tbuckley/cabot-search huggingface dataset:
Decade-long trends in surgery for acute Type A aortic dissection in England: A retrospective cohort study
Authors: Umberto Benedetto, Shubhra Sinha, Arnaldo Dimagli, Graham Cooper, Giovanni Mariscalco, Rakesh Uppal, Narain Moorjani, George Krasopoulos, Amit Kaura, Mark Field, Uday Trivedi, Simon Kendall, Gianni D Angelini, Enoch F Akowuah, Geoffrey Tsang
Journal: The Lancet Regional Health - Europe (2021)

Little is known about variations in care and outcomes of patients undergoing surgical repair for type A aortic dissection(TAAD). We aim to investigate decade-long trends in TAAD surgical repair in England.Retrospective review of the National Adult Cardiac Surgery Audit, which prospectively collects demographic and peri‑operative information for all major adult cardiac surgery procedures performed in the UK. We identified patients undergoing surgery for TAAD from January 2009-December 2018, reviewed trends in operative frequency, patient demographics, and mortality.Over the 10-year period,3,680 TAAD patients underwent surgical repair in England. A doubling in the overall number of operations conducted in England was observed (235 cases in 2009 to 510 in 2018). Number of procedures per hospital per year also doubled(9 in 2009 to 23 in 2018). Overall, in-hospital mortality was 17.4% with a trend toward lower mortality in recent years(23% in 2009 to 14.7% in 2018). There was a significant variation in operative mortality between hospitals and surgeons. We also found that most patients presented towards the middle of the week and during winter.Surgery is the only treatment for acute TAAD but is associated with high mortality. Prompt diagnosis and referral to a specialist center is paramount. The number of operations conducted in England has doubled in 10 years and the associated survival has improved. Variations exist in service provision with a trend towards better survival in high volume centers.British Heart Foundation and NIHR Biomedical Research center(University Hospitals Bristol and Weston NHS Foundation Trust and University of Bristol).
Cost-effectiveness analysis of p53 immunohistochemical testing in stage I and II high-risk endometrial cancer.
Authors: Taylor Orellana, Jessica L. Berger, Michelle M. Boisen, Ronald J. Buckanovich, Lan Gardner Coffman, Madeleine Courtney-Brooks, Robert P. Edwards, Haider Mahdi, Alexander Olawaiye, Paniti Sukumvanich, John Vargo, Rohit Bhargava, Sushil Beriwal, Sarah E. Taylor, Kenneth Smith, Jamie Lee Lesnock
Journal: Journal of Clinical Oncology (2021)

e18838 Background: PORTEC-3, a phase III clinical trial comparing adjuvant radiation alone (RT) to combined chemoradiation therapy (CTRT) in patients with high-risk endometrial cancer (EC), demonstrated no benefit with CTRT compared to RT for patients with stage I and II EC. However, a subsequent tumor molecular analysis revealed that individuals with stage I and II high-risk EC with p53 mutations had statistically significantly improved progression-free survival (PFS) and clinically significantly improved overall survival (OS) with combined CTRT. As p53 immunohistochemical (IHC) testing and CTRT adds to cost and toxicity, we sought to evaluate the cost-effectiveness of p53 IHC tumor testing in patients with stage I and II high-risk EC. Methods: A Markov decision model was developed to compare two testing strategies in patients with stage I and II high-risk EC: p53 IHC testing vs. no IHC testing. IHC staining for p53 is an accurate and validated surrogate for TP53 mutational status. As a result, p53 IHC testing alone was used in the decision analysis. Data from PORTEC-3 and the subsequent molecular analysis were used for the base case model parameters, including treatment regimen, PFS, OS, and incidence of p53-mutated tumors. Cost and utility data were derived from the Federal Supply Schedule, the Centers for Medicare and Medicaid Services (CMS) Fee Schedules, the Tufts CEA registry, peer-reviewed literature, and expert input. Data analysis was performed using TreeAge Pro Software, 2021. Effectiveness outcomes included quality-adjusted life-years (QALYs) and incremental cost-effectiveness ratios (ICERs). Sensitivity analyses were performed in order to identify the influence of individual variables on the overall model. Results: When compared to no testing, p53 IHC testing resulted in a cost savings of $471 per patient while providing an additional 0.310 QALYs. Therefore, p53 IHC testing was less expensive and more effective than no IHC testing and was a dominant strategy in this model. In one-way sensitivity analyses, CTRT and RT costs, discount rate, and percentage of p53 mutations detected had the most impact on the model; however, p53 IHC testing remained a cost-saving strategy over all parameter ranges examined. Conclusions: For patients with high-risk stage I and II EC, this analysis suggests that p53 IHC testing is cost-effective compared to no testing in determining the costs and benefits of adjuvant chemotherapy. Although additional studies are warranted, this data provides further support for the role of molecular-based treatment decisions for high-risk stage I and II endometrial cancer.
Real-world treatment patterns, clinical outcomes, and health care resource utilization in extensive-stage small cell lung cancer in Canada.
Authors: Dylan E. O'Sullivan, Darren Brenner, Iqra Syed, Mary Kate Shanahan, Daniel Moldaver, Christina Sit, D. Gwyn Bebb, Winson Y. Cheung, Devon J. Boyne
Journal: Journal of Clinical Oncology (2021)

