tbuckley/cabot-search huggingface dataset:
The multidisciplinary clinic approach for bladder cancer treatment in the neoadjuvant therapy era.
Authors: Katherine E. Smentkowski, Timothy M. Han, Lydia Glick, Costas D. Lallas, Anne Calvaresi, Mark Jonathan Mann, James Ryan Mark, Leonard G. Gomella, William Kevin Kelly, Nathan Handley, Robert Benjamin Den, Mark Hurwitz, William J. Tester, Adam P. Dicker, Thenappan Chandrasekar, Edouard John Trabulsi
Journal: Journal of Clinical Oncology (2020)

475 Background: As urologic oncology becomes increasingly complex, the coordination of optimal and efficient care to patients can be challenging. Within our institution, we initiated a multidisciplinary center (MDC) comprised of urology, oncology and radiation oncology in 1996 to help meet these needs. The positive benefits of this approach have been demonstrated in other settings, but outcomes related to bladder cancer remain unclear, especially in the era of neoadjuvant (NA) therapy. Methods: Patients with localized or node positive muscle invasive bladder cancer (MIBC) without prior treatment were obtained from available multidisciplinary appointment records, dating from 7/5/17 to 9/25/19. Charts were then retrospectively reviewed to gather demographic data, treatment data, and pathological outcomes. Results: 66 patients fitting study criteria were identified. Average age was 71.3 years. 45 (68%) patients from this cohort were deemed to be radical cystectomy (RC) candidates, with 37 RC operations completed at time of record review. Of RC-eligible patients, 35/45 (77%) had received NA therapy, either in the form of neoadjuvant chemotherapy (NAC) and/or immunotherapy (NAI). 3 patients declined RC after receiving NAC. 15 patients underwent chemoradiation treatment (23%), while 7 (11%) underwent supportive care without definitive treatment. Downstaging at RC from MIBC (&lt;=T1) was seen in 12/37 patients (32%), with a pT0 rate of 10% (4/37). Conclusions: The coordination of care in bladder cancer remains a challenge for patients and physicians alike. We believe by utilizing a multidisciplinary approach, efficiency and quality of care increases. National database studies have reported overall utilization of neoadjuvant chemotherapy over the past 10 years, with most recent rates ranging from 14.8-20.9%. Our utilization of neoadjuvant therapy is notably higher at 77%, which also includes early adaptation of NAI in patients deemed ineligible for neoadjuvant NAC. Further studies are needed to examine a contemporary control population outside the multidisciplinary setting, however the above outcomes provide a basis for the integration of care and its positive outcomes in quality improvement.
Prognostic factors for VTE and bleeding in hospitalized medical patients: a systematic review and meta-analysis
Authors: Andrea J. Darzi, Samer G. Karam, Rana Charide, Itziar Etxeandia-Ikobaltzeta, Mary Cushman, Michael K. Gould, Lawrence Mbuagbaw, Frederick A. Spencer, Alex C. Spyropoulos, Michael B. Streiff, Scott Woller, Neil A. Zakai, Federico Germini, Marta Rigoni, Arnav Agarwal, Rami Z. Morsi, Alfonso Iorio, Elie A. Akl, Holger J. Schünemann
Journal: Blood (2020)
Abstract 10426: Body Weight Fluctuations and the Risk of Hypertension Among Normotensive Middle Aged Adults
Authors: Yoni Grossman, Ehud Grossman, Shay Kivity, Anat Berkovitch, Ruth Percik, Shlomo Segev, Ilan Goldenberg, Elad Maor
Journal: Circulation (2018)

Background: Data on the association between body weight fluctuations and the risk of future hypertension is limited and conflicting. Purpose: The aim of the present study was to examine whether tem...
INTACT: Phase III randomized trial of concurrent chemoradiotherapy with or without atezolizumab in localized muscle invasive bladder cancer—SWOG/NRG1806.
