tbuckley/cabot-search huggingface dataset:
AB0423 NEUROPSYCHIATRIC OUTCOME OF CHILDREN BORN TO WOMEN WITH SYSTEMIC LUPUS ERYTHEMATOSUS (SLE) WOMEN AND EXPOSED IN UTERO TO AZATHIOPRINE: A CASE-CONTROL STUDY.
Authors: M. G. Lazzaroni, F. Crisafulli, I. Debeni, C. Nalli, L. Andreoli, J. Galli, A. Merlini, E. Fazzi, F. Franceschini, A. Tincani
Journal: Annals of the Rheumatic Diseases (2020)

Background: A possible increase in neurodevelopmental (ND) and learning disorders (LD) in the offspring of mothers affected by SLE have been suggested in some studies, along with the identification of different possible risk factors. Azathioprine (AZA) is commonly used during pregnancy, based on its non-teratogenicity and extended experience in women with different diseases. However, a few small studies suggested an association between in utero exposure to AZA and possible increased frequency of ND/LD in children, indirectly derived from increased request of supportive educational services. Objectives: To evaluate the medium-long term outcome in terms of ND/LD in children of school age (≥6 years) born to SLE women treated with AZA during pregnancy, as compared to that of children born to SLE mothers not treated with AZA during pregnancy. Methods: Data from our Pregnancy Clinic registry were collected for prospectively followed pregnancies of SLE women treated with AZA (cases) and compared to pregnancies of SLE women not treated with AZA (controls), that were matched for age at pregnancy, presence of renal involvement and aPL positivity. SLE patients (cases and controls) were interviewed by phone to collect data about their children, focusing on the presence of ND/LD certified by Neuropsychiatrists. Results: Data were collected for 14 SLE mothers in the AZA group and 31 in the control group, with similar age at pregnancy (30.3±5.21 vs 31.4±4.70 years, p:0.45) and frequency of renal involvement (50.0% vs 44.1%, p:0.77), aPL positivity (33.3% vs 29.4%, p:0.76) and anti-Ro/SSA positivity (27.8% vs. 26.5%, p:0.55). A SLE flare during pregnancy was more frequently recorded in the AZA group (27.8% vs. 2.94%, p:0.02). Other medications included HCQ (55.6% vs. 70.6%, p:0.36) and corticosteroids (100% vs 79.4%, p:0.08). We collected data for 18 children in the AZA group and 34 children in the control group, that had a similar mean age at the time of the interview (12.7±4.80 vs. 12.9±5.61 years, p:0.91). The two groups had also similar gestational age (37.4±2.20 weeks vs. 38.0±1.29 weeks, p:0.23), birth weight (3003±433 g vs 3011±453 g, p:0.95) and rate of male sex (61.1% vs 44.1%, p:0.38). We recorded similar frequency of ND/LD in the two groups. In particular, a ND was present in 2/18 (11.1%) of children exposed to AZA vs. 2/34 (5.88%) in the control group (p:0.60). A LD was present in 1/18 cases (5.56%) and 6/34 controls (17.6%) (p:0.40). Conclusion: The medium-long term outcome of children born to SLE mothers in the whole cohort was characterized by the presence of ND in 4/54 (7.69%) and LD in 7/52 (13.5%). ND/LD do not seem to be related to in utero exposure to AZA. Disclosure of Interests: None declared
Abstract 11736: Semaphorin 3F Inhibits Transendothelial Monocyte Migration and Protects Against Atherosclerosis
Authors: Chutima Rattanasopa, Crystal Kok Yan Pang, Elisa Liehn, David Castano, Roshni R Singaraja, Sujoy Ghosh
Journal: Circulation (2019)

Objectives: Accumulating evidence suggests a role of semaphorin 3F (Sema3F) in heart development, immune responses and tumor growth inhibition. Genetic analyses suggest that semaphorin signaling as...
Peptide–Oleate Complexes Create Novel Membrane-Bound Compartments
Authors: Jesper S Hansen, Tuan Hiep Tran, Michele Cavalera, Sanchari Paul, Arunima Chaudhuri, Karin Lindkvist-Petersson, James C S Ho, Catharina Svanborg
Journal: Molecular Biology and Evolution (2020)

