tbuckley/cabot-search huggingface dataset:
Abstract 17056: Report Of An Adult Living With Undiagnosed Total Anomalous Pulmonary Venous Return
Authors: Kent Beam, Jorge Alegria, Matthew Schwartz
Journal: Circulation (2021)

Case Presentation: 25-year-old male presented with cellulitis and abscess of the lower extremity. He was an immigrant from Guatemala. He worked in landscaping and played soccer with limited exertion. His exam was notable for cyanosis and clubbing of all digits. A II/VI systolic ejection murmur at the left upper sternal border and a mildly accentuated P2 was auscultated. ECG was notable for right axis deviation and right ventricle hypertrophy. Chest x-ray showed a widened mediastinum with perihilar vascular prominence. CT chest with contrast demonstrated all pulmonary veins forming a large, coalescing venous structure draining into the left innominate vein. Transthoracic echocardiogram confirmed total pulmonary venous return by way of a large vertical vein draining into a dilated innominate vein and a 2.7 cm ostium secundum ASD. Discussion: Total anomalous pulmonary venous return (TAPVR) is a rare, often deadly condition. Most patients die in infancy. In the rare adult patient with unrepaired TAPVR, exercise intolerance, cyanosis, clubbing of the digits, and growth retardation is often noted. A right ventricular heave with auscultation of a fixed, split second heart sound with a loud pulmonic component is common. On chest x-ray, the classic “snowman” appearance is seen with vertical vein connections as in our patient. Right heart enlargement represents the base, and an enlarged connecting vertical vein and SVC make up the upper portion. Echocardiography can demonstrate the anomalous pulmonary venous conduit coursing behind the left atrium. CT angiography can also reveal TAPVR and the patient’s specific anatomy. Amongst the few surviving adult TAPVR patients, similar characteristics include large ASDs, short anomalous veins, and absence of pulmonary venous obstruction. A large interatrial connection provides adequate systemic flow. The latter two factors reduce pulmonary vascular resistance, hence improving pulmonary flow and systemic oxygen concentrations.
Risk for Myocardial Infarction Following 5-Fluorouracil Treatment in Patients With Gastrointestinal Cancer
Authors: Jan Walter Dhillon Shanmuganathan, Kristian Kragholm, Bhupendar Tayal, Christoffer Polcwiartek, Laurids Østergaard Poulsen, Tarec Christoffer El-Galaly, Emil Loldrup Fosbøl, Maria D’Souza, Gunnar Gislason, Lars Køber, Morten Schou, Dorte Nielsen, Peter Søgaard, Christian Tobias Torp-Pedersen, Mamas A. Mamas, Phillip Freeman
Journal: JACC CardioOncology (2021)