e20575 Background: Extensive stage small cell lung cancer (ES-SCLC) patients face a high risk of recurrence and a uniformly poor prognosis. Real-world evidence related to treatment patterns, clinical outcomes, and healthcare resource utilization is needed to highlight the unmet clinical need and demand for novel therapies within this patient population. Methods: A population-based, retrospective, longitudinal study of adult ES-SCLC patients diagnosed in the province of Alberta, Canada between January 2010 and December 2018 was conducted using provincial electronic medical records and administrative claims data. Results: A total of 1,941 ES-SCLC patients were included of which 1,465 (75%) initially presented with ES-SCLC and 476 (25%) had recurrent disease. Among newly diagnosed ES-SCLC patients, front-line therapy was as follows: 523 (35.7%) chemotherapy and radiotherapy, 280 (19.1%) chemotherapy alone, 133 (9.1%) radiotherapy alone, and 529 (36.1%) best supportive care. The primary sites of radiation were the chest (67.1%) and the brain (45.7%). Median age at diagnosis was 70 years (range: 39-94) and 50.2% were men. In contrast to the de novo patients, the majority of recurrent cases (71.6%) received no front-line therapy. In the full cohort (de novo and recurrent cases), 46.5% of patients initiated first-line, 8.7% second-line, and 1.4% third-line chemotherapy. The majority of patients received either carboplatin plus etoposide (49.5%) or cisplatin plus etoposide (43.0%) in first-line. Median overall survival was higher for patients who were treated with chemotherapy and radiotherapy (10.59 months; 95% CI: 10.03-11.61) compared to patients who received chemotherapy alone (5.65 months; 95% CI: 5.06-6.12), radiotherapy alone (3.02 months; 95% CI: 2.47-4.01), or best supportive care (0.82 months; 95% CI: 0.72-0.92; log-rank p-value &lt; 0.001). Among patients who received first-line systemic therapy, the 1-year, 2-year and 5-year survival was 29.1% (95% CI: 26.3-32.3), 7.3% (95% CI: 5.7-9.2) and 2.9% (95% CI: 1.8-4.5), respectively and the average time spent in hospital was 17, 11, and 10 days per patient within years 1, 2, and 3, respectively. Conclusions: In a Canadian real-world setting, the initiation of first-line treatment in ES-SCLC was low with significant attrition in subsequent lines. It was evident that patients who received treatment had greater survival compared to those who do not. Collectively, these results underscore the need for effective front-line therapeutic options and highlight the potential for novel therapies to improve patient outcomes.
Adaptive and maladaptive coping strategies among patients with advanced cancer.
Authors: Rony Dev, Akhila Sunkepally Reddy, Joseph Anthony Arthur, Ali Haider, Ishwaria Mohan Subbiah, Marvin Omar Delgado-Guay, Cindy L. Carmack, Eduardo Bruera, David Hui
Journal: Journal of Clinical Oncology (2021)

