tbuckley/cabot-search huggingface dataset:
Surgical Treatments of Hepatobiliary Cancers
Authors: Ganesh Gunasekaran, Yuki Bekki, Vennis Lourdusamy, Myron Schwartz
Journal: Hepatology (2020)

Hepatobiliary cancers which include hepatocellular carcinoma (HCC) and biliary tract cancers (i.e., cholangiocarcinoma and gallbladder carcinoma) are associated with significant morbidity and mortality based on the stage of the disease at presentation. With improved screening for hepatobiliary malignancies in patients with risk factors and with widespread use of laparoscopic cholecystectomy, hepatobiliary malignancies, including incidental diagnosis of gallbladder carcinoma, are on the rise. Definitive treatment of hepatobiliary malignancies include surgical resection, ablation, and liver transplantation. However, management of these cancers is challenging due to the complex hepatobiliary anatomy and the need for meticulous perioperative management especially in patients with advanced liver disease. The management and prognosis of hepatobiliary malignancies vary widely based on the stage of presentation, with surgical options providing the possibility of definitive cure in patients presenting with early-stage disease. Surgical resection for HCC results in good outcomes if performed in ideal candidates. For patients with early HCC who are not candidates for surgical resection, ablation and liver transplantation should be considered. Similarly, surgical resection is also the definitive treatment for biliary tract cancers, and liver transplantation can be curative in selected patients with perihilar cholangiocarcinoma after neoadjuvant chemoradiotherapy. The role of routine adjuvant chemotherapy and radiotherapy is not clearly established, but adjuvant therapies can offer better outcomes in patients with advanced disease at presentation. Outcomes of surgical management of hepatobiliary cancers seem to be improving. Given the complex decision-making process involved, multidisciplinary evaluation is essential to provide and coordinate the best treatments for these patients.
Real‐life assessment of chronic rhinosinusitis patients using mobile technology: The mySinusitisCoach project by EUFOREA
Authors: Sven F. Seys, Shana De Bont, Wytske J. Fokkens, Claus Bachert, Isam Alobid, Manuel Bernal‐Sprekelsen, Leif Bjermer, Ina Callebaut, Lars‐Olaf Cardell, Sean Carrie, Paolo Castelnuovo, Russell Cathcart, Jannis Constantinidis, Leen Cools, Marjolein Cornet, Gregory Clement, Tony Cox, Lieve Delsupehe, Jaime Correia‐de‐Sousa, Lauren Deneyer, Geert De Vos, Zuzana Diamant, Maria Doulaptsi, Simon Gane, Philippe Gevaert, Claire Hopkins, Valérie Hox, Thomas Hummel, Werner Hosemann, Raf Jacobs, Mark Jorissen, Anette Kjeldsen, Basile N. Landis, Winde Lemmens, Andreas Leunig, Valerie Lund, Gert Mariën, Joaquim Mullol, Metin Onerci, Susanna Palkonen, Isabel Proano, Emmanuel Prokopakis, Dermot Ryan, Herbert Riechelmann, Pernilla Sahlstrand‐Johnson, Sanna Salmi‐Toppila, Christine Segboer, Kato Speleman, Andreas Steinsvik, Pavol Surda, Peter‐Valentin Tomazic, Olivier Vanderveken, Laura Van Gerven, Thibaut Van Zele, Jan Verfaillie, Benedicte Verhaeghe, Kathie Vierstraete, Stephan Vlaminck, Martin Wagenmann, Benoit Pugin, Peter W. Hellings
Journal: Allergy (2020)

