tbuckley/cabot-search huggingface dataset:
Unilateral facial swelling in a thyrotoxic patient
Authors: Matthew Seymour, Adam Morton
Journal: BMJ (2017)

A 70 year old man presented with a critically ischaemic left foot. On pre-operative work-up he was found to be thyrotoxic. His free thyroxine (T4) was 77 pmol/L (normal range 9-19), free tri-iodothyronine (T3) 13 pmol/L (normal 2-6), and he had undetectable thyroid stimulating hormone (TSH). He had a history of peripheral vascular disease, well controlled type 2 diabetes mellitus, ischaemic cardiomyopathy, atrial fibrillation, and a past ventricular fibrillation arrest. His medications included amiodarone (commenced three years previously), rivaroxaban, and metformin. In the preceding two months he had undergone several radiological vascular procedures of the lower limb that had involved the administration of radiocontrast. TSH receptor antibody was not detected, and on ultrasound thyroid volume was 20 mL with no nodules and normal vascularity on colour flow doppler sonography. A thyroid nuclear medicine scan was not performed in view of the recent radiocontrast.

Amiodarone was ceased and he was started on carbimazole (20 mg twice daily) and prednisone (50 mg daily) concurrently. When he did not respond to initial management, lithium and cholestyramine were later introduced. The patient underwent surgical revascularisation for his ischaemic left foot, which occurred without complication. He remained in hospital for management of his thyrotoxicosis. During this period, he developed acute painful swelling of the right side of his face, associated with fever and rigors. He was neutropenic with a neutrophil count of 0.01 x109/L (normal 1.8-7.7). A computed tomography (CT) scan was performed (fig 1⇓). 



Fig 1  Transverse facial computed tomography image





### 1. What is the cause of the neutropenia?

#### Short answer

Thionamide induced agranulocytosis.

#### Discussion

Agranulocytosis is a severe reduction in circulating neutrophils, which predisposes the patient …
Biofluid‐Triggered Burst Release from an Adaptive Covalently Assembled Dipeptide Nanocontainer for Emergency Treatment
Authors: Jinbo Fei, He Zhang, Anhe Wang, Chenchen Qin, Huimin Xue, Junbai Li
Journal: Advanced Healthcare Materials (2017)

The construction of quickly dissociating containers holding bioactive components that meet the extreme requirements of emergency treatment is highly desirable but remains a great challenge. Here the use of small-molecule-induced dynamic covalent assembly is reported for simple and tunable fabrication of a biocompatible diphenylalanine-based nanocontainer toward rapidly responsive cargo delivery. The assembled nanocontainer can adaptively encapsulate various charged or neutral molecules. Upon biofluid trigger, the encapsulated molecules and bioactive proteins are released in a burst (within 5 s) from the nanocontainer due to highly sensitive deprotonation-mediated disruption of hydrogen bonding. This highlighted feature allows the nanocontainer as an excellent "fast dissolving" delivery vehicle available in spray dosage form for medical emergencies, as demonstrated by in vivo application for massive hemorrhage.
Basophil Activation Test in Clavulanic Acid Selective Patients. Decrease of IgE Recognition over Time
Authors: Tahia D. Fernandez, Maria Salas, Rubén Fernández, Maria I. Montañez, Angela Martín-Serrano, Nekane Barbero, Ezequiel Perez-Inestrosa, Cristobalina Mayorga, Maria J. Torres
Journal: Journal of Allergy and Clinical Immunology (2017)
Outcome of Risk Adapted Therapy for Relapsed/Refractory Acute Lymphoblastic Leukemia in Children: Results From a Single Institution
Authors: Asim F Belgaumi, Asem Bukhari, Mohammed Al-Mahr, Amal Al-Seraihy, Hazem Mahmoud, Abdulrahman Al-Musa, Mahasen Saleh, Ali Al-Ahmari, Mouhab F Ayas, Viqaruddin Khaja, Hassan El-Solh
Journal: Blood (2011)
Hemoglobin F Induction Is Frequent during Low-Dose 5-aza-2′-Deoxycytidine Treatment of Older AML/MDS Patients.
Authors: Rainer Claus, Björn Hackanson, Lena Kasten, Björn Rüter, Emmanuel Bisse, Dieter Pfeifer, Michael Lübbert
Journal: Blood (2006)
The APC/C E3 Ligase Complex Activator FZR1 Restricts BRAF Oncogenic Function
Authors: Lixin Wan, Ming Chen, Juxiang Cao, Xiangpeng Dai, Qing Yin, Jinfang Zhang, Su-Jung Song, Ying Lu, Jing Liu, Hiroyuki Inuzuka, Jesse M. Katon, Kelsey Berry, Jacqueline Fung, Christopher Ng, Pengda Liu, Min Sup Song, Lian Xue, Roderick T. Bronson, Marc W. Kirschner, Rutao Cui, Pier Paolo Pandolfi, Wenyi Wei
Journal: Cancer Discovery (2017)