A challenging question in evolutionary theory is the origin of cell division and plausible molecular mechanisms involved. Here, we made the surprising observation that complexes formed by short alpha-helical peptides and oleic acid can create multiple membrane-enclosed spaces from a single lipid vesicle. The findings suggest that such complexes may contain the molecular information necessary to initiate and sustain this process. Based on these observations, we propose a new molecular model to understand protocell division.
Abstract 20304: Electron Leak Through Partial Loss of Ndufa13 in Mitochondrial Complex I Attenuates Ischemia-Reperfusion Injury Via Dimerized Stat3
Authors: Hengxun Hu, Jinliang Nan, Yong Sun, Dan Zhu, Xinyang Hu, Wei Zhu, Jian-an Wang
Journal: Circulation (2017)

Introduction: Electron leak from mitochondria can react with oxygen to generate reactive oxygen species (ROS) that either serve as signals for triggering various physiological process or cause seve...
Abstract 11997: Impact of Barriers to Physical Activity on Daily Step Counts in Pulmonary Hypertension Patients
Authors: Thomas Cascino, Elizabeth A Jackson, Caroline R Richardson, Vallerie V McLaughlin
Journal: Circulation (2018)

Introduction: Pulmonary hypertension (PH) patients have low levels of physical activity (PA) and poor health-related quality of life (HRQOL). Increased PA has been shown to have several health bene...
Disseminated Coccidioidomycosis Treated with Interferon-γ and Dupilumab
Authors: Monica Tsai, Timothy J. Thauland, Alden Y. Huang, Chantana Bun, Sean Fitzwater, Paul Krogstad, Emilie D. Douine, Stanley F. Nelson, Hane Lee, Maria I. Garcia-Lloret, Manish J. Butte
Journal: New England Journal of Medicine (2020)

We describe a case of life-threatening disseminated coccidioidomycosis in a previously healthy child. Like most patients with disseminated coccidioidomycosis, this child had no genomic evidence of any known, rare immune disease. However, comprehensive immunologic testing showed exaggerated production of interleukin-4 and reduced production of interferon-γ. Supplementation of antifungal agents with interferon-γ treatment slowed disease progression, and the addition of interleukin-4 and interleukin-13 blockade with dupilumab resulted in rapid resolution of the patient's clinical symptoms. This report shows that blocking of type 2 immune responses can treat infection. This immunomodulatory approach could be used to enhance immune clearance of refractory fungal, mycobacterial, and viral infections. (Supported by the Jeffrey Modell Foundation and the National Institutes of Health.).
Abstract 10873: Left Ventricular Function Recovery In Peripartum Cardiomyopathy: A Cardiovascular Magnetic Resonance Study By Myocardial T1 And T2 Mapping
Authors: Yaodan Liang, Yuanwei Xu, Weihao Li, Ke Wan, Qing Zhang, Yucheng Chen
Journal: Circulation (2019)

Background: Peripartum cardiomyopathy (PPCM) is a rare, pregnancy-associated disease with unclear etiology. Imaging characteristics on cardiovascular magnetic resonance (CMR) imaging is rarely stud...
TCR Repertoire Changes during TIL Expansion: Clonal Selection or Drifting?
Authors: Maria Lozano-Rabella, Alena Gros
Journal: Clinical Cancer Research (2020)

T-cell receptor β analysis can be exploited to monitor changes in the clonotypic composition of tumor-infiltrating lymphocyte (TIL) during ex vivo expansion in IL2. Oligoclonal TILs are often outgrown by infrequent clonotypes with greater proliferative capacity, and this could impact the antitumor reactivity of the expanded TILs.See related article by Poschke et al., p. 4289.
Metabolism in tumor microenvironment: Implications for cancer immunotherapy
Authors: Rongchen Shi, Yi‐Quan Tang, Hongming Miao
Journal: MedComm (2020)

Abstract Tumor microenvironment is a special environment for tumor survival, which is characterized by hypoxia, acidity, nutrient deficiency, and immunosuppression. The environment consists of the vasculature, immune cells, extracellular matrix, and proteins or metabolic molecules. A large number of recent studies have shown that not only tumor cells but also the immune cells in the tumor microenvironment have undergone metabolic reprogramming, which is closely related to tumor drug resistance and malignant progression. Tumor immunotherapy based on T cells gives patients new hope, but faces the dilemma of low response rate. New strategies sensitizing cancer immunotherapy are urgently needed. Metabolic reprogramming can directly affect the biological activity of tumor cells and also regulate the differentiation and activation of immune cells. The authors aim to review the characteristics of tumor microenvironment, the metabolic changes of tumor‐associated immune cells, and the regulatory role of metabolic reprogramming in cancer immunotherapy.
Tumor Microenvironment Immune Response in Pancreatic Ductal Adenocarcinoma Patients Treated With Neoadjuvant Therapy
Authors: Theodoros Michelakos, Lei Cai, Vincenzo Villani, Francesco Sabbatino, Filippos Kontos, Carlos Fernández-del Castillo, Teppei Yamada, Azfar Neyaz, Martin S Taylor, Vikram Deshpande, Tomohiro Kurokawa, David T Ting, Motaz Qadan, Colin D Weekes, Jill N Allen, Jeffrey W Clark, Theodore S Hong, David P Ryan, Jennifer Y Wo, Andrew L Warshaw, Keith D Lillemoe, Soldano Ferrone, Cristina R Ferrone
Journal: JNCI Journal of the National Cancer Institute (2020)

