tbuckley/cabot-search huggingface dataset:
“Coming out” against cancer: How local outreach to the LGBT community can reduce cancer disparities.
Authors: Tyler Stimpert
Journal: Journal of Clinical Oncology (2020)

131 Background: Lesbian, Gay, Bisexual, and Transgender (LGBT) individuals make up an estimated 4% of the population, qualifying them as a sexual minority. LGBT individuals are also more likely to be a racial or gender minority, to live in poverty, and to have less social support than their heterosexual peers. LGBT populations are disproportionately affected by mental health issues such as depression, which are correlated not only with behavioral risk factors, but with less likelihood to comply with healthcare screening or treatment. Approximately 30% of LGBT adults do not seek health care services or lack a regular health care provider, compared with 10% of heterosexuals. Research studies demonstrate that knowledge about increased risks and need for screening is low in LGBT populations. Sub-populations are less likely to have had a recent mammogram, anal or cervical Pap, or a prostate exam. Methods: We implemented a population-oriented program into our community outreach team in 2019 to address LGBT cancer disparities. A program manager partnered with community resources and leaders, including the Cleveland LGBT Community Center, Plexus LGBT Chamber of Commerce, and Trans Ohio. First year programming included a mammogram clinic for sexual/gender minority (SGM) women, “Cancer is a DRAG” show, and a tobacco-free campaign for LGBT pride month. Results: Creating meaningful partnerships was extremely important to community leaders and organizations. Strategic plans include direct community input and engagement through a community council, in conjunction with the LGBT Community Center, a breast cancer awareness campaign, in conjunction with local entertainers, and a tobacco cessation program, through our Center for LGBT Care. We educated over 150 people and screened over 85 within the first year. Conclusions: When our healthcare institution met local LGBT people within their community, the result was quite impactful. This pilot program proved successful at educating members of the community about their increased cancer risk, which resulted in higher cancer screening rates for LGBT people. More programs tailored to LGBT-specific health concerns are important to continue reaching these populations and eventually decrease health disparities in the community.
Functional Precision Medicine Identifies New Therapeutic Candidates for Medulloblastoma
Authors: Jessica M. Rusert, Edwin F. Juarez, Sebastian Brabetz, James Jensen, Alexandra Garancher, Lianne Q. Chau, Silvia K. Tacheva-Grigorova, Sameerah Wahab, Yoko T. Udaka, Darren Finlay, Huriye Seker-Cin, Brendan Reardon, Susanne Gröbner, Jonathan Serrano, Jonas Ecker, Lin Qi, Mari Kogiso, Yuchen Du, Patricia A. Baxter, Jacob J. Henderson, Michael E. Berens, Kristiina Vuori, Till Milde, Yoon-Jae Cho, Xiao-Nan Li, James M. Olson, Iris Reyes, Matija Snuderl, Terence C. Wong, David P. Dimmock, Shareef A. Nahas, Denise Malicki, John R. Crawford, Michael L. Levy, Eliezer M. Van Allen, Stefan M. Pfister, Pablo Tamayo, Marcel Kool, Jill P. Mesirov, Robert J. Wechsler-Reya
Journal: Cancer Research (2020)

Medulloblastoma is among the most common malignant brain tumors in children. Recent studies have identified at least four subgroups of the disease that differ in terms of molecular characteristics and patient outcomes. Despite this heterogeneity, most patients with medulloblastoma receive similar therapies, including surgery, radiation, and intensive chemotherapy. Although these treatments prolong survival, many patients still die from the disease and survivors suffer severe long-term side effects from therapy. We hypothesize that each patient with medulloblastoma is sensitive to different therapies and that tailoring therapy based on the molecular and cellular characteristics of patients' tumors will improve outcomes. To test this, we assembled a panel of orthotopic patient-derived xenografts (PDX) and subjected them to DNA sequencing, gene expression profiling, and high-throughput drug screening. Analysis of DNA sequencing revealed that most medulloblastomas do not have actionable mutations that point to effective therapies. In contrast, gene expression and drug response data provided valuable information about potential therapies for every tumor. For example, drug screening demonstrated that actinomycin D, which is used for treatment of sarcoma but rarely for medulloblastoma, was active against PDXs representing Group 3 medulloblastoma, the most aggressive form of the disease. Functional analysis of tumor cells was successfully used in a clinical setting to identify more treatment options than sequencing alone. These studies suggest that it should be possible to move away from a one-size-fits-all approach and begin to treat each patient with therapies that are effective against their specific tumor. SIGNIFICANCE: These findings show that high-throughput drug screening identifies therapies for medulloblastoma that cannot be predicted by genomic or transcriptomic analysis.
Managing head injury risks in competitive skateboarding: what do we know?
Authors: Andrew Stuart McIntosh, Declan Alexander Patton, Alexander GD McIntosh
Journal: British Journal of Sports Medicine (2020)