BRAF drives tumorigenesis by coordinating the activation of the RAS/RAF/MEK/ERK oncogenic signaling cascade. However, upstream pathways governing BRAF kinase activity and protein stability remain undefined. Here, we report that in primary cells with active APCFZR1, APCFZR1 earmarks BRAF for ubiquitination-mediated proteolysis, whereas in cancer cells with APC-free FZR1, FZR1 suppresses BRAF through disrupting BRAF dimerization. Moreover, we identified FZR1 as a direct target of ERK and CYCLIN D1/CDK4 kinases. Phosphorylation of FZR1 inhibits APCFZR1, leading to elevation of a cohort of oncogenic APCFZR1 substrates to facilitate melanomagenesis. Importantly, CDK4 and/or BRAF/MEK inhibitors restore APCFZR1 E3 ligase activity, which might be critical for their clinical effects. Furthermore, FZR1 depletion cooperates with AKT hyperactivation to transform primary melanocytes, whereas genetic ablation of Fzr1 synergizes with Pten loss, leading to aberrant coactivation of BRAF/ERK and AKT signaling in mice. Our findings therefore reveal a reciprocal suppression mechanism between FZR1 and BRAF in controlling tumorigenesis.Significance: FZR1 inhibits BRAF oncogenic functions via both APC-dependent proteolysis and APC-independent disruption of BRAF dimers, whereas hyperactivated ERK and CDK4 reciprocally suppress APCFZR1 E3 ligase activity. Aberrancies in this newly defined signaling network might account for BRAF hyperactivation in human cancers, suggesting that targeting CYCLIN D1/CDK4, alone or in combination with BRAF/MEK inhibition, can be an effective anti-melanoma therapy. Cancer Discov; 7(4); 424-41. ©2017 AACR.See related commentary by Zhang and Bollag, p. 356This article is highlighted in the In This Issue feature, p. 339.
Mizutani A, Okajima K, Uchiba M, Noguchi T. Activated protein C reduces ischemia/reperfusion-induced renal injury in rats by inhibiting leukocyte activation. Blood. 2000;95(12):3781-3787. Mizutani A, Okajima K, Uchiba M, Isobe H, Harada N, Mizutani S, Noguchi T. Antithrombin reduces ischemia/reperfusion-induced renal injury in rats by inhibiting leukocyte activation through promotion of prostacyclin production. Blood. 2003;101(8):3029-3036.
Journal: Blood (2013)
Antibody Prevalence in Epilepsy (APE) Score—Evolution in Autoimmune Epilepsy Practice
Authors: Andrew McKeon
Journal: JAMA Neurology (2017)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Neurology HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Neurology journal
Efficacy and safety of pasireotide LAR or everolimus alone, or in combination in patients with advanced carcinoids (NET) of the lung/thymus: Results from the randomized, phase 2 LUNA study
Authors: P. Ferolla, M.P. Brizzi, T. Meyer, W. Mansoor, J. Mazieres, C.D. Cao, H. Lena, A. Berruti, V. Damiano, W. Buikhuisen, M. Stankovic, N. Singh, E. Chiodini, G. Gislimberti, K. Oberg, E. Baudin
Journal: Annals of Oncology (2016)
A video decision support tool for CPR in advanced cancer: A randomized controlled trial.
Authors: Angelo E. Volandes, Michael Paasche-Orlow, Areej El-Jawahri, Susan L. Mitchell, Margaret Kemeny, Kevan L. Hartshorn, Vicki A. Jackson, Michael J Barry, Aretha Delight Davis, Lenny Lopez, Elizabeth Walker-Corkery, Yuchiao Chang, Andrew S. Epstein, Linda Bulone, Sumathi Misra, Matt Peachey, Ariela Noy, Tomer Levin, April F. Eichler, Jennifer S. Temel
Journal: Journal of Clinical Oncology (2012)