Authors: Parminder Singh, Cathy Tangen, Jason A. Efstathiou, Seth P. Lerner, Sameer G. Jhavar, Noah M. Hahn, Brian Addis Costello, Srikala S. Sridhar, Weliang Du, Joshua J. Meeks, Bishoy Morris Faltas, Petros Grivas, Felix Y Feng, Ronald C. Chen, Alicia K. Morgans, Amit Gupta, Richard Carlton Bangs, Kathryn A. Winter, Nicholas J. Vogelzang, Ian Murchie Thompson
Journal: Journal of Clinical Oncology (2020)

TPS586 Background: Chemoradiotherapy(CRT) is a SOC for patients with muscle invasive bladder cancer (MIBC) who refuse or are not fit for radical cystectomy. Radiotherapy and chemotherapy are known to increases the PD-L1 expression in bladder cancer. Based on these observations, we hypothesized that addition of atezolizumab to CRT will increase its efficacy. Methods: This is a randomized phase III trial testing CRT with and without atezolizumab for 6 months in 475 patients with MIBC. Pts will be stratified on performance status (0-1 vs. 2); clinical stage (T2 vs T3/T4a, chemotherapy(cisplatin vs 5FU+mitomycin vs gemcitabine); and radiation field (bladder only vs small pelvis). Patients will undergo biopsy 18 week from registration. If they have residual disease they will be taken off protocol treatment and can proceed with alternative SOC option including radical cystectomy. Patients will be followed for 5 years. The primary end point of the study is bladder intact event –free survival (BIEFS). The event is comprised of: recurrence or residual muscle-invasive bladder cancer at 18 weeks or later, clinical evidence of nodal or metastatic disease, radical cystectomy, or death due to any cause. This composite endpoint is reflective of the intent of bladder preservation strategy with radical cystectomy included as one of the outcomes. Secondary end points include overall survival, modified event free survival, pathologic response at 18 weeks, metastasis free survival, cancer specific survival, rate of salvage cystectomy, rate of adverse event and QOL &amp; PRO end points. The expected 3 year BIEFS for the control arm is 52%. The study leadership concluded that a 12% improvement in this endpoint is meaningful for this patient population. With a sample size of 475 patients the study has 85% power to detect the improvement from 52% to 64% in the BIEFS at 3 years (hazard ratio=0.68). The study team will perform translational studies evaluating tumor tissue, whole blood and urine for molecular and immunologic markers of immune response and response to RT. Successful completion of this trial could lead to a new treatment paradigm for patients with muscle invasive bladder cancer. Clinical trial information: NCT03775265.
Site-specific methylation of 18S ribosomal RNA by SNORD42A is required for acute myeloid leukemia cell proliferation
Authors: Cornelius Pauli, Yi Liu, Christian Rohde, Chunhong Cui, Daria Fijalkowska, Dennis Gerloff, Carolin Walter, Jeroen Krijgsveld, Martin Dugas, Bayram Edemir, Caroline Pabst, Lutz P. Müller, Fengbiao Zhou, Carsten Müller-Tidow
Journal: Blood (2020)
Phase III study of perioperative pembrolizumab (pembro) plus neoadjuvant chemotherapy (chemo) versus placebo plus neoadjuvant chemo in cisplatin-eligible patients (pts) with muscle-invasive bladder cancer (MIBC): KEYNOTE-866.
