tbuckley/cabot-search huggingface dataset:
Locally advanced scrotal squamous cell carcinoma: Does chemotherapy affect survival?
Authors: Bhaskara Reddy Madhira, Gary Brooks, Rashad Khan, Komal Akhtar, Alina Basnet
Journal: Journal of Clinical Oncology (2020)

3 Background: Scrotal squamous cell carcinoma (SSCC)thoughrare, represents the most common forms of scrotal malignancies.40-50% of patients present with locally advanced disease, and treatment is extrapolated from penile cancer. Here we report practice trend and overall survival (OS) outcome of locally advanced SSCC patients who underwent surgery with or without chemotherapy. Methods: We performed a retrospective analysis using the national cancer center database (NCDB) (2004-2016). All patients aged ≥ 18 years with locally advanced SSCC who underwent surgery with or without chemotherapy were included. OS is estimated with Kaplan-Meier curves, with an adjusted hazard ratio (aHR) calculated from Cox proportional hazard regression model. Results: 638 patients were identified with SSCC without distant metastasis. Of these 49 underwent surgery with perioperative chemotherapy and 589 underwent surgery alone. At the median follow up of 39.9 months (mo), median OS is 41.4 mo and 145.7 mo for surgery with chemotherapy group versus surgery alone respectively (P-value &lt;0.0001), with aHR for OS 1.673 (95%CI 0.966-2.897). Patients age ≥ 65 (HR= 3.081, 95% CI=2.107- 4.505, p&lt;0.001), Charlson-Deyo Score (CCI) 2 or more (HR=3.441, 95% CI=2.140- .533, p &lt;0.0001), moderately-poorly differentiated carcinoma (HR=1.713, 95% CI=1.038- 2.829, p=0.0352), and higher clinical nodal status N1,N2 and N3 (HR=2.543, 95% CI=1.42-4.548, p=0.0016)were observed to do worse with surgery and chemotherapy. Patients with CCI of 2 or more, moderate to poorly differentiated carcinoma, higher clinical T and N stage (T2- T4 and N1-N3 respectively) were observed more likely to receive surgery and chemotherapy. Conclusions: No OS improvement was seen in locally advanced SSCC with addition of chemotherapy to surgery. Patients who received chemotherapy along with surgery are observed to have higher risk of mortality vs surgery alone. The study is limited by retrospective nature, lack of randomization, patient selection bias, patient’s choice of therapy, small sample size, and missing information.
Novel coronavirus disease (Covid-19): The first two patients in the UK with person to person transmission
Authors: Patrick J. Lillie, Anda Samson, Ang Li, Kate Adams, Richard Capstick, Gavin D. Barlow, Nicholas Easom, Eve Hamilton, Peter J. Moss, Adam Evans, Monica Ivan, None PHE Incident Team, Yusri Taha, Christopher J.A. Duncan, Matthias L. Schmid, None the Airborne HCID Network
Journal: Journal of Infection (2020)
TNFα Blockade in Checkpoint Inhibition: The Good, the Bad, or the Ugly?
Authors: Jeffrey S. Weber, Michael A. Postow
Journal: Clinical Cancer Research (2020)

The impact on survival of steroids and TNFα blockade to treat immune-related toxicity from checkpoint blockade with ipilimumab, nivolumab/pembrolizumab, or combined ipilimumab and nivolumab was assessed using data from a large national database. Using steroids was associated with better survival than the use of TNFα-blocking antibodies such as infliximab.See related article by Verheijden et al., p. 2268.
Radical Prostatectomy or Observation for Clinically Localized Prostate Cancer: Extended Follow-up of the Prostate Cancer Intervention Versus Observation Trial (PIVOT)
Authors: Timothy J. Wilt, Tien N. Vo, Lisa Langsetmo, Philipp Dahm, Thomas Wheeler, William J. Aronson, Matthew R. Cooperberg, Brent C. Taylor, Michael K. Brawer
Journal: European Urology (2020)
Health-related quality of life in Japanese patients with bladder cancer according to a newly developed Japanese version of the Bladder Cancer Index.
Authors: Takahiro Osawa, John Wei, Takashige Abe, Shuhei Yamada, Jun Frumido, Haruka Miyata, Hiroshi Kikuchi, Ryuji Matsumoto, Yasuyuki Sato, Kazushi Hirakawa, Yoshihiro Sasaki, Hiroshi Tanaka, Akira Kashiwagi, Ken Morita, Norikata Takada, Keita Minami, Toru Harabayashi, Sachiyo Murai, Nobuo Shinohara
Journal: Journal of Clinical Oncology (2020)

