tbuckley/cabot-search huggingface dataset:
AGAP2-AS1 as a potential marker for development of distant metastases in surgically treated low-risk clear cell renal cell carcinoma.
Authors: Sigrid Nakken, Øystein Eikrem, Hans-Peter Marti, Christian Beisland, Leif Bostad, Andreas Scherer, Arnar Flatberg, Vidar Beisvag, Philipp Strauss
Journal: Journal of Clinical Oncology (2020)

732 Background: Historically, 30 % of patients with localized kidney cancer develop distant metastases during follow-up. There is an urgent need to improve the individual risk assessment for clear cell renal cell carcinoma (ccRCC) patients. We therefore aim to characterize the gene expression profile of low-risk patients both with and without progressive disease to define predictive outcome candidate markers. Methods: Formalin-fixed tissue blocks from ccRCC patients (n=24, eight progressors and 16 non-progressors) with a low Leibovich score were collected. Patients had a mean age of 65 years (5 females and 19 males). The non-progressors were matched 2:1 to the progressors for gender, age, pT tumor stage, size, Fuhrman grade, and eGFR. Total RNA was extracted(miRNeasy FFPE Kit, Qiagen) and sequenced (TruSeq RNA Access Library Kit, Illumina). RNA-seq results were analyzed by ingenuity pathway analysis, K Nearest Neighbors algorithm, and survival analysis. Results: 1167 differentially expressed genes (abs.FC≥2, p≤0.05) were detected. Progressors overexpressed genes related to cancer, B-cell infiltration and other immune-system related pathways. Principal component analyses and hierarchical clustering depicted a systematic transcriptomic difference between progressors and non-progressors. Combinations of up to 10 genes were evaluated as classifiers. The AGAP2-AS1 mRNA classified 23 out of 24 samples correctly, without the need for a larger gene panel. The trend of expression was confirmed with RT-PCR.The correlation between sample status as either progressor or non-progressor and AGAP2-AS1 level was R 2 =0.69, p &lt;0.01. Patients were split into groups based on AGAP2-AS1 expression (cut-off log 2 cpm&gt;1), where higher expression correlated with shorter survival; Wilcoxon (p&lt;0.0001),Log-rank test (p&lt;0.0001), Hazard ratio; 9.24E-11. Immunohistochemistry of AGAP2, USP10 and KI-67 confirmed results from the mRNA level. Conclusions: RNA-seq results show a transcriptomic difference between low-risk ccRCC progressors and low-risk non-progressors. AGAP2-AS1 may serve as a potential classifier for the identification of low-risk progressors.
Is Avidity Of Ovomucoid-specific IgE Predictable For Immediate Allergic Reaction To Egg In Children With Low Levels Of sIgE ?
Authors: Miori Sato, Kiwako Yamamoto-Hanada, Hitomi Tada, Makoto Irahara, Mayako Saito-Abe, Kenji Matsumoto, Hiroshi Kido, Yukihiro Ohya
Journal: Journal of Allergy and Clinical Immunology (2020)
Enhancing global access to cancer medicines
Authors: Javier Cortes, Jose Manuel Perez‐García, Antonio Llombart‐Cussac, Giuseppe Curigliano, Nagi S. El Saghir, Fatima Cardoso, Carlos H. Barrios, Shama Wagle, Javier Roman, Nadia Harbeck, Alexandru Eniu, Peter A. Kaufman, Josep Tabernero, Laura García‐Estévez, Peter Schmid, Joaquín Arribas
Journal: CA A Cancer Journal for Clinicians (2020)

Abstract Globally, cancer is the second leading cause of death, with numbers greatly exceeding those for human immunodeficiency virus/acquired immunodeficiency syndrome, tuberculosis, and malaria combined. Limited access to timely diagnosis, to affordable, effective treatment, and to high‐quality care are just some of the factors that lead to disparities in cancer survival between countries and within countries. In this article, the authors consider various factors that prevent access to cancer medicines (particularly access to essential cancer medicines). Even if an essential cancer medicine is included on a national medicines list, cost might preclude its use, it might be prescribed or used inappropriately, weak infrastructure might prevent it being accessed by those who could benefit, or quality might not be guaranteed. Potential strategies to address the access problems are discussed, including universal health coverage for essential cancer medicines, fairer methods for pricing cancer medicines, reducing development costs, optimizing regulation, and improving reliability in the global supply chain. Optimizing schedules for cancer therapy could reduce not only costs, but also adverse events, and improve access. More and better biomarkers are required to target patients who are most likely to benefit from cancer medicines. The optimum use of cancer medicines depends on the effective delivery of several services allied to oncology (including laboratory, imaging, surgery, and radiotherapy). Investment is necessary in all aspects of cancer care, from these supportive services to technologies, and the training of health care workers and other staff.
Recurrence of surgically resected chromophobe renal cell carcinoma: Recommendations for follow-up.
Authors: Leyre Vanaclocha Saiz, Joana B. Neves, Marta Marchetti, Ravi Barod, Prasad Patki, Faiz Mumtaz, Saeed Dabestani, Maxine Gia Binh Tran, Axel Bex
Journal: Journal of Clinical Oncology (2020)