Authors: Arlene O. Siefker-Radtke, Gary D. Steinberg, Jens Bedke, Hiroyuki Nishiyama, Xiao Fang, Ritesh Kataria, Blanca Homet Moreno, Christopher J. Hoimes
Journal: Journal of Clinical Oncology (2020)

TPS599 Background: MIBC prognosis is poor, despite standard neoadjuvant cisplatin-based chemo. PD-1/PD-L1 pathway inhibition is an effective first-line option for cisplatin-ineligible pts and a second-line option for platinum-based chemo pretreated pts. Neoadjuvant chemo + pembro, a PD-1 inhibitor, recently showed encouraging pathologic complete response rates, in cisplatin-eligible patients with MIBC (NCT02365766), warranting further investigation. Methods: KEYNOTE-866 (NCT03924856) is a randomized phase 3 study to assess efficacy and safety of chemo+perioperative pembro versus chemo+perioperative placebo for pts with MIBC. An estimated 790 patients will be randomly assigned 1:1 to neoadjuvant pembro+chemo (4 cycles) followed by adjuvant pembro after radical cystectomy+pelvic lymph node dissection (RC+PLND, 13 cycles) or neoadjuvant placebo+chemo (4 cycles) followed by adjuvant placebo after RC+PLND (13 cycles). Pts will receive neoadjuvant and adjuvant pembro 200 mg IV Q3W; neoadjuvant chemo will be gemcitabine 1000 mg/m 2 +cisplatin 70 mg/m 2 IV Q3W. Pts will be stratified by tumor PD-L1 status (combined positive score [CPS] ≥10 vs CPS &lt;10), disease stage (T2 vs T3/4), and region of treatment (Unites States vs Europe vs most of world). Adults (≥18 y) with histologically confirmed MIBC (T2-T4aN0M0) who are cisplatin-eligible, are clinically nonmetastatic (N0M0), and have an ECOG PS 0 or 1 will be enrolled. Pts are required to provide tumor tissue for histology and PD-L1 analysis. Pts will not be permitted to have previously received systemic antineoplastic treatment for MIBC or radiotherapy to the bladder. Imaging by CT/MRI will be performed Q12W for up to 96 wk after cystectomy, at discontinuation, and during follow-up starting at 3 y (Q24W). Primary end points are pathologic complete response and event-free survival in all pts and pts with PD-L1 CPS ≥10. Secondary end points are OS, disease-free survival, and pathologic downstaging rate in all pts and pts with PD-L1 CPS ≥10, and safety. Accrual began June 13, 2019. Clinical trial information: NCT03924856.
Preoperative Chemoradiotherapy Versus Immediate Surgery for Resectable and Borderline Resectable Pancreatic Cancer: Results of the Dutch Randomized Phase III PREOPANC Trial
Authors: Eva Versteijne, Mustafa Suker, Karin Groothuis, Janine M. Akkermans-Vogelaar, Marc G. Besselink, Bert A. Bonsing, Jeroen Buijsen, Olivier R. Busch, Geert-Jan M. Creemers, Ronald M. van Dam, Ferry A.L.M. Eskens, Sebastiaan Festen, Jan Willem B. de Groot, Bas Groot Koerkamp, Ignace H. de Hingh, Marjolein Y.V. Homs, Jeanin E. van Hooft, Emile D. Kerver, Saskia A.C. Luelmo, Karen J. Neelis, Joost Nuyttens, Gabriel M.R.M. Paardekooper, Gijs A. Patijn, Maurice J.C. van der Sangen, Judith de Vos-Geelen, Johanna W. Wilmink, Aeilko H. Zwinderman, Cornelis J. Punt, Casper H. van Eijck, Geertjan van Tienhoven
Journal: Journal of Clinical Oncology (2020)

Preoperative chemoradiotherapy may improve the radical resection rate for resectable or borderline resectable pancreatic cancer, but the overall benefit is unproven.In this randomized phase III trial in 16 centers, patients with resectable or borderline resectable pancreatic cancer were randomly assigned to receive preoperative chemoradiotherapy, which consisted of 3 courses of gemcitabine, the second combined with 15 × 2.4 Gy radiotherapy, followed by surgery and 4 courses of adjuvant gemcitabine or to immediate surgery and 6 courses of adjuvant gemcitabine. The primary end point was overall survival by intention to treat.Between April 2013 and July 2017, 246 eligible patients were randomly assigned; 119 were assigned to preoperative chemoradiotherapy and 127 to immediate surgery. Median overall survival by intention to treat was 16.0 months with preoperative chemoradiotherapy and 14.3 months with immediate surgery (hazard ratio, 0.78; 95% CI, 0.58 to 1.05; P = .096). The resection rate was 61% and 72% (P = .058). The R0 resection rate was 71% (51 of 72) in patients who received preoperative chemoradiotherapy and 40% (37 of 92) in patients assigned to immediate surgery (P < .001). Preoperative chemoradiotherapy was associated with significantly better disease-free survival and locoregional failure-free interval as well as with significantly lower rates of pathologic lymph nodes, perineural invasion, and venous invasion. Survival analysis of patients who underwent tumor resection and started adjuvant chemotherapy showed improved survival with preoperative chemoradiotherapy (35.2 v 19.8 months; P = .029). The proportion of patients who suffered serious adverse events was 52% versus 41% (P = .096).Preoperative chemoradiotherapy for resectable or borderline resectable pancreatic cancer did not show a significant overall survival benefit. Although the outcomes of the secondary end points and predefined subgroup analyses suggest an advantage of the neoadjuvant approach, additional evidence is required.