9004 Background: End-of-life decision-making is important to patients, including whether or not to attempt cardiopulmonary resuscitation (CPR). Doctors often rely solely on verbal descriptions to communicate information regarding CPR. Video decision support tools have the potential to improve patients’ understanding of CPR by providing visual images of what this intervention entails. The objective of this study was to examine the effect of a CPR video among patients with advanced cancer on their preferences and knowledge of CPR. Methods: A randomized controlled trial of 150 subjects with diverse advanced cancers (&lt; 1-year prognosis) recruited from 4 cancer centers in the United States. Subjects were randomized to either a verbal narrative describing CPR, or to a video with verbal narrative. The video depicts CPR and reviews the success rate in advanced cancer. Study endpoints were subjects’ CPR preferences, knowledge of CPR (knowledge scores ranged from 0-4, higher score indicating more knowledge), and perceived value of the video. Chi-square tests were used to compare the distributions of categorical outcomes and two-sample t-tests were used to compare the means between the two groups. Results: A total of 150 subjects were randomized to a verbal narrative (n=80) or video with verbal narrative (n=70). Mean age was 62, 49% were women, 47% White, 34% Black, and 47% had lung or colon cancer. Among subjects receiving the verbal narrative, 38 (47.5%) preferred to have CPR attempted; 41 (51.2%) chose not to have CPR; and 1 (1.3%) was uncertain. In the video group, 14 (20%) preferred to have CPR attempted; 55 (78.6%) chose not to have CPR; and 1 (1.4%) was uncertain (P&lt;0.001). The mean knowledge score was higher in the video group than in the verbal group (3.3 vs. 2.6 respectively; P&lt;0.001). Of the subjects who viewed the video, 94.1% stated they were comfortable watching the video, 97.1% found the video helpful, and 100% would recommend the video. Conclusions: Compared to subjects who only heard a verbal description, subjects with advanced cancer who viewed a CPR video were more likely to prefer not having CPR, and were more knowledgeable about CPR. The majority of subjects found the video helpful, comfortable to view, and would recommend it to others.
360O_PR Efficacy and safety of nivolumab for recurrent or metastatic (R/M) squamous cell carcinoma of the head and neck (SCCHN) in Asia: CheckMate 141 subgroup analysis
Authors: Y. Hasegawa, N. Kiyota, S. Takahashi, T. Yokota, C.-J. Yen, S. Iwae, Y. Shimizu, R.-L. Hong, M. Goto, Y. Namba, R.L. Ferris, M. Monga, M. Lynch, S. Hagihara, M. Tahara
Journal: Annals of Oncology (2016)
Do Results From Clinical Trials in Acute Myeloid Leukemia Reflect Clinical Reality? A Danish National Cohort Study of 813 Patients
Authors: Lene Sofie Granfeldt Ostgard, Mette Nørgaard, Henrik Sengeløv, Lars Kjeldsen, Lone S. Friis, Morten K. Jensen, Maria Kallenbach, Jan M. Norgaard
Journal: Blood (2012)
Adult Human Stem Cells Exert Therapeutic Effects To Repair Damaged Tissues in Xenograft Systems through Secretion of Trophic Factors Rather Than Direct Incorporation and Expansion.
Authors: Claus Sondergaard, David Hess, Ivana Rosova, Sarah Hohm, Louisa Wirthlin, Ryan Lahey, Matt Lindsey, Jon Walker, Gerhard Bauer, Ping Zhou, Jan Nolta
Journal: Blood (2007)
RNA-binding protein PSPC1 promotes the differentiation-dependent nuclear export of adipocyte RNAs
Authors: Jiexin Wang, Prashant Rajbhandari, Andrey Damianov, Areum Han, Tamer Sallam, Hironori Waki, Claudio J. Villanueva, Stephen D. Lee, Ronni Nielsen, Susanne Mandrup, Karen Reue, Stephen G. Young, Julian Whitelegge, Enrique Saez, Douglas L. Black, Peter Tontonoz
Journal: Journal of Clinical Investigation (2017)