755 Background: Post-operative follow-up protocols for renal cell carcinoma (RCC) are based on outcomes of the clear cell subtype and often rely on variables not applicable to chromophobe RCC (chRCC), such as Fuhrman nuclear grading. We aimed to evaluate predictors of recurrence to guide follow-up regimes in the context of chRCC. Methods: Combined retrospective analysis of non-metastatic surgical cases with a final diagnosis of chRCC from an institutional database at a UK tertiary high-volume centre (June/2013 to March/2019) and from the international collaborative database RECUR (12 institutes across 8 European countries; 2006 to 2011). TNM risk group, tumour size, histopathological features, cancer specific survival (CSS) and recurrence free survival (RFS) were analysed. Kaplan Meier plots and Cox regression analysis were performed to determine factors associated with recurrence (local or distant). Results: 295 cases were identified (57.3% male, median age 60). After a median follow up of 58 months, 17 (5.8%) recurrences were observed, the majority of which were distant recurrences (n = 13). CSS was 96.3%. Tumours staged ≥pT2b (HR 13.7; 95%CI 3 to 63.1; p = 0.001), with coagulative necrosis (HR 3.9; 95%CI 1.3 to 11.1; p = 0.012) and sarcomatoid differentiation (HR 33; 95%CI 8.1 to 134.6.1; p = 0.000) were more likely to recur during follow-up. Only two cases of pT1a lesions had local recurrence, both after a positive surgical margin. All patients with early recurrences ( &lt; 18 months after surgery; n = 6) had tumours staged ≥pT2b with coagulative necrosis; sarcomatoid differentiation was also present in 3 cases. Conclusions: Recurrence of surgically resected chRCC is not common. For patients with pT1 lesions, negative margins, no coagulative necrosis or sarcomatoid features, prognosis is excellent. Follow up can be curtailed to avoid excess radiation exposure and patient anxiety.
Effect of prophylactic anticoagulation on incidence of venous thromboembolism in testicular germ cell tumor patients.
Authors: Nikola Hapakova, Michal Chovanec, Katarina Rejlekova, Katarina Kalavska, Jana Obertova, Patrik Palacka, Valentina De Angelis, Zuzana Sycova, Jozef Mardiak, Michal Mego
Journal: Journal of Clinical Oncology (2020)

422 Background: Testicular germ cell tumors (GCTs) are among the most common solid tumors in young males. With the availability of highly effective treatment, improving patients’ quality of life has gained more focus in recent years. Venous thromboembolism (VTE), commonly occurring in GCT patients, is associated with increased morbidity and mortality. Prophylactic anticoagulation has been shown to decrease the risk of VTE in cancer patients. In this retrospective study we evaluated the effect of low molecular weight heparin (LMWH) prophylaxis during hospitalization on incidence of VTE and outcome in GCT patients treated with first-line chemotherapy. Methods: Study population included 394 chemotherapy-naive GCT patients treated with first-line chemotherapy at the National Cancer Institute, Bratislava, Slovakia from January 2000 to December 2017. VTE was defined as any venous thrombosis or pulmonary embolism, confirmed by imaging, occurring during first-line chemotherapy. No visceral thromboses were observed. Results: Forty-one out of 394 patients (10.4%) were diagnosed with VTE on initial staging and were excluded from the analysis. Final cohort included 353 patients. LMWH prophylaxis was administered to 104 patients (29.5%), 249 patients (70.5%) did not receive prophylaxis. We observed 14 (4.0%) VTE events. The difference in VTE incidence between patients with and without prophylaxis was not statistically significant (5.8% vs. 3.2% p = 0.37). We have observed a trend to longer overall survival in patients without prophylaxis (HR = 0.61, 95%CI = 0.32-1.13, p = 0.08). Patients with extragonadal GCT receiving VTE prophylaxis had significantly shorter survival compared to patients without prophylaxis (HR = 0.29, 95%CI = 0.08-1.12, p = 0.04). Conclusions: LMWH prophylaxis was not associated with decreased VTE incidence. Moreover, it was associated with shorter survival in extragonadal GCTs. Taking into account these data, LMWH prophylaxis during hospitalization should not be used in GCT patients receiving chemotherapy.
Systemic therapy for nonmetastatic castrate-resistant prostate cancer (M0 CRPC): A systematic review and network meta-analysis (NMA).
Authors: Ellen Cusano, Richard M. Lee-Ying, Devon J. Boyne, Darren Brenner, Marcus Vaska
Journal: Journal of Clinical Oncology (2020)