Abstract Background Chronic rhinosinusitis (CRS) is a chronic inflammatory disease associated with a substantial personal and socioeconomic burden. Monitoring of patient‐reported outcomes by mobile technology offers the possibility to better understand real‐life burden of CRS. Methods This study reports on the cross‐sectional evaluation of data of 626 users of mySinusitisCoach (mSC), a mobile application for CRS patients. Patient characteristics of mSC users were analysed as well as the level of disease control based on VAS global rhinosinusitis symptom score and adapted EPOS criteria. Results The mSC cohort represents a heterogeneous group of CRS patients with a diverse pattern of major symptoms. Approximately half of patients reported nasal polyps. 47.3% of all CRS patients were uncontrolled based on evaluation of VAS global rhinosinusitis symptom score compared to 40.9% based on adapted EPOS criteria. The impact of CRS on sleep quality and daily life activities was significantly higher in uncontrolled versus well‐controlled patients. Half of patients had a history of FESS (functional endoscopic sinus surgery) and reported lower symptom severity compared to patients without a history of FESS, except for patients with a history of more than 3 procedures. Patients with a history of FESS reported higher VAS levels for impaired smell. Conclusion Real‐life data confirm the high disease burden in uncontrolled CRS patients, clearly impacting quality of life. Sinus surgery improves patient‐reported outcomes, but not in patients with a history of more than 3 procedures. Mobile technology opens a new era of real‐life monitoring, supporting the evolution of care towards precision medicine.
Label-free, High-Resolution Optical Metabolic Imaging of Human Cervical Precancers Reveals Potential for Intraepithelial Neoplasia Diagnosis
Authors: Dimitra Pouli, Hong-Thao Thieu, Elizabeth M. Genega, Laura Baecher-Lind, Michael House, Brian Bond, Danielle M. Roncari, Megan L. Evans, Francisca Rius-Diaz, Karl Munger, Irene Georgakoudi
Journal: Cell Reports Medicine (2020)

While metabolic changes are considered a cancer hallmark, their assessment has not been incorporated in the detection of early or precancers, when treatment is most effective. Here, we demonstrate that metabolic changes are detected in freshly excised human cervical precancerous tissues using label-free, non-destructive imaging of the entire epithelium. The images rely on two-photon excited fluorescence from two metabolic co-enzymes, NAD(P)H and FAD, and have micron-level resolution, enabling sensitive assessments of the redox ratio and mitochondrial fragmentation, which yield metrics of metabolic function and heterogeneity. Simultaneous characterization of morphological features, such as the depth-dependent variation of the nuclear:cytoplasmic ratio, is demonstrated. Multi-parametric analysis combining several metabolic metrics with morphological ones enhances significantly the diagnostic accuracy of identifying high-grade squamous intraepithelial lesions. Our results motivate the translation of such functional metabolic imaging to in vivo studies, which may enable improved identification of cervical lesions, and other precancers, at the bedside.
Human CD83-targeted chimeric antigen receptor T cells prevent and treat graft-versus-host disease
Authors: Bishwas Shrestha, Kelly Walton, Jordan Reff, Elizabeth M. Sagatys, Nhan Tu, Justin Boucher, Gongbo Li, Tayyebb Ghafoor, Martin Felices, Jeffrey S. Miller, Joseph Pidala, Bruce R. Blazar, Claudio Anasetti, Brian C. Betts, Marco L. Davila
Journal: Journal of Clinical Investigation (2020)

Graft-versus-host disease (GVHD) remains an important cause of morbidity and mortality after allogeneic hematopoietic cell transplantation (allo-HCT). For decades, GVHD prophylaxis has included calcineurin inhibitors, despite their incomplete efficacy and impairment of graft-versus-leukemia (GVL). Distinct from pharmacologic immune suppression, we have developed what we believe is a novel, human CD83-targeted chimeric antigen receptor (CAR) T cell for GVHD prevention. CD83 is expressed on allo-activated conventional CD4+ T cells (Tconvs) and proinflammatory dendritic cells (DCs), which are both implicated in GVHD pathogenesis. Human CD83 CAR T cells eradicate pathogenic CD83+ target cells, substantially increase the ratio of regulatory T cells (Tregs) to allo-activated Tconvs, and provide durable prevention of xenogeneic GVHD. CD83 CAR T cells are also capable of treating xenogeneic GVHD. We show that human acute myeloid leukemia (AML) expresses CD83 and that myeloid leukemia cell lines are readily killed by CD83 CAR T cells. Human CD83 CAR T cells are a promising cell-based approach to preventing 2 critical complications of allo-HCT — GVHD and relapse. Thus, the use of human CD83 CAR T cells for GVHD prevention and treatment, as well as for targeting CD83+ AML, warrants clinical investigation.
Engineering bionic T cells: signal 1, signal 2, signal 3, reprogramming and the removal of inhibitory mechanisms
Authors: Iñaki Etxeberria, Irene Olivera, Elixabet Bolaños, Asunta Cirella, Álvaro Teijeira, Pedro Berraondo, Ignacio Melero
Journal: Cellular and Molecular Immunology (2020)
Progesterone receptor ligands for the treatment of endometriosis: the mechanisms behind therapeutic success and failure
Authors: Fernando M Reis, Larissa M Coutinho, Silvia Vannuccini, Frédéric Batteux, Charles Chapron, Felice Petraglia
Journal: Human Reproduction Update (2020)

