tbuckley/cabot-search huggingface dataset:
Safety and Efficacy of Checkpoint Inhibition in Patients With Melanoma and Preexisting Autoimmune Disease
Authors: Monique K. van der Kooij, Karijn P.M. Suijkerbuijk, Olaf M. Dekkers, Ellen Kapiteijn
Journal: Annals of Internal Medicine (2021)

LettersSeptember 2021Safety and Efficacy of Checkpoint Inhibition in Patients With Melanoma and Preexisting Autoimmune DiseaseMonique K. van der Kooij, MD, Karijn P.M. Suijkerbuijk, MD, PhD, Olaf M. Dekkers, MD, PhD, Ellen Kapiteijn, MD, PhDMonique K. van der Kooij, MD, Karijn P.M. Suijkerbuijk, MD, PhD, Olaf M. Dekkers, MD, PhD, Ellen Kapiteijn, MD, PhDAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/L21-0442 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail IN RESPONSE: We thank Dr. Yang and colleagues for their interest in our article and would like to respond to the concerns that they raised.First, Dr. Yang and colleagues contend that the prevalence and severity of immune-related adverse events would have differed if we had excluded patients with preexisting thyroid disorders. They refer to a phase 1b trial in which—as in most currently recruiting checkpoint inhibitor trials—thyroid disorders are not an exclusion criterion. Because our aim was to include all autoimmune disorders, we explicitly included both hypo- and hyperthyroidism. However, in Appendix Tables 5 to 7 of our article, ... Author, Article, and Disclosure InformationAffiliations: Disclosures: Disclosures can be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=M20-3419. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetailsSee AlsoSafety and Efficacy of Checkpoint Inhibition in Patients With Melanoma and Preexisting Autoimmune Disease Monique K. van der Kooij , Karijn P.M. Suijkerbuijk , Maureen J.B. Aarts , Franchette W.P.J. van den Berkmortel , Christian U. Blank , Marye J. Boers-Sonderen , Jesper van Breeschoten , Alfonsus J.M. van den Eertwegh , Jan Willem B. de Groot , John B.A.G. Haanen , Geke A.P. Hospers , Djura Piersma , Rozemarijn S. van Rijn , Albert J. ten Tije , Astrid A.M. van der Veldt , Gerard Vreugdenhil , Michiel C.T. van Zeijl , Michel W.J.M Wouters , Olaf M. Dekkers , and Ellen Kapiteijn Safety and Efficacy of Checkpoint Inhibition in Patients With Melanoma and Preexisting Autoimmune Disease Xi Yang , Lilit Karapetyan , and John M. Kirkwood Metrics September 2021Volume 174, Issue 9Page: 1345-1346 ePublished: 21 September 2021 Issue Published: September 2021 Copyright & PermissionsCopyright © 2021 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
Endoscopic treatment of Zenker’s diverticulum: a never ending (r)evolution
Authors: Pietro Familiari
Journal: Endoscopy (2021)

Friedrich Albert von Zenker was a German pathologist, who lived and worked in Erlangen, Germany, in the nineteenth century. In 1877, he meticulously described the precise anatomy and pathology of the posterior pulsion pharyngeal diverticulum that bears his name [1].
E-Cigarette Toxicology
Authors: Terry Gordon, Emma Karey, Meghan E. Rebuli, Yael-Natalie H. Escobar, Ilona Jaspers, Lung Chi Chen
Journal: The Annual Review of Pharmacology and Toxicology (2021)

Since the spread of tobacco from the Americas hundreds of years ago, tobacco cigarettes and, more recently, alternative tobacco products have become global products of nicotine addiction. Within the evolving alternative tobacco product space, electronic cigarette (e-cigarette) vaping has surpassed conventional cigarette smoking among adolescents and young adults in the United States and beyond. This review describes the experimental and clinical evidence of e-cigarette toxicity and deleterious health effects. Adverse health effects related to e-cigarette aerosols are influenced by several factors, including e-liquid components, physical device factors, chemical changes related to heating, and health of the e-cigarette user (e.g., asthmatic). Federal, state, and local regulations have attempted to govern e-cigarette flavors, manufacturing, distribution, and availability, particularly to underaged youths. However, the evolving e-cigarette landscape continues to impede timely toxicological studies and hinder progress made toward our understanding of the long-term health consequence of e-cigarettes.
Human cytomegalovirus expands a CD8 <sup>+</sup> T cell population with loss of <i>BCL11B</i> expression and gain of NK cell identity
Authors: Rosa Sottile, M. Kazim Panjwani, Colleen M. Lau, Anthony F. Daniyan, Kento Tanaka, Juliet N. Barker, Renier J. Brentjens, Joseph C. Sun, Jean-Benoît Le Luduec, Katharine C. Hsu
Journal: Science Immunology (2021)