A survey of the background underlying allergic symptoms in children with food allergy induced by accidental ingestion of or contact with the allergen
Authors: Toshiko Itazawa, Moeka Oguri, Taisuke Kato, Muneyuki Shimizu, Motokazu Nakabayashi, Takuya Wada, Yasunori Ito, Osamu Higuchi, Junko Yamamoto, MIWA KAWASHIRI, Yoichi Onoue, MIKI TAKAO, Gyokei Murakami, Yoko Adachi, Yuichi Adachi
Journal: Journal of Allergy and Clinical Immunology (2020)
Evaluation of the Frequency of “Not Relevant” Responses on the Dermatology Life Quality Index by Sociodemographic Characteristics of Patients With Psoriasis
Authors: John S. Barbieri, Daniel B. Shin, Maha N. Syed, Junko Takeshita, Joel M. Gelfand
Journal: JAMA Dermatology (2020)

"Not relevant" responses (NRRs) on the Dermatology Life Quality Index (DLQI) are common among patients with psoriasis and may be associated with an underestimation of disease severity.To evaluate the associations between (1) patient sociodemographic characteristics and the frequency of NRRs on the DLQI and (2) NRR frequency and treatment satisfaction.This cross-sectional study using data from the Dermatology Clinical Effectiveness Research Network from February 2010 to June 2011 assessed the responses on the DLQI of 1733 patients with psoriasis.Differences in the frequency of NRRs by sex, race/ethnicity, insurance type, income, educational attainment, marital status, and employment status were evaluated using the 2-tailed χ2 test. Multivariable logistic regression analysis was used to evaluate the associations between sociodemographic characteristics and having at least 1 NRR. Multivariable linear regression analysis was used to evaluate the association between having a DLQI score reclassified from 10 or less to more than 10 using the DLQI-Relevant scoring modification and the scores on the Treatment Satisfaction Questionnaire for Medication. Data were analyzed between July 2019 and November 2019.Of 1733 patients with psoriasis, 879 (50.7%) were female, and 1470 (84.8%) were non-Hispanic white individuals. The DLQI items 6 (sport, 223 patients [12.9%]), 9 (sexual difficulties, 214 patients [12.3%]), and 7 (work or study, 126 patients [7.3%]) had the greatest frequency of NRRs. In multivariable logistic regression analysis, male sex (odds ratio [OR], 0.63; 95% CI, 0.48-0.82) and income of more than $100 000 (OR, 0.45; 95% CI, 0.26-0.79) were associated with decreased odds of NRRs. By contrast, single (OR, 1.85; 95% CI, 1.31-2.61) or widowed or divorced (OR, 2.60; 95% CI, 1.80-3.74) marital status and unemployed or disabled employment status (OR, 1.98; 95% CI, 1.35-2.89) were associated with increased odds of NRRs. Having a DLQI score that would be reclassified from 10 or less to more than 10 using the DLQI-Relevant scoring modification was associated with lower global satisfaction scores on the Treatment Satisfaction Questionnaire for Medication (coefficient, -9.8; 95% CI, -16.3 to -3.4).There were sociodemographic differences in the frequency of NRRs on the DLQI among this cohort of patients with psoriasis. These differences may be associated with an underestimation of disease burden and treatment disparities owing to subsequent undertreatment among certain sociodemographic groups. Further study is needed to optimize the quality-of-life assessment among patients with psoriasis or other inflammatory skin diseases in diverse settings.
Clinical outcomes of metastatic renal carcinoma following disease progression to programmed death (PD)-1 or PD-L1 inhibitors (I-O): A Meet-URO group real-world study (Meet-Uro 7).