427 Background: We developed a Japanese version of the Bladder Cancer Index (BCI) to measure HRQOL in Japanese patients treated with various surgical methods. In addition, we performed a cross-cultural comparison of sexual function and bother in bladder cancer patients between the United States and Japan. Methods: The Japanese version of the BCI was developed through a multistage process after a pilot study. Its reliability and validity were examined in Japanese bladder cancer patients via a cross-sectional analysis. The patients were enrolled from August 2016 to March 2018. They also completed the Japanese version of Short Form (SF)-12, the EuroQol five-dimension scale (EQ-5D), and the Functional Assessment of Cancer Therapy-Bladder (FACT-BL). We also compared the Japanese cohort with an American cohort; i.e., the validation cohort used to develop the original version of the English BCI. Results: In total, 371 patients with a median age of 72 years and a median disease duration of 29 months were enrolled. Of these patients, 221 underwent transurethral resection of the bladder tumor, and 150 underwent radical cystectomy. The internal consistency value was ≥0.7 for all subscales, except the bowel function subscale. Each BCI domain was poorly correlated with the SF-12 and EQ-5D, but moderately well correlated with the FACT-BL. The urinary function and bowel function scales exhibited minimal (2.1–9.7%) amounts of missing data, whereas relatively high (≥15%) levels of missing data were seen in items relating to urinary bother, bowel bother, sexual function, or sexual bother. A missing data value of ≥15% was correlated with higher age (p&lt;0.05). Japanese patients were more likely than American patients to report poor sexual function. However, Japanese were less likely than American to be concerned about sexual function. Conclusions: We confirmed the reliability and validity of the Japanese version of the BCI, although it needs to be revised to make it more comprehensible for elderly patients. We found differences between American and Japanese patients with bladder cancer. The BCI can be used for cross-cultural assessments of HRQOL in bladder cancer patients.
Purification and biochemical characterisation of linden (Tilia cordata) pollen allergens
Authors: M. Blanusa, M. Milovanovic, Marina Atanasković-Marković, Lidija M. Burazer, Marija Gavrović-Jankulović, Ratko M. Jankov, Tanja Ćirković-Veličković
Journal: Allergy (2008)
The new WHO classification for essential thrombocythemia calls for revision of available evidences
Authors: Tiziano Barbui, Jürgen Thiele, Alberto Ferrari, Alessandro M. Vannucchi, Ayalew Tefferi
Journal: Blood Cancer Journal (2020)

Abstract In the 2016 revised classification of myeloproliferative neoplasms pre-fibrotic primary myelofibrosis (pre-PMF) was recognized as a separate entity, distinct from essential thrombocythemia (ET). Owing that the majority of cases falling in the pre-PMF category were previously diagnosed as ET, one may question about the need to re-evaluate the results of epidemiologic, clinical, and molecular studies, and the results of clinical trials in the two entities. Based on a critical review of recently published studies, pre-PMF usually presents with a distinct clinical and hematological presentation and higher frequency of constitutional symptoms. JAK2V617F and CALR mutations in pre-PMF patients are superimposable to ET, whereas non-driver high-risk mutations are enriched in pre-PMF compared with ET. Thrombosis is not significantly different, whereas bleeding is more frequent in pre-PMF. Median survival is significantly shorter in pre-PMF and 10-year cumulative rates progression to overt myelofibrosis is 0–1% vs. 10–12%, and leukemic transformation is 1–2% vs. 2–6%, in ET and pre-fibrotic-PMF, respectively. Most patients fall in the lower prognostic IPSS group in which observation alone can be recommended. Patients at intermediate risk may require a symptom-driven treatment for anemia, splenomegaly or constitutional symptoms while cytoreductive drugs are indicated in the high-risk category.
Meta-analysis Demonstrates Altered Antigen Presentation and Maladaptive Immune Response in Chronic Urticaria
Authors: Jihad Aljabban, Mohamed Mukhtar, Saad Syed, Sharjeel Syed, Nabeal Aljabban, Kalyn Hoffman, Mohammed Mohammed, Zahir Allarakhia, Habeeb Sura, Maryam Panahiazar, Dexter Hadley
Journal: Journal of Allergy and Clinical Immunology (2020)
Cytoreductive Surgery in Recurrent Ovarian Cancer. The Desktop Series of the AGO Study Group, Noggo, Mito, AGO-Austria, Sgog and Gineco
Authors: J. Sehouli, A. Du Bois, A. Zeimet, A. Reuss, G. Scambia, R. Zang, W. Meier, S. Greggi, F. Lécuru, P. Harter
Journal: Annals of Oncology (2012)
Muscle-derived interleukin 6 increases exercise capacity by signaling in osteoblasts
Authors: Subrata Chowdhury, Logan Schulz, Biagio Palmisano, Parminder Singh, Julian M. Berger, Vijay K. Yadav, Paula Mera, Helga Ellingsgaard, Juan Hidalgo, Jens Brüning, Gerard Karsenty
Journal: Journal of Clinical Investigation (2020)