e24129 Background: Few studies have examined the coping mechanisms among patients with advanced cancer seen by palliative care. The objective of the study was to evaluate coping strategies in advanced cancer patients and identity risk factors for maladaptive coping. Methods: The authors conducted a secondary analysis of a cross-sectional survey on chemical coping. We prospectively enrolled patients with advanced cancer from a Supportive Care Clinic and documented the patient demographics, symptom expression (Edmonton Symptom Assessment System), Zubrod performance status, substance use history including tobacco, and coping strategies (the Brief COPE Questionnaire). Univariate and multivariate analyses were performed to identify risk factors for the use of maladaptive coping strategies. Results: Among 399 patients, the most common malignancies were gastrointestinal (21%) and breast (19%). Cancer patients frequently incorporated adaptive coping strategies including acceptance (86.7%), emotional support (79.9%), religion (69.4%), active coping (62.4%), instrumental support (48.4%), positive reframing (48.6%), planning (49.6%), and infrequently, humor (18.5%). Common maladaptive strategies included self-distraction (36.6%) and venting (14.5%), while self-blame (6.3%), denial (4.5%), behavioral disengagement (1.8%), and substance use (1.0%) were infrequently reported. On univariate analysis, venting was significantly associated with anxiety and depression, female gender, and tobacco use; and self-distraction was significantly associated with younger age, gender, depression, dyspnea, and a post-secondary education (P&lt;0.05 for all). On multivariate analysis, male gender (OR -1.22, p&lt;0.0001) and smoking (non-smoker vs everyday OR -1.9, P=0.008 ) remained significant for maladaptive venting; and age (HR -0.026, p=0.005), male gender (OR -0.65, p=0.004), dyspnea (OR -0.12, p=0.01) and post-secondary education (OR 0.596, p=0.022) remained significant for self-distraction. Conclusions: The vast majority of patients with advanced cancer seen by palliative care reported using adaptive coping strategies. We identified subgroup of patients who may be more likely to use maladapative coping strategies and may benefit from further psychological support.
Pembrolizumab plus enzalutamide for enzalutamide-resistant metastatic castration-resistant prostate cancer (mCRPC): Updated analyses after one additional year of follow-up from cohorts 4 and 5 of the KEYNOTE-199 study.
Authors: Julie N Graff, Scott T. Tagawa, Christopher J. Hoimes, Winald R. Gerritsen, Ulka N. Vaishampayan, Tony Elliott, Clara Hwang, A. J. Ten Tije, Aurelius Omlin, Raymond S. McDermott, Yves Fradet, Deepak Kilari, Cristiano Ferrario, Hiroji Uemura, Cuizhen Niu, Christian Heinrich Poehlein, Ronald De Wit, Charles Schloss, Johann S. De Bono, Emmanuel S. Antonarakis
Journal: Journal of Clinical Oncology (2021)

5042 Background: KEYNOTE-199 (NCT02787005) is a multicohort phase 2 study to evaluate pembrolizumab (pembro) in mCRPC. A previous analysis of patients with RECIST-measurable (cohort 4 [C4]) or bone-predominant nonmeasurable (cohort 5 [C5]) disease who were chemotherapy-naive and had progression while on enzalutamide (enza) found that pembro + enza showed antitumor activity and manageable safety. Long-term outcomes are of interest with immunotherapy; hence, updated efficacy and safety data after an additional 1 year of follow-up are presented. Methods: Pts were eligible if they had resistance to enza after prior response. Prior treatment with abiraterone was allowed. Pts received pembro 200 mg Q3W for up to 35 cycles + enza QD until progression, unacceptable toxicity, or withdrawal. Primary end point was ORR per RECIST v1.1 by blinded independent central review (BICR) in C4. Secondary end points were DOR (C4), and DCR, rPFS, OS and safety (both cohorts). Results: 126 pts (C4, 81; C5, 45) were treated. Median age was 72 years (range 43-92), 32.5% had visceral disease and 87.3% previously received ≥6 mo of enzalutamide; 121 pts (96.0%) discontinued, most because of progressive disease. Median (range) time from enrollment to data cutoff was 31.7 mo (23.1-37.1) in C4 and 35.5 mo (22.9-37.3) in C5. In C4, confirmed ORR was 12.3% (95% CI 6.1-21.5) (2 CRs, 8 PRs); median (range) DOR was 8.1 mo (2.5+ to 15.2), and 62.5% had a response ≥6 mo (Kaplan-Meier estimate). Additional efficacy analyses are outlined in the table. A total of 27.2% and 28.9% of pts in C4 and C5, respectively, experienced grade ≥3 treatment-related adverse events. Two pts in C4 died of immune-related AEs (Miller Fisher syndrome and myasthenia gravis). Incidence of any-grade (34.1%) and grade 3 or 4 (5.6%) rash, regardless of relatedness to treatment, was higher than previously reported for individual agents but manageable with standard-of-care treatments; 2 pts discontinued because of rash. Conclusions: After an additional 1 year of follow-up, pembro + enza continued to show antitumor activity and a manageable safety profile in pts with mCRPC who became resistant to enza. The treatment combination is being further evaluated in the ongoing phase 3 KEYNOTE-641 trial (NCT03834493). Clinical trial information: NCT02787005. [Table: see text]
Rab27aは,腫瘍微小環境を変更し,腫瘍進行を促進することができるエキソソーム依存性および非依存性のメカニズムをサポートする
Authors: Bobrie Angelique, Krumeich Sophie, Reyal Fabien, Recchi Chiara, F Moita Luis, C Seabra Miguel, Ostrowski Matias, Thery Clotilde
Journal: Cancer Research (2012)
Adoption of consolidative durvalumab among patients with locally advanced non-small cell lung cancer.
Authors: Vikram Jairam, Saamir Pasha, Pamela R. Soulos, Sarah B. Goldberg, James B. Yu, Roy H. Decker, Cary Philip Gross, Henry S. Park
Journal: Journal of Clinical Oncology (2021)