Despite intense research, it remains intriguing why hormonal therapies in general and progestins in particular sometimes fail in endometriosis.We review here the action mechanisms of progesterone receptor ligands in endometriosis, identify critical differences between the effects of progestins on normal endometrium and endometriosis and envisage pathways to escape drug resistance and improve the therapeutic response of endometriotic lesions to such treatments.We performed a systematic Pubmed search covering articles published since 1958 about the use of progestins, estro-progestins and selective progesterone receptor modulators, to treat endometriosis and its related symptoms. Two reviewers screened the titles and abstracts to select articles for full-text assessment.Progesterone receptor signalling leads to down-regulation of estrogen receptors and restrains local estradiol production through interference with aromatase and 17 beta-hydroxysteroid dehydrogenase type 1. Progestins inhibit cell proliferation, inflammation, neovascularisation and neurogenesis in endometriosis. However, progesterone receptor expression is reduced and disrupted in endometriotic lesions, with predominance of the less active isoform (PRA) over the full-length, active isoform (PRB), due to epigenetic abnormalities affecting the PGR gene transcription. Oxidative stress is another mechanism involved in progesterone resistance in endometriosis. Among the molecular targets of progesterone in the normal endometrium that resist progestin action in endometriotic cells are the nuclear transcription factor FOXO1, matrix metalloproteinases, the transmembrane gap junction protein connexin 43 and paracrine regulators of estradiol metabolism. Compared to other phenotypes, deep endometriosis appears to be more resistant to size regression upon medical treatments. Individual genetic characteristics can affect the bioavailability and pharmacodynamics of hormonal drugs used to treat endometriosis and, hence, explain part of the variability in the therapeutic response.Medical treatment of endometriosis needs urgent innovation, which should start by deeper understanding of the disease core features and diverse phenotypes and idiosyncrasies, while moving from pure hormonal treatments to drug combinations or novel molecules capable of restoring the various homeostatic mechanisms disrupted by endometriotic lesions.
Psychological well-being, physical health and social prescribing in the context of social research
Authors: Susan Nunn
Journal: Thorax (2020)

Anticoagulation with non-vitamin K antagonists (Non vitamin K oral anticoagulant (NOACs)) including dabigatran, rivaroxaban, apixaban and edoxaban is at least as effective as warfarin, has fewer drug and food interactions and does not require monthly monitoring. Although major bleeding with NOACs is infrequent, there remains concern about the ability to effectively treat episodes of major bleeding. New agents have been developed that are capable of providing rapid reversal of the anticoagulation effect of NOACs. Idarucizumab normalises the dilute thrombin time and the ecarin clotting time, both of which are elevated with dabigatran. Andexanet alfa reduces increased anti-factor Xa activity seen with the use of rivaroxaban and apixaban. A universal reversal agent is in development. These agents, unlike agents to reverse the anticoagulation effect of vitamin K antagonists, appear to reverse the specific NOAC anticoagulant. The development of reversal agents is a major advancement in managing bleeding in the era of NOACs. Future studies will be required to determine the impact on important clinical outcomes.
A piece of my mind. View from a room
Authors: T. L. Warren
Journal: JAMA (1990)

I may forget a few patients over the years, fail to recall their faces, their specific diseases, their complications, but if you mention one of the 24 rooms on 4 North, the medical oncology floor, a flood of names will rush before me. I don't know why, but I usually shun the superstitious—the uncanny occurrences of life. I never felt I had to use the same bat in Little League or the same pencil during a test, or even to pick lottery numbers of a certain significance. But it seems that a few rooms on 4 North definitely have it in for me. Whenever I enter one of these rooms, pushing through the oversized, intentionally heavy doors, I feel deep within my gut that the victim inside will touch me, teach me, sense me, in a manner no other one would in some different room. These certain rooms will play host to a human being I will come to know, to hold his hand while a resident performs some painful but hopefully necessary procedure, or perhaps share his grief, his foreboding of that inevitable event, through mutual tears. But eventually I will have to walk once again to the medical supply room, to find a small plastic bag containing
Weathering the Storm: Managing Older Adults With Breast Cancer Amid COVID-19 and Beyond
Authors: Rachel A Freedman, Mina S Sedrak, Jennifer R Bellon, Caroline C Block, Nancy U Lin, Tari A King, Christina Minami, Noam VanderWalde, Trevor A Jolly, Hyman B Muss, Eric P Winer
Journal: JNCI Journal of the National Cancer Institute (2020)