Given the numerous health benefits of exercise, understanding how exercise capacity is regulated is a question of paramount importance. Circulating interleukin 6 (IL-6) levels surge during exercise and IL-6 favors exercise capacity. However, neither the cellular origin of circulating IL-6 during exercise nor the means by which this cytokine enhances exercise capacity has been formally established yet. Here we show through genetic means that the majority of circulating IL-6 detectable during exercise originates from muscle and that to increase exercise capacity, IL-6 must signal in osteoblasts to favor osteoclast differentiation and the release of bioactive osteocalcin in the general circulation. This explains why mice lacking the IL-6 receptor only in osteoblasts exhibit a deficit in exercise capacity of similar severity to the one seen in mice lacking muscle-derived IL-6 (mIL-6), and why this deficit is correctable by osteocalcin but not by IL-6. Furthermore, in agreement with the notion that IL-6 acts through osteocalcin, we demonstrate that mIL-6 promotes nutrient uptake and catabolism into myofibers during exercise in an osteocalcin-dependent manner. Finally, we show that the crosstalk between osteocalcin and IL-6 is conserved between rodents and humans. This study provides evidence that a muscle-bone-muscle endocrine axis is necessary to increase muscle function during exercise in rodents and humans.
Mismatch repair deficiency in metastatic prostate cancer (PC): Response to PD-1 blockade and standard therapies.
Authors: Laura Graham, Robert B. Montgomery, Heather H. Cheng, Evan Y. Yu, Ajjai Shivaram Alva, Michael Thomas Schweizer
Journal: Journal of Clinical Oncology (2020)

194 Background: While response rates to anti-PD1 therapy are low in unselected metastatic castration resistant PC (mCRPC) patients, those with inactivating mutations in mismatch repair (MMR) genes (i.e. MMR deficiency; MMRd) or microsatellite instability (MSI) are thought likely to respond favorably. To date, there is limited published data on this biologically distinct, yet clinically relevant subgroup’s natural history and response to treatment. Methods: We retrospectively identified patients at two academic institutions who had MMRd/MSI-high metastatic PC. Clinical and pathologic characteristics at time of diagnosis and response to standard therapies and immune checkpoint therapy were abstracted. Descriptive statistics, including PSA50 response (≥50% decline in PSA from baseline) and clinical/radiographic progression free survival (PFS), are reported. Results: 28 men with MMRd and/or MSI-high metastatic PC were identified. 14 (50%) men had M1 disease at diagnosis and 19 (76%) of 25 men that underwent prostate biopsy had a Gleason score (GS) ≥8. Median overall survival from time of metastasis was not reached (95% CI: 33.7-NR mos) after median follow up of 43.6 mos (95% CI: 25.8-65.2 mos). PSA responses to standard therapies were similar to historic controls (Table). 17 patients received pembrolizumab and 15 had PSA response data available. PSA50 responses to pembrolizumab occurred in 8 (53%) men. Median PFS was not reached (95% CI: 1.87-NR mos) and estimated PFS at 6 months was 64.1% (95% CI: 33.7%-83.4%). Of those who had a PSA50 response, 7 (87.5%) remain on treatment without evidence of progression. Conclusions: MMRd PC is associated with high GS and advanced disease at presentation. Response rates to standard therapies are comparable to those reported in unselected patients and response rate to checkpoint blockade is high.[Table: see text]
Behavioral Heuristics in Coronary-Artery Bypass Graft Surgery
Authors: Andrew R Olenski, André Zimerman, Stephen Coussens, Anupam B Jena
Journal: New England Journal of Medicine (2020)

