tbuckley/cabot-search huggingface dataset:
Prospective randomized trial of gene expression classifier utility following radical prostatectomy (G-MINOR).
Authors: Todd Matthew Morgan, Linda A. Okoth, Daniel Eidelberg Spratt, Rodney Dunn, Felix Y Feng, Anna M. Johnson, Brian R. Lane, Susan Linsell, Khurshid R. Ghani, James E. Montie, Rohit Mehra, Stephanie Daignault-Newton, Huei-Chung Huang, Tamara Todorovic, Elai Davicioni, Frank Burks, Paul Rodriguez, Richard Sarle, David Christopher Miller, Michael L. Cher
Journal: Journal of Clinical Oncology (2021)

15 Background: Decipher is a tissue-based genomic classifier (GC) developed and validated in the post-radical prostatectomy (RP) setting as a predictor of metastasis. We conducted the first prospective randomized controlled trial assessing the use of a prostate cancer GC, with a primary objective to determine the impact of test results on adjuvant treatment decisions. Methods: The Genomics in Michigan ImpactiNg Observation or Radiation (G-MINOR) randomized trial enrolled participants across 12 centers between January 2017-August 2018. Eligible patients had undergone RP within 9 months of enrollment, had pT3-4 disease and/or positive surgical margins, and a PSA &lt; 0.1ng/mL. Patients were assigned to either the GC or Usual Care (UC) group using cluster-crossover block randomization. Patients and providers in both arms received a CAPRA-S recurrence risk score. Decipher scores were obtained on RP tissue of all patients, but patients and providers in the UC arm were blinded to the results. The primary endpoint was the impact of impact of GC test result on adjuvant treatment decisions compared to clinical factors alone within 18 months of RP. Results: 356 patients were randomized and 340 had at least 18 months of follow-up. Of these, all but 2 control (UC) patients had sufficient tissue to pass quality control for GC testing. Randomization resulted in 175 (51.5%) GC and 165 (48.5%) UC patients. There were no significant differences in clinical variables or Decipher scores between arms. At 18 months post-RP, 19 (10.9%) patients in the GC group and 12 (7.3%) patients in the UC group had received adjuvant treatment. In the primary analysis, availability of the GC score in the GC arm was significantly associated with adjuvant treatment in GC high-risk patients after controlling for CAPRA-S risk (OR 7.6, 95%CI 1.95-29.6, p = 0.009). In the GC arm, both GC score (OR 8.8, 95%CI 1.9-39.7, p = 0.005) and CAPRA-S score (OR 3.8, 95%CI 1.09-12.9, p = 0.04) were independently associated with adjuvant treatment in a multivariable logistic regression model. Conclusions: In the first ever randomized trial testing the impact of a prostate cancer genomic classifier on treatment decisions, the use of a GC post-RP impacted post-operative treatment in a manner concordant with classifier risk. Further follow-up will be necessary to assess the impact of GC testing on oncologic outcomes. Clinical trial information: NCT02783950. [Table: see text]
Anterior cruciate ligament injury: towards a gendered environmental approach
Authors: Joanne L Parsons, Stephanie E Coen, Sheree Bekker
Journal: British Journal of Sports Medicine (2021)

Background The anterior cruciate ligament (ACL) injury rate for girls/women has not changed in over 20 years, and they remain 3–6 times more likely to experience injury compared with boys/men. To date, ACL injury prevention and management has been approached from a sex-based biological point of view which has furthered our understanding of injury risk factors, mechanisms, and prevention and rehabilitation programmes. However, the traditional sex-based approach does not take into account the growing recognition of how sex and gender (a social construct) are ‘entangled’ and influence each other. Objective This paper discusses the curious absence of gender as an influencer in the dialogue surrounding ACL injuries. We propose adding gender as a pervasive developmental environment as a new theoretical overlay to an established injury model to illustrate how gender can operate as an extrinsic determinant from the presport, training and competition environments through to ACL injury and the treatment environment. Approach We draw on social epidemiological theories of the embodiment of gender and health to provide plausible examples of how gender may influence ACL injury, and demonstrate the opportunity for new, interdisciplinary research in the field. Conclusion Over 20 years of research has failed to decrease the ACL injury rate disparity between girls/women and boys/men. Embedding gender in the study of ACL injury will heighten awareness of possible influences outside the traditional biological elements, challenge us to think about the inextricable ‘entanglement’ of sex and gender, and inform more effective approaches to ACL injury prevention and treatment.
Impact of inflammatory bowel disease on radical prostatectomy outcomes and costs of care.
Authors: Ilana Goldberg, Steven Lee Chang, Shilajit Kundu, Benjamin I. Chung, Eric A. Singer
Journal: Journal of Clinical Oncology (2021)

