tbuckley/cabot-search huggingface dataset:
Long-term natural history and patterns of sporadic vestibular schwannoma growth: A multi-institutional volumetric analysis of 952 patients
Authors: John P Marinelli, Zane Schnurman, Daniel E Killeen, Ashley M Nassiri, Jacob B Hunter, Katherine A Lees, Christine M Lohse, J Thomas Roland, John G Golfinos, Douglas Kondziolka, Michael J Link, Matthew L Carlson
Journal: Neuro-Oncology (2021)

The current study aims to characterize the natural history of sporadic vestibular schwannoma volumetric tumor growth, including long-term growth patterns following initial detection of growth.Volumetric tumor measurements from 3505 serial MRI studies were analyzed from unselected consecutive patients undergoing wait-and-scan management at three tertiary referral centers between 1998 and 2018. Volumetric tumor growth was defined as a change in volume ≥20%.Among 952 patients undergoing observation, 622 experienced tumor growth with initial growth-free survival rates (95% CI) at 1, 3, and 5 years following diagnosis of 66% (63-69), 30% (27-34), and 20% (17-24). Among 405 patients who continued to be observed despite demonstrating initial growth, 210 experienced subsequent tumor growth with subsequent growth-free survival rates at 1, 3, and 5 years following initial growth of 77% (72-81), 37% (31-43), and 24% (18-31). Larger tumor volume at initial growth (HR 1.13, P = .02) and increasing tumor growth rate (HR 1.31; P < .001) were significantly associated with an increased likelihood of subsequent growth, whereas a longer duration of time between diagnosis and detection of initial growth was protective (HR 0.69; P < .001).While most vestibular schwannomas exhibit an overall propensity for volumetric growth following diagnosis, prior tumor growth does not perfectly predict future growth. Tumors can subsequently grow faster, slower, or demonstrate quiescence and stability. Larger tumor size and increasing tumor growth rate portend a higher likelihood of continued growth. These findings can inform timing of intervention: whether upfront at initial diagnosis, after detection of initial growth, or only after continued growth is observed.
Dual-functional porous and cisplatin-loaded polymethylmethacrylate cement for reconstruction of load-bearing bone defect kills bone tumor cells
Authors: Zhule Wang, Liebert Parreiras Nogueira, Håvard Jostein Haugen, Ingrid CM. Van Der Geest, Patricia Caetano de Almeida Rodrigues, Dennis Janssen, Thom Bitter, Jeroen J.J.P. van den Beucken, Sander CG. Leeuwenburgh
Journal: Bioactive Materials (2021)