NKG2C + CD8 + T cells, found in 40% of HCMV-seropositive individuals, have lost BCL11B expression and adopt an innate-like identity.
Endoscopic ultrasonography-guided double-balloon-occluded gastrojejunostomy bypass (EPASS) for malignant gastric outlet obstruction
Authors: John Alexander Lata Guacho, Marcelo Mochate Flor, Marina Tucci G. B. Ferreira, Caio de Almeida Perez, Bruno da Costa Martins, Fauze Maluf-Filho
Journal: Endoscopy (2021)

Our patient, a 58-year-old woman, was being followed-up for ulcerative colitis. Computed tomography (CT) showed the presence of a pancreatic nodule, which after endoscopic ultrasonography (EUS)-guided puncture and biopsy was diagnosed as pancreatic head adenocarcinoma. The patient developed jaundice and acute cholangitis, and biliary drainage by endoscopic retrograde cholangiopancreatography was carried out.
Signature morpho-electric, transcriptomic, and dendritic properties of human layer 5 neocortical pyramidal neurons
Authors: Brian E Kalmbach, Rebecca D Hodge, Nikolas L Jorstad, Scott Owen, Rebecca de Frates, Anna Marie Yanny, Rachel Dalley, Matt Mallory, Lucas T Graybuck, Cristina Radaelli, C Dirk Keene, Ryder P Gwinn, Daniel L Silbergeld, Charles Cobbs, Jeffrey G Ojemann, Andrew L Ko, Anoop P Patel, Richard G Ellenbogen, Trygve E Bakken, Tanya L Daigle, Nick Dee, Brian R Lee, Medea McGraw, Philip R Nicovich, Kimberly Smith, Staci A Sorensen, Bosiljka Tasic, Hongkui Zeng, Christof Koch, Ed S Lein, Jonathan T Ting
Journal: Neuron (2021)
Physician satisfaction with electronic medical records (EMRs): Time for an intelligent health record?
Authors: Ajeet Gajra, Dewilka Simons, Yolaine Jeune-Smith, Amy W. Valley, Bruce A. Feinberg
Journal: Journal of Clinical Oncology (2021)

318 Background: EMRs are devised to improve the quality and efficiency of healthcare delivery and to reduce medical errors. Despite the widespread use of EMRs, various factors can limit their effectiveness in improving healthcare quality. General EMR use has been cited as a factor contributing to increased workload and clinician burnout in oncology and other specialties. The objective of this qualitative research study was to identify barriers perceived by medical oncologists and hematologists (mO/H) in utilizing EMR software and factors associated with levels of satisfaction. Methods: Between January and April 2021, mO/H from across the U.S. were invited to complete a web-based survey about various trends and critical issues in oncology care. Demographics about the physicians and characteristics of their practices were captured as well in the survey. Responses were aggregated and analyzed using descriptive statistics. Results: A total of 369 mO/H completed the survey: 72% practice in a community setting; 47% identified as a hospital employee; they have an average of 19 years of clinical experience and spend on average 86% of their working time in direct patient care, seeing 17 patients per day on average on clinic days. Most (99%) of mO/H surveyed use an EMR software at their practice, with Epic (45%) and OncoEMR (16%) being the most common. Regarding satisfaction, 16% and 50% reported feeling highly satisfied and satisfied, respectively, with their current EMR, and 3% and 11% reported feeling very dissatisfied or dissatisfied, respectively. Some (19%) stated that they have considered changing their EMR, and 68% are unsure how EMR licensing fees for their practice are paid. EMR pain points most commonly experienced were: time-consuming, e.g., too many steps/click (70%); interoperability, e.g., difficulty sharing information across institutions or other EMR software (45%); data entry issues, e.g., difficulty entering clinical information, scheduling patient visits and reminders, or ordering multiple labs (38%); and poor workflow support (31%). The most useful aspects/features of their EMR software reported were availability of information, e.g., preloaded protocols, chemotherapy regimens and pathways (64%); data access (64%); and multiple access points, including remote access (37%). Conclusions: Satisfaction with EMR were generally positive among the mO/H surveyed. However, there are multiple deterrents to the efficient use of current EMR systems. This information is essential in the design of next-generation EMR (an Intelligent Medical Records system) to allow for incorporation of aspects most useful to the end-users, such as pathway access, preloaded information on cancer management as well as ease of access and portability, and a user experience that minimizes clicks and reduces physician time with EMR.
Inhibition of viral suppressor of RNAi proteins by designer peptides protects from enteroviral infection in vivo
Authors: Yuan Fang, Zezhong Liu, Yang Qiu, Jing Kong, Yuhong Fu, Yujie Liu, Chong Wang, Jia Quan, Qian Wang, Wei Xu, Lei Yin, Jie Cui, Yi Xu, Stephen Curry, Shibo Jiang, Lu Lu, Xi Zhou
Journal: Immunity (2021)
Ruscogenin alleviates LPS-triggered pulmonary endothelial barrier dysfunction through targeting NMMHC IIA to modulate TLR4 signaling
Authors: Yunhao Wu, Xiu Yu, Yuwei Wang, Yalin Huang, Jiahui Tang, Shuaishuai Gong, Siyu Jiang, Yuanli Xia, Fang Li, Boyang Yu, Yuanyuan Zhang, Junping Kou
Journal: Acta Pharmaceutica Sinica B (2021)