Objectives The broad objective of this paper is to inform policy, practice and research regarding the management of head injury risks in competitive skateboarding. The main motivation for the current study was the question of mandating helmet use in competitive skateboarding. The specific aims are to present current knowledge on (A) head injury risks in skateboarding, (B) preliminary biomechanical data on falls and head injury risks in a selection of competitive skateboarding events similar to those planned for the Summer Olympics, (C) standards for skateboard-styled helmets and (D) impact performance of helmets commonly used in skateboarding. Methods A narrative review of the published literature on head injuries in skateboarding was conducted. Videos of skateboarding competitions from Vans Park Professional League, Street League Skateboarding and Dew Tour were reviewed to describe crashes and falls. Standards databases including the International Organization for Standardization (ISO), British Standards Institution (BSI), Snell, United States Consumer Product Safety Commission (CPSC) and American Society for Testing and Materials (ASTM) were searched for skateboarding-styled helmet standards. A sample of helmets considered suitable for skateboarding was tested in standard impact tests. Results The majority of previous literature focused on the paediatric population in a recreational setting with little data from competitive skateboarding. Head injuries comprised up to 75% of all injuries and helmet use was less than 35%. Video analysis identified high rates of falls and crashes during competitive skateboarding, but also a capacity for the athletes to control falls and limit head impacts. Less than 5% of competitive skateboarders wore helmets. In addition to dedicated national skateboard helmet standards, there are several national standards for skateboard-styled helmets. All helmets, with the exception of one uncertified helmet, had similar impact attenuation performance; that is, at 0.8 m drop height, 114–148 g; at 1.5 m, 173–220 g; and at 2.0 m, 219–259 g. Impact performance in the second impact was degraded in all helmets tested. Conclusion Helmets styled for skateboarding are available ‘off the shelf’ that will offer protection to the head against skull fractures and intracranial injuries in competitive skateboarding. There is an urgent need to commence a programme of research and development to understanding and control head injury risks.
Survey of challenges in access to diagnostics and treatment for neuroendocrine tumor (NET) patients (SCAN): Global disparities in quality healthcare for NETs.
Authors: Dirk Van Genechten, Mark McDonnell, Christine Rodien-Louw, Sugandha Dureja, Simone Leyden, Elyse Gellerman, Teodora Kolarova, Catherine Bouvier
Journal: Journal of Clinical Oncology (2020)

127 Background: Neuroendocrine tumors (NETs) are rare and complex neoplasms with increasing incidence and prevalence worldwide. SCAN assessed global delivery of healthcare to NET patients. This analysis focused for the first time on healthcare quality evaluation by economic areas–Advanced Economies (AE) and Emerging and Developing Economies (EDE) classification used as per the International Monetary Fund. Methods: During Sept-Nov 2019, NET patients and healthcare professionals (HCPs) completed an online survey (available in 14 languages). Results: There were 2795 respondents from 68 countries across 6 continents. AE NET patients/carers were 88% [2076/2359], EDE were 12% [283/2359]. HCPs were evenly spread 51% AE [221/436] vs. 49% EDE [215/436]. The average evaluation score provided by NET patients to the healthcare received in the country they reside in for more than 6 months was 3.6 in AE, while one point lower 2.5 in EDE on a 5-point Likert scale (1-poor, 5-excellent). HCPs’ and NET patients’ scores were aligned: 3.9 as per AE HCPs (94% [208/221]), vs. 2.6 by EDE HCPs (68% [190/283]). The availability of top 3 most used NET treatments over the past 12 months was significantly lower in EDE: surgery in AE reached 85% (1765/2076) vs. EDE 71% (201/283) p&lt;0.0001 [Chi-squared], somatostatin analogues - in AE 67% (1391/2076) vs. EDE 59% (167/283) p&lt;0.0001, PRRT was 57% in AE countries (1183/2076), vs. EDE 33% (93/283) p&lt;0.0001. Specialized services were of low usage globally and in deep disparity by economic areas, namely: NET specialist consultations (AE 55% [1143/2076] vs. EDE 40% [112/283] p&lt;0.0001), multidisciplinary team care 34% (AE 34% [706/2076] vs. EDE 22% [63/283] p&lt;0.0001), a clinical nurse specialized in NETs (AE 28% [589/2076] vs. EDE 7% [21/283] p&lt;0.0001), psychological care (AE 13% [261/2076] vs. EDE 5% [15/283] p&lt;0.0001), physical activities like yoga classes, trainings designed for cancer patients (AE 11% [220/2076] vs. EDE 3% [7/283] p&lt;0.0001). State healthcare coverage was claimed by half of AE NET patients (51% [1064/2076]). National healthcare plan that covered NETs was mentioned by only a third of EDE NET patients (30% [85/283]. Conclusions: Availability of treatments and access to specialized NET healthcare is a global challenge and is in need of improvement. Additionally, the gap between AE and EDE in terms of treatments availability, support services usage, and state healthcare coverage is significant and manifests deep inequality.
IL-18-dependent MAIT cell activation in COVID-19
Authors: Ester Gea-Mallorquí
Journal: Nature reviews. Immunology (2020)