Malignant bone tumors are usually treated by resection of tumor tissue followed by filling of the bone defect with bone graft substitutes. Polymethylmethacrylate (PMMA) cement is the most commonly used bone substitute in clinical orthopedics in view of its reliability. However, the dense nature of PMMA renders this biomaterial unsuitable for local delivery of chemotherapeutic drugs to limit the recurrence of bone tumors. Here, we introduce porosity into PMMA cement by adding carboxymethylcellulose (CMC) to facilitate such local delivery of chemotherapeutic drugs, while retaining sufficient mechanical properties for bone reconstruction in load-bearing sites. Our results show that the mechanical strength of PMMA-based cements gradually decreases with increasing CMC content. Upon incorporation of ≥3% CMC, the PMMA-based cements released up to 18% of the loaded cisplatin, in contrast to cements containing lower amounts of CMC which only released less than 2% of the cisplatin over 28 days. This release of cisplatin efficiently killed osteosarcoma cells in vitro and the fraction of dead cells increased to 91.3% at day 7, which confirms the retained chemotherapeutic activity of released cisplatin from these PMMA-based cements. Additionally, tibias filled with PMMA-based cements containing up to 3% of CMC exhibit comparable compressive strengths as compared to intact tibias. In conclusion, we demonstrate that PMMA cements can be rendered therapeutically active by introducing porosity using CMC to allow for release of cisplatin without compromising mechanical properties beyond critical levels. As such, these data suggest that our dual-functional PMMA-based cements represent a viable treatment option for filling bone defects after bone tumor resection in load-bearing sites.
Effects of BNT162b2 Covid-19 Vaccine Booster in Long-Term Care Facilities in Israel
Authors: Khitam Muhsen, Nimrod Maimon, Ami Mizrahi, Baruch Varticovschi, Omri Bodenheimer, Udi Gelbshtein, Itamar Grotto, Dani Cohen, Ron Dagan
Journal: New England Journal of Medicine (2021)
Re: Masayuki Hagiwara, Atsushi Fushimi, Kazuhiro Matsumoto, Mototsugu Oya. The Significance of PARP1 as a Biomarker for Predicting the Response to PD-L1 Blockade in Patients with PBRM1-mutated Clear Cell Renal Cell Carcinoma. Eur Urol. 2022;81:145–8
Authors: Zhan Wang, Yang Zhao, Yushi Zhang
Journal: European Urology (2021)
Survivorship for Individuals Living With Advanced and Metastatic Cancers: National Cancer Institute Meeting Report
Authors: Michelle A Mollica, Ashley Wilder Smith, Emily Tonorezos, Kathleen Castro, Kelly K Filipski, Jennifer Guida, Frank Perna, Paige Green, Paul B Jacobsen, Angela Mariotto, Gina Tesauro, Lisa Gallicchio
Journal: JNCI Journal of the National Cancer Institute (2021)

An important and often overlooked subpopulation of cancer survivors is individuals who are diagnosed with or progress to advanced or metastatic cancer. Living longer with advanced or metastatic cancer often comes with a cost of burdensome physical and psychosocial symptoms and complex care needs; however, research is limited on this population. Thus, in May 2021, the National Cancer Institute convened subject matter experts, researchers, clinicians, survivors, and advocates for a 2-day virtual meeting. The purpose of this report is to provide a summary of the evidence gaps identified by subject matter experts and attendees and key opportunities identified by the National Cancer Institute in 5 research areas: epidemiology and surveillance, symptom management, psychosocial research, health-care delivery, and health behaviors. Identified gaps and opportunities include the need to develop new strategies to estimate the number of individuals living with advanced and metastatic cancers; understand and address emerging symptom trajectories; improve prognostic understanding and communication between providers, patients, and caregivers; develop and test models of comprehensive survivorship care tailored to these populations; and assess patient and provider preferences for health behavior discussions throughout the survivorship trajectory. To best address the needs of individuals living with advanced and metastatic cancer and to deliver comprehensive evidence-based quality care, research is urgently needed to fill evidence gaps, and it is essential to incorporate the survivor perspective. Developing such an evidence base is critical to inform policy and practice.
Abstract 10617: Antiarrhythmic Use and the Posterior Probability of Neurologically Intact Survival in a Reanalysis of the Amiodarone, Lidocaine or Placebo Study in Out-of-Hospital Cardiac Arrest
Authors: Frederick J Brown, Steven E Rigdon, David L Brown
Journal: Circulation (2021)

