tbuckley/cabot-search huggingface dataset:
Abstract 12657: Congenital Pseudoaneurysm of the Mitral-Aortic Intervalvular Fibrosa: A Case Report
Authors: Jamie K Harrington, Julie Glickstein, Amee Shah
Journal: Circulation (2016)

Introduction: The mitral-aortic intervalvular fibrosa (MAIVF) is the area of fibrous continuity between the mitral and aortic valves. Pseudoaneurysm formation can rarely occur here after trauma, commonly surgical or infectious. We describe the first case of a congenital pseudoaneurysm of the MAIVF (PMAIVF) seen prenatally as an isolated cardiac defect and followed conservatively postnatally. Case Report: A fetal echocardiogram was performed at 30 weeks gestation after an echogenic cardiac focus was seen on fetal ultrasound. A large left atrial mass with mixed echogenicity was seen oriented along the atrial septum with suggestion of flow in the lesion on color Doppler (Fig 1A-B). The mass was not obstructing mitral, aortic or foramen ovale flow and the rest of the cardiac anatomy was normal. A comparative view on the postnatal echocardiogram confirmed the presence of an echolucent mass with flow into the lesion on color Doppler (Fig 1C-D). The parasternal long axis demonstrated the neck of the aneurysm arising between the mitral and aortic annuli with lack of fibrous continuity (Fig 2A). Color Doppler demonstrated blood flow into the pouch during systole and into the left ventricular outflow tract during diastole consistent with a congenital PMAIVF (Fig 2B-C). Pulsed-Doppler showed antegrade and retrograde flow in the neck (Fig 2D). The infant is now 4 months old and serial echocardiograms have shown stable size and appearance of the PMAIVF, with low velocity bidirectional flow into the neck, and it has remained non-obstructive. Conclusion: PMAIVF can exist without preceding trauma as a rare, isolated congenital cardiac defect. The natural history of a congenital PMAIVF is unclear.
Successful treatment of giant esophageal diverticulum by per-oral endoscopic myotomy
Authors: Chuncheng Wu, Qiongying Zhang, Wei Liu, Bing Hu
Journal: Endoscopy (2018)

A 79-year-old woman was referred to our department with a 20-year history of dysphagia, retrosternal pain, and several episodes of aspiration and pneumonia. Esophageal radiograph showed a giant diverticulum in the mid-esophagus containing a large amount of the barium ([Fig. 1]). Gastroscopy revealed food impaction in the giant esophageal diverticulum; the real opening of the esophagus was relatively narrow and compressed at the side ([Fig. 2]). Given the advanced age of the patient and the potential complications of a surgical procedure, the patient underwent per-oral endoscopic myotomy (POEM) ([Video 1]).
EMPIRE Registry, Czech Part: Impact of Demographics, PulmonaryFunction and HRCT on Survival and Clinical Course inIdiopathic Pulmonary Fibrosis
Authors: Martina Doubková, Jan Švancara, Michal Svoboda, Martina Šterclová, Vladimír Bartoš, Martina Plačková, Ladislav Lacina, Monika Žurková, Ilona Binková, Radka Bittenglová, Vladimíra Lošťáková, Zdeněk Merta, Lenka Šišková, Richard Tyl, Pavlína Lisá, Hana Šuldová, František Petřík, Jana Pšikalová, Vladimír Řihák, Tomáš Snížek, Pavel Reiterer, Jiří Homolka, Pavlína Musilová, Jaroslav Lněnička, Peter Palúch, Roman Hrdina, Renata Králová, Hana Hortvíková, Jana Strenková, Martina Vašáková
Journal: European Respiratory Journal (2018)