NATuRe RevIewS | Immunology in inflammatory lung diseases compared with in healthy lungs.Compared with controls, Adamts4 -/-mice showed improved survival following a lethal dose of influenza virus, and this was associated with reduced inflammation and improved lung function.The lungs of infected Adamts4 -/-mice also showed higher levels of intact versican, and a series of additional experiments suggested that degradation of versican by ADAMTS4-expressing DRFibs permits the recruitment of CD8 + T cells, which are one of the main drivers of immunopathology during influenza virus infection.
Preclinical Activity of SAR408701: A Novel Anti-CEACAM5–maytansinoid Antibody–drug Conjugate for the Treatment of CEACAM5-positive Epithelial Tumors
Authors: Stéphanie Decary, Pierre-François Berne, Céline Nicolazzi, Anne-Marie Lefebvre, Tarik Dabdoubi, Béatrice Cameron, Pierrick Rival, Catherine Devaud, Catherine Prades, Hervé Bouchard, Alhassan Cassé, Christophe Henry, Céline Amara, Claire Brillac, Paul Ferrari, Laetitia Maçon, Eric Lacoste, Cecile Combeau, Eric Beys, Souad Naimi, Carlos García-Echeverría, Jean-François Mayaux, Véronique Blanc
Journal: Clinical Cancer Research (2020)

Carcinoembryonic antigen-related cell adhesion molecule 5 (CEACAM5) is a glycoprotein that has limited expression in normal adult tissues, but is overexpressed in carcinomas of the gastrointestinal tract, the genitourinary and respiratory systems, and breast cancer. As such, CEACAM5 is an attractive target for antibody-based therapies designed to selectively deliver cytotoxic drugs to certain epithelial tumors. Here, we describe preclinical data for a novel antibody-drug conjugate (ADC), SAR408701, which consists of an anti-CEACAM5 antibody (SAR408377) coupled to a maytansinoid agent DM4 via a cleavable linker.The specificity and binding affinity of SAR408701 to human and cynomolgus monkey CEACAM5 were tested in vitro. The cytotoxic activity of SAR408701 was assessed in CEACAM5-expressing tumor cell lines and using patient-derived xenograft mouse models of CEACAM5-positive tumors. Pharmacokinetic-pharmacodynamic and pharmacokinetic-efficacy relationships were established. SAR408701 toxicity was evaluated in cynomolgus monkey.SAR408701 bound selectively to human and cynomolgus monkey CEACAM5 with similar apparent Kd values (0.017 nmol/L and 0.024 nmol/L, respectively). Both in vitro and in vivo evaluations showed that SAR408701 has cytotoxic activity, leading to in vivo efficacy in single and repeated dosing. Single doses of SAR408701 induced significant increases in the tumor expression of phosphorylated histone H3, confirming the tubulin-targeting mechanism of action. The overall toxicity profile of SAR408701 in cynomolgus monkey was similar to that observed after intravenous administration of DM4 alone.On the basis of these preclinical data, the ADC SAR408701 is a promising candidate for development as a potential treatment for patients with CEACAM5-positive tumors.
Prognostic Significance of Monosomy 7 with and without Complex Karyotypes in Acute Myeloid Leukemia (AML): A Single Institutional Analysis
Authors: Daniel E Ezekwudo, Bolanle Gbadamosi, Leann Blankenship, Sanjog Bastola, Susanna Gaikazian, Dana Zakalik, Ishmael Jaiyesimi
Journal: Blood (2017)
Investigating factors associated with postmastectomy emergency department visits: A population-based analysis.
Authors: Steven Langer, May Lynn Quan, Shiying Kong, Yuan Xu
Journal: Journal of Clinical Oncology (2020)