Introduction: There are no randomized controlled trials (RCT) demonstrating improvement in neurologically intact survival from antiarrhythmic therapy given during out-of-hospital cardiac arrest (OHCA) from ventricular fibrillation/tachycardia (VF/VT). The Amiodarone, Lidocaine or Placebo Study in Out-of-Hospital Cardiac Arrest (ALPS) was an RCT of amiodarone, lidocaine or placebo whose primary end-point was survival to hospital discharge. We sought to estimate the posterior probability of the absolute risk difference of neurologically intact survival (modified Rankin Score ≤ 3) from antiarrhythmic use (amiodarone or lidocaine) compared to placebo and from the use amiodarone versus lidocaine. Methods: We performed a Bayesian reanalysis on the per-protocol population of the ALPS trial in order to calculate the posterior probability of neurologically intact survival. We derived prior probabilities from the Amiodarone for Resuscitation after Out-of-Hospital Cardiac Arrest Due to Ventricular Fibrillation (ARREST) and Amiodarone Compared with Lidocaine for Shock-Resistant Ventricular Fibrillation (ALIVE) trials. We considered a clinically meaningful absolute difference to be ≥ 1%. Results: The posterior median probability of the absolute difference in neurologically intact survival between antiarrhythmic therapy and placebo was 2.2% (95% credible interval of -0.15% to 4.7%). There is a 96% chance that antiarrhythmic improves neurologic outcome and 86% chance of a clinically meaningful improvement. The posterior median probability of the absolute difference in neurologically intact survival between amiodarone and lidocaine was 1.5% (95% credible interval -1.6% to 4.5%). Conclusion: The results of this Bayesian analysis of the ALPS trial using likely optimistic prior probabilities derived from the ARREST trial may help inform clinicians of the value of antiarrhythmic therapy in OHCA.
Case 38-2021: A 76-Year-Old Woman with Abdominal Pain, Weight Loss, and Memory Impairment
Authors: Lisa L. Willett, Gabrielle K. Bromberg, Ryan Chung, Rebecca K. Leaf, Rose H. Goldman, Amy K. Dickey
Journal: New England Journal of Medicine (2021)

A 76-year-old woman presented with abdominal pain, anorexia, memory impairment, and suicidal ideation. CT of the abdomen and pelvis revealed multiple dilated, fluid-filled loops of small bowel measuring up to 4 cm in diameter, with air–fluid levels and a transition point in the right lower quadrant. The urinary porphyrin levels were elevated. A diagnosis was made.
Response-adapted omission of radiotherapy and comparison of consolidation chemotherapy in children and adolescents with intermediate-stage and advanced-stage classical Hodgkin lymphoma (EuroNet-PHL-C1): a titration study with an open-label, embedded, multinational, non-inferiority, randomised controlled trial
Authors: Christine Mauz-Körholz, Judith Landman-Parker, Walentyna Balwierz, Roland A Ammann, Richard A Anderson, Andische Attarbaschi, Jörg M Bartelt, Auke Beishuizen, Sabah Boudjemaa, Michaela Cepelova, Alexander Claviez, Stephen Daw, Karin Dieckmann, Ana Fernández-Teijeiro, Alexander Fosså, Stefan Gattenlöhner, Thomas Georgi, Lisa L Hjalgrim, Andrea Hraskova, Jonas Karlén, Regine Kluge, Lars Kurch, Thiery Leblanc, Georg Mann, Francoise Montravers, Jean Pears, Tanja Pelz, Vladan Rajić, Alan D Ramsay, Dietrich Stoevesandt, Anne Uyttebroeck, Dirk Vordermark, Dieter Körholz, Dirk Hasenclever, William Hamish Wallace
Journal: The Lancet Oncology (2021)
Table of Contents
Authors: Youkyung Roh, Justin Choi, Nishadh Sutaria, Shawn Kwatra, Waleed Adawi, Rebecca Goldberg, Dirk Elston, Steven Sloan, Jonathan Kantor, Morgan Murphrey, Reid Waldman, Timothy Durso, Jane Grant-Kels, Warren Heymann, Laura Fitzpatrick, Jennifer Hsiao, Rachel Tannenbaum, Andrew Strunk, Amit Garg, Shari Wright, Clinton Enos, Vanessa Ramos, Robert Mclean, Tin-Chi Lin, Nicole Foster, Blessing Dube, Abby Van Voorhees, Linda Gold, Kim Papp, David Pariser, Lawrence Green, Neal Bhatia, Howard Sofen, Lorne Albrecht, Melinda Gooderham, Mindy Chen, Maria Paris, Yao Wang, Kristina Duffin, Francesco Bellinato, Paolo Gisondi, Giampiero Girolomoni, Jeffrey Seiler, Richard Keech, Julie Aker, William Miller, Christopher Belcher, Kerry Mettert, Andrew Blauvelt, Jonathan Silverberg, Charles Lynde, Thomas Fcda, Samantha Eisman, Jacek Zdybski, Walter Gubelin, Eric Simpson, Fernando Valenzuela, Paulo Criado, Mark Lebwohl, Claire Feeney, Tahira Khan, Pinaki Biswas, Marco Dibonaventura, Hernan Valdez, Michael Cameron, Ricardo Rojo
Journal: Journal of the American Academy of Dermatology (2021)
Small Cell Lung Cancer, Version 2.2022, NCCN Clinical Practice Guidelines in Oncology
Authors: Apar Kishor P. Ganti, Billy W. Loo, Michael Bassetti, Collin Blakely, Anne Chiang, Thomas A. D'Amico, Christopher D'Avella, Afshin Dowlati, Robert J. Downey, Martin Edelman, Charles Florsheim, Kathryn A. Gold, Jonathan W. Goldman, John C. Grecula, Christine Hann, Wade Iams, Puneeth Iyengar, Karen Kelly, Maya Khalil, Marianna Koczywas, Robert E. Merritt, Nisha Mohindra, Julian Molina, Cesar Moran, Saraswati Pokharel, Sonam Puri, Angel Qin, Chad Rusthoven, Jacob Sands, Rafael Santana-Davila, Michael Shafique, Saiama N. Waqar, Kristina M. Gregory, Miranda Hughes
Journal: Journal of the National Comprehensive Cancer Network (2021)

The NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Small Cell Lung Cancer (SCLC) provide recommended management for patients with SCLC, including diagnosis, primary treatment, surveillance for relapse, and subsequent treatment. This selection for the journal focuses on metastatic (known as extensive-stage) SCLC, which is more common than limited-stage SCLC. Systemic therapy alone can palliate symptoms and prolong survival in most patients with extensive-stage disease. Smoking cessation counseling and intervention should be strongly promoted in patients with SCLC and other high-grade neuroendocrine carcinomas. The “Summary of the Guidelines Updates” section in the SCLC algorithm outlines the most recent revisions for the 2022 update, which are described in greater detail in this revised Discussion text.
Impact of anaemia and the effect of empagliflozin in heart failure with reduced ejection fraction: findings from <scp>EMPEROR‐</scp>Reduced
Authors: João Pedro Ferreira, Stefan D. Anker, Javed Butler, Gerasimos Filippatos, Tomoko Iwata, Afshin Salsali, Cordula Zeller, Stuart J. Pocock, Faiez Zannad, Milton Packer
Journal: European Journal of Heart Failure (2021)
Long-Term Outcome of Multidisciplinary Versus Standard Gastroenterologist Care for Functional Gastrointestinal Disorders: A Randomized Trial
Authors: Chamara Basnayake, Michael A Kamm, Annalise Stanley, Amy Wilson-O'Brien, Kathryn Burrell, Isabella Lees-Trinca, Angela Khera, Jim Kantidakis, Olivia Wong, Kate Fox, Nicholas J Talley, Danny Liew, Michael R Salzberg, Alexander J Thompson
Journal: Clinical Gastroenterology and Hepatology (2021)
NRSF- <i>GNAO1</i> Pathway Contributes to the Regulation of Cardiac Ca <sup>2+</sup> Homeostasis
Authors: Hideaki Inazumi, Koichiro Kuwahara, Yasuaki Nakagawa, Yoshihiro Kuwabara, Takuro Numaga-Tomita, Toshihide Kashihara, Tsutomu Nakada, Nagomi Kurebayashi, Miku Oya, Miki Nonaka, Masami Sugihara, Hideyuki Kinoshita, Kenji Moriuchi, Hiromu Yanagisawa, Toshio Nishikimi, Hirohiko Motoki, Mitsuhiko Yamada, Sachio Morimoto, Kinya Otsu, Richard M. Mortensen, Kazuwa Nakao, Takeshi Kimura
Journal: Circulation Research (2021)