Authors: Daniele Santini, Marco Stellato, Ugo De Giorgi, Sandro Pignata, Francesco Pantano, Delia De Lisi, Chiara Casadei, Marco Maruzzo, Emanuele Naglieri, Sebastiano Buti, Rocco De Vivo, Giuseppe Di Lorenzo, Andrea Sbrana, Mariella Soraru', Giuseppe Fornarini, Claudia Mucciarini, Francesco Grillone, Giandomenico Roviello, Francesca Vignani, Giuseppe Procopio
Journal: Journal of Clinical Oncology (2020)

691 Background: In metastatic renal cell carcinoma (mRCC), immune-oncology (IO), alone or in combination, (IO-IO or IO-TKI) has changed the therapeutic scenario. Few real-world data are available about safety and outcome after IO progression. Methods: Baseline characteristics, outcome data including progression-free survival (PFS) and toxicities were retrospectively collected from 162 eligible pts treated in 16 Italian referral centers adhering to the Meet-Uro group and progressing to IO. Results: 111 pts (68,5%) were treated after progression to IO. 142 (87.6%) pts received IO as second line, 5 pts as first line and 16 pts as further line. Subsequent therapy included cabozantinib (n = 79, 48.0%), everolimus (n = 11, 6.7%), sunitinib (n = 6, 3.7%) and others (n = 15, 9.25%). Median IO-PFS was 4 months (95%CI 3.1-4.8) with no difference in pts pretreated with pazopanib or sunitinib (4 months (95%CI 2.4-5.5) vs 3,9 months (95%CI 2.9-4.9) p = 0.5). PFS tends to be longer in pts reporting adverse events of any grade (5.03 (95%CI 3.8-6.1) vs 2,99 (95%CI 2.4-3.5) months p = 0.004) or without nephrectomy (4.1 vs 2.9 months p = 0.071). Median PFS, in pts treated post-IO, was 6.5 months (95%CI 5.1-7.8). In term of best response, 55 pts (49%) had stability of disease/partial response and 29 pts (26%) had progressive disease, for the other pts treatment is still ongoing. Pts with ECOG PS 0 at progression to IO, had longer PFS, 11 months (95%CI 5.7-17.5) as well as those treated with cabozantinib (7.6 months, 95%CI 5.2-10.1) compared to everolimus, (3.2 months, 95%CI 1.8-4.5) or other drugs (4.3 months, 95%CI 1.3-7.4) p = 0.001. All grade adverse events were reported in 83 pts (74%) with G3-G4 adverse events in 39 pts (35%). Median overall survival, from first line, was 41,1 months (95%CI 30.4-51.8). Conclusions: In our real world experience after progression to IO, most pts received VEGF-TKI and mTOR inhibitors that showed to be active and safe choices. Cabozantinib was associated with a longer mPFS.
The IPSS-R more accurately captures fatigue severity of newly diagnosed patients with myelodysplastic syndromes compared with the IPSS index
Authors: Fabio Efficace, Francesco Cottone, Laura B. Oswald, David Cella, Andrea Patriarca, Pasquale Niscola, Massimo Breccia, Uwe Platzbecker, Giuseppe A. Palumbo, Giovanni Caocci, Reinhard Stauder, Alessandra Ricco, Duska Petranovic, Jo Caers, Mario Luppi, Luana Fianchi, Chiara Frairia, Isabella Capodanno, Elena Follini, Chiara Sarlo, Paola Fazi, Marco Vignetti
Journal: Leukemia (2020)
Biofabrication Strategies and Engineered In Vitro Systems for Vascular Mechanobiology
Authors: Shantanu Pradhan, Omar A. Banda, Cindy J. Farino, John L. Sperduto, Keely A. Keller, Ryan Taitano, John H. Slater
Journal: Advanced Healthcare Materials (2020)

Abstract The vascular system is integral for maintaining organ‐specific functions and homeostasis. Dysregulation in vascular architecture and function can lead to various chronic or acute disorders. Investigation of the role of the vascular system in health and disease has been accelerated through the development of tissue‐engineered constructs and microphysiological on‐chip platforms. These in vitro systems permit studies of biochemical regulation of vascular networks and parenchymal tissue and provide mechanistic insights into the biophysical and hemodynamic forces acting in organ‐specific niches. Detailed understanding of these forces and the mechanotransductory pathways involved is necessary to develop preventative and therapeutic strategies targeting the vascular system. This review describes vascular structure and function, the role of hemodynamic forces in maintaining vascular homeostasis, and measurement approaches for cell and tissue level mechanical properties influencing vascular phenomena. State‐of‐the‐art techniques for fabricating in vitro microvascular systems, with varying degrees of biological and engineering complexity, are summarized. Finally, the role of vascular mechanobiology in organ‐specific niches and pathophysiological states, and efforts to recapitulate these events using in vitro microphysiological systems, are explored. It is hoped that this review will help readers appreciate the important, but understudied, role of vascular‐parenchymal mechanotransduction in health and disease toward developing mechanotherapeutics for treatment strategies.