Pulmonary endothelial barrier dysfunction is a hallmark of clinical pulmonary edema and contributes to the development of acute lung injury (ALI). Here we reported that ruscogenin (RUS), an effective steroidal sapogenin of Radix Ophiopogon japonicus, attenuated lipopolysaccharides (LPS)-induced pulmonary endothelial barrier disruption through mediating non-muscle myosin heavy chain IIA (NMMHC IIA)‒Toll-like receptor 4 (TLR4) interactions. By in vivo and in vitro experiments, we observed that RUS administration significantly ameliorated LPS-triggered pulmonary endothelial barrier dysfunction and ALI. Moreover, we identified that RUS directly targeted NMMHC IIA on its N-terminal and head domain by serial affinity chromatography, molecular docking, biolayer interferometry, and microscale thermophoresis analyses. Downregulation of endothelial NMMHC IIA expression in vivo and in vitro abolished the protective effect of RUS. It was also observed that NMMHC IIA was dissociated from TLR4 and then activating TLR4 downstream Src/vascular endothelial cadherin (VE-cadherin) signaling in pulmonary vascular endothelial cells after LPS treatment, which could be restored by RUS. Collectively, these findings provide pharmacological evidence showing that RUS attenuates LPS-induced pulmonary endothelial barrier dysfunction by inhibiting TLR4/Src/VE-cadherin pathway through targeting NMMHC IIA and mediating NMMHC IIA‒TLR4 interactions.
Activation of immune cell proteasomes in peripheral blood of smokers and COPD patients: implications for therapy
Authors: Ilona E. Kammerl, Sophie Hardy, Claudia Flexeder, Andrea Urmann, Julia Peierl, Yuqin Wang, Oliver Vosyka, Marion Frankenberger, Katrin Milger, Jürgen Behr, Andrea Koch, Juliane Merl-Pham, Stefanie M. Hauck, Charles Pilette, Holger Schulz, Silke Meiners
Journal: European Respiratory Journal (2021)

Background Immune cells contain a specialised type of proteasome, i.e. the immunoproteasome, which is required for intracellular protein degradation. Immunoproteasomes are key regulators of immune cell differentiation, inflammatory activation and autoimmunity. Immunoproteasome function in peripheral immune cells might be altered by smoking and in chronic obstructive pulmonary disease (COPD), thereby affecting immune cell responses. Methods We analysed the expression and activity of proteasome complexes in peripheral blood mononuclear cells (PBMCs) isolated from healthy male young smokers as well as from patients with severe COPD and compared them with matching controls. Results Proteasome expression was upregulated in COPD patients as assessed by quantitative reverse transcriptase-PCR and mass spectrometry-based proteomic analysis. Proteasome activity was quantified using activity-based probes and native gel analysis. We observed distinct activation of immunoproteasomes in the peripheral blood cells of young male smokers and severely ill COPD patients. Native gel analysis and linear regression modelling confirmed robust activation and elevated assembly of 20S proteasomes, which correlated significantly with reduced lung function parameters in COPD patients. The immunoproteasome was distinctly activated in COPD patients upon inflammatory cytokine stimulation of PBMCs in vitro . Inhibition of the immunoproteasome reduced pro-inflammatory cytokine expression in COPD-derived blood immune cells. Conclusions Given the crucial role of chronic inflammatory signalling and the emerging involvement of autoimmune responses in COPD, therapeutic targeting of the immunoproteasome might represent a novel therapeutic concept for COPD.
Risk of tuberculosis in patients with cancer treated with immune checkpoint inhibitors: a nationwide observational study
Authors: Seongman Bae, Ye-Jee Kim, Min-ju Kim, Jwa Hoon Kim, Sung-Cheol Yun, Jiwon Jung, Min Jae Kim, Yong Pil Chong, Sung-Han Kim, Sang-Ho Choi, Yang Soo Kim, Sang-Oh Lee
Journal: Journal for ImmunoTherapy of Cancer (2021)