A highly orchestrated gene expression program establishes the properties that define mature adipocytes, but the contribution of posttranscriptional factors to the adipocyte phenotype is poorly understood. Here we have shown that the RNA-binding protein PSPC1, a component of the paraspeckle complex, promotes adipogenesis in vitro and is important for mature adipocyte function in vivo. Cross-linking and immunoprecipitation followed by RNA sequencing revealed that PSPC1 binds to intronic and 3'-untranslated regions of a number of adipocyte RNAs, including the RNA encoding the transcriptional regulator EBF1. Purification of the paraspeckle complex from adipocytes further showed that PSPC1 associates with the RNA export factor DDX3X in a differentiation-dependent manner. Remarkably, PSPC1 relocates from the nucleus to the cytoplasm during differentiation, coinciding with enhanced export of adipogenic RNAs. Mice lacking PSPC1 in fat displayed reduced lipid storage and adipose tissue mass and were resistant to diet-induced obesity and insulin resistance due to a compensatory increase in energy expenditure. These findings highlight a role for PSPC1-dependent RNA maturation in the posttranscriptional control of adipose development and function.
Middle East Respiratory Syndrome
Authors: Yaseen M. Arabi, Hanan H. Balkhy, Frederick G. Hayden, Abderrezak Bouchama, Thomas Luke, J. Kenneth Baillie, Awad Al-Omari, Ali H. Hajeer, Mikiko Senga, Mark R. Denison, Jonathan S. Nguyen-Van-Tam, Nahoko Shindo, Alison Bermingham, James D. Chappell, Maria D. Van Kerkhove, Robert A. Fowler
Journal: New England Journal of Medicine (2017)

Between September 2012 and January 20, 2017, the World Health Organization (WHO) received reports from 27 countries of 1879 laboratory-confirmed cases in humans of the Middle East respiratory syndrome (MERS) caused by infection with the MERS coronavirus (MERS-CoV) and at least 659 related deaths. Cases of MERS-CoV infection continue to occur, including sporadic zoonotic infections in humans across the Arabian Peninsula, occasional importations and associated clusters in other regions, and outbreaks of nonsustained human-to-human transmission in health care settings. Dromedary camels are considered to be the most likely source of animal-to-human transmission. MERS-CoV enters host cells after binding the dipeptidyl peptidase 4 (DPP-4) receptor and the carcinoembryonic antigen–related cell-adhesion molecule 5 (CEACAM5) cofactor ligand, and it replicates efficiently in the human respiratory epithelium. Illness begins after an incubation period of 2 to 14 days and frequently results in hypoxemic respiratory failure and the need for multiorgan support. However, asymptomatic and mild cases also occur. Real-time reverse-transcription–polymerase-chain-reaction (RT-PCR) testing of respiratory secretions is the mainstay for diagnosis, and samples from the lower respiratory tract have the greatest yield among seriously ill patients. There is no antiviral therapy of proven efficacy, and thus treatment remains largely supportive; potential vaccines are at an early developmental stage. There are multiple gaps in knowledge regarding the evolution and transmission of the virus, disease pathogenesis, treatment, and prospects for a vaccine. The ongoing occurrence of MERS in humans and the associated high mortality call for a continued collaborative approach toward gaining a better understanding of the infection both in humans and in animals.MERS-CoV was first identified in September 2012 in a patient from Saudi Arabia who had hypoxemic respiratory failure and multiorgan illness. Subsequent cases have included infections in humans across the Arabian Peninsula, occasional importations and associated clusters in other regions, and outbreaks of nonsustained human-to-human transmission in health care settings (Fig. 1).
Is Oral Route an Option for Intravenous Human Immunoglobulin As an Adjunctive Treatment for Recurrent Diarrhea in Immunocompromised Pediatric Patients? Extended Follow-up
Authors: Pere Soler-Palacin, Jacques G. Riviere, Olga Oller, Aurora Fernandez-Polo, Marina Garcia-Prat, Marina Garcia-Prat, Andrea Martin-Nalda
Journal: Journal of Allergy and Clinical Immunology (2017)
Observer variation in FDG PET-CT for staging of lymphoma
Authors: M. Hofman, N. C. Smeeton, S. C. Rankin, S. C. Rankin, T. Nunan, M. J. O'Doherty
Journal: Journal of Clinical Oncology (2009)