Peanut Allergy Burden Survey: Impact of Peanut Allergy on Global Quality of Life in Adolescent Patients
Authors: Anna Nowak-Wegrzyn, Steven Hass, Stephen Tilles, Sarah Donelson, Dan Robison, Kevin Norrett, Ann Cameron, Martine Etschmaier, Amy Duhig, William McCann
Journal: Journal of Allergy and Clinical Immunology (2020)
Phase II trial of atezolizumab plus chemotherapy after progression on single-agent PD-1 or PD-L1 inhibitor in cisplatin ineligible patients with advanced urothelial carcinoma HCRN GU17-295.
Authors: Nabil Adra, Ralph J. Hauke, Hristos Z. Kaimakliotis, Shuchi Gulati, Neda Hashemi, Roberto Pili
Journal: Journal of Clinical Oncology (2020)

TPS587 Background: Patients (pts) with cisplatin ineligible metastatic urothelial carcinoma (mUC) who progress after first-line PD1/PDL1 inhibition have limited treatment options. The concept of maintenance therapy with targeted agents and adding onto it at time of progression is a proven effective strategy. Preclinical data indicate that carboplatin+gemcitabine have immunomodulatory effect to potentially augment immune response. We hypothesize that in pts with cisplatin ineligible mUC, the use of atezolizumab+chemotherapy after progression on single-agent PD1/PDL1 inhibitor will result in clinical benefit. Methods: Multi-center, single arm, open label phase 2 trial of atezolizumab+carboplatin+gemcitabine in pts with cisplatin ineligible mUC. Eligible pts are adults with mUC (mixed histology allowed) who progressed after first line PD1/PDL1 inhibitor. Pts should be cisplatin ineligible based on consensus criteria. Neoadjuvant/adjuvant chemotherapy completed ≥12 months prior to enrollment is allowed. Treatment with atezolizumab will continue until disease progression or unacceptable toxicity while carboplatin+gemcitabine can be stopped after 4-6 cycles. Primary objective is progression-free survival per RECIST and secondary objectives are overall response rate, clinical benefit rate, and overall survival (OS). Exploratory endpoints include to compare OS of atezolizumab+carboplatin+gemcitabine in this trial compared to a virtual control arm of carboplatin+gemcitabine in mUC after progression on first-line PD1/PDL1 inhibitors. Other exploratory endpoints include to compare PD-L1 status at time of diagnosis and at time of enrollment (after progression on PD1/PDL1 inhibitor). Using an alternate hypothesis that atezolizumab+carboplatin+gemcitabine will have a median PFS of 9 months compared to historical control of 5 months with a platinum regimen in 2nd line setting, we plan to enroll 33 patients. This study is currently enrolling pts. A protocol amendment is under way that will allow pts with prior platinum-based chemotherapy to enroll on this trial. Clinical trial information: NCT03737123.
Microglia and macrophages promote corralling, wound compaction and recovery after spinal cord injury via Plexin-B2
Authors: Xiang Zhou, Shalaka Wahane, Marie-Sophie Friedl, Michael Kluge, Caroline C. Friedel, Kleopatra Avrampou, Venetia Zachariou, Lei Guo, Bin Zhang, Xijing He, Roland H. Friedel, Hongyan Zou
Journal: Nature Neuroscience (2020)