241 Background: In 2016, a multi-pronged pathway was implemented in 13 hospitals across the province of Alberta, Canada to improve the mastectomy perioperative care experience focused on two objectives: 1) to increase same day surgery mastectomy rates and 2) decrease the number of unnecessary postoperative ED visits. The pathway successfully increased same day mastectomy rates from 1.7% to 47.8%, however the rate of postoperative ED visits remained high at 22-27%, a rate several-fold greater than described at other centers (3.1-12.8%) in spite of focused interventions at the patient and provider level to enhance perioperative support. Objective: To investigate potential factors associated with high postoperative ED visits following mastectomies in Alberta, Canada. Methods: Data was collected using the Discharge Abstract Database, and the National Ambulatory Care Reporting System database. Eligible patients included all women over 18 years old who underwent a mastectomy in the province of Alberta between 2004 and 2018. Patient demographics and operative variables including age, SES, Charlson comorbidities, date of surgery, surgery type (same-day vs. overnight) and health regions were collected. Primary outcome of interest was an ED visit within 30 days of mastectomy. Univariate and multivariate analyses were performed to identify independent predictors for post-operative ED visits. Results: A total of 18,076 patients had mastectomy during the study period, of which 4219 (23.3%) had an ED visit within 30 days of surgery. The most common causes of ED visits were infection, pain, and nausea/vomiting. Independent factors associated with ED visits were increasing age, overnight stay mastectomy, having reconstruction, cerebrovascular disease, chronic pulmonary disease, peptic ulcer disease, diabetes, depression, and living rurally. There was a slight decrease in ED visits post-implementation of the perioperative pathway (21.6% vs. 23.7%) but it was not statistically significant in the multivariable analysis. Conclusions: Post-operative ED visits remain high despite initiating a province-wide surgical pathway in 2016 which emphasizes patient education and improved perioperative care and supports. ED visits are associated with geographic location, specific comorbidities, and overnight stays. Currently, the majority of ED visits are manageable in non-emergent settings. Further investigations are necessary to discern whether additional perioperative interventions can curb the high ED visit rate.
Chronic exposure to benzo(a)pyrene‐coupled nanoparticles worsens inflammation in a mite‐induced asthma mouse model
Authors: Julie Carrard, Philippe Marquillies, Muriel Pichavant, Nicolas Visez, Sophie Lanone, Anne Tsicopoulos, Cécile Chenivesse, Arnaud Scherpereel, Patricia de Nadaï
Journal: Allergy (2020)

Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
Screening and Intervention to Prevent Falls and Fractures in Older People
Authors: Sarah E. Lamb, Julie Bruce, Anower Hossain, Chen Ji, Roberta Longo, Ranjit Lall, Chris Bojke, Claire Hulme, Emma Withers, Susanne Finnegan, Ray Sheridan, Keith Willett, Martin Underwood
Journal: New England Journal of Medicine (2020)

Community screening and therapeutic prevention strategies may reduce the incidence of falls in older people. The effects of these measures on the incidence of fractures, the use of health resources, and health-related quality of life are unknown.
Cost-effectiveness of filgrastim-sndz as primary prophylaxis (PP) versus secondary prophylaxis (SP) to prevent chemotherapy-induced febrile neutropenia (FN) in breast cancer patients at intermediate risk.
Authors: Edward C. Li, Dylan Mezzio, Kimberley J. Campbell, Andrew Spargo, Gary H. Lyman
Journal: Journal of Clinical Oncology (2020)