Abstract Background Neoadjuvant folinic acid, fluorouracil, irinotecan, and oxaliplatin (FOLFIRINOX) and chemoradiation have been used to downstage borderline and locally advanced pancreatic ductal adenocarcinoma (PDAC). Whether neoadjuvant therapy-induced tumor immune response contributes to the improved survival is unknown. Therefore, we evaluated whether neoadjuvant therapy induces an immune response towards PDAC. Methods Clinicopathological variables were collected for surgically resected PDACs at the Massachusetts General Hospital (1998-2016). Neoadjuvant regimens included FOLFIRINOX with or without chemoradiation, proton chemoradiation (25 Gy), photon chemoradiation (50.4 Gy), or no neoadjuvant therapy. Human leukocyte antigen (HLA) class I and II expression and immune cell infiltration (CD4+, FoxP3+, CD8+, granzyme B+ cells, and M2 macrophages) were analyzed immunohistochemically and correlated with clinicopathologic variables. The antitumor immune response was compared among neoadjuvant therapy regimens. All statistical tests were 2-sided. Results Two hundred forty-eight PDAC patients were included. The median age was 64 years and 50.0% were female. HLA-A defects were less frequent in the FOLFIRINOX cohort (P = .006). HLA class II expression was lowest in photon and highest in proton patients (P = .02). The FOLFIRINOX cohort exhibited the densest CD8+ cell infiltration (P &amp;lt; .001). FOLFIRINOX and proton patients had the highest CD4+ and lowest T regulatory (FoxP3+) cell density, respectively. M2 macrophage density was statistically significantly higher in the treatment-naïve group (P &amp;lt; .001) in which dense M2 macrophage infiltration was an independent predictor of poor overall survival. Conclusions Neoadjuvant FOLFIRINOX with or without chemoradiation may induce immunologically relevant changes in the tumor microenvironment. It may reduce HLA-A defects, increase CD8+ cell density, and decrease T regulatory cell and M2 macrophage density. Therefore, neoadjuvant FOLFIRINOX therapy may benefit from combinations with checkpoint inhibitors, which can enhance patients’ antitumor immune response.
AB1120 A TRIAD OF ULTRASOUND DETECTED HIGH-GRADE SYNOVITIS (MID TARSAL &amp; ANKLE JOINTS), HIGH-GRADE TENOSYNOVITIS IN (TIBIALIS POSTERIOR &amp; PERONEAL TENDONS) AND EROSIONS OF FIBULAR DISTAL END IS HIGHLY SUGGESTIVE OF CHARCOT ARTHROPATHY
Authors: M. A. Mortada, N. Ezz El_din, M. Hammad
Journal: Annals of the Rheumatic Diseases (2020)

Background: Charcot arthropathy poses many clinical challenges in its diagnosis and management. Ultrasonography (US) may be able to identify pathological changes in cases of Charcot arthropathy (1). Objectives: to characterize the ultrasonographicfeatures of patients in early pre-radiographic stages of neuropathic (Charcot) arthropathy. Methods: This is an extension of our previous study of ultrasonographic features Charcot ankle and foot (1). an observational studywhere 42 patients with neuropathic (Charcot) arthropathy of the footbetween January 2013 and october 2019 were enrolled. Inclusion criteria included: 1- Foot pain and swelling. 2- Typical MRI findings of Charcot arthropathy in the form of subcondral bone marrow edema with or without sub-chondralmicrofractures, joint effusion or soft-tissue inflammation. 3- Grade 0 Modified Eichenholtz classification system which means normal radiography of the affected foot. Patients with other forms of arthropathy that may mimic Charcot arthropathy e.g. gouty arthritis and rheumatoid arthritis, were excluded from the study.Ultrasonographic (grey scale and Doppler US) examination of mid-tarsal and ankle joints was performed according to the EULAR guidelines. Results: Synovitis and effusionatmid tarsal joints were found in all patients and to a lesser extent in the ankle joints. High degree Doppler activity at both ankle and mid tarsal joints could be observed in most patients. Bony erosions were also common as well as tendonitis. A triad of active synovitis (in mid tarsal joints and ankle joints), active tendonitis (of tibialis posterior and peroneal tendons) and erosions in the distal end of fibula was present in 40 (95.2%) cases. Conclusion: our study confirms the ability of ultrasonography to detect inflammatory lesions in early stages of Charcot arthropathy. References: [1]Mortada M, Hammad M, Ezzeldin N..Annals of the Rheumatic Diseases 2016;75:1231-1232. Disclosure of Interests: None declared
Clinical outcomes in a large pediatric cohort of patients with ependymoma treated with proton radiotherapy
Authors: Brooke E Patteson, Sujith Baliga, Benjamin V M Bajaj, Shannon M MacDonald, Beow Y Yeap, Sara L Gallotto, Megan J Giblin, Elizabeth A Weyman, David H Ebb, Mary S Huang, Robin M Jones, Nancy J Tarbell, Torunn I Yock
Journal: Neuro-Oncology (2020)