Behavioral Heuristics in Coronary-Artery Bypass Graft SurgeryTo the Editor: Behavioral heuristics (mental shortcuts that simplify decision making) are common in medicine and can lead to cognitive biases that affect clinical decisions. 1Left-digit bias is the tendency to categorize continuous variables on the basis of the left-most numeric digit. 2 Left-digit bias explains why items are often priced at $4.99 as opposed to $5.00.This bias may affect treatment decisions.For example, patients who are hospitalized with acute myocardial infarction and who are 80 years and 2 weeks of age may be perceived by physicians as being at greater risk for complications -and thus may receive more conservative treatment -than patients who are 79 years and 50 weeks of age, if cognitive biases lead physicians to discretely categorize patients as being "in their 80s" rather than "in their 70s."We used data on Medicare beneficiaries from 2006 through 2012 to evaluate how frequently inpatient coronary-artery bypass grafting (CABG)
Increased reporting of fatal pneumonitis associated with immune checkpoint inhibitors: a WHO pharmacovigilance database analysis
Authors: Melissa Y.Y. Moey, Paul Gougis, Vincent Goldschmidt, Douglas B. Johnson, Bénédicte Lebrun-Vignes, Javid Moslehi, Jacques Cadranel, Joe-Elie Salem
Journal: European Respiratory Journal (2020)

<b>There was an increased reporting of immune checkpoint inhibitor (ICI)-pneumonitis over the past few years with earlier time to onset of fatal ICI-pneumonitis, which was associated with more respiratory failure and tumour progression</b>http://bit.ly/32GW51a
IL-37e, a Major Isoform in Airway Epithelial Cells, Responds to Cockroach Allergen Exposure
Authors: Wei Tu, Yan Zhang, Xiaojun Xiao, Hui Bao, Eryi Wang, Hui Cao, Danh Do, Zhigang Liu, Peisong Gao
Journal: Journal of Allergy and Clinical Immunology (2020)
Which biomarkers in atopic dermatitis (AD) can be used in real life?
Authors: Raissa Roque, Marilia Moraes, Luiza Marino, Fernanda Vaz, Rafael Saldanha, Isabella Manhães, Pedro Henrique De Angeli Bubach, Nathalia Vital, Caroline Ferreira, Carolina Aranda, Marcia Mallozi, Dirceu Sole
Journal: Journal of Allergy and Clinical Immunology (2020)
MicroRNA-based biomarkers of the radiation response in prostate cancer.
Authors: Joanne B. Weidhaas, Donatello Telesca, Amar Upadhyaya Kishan, Ingrid Jenny Guldvik, Melanie-Birte Schulz-Jaavall, Andreas Stensvold, Phuoc T. Tran, Wolfgang Lilleby
Journal: Journal of Clinical Oncology (2020)

163 Background: Intermediate and high-risk prostate cancer can be cured with radiation (RT) to the prostate and pelvic lymph nodes with androgen deprivation therapy (ADT), but both acute and late toxicity of the GU and GI systems are common. There are no biomarkers predicting radiation outcomes, limiting the opportunity to best personalize prostate radiation therapy. Methods: A prospectively enrolled single arm trial for locally advanced prostate cancer patients (T1-T4N0-N1M0) treated with definitive RT (74Gy IMRT) plus ADT was studied. Biologic samples were available in 108 of 138 patients. Toxicity was recorded using the RTOG morbidity grading system. We applied a panel of microRNA-based germline mutations shown to predict cancer therapy endpoints. Machine learning techniques were used to simultaneously identify prognostic features and perform classification of the biomarkers. Upsampling nested LOO-CV was used to assess performance and generality. Independent Fisher’s exact tests were performed to identify statistically significant marginal associations. Three classifiers were studied: logistic regression with elastic net regularization (EN-LR), classification trees (CT), and random forests (RF), with corresponding hyper-parameters of regularization weights (EN-LR), minimum split and bucket level sample size (CT), number of trees and mtry (RF). Normalized on the simplex, feature importance was defined as absolute value of regression weights for EN-LR, and cumulative decrease in Gini impurity for primary and surrogate splits at each node/splits for CT and RF. Results: Grade 2 or higher toxicity included acute GI (11%), acute GU (34%), late GI (3%) and late GU (16%). GI and GU toxicity and acute and late toxicity had unique predictive biomarkers. The top three marginal genetic associations for late GU toxicity were microRNA site variants in CD6 and CD274 (PDL1)(p.val &lt; 0.01) and BRCA2 (p.val = 0.014). Using RF, CT and EN_LR we could predict late GU toxicity with up to 70% sensitivity, 96% specificity, and 90% accuracy. Conclusions: We have identified microRNA-based biomarkers that can predict late GU toxicity. Work incorporating patient reported outcomes and to identify biomarkers for additional endpoints is ongoing.
A phase Ib/II, open-label, platform study evaluating the efficacy and safety of AB928-based treatment combinations in participants with metastatic castrate-resistant prostate cancer.
Authors: David R. Wise, Olivia Gardner, Houston N. Gilbert, Aimee Rieger, Melissa Constance Paoloni, Kartik Krishnan
Journal: Journal of Clinical Oncology (2020)