Prognostic factors of idiopathic pulmonary fibrosis (IPF)
currently recognized include changes in vital capacity and
radiologic findings. However, most of the prognostic studies in
IPF are based on clinical studies with preselected IPF
populations. Therefore, we decided to analyze the factors
influencing IPF prognosis based on the real-practice data from
our IPF registry. Data of 514 subjects consecutively entered
since 2012 into Czech EMPIRE IPF registry were analyzed.
A Macrophage Colony-Stimulating-Factor-Producing γδ T Cell Subset Prevents Malarial Parasitemic Recurrence
Authors: Murad R. Mamedov, Anja Scholzen, Ramesh V. Nair, Katherine Cumnock, Justin A. Kenkel, Jose Henrique M. Oliveira, Damian L. Trujillo, Naresha Saligrama, Yue Zhang, Florian Rubelt, David S. Schneider, Yueh-hsiu Chien, Robert W. Sauerwein, Mark M. Davis
Journal: Immunity (2018)
Real-time continuous glucose monitoring in adults with type 1 diabetes and impaired hypoglycaemia awareness or severe hypoglycaemia treated with multiple daily insulin injections (HypoDE): a multicentre, randomised controlled trial
Authors: Lutz Heinemann, Guido Freckmann, Dominic Ehrmann, Gabriele Faber-Heinemann, Stefania Guerra, Delia Waldenmaier, Norbert Hermanns
Journal: The Lancet (2018)
Tocilizumab for the management of immune mediated adverse events secondary to PD-1 blockade.
Authors: Chipman Robert Geoffrey Stroud, Cynthia R. Cherry, Abdul Rafeh Naqash, Nitika Sharma, Sulochana Devi Cherukuri, Teresa Parent, Jessica Hardin, Paul R. Walker
Journal: Journal of Clinical Oncology (2017)

e21712 Background: Immune checkpoint inhibitors are poised to revolutionize the management of a growing number of malignancies. Unfortunately, the management of steroid-refractory immune mediated adverse events (irAEs) is based on a paucity of randomized data and limited to single center experiences. Our initial experience with the IL-6 receptor antagonist tocilizumab showed clinical improvement in a wide variety of irAEs. As a result, we adopted the use of tocilizumab for the management of steroid-refractory irAEs. Methods:The character and clinical course of irAEs were abstracted from the medical record and analyzed. The dose of tocilizumab was 4 mg/kg given IV over 1 hour. C-reactive protein was drawn at first nivolumab infusion and at q 2 weeks (and with irAEs) thereafter. Clinical improvement was defined as either: documentation of resolution of symptoms or hospital d/c within 7 days. Results:Of the initial 87 patients that were treated with nivolumab, 34 required tocilizumab (39.1%). All pts were on corticosteroids. The majority (88.2%) were lung cancer patients. The index grade 3/4 irAE was pneumonitis in 35.3%, cytokine release syndrome/SIRS in 35.3%, cerebritis in 14.7% and one case each of hypophysitis, colitis, pancreatitis, hepatitis and immune mediated coagulopathy. Median time between first nivolumab and initiation of tocilizumab was 76 days (range 1-429). Median CRP at initial tocilizumab dose was 100.5 mg/L (2.0 -350.4). Clinical improvement was noted in 27/34 pts (79.4%). 52.9% of pts required a single dose, while 35.3% required two, 8.8% required three and 1 pt required 4 doses. Twenty seven doses were given in the inpatient setting (49.1%). Median time to discharge was 4 days (range 1-27). Seventy four percent of pts were discharged home. For the 55 doses of tocilizumab that were delivered there was a cost savings of $147,174.94 (WAC) during the 18 month period versus infliximab 5 mg/kg IV dose. Conclusions: Tocilizumab is a therapeutic option for the management of steroid refractory irAEs secondary to immune checkpoint blockade. However, randomized trials are needed to better elucidate the relative efficacy and safety of these agents.
CDK4 is an important target for hepatocellular cancer with inactivation of TGF-beta signaling through Smad and ELF
Authors: Michael Pishvaian, Geeta Upadhyay, Zhixing Yao, Young Kim, Anan Said, Jon Mendelson, Krit Kitisin, Eugene Volpe, Tiffany Blake, Sang Kim, Hae Baek, Anthony Kang, Bibhuti Mishra, E. Premkumar Reddy, Lopa Mishra
Journal: Cancer Research (2008)