Myocardial infarction is a cardiac adverse event associated with 5-fluorouracil (5-FU). There are limited data on the incidence, risk, and prognosis of 5-FU-associated myocardial infarction.The aim of this study was to examine the risk for myocardial infarction in patients with gastrointestinal (GI) cancer treated with 5-FU compared with age- and sex-matched population control subjects without cancer (1:2 ratio).Patients with GI cancer treated with 5-FU between 2004 and 2016 were identified within the Danish National Patient Registry. Prevalent ischemic heart disease in both groups was excluded. Cumulative incidences were calculated, and multivariable regression and competing risk analyses were performed.A total of 30,870 patients were included in the final analysis, of whom 10,290 had GI cancer and were treated with 5-FU and 20,580 were population control subjects without cancer. Differences in comorbid conditions and select antianginal medications were nonsignificant (P > 0.05 for all). The 6-month cumulative incidence of myocardial infarction was significantly higher for 5-FU patients at 0.7% (95% CI: 0.5%-0.9%) versus 0.3% (95% CI: 0.3%-0.4%) in population control subjects, with a competing risk for death of 12.1% versus 0.6%. The 1-year cumulative incidence of myocardial infarction for 5-FU patients was 0.9% (95% CI: 0.7%-1.0%) versus 0.6% (95% CI: 0.5%-0.7%) among population control subjects, with a competing risk for death of 26.5% versus 1.4%. When accounting for competing risks, the corresponding subdistribution hazard ratios suggested an increased risk for myocardial infarction in 5-FU patients, compared with control subjects, at both 6 months (hazard ratio: 2.10; 95% CI: 1.50-2.95; P < 0.001) and 12 months (hazard ratio: 1.39; 95% CI: 1.05-1.84; P = 0.022).Despite a statistically significantly higher 6- and 12-month risk for myocardial infarction among 5-FU patients compared with population control subjects, the absolute risk for myocardial infarction was low, and the clinical significance of these differences appears to be limited in the context of the significant competing risk for death in this population.
Early disappearance of tumor antigen-reactive T cells from peripheral blood correlates with superior clinical outcomes in melanoma under anti-PD-1 therapy
Authors: Jonas Bochem, Henning Zelba, Janine Spreuer, Teresa Amaral, Nikolaus B Wagner, Andrea Gaissler, Oltin T Pop, Karolin Thiel, Can Yurttas, Daniel Soffel, Stephan Forchhammer, Tobias Sinnberg, Heike Niessner, Friedegund Meier, Patrick Terheyden, Alfred Königsrainer, Claus Garbe, Lukas Flatz, Graham Pawelec, Thomas K Eigentler, Markus W Löffler, Benjamin Weide, Kilian Wistuba-Hamprecht
Journal: Journal for ImmunoTherapy of Cancer (2021)

Background Anti-programmed cell death protein 1 (PD-1) antibodies are now routinely administered for metastatic melanoma and for increasing numbers of other cancers, but still only a fraction of patients respond. Better understanding of the modes of action and predictive biomarkers for clinical outcome is urgently required. Cancer rejection is mostly T cell-mediated. We previously showed that the presence of NY-ESO-1-reactive and/or Melan-A-reactive T cells in the blood correlated with prolonged overall survival (OS) of patients with melanoma with a heterogeneous treatment background. Here, we investigated whether such reactive T cells can also be informative for clinical outcomes in metastatic melanoma under PD-1 immune-checkpoint blockade (ICB). Methods Peripheral blood T cell stimulation by NY-ESO-1 and Melan-A overlapping peptide libraries was assessed before and during ICB in two independent cohorts of a total of 111 patients with stage IV melanoma. In certain cases, tumor-infiltrating lymphocytes could also be assessed for such responses. These were characterized using intracellular cytokine staining for interferon gamma (IFN-γ), tumor negrosis factor (TNF) and CD107a. Digital pathology analysis was performed to quantify NY-ESO-1 and Melan-A expression by tumors. Endpoints were OS and progression-free survival (PFS). Results The initial presence in the circulation of NY-ESO-1- or Melan-A-reactive T cells which became no longer detectable during ICB correlated with validated, prolonged PFS (HR:0.1; p&gt;0.0001) and OS (HR:0.2; p=0.021). An evaluation of melanoma tissue from selected cases suggested a correlation between tumor-resident NY-ESO-1- and Melan-A-reactive T cells and disease control, supporting the notion of a therapy-associated sequestration of cells from the periphery to the tumor predominantly in those patients benefitting from ICB. Conclusions Our findings suggest a PD-1 blockade-dependent infiltration of melanoma-reactive T cells from the periphery into the tumor and imply that this seminally contributes to effective treatment.
Management of pneumonia in critically ill patients
Authors: Catia Cillóniz, Antoni Torres, Michael S Niederman
Journal: BMJ (2021)