TPS272 Background: The tumor microenvironment contains high levels of immunosuppressive adenosine, which binds to and activates the A 2a and A 2b receptors (R) on immune cells, resulting in an ineffective anti-tumor immune response. Extracellular adenosine is primarily produced by the enzyme CD73. In prostate cancer (PC), the activity of prostatic acid phosphatase produces additional adenosine. AB928 is the first clinical-stage small molecule dual antagonist of both A 2a R and A 2b R, which is highly potent, pharmacodynamically active, and has been well tolerated in dose escalation studies as a single agent or in combination with chemo/immunotherapy. Targeting the adenosine pathway in combination with standard of care regimens may have a more profound effect on activating and inducing sustained anti-tumor immunity. Methods: This Phase 1b/2, open-label, multi-cohort platform study will evaluate the efficacy and safety of AB928 combination therapy in participants with metastatic castrate resistant PC (mCRPC). Each cohort will independently assess AB928 plus AB122 (anti-PD-1 antibody) in combination with standard of care (SOC; enzalutamide, docetaxel) or AB928 plus AB680 (CD73 inhibitor) with or without AB122. Cohort eligibility is informed by prior treatment history. In Ph1b, up to 15 participants will receive investigational products at the single-agent recommended dose with SOC per label guidance. Provided safety and activity stopping criteria are not met, further accrual will proceed in Ph2 and, depending on treatment cohort, may involve randomization to enzalutamide or docetaxel; crossover to experimental therapy will be allowed following progression on control treatment. Investigator-assessed antitumor response (radiologic, prostate specific antigen) will follow PCWG3 criteria. Conclusions: This Ph1b/2 study is the first to target the adenosine axis using a dual A 2a R/A 2b R antagonist (AB928) together with a small molecule CD73 inhibitor (AB680), anti-PD-1 antibody (AB122), and SOC for mCRPC. Study enrollment is proceeding in the United States; results will be shared in upcoming scientific conferences.
Abstracts PDS
Journal: Allergy (2019)

Background: Exercise-induced bronchoconstriction (EIB) is a common cause of breathing difficulty in athletes. Fractional exhaled nitric oxide (FeNO) is an indirect marker of airway inflammation, recommended for the assessment and management of asthma; however, the role of FeNO in detecting and monitoring EIB has yet to be fully established. The aim of this study was therefore to evaluate the predictive value of FeNO to confirm or refute EIB in athletes presenting with exertional dyspnoea. Method: Seventy athletes (male: n = 45) (age: 35 ± 11 years) reporting respiratory symptoms (i.e. wheeze, cough and dyspnoea) during exercise attended the laboratory on a single occasion. All athletes performed resting FeNO and spirometry pre-and-post a eucapnic voluntary hyperpnoea challenge (EVH) in accordance with international guidelines. Sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) were calculated for established FeNO thresholds: (intermediate [≥25ppb] and high [>50ppb]) and evaluated against objective evidence of EIB: (EVH diagnostic cut-off [-10% ΔFEV1 at two consecutive time-points] and [-15% ΔFEV1 at one time-point]). The diagnostic accuracy of FeNO was calculated using receiver operating characteristics area under the curve (ROC-AUC). Results: All had normal resting lung function (>80% FEV1 pred). The prevalence of EIB was 33% (-10% ΔFEV1) and 23% (-15% ΔFEV1) (median (IQR) ΔFEV1 = -7% (10.02)). FeNO values ≥25ppb and >50ppb were observed in 49% and 23% of the cohort, respectively. ROC-AUC for FeNO was 75% (-10% ΔFEV1) and 86% (-15% ΔFEV1). Sensitivity, specificity, PPV and NPV are presented in Table 1. Conclusion: Our findings indicate that FeNO >50ppb provides good specificity for a positive EVH test; however, should not replace indirect bronchoprovocation for diagnostic purposes. The high proportion of athletes reporting breathing difficulty in the absence of EIB highlights the requirement to consider alternative causes of exertional dyspnoea during clinical work-up.