e20550 Background: Soon after the publication of the PACIFIC trial, the Food and Drug Administration (FDA) approved durvalumab following definitive chemoradiation in patients with unresectable stage III non-small cell lung cancer (NSCLC). However, patterns of durvalumab adoption within the United States are currently unknown. We investigated the pace of uptake of durvalumab as well as patient and tumor characteristics associated with receipt of durvalumab following FDA approval. Methods: This study used the nationwide Flatiron Health database, a longitudinal electronic health record-derived de-identified database. During the study period, the de-identified data originated from approximately 280 US cancer clinics (̃800 sites of care). From this de-identified database, we selected patients with stage IIIB-C NSCLC who completed at least two cycles of first-line (1L) platinum doublet chemotherapy between February 16, 2018 (FDA approval date for durvalumab) and August 16, 2019, and did not develop disease progression over a follow-up period of at least 120 days after 1L chemotherapy. In the absence of radiation therapy and surgery details in the database, these criteria served as a proxy for selecting patients who were most likely to be eligible for consolidative durvalumab. We evaluated temporal trends in the uptake of durvalumab after completion of 1L chemotherapy using the Cochran-Armitage test, clustering the time periods in 3-month intervals. We also characterized patient and tumor characteristics associated with durvalumab receipt using the chi-square test and multivariable logistic regression. Results: A total of 424 patients were included in our study sample, among whom 282 (66.5%) patients had documentation of having received durvalumab after 1L chemotherapy. Within the first 3 months after FDA approval, 60.4% of potentially eligible patients received durvalumab, while in the final 3 months of the study period, this proportion rose modestly to 68.3% (p = 0.19). On univariable and multivariable analysis, patient characteristics like age, sex, race, insurance, smoking status, performance status, and comorbidity score, as well as tumor characteristics like histology, EGFR status, and PD-L1 status, were not significantly associated with receipt of durvalumab. However, there was significant geographic variability in receipt of durvalumab, ranging from 65.7% in the South to 85.3% in the Midwest (chi-square p = 0.04). Conclusions: Early adoption of durvalumab upon completion of 1L chemotherapy for stage IIIB-C lung cancer was rapid across the United States, starting at over 60% in the first three months after FDA approval. Regional variation appears to be a more powerful driver than patient characteristics in discrepancies of durvalumab dissemination. Further exploration into these regional variations may help improve guideline-concordant care.
Association of Cannabis Use During Adolescence With Neurodevelopment
Authors: Matthew D. Albaugh, Jonatan Ottino-Gonzalez, Amanda Sidwell, Claude Lepage, Anthony Juliano, Max M. Owens, Bader Chaarani, Philip Spechler, Nicholas Fontaine, Pierre Rioux, Lindsay Lewis, Seun Jeon, Alan Evans, Deepak D’Souza, Rajiv Radhakrishnan, Tobias Banaschewski, Arun L. W. Bokde, Erin Burke Quinlan, Patricia Conrod, Sylvane Desrivières, Herta Flor, Antoine Grigis, Penny Gowland, Andreas Heinz, Bernd Ittermann, Jean-Luc Martinot, Marie-Laure Paillère Martinot, Frauke Nees, Dimitri Papadopoulos Orfanos, Tomáš Paus, Luise Poustka, Sabina Millenet, Juliane H. Fröhner, Michael N. Smolka, Henrik Walter, Robert Whelan, Gunter Schumann, Alexandra Potter, Hugh Garavan
Journal: JAMA Psychiatry (2021)