230 Background: Recent studies suggest an association between prostate cancer and inflammatory bowel disease (IBD). Our objectives were to investigate clinical and financial impacts of IBD on radical prostatectomy (RP), and to determine the impact of surgical approach on our findings. Methods: The Premier Hospital Database was queried for patients who underwent RP from 2003 to 2017. Multivariable logistic regression models were used to determine the independent impact of IBD on complications and readmission rates. We determined 90-day readmissions and examined 90-day hospital costs adjusted to 2019 US dollars with multivariable quantile regression models. Results: Our study population included 262,189 men with prostate cancer, including 3,408 (1.3%) with IBD. There were higher odds for any complication for IBD patients compared to non-IBD controls for RP (15.64% vs. 10.66%). IBD patients had overall complication rates of 14.1% ( P &lt; 0.05) for open surgery and 17.2% for MIS ( P &lt; 0.01). Between 2013-2017, the IBD cohort had significantly more complications (OR: 2; 95% CI: 1.5 to 2.67; P &lt; 0.0001), was more likely to have surgical costs in the top quartile (OR: 1.6; 95% CI: 1.23 to 2.1; P &lt; 0.01), and had higher readmission rates (OR: 1.51; 95% CI: 1.1 to 2.06; P = 0.01). Conclusions: The IBD cohort who underwent MIS had the highest complication rates. Hospital readmissions and surgical costs were significantly higher for the IBD cohort who underwent RP between 2013-2017, when a minimally invasive approach was more prevalent than an open approach. These findings may be important when deciding which surgical approach to take when performing RP on men with IBD. [Table: see text]
RNA-seq analysis of non-muscular invasive bladder cancer to reveal different gene expression profiles between smoking and non-smoking patients.
Authors: Zhichao Fu, Shenghua Liu, Jianfei Wang, Ning He, Yadong Yang, Tianyuan Xu, Shrestha Anil, Yang Yan, Cheng Li, Zongtai Zheng, Xin Li, Xudong Yao
Journal: Journal of Clinical Oncology (2021)

478 Background: Bladder cancer is the ninth most common malignancy in the world, approximately 75% of patients are diagnosed with non-muscle invasive bladder cancer (NMIBC). Smoking has been established to be a carcinogenic risk factor of bladder cancer. Nevertheless, the detailed relationship between smoking and progression of NMIBC are poorly understood. In this study, we revealed high expressed genes in smoking patients were significantly related to tumor progression in NMIBC patients. Methods: A total of 54 NMIBC patients including 19 never smokers and 35 smokers (current smokers and previous smokers) were enrolled in this study.The gene expression profiles were obtained by RNA-seq and the differentially expressed genes between smoking and non-smoking patients were identified using DESeq2 .The further analysis of the association between genes expression and patient survival in NMIBC cohorts(Jakob et al., 2016)and IMvigor 210 cohorts(Jonathan et al., 2016)by Kaplan-Meier survival estimate. Results: We identified 46 differentially expressed genes (p&lt;0.05) in smoking and non-somking NMIBC patients. IDO1 and KRT14 gene, which related to bladder cancer progression and poor prognosis, was identified significantly higher expressed in somking group compared with non-smoking and they have a logFC of 2.6,3.9 with FDR 1.83E-5,3.40E-5 respectively. The expression of other genes, including KRT6A, CASP14, SERPINA1, MYO3A and IL20RB, were significantly higher in smoking patients compared to non-somking. Notably, survival data analysis from 476 NMIBC cohorts showed that IL20RB had a significant relationship with poor PFS(p = 0.021) and in the Mvigor 210 Cohort including 310 advanced or metastatic urothelial carcinoma patients treated with atezolizumab, we found that the high expression of IL20RB was significantly related to poor OS(p = 0.002). Conclusions: We identified 14 genes related to tumor progression were significantly higher in smoking NMIBC patients than in non-smoking. Among these genes, the expression of IL20RB was related to the poor prognosis of NMIBC, and it may correlates with reduced clinical benefit of immunotherapeutic in patients with urothelial carcinoma.
Financial toxicity and patient-provider communication about cancer-related cost among prostate cancer patients and survivors.
Authors: Elissa C. Kranzler, Melissa F. Miller, Erica E. Fortune, Daniel M. Geynisman, Linda S. Bohannon, Heather Badt, Alexandra Katherine Zaleta
Journal: Journal of Clinical Oncology (2021)

