing athletes is crucial to ensure that the sport continues to be largely safe and injury-free and to prevent doping cases as extensively as possible.
Combined Inhibition of SHP2 and MEK Is Effective in Models of NF1-Deficient Malignant Peripheral Nerve Sheath Tumors
Authors: Jiawan Wang, Kai Pollard, Amy N. Allen, Tushar Tomar, Dirk Pijnenburg, Zhan Yao, Fausto J. Rodriguez, Christine A. Pratilas
Journal: Cancer Research (2020)

Abstract Loss of the RAS GTPase-activating protein (RAS-GAP) NF1 drives aberrant activation of RAS/MEK/ERK signaling and other effector pathways in the majority of malignant peripheral nerve sheath tumors (MPNST). These dysregulated pathways represent potential targets for therapeutic intervention. However, studies of novel single agents including MEK inhibitors (MEKi) have demonstrated limited efficacy both preclinically and clinically, with little advancement in overall patient survival. By interrogation of kinome activity through an unbiased screen and targeted evaluation of the signaling response to MEK inhibition, we have identified global activation of upstream receptor tyrosine kinases (RTK) that converges on activation of RAS as a mechanism to limit sensitivity to MEK inhibition. As no direct inhibitors of pan-RAS were available, an inhibitor of the protein tyrosine phosphatase SHP2, a critical mediator of RAS signal transduction downstream of multiple RTK, represented an alternate strategy. The combination of MEKi plus SHP099 was superior to MEKi alone in models of NF1-MPNST, including those with acquired resistance to MEKi. Our findings have immediate translational implications and may inform future clinical trials for patients with MPNST harboring alterations in NF1. Significance: Combined inhibition of MEK and SHP2 is effective in models of NF1-MPNST, both those naïve to and those resistant to MEKi, as well as in the MPNST precursor lesion plexiform neurofibroma.