tbuckley/cabot-search huggingface dataset:
COVID-19 and Excess All-Cause Mortality in the US and 18 Comparison Countries
Authors: Alyssa Bilinski, Ezekiel J. Emanuel
Journal: JAMA (2020)

This Viewpoint compares the COVID-19 per capita overall and excess mortality rates in the US vs that of 18 OECD countries and the timing of any increases in excess mortality between February and September 2020.
Intratumoral Injection of <i>Clostridium novyi</i>-NT Spores in Patients with Treatment-refractory Advanced Solid Tumors
Authors: Filip Janku, Halle Huihong Zhang, Abdulmohammad Pezeshki, Sanjay Goel, Ravi Murthy, Andrea Wang-Gillam, Dale R. Shepard, Thorunn Helgason, Tyler Masters, David S. Hong, Sarina A. Piha-Paul, Daniel D. Karp, Mark Klang, Steven Y. Huang, Divya Sakamuri, Anjali Raina, Jean Torrisi, Stephen B. Solomon, Alice Weissfeld, Ernest Trevino, Gary DeCrescenzo, Amanda Collins, Maria Miller, Jennifer L. Salstrom, Ronald L. Korn, Linping Zhang, Saurabh Saha, Alexey A. Leontovich, David Tung, Brent Kreider, Mary Varterasian, Khashayarsha Khazaie, Mrinal M. Gounder
Journal: Clinical Cancer Research (2020)

Intratumorally injected Clostridium novyi-NT (nontoxic; lacking the alpha toxin), an attenuated strain of C. novyi, replicates within hypoxic tumor regions resulting in tumor-confined cell lysis and inflammatory response in animals, which warrants clinical investigation.This first-in-human study (NCT01924689) enrolled patients with injectable, treatment-refractory solid tumors to receive a single intratumoral injection of C. novyi-NT across 6 dose cohorts (1 × 104 to 3 × 106 spores, 3+3 dose-escalation design) to determine dose-limiting toxicities (DLT), and the maximum tolerated dose.Among 24 patients, a single intratumoral injection of C. novyi-NT led to bacterial spores germination and the resultant lysis of injected tumor masses in 10 patients (42%) across all doses. The cohort 5 dose (1 × 106 spores) was defined as the maximum tolerated dose; DLTs were grade 4 sepsis (n = 2) and grade 4 gas gangrene (n = 1), all occurring in three patients with injected tumors >8 cm. Other treatment-related grade ≥3 toxicities included pathologic fracture (n = 1), limb abscess (n = 1), soft-tissue infection (n = 1), respiratory insufficiency (n = 1), and rash (n = 1), which occurred across four patients. Of 22 evaluable patients, nine (41%) had a decrease in size of the injected tumor and 19 (86%) had stable disease as the best overall response in injected and noninjected lesions combined. C. novyi-NT injection elicited a transient systemic cytokine response and enhanced systemic tumor-specific T-cell responses.Single intratumoral injection of C. novyi-NT is feasible. Toxicities can be significant but manageable. Signals of antitumor activity and the host immune response support additional studies of C. novyi-NT in humans.
Peripheral Photopenia on Whole-Body PET/CT Imaging With 18F-FDG in Patients With Compartment Syndrome and Mesenteric Venous Thrombosis
Authors: Erik T. te Beek, Peter L. Tangkau, Stijn van Esser, Rolf E. Brouwer, Marc R. J. ten Broek
Journal: Clinical Nuclear Medicine (2020)

Abstract We present 2 cases that demonstrate photopenia in peripheral areas on whole-body PET/CT imaging with 18 F-FDG as a sign of absent perfusion with severe short-term complications. The scan of the first patient shows photopenia in the right ankle and foot, resulting from compartment syndrome, caused by hemolytic group A streptococcus bacteremia with endocarditis and septic emboli, necessitating lower leg amputation. The scan of the second patient shows photopenia in the transverse colon, resulting from mesenteric venous thrombosis caused by polycythemia vera, leading to necrosis and perforation of the transverse colon, necessitating transverse and right hemicolectomy.
Interval cancer after colonoscopy in the Austrian National Screening Programme: influence of physician and patient factors
Authors: Elisabeth Waldmann, Daniela Penz, Hana Šinkovec, Georg Heinze, Christoph Rinner, Lena Jiricka, Barbara Majcher, Anna Hinterberger, Michael Trauner, Monika Ferlitsch
Journal: Gut (2020)