Background: During the development of heart failure, a fetal cardiac gene program is reactivated and accelerates pathological cardiac remodeling. We previously reported that a transcriptional repressor, NRSF (neuron restrictive silencer factor), suppresses the fetal cardiac gene program, thereby maintaining cardiac integrity. The underlying molecular mechanisms remain to be determined, however. Methods: We aim to elucidate molecular mechanisms by which NRSF maintains normal cardiac function. We generated cardiac-specific NRSF knockout mice and analyzed cardiac gene expression profiles in those mice and mice cardiac-specifically expressing a dominant-negative NRSF mutant. Results: We found that cardiac expression of Gα o , an inhibitory G protein encoded in humans by GNAO1 , is transcriptionally regulated by NRSF and is increased in the ventricles of several mouse models of heart failure. Genetic knockdown of Gnao1 ameliorated the cardiac dysfunction and prolonged survival rates in these mouse heart failure models. Conversely, cardiac-specific overexpression of GNAO1 in mice was sufficient to induce cardiac dysfunction. Mechanistically, we observed that increasing Gα o expression increased surface sarcolemmal L-type Ca 2+ channel activity, activated CaMKII (calcium/calmodulin-dependent kinase-II) signaling, and impaired Ca 2+ handling in ventricular myocytes, which led to cardiac dysfunction. Conclusions: These findings shed light on a novel function of Gα o in the regulation of cardiac Ca 2+ homeostasis and systolic function and suggest Gα o may be an effective therapeutic target for the treatment of heart failure.
Molecular damage in aging
Authors: Vadim N. Gladyshev, Stephen B. Kritchevsky, Steven G. Clarke, Ana Maria Cuervo, Oliver Fiehn, João Pedro de Magalhães, Theresa Mau, Michal Maes, Robert L. Moritz, Laura J. Niedernhofer, Emile Van Schaftingen, Gregory J. Tranah, Kenneth Walsh, Yoshimitsu Yura, Bohan Zhang, Steven R. Cummings
Journal: Nature Aging (2021)
Letter to the editor: Autoimmune hepatitis after COVID‐19 vaccination: Need for population‐based epidemiological study
Authors: Yuji Suzuki, Keisuke Kakisaka, Yasuhiro Takikawa
Journal: Hepatology (2021)

We have read with interest the study published by Palla et al.[1] regarding a possible link between COVID-19 vaccination and the development of autoimmune hepatitis (AIH).[2, 3] We propose the need for population-based studies to gather data on the incidence, severity, and clinical features of COVID-19 vaccination-induced AIH by describing three cases of COVID-19 vaccination-induced AIH from our institution between January and October 2021. Case 1 involves an 80-year-old woman diagnosed with a liver injury (aspartate aminotransferase 995 U/L, alanine aminotransferase 974 U/L, total bilirubin 3.5 mg/dl), based on her laboratory results 10 days after receiving the second dose of the BNT162b2 (Pfizer-BioNTech) COVID-19 vaccine. The antinuclear antibody test was positive at a titer of 1:40. The serum immunoglobulin G level was 1936 mg/dl. A full serological screen excluded other causes of acute liver disease. Liver biopsy revealed lymphoplasmacytic infiltration in the portal area with moderate interface hepatitis, compatible with AIH (Figure 1A,B). She was treated with prednisone at an initial dose of 0.8 mg/kg/day. The dose was subsequently tapered to 10 mg/week on noting progressive improvement in her laboratory results (Figure 1C). Two other patients exhibited similar findings. One was a 75-year-old woman who developed AIH 4 days after the second dose of BNT162b2, whereas the other was a 78-year-old woman who developed AIH 7 days after her first dose of BNT162b2. The histological features of the liver biopsy specimen and the clinical course of the two patients are presented in Figures S1 and S2. The clinical characteristics of the patients are presented in Table S1. All 3 patients underwent regular blood testing because of underlying diseases without anterior liver injury. Epidemiological studies on post-COVID-19 vaccination myocarditis have shown that most cases occurred within 1 month of vaccination.[4] This was consistent with the three reported cases. Approximately 0.9 million people had received two vaccine doses in our medical region by October 31, 2021. Therefore, the incidence of AIH due to COVID-19 vaccination was estimated to be three cases per million people. When managing new or exacerbated AIH cases, the patient's COVID-19 vaccination history should be investigated. Rigorous population-based studies are required in the future to evaluate the incidence of COVID-19 vaccine–induced AIH. We thank Masao Nishiya for a valuable discussion on the interpretation of the liver biopsy specimens. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
Error in Figure
Authors: Thomas Martens, Roy Beck, Richard Bergenstal
Journal: JAMA (2021)