Abstract Severe pneumonia is associated with high mortality (short and long term), as well as pulmonary and extrapulmonary complications. Appropriate diagnosis and early initiation of adequate antimicrobial treatment for severe pneumonia are crucial in improving survival among critically ill patients. Identifying the underlying causative pathogen is also critical for antimicrobial stewardship. However, establishing an etiological diagnosis is challenging in most patients, especially in those with chronic underlying disease; those who received previous antibiotic treatment; and those treated with mechanical ventilation. Furthermore, as antimicrobial therapy must be empiric, national and international guidelines recommend initial antimicrobial treatment according to the location’s epidemiology; for patients admitted to the intensive care unit, specific recommendations on disease management are available. Adherence to pneumonia guidelines is associated with better outcomes in severe pneumonia. Yet, the continuing and necessary research on severe pneumonia is expansive, inviting different perspectives on host immunological responses, assessment of illness severity, microbial causes, risk factors for multidrug resistant pathogens, diagnostic tests, and therapeutic options.
Reply to Deepansh Dalela and Kristina Suson’s Letter to the Editor re: Luke Harper, T. Blanc, M. Peycelon, et al. Circumcision and Risk of Febrile Urinary Tract Infection in Boys with Posterior Urethral Valves: Result of the CIRCUP Randomized Trial. Eur Urol. 2022;81:64–72
Authors: Luke Harper
Journal: European Urology (2021)
Exploring the Potential of Stem Cell-Based Therapy for Aesthetic and Plastic Surgery
Authors: Dang-Khoa Tran, Thuy Nguyen Thi Phuong, Nhat-Le Bui, Vijai Singh, Qi Hao Looi, Benson Koh, Ungku Mohd Shahrin B Mohd Zaman, Jhi Biau Foo, Chia-Ching Wu, Pau Loke Show, Dinh-Toi Chu
Journal: IEEE Reviews in Biomedical Engineering (2021)

Over the last decade, stem cell-associated therapies are widely used because of their potential in self-renewable and multipotent differentiation ability. Stem cells have become more attractive for aesthetic uses and plastic surgery, including scar reduction, breast augmentation, facial contouring, hand rejuvenation, and anti-aging. The current preclinical and clinical studies of stem cells on aesthetic uses also showed promising outcomes. Adipose-derived stem cells are commonly used for fat grafting that demonstrated scar improvement, anti-aging, skin rejuvenation properties, etc. While stem cell-based products have yet to receive approval from the FDA for aesthetic medicine and plastic surgery. Moving forward, the review on the efficacy and potential of stem cell-based therapy for aesthetic and plastic surgery is limited. In the present review, we discuss the current status and recent advances of using stem cells for aesthetic and plastic surgery. The potential of cell-free therapy and tissue engineering in this field is also highlighted. The clinical applications, advantages, and limitations are also discussed. This review also provides further works that need to be investigated to widely apply stem cells in the clinic, especially in aesthetic and plastic contexts.
A Novel Early Relapse Prediction Score Based on Age, ISS and Disease Status at the Time of Transplant in Patients with Newly Diagnosed Multiple Myeloma. a Study of the EBMT Chronic Malignancies Working Party
Authors: Meral Beksac, Simona Iacobelli, Linda Koster, Didier Blaise, Jan J. Cornelissen, Péter Reményi, Xavier Leleu, Tobias Gedde-Dahl, Xavier Poire, Laimonas Griskevicius, Edouard Forcade, Stig Lenhoff, Neil K Rabin, Guido Kobbe, Tanja Netelenbos, William Arcese, Jean-Baptiste Mear, Monika Engelhardt, Thomas Pabst, Nicolaas Schaap, Claudia Lucia Sossa, Ahmet Elmaagacli, Patrick John Hayden, Stefan Schoenland, Ibrahim Yakoub-Agha
Journal: Blood (2021)
Polysalicylic Acid Polymer Microparticle Decoys Therapeutically Treat Acute Respiratory Distress Syndrome
Authors: Emma R. Brannon, William J. Kelley, Michael W. Newstead, Alison L. Banka, Kathryn E. Uhrich, Colleen E. O'Connor, Theodore J. Standiford, Omolola Eniola‐Adefeso
Journal: Advanced Healthcare Materials (2021)

Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) remain problematic due to high mortality rates and lack of effective treatments. Neutrophilic injury contributes to mortality in ALI/ARDS. Here, technology for rapid ARDS intervention is developed and evaluated, where intravenous salicylic acid-based polymer microparticles, i.e., Poly-Aspirin (Poly-A), interfere with neutrophils in blood, reducing lung neutrophil infiltration and injury in vivo in mouse models of ALI/ARDS. Importantly, Poly-A particles reduce multiple inflammatory cytokines in the airway and bacterial load in the bloodstream in a live bacteria lung infection model of ARDS, drastically improving survival. It is observed that phagocytosis of the Poly-A microparticles, with salicylic acid in the polymer backbone, alters the neutrophil surface expression of adhesion molecules, potentially contributing to their added therapeutic benefits. Given the proven safety profile of the microparticle degradation products-salicylic acid and adipic acid-it is anticipated that the Poly-A particles represent a therapeutic strategy in ARDS with a rare opportunity for rapid clinical translation.
LIM Homeobox-2 Suppresses Hallmarks of Adult and Pediatric Liver Cancers by Inactivating MAPK/ERK and Wnt/Beta-Catenin Pathways
Authors: Nicola Mosca, Fatma Zohra Khoubai, Sandrine Fedou, Juan Carrillo-Reixach, Stefano Caruso, Alvaro Del Rio-Alvarez, Emeric Dubois, Christophe Avignon, Nathalie Dugot-Senant, Catherine Guettier, Charlotte Mussini, Jessica Zucman-Rossi, Carolina Armengol, Pierre Thiébaud, Philippe Veschambre, Christophe François Grosset
Journal: Liver Cancer (2021)

&lt;b&gt;&lt;i&gt;Introduction:&lt;/i&gt;&lt;/b&gt; Hepatocellular carcinoma and hepatoblastoma are two liver cancers characterized by gene deregulations, chromosomal rearrangements, and mutations in Wnt/beta-catenin (Wnt) pathway-related genes. LHX2, a transcriptional factor member of the LIM homeobox gene family, has important functions in embryogenesis and liver development. LHX2 is oncogenic in many solid tumors and leukemia, but its role in liver cancer is unknown. &lt;b&gt;&lt;i&gt;Methods:&lt;/i&gt;&lt;/b&gt; We analyzed the expression of &lt;i&gt;LHX2&lt;/i&gt; in hepatocellular carcinoma and hepatoblastoma samples using various transcriptomic datasets and biological samples. The role of LHX2 was studied using lentiviral transduction, in vitro cell-based assays (growth, migration, senescence, and apoptosis), molecular approaches (phosphokinase arrays and RNA-seq), bioinformatics, and two in vivo models in chicken and &lt;i&gt;Xenopus&lt;/i&gt; embryos. &lt;b&gt;&lt;i&gt;Results:&lt;/i&gt;&lt;/b&gt; We found a strong connection between LHX2 downregulation and Wnt activation in these two liver cancers. In hepatoblastoma, LHX2 downregulation correlated with multiple poor outcome parameters including higher patient age, intermediate- and high-risk tumors, and low patient survival. Forced expression of LHX2 reduced the proliferation, migration, and survival of liver cancer cells in vitro through the inactivation of MAPK/ERK and Wnt signals. In vivo, LHX2 impeded the development of tumors in chick embryos and repressed the Wnt pathway in &lt;i&gt;Xenopus&lt;/i&gt; embryos. RNA-sequencing data and bioinformatic analyses confirmed the deregulation of many biological functions and molecular processes associated with cell migration, cell survival, and liver carcinogenesis in LHX2-expressing hepatoma cells. At a mechanistic level, LHX2 mediated the disassembling of beta-catenin/T-cell factor 4 complex and induced expression of multiple inhibitors of Wnt (e.g., TLE/Groucho) and MAPK/ERK (e.g., DUSPs) pathways. &lt;b&gt;&lt;i&gt;Conclusion:&lt;/i&gt;&lt;/b&gt; Collectively, our findings demonstrate a tumor suppressive function of LHX2 in adult and pediatric liver cancers.
BRE12-158: A Postneoadjuvant, Randomized Phase II Trial of Personalized Therapy Versus Treatment of Physician's Choice for Patients With Residual Triple-Negative Breast Cancer
Authors: Bryan P. Schneider, Guanglong Jiang, Tarah J. Ballinger, Fei Shen, Christopher Chitambar, Rita Nanda, Carla Falkson, Filipa C. Lynce, Christopher Gallagher, Claudine Isaacs, Marcelo Blaya, Elisavet Paplomata, Radhika Walling, Karen Daily, Reshma Mahtani, Michael A. Thompson, Robert Graham, Maureen E. Cooper, Dean C. Pavlick, Lee A. Albacker, Jeffrey Gregg, Jeffrey P. Solzak, Yu-Hsiang Chen, Casey L. Bales, Erica Cantor, Bradley A. Hancock, Nawal Kassem, Paul Helft, Bert O'Neil, Anna Maria V. Storniolo, Sunil Badve, Kathy D. Miller, Milan Radovich
Journal: Journal of Clinical Oncology (2021)