Postscreening colorectal cancer (PSCRC) after screening colonoscopy is associated with endoscopists' performance and characteristics of resected lesions. Prior studies have shown that adenoma detection rate (ADR) is a decisive factor for PSCRC, but correlations with other parameters need further analysis and ADR may change over time.Cohort study including individuals undergoing screening colonoscopy between 1/2008 and 12/2019 performed by physicians participating in a quality assurance programme in Austria. Data were linked with hospitalisation data for the diagnosis of PSCRC (defined as CRC diagnosis >6 months after colonoscopy). ADR was defined dynamically in relation to the time point of subsequent colonoscopies; high-risk groups of patients were those with an adenoma ≥10 mm, or with high-grade dysplasia, or villous or tubulovillous histology, or a serrated lesion ≥10 mm or with dysplasia, or colonoscopies with ≥3 lesions. Main outcome was PSCRC for each risk group (negative colonoscopy, hyperplastic polyps, low-risk and high-risk group of patients) after colonoscopy by endoscopists with an ADR <20% compared with endoscopists with an ADR ≥20%.352 685 individuals were included in the study (51.0% women, median age 60 years) of which 10.5% were classified as high-risk group. During a median follow-up of 55.4 months, 241 (0.06%) PSCRC were identified; of 387 participating physicians, 19.6% had at least one PSCRC (8.4% two or more). While higher endoscopist ADR decreased PSCRC incidence (HR per 1% increase 0.97, 95% CI 0.95 to 0.98), affiliation to the high-risk group of patients was also associated with higher PSCRC incidence (HR 3.27, 95% CI 2.36 to 4.00). Similar correlations were seen with regards to high-risk, and advanced adenomas. The risk for PSCRC was significantly higher after colonoscopy by an endoscopist with an ADR <20% as compared with an endoscopist with an ADR ≥20% in patients after negative colonoscopy (HR 2.01, 95% CI 1.35 to 3.0, p<0.001) and for the high-risk group of patients (HR 2.51, 95% CI 1.49 to 4.22, p<0.001).A dynamic calculation of the ADR takes into account changes over time but confirms the correlation of ADR and interval cancer. Both lesion characteristics and endoscopists ADR may play a similar role for the risk of PSCRC. This should be considered in deciding about appropriate surveillance intervals in the future.
Initial implementation of an electronic oncology trigger tool for adverse event detection.
Authors: William Lyons
Journal: Journal of Clinical Oncology (2020)

298 Background: In 2009, the Institute for Healthcare Improvement (IHI) conceived the Global Trigger Tool (GTT), a method for identifying adverse events that relies on correlated clinical documentation, “triggers”, in the medical record. This method is intended to augment traditional quality of care, data collection initiatives that primarily depend on voluntary reporting or error tracking. However, the original trigger tool called for a manual identification of trigger events and is too broad to be useful in an oncology setting. We propose a method for the development, selection, electronic extraction and management of triggers relevant to an oncology setting, with the primary aim of improving our understanding of the prevalence of adverse events occurring during an inpatient stay. Methods: Our implementation of an Electronic Trigger Tool includes three parts: trigger selection, review system development, and the chart review process. Through literature review, we developed a library of 40 oncology-relevant trigger tools. We then selected two pilot triggers based on expert opinion and a trigger analysis on length of stay, cost, and patient satisfaction. Next, we developed a web-app that allows reviewers to automatically receive trigger events. Finally, two clinical professionals reviewed five trigger events from each trigger for five subsequent weeks. Results: We selected Narcan administration (M9) and unexpected/unplanned ICU admission after non-emergent surgical procedure (S3) as pilot triggers. Our reviewers each performed a chart review on 25 for each trigger, resulting in 100 independent reviews. We found that M9 had a positive predictive value (PPV) of .52 (26 AEs / 50 reviews) and S3 had a positive predictive value of .88 (44 AEs / 50 reviews). We also found that most of these adverse events were not found by other quality systems. Conclusions: Our pilot of two triggers demonstrated we can capture adverse events that exist outside known quality and safety resources on a small scale and with high PPV. We anticipate using novel trigger information to inform process improvement and quality of care for patients with cancer at our hospital.
Prevalence and clinical outcomes of COVID-19 in patients with autoimmune diseases: a systematic review and meta-analysis
Authors: Shintaro Akiyama, Shadi Hamdeh, Dejan Micic, Atsushi Sakuraba
Journal: Annals of the Rheumatic Diseases (2020)