113 Background: The treatment landscape for M0 CRPC has changed following the demonstrated efficacy of new agents in recent randomized control trials (RCT). However, the comparative effectiveness of these novel agents is unknown. This NMA indirectly compared the efficacy and safety of available therapies for M0 CRPC. Methods: A literature search of MEDLINE (Ovid), EBM Reviews, HealthSTAR, PubMed, PubMed Central, CINAHL, and TRIP Database was performed. Studies were screened by two independent reviewers. Hazard ratios (HR) and confidence intervals were extracted for the primary outcome metastasis-free survival (MFS) and the secondary outcomes overall survival (OS) and grade 3 or higher adverse events (AE). Bone MFS was used as a surrogate for MFS when MFS was not reported. Risk of bias was assessed using the Cochrane Collaboration tool. A Bayesian NMA was performed using a fixed-effects model. Results: Four RCT were analyzed (n=5549). Each trial compared either apalutamide (APA), enzalutamide (ENZA), darolutamide (DARO), or denosumab (DENO) plus androgen deprivation therapy (ADT) to placebo plus ADT. Risk of bias was low. For MFS, APA and ENZA had similar efficacy (Table), and Surface Under the Cumulative Ranking Analysis demonstrated a 59% probability that APA was preferred for MFS, followed by ENZA (41%). There was a trend for improved OS for APA, DARO and ENZA, but no meaningful differences between these agents. APA, ENZA, and DARO had a similar risk of AEs and all had a greater risk of AEs compared to DENO. Conclusions: APA and ENZA appear to be the most efficacious treatments for MFS in M0 CRPC, though more data for OS is required. Compared to DARO, APA and ENZA’s demonstrated efficacy is not at the expense of added toxicity.[Table: see text]
Raman Spectroscopy Reveals That Biochemical Composition of Breast Microcalcifications Correlates with Histopathologic Features
Authors: Renzo Vanna, Carlo Morasso, Beatrice Marcinnò, Francesca Piccotti, Emanuele Torti, Davide Altamura, Sara Albasini, Manuela Agozzino, Laura Villani, Luca Sorrentino, Oliver Bunk, Francesco Leporati, Cinzia Giannini, Fabio Corsi
Journal: Cancer Research (2020)

Breast microcalcifications are a common mammographic finding. Microcalcifications are considered suspicious signs of breast cancer and a breast biopsy is required, however, cancer is diagnosed in only a few patients. Reducing unnecessary biopsies and rapid characterization of breast microcalcifications are unmet clinical needs. In this study, 473 microcalcifications detected on breast biopsy specimens from 56 patients were characterized entirely by Raman mapping and confirmed by X-ray scattering. Microcalcifications from malignant samples were generally more homogeneous, more crystalline, and characterized by a less substituted crystal lattice compared with benign samples. There were significant differences in Raman features corresponding to the phosphate and carbonate bands between the benign and malignant groups. In addition to the heterogeneous composition, the presence of whitlockite specifically emerged as marker of benignity in benign microcalcifications. The whole Raman signature of each microcalcification was then used to build a classification model that distinguishes microcalcifications according to their overall biochemical composition. After validation, microcalcifications found in benign and malignant samples were correctly recognized with 93.5% sensitivity and 80.6% specificity. Finally, microcalcifications identified in malignant biopsies, but located outside the lesion, reported malignant features in 65% of in situ and 98% of invasive cancer cases, respectively, suggesting that the local microenvironment influences microcalcification features. This study confirms that the composition and structural features of microcalcifications correlate with breast pathology and indicates new diagnostic potentialities based on microcalcifications assessment. SIGNIFICANCE: Raman spectroscopy could be a quick and accurate diagnostic tool to precisely characterize and distinguish benign from malignant breast microcalcifications detected on mammography.
Assessing the effect of clinical trial evidence and anecdote on caregivers’ willingness to use corticosteroids: a randomized controlled trial: a critical appraisal
Authors: A. Brown, Z. Tsianou, H.C. Williams
Journal: British Journal of Dermatology (2020)