Patients with triple-negative breast cancer (TNBC) with residual disease after neoadjuvant chemotherapy (NAC) have high risk of recurrence with prior data suggesting improved outcomes with capecitabine. Targeted agents have demonstrated activity across multiple cancer types. BRE12-158 was a phase II, multicenter trial that randomly allocated patients with TNBC with residual disease after NAC to genomically directed therapy versus treatment of physician choice (TPC).From March 2014 to December 2018, 193 patients were enrolled. Residual tumors were sequenced using a next-generation sequencing test. A molecular tumor board adjudicated all results. Patients were randomly allocated to four cycles of genomically directed therapy (arm A) versus TPC (arm B). Patients without a target were assigned to arm B. Primary end point was 2-year disease-free survival (DFS) among randomly assigned patients. Secondary/exploratory end points included distant disease-free survival, overall survival, toxicity assessment, time-based evolution of therapy, and drug-specific outcomes.One hundred ninety-three patients were randomly allocated or were assigned to arm B. The estimated 2-year DFS for the randomized population only was 56.6% (95% CI, 0.45 to 0.70) for arm A versus 62.4% (95% CI, 0.52 to 0.75) for arm B. No difference was seen in DFS, distant disease-free survival, or overall survival for the entire or randomized populations. There was increased uptake of capecitabine for TPC over time. Patients randomly allocated later had less distant recurrences. Circulating tumor DNA status remained a significant predictor of outcome with some patients demonstrating clearance with postneoadjuvant therapy.Genomically directed therapy was not superior to TPC for patients with residual TNBC after NAC. Capecitabine should remain the standard of care; however, the activity of other agents in this setting provides rationale for testing optimal combinations to improve outcomes. Circulating tumor DNA should be considered a standard covariate for trials in this setting.
Suppressed farnesoid X receptor by iron overload in mice and humans potentiates iron‐induced hepatotoxicity
Authors: Hui Xiong, Chunze Zhang, Lifeng Han, Tong Xu, Khawar Saeed, Jing Han, Jing Liu, Curtis D. Klaassen, Frank J. Gonzalez, Yuanfu Lu, Youcai Zhang
Journal: Hepatology (2021)

Iron overload (IO) is a frequent finding in the general population. As the major iron storage site, the liver is subject to iron toxicity. Farnesoid X receptor (FXR) regulates bile acid metabolism and is implicated in various liver diseases. We aimed to determine whether FXR plays a role in regulating iron hepatotoxicity.Human and mouse hepatocytes were treated with ferric ammonium citrate or iron dextran (FeDx). Mice were orally administered ferrous sulfate or injected i.p. with FeDx. Wild-type and Fxr-/- mice were fed an iron-rich diet for 1 or 5 weeks. Mice fed an iron-rich diet were coadministered the FXR agonist, GW4064. Forced expression of FXR was carried out with recombinant adeno-associated virus 1 week before iron-rich diet feeding. Serum levels of bile acids and fibroblast growth factor 19 (FGF19) were quantified in adults with hyperferritinemia and children with β-thalassemia. The data demonstrated that iron suppressed FXR expression and signaling in human and mouse hepatocytes as well as in mouse liver and intestine. FXR deficiency potentiated iron hepatotoxicity, accompanied with hepatic steatosis as well as dysregulated iron and bile acid homeostasis. FXR negatively regulated iron-regulatory proteins 1 and 2 and prevented hepatic iron accumulation. Forced FXR expression and ligand activation significantly suppressed iron hepatotoxicity in iron-fed mice. The FXR agonist, GW4064, almost completely restored dysregulated bile acid signaling and metabolic syndrome in iron-fed mice. Conjugated primary bile acids were increased and FGF19 was decreased in serum of adults with hyperferritinemia and children with β-thalassemia.FXR plays a pivotal role in regulating iron homeostasis and protects mice against iron hepatotoxicity. Targeting FXR may represent a therapeutic strategy for IO-associated chronic liver diseases.
Independent evaluation of melanoma polygenic risk scores in <scp>UK</scp> and Australian prospective cohorts*
Authors: Julia Steinberg, Mark M. Iles, Jin Yee Lee, Xiaochuan Wang, Matthew H. Law, Amelia K. Smit, Tu Nguyen‐Dumont, Graham G. Giles, Melissa C. Southey, Roger L. Milne, Graham J. Mann, D. Timothy Bishop, Robert J. MacInnis, Anne E. Cust
Journal: British Journal of Dermatology (2021)