8557 Background: Evaluation of observer agreement is fundamental in the assessment of any new imaging modality. While many studies demonstrate high accuracy of positron emission tomography (PET) for lymphoma staging, few assess observer variation. This study aims to quantify intra- and inter- observer agreement amongst experienced readers for staging lymphoma with PET-CT. Methods: One hundred consecutive patients with biopsy proven lymphoma deemed appropriate for staging with PET-CT were reported independently by three experienced readers, with two readers reviewing each series a second time. Primary outcome variables were agreement of Ann Arbor stage, number of nodal regions and presence of extra-nodal involvement. Secondary outcome variables were agreement of specific nodal and extra-nodal sites. Weighted kappa (κ w ) was used to compare ratings from two readers, and interpreted according to the Landis-Koch benchmarks. Interclass-correlation coefficient (ICC) was used to assess total of nodal regions involved. Results: Both intra- and inter-reporter agreement for Ann-Arbor stage (κ w =0.79–0.91), total number of nodal regions involved (ICC=0.83–0.93) and presence of extra-nodal disease (κ=0.74–0.86) was substantial or almost perfect. High agreement was also observed for specific nodal regions (κ w &gt;0.60) except hilar (κ w =0.56–0.63) and infra-clavicular regions (κ w =0.14–0.37). Conclusions: Amongst experienced readers there was a high level of agreement utilising PET-CT for lymphoma staging. This complements other studies demonstrating high accuracy and supports use of PET-CT as a robust non-invasive staging tool. Further research is needed to evaluate reporter variability for restaging during and after completion of chemotherapy. [Table: see text] No significant financial relationships to disclose.
GENT-10. CHARACTERIZING AND TARGETING PDGFRA ALTERATIONS IN PEDIATRIC HIGH-GRADE GLIOMA
Authors: Carl Koschmann, Dan Zamler, Alan MacKay, Dan Robinson, Yi-Mi Wu, Robert Doherty, Bernard Marini, Dustin Tran, Hugh Garton, Karin Muraszko, Patricia Robertson, Marcia Leonard, Lili Zhao, Dale Bixby, Luke Peterson, Sandra Camelo-Piragua, Chris Jones, Rajen Mody, Pedro R. Lowenstein, Maria G. Castro
Journal: Neuro-Oncology (2016)