Johnson et al. aimed to assess caregivers' willingness to treat childhood atopic dermatitis (AD) with a corticosteroid when presented with clinical trial evidence, anecdote, or both.This prospective parallel group (1: 1; eight groups) randomized control trial (RCT) was carried out with caregivers recruited from a tertiary care dermatology clinic in the USA and an online crowdsourcing platform using caregivers who may not have had a child with AD.Caregivers were randomized to eight groups. The three main groups were given clinical trial evidence, anecdote, or a combination of both. Each of these three groups was further divided and presented with either the term 'medication' or 'topical steroid'. These were compared with the two remaining groups, which included a group told that they would not be informed of a medication's efficacy or safety profile, and a group informed that the medication was recommended by the doctor.Caregivers were asked about their willingness to treat based on the information they had received using a 10-point Likert scale where 1 was 'not willing' and 10 'completely willing'.A total of 476 caregivers were recruited (80 clinic, 396 online), 48% of whom had a history of a child with AD. Caregivers' willingness to treat was higher in all information assignment groups compared with those not provided with safety information: clinical trial evidence of a 'medication' (P = 0·003; Cohen's d = 0·83) or 'topical steroid' (P = 0·030; d = 0·55), anecdote of a 'medication' (P < 0·0001; d = 1·37) or 'topical steroid' (P < 0·0001; d = 0·85), both clinical trial evidence and anecdote of a 'medication' (P < 0·0001; d = 1·00) or 'topical steroid' (P = 0·000; d = 0·89), and simply the doctor's recommendation (P < 0·0001; d = 0·92).Johnson et al. conclude that the provision of anecdotal reassurance may be an effective strategy to improve caregivers' willingness to use topical steroids.Exploring factors that affect caregivers' willingness to adhere to topical corticosteroids is an important area of research. This study was a potentially efficient way of conducting a rapid RCT to explore such factors. The study conclusions are significantly undermined by lack of a registered trial protocol, poor trial reporting, the use of caregivers who did not have experience of AD, the multiplicity and complexity of treatment arms, and the use of an unvalidated primary outcome.
Association of Nonprofit Hospitals’ Charitable Activities With Unreimbursed Medicaid Care After Medicaid Expansion
Authors: Charles Stoecker, Mollye Demosthenidy, Yixue Shao, Hugh Long
Journal: JAMA Network Open (2020)

<h3>Importance</h3> In the United States, nonprofit hospitals receive tax-exempt status with the expectation that they provide a high level of benefit to local communities. Prior work has shown that Medicaid expansion reduced hospital spending on uncompensated care. <h3>Objective</h3> To measure the association of tax-exempt hospital spending with community benefit and changes in uncompensated care after Medicaid expansion. <h3>Design, Setting, and Participants</h3> This cohort study was performed using a difference-in-differences analysis (ie, a pre-post treatment-control design) to estimate changes in reported charitable categories associated with Medicaid expansion. Data from Internal Revenue Service form 990, Schedule H, tax filings for 2253 tax-exempt hospitals in the United States from 2012 to 2016 were used. Data were analyzed from June to November 2019. <h3>Exposure</h3> The proportion of the hospital’s tax filing that spanned the period after Medicaid expansion. <h3>Main Outcomes and Measures</h3> Hospital-reported spending on uncompensated care, unreimbursed Medicaid expenses, and other community benefit spending categories. <h3>Results</h3> Across 2253 hospitals, mean (SD) uncompensated care costs between 2012 and 2016 were $4.20 million ($8.80 million) and unreimbursed Medicaid expenses were $7.60 million ($18.62 million). Compared with tax-exempt hospitals in states that did not expand Medicaid, those in states that did expand Medicaid reported mean reductions in their provision of uncompensated care of $1.11 million (95% CI, $0.35 million to $1.87 million;<i>P</i> &lt; .001), representing a mean change of −2% (95% CI, −6% to 2%;<i>P</i> &lt; .001). These reductions have been offset by mean reported increases in the provision of unreimbursed Medicaid expenses of $1.63 million (95% CI, $0.31 million to $2.94 million;<i>P</i> = .02), representing a mean increase of 2% (95% CI, 1% to 4%;<i>P</i> = .01). Tax-exempt hospitals in states that expanded Medicaid reported no statistically significant mean increase in spending on other community benefit activities. <h3>Conclusions and Relevance</h3> In this study, large decreases in uncompensated care among tax-exempt hospitals associated with Medicaid expansion were not accompanied by increases in other reportable categories of community health benefit spending. Instead, they were accompanied by increased spending on unreimbursed Medicaid expenses.
Variation of Residential Levels of Nitrogen Dioxide in a Mixed Rural-Urban Setting and its Implication in Childhood Asthma
Authors: Chung-Il Wi, Janneane Gent, Katherine King, Joshua Bublitz, Euijung Ryu, Keli Sorrentino, Julie Plano, Julie Porcher, Philip Wheeler, Young Juhn
Journal: Journal of Allergy and Clinical Immunology (2020)
A Phase 1 study of AK104, a tetrameric bispecific antibody that targets PD-1 and CTLA-4 in patients with advanced solid tumors
Authors: Ben Markman, Ben Tran, Hui Gan, Amy Prawira, Jermaine Coward, Xiaoping Jin, Baiyong Li, Max Wang, Yu Xia, Jayesh Desai, Michael Millward
Journal: Journal for ImmunoTherapy of Cancer (2019)
Risk of Offspring Birth Defects in Women After Bariatric Surgery—Reply
Authors: Martin Neovius, Kari Johansson, Olof Stephansson
Journal: JAMA (2020)