215 Background: With early screening and advances in treatment, prostate cancer (PC) patients are living longer and facing increasingly complex therapeutic decisions alongside significant financial burden related to care (e.g., copays, coinsurance, other out-of-pocket (OOP) costs). Conversations with providers about financial concerns can help patients navigate these decisions, thereby promoting delivery of quality care and improving quality of life. We characterized financial toxicity (FT) and patient-provider communication about cancer-related cost among PC patients and survivors. Methods: 107 PC patients and survivors enrolled in Cancer Support Community’s Cancer Experience Registry completed items assessing FT (11-item FACIT-COST measure; range = 0-44, lower scores indicate greater FT). Items include ability to meet monthly expenses, financial stress, and cancer/treatment influence on financial situation. Frequencies and correlations between FT, health care team (HCT) communication, and socio-demographics were examined. Results: Participants were 89% non-Hispanic White, 5% Black, 2% Hispanic; mean age was 68 years (SD = 7.5). Median time since diagnosis was 3 years; 19% reported experiencing symptoms of PC at the time of diagnosis. 21% were ever metastatic, 22% experienced a recurrence, and 48% reported currently receiving treatment. 29% were employed full- or part-time; 52% spent at least $100/month on all OOP PC costs, 30% spent $250 or more, 16% spent $500 or more. Mean FT score was 28 (SD = 11.9). 67% reported members of their HCT did not discuss cost of treatment, 55% did not discuss impact of PC and treatment on work, 77% did not discuss financial distress. While most participants were satisfied with their doctor’s explanation of benefits (89%) and risks/side effects (79%) for each treatment option, only 49% were satisfied with how much their HCT discussed financial costs of each option. Greater patient confidence in communicating with doctor about PC was significantly associated with less FT ( r= .19, p&lt; .05), but experiencing more FT was not correlated with a greater likelihood of HCT discussing cost of treatment ( r= -.05, p= .63) or discussing impact of cancer and treatment on work ( r= .04, p= .67). Conclusions: Results indicate that patients with greater financial toxicity report less confidence in communicating with their doctor about PC, however providers are not frequently or systematically initiating discussions around cost and impact on work even among those experiencing the highest levels of financial burden. Findings underscore the critical value of transparency about health care costs and impact, as well as support for providers in communicating effectively with patients about costs and available resources, to improve patient quality of life and health outcomes.
Treatment sequence after first-line nivolumab plus ipilimumab or sunitinib monotherapy in patients with metastatic renal cell carcinoma (mRCC) using real-world data.
Authors: Daniel M. Geynisman, Jillian Faccone, Ying Zhang, Flavia Ejzykowicz, Brian Stwalley, Melissa Hamilton, Trong Kim Le, Stephen Huo
Journal: Journal of Clinical Oncology (2021)