Abstract Caring for older patients with breast cancer presents unique clinical considerations because of preexisting and competing comorbidity, the potential for treatment-related toxicity, and the consequent impact on functional status. In the context of the COVID-19 pandemic, treatment decision making for older patients is especially challenging and encourages us to refocus our treatment priorities. While we work to avoid treatment delays and maintain therapeutic benefit, we also need to minimize the risk for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) exposures, myelosuppression, general chemotherapy toxicity, and functional decline. Herein, we propose multidisciplinary care considerations for the aging patient with breast cancer, with the goal to promote a team-based, multidisciplinary treatment approach during the COVID-19 pandemic and beyond. These considerations remain relevant as we navigate the “new normal” for the approximately 30% of breast cancer patients aged 70 years and older who are diagnosed in the United States annually and for the thousands of older patients living with recurrent and/or metastatic disease.
Antigen‐presenting cells and tolerance induction
Authors: D. Von Bubnoff, H. De La Salle, J. Weßendorf, S. Koch, D. Hanau, T. Bieber
Journal: Allergy (2002)

T cell tolerance induction to foreign and self‐antigens has occupied research since the beginning of the understanding of the immune system. Much controversy still exists on this question even though new methods became available to investigate immunoregulatory mechanisms. Antigen‐presenting cells play a pivotal role in transferring information from the periphery of the organism to lymphoid organs. There, they initiate not only the activation of naive T cells but seem to deliver important signals which result in T cell unresponsiveness with antigen‐specific tolerance induction.
Outcome of autoimmune cytopenia after hematopoietic cell transplantation in primary immunodeficiency
Authors: Su Han Lum, Sabeena Selvarajah, Angela Deya-Martinez, Peter McNaughton, Ali Sobh, Sheila Waugh, Shirelle Burton-Fanning, Lisa Newton, Julie Gandy, Zohreh Nademi, Stephen Owens, Eleri Williams, Marieke Emonts, Terry Flood, Andrew Cant, Mario Abinun, Sophie Hambleton, Andrew R. Gennery, Mary Slatter
Journal: Journal of Allergy and Clinical Immunology (2020)
Epidemic Neuropathy in Cuba
Authors: Douglas M. De Long
Journal: Annals of Internal Medicine (1995)

Letters1 November 1995Epidemic Neuropathy in CubaDouglas M. De Long, MDDouglas M. De Long, MDMarshfield Clinic; Ladysmith, WI 54848Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-123-9-199511010-00027 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail TO THE EDITOR:The article by Roman on the epidemic of nutritional neuropathy in Cuba [1] was timely. I recently spent a week in Cuba with a group of medical students, physicians, and medical anthropologists. Our purpose was to study the health care system of Cuba and to provide humanitarian relief supplies.The Cuban health care system has much to teach us. For example, access to care is not an issue in Cuba. “Consultorios” are on every block and in every school and work place. Specialty maldistribution is also not a problem. Cuba has approximately as many medical students as ...References1. Roman, GC. On politics and health: an epidemic of neurologic disease in Cuba. Ann Intern Med. 1995; 122:530-3. Google Scholar Author, Article, and Disclosure InformationAuthors: Douglas M. De Long, MDAffiliations: Marshfield Clinic; Ladysmith, WI 54848 PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited byTreatment and Outcomes in Nutritional Optic NeuropathyNutritional optic neuropathiesNutritional Amblyopia and B Complex Vitamin Deficiencies 1 November 1995Volume 123, Issue 9Page: 734KeywordsHealth careHealth care qualityInfantsLife expectancyMortalityMotivationNeuropathyNutritionQuality of lifeSub-specialty care ePublished: 15 August 2000 Issue Published: 1 November 1995 Copyright & PermissionsCopyright © 1995 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
A comprehensive echocardiographic method for risk stratification in pulmonary arterial hypertension
Authors: Stefano Ghio, Valentina Mercurio, Federico Fortuni, Paul R. Forfia, Henning Gall, Ardeschir Ghofrani, Stephen C. Mathai, Jeremy A. Mazurek, Monica Mukherjee, Manuel Richter, Laura Scelsi, Paul M. Hassoun, Khodr Tello
Journal: European Respiratory Journal (2020)