2583   Background: Transforming growth factor (TGF-β) signaling inhibits cell cycle progression through an increase in cell cycle inhibitors and decrease in cell cycle activators. We have shown that the Smad3/4 adaptor protein embryonic liver fodrin (ELF) is crucial for normal TGF-β signaling. ELF facilitates the association and nuclear translocation of the TGF-β signaling proteins, Smad3 and Smad4. Our results demonstrate that  elf +/- /CDK4 +/+   mice develop hepatocellular cancers (HCC) spontaneously within 12 months. Our results also show that most human HCCs exhibit decreased expression of ELF and a concomitant increase in the expression of Cyclin D1 and CDK4. Interestingly, Smad3 is a CDK4 substrate, yet Smad3 mice mostly do not develop tumors. Our hypothesis is that ELF is a potential CDK4 substrate Methods and Results: To further assess whether the development of HCC in  elf +/- /CDK4 +/+   mice is dependent upon CDK4 expression, we intercrossed  elf +/- /CDK4 +/+   and  elf +/+ /CDK4 +/-   mice. To date, only 5% (1/20) of the  elf +/- /CDK4 +/-   mice developed HCC. Specifically, at 12 months, only 1/10 (10%) of the  elf +/- /CDK4 +/-   mice developed HCC, compared to 25% of age matched  elf +/- /CDK4 +/+   mice based on our historical controls. More impressively, 0/10 of the 18 month old  elf +/- /CDK4 +/-   mice developed HCC, compared with nearly 50% of age matched  elf +/- /CDK4 +/+   mice based on our historical controls. These data correspond to a median disease free survival of >3 years in the  elf +/- /CDK4 +/-   mice compared with only 18 months in the  elf +/- /CDK4 +/+   mice. ELF and CDK4 interact endogenously as well as in vitro. ELF is also phosphorylated by CDK4. Moreover, ELF, CDK4, and Smad3 complex together through an interaction that is likely mediated by the N-terminal domain of ELF. Conclusions: These data strongly suggest that haploinsufficiency of CDK4 can prevent the HCCs seen in  elf +/- /CDK4 +/+   mice, and provides the genetic foundation for further exploring the benefits of specific inhibitors of CDK4 in the treatment of HCC. These results demonstrate that haploinsufficiency of CDK4 prevents the formation of HCC, and thus targeted-inhibition of CDK4 activity may be a logical treatment for HCC in humans interaction with CDK4.
The Formation and Function of Granulomas
Authors: Antonio J. Pagán, Lalita Ramakrishnan
Journal: Annual Review of Immunology (2018)

Granulomas are organized aggregates of macrophages, often with characteristic morphological changes, and other immune cells. These evolutionarily ancient structures form in response to persistent particulate stimuli-infectious or noninfectious-that individual macrophages cannot eradicate. Granulomas evolved as protective responses to destroy or sequester particles but are frequently pathological in the context of foreign bodies, infections, and inflammatory diseases. We summarize recent findings that suggest that the granulomatous response unfolds in a stepwise program characterized by a series of macrophage activations and transformations that in turn recruit additional cells and produce structural changes. We explore why different granulomas vary and the reasons that granulomas are protective and pathogenic. Understanding the mechanisms and role of granuloma formation may uncover new therapies for the multitude of granulomatous diseases that constitute serious medical problems while enhancing the protective function of granulomas in infections.
Bolus Versus Prolonged Infusion of Broad-Spectrum Beta-Lactams for Patients with Hematologic Malignancies and High Risk Febrile Neutropenia - a Single Center Prospective Unblinded Randomized Trial
Authors: Ron Ram, Irit Avivi, Odelia Amit, Yael Halavy, Yael Paran, Eugene Katchman, Bruria Yachini, Kor Svetlana, Ronen Ben Ami
Journal: Blood (2017)
Management of Immune-Related Adverse Events in Patients Treated With Immune Checkpoint Inhibitor Therapy: American Society of Clinical Oncology Clinical Practice Guideline
Authors: Julie R. Brahmer, Christina Lacchetti, Bryan J. Schneider, Michael B. Atkins, Kelly J. Brassil, Jeffrey M. Caterino, Ian Chau, Marc S. Ernstoff, Jennifer M. Gardner, Pamela Ginex, Sigrun Hallmeyer, Jennifer Holter Chakrabarty, Natasha B. Leighl, Jennifer S. Mammen, David F. McDermott, Aung Naing, Loretta J. Nastoupil, Tanyanika Phillips, Laura D. Porter, Igor Puzanov, Cristina A. Reichner, Bianca D. Santomasso, Carole Seigel, Alexander Spira, Maria E. Suarez-Almazor, Yinghong Wang, Jeffrey S. Weber, Jedd D. Wolchok, John A. Thompson
Journal: Journal of Clinical Oncology (2018)