288 Background: The introduction of second-line (2L) nivolumab (NIVO) in 2015 (CheckMate 025) and first-line (1L) NIVO plus ipilimumab (NIVO+IPI) in 2018 (CheckMate 214) revolutionized the management of mRCC in the US. This study sought to leverage real-world (RW) data by applying CheckMate 214 inclusion criteria to develop a RW comparator for the trial to assess treatment patterns and sequences in RW patients (pts) with mRCC after receiving 1L NIVO+IPI or sunitinib (SUN). Methods: This retrospective study identified pts with clear cell mRCC from the Flatiron Health EHR-derived de-identified database who received 1L NIVO+IPI or SUN monotherapy on or after December 2015. Pts must have met the strict selection criteria from CheckMate 214 for this analysis. Evaluation of 1L, 2L, and third-line (3L) therapies was stratified by International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) risk (favorable [FAV] and intermediate/poor [I/P]). Results: Of 401 mRCC pts included in the study, 197 (49.1%) received NIVO+IPI and 204 (50.9%) received SUN as 1L therapy (Table). The median follow-up time was 10.1 months in NIVO+IPI pts and 20.2 months in SUN pts ( P &lt; 0.0001). Among 66 (33.5%) NIVO+IPI pts who received 2L line therapy, the 2 most common therapies were cabozantinib (CABO; 50.0%), and pazopanib (PAZO; 12.1%). Among 119 (58.3%) SUN pts who received 2L therapy, the most common therapies were NIVO (48.7%), and PAZO (8.4%). The 2 most common 3L therapies were axitinib (AXI; 18.2%) or everolimus plus lenvatinib (EVE+LEN; 18.2%) for NIVO+IPI pts, and CABO (26.7%) or NIVO (15.0%) for SUN pts. The treatment sequence is similar between patients with FAV and I/P risk. Conclusions: In the RW setting, the treatment sequences after NIVO+IPI and SUN were largely similar across the IMDC risk groups. CABO was the most common therapy in 2L after NIVO+IPI in RW pts, and NIVO was the most common 2L therapy after SUN monotherapy, which was consistent with the sequence in the trial. [Table: see text]
Decreased butyric acid‐producing bacteria in gut microbiota of children with egg allergy
Authors: Mitsuru Yamagishi, Shohei Akagawa, Yuko Akagawa, Yoko Nakai, Sohsaku Yamanouchi, Takahisa Kimata, Masaki Hashiyada, Atsushi Akane, Shoji Tsuji, Kazunari Kaneko
Journal: Allergy (2021)

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In T2DM, weekly insulin icodec did not differ from daily glargine for reducing HbA<sub>1c</sub> or significant/severe hypoglycemia
Authors: Tomás P. Griffin, Sean F. Dinneen
Journal: Annals of Internal Medicine (2021)

ACP Journal ClubMarch 2021In T2DM, weekly insulin icodec did not differ from daily glargine for reducing HbA1c or significant/severe hypoglycemiaTomás P. Griffin, MB, BCh, BAO, MSc, Dip Clin Ed, Sean F. Dinneen, MD, MScTomás P. Griffin, MB, BCh, BAO, MSc, Dip Clin EdGalway University Hospitals, Galway, Ireland (T.P.G., S.F.D.)Search for more papers by this author, Sean F. Dinneen, MD, MScGalway University Hospitals, Galway, Ireland (T.P.G., S.F.D.)Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/ACPJ202103160-034 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail Source CitationRosenstock J, Bajaj HS, Janež A, et al. Once-weekly insulin for type 2 diabetes without previous insulin treatment. N Engl J Med. 2020:383:2107-16. https://pubmed.ncbi.nlm.nih.gov/32960514Clinical Impact RatingsGIM/FP/GP: Endocrinology: References1 Qiao Q, Ouwens MJ, Grandy S, et al. Adherence to GLP-1 receptor agonist therapy administered by once-daily or once-weekly injection in patients with type 2 diabetes in Germany. Diabetes Metab Syndr Obes. 2016;9:201-5. [PMID: 27418849] Google Scholar2 American Diabetes Association. 6. Glycemic targets: standards of medical care in diabetes–2020. Diabetes Care. 2020;43:S66–76. [PMID: 31862749] Google Scholar3 Zinman B, Philis-Tsimikas A, Cariou B, et al. Insulin degludec versus insulin glargine in insulin-naive patients with type 2 diabetes: a 1-year, randomized, treat-to-target trial (BEGIN Once Long). Diabetes Care. 2012;35:2464-71. [PMID: 23043166] Google Scholar Author, Article, and Disclosure InformationAffiliations: Galway University Hospitals, Galway, Ireland (T.P.G., S.F.D.)Disclosures: The commentators have disclosed no conflicts of interest. The forms can be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=M20-7314.This article was published at Annals.org on 2 March 2021. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited byWeekly Insulin Becoming a Reality March 2021Volume 174, Issue 3Page: JC34KeywordsAlgorithmsCognitive impairmentGlucoseHbA1cHemoglobinHypoglycemiaHypoglycemicsInsulinSafetyType 2 diabetes ePublished: 2 March 2021 Issue Published: March 2021 Copyright & PermissionsCopyright © 2021 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
Association of Cannabis Retailer Proximity and Density With Cannabis Use Among Pregnant Women in Northern California After Legalization of Cannabis for Recreational Use
Authors: Kelly C. Young-Wolff, Sara R. Adams, Alisa Padon, Lynn D. Silver, Stacey E. Alexeeff, Stephen K. Van Den Eeden, Lyndsay A. Avalos
Journal: JAMA Network Open (2021)