Background While some recent studies have reported the development of tuberculosis (TB) in patients exposed to immune checkpoint inhibitors (ICIs), there is limited evidence to date. Therefore, we evaluated the risk of TB in patients with cancer exposed to ICIs using the National Health Insurance claims data in South Korea. Methods Patients with diagnostic codes for non-small cell lung cancer, urothelial carcinoma or melanoma between August 2017 and June 2019 were identified. The incidence rate and standardized incidence ratio (SIR) of TB were calculated for both the ICI exposure and non-exposure groups. The risk of TB according to ICI exposure was assessed using a multivariable Cox regression model. Results During the study period, 141 550 patients with cancer and 916 new TB cases were identified. Among the 5037 patients exposed to ICIs, 20 were diagnosed with TB at a median of 2.2 months after the ICI was initiated. The crude incidence rate of TB per 100,000 person-years was 675.8 (95% CI 412.8 to 1043.8) for the ICI exposure group and 599.1 (95% CI 560.5 to 639.6) for the non-exposure group. The SIR for TB was 8.1 (95% CI 8.0 to 8.2) in the ICI exposure group. After adjusting for potential confounding factors, ICI treatment was not significantly associated with an increased risk of TB (HR: 0.73; 95% CI 0.47 to 1.14). Conclusions While the incidence of TB in cancer patients exposed to ICIs was eightfold higher than in the general population, the risk of patients with cancer developing TB did not significantly differ according to ICI exposure.
Hemostatic characterization of post-covid-19 convalescent plasma donors: The bergamo experience
Authors: C. J. Tartari, G. Milani, F. Salvetti, M. Marchetti, L. Russo, A. Vignoli, M. Vitali, L. Barcella, M. Cefis, P. Gomez-Rosas, F. Schieppati, G. Ravasio, L. Castellani, G. Marchesi, E. Sanga, D. Romeo, A. Falanga
Journal: HemaSphere (2021)

Background: Severe COVID-19 is associated with a profound derangement of the hemostatic system characterized by hypercoagulability, complement activation and endothelial cell perturbation. After disease resolution, some convalescent subjects still experience post-COVID-19 symptoms. No information is available on persistence of hemostatic alterations in this setting. Bergamo city, represents one of the first and most affected area by SARS-CoV-2 infection in the world. For this reason, since the beginning we were actively involved in hyperimmune plasma collection from COVID-19 convalescent subjects. Aims: In this study, in a large cohort of convalescent donors of hyperimmune plasma, we aimed to characterize select hemostatic parameters of hypercoagulability and endothelial cell perturbation and their association with disease severity, demographic characteristics, and antibody levels. Methods: Recovered COVID-19 patients eligible to plasma donation were tested for the SARS-CoV-2 antibodies by the anti-N IgG SARSCoV- 2 antibodies (Abbott Laboratories, IL, USA, Anti-N Abs), and/or the anti-S IgG SARS-CoV-2 antibodies (Liaison-Diasorin, Sallugia-VC, Italy, Anti-S Abs), according to the manufacturer's instructions. Fibrinogen, protein C, protein S, factor V, factor VIII, factor XIII, D-dimer, and von Willebrand factor (vWF) were assessed. Results: 425 subjects have been included (275M/150F) with a median age of 48 years (range: 19-67 years). Among convalescent subjects admitted to the donation, male gender, age > 40 years, and previous hospitalization for COVID-19, were identified as independent predictive factors for significantly (p<0.001) higher levels of SARS-CoV-2 IgG (both anti-S and anti-N). Hemostatic parameters including fibrinogen, protein S, factor V, factor VIII, factor XIII, and D-dimer were not different between severe and non-severe COVID-19. Differently, convalescent subjects with previous severe COVID-19 showed significantly higher levels of vWF (124±40 vs 121±41 %, p<0.001) and PC (119±19 vs 109±19 %, p<0.001) compared with non-severe COVID-19 subjects. In addition, significant positive correlations were found between vWF levels and anti-S Abs (vWF antigen r=0.216;vWF activity r=0.257 and vWF RiCof r=0.226, p<0.01). Summary/Conclusion: Our data show that gender, age and severe disease can be potential predictors of an increased immunological response. Furthermore, convalescent subjects show a persistently high vWF levels, suggesting a persistence of the endothelial activation, despite of clinical disease remission.
A Novel Paradigm for Surgical Skills Training and Assessment of Competency
Authors: Mark W. Bowyer, Pamela B. Andreatta, John H. Armstrong, Kyle N. Remick, Eric A. Elster
Journal: JAMA Surgery (2021)