Abstract Background Treatment for pediatric ependymoma includes surgical resection followed by local radiotherapy (RT). Proton RT (PRT) enables superior sparing of critical structures compared with photons, with potential to reduce late effects. We report mature outcomes, patterns of failure, and predictors of outcomes in patients treated with PRT. Methods One hundred fifty patients (&amp;lt;22 y) with World Health Organization grades II/III ependymoma were treated with PRT between January 2001 and January 2019 at Massachusetts General Hospital. Demographic, tumor, and treatment-related characteristics were analyzed. Event-free survival (EFS), overall survival (OS), and local control (LC) were assessed. Results Median follow-up was 6.5 years. EFS, OS, and LC for the intracranial cohort (n = 145) at 7 years were 63.4%, 82.6%, and 76.1%. Fifty-one patients recurred: 26 (51.0%) local failures, 19 (37.3%) distant failures, and 6 (11.8%) synchronous failures. One hundred sixteen patients (77.3%) underwent gross total resection (GTR), 5 (3.3%) underwent near total resection (NTR), and 29 (19.3%) underwent subtotal resection (STR). EFS for the intracranial cohort at 7 years for GTR/NTR and STR was 70.3% and 35.2%. With multivariate analysis, the effect of tumor excision persisted after controlling for tumor location. There was no adverse effect on disease control if surgery to RT interval was within 9 weeks of GTR/NTR. Conclusion PRT is effective and safe in pediatric ependymoma. Similar to previous studies, GTR/NTR was the most important prognostic factor. Intervals up to 9 weeks from surgery to PRT did not compromise disease outcomes. There was no LC benefit between patients treated with &amp;gt;54 Gray relative biological effectiveness (GyRBE) versus ≤54 GyRBE.
Restoration of antitumor immunity through anti-MICA antibodies elicited with a chimeric protein
Authors: Nicolas Torres, María Victoria Regge, Florencia Secchiari, Adrián David Friedrich, Raúl Germán Spallanzani, Ximena Lucía Raffo Iraolagoitia, Sol Yanel Núñez, Jessica Mariel Sierra, Andrea Ziblat, María Cecilia Santilli, Nicolás Gilio, Evangelina Almada, Constanza Lauche, Romina Pardo, Carolina Inés Domaica, Mercedes Beatriz Fuertes, Kevin Patrick Madauss, Kenneth W Hance, Israel S Gloger, Vanesa Zylberman, Fernando Alberto Goldbaum, Norberto Walter Zwirner
Journal: Journal for ImmunoTherapy of Cancer (2020)