Jean M. Lawrence, ScD, MPH, MSSA; Jasmin Divers, PhD; Scott Isom, MS; Sharon Saydah, PhD; Giuseppina Imperatore, MD, PhD; Catherine Pihoker, MD; Santica M. Marcovina, PhD, ScD; Elizabeth J. Mayer-Davis, PhD; Richard F. Hamman, MD, DrPH; Lawrence Dolan, MD; Dana Dabelea, MD, PhD; David J. Pettitt, MD; Angela D. Liese, PhD; SEARCH for Diabetes in Youth Study Group
Case 39-2021: A 26-Year-Old Woman with Respiratory Failure and Altered Mental Status
Authors: Aran Kadar, Viral S. Shah, Dexter P. Mendoza, Peggy S. Lai, Yasmin Aghajan, Gregory Piazza, Erica C. Camargo, Kartik Viswanathan
Journal: New England Journal of Medicine (2021)

A 26-year-old woman was transferred to this hospital because of respiratory failure and altered mental status. Three days earlier, she had undergone elective liposuction. CT of the chest showed diffuse opacities involving all lung lobes; CT of the head showed cerebral edema and a hypodensity in the globus pallidus. A diagnosis was made.
Use of Belimumab for Prophylaxis of Chronic Graft-Versus-Host Disease
Authors: Iskra Pusic, Tanner Johanns, Stefanie Sarantopoulos, Haley Record, Kaitlynn Zeisset, Peter Westervelt, Amanda F. Cashen, Geoffrey L. Uy, Camille Abboud, John F. DiPersio
Journal: Blood (2021)
Inhibition of ADAM17 impairs endothelial cell necroptosis and blocks metastasis
Authors: Julia Bolik, Freia Krause, Marija Stevanovic, Monja Gandraß, Ilka Thomsen, Sarah-Sophie Schacht, Eva Rieser, Miryam Müller, Neele Schumacher, Jürgen Fritsch, Rielana Wichert, Eithan Galun, Juri Bergmann, Christian Röder, Clemens Schafmayer, Jan-Hendrik Egberts, Christoph Becker-Pauly, Paul Saftig, Ralph Lucius, Wulf Schneider-Brachert, Roja Barikbin, Dieter Adam, Matthias Voss, Wolfgang Hitzl, Achim Krüger, Boris Strilic, Irit Sagi, Henning Walczak, Stefan Rose-John, Dirk Schmidt-Arras
Journal: The Journal of Experimental Medicine (2021)

Metastasis is the major cause of death in cancer patients. Circulating tumor cells need to migrate through the endothelial layer of blood vessels to escape the hostile circulation and establish metastases at distant organ sites. Here, we identified the membrane-bound metalloprotease ADAM17 on endothelial cells as a key driver of metastasis. We show that TNFR1-dependent tumor cell–induced endothelial cell death, tumor cell extravasation, and subsequent metastatic seeding is dependent on the activity of endothelial ADAM17. Moreover, we reveal that ADAM17-mediated TNFR1 ectodomain shedding and subsequent processing by the γ-secretase complex is required for the induction of TNF-induced necroptosis. Consequently, genetic ablation of ADAM17 in endothelial cells as well as short-term pharmacological inhibition of ADAM17 prevents long-term metastases formation in the lung. Thus, our data identified ADAM17 as a novel essential regulator of necroptosis and as a new promising target for antimetastatic and advanced-stage cancer therapies.