Objectives The prevalence and clinical outcomes of COVID-19 in patients with autoimmune diseases who are frequently treated with disease modifying therapies remains poorly understood. This meta-analysis aims to assess the prevalence and clinical outcomes of COVID-19 in autoimmune diseases. Methods Electronic databases were searched for observational and case–controlled studies. We sorted medications into glucocorticoids, conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) and biologic or targeted synthetic DMARDs (b/tsDMARDs), which was also divided into monotherapy and b/tsDMARDs–csDMARDs combination therapy. Results We analysed 62 observational studies with a total of 319 025 patients with autoimmune diseases. The prevalence of COVID-19 was 0.011 (95% CI: 0.005 to 0.025). Meta-analysis of seven case–controlled studies demonstrated that the risk of COVID-19 in autoimmune diseases was significantly higher than in control patients (OR: 2.19, 95% CI: 1.05 to 4.58, p=0.038). Meta-regression analysis showed glucocorticoids were significantly associated with the risk of COVID-19. For clinical outcomes, we assessed 65 studies with 2766 patients with autoimmune diseases diagnosed with COVID-19. The rates of hospitalisation and mortality were 0.35 (95% CI: 0.23 to 0.50) and 0.066 (95% CI: 0.036 to 0.12), respectively. Glucocorticoids, csDMARDs and b/tsDMARDs–csDMARDs combination therapy increased the risk of these outcomes, whereas b/tsDMARDs monotherapy, particularly antitumour necrosis factor agents, were associated with a lower risk of hospitalisation and death. Conclusions Our meta-analysis demonstrated that patients with autoimmune diseases had an increased risk of COVID-19, primarily attributed to glucocorticoid use. b/tsDMARDs monotherapy was associated with a lower risk of severe COVID-19 suggesting its safety in the COVID-19 pandemic.
Alcohol and hepatocarcinogenesis
Authors: Makiko Taniai
Journal: Clinical and Molecular Hepatology (2020)

An excessive alcohol intake may result in fatty liver, acute/chronic hepatitis, cirrhosis, and lead to hepatocellular carcinoma (HCC). The aim of this review is to clarify the present condition and the mechanisms of alcohol-related hepatocarcinogenesis and clinical risk factors for alcohol-related HCC. There are several possible mechanisms through which alcohol may induce hepatocarcinogenesis, including the mutagenic effects of acetaldehyde toxicity through the formation of protein and DNA adducts and the production of reactive oxygen species due to the excessive hepatic deposition of iron, changes to lipid peroxidation and metabolism, inflammation and an impaired immune response and modifications to DNA methylation. Furthermore, it has been reported that alcohol accelerates liver carcinogenesis through several signaling pathways including gut-liver axis. From a clinical perspective, it is well known that alcohol interacts with other factors, such as age, gender, viral hepatitis, obesity, and diabetes leading to an increased risk of HCC.
Leveraging patient-reported outcomes (PROs) in patients with pancreatic cancer: The Pancreatic Cancer Action Network (PanCAN) online patient registry experience.
Authors: Arjun Gupta, Omar Khalid, Dennis Ladnier, Cassadie Moravek, Anica Lamkin, Lynn McCormick Matrisian, Sudheer Doss, Crystal S. Denlinger, Andrew L. Coveler, Colin D. Weekes, Eric Roeland, Andrew Eugene Hendifar, Ryan David Nipp
Journal: Journal of Clinical Oncology (2020)