Purpose To increase awareness, outline strategies, and offer guidance on the recommended management of immune-related adverse events in patients treated with immune checkpoint inhibitor (ICPi) therapy. Methods A multidisciplinary, multi-organizational panel of experts in medical oncology, dermatology, gastroenterology, rheumatology, pulmonology, endocrinology, urology, neurology, hematology, emergency medicine, nursing, trialist, and advocacy was convened to develop the clinical practice guideline. Guideline development involved a systematic review of the literature and an informal consensus process. The systematic review focused on guidelines, systematic reviews and meta-analyses, randomized controlled trials, and case series published from 2000 through 2017. Results The systematic review identified 204 eligible publications. Much of the evidence consisted of systematic reviews of observational data, consensus guidelines, case series, and case reports. Due to the paucity of high-quality evidence on management of immune-related adverse events, recommendations are based on expert consensus. Recommendations Recommendations for specific organ system-based toxicity diagnosis and management are presented. While management varies according to organ system affected, in general, ICPi therapy should be continued with close monitoring for grade 1 toxicities, with the exception of some neurologic, hematologic, and cardiac toxicities. ICPi therapy may be suspended for most grade 2 toxicities, with consideration of resuming when symptoms revert to grade 1 or less. Corticosteroids may be administered. Grade 3 toxicities generally warrant suspension of ICPis and the initiation of high-dose corticosteroids (prednisone 1 to 2 mg/kg/d or methylprednisolone 1 to 2 mg/kg/d). Corticosteroids should be tapered over the course of at least 4 to 6 weeks. Some refractory cases may require infliximab or other immunosuppressive therapy. In general, permanent discontinuation of ICPis is recommended with grade 4 toxicities, with the exception of endocrinopathies that have been controlled by hormone replacement. Additional information is available at www.asco.org/supportive-care-guidelines and www.asco.org/guidelineswiki .
Imatinib Is Safe and Effective In Patients with Refractory Chronic Graft Versus Host Disease: Analysis of Two Consecutive Prospective GITMO Studies
Authors: A Olivieri, M Cimminiello, F Locatelli, M Zecca, P Corradini, F Patriarca, N Mordini, P Iacopino, A Donelli, Carmine Selleri, M Badiali, G Lucchini, G Gini, P Leoni, A Bosi, A. Bacigalupo
Journal: Blood (2010)
Allogeneic hematopoietic cell transplantation in intermediate risk acute myeloid leukemia negative forFLT3-ITD,NPM1- or biallelicCEBPA mutations
Authors: K. Heidrich, C. Thiede, K. Schäfer-Eckart, N. Schmitz, W.E. Aulitzky, A. Krämer, W. Rösler, M. Hänel, H. Einsele, C.D. Baldus, R.U. Trappe, F. Stölzel, J.M. Middeke, C. Röllig, F. Taube, M. Kramer, H. Serve, W.E. Berdel, G. Ehninger, M. Bornhäuser, J. Schetelig
Journal: Annals of Oncology (2017)
SCCA2 is a reliable biomarker for evaluating pediatric atopic dermatitis
Authors: Mizuho Nagao, Shinichiro Inagaki, Toshiki Kawano, Yoshinori Azuma, Noriko Nomura, Yasuhiko Noguchi, Shoichiro Ohta, Atsushi Kawaguchi, Hiroshi Odajima, Yukihiro Ohya, Takao Fujisawa, Kenji Izuhara
Journal: Journal of Allergy and Clinical Immunology (2018)
Role of Surveillance Biopsy with No Cancer as a Prognostic Marker for Reclassification: Results from the Canary Prostate Active Surveillance Study
Authors: James T. Kearns, Anna V. Faino, Lisa F. Newcomb, James D. Brooks, Peter R. Carroll, Atreya Dash, William J. Ellis, Michael Fabrizio, Martin E. Gleave, Todd M. Morgan, Peter S. Nelson, Ian M. Thompson, Andrew A. Wagner, Yingye Zheng, Daniel W. Lin
Journal: European Urology (2018)
Impact of food allergy on the growth of children with moderate-severe atopic dermatitis
Authors: Rekha D. Jhamnani, Samara Levin, Marjohn Rasooly, Kelly D. Stone, Joshua D. Milner, Celeste Nelson, Tom DiMaggio, Nina Jones, Anthony L. Guerrerio, Pamela A. Frischmeyer-Guerrerio
Journal: Journal of Allergy and Clinical Immunology (2018)
Abstract 11920: Forecasting Short-term Atrial Fibrillation Recurrence Based on Past Atrial Fibrillation Recurrence Patterns
Authors: Efstratios I Charitos, Paul D Ziegler
Journal: Circulation (2015)