Sustainment of comprehensive procedural skills in trauma surgery is a particular problem for surgeons in rural, global, and combat settings. Trauma care often requires open surgical procedures for low-frequency/high-risk injuries at a time when open surgical experience is declining in general and trauma surgery training.To determine whether general surgeons participating in a 2-day standardized trauma skills course demonstrate measurable improvement in accuracy and independent performance of specific trauma skills.General surgeons in active surgical practice were enrolled from a simulation center with anatomic laboratory from October 2019 to October 2020. Differences in pretraining/training and posttraining performance outcomes were examined using (1) pretraining/posttraining surveys, (2) pretraining/posttraining knowledge assessment, and (3) training/posttraining faculty assessment. Analysis took place in November 2020.A 2-day standardized, immersive, cadaver-based skills course, developed with best practices in instructional design, that teaches and assesses 24 trauma surgical procedures was used.Trauma surgery capability, as measured by confidence, knowledge, abilities, and independent performance of specific trauma surgical procedures; 3-month posttraining skill transfer.The study cohort included 65 active-duty general surgeons, of which 16 (25%) were women and 49 (75%) were men. The mean (SD) age was 38.5 (4.2) years. Before and during training, 1 of 65 participants (1%) were able to accurately perform all 24 procedures without guidance. After course training, 64 participants (99%) met the benchmark performance requirements for the 24 trauma procedures, and 51 (78%) were able to perform them without guidance. Procedural confidence and knowledge increased significantly from before to after the course. At 3 months after training, 37 participants (56%) reported skill transfer to trauma or other procedures.In this study, direct measurement of procedural performance following standardized training demonstrated significant improvement in skill performance in a broad array of trauma procedures. This model may be useful for assessment of procedural competence in other specialties.
Rates of Opioid Prescriptions Obtained After Mohs Surgery
Authors: Surya A. Veerabagu, Brian Cheng, Sonia Wang, Jeremy R. Etzkorn, Austin S. Kilaru, Megan H. Noe, Christopher J. Miller, Joseph F. Sobanko, Thuzar M. Shin, H. William Higgins, Stacy L. McMurray, Aimee E. Krausz, Joanna L. Walker, Cerrene N. Giordano
Journal: JAMA Dermatology (2021)

To curtail the opioid epidemic, physicians have been advised to limit opioid prescriptions.To characterize the frequency and changes over time (2009-2020) of opioid prescriptions following Mohs micrographic surgery.This cross-sectional study using Optum Clinformatics DataMart (Optum CDM), a nationally representative insurance claims database, included patients aged 18 years and older who had Mohs micrographic surgery insurance claims in the Optum CDM database from 2009 to 2020. Data were analyzed from November 11, 2020, to March 30, 2021.Opioid prescription following Mohs surgery.The primary outcome was the proportion of patients who underwent Mohs surgery and obtained an opioid prescription within 2 days of surgery. Secondary outcomes included type and opioid quantity prescribed.Among 358 012 patients with Mohs micrographic surgery claims (mean [SD] age, 69 [13] years; 205 609 [57.4%] were men), the proportion of patients obtaining an opioid prescription after Mohs micrographic surgery increased from 2009 (34.6%) to 2011 (39.6%). This proportion then declined each year, reaching a low of 11.7% in 2020 (27.9% absolute decrease from 2011 to 2020). Hydrocodone, codeine, oxycodone, and tramadol were the 4 most commonly prescribed opioids. By 2020, hydrocodone was obtained less (2009: 47.5%; 2011: 67.1%; 2020: 45.4%; 21.7% absolute decrease from 2011 to 2020) and tramadol was obtained more (2009: 1.6%; 2020: 27.9%; 26.3% absolute increase from 2009 to 2020).In this cross-sectional study of Mohs micrographic surgery claims, patients obtained fewer postsurgery opioid prescriptions over the study period, suggesting responsiveness of patients and dermatologic surgeons to public health concerns regarding the opioid epidemic. During this decline, prescriptions for hydrocodone decreased and tramadol increased.