154 Background: By allowing patients (pts) to self-report key issues related to their quality of life and symptoms, PROs have important clinical and research implications. The PanCAN Registry, which began collecting data in July 2015, is a pancreatic cancer-specific global online registry enabling pts to report sociodemographics, disease/management characteristics, and PROs via online surveys. We sought to describe pt experiences with the PanCAN Registry. Methods: We assessed individual characteristics and interactions with the registry (visits, survey completions, and longitudinal use) from 7/2015-10/2019 for pts who provided permission to use their data. The registry allows pts to complete surveys about their experience (e.g. basics of pancreatic cancer, general information), symptoms (e.g. fatigue, pain), diagnostics (e.g. labs, scans), and drug therapy (e.g. type, frequency). We validated PROs using the PanCAN Know Your Tumor database. For a subset of pts (those with de novo metastatic disease), we compared PROs, treatment patterns, and side effects by age (+/- 65 years) and treatment site (community or academic). Results: Of 2,836 pts who visited the registry, 2,076 (73%) completed at least one survey (median age = 64 [range: 18-97], 48% women, 92% white, 32% metastatic disease). Pts most commonly completed the basics (73%), general information (39%), and drug therapy (37%) surveys. Overall, 10% answered surveys longitudinally. We observed 95% concordance between PROs and the PanCAN Know Your Tumor database. Among the 667 pts with de novo metastatic disease, 34% were older (age 65+) and 50% were treated at academic sites. Younger pts were more hopeful about the treatment plan (strongly agree: 24% v 12%, p &lt; .01) and reported less constipation (moderate/severe: 33% v 48%, p &lt; .01) compared with older pts. Pts treated at academic sites reported less frequent treatment breaks of &gt; 2 weeks (28% v 58%, p = 0.01) and more frequent severe cytopenias (27% v 12%, p = 0.01) compared with those treated at community sites. Conclusions: With &gt; 2,800 pts visiting the PanCAN registry and &gt; 70% completing a survey, these findings demonstrate the feasibility, robustness, and research potential of an online PRO registry. We observed important differences by age and treatment site regarding pts’ outlook, symptoms, treatment patterns, and side effects. With increasing focus on PROs, registries like this can facilitate standardized PRO reporting and monitoring, while also providing a valuable research database.
Cellular senescence: friend or foe to respiratory viral infections?
Authors: William J. Kelley, Rachel L. Zemans, Daniel R. Goldstein
Journal: European Respiratory Journal (2020)

Cellular senescence permanently arrests the replication of various cell types and contributes to age-associated diseases. In particular, cellular senescence may enhance chronic lung diseases including COPD and idiopathic pulmonary fibrosis. However, the role cellular senescence plays in the pathophysiology of acute inflammatory diseases, especially viral infections, is less well understood. There is evidence that cellular senescence prevents viral replication by increasing antiviral cytokines, but other evidence shows that senescence may enhance viral replication by downregulating antiviral signalling. Furthermore, cellular senescence leads to the secretion of inflammatory mediators, which may either promote host defence or exacerbate immune pathology during viral infections. In this Perspective article, we summarise how senescence contributes to physiology and disease, the role of senescence in chronic lung diseases, and how senescence impacts acute respiratory viral infections. Finally, we develop a potential framework for how senescence may contribute, both positively and negatively, to the pathophysiology of viral respiratory infections, including severe acute respiratory syndrome due to the coronavirus SARS-CoV-2.
Blood pressure targets for young adults: are we being too stringent?
Authors: Divyani Garg, Ayush Agarwal
Journal: BMJ (2020)

Hypertension is a harbinger of a huge cardiovascular disease burden globally, with an estimated one in three adults in low and middle income countries having hypertension, previously defined as blood pressure ≥140/90 mm Hg.1 The burden is probably greater, given the current definition of ≥130/80 mm Hg.2

Luo and colleagues pooled data from 17 observational studies of more than 4.5 million young adults (18-45 years), with …
Role of oncology-advanced practitioners to enhance clinical research.
Authors: Christa Marie Braun-Inglis, Leigh Boehmer, Laura J Zitella, Brianna Hoffner, Jessica Rhee, Yurii B Shvetsov, Randall A. Oyer, Al Bowen Benson
Journal: Journal of Clinical Oncology (2020)

95 Background: Oncology Advanced Practitioners (APs), including Nurse Practitioners, Physician Assistants, Clinical Nurse Specialists, and Pharmacists are highly trained health care providers that contribute significantly to quality cancer care. Given low clinical trial enrollment among adult oncology patients, understanding current research responsibilities of APs could lead to identification of opportunities to leverage this workforce to enhance accrual and conduct of clinical trials. Methods: A 65-item validated survey addressing attitudes, beliefs and responsibilities of oncology APs participating in clinical research was distributed from January 22 through March 6, 2020. Outreach via the Association of Community Cancer Centers (ACCC) and Harborside was utilized to reach a sample set of 14,601 oncology APs’ emails. The survey was administered and data were analyzed using Survey Monkey. Results: 408 U.S. oncology APs completed the survey. Respondents were primarily white (83%), female (92%) and nurse practitioners (71%). Thirty-five percent practiced in an academic setting and 62% practiced in a community setting. Nearly all respondents believed that clinical trials are important to improve oncology care standards and more than 90% reported that clinical trials were available at their practice. Nearly 80% reported that they are comfortable discussing treatment options with patients, discussing clinical trials in general, and know where to find clinical trials. Furthermore, 80% participate in the care of patients enrolled on clinical trials. Only 60%, however, are comfortable discussing trials available at their practice and only 38% routinely explore whether a clinical trial is available for their patients. While 70% of APs approach eligible patients about clinical trials at their practice, only 20% reported doing so “a great deal” or “a lot”. Ninety percent of APs reported that they should play a role in clinical research and 75% would like to be more involved in the clinical trial process. Barriers to greater involvement in clinical trials include lack of time, inadequate awareness of clinical trial specifics, and under-representation on research committees. Conclusions: The majority of oncology APs are engaged and interested in clinical trials and believe that research is important to improve cancer care. However, they are not being utilized to their full scope. Multidisciplinary team integration, trials-related education, and policy change is needed to allow this group of skilled professionals to realize their full potential within cancer clinical trials.
Going Beyond Cost-Sharing Parity to Improve Behavioral Health Access
Authors: Krisda H. Chaiyachati, Cecilia Livesey, Joshua M. Liao
Journal: JAMA Network Open (2020)