Introduction: Atrial fibrillation (AF) is considered a random phenomenon with regards to its initiation, recurrence pattern, and termination. Hypothesis: We sought to investigate if and how well the amount and pattern of past AF recurrence can forecast short term (30 day) future AF recurrence. Methods: We reconstructed the cardiac rhythm histories of 1195 patients with implantable cardiac devices (age 73 ± 10 years, follow-up: 349 ± 40 days, mean AF burden: 11%). The weekly amount (AF burden) and pattern of AF recurrence (AF density) of the 1st 150 days (1st half of the rhythm history) for each patient was used to construct a supervised machine learning algorithm (random forest regression model) with the aim to predict the amount of AF recurrence during days 151-180. Validation of the algorithm was performed on the 2nd half of the observation period of the same patients (AF pattern of days 150-300 to predict AF recurrence in days 301-330). An additional 2nd external validation of the algorithm was performed on a separate patient cohort consisting of 574 patients (age 69 ± 13 years, follow-up: 365 days, mean AF burden: 12%). Results: In the training cohort, the algorithm accounted for 86% of the observed variance with a mean squared error rate of 0.01. Variable importance measures revealed that the past amount (AF burden) and pattern (AF density) exhibited an important influence on future AF recurrence with decreasing importance for more remote events. AF recurrence up to 6 weeks in the past influenced short term (30 day) future AF recurrence. Validation of the algorithm on the 2nd half of the observation period and the external patient cohort revealed low median AF burden prediction errors of 0.004 [0.002-0.004] and 0.004 [0.003-0.028], respectively (Figure). Conclusions: The amount and temporal pattern of past AF recurrence (up to 6 weeks) is associated with short term future AF recurrence. This predictive ability attenuates progressively over time and merits further investigation.
Gut microbiota modulate T cell trafficking into human colorectal cancer
Authors: Eleonora Cremonesi, Valeria Governa, Jesus Francisco Glaus Garzon, Valentina Mele, Francesca Amicarella, Manuele Giuseppe Muraro, Emanuele Trella, Virginie Galati-Fournier, Daniel Oertli, Silvio Raffael Däster, Raoul A Droeser, Benjamin Weixler, Martin Bolli, Raffaele Rosso, Ulrich Nitsche, Nina Khanna, Adrian Egli, Simone Keck, Julia Slotta-Huspenina, Luigi M Terracciano, Paul Zajac, Giulio Cesare Spagnoli, Serenella Eppenberger-Castori, Klaus-Peter Janssen, Lubor Borsig, Giandomenica Iezzi
Journal: Gut (2018)