Previous studies suggest that polygenic risk scores (PRSs) may improve melanoma risk stratification. However, there has been limited independent validation of PRS-based risk prediction, particularly assessment of calibration (comparing predicted to observed risks).
CBTRUS Statistical Report: Primary Brain and Other Central Nervous System Tumors Diagnosed in the United States in 2014–2018
Authors: Quinn T Ostrom, Gino Cioffi, Kristin Waite, Carol Kruchko, Jill S Barnholtz-Sloan
Journal: Neuro-Oncology (2021)

The Central Brain Tumor Registry of the United States (CBTRUS), in collaboration with the CDC and NCI, is the largest population-based registry focused exclusively on primary brain and other central nervous system (CNS) tumors in the United States (US) and represents the entire US population. This report contains the most up-to-date population-based data on primary brain tumors available and supersedes all previous reports in terms of completeness and accuracy and is the first CBTRUS Report to provide the distribution of molecular markers for selected brain and CNS tumor histologies. All rates are age-adjusted using the 2000 US standard population and presented per 100,000 population. The average annual age-adjusted incidence rate (AAAIR) of all malignant and non-malignant brain and other CNS tumors was 24.25 (Malignant AAAIR=7.06, Non-malignant AAAIR=17.18). This overall rate was higher in females compared to males (26.95 versus 21.35) and non-Hispanics compared to Hispanics (24.68 versus 22.12). The most commonly occurring malignant brain and other CNS tumor was glioblastoma (14.3% of all tumors and 49.1% of malignant tumors), and the most common non-malignant tumor was meningioma (39% of all tumors and 54.5% of non-malignant tumors). Glioblastoma was more common in males, and meningioma was more common in females. In children and adolescents (age 0-19 years), the incidence rate of all primary brain and other CNS tumors was 6.21. An estimated 88,190 new cases of malignant and non-malignant brain and other CNS tumors are expected to be diagnosed in the US population in 2021 (25,690 malignant and 62,500 non-malignant). There were 83,029 deaths attributed to malignant brain and other CNS tumors between 2014 and 2018. This represents an average annual mortality rate of 4.43 per 100,000 and an average of 16,606 deaths per year. The five-year relative survival rate following diagnosis of a malignant brain and other CNS tumor was 66.9%, for a non-malignant brain and other CNS tumors the five-year relative survival rate was 92.1%.
Errors in Table 3
Authors: Pierre-Marie Roy, Thomas Moumneh, Andrea Penaloza
Journal: JAMA Cardiology (2021)

Douglas Darden, MD; Thao Duong, MD; Chengan Du, PhD; Muhammad Bilal Munir, MD; Frederick T. Han, MD; Ryan Reeves, MD; Jacqueline Saw, MD; Emily P. Zeitler, MD, MHS; Sana M. Al-Khatib, MD, MHS; Andrea M. Russo, MD; Karl E. Minges, PhD, MPH; Jeptha P. Curtis, MD; James V. Freeman, MD; Jonathan C. Hsu, MD, MAS