Question addressed Echocardiography is not currently considered as providing sufficient prognostic information to serve as an integral part of treatment goals in pulmonary arterial hypertension (PAH). We tested the hypothesis that incorporation of multiple parameters reflecting right heart function would improve the prognostic value of this imaging modality. Methods and main results We pooled individual patient data from a total of 517 patients (mean age 52±15 years, 64.8% females) included in seven observational studies conducted at five European and United States academic centres. Patients were subdivided into three groups representing progressive degrees of right ventricular dysfunction based on a combination of echocardiographic measurements, as follows. Group 1 (low risk): normal tricuspid annular plane systolic excursion (TAPSE) and nonsignificant tricuspid regurgitation (TR) (n=129); group 2 (intermediate risk): normal TAPSE and significant TR or impaired TAPSE and nondilated inferior vena cava (IVC) (n=256); group 3 (high risk): impaired TAPSE and dilated IVC (n=132). The 5-year cumulative survival rate was 82% in group 1, 63% in group 2 and 43% in group 3. Low-risk patients had better survival rates than intermediate-risk patients (log-rank Chi-squared 12.25; p&lt;0.001) and intermediate-risk patients had better survival rates than high-risk patients (log-rank Chi-squared 26.25; p&lt;0.001). Inclusion of other parameters such as right atrial area and pericardial effusion did not provide added prognostic value. Answer to the question The proposed echocardiographic approach integrating the evaluation of TAPSE, TR grade and IVC is effective in stratifying the risk for all-cause mortality in PAH patients, outperforming the prognostic parameters suggested by current guidelines.
El Niño and Incidence of Hemorrhagic Fever With Renal Syndrome in China
Authors: Peng Bi, Kevin A. Parton
Journal: JAMA (2003)

In Reply: Drs Kennell and Klaus used our definition of compliance to infer that all women in the experimental group received intermittent support.On the contrary, the nurses aimed to provide 100% continuous labor support.We selected 80% minimum time as our standard for compliance, in recognition of the nurses' needs for meals and personal hygiene breaks at times when another nurse trained in labor support might be unavailable, and in anticipation of rare instances of emergencies with other patients.Because nearly all women had husbands and/or other family members with them, we doubt that any women were ever left completely alone.We did assess compliance and contamination.Compliance was very high; the appropriate form of care was provided to more than 95% of the patients.We cited evidence that contamination of the control group did not occur.Participants' reports of the supportive care activities they received indicated that each activity was provided significantly more often to the experimental group, and the results were the same when we compared responses in the first and second years of the trial.The aim of our trial was to determine if nurses could be effective providers of labor support, within the context of typical North American hospitals.The nurses were not doulas; they were hospital employees and responsible for all other aspects of the nursing care of their patients.However, they were trained in labor support by an instructor certified by Doulas of North America.
Abstract 16681: Early Left Ventricular Dysfunction in Healthy Young Adults Born Premature
Authors: Kara N Goss, Arij G Beshish, Jacob Macdonald, Gregory P Barton, Naomi C Chesler, Christopher J Francois, Oliver Wieben, Marlowe W Eldridge
Journal: Circulation (2018)

Rationale: Preterm birth, or less than 37 weeks completed gestation, affects one in 10 live births in the United States. Moderate to extreme premature birth, or less than 32 weeks gestation, is associated with up to a 17-fold increased risk for the development of heart failure in adolescents and young adults. Here, we sought to characterize left ventricular (LV) function in young adults born premature. Methods: Adults born preterm (n=11; gestational age 28.2±0.8 weeks; current age 27±1 years) were recruited from the Newborn Lung Project at the University of Wisconsin-Madison, a prospective cohort of infants born 1988-1991 with birth weight &lt;1500 g. Controls were recruited from the general population (n=12; age 26±1 years). All subjects were free from adult cardiopulmonary disease. Subjects underwent cardiac magnetic resonance imaging (MRI) on a 3.0T scanner. Measures included standard assessment of LV function and LV strain. 4D flow imaging was acquired with a radially-undersampled PC VIPR sequence to assess systolic and diastolic LV kinetic energy, and corresponding LV energetic efficiency was defined as stroke volume normalized by the systolic and diastolic kinetic energy . Mann-Whitney tests were performed to assess for statistical significance (p&lt;0.05). Results: Young adults born premature had significantly smaller chamber volumes, even when indexed to body size (table 1). However, stroke volume was maintained due to a higher ejection fraction. Cardiac output and index were significantly higher in young adults born premature, due to a higher resting heart rate. Strain analysis confirmed a hyperdynamic LV. 4D flow demonstrated a significantly higher LV energy cost, resulting in an energetically inefficient LV. Conclusions: Otherwise healthy young adults born premature demonstrate a hypercontractile, energetically inefficient LV, which may provide mechanistic insight into the increased risk for heart failure in this high-risk population.