Objective Tumour-infiltrating lymphocytes (TILs) favour survival in human colorectal cancer (CRC). Chemotactic factors underlying their recruitment remain undefined. We investigated chemokines attracting T cells into human CRCs, their cellular sources and microenvironmental triggers. Design Expression of genes encoding immune cell markers, chemokines and bacterial 16S ribosomal RNA (16SrRNA) was assessed by quantitative reverse transcription-PCR in fresh CRC samples and corresponding tumour-free tissues. Chemokine receptor expression on TILs was evaluated by flow cytometry on cell suspensions from digested tissues. Chemokine production by CRC cells was evaluated in vitro and in vivo, on generation of intraperitoneal or intracecal tumour xenografts in immune-deficient mice. T cell trafficking was assessed on adoptive transfer of human TILs into tumour-bearing mice. Gut flora composition was analysed by 16SrRNA sequencing. Results CRC infiltration by distinct T cell subsets was associated with defined chemokine gene signatures, including CCL5, CXCL9 and CXCL10 for cytotoxic T lymphocytes and T-helper (Th)1 cells; CCL17, CCL22 and CXCL12 for Th1 and regulatory T cells; CXCL13 for follicular Th cells; and CCL20 and CCL17 for interleukin (IL)-17-producing Th cells. These chemokines were expressed by tumour cells on exposure to gut bacteria in vitro and in vivo. Their expression was significantly higher in intracecal than in intraperitoneal xenografts and was dramatically reduced by antibiotic treatment of tumour-bearing mice. In clinical samples, abundance of defined bacteria correlated with high chemokine expression, enhanced T cell infiltration and improved survival. Conclusions Gut microbiota stimulate chemokine production by CRC cells, thus favouring recruitment of beneficial T cells into tumour tissues.
Revision of the International Society of Nephrology/Renal Pathology Society classification for lupus nephritis: clarification of definitions, and modified National Institutes of Health activity and chronicity indices
Authors: Ingeborg M. Bajema, Suzanne Wilhelmus, Charles E. Alpers, Jan A. Bruijn, Robert B. Colvin, H. Terence Cook, Vivette D. D’Agati, Franco Ferrario, Mark Haas, J. Charles Jennette, Kensuke Joh, Cynthia C. Nast, Laure-Hélène Noël, Emilie C. Rijnink, Ian S.D. Roberts, Surya V. Seshan, Sanjeev Sethi, Agnes B. Fogo
Journal: Kidney International (2018)
Cytosolic and Secreted Peptidoglycan-Degrading Enzymes in Drosophila Respectively Control Local and Systemic Immune Responses to Microbiota
Authors: Bernard Charroux, Florence Capo, C. Léopold Kurz, Sabine Peslier, Delphine Chaduli, Annelise Viallat-lieutaud, Julien Royet
Journal: Cell Host & Microbe (2018)
Association of Surgeons in Training responds to GMC erasure case
Authors: Gemma L Humm, Paul Sutton, Vimal Gokani, Helen Mohan
Journal: BMJ (2018)

The case of Hadiza Bawa-Garba highlights problems with the developing blame culture, the use of a junior doctor’s educational reflective practice in court, and senior supervision.1

In November 2016, the Academy of Medical Royal Colleges issued guidance on entering information on e-portfolios.2 This guidance is chiefly concerned with the anonymity of patient data. The exclusion of patient identifiable …
Role of local CpG DNA methylation in mediating the 17q21 asthma susceptibility gasdermin B (GSDMB)/ORMDL sphingolipid biosynthesis regulator 3 (ORMDL3) expression quantitative trait locus
Authors: Parul H. Kothari, Weiliang Qiu, Damien C. Croteau-Chonka, Fernando D. Martinez, Andrew H. Liu, Robert F. Lemanske, Carole Ober, Jerry A. Krishnan, Dan L. Nicolae, Kathleen C. Barnes, Stephanie J. London, Albino Barraza-Villarreal, Steven R. White, Edward T. Naureckas, Joshua Millstein, W. James Gauderman, Frank D. Gilliland, Vincent J. Carey, Scott T. Weiss, Benjamin A. Raby
Journal: Journal of Allergy and Clinical Immunology (2018)