Vicki Fung, PhD; Mary Price, MA; Andrew A. Nierenberg, MD; John Hsu, MD, MBA, MSCE; Joseph P. Newhouse, PhD; Benjamin L. Cook, PhD
Cytogenetic and molecular aberrations and worse outcome for male patients in systemic mastocytosis
Authors: Hanneke C. Kluin-Nelemans, Mohamad Jawhar, Andreas Reiter, Bjorn van Anrooij, Jason Gotlib, Karin Hartmann, Anja Illerhaus, Hanneke N.G. Oude Elberink, Aleksandra Gorska, Marek Niedoszytko, Magdalena Lange, Luigi Scaffidi, Roberta Zanotti, Patrizia Bonadonna, Cecelia Perkins, Chiara Elena, Luca Malcovati, Khalid Shoumariyeh, Nikolas von Bubnoff, Sabine Müller, Massimo Triggiani, Roberta Parente, Juliana Schwaab, Michael Kundi, Anna Belloni Fortina, Francesca Caroppo, Knut Brockow, Alexander Zink, David Fuchs, Irena Angelova-Fischer, Akif Selim Yavuz, Michael Doubek, Mattias Mattsson, Hans Hagglund, Jens Panse, Anne Simonowski, Vito Sabato, Tanja Schug, Madlen Jentzsch, Christine Breynaert, Judit Várkonyi, Vanessa Kennedy, Olivier Hermine, Julien Rossignol, Michel Arock, Peter Valent, Wolfgang R. Sperr
Journal: Theranostics (2020)

In systemic mastocytosis (SM), the clinical features and survival vary greatly.Patient-related factors determining the outcome in SM are largely unknown. Ivyspring International
Long-Term m5C Methylome Dynamics Parallel Phenotypic Adaptation in the Cyanobacterium<i>Trichodesmium</i>
Authors: Nathan G Walworth, Michael D Lee, Egor Dolzhenko, Fei-Xue Fu, Andrew D Smith, Eric A Webb, David A Hutchins
Journal: Molecular Biology and Evolution (2020)

Abstract A major challenge in modern biology is understanding how the effects of short-term biological responses influence long-term evolutionary adaptation, defined as a genetically determined increase in fitness to novel environments. This is particularly important in globally important microbes experiencing rapid global change, due to their influence on food webs, biogeochemical cycles, and climate. Epigenetic modifications like methylation have been demonstrated to influence short-term plastic responses, which ultimately impact long-term adaptive responses to environmental change. However, there remains a paucity of empirical research examining long-term methylation dynamics during environmental adaptation in nonmodel, ecologically important microbes. Here, we show the first empirical evidence in a marine prokaryote for long-term m5C methylome modifications correlated with phenotypic adaptation to CO2, using a 7-year evolution experiment (1,000+ generations) with the biogeochemically important marine cyanobacterium Trichodesmium. We identify m5C methylated sites that rapidly changed in response to high (750 µatm) CO2 exposure and were maintained for at least 4.5 years of CO2 selection. After 7 years of CO2 selection, however, m5C methylation levels that initially responded to high-CO2 returned to ancestral, ambient CO2 levels. Concurrently, high-CO2 adapted growth and N2 fixation rates remained significantly higher than those of ambient CO2 adapted cell lines irrespective of CO2 concentration, a trend consistent with genetic assimilation theory. These data demonstrate the maintenance of CO2-responsive m5C methylation for 4.5 years alongside phenotypic adaptation before returning to ancestral methylation levels. These observations in a globally distributed marine prokaryote provide critical evolutionary insights into biogeochemically important traits under global change.