Natural killer and cytotoxic CD8+ T cells are major players during antitumor immunity. They express NKG2D, an activating receptor that promotes tumor elimination through recognition of the MHC class I chain-related proteins A and B (MICA and MICB). Both molecules are overexpressed on a great variety of tumors from different tissues, making them attractive targets for immunotherapy. However, tumors shed MICA and MICB, and the soluble forms of both (sMICA and sMICB) mediate tumor-immune escape. Some reports indicate that anti-MICA antibodies (Ab) can promote the restoration of antitumor immunity through the induction of direct antitumor effects (antibody-dependent cell-mediated cytotoxicity, ADCC) and scavenging of sMICA. Therefore, we reasoned that an active induction of anti-MICA Ab with an immunogenic protein might represent a novel therapeutic and prophylactic alternative to restore antitumor immunity.We generated a highly immunogenic chimeric protein (BLS-MICA) consisting of human MICA fused to the lumazine synthase from Brucella spp (BLS) and used it to generate anti-MICA polyclonal Ab (pAb) and to investigate if these anti-MICA Ab can reinstate antitumor immunity in mice using two different mouse tumors engineered to express MICA. We also explored the underlying mechanisms of this expected therapeutic effect.Immunization with BLS-MICA and administration of anti-MICA pAb elicited by BLS-MICA significantly delayed the growth of MICA-expressing mouse tumors but not of control tumors. The therapeutic effect of immunization with BLS-MICA included scavenging of sMICA and the anti-MICA Ab-mediated ADCC, promoting heightened intratumoral M1/proinflammatory macrophage and antigen-experienced CD8+ T cell recruitment.Immunization with the chimeric protein BLS-MICA constitutes a useful way to actively induce therapeutic anti-MICA pAb that resulted in a reprogramming of the antitumor immune response towards an antitumoral/proinflammatory phenotype. Hence, the BLS-MICA chimeric protein constitutes a novel antitumor vaccine of potential application in patients with MICA-expressing tumors.
“Women and children last”—effects of the covid-19 pandemic on reproductive, perinatal, and paediatric health
Authors: Peter von Dadelszen, Asma Khalil, Ingrid Wolfe, Nikos A Kametas, Patrick O’Brien, Laura A Magee
Journal: BMJ (2020)

The covid-19 pandemic has led to abrupt changes in health service delivery—from face-to-face to largely virtual interactions—to protect those vulnerable to the virus (beneficial) and to cope with staff shortages (potentially harmful). This was evidence based for those with substantial comorbidities; pregnant women have been labelled as vulnerable from the beginning. But, as Green says, the secondary harms to vulnerable children have not been properly considered. …
18F-FDG PET/CT Findings in a Patient With Neurosarcoidosis
Authors: Xueqi Chen, Guoqian Chen, Zhanli Fu, Qian Li
Journal: Clinical Nuclear Medicine (2020)

Abstract A 58-year-old woman experienced 4 months of headache, fatigue, and depression, as well as 1 week of confusion and hallucinations. 18 F-FDG PET/CT showed numerous hypermetabolic lesions in the pituitary gland and stalk, dura mater, glossopharyngeal nerve, and cauda equina, as well as in cervical and mediastinal lymph nodes. Surgical biopsy of the mediastinal lymph node confirmed the diagnosis of sarcoidosis. The follow-up 18 F-FDG PET/CT, performed at the eighth month after the treatment of glucocorticoids and immunosuppressive agents, demonstrated complete remission of the previous hypermetabolic lesions.
Salvage Therapies After 18F-Fluciclovine Detected Prostate Cancer Recurrences
Authors: Lindsay Hwang, Jeremy Paluch, Hossein Jadvar, Joseph R. England, Bhushan Desai, Leslie K. Ballas
Journal: Clinical Nuclear Medicine (2020)

Background 18 F-Fluciclovine is the most recent prostate cancer (PCa)–directed PET radiotracer approved by the US Food and Drug Administration for detection of recurrent PCa. We report the treatments and outcomes of patients at our institution with PCa recurrences detected on 18 F-fluciclovine PET/CT. Methods We identified men with recurrent PCa detected on 18 F-fluciclovine PET/CT performed between 2017 and 2018 who were previously treated definitively and analyzed their patterns of care and cancer-specific outcomes. Results We identified 28 men with recurrent PCa detected on 18 F-fluciclovine PET/CT. Twenty-three were initially treated with surgery and 13 also received postoperative radiation therapy (RT). Five patients were initially treated with definitive radiation. After surgery, the median time to 18 F-fluciclovine PET/CT was 67 months (median prostate-specific antigen [PSA] of 1.63 ng/mL). After RT, the median time to 18 F-fluciclovine PET/CT was 95 months with median PSA of 13.31 ng/mL. Six men recurred locally, 9 recurred in the pelvic nodes, 9 had distant nodal recurrences, and 4 had osseous metastases. Of the patients initially treated with surgery, 4 received salvage radiation and 3 received androgen deprivation therapy (ADT). Of the patients initially treated with surgery and postoperative RT, 3 received salvage pelvic nodal dissection, 4 received salvage radiation, and 2 received ADT. Of the patients initially treated with radiation, 4 received salvage ADT. All had PSA decline after salvage therapy. Conclusions 18 F-fluciclovine PET/CT can localize PCa recurrences, and subsequent salvage therapies appear effective with decreasing PSA. Longer follow-up will reveal if these diagnostic tests and subsequent therapies will improve PCa survival.