Pediatric high-grade glioma (HGG, WHO Grade III and IV) is a devastating brain tumor with a median survival of less than two years. PDGFRA is frequently mutated/ amplified in pediatric HGG. Previous analysis by FISH hybridization did not reveal any prognostic impact of PDGFRA amplification in tumors, but its significance has not been assessed in a large genomic dataset. We hypothesize that alterations of PDGFRA promote distinct prognostic and treatment implications in pediatric HGG. In order to characterize the impact of PDGFR pathway alterations, we integrated genomic data from pediatric HGG patients (n=290) from multiple pediatric datasets and sequencing platforms. Analysis of our pediatric HGG genomic dataset showed that PDGFRA mutation, but not amplification, was associated with older age in pediatric HGG (P= <0.0001). PDGFRA amplification was associated with worse prognosis, overall (P=0.0058) and in non-brainstem HGG (P=0.021). There were no pediatric patients with PDGFRA-amplified HGG that survived longer than two years. Additionally, we performed paired molecular profiling (germline/ tumor/ primary cell culture) and targeting of an infant thalamic HGG with amplification and outlier increased expression of PDGFRA. These cells were treated with traditional cytotoxic agents and tyrosine kinase inhibitors known to target PDGFR signaling. Dasatinib inhibited proliferation most effectively. In summary, integration of the largest genomic dataset of pediatric HGG to date allowed us to highlight that PDGFRA mutation is found in older pediatric patients and that PDGFRA amplification is prognostic in non-brainstem HGG. Our work highlights the importance of genomic characterization of pediatric HGG. Future precision-medicine based clinical trials for pediatric patients with PDGFRA-altered HGG should consider the optimized delivery of tyrosine kinase inhibitors. Supported by St. Baldrick’s Fellowship and Alex’s Lemonade Stand/ Northwest Mutual Young Investigator Award to CK, NIH grants to MGC and PRL, and NHS grants to AM and CJ.
Reactive Hemophagocytic Syndrome after Hematopoietic Stem Cell Transplantation: A Multicenter Retrospective Study on Behalf of the Francophone Society of Stem Cell Transplantation and Cellular Therapy (SFGM-TC)
Authors: Federico Simonetta, Hélène Labussière-Wallet, Maciej J Machaczka, Flore Sicre de Fontbrune, Michael Medinger, Sylvain Chantepie, Tony Marchand, Stavroula Masouridi-Levrat, Marie-Thérèse Rubio, Oumedaly Reman, Nathalie Dhedin, Loic Fouillard, Olivier Lambotte, Lionel Galicier, Paul Coppo, Jakob Passweg, Ibrahim Yakoub-Agha, Regis Peffault De Latour, Yves Chalandon
Journal: Blood (2016)
Medical management of pulmonary carcinoid tumors.
Authors: Curtis Robert Chong, Lori J. Wirth, Aileen B. Chen, Lynette M. Sholl, Pasi Antero Janne, Bruce E Johnson
Journal: Journal of Clinical Oncology (2013)

e18512 Background: The optimal medical management of pulmonary carcinoid tumors, which comprise 1-2% of all lung cancers, remains to be determined. Methods: We conducted a retrospective review of patients with typical and atypical pulmonary carcinoid tumors treated at our institution between 1990-present. Results: We identified 29 patients treated with chemotherapy, including 21 patients with metastatic disease (19 atypical, 2 typical), and 8 patients treated with adjuvant platinum-etoposide chemoradiation (6 atypical, 2 typical, 6 stage IIIA, 2 stage IIB). At an average follow-up of 12 months there were two recurrences in the 8 patients receiving adjuvant treatment, both of whom had atypical carcinoid (1 stage IIIA, 1 stage IIB). Of patients with metastatic disease, the principal sites of metastasis were the liver (70%), bone (40%), and brain (25%); median survival after diagnosis of metastatic disease was 3.8 y with a 5 y survival of 37%. Regimens showing efficacy in metastatic disease include octreotide (92% stable disease), etoposide-cisplatin (25% disease control, 2 partial response, 1 stable disease), and temozolomide (44% disease control, 2 partial responses, 2 stable disease). Conclusions: These results support our previous finding that pulmonary carcinoid tumors are responsive to chemotherapy and that adjuvant therapy should be offered to patients with stage II or IIIA resected disease.