Prenatal cannabis use is associated with adverse perinatal outcomes1 and is increasing with expanding legalization.2,3 While it is known that retail availability of cannabis is associated with adult cannabis use,4,5 it is less clear whether living closer to a cannabis retailer or in a neighborhood with greater cannabis retailer density is associated with prenatal cannabis use. This cross-sectional study assessed the association between recreational use cannabis retailer availability and cannabis use among pregnant women served by the Kaiser Permanente Northern California (KPNC) heath system during the first year of California’s 2018 initiation of recreational cannabis sales.
Associations of circulating cell-free DNA (cfDNA) and clinical outcomes in metastatic castrate-resistant prostate cancer (mCRPC).
Authors: Daniel H. Shevrin, Mathew Yang, Polina Imas, Kamalakar Gulukota
Journal: Journal of Clinical Oncology (2021)

137 Background: Genomic profiling of patients (pts) with mCRPC is becoming more widely utilized to assist in prognosis and treatment. Liquid biopsies offer a non-invasive method of assessing gene alterations but questions remain regarding their validity, as well as the association of these alterations with relevant clinical outcomes. Methods: We present a retrospective analysis of 82 pts who underwent genomic profiling at the onset of mCRPC using the Guardant360 cfDNA assay. Clinical outcomes data was recorded in a structured note in the electronic medical record that allowed discrete data elements to be stored and analyzed. Patients received standard treatment with Abiraterone (Abi) and Enzalutamide (Enza) as well as chemotherapy. Relevant clinical outcome endpoints included overall survival (OS) and time on treatment with Abi and Enza (TT). These endpoints were compared between patients grouped by their gene alterations and treatment. Univariate and multivariate association analyses were performed. Results: The structured note was found to be valuable in capturing relevant discrete clinical outcomes data for detailed analysis. Median OS for the 82 pts was 58 months. 15 pts had insufficient cfDNA to perform the assay and these pts had a significantly longer OS than the 67 pts with sufficient cfDNA (median not reached vs 36 months, p = 0.004). The most commonly altered genes were AR and TP53 with 45% pts having alterations in both genes. Our analysis showed significantly shorter OS with BRAF (24 months, p = 0.008) and NF1 (20 months, p = 0.036) alterations. However, the significance was lost after multiple hypothesis correction. We observed that pts with co-occurrence of AR and BRAF had a significantly shorter OS (18.7 months, p = 0.031). BRCA2 mutations were observed in 9 pts and were associated with a significantly shorter TT (23 vs 38 months, p = 0.022) but lost significance after multiple hypothesis correction. Patients who received Abi followed by Enza had a significantly longer TT compared to pts who received the reverse sequence (38 months vs 23 months, p = 0.02). Conclusions: In this retrospective analysis, we did not identify any significant associations between specific gene alterations and relevant clinical outcomes. We observed a trend of shorter OS with BRAF and NF1 alterations and a shortened OS with co-occurrence of AR and BRAF alterations. These associations will require validation in a larger study. The presence of sufficient DNA to perform the assay was associated with shorter OS. The treatment sequence of Abi followed by Enza showed longer TT than the reverse sequence. The structured note allowed capture of relevant clinical outcomes data and is currently being utilized in a larger prospective genomic study of mCRPC.