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Predictive Accuracy of a Polygenic Risk Score–Enhanced Prediction Model vs a Clinical Risk Score for Coronary Artery Disease
Authors: Joshua Elliott, Barbara Bodinier, Tom A. Bond, Marc Chadeau-Hyam, Evangelos Evangelou, Karel G. M. Moons, Abbas Dehghan, David C. Muller, Paul Elliott, Ioanna Tzoulaki
Journal: JAMA (2020)

<h3>Importance</h3> The incremental value of polygenic risk scores in addition to well-established risk prediction models for coronary artery disease (CAD) is uncertain. <h3>Objective</h3> To examine whether a polygenic risk score for CAD improves risk prediction beyond pooled cohort equations. <h3>Design, Setting, and Participants</h3> Observational study of UK Biobank participants enrolled from 2006 to 2010. A case-control sample of 15 947 prevalent CAD cases and equal number of age and sex frequency–matched controls was used to optimize the predictive performance of a polygenic risk score for CAD based on summary statistics from published genome-wide association studies. A separate cohort of 352 660 individuals (with follow-up to 2017) was used to evaluate the predictive accuracy of the polygenic risk score, pooled cohort equations, and both combined for incident CAD. <h3>Exposures</h3> Polygenic risk score for CAD, pooled cohort equations, and both combined. <h3>Main Outcomes and Measures</h3> CAD (myocardial infarction and its related sequelae). Discrimination, calibration, and reclassification using a risk threshold of 7.5% were assessed. <h3>Results</h3> In the cohort of 352 660 participants (mean age, 55.9 years; 205 297 women [58.2%]) used to evaluate the predictive accuracy of the examined models, there were 6272 incident CAD events over a median of 8 years of follow-up. CAD discrimination for polygenic risk score, pooled cohort equations, and both combined resulted in C statistics of 0.61 (95% CI, 0.60 to 0.62), 0.76 (95% CI, 0.75 to 0.77), and 0.78 (95% CI, 0.77 to 0.79), respectively. The change in C statistic between the latter 2 models was 0.02 (95% CI, 0.01 to 0.03). Calibration of the models showed overestimation of risk by pooled cohort equations, which was corrected after recalibration. Using a risk threshold of 7.5%, addition of the polygenic risk score to pooled cohort equations resulted in a net reclassification improvement of 4.4% (95% CI, 3.5% to 5.3%) for cases and −0.4% (95% CI, −0.5% to −0.4%) for noncases (overall net reclassification improvement, 4.0% [95% CI, 3.1% to 4.9%]). <h3>Conclusions and Relevance</h3> The addition of a polygenic risk score for CAD to pooled cohort equations was associated with a statistically significant, yet modest, improvement in the predictive accuracy for incident CAD and improved risk stratification for only a small proportion of individuals. The use of genetic information over the pooled cohort equations model warrants further investigation before clinical implementation.