73 Background: According to clinical practice guidelines, the threshold for routine myeloid growth factor (MGF) PP is a high risk (&gt;20%) of developing FN. However, in response to the COVID-19 pandemic, a recent recommendation expands this threshold for using MGF PP to include patients at intermediate risk (10-20%) of developing FN, with the goal of reducing emergency room and hospital visits. Patients with breast cancer receiving potentially curative chemotherapy consisting of docetaxel or paclitaxel (every 21 days) are at an intermediate risk (10-20%) of developing FN. This study evaluates the cost-effectiveness of PP vs. SP using a biosimilar MGF, filgrastim-sndz, in early-stage breast cancer patients at intermediate risk of FN. Methods: A Markov model with a lifetime horizon was constructed to evaluate the total costs and clinical outcomes when using filgrastim-sndz as PP vs. SP in 56 year old early-stage breast cancer patients receiving adjuvant docetaxel (following doxorubicin/cyclophosphamide) every 3 weeks for 4 cycles. Patients had ≥1 FN risk factor (i.e., recent surgery) without the receipt of anti-HER2 therapy, representing a 16% baseline FN risk. Average Sales Price (ASP) calculated from the Centers for Medicare &amp; Medicaid Services July 2020 ASP Drug Pricing File was used as the filgrastim-sndz cost. Incremental cost-effectiveness ratios (ICERs) were calculated for cost per FN event avoided, life-year saved (LYS), and quality-adjusted life-year (QALY) gained from a United States payer perspective. Deterministic and probabilistic sensitivity analyses (PSA) were conducted. Results: Filgrastim-sndz as PP vs. SP provided an additional 0.102 FN events avoided, 0.065 LYS, and 0.056 QALYs at an incremental cost of $2,106. The ICERs were $20,656, $32,624 and $37,333 for cost per FN event avoided, cost per LYS, and cost per QALY gained, respectively. In the PSA, the likelihood of cost-effectiveness at a willingness-to-pay (WTP) threshold of $50,000 per QALY gained was 71.3%. Conclusions: For early-stage breast cancer patients at intermediate risk of FN receiving adjuvant docetaxel with 1 or more risk factors, PP with filgrastim-sndz compared to SP is cost-effective based on a WTP threshold of $50,000/QALY. [Table: see text]
Accuracy of Post–Neoadjuvant Chemotherapy Image-Guided Breast Biopsy to Predict Residual Cancer
Authors: Marios Konstantinos Tasoulis, Han-Byoel Lee, Wei Yang, Romney Pope, Savitri Krishnamurthy, Soo-Yeon Kim, Nariya Cho, Victoria Teoh, Gaiane M. Rauch, Benjamin D. Smith, Vicente Valero, Kabir Mohammed, Wonshik Han, Fiona MacNeill, Henry M. Kuerer
Journal: JAMA Surgery (2020)

Image-guided breast biopsy of a residual imaging abnormality or tumor bed after neoadjuvant chemotherapy (NACT) is increasingly used to assess residual cancer, facilitate risk-adaptive surgery, and potentially identify exceptional responders in whom local therapy may be de-escalated.To further assess the accuracy of post-NACT image-guided biopsy to predict residual cancer in the breast.This diagnostic study analyzed multicenter patient-level data of patients with breast cancer who were treated with NACT and underwent image-guided biopsy before surgery at Royal Marsden Hospital in London, UK; Seoul National University Hospital in Seoul, South Korea; and MD Anderson Cancer Center in Houston, Texas. Data were analyzed from June to July 2019.Diagnostic accuracy of post-NACT image-guided biopsy. Final surgical pathology was used as reference standard.Data from 166 women were analyzed. The median (range) age was 49 (25-76) years. The median (range) tumor size on pretreatment and posttreatment imaging was 33.5 (12-100) mm and 10 (0-100) mm, respectively. The overall pathologic complete response rate was 51.2% (n = 85) (16.1% [5 of 31] for hormone receptor-positive/ERBB2 (formerly HER2)-negative; 44.7% [21 of 47] for hormone receptor-positive/ERBB2-positive; 69% [20 of 29] for hormone receptor-negative/ERBB2-positive; and 66.1% [39 of 59] for triple negative). The majority (143 [86.1%]) underwent image-guided vacuum-assisted biopsy (VAB), and 23 had core-cut biopsy. The median (range) needle gauge was 10 (7-14), and the median (range) number of samples was 6 (2-18). When image-guided biopsy (VAB and core-cut biopsy) was representative (159 [95.8%]), the false-negative rate across the whole cohort was 18.7% (95% CI, 10.6%-29.3%). Subgroup analysis of patients with a complete/partial clinical response and residual imaging abnormality of 2 cm or smaller with at least 6 VABs taken (76 [45.8%]) demonstrated a false-negative rate of 3.2% (95% CI, 0.1%-16.7%), a negative predictive value of 97.4% (95% CI, 86.5%-99.9%), and an overall accuracy of 89.5% (95% CI, 80.3%-95.3%).This large multicenter pooled data analysis suggests that a standardized protocol using image-guided VAB of a tumor bed measuring 2 cm or smaller with 6 or more representative samples allows reliable prediction of residual disease. These results could inform the design of de-escalation trials in NACT exceptional responders testing the safety of eliminating surgery.
Tazemetostat for patients with relapsed or refractory follicular lymphoma: an open-label, single-arm, multicentre, phase 2 trial
Authors: Franck Morschhauser, Hervé Tilly, Aristeidis Chaidos, Pamela McKay, Tycel Phillips, Sarit Assouline, Connie Lee Batlevi, Phillip Campbell, Vincent Ribrag, Gandhi Laurent Damaj, Michael Dickinson, Wojciech Jurczak, Maciej Kazmierczak, Stephen Opat, John Radford, Anna Schmitt, Jay Yang, Jennifer Whalen, Shefali Agarwal, Deyaa Adib, Gilles Salles
Journal: The Lancet Oncology (2020)