Animal studies have shown that the adolescent brain is sensitive to disruptions in endocannabinoid signaling, resulting in altered neurodevelopment and lasting behavioral effects. However, few studies have investigated ties between cannabis use and adolescent brain development in humans.
The effect of sex and BMI on outcomes in patients with metastatic non-small cell lung cancer treated with immunotherapy.
Authors: Jingxiao Jin, Jacqueline Visina, Timothy F. Burns, Brenda Diergaarde, Laura P. Stabile
Journal: Journal of Clinical Oncology (2021)

e21085 Background: Recent studies suggest that among non-small cell lung cancer (NSCLC) patients treated with immunotherapy (IT), those who are male and/or have higher body mass index (BMI) benefit most; however, the role of other factors such as pretreatment weight loss is not clear. We conducted a retrospective study to further characterize the relationship between sex, BMI and response to IT in NSCLC. Methods: Patients with stage IV NSCLC treated with IT between 2017 and 2019 at UPMC Hillman Cancer Center were included. Demographic and clinical data were obtained from medical records. Chi-square test was used to compare baseline patient characteristics, best response (CR, PR and SD vs. PD), and presence of immune-related adverse events (iRAEs) between BMI and sex categories. Cox proportional hazards models were used to assess the effect of BMI and sex on progression free survival (PFS) and overall survival (OS). Analyses were conducted overall as well as stratified by treatment regime (1st line monotherapy, non-1st line monotherapy, and concurrent chemotherapy). Results: The study population consisted of 297 patients; 50.2% female (N=149), 87.8% white (N=261), and mean age at IT initiation 68 yrs (range: 36-91 yrs). Median follow-up time: 21 months. At IT initiation, 27 patients were underweight (BMI &lt;18.5), 107 normal weight (BMI 18.5-24.9), 96 overweight (BMI 25-29.9), and 67 obese (BMI ≥30). Among underweight patients, weight loss pretreatment (≥10 lbs) was significantly more common ( P=0.02), and response to IT significantly worse (33% vs 61% good response; P=0.005) compared to those with BMI ≥18.5. No significant difference in response was observed between normal, overweight and obese patients, nor between men and women. The presence of iRAEs did not differ by BMI or sex. Females had better OS than males [HR (95%CI): 0.65 (0.47-0.90)] but PFS was similar. In stratified analyses, better OS among females was limited to the concurrent chemotherapy group [0.52 (0.30-0.92)]. Overall, underweight patients had worse OS than those with BMI ≥18.5 [1.71 (1.01-2.92)]; this was not significant after adjusting for pretreatment weight loss [1.48 (0.87-2.53)]. No difference was observed in OS and PFS between normal, overweight and obese patients. In stratified analyses, underweight individuals had worse OS [4.12 (1.55-10.94)] and PFS [3.87 (1.44-10.38)] than those with BMI ≥18.5 when treated with 1st line monotherapy. Weight loss pretreatment was independently associated with worse OS [2.20 (1.51-3.20)] and PFS [1.47 (1.05-2.05)]. Conclusions: In contrast to prior reports, NSCLC patients receiving IT did not benefit from higher BMI or male sex. Females treated with concurrent chemotherapy had improved OS, and pretreatment weight loss was an indicator of poor prognosis. Further study is required to understand the pathobiology behind these predictors.
Correspondence on ‘Warfarin use and risk of knee and hip replacements’
Authors: Na He, Zhenwei Fang, Xiaotong Li, Suodi Zhai
Journal: Annals of the Rheumatic Diseases (2021)

limited attention has been paid to patient-reported outcome (ie, joint pain) in previous studies.Also, further large populationbased studies are warranted to investigate the duration-response of warfarin-associated OA risk, which plays an important role in making causal inference. 10n conclusion, no signals of disproportionate reporting of OA with NOACs were identified, while significantly disproportionate association was found for warfarin.Warfarin's chronic adverse effect by interfacing with off-target vitamin K-dependent proteins deserves health professionals' attention.
Risk factors for SARS-CoV-2 transmission in non-household clusters
Authors: Ji Yun Noh, Joon Young Song, Hak Jun Hyun, Jin Gu Yoon, Hye Seong, Hee Jin Cheong, Soo-Young Yoon, Jeong-Sun Yang, Joo-Yeon Lee, Woo Joo Kim
Journal: Journal of Infection (2021)
PES(TAXUS)stentにおけるstent fractureに関して
Authors: 宮本真和, 光藤和明, 井上勝美, 後藤剛, 門田一繁, 藤井理樹, 山本浩之, 加藤晴美, 岡直樹, 福康志, 細木信吾, 廣野明寿, 川上徹, 丸尾健, 田中裕之, 羽原誠二, 長谷川大爾, 田坂浩嗣, 今井逸雄, 山田千夏, 岡本陽地, 大鶴優, 齋藤直樹, 柴山謙太郎
Journal: Circulation (2008)