tbuckley/cabot-search huggingface dataset:
Are Retrospective Self-reports Accurate Representations or Existential Recollections?
Authors: Cathy Spatz Widom
Journal: JAMA Psychiatry (2019)

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Inhibitory effects of midostaurin and avapritinib on myeloid progenitors derived from patients with KIT D816V positive advanced systemic mastocytosis
Authors: Johannes Lübke, Nicole Naumann, Sebastian Kluger, Juliana Schwaab, Georgia Metzgeroth, Erica Evans, Alexandra K. Gardino, Christoph Lengauer, Wolf-Karsten Hofmann, Alice Fabarius, Nicholas C. P. Cross, Andreas Reiter, Mohamad Jawhar
Journal: Leukemia (2019)

Advanced systemic mastocytosis (advSM) is characterized by the presence of an acquired KIT D816V mutation in >90% of patients. In the majority of patients, KIT D816V is not only detected in mast cells but also in other hematopoietic lineages. We sought to investigate the effects of the KIT-inhibitors midostaurin and avapritinib on single-cell-derived myeloid progenitor cells using granulocyte-macrophage colony-forming-units of patients with KIT D816V positive advSM. Colonies obtained prior to treatment were incubated in vitro with midostaurin (n = 10) or avapritinib (n = 11) and showed a marked reduction (≥50%) of KIT D816V positive colonies in 3/10 (30%) and 7/11 (64%) patient samples, respectively. Three of those 7 (43%) avapritinib responders were resistant to midostaurin in both, in vitro and in vivo. Colonies from four patients with high-risk molecular profile and aggressive clinical course were resistant to both drugs. The in vitro activity of midostaurin strongly correlated with clinical and molecular responses, e.g., relative reduction of KIT D816V allele burden and the proportion of KIT D816V positive colonies obtained after six months midostaurin-treatment in vivo. We conclude that the colony inhibition assay provides useful information for prediction of responses on midostaurin and that avapritinib has a superior in vitro activity compared to midostaurin.
Abstract P6-19-06: Breast conservation surgery in male breast cancer: A systematic literature review
Authors: CS Fisher, L de la Cruz, S Joshi, T-J Mah, S Blankenship, P Thiruchelvam
Journal: Cancer Research (2019)

Abstract BACKGROUND Male breast cancer (BC) incidence is low and management is extrapolated from female BC. Breast conservation surgery (BCS) is commonly used for female BC, however, mastectomy remains the most frequently used surgical procedure for male breast cancer. We performed a literature review to assess the use of BCS in male BC as well as outcomes following BCS. METHODS A systematic literature review identified peer-reviewed articles in PubMed evaluating male BC and surgery. Abstracts were screened to identify studies that measured overall survival (OS), disease-free survival (DFS), or local recurrence (LR) in patients undergoing BCS. For all studies, we extracted the total number of patients and number of BCS cases. Of patients undergoing BCS, we further extracted mean age, mean follow-up time, clinical stage, type of axillary surgery [sentinel lymph node biopsy (SLNB), axillary lymph node dissection (ALND)], radiation therapy, hormonal therapy, and chemotherapy. Weighted averages, based on number of patients in each study, were performed for LR, DFS and 5-year OS. The time period for LR and DFS was the duration of follow-up time for each study. RESULTS The literature search yielded 4341 articles. Twelve studies published from 1998 to 2016 met the inclusion criteria and were selected for the systematic literature review. Among the 12,616 male breast surgery cases included, 1,633 (12.9%) underwent BCS. Only patients who underwent BCS were included in our analysis. The mean follow-up time was 54.4 months and mean age was 62.4 with stage II as the most common presentation. Two studies reported that 50-71.4% of patients underwent SLNB and 4 studies reported ALND in 14.3-100%. Seven studies reported that adjuvant radiation therapy was administered in 12.0-100% of 474 total patients undergoing BCS. Four studies reported use of hormonal therapy in 73.8-100% of patients. Four studies reported use of chemotherapy in 25-66.7% of patients. Seven studies reported LR among 122 patients, with a weighted average 11.8%. Four studies reported on 5-year OS in 1511 patients, with a weighted average of 85.8%. CONCLUSION While less commonly used than mastectomy, BCS can be considered a safe alternative in the surgical treatment of male BC. We have demonstrated that the use of adjuvant radiation following BCS is variable in this patient group. Future research should focus on better standardization of local therapy for male BC and improved reporting of outcomes. Citation Format: Fisher CS, de la Cruz L, Joshi S, Mah T-J, Blankenship S, Thiruchelvam P. Breast conservation surgery in male breast cancer: A systematic literature review [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P6-19-06.
Extracellular DNA, Neutrophil Extracellular Traps, and Inflammasome Activation in Severe Asthma
Authors: Marrah E. Lachowicz-Scroggins, Eleanor M. Dunican, Annabelle R. Charbit, Wilfred Raymond, Mark R. Looney, Michael C. Peters, Erin D. Gordon, Prescott G. Woodruff, Emma Lefrançais, Brenda R. Phillips, David T. Mauger, Suzy A. Comhair, Serpil C. Erzurum, Mats W. Johansson, Nizar N. Jarjour, Andrea M. Coverstone, Mario Castro, Annette T. Hastie, Eugene R. Bleecker, Merritt L. Fajt, Sally E. Wenzel, Elliot Israel, Bruce D. Levy, John V. Fahy
Journal: American Journal of Respiratory and Critical Care Medicine (2019)

Extracellular DNA (eDNA) and neutrophil extracellular traps (NETs) are implicated in multiple inflammatory diseases. NETs mediate inflammasome activation and IL-1β secretion from monocytes and cause airway epithelial cell injury, but the role of eDNA, NETs, and IL-1β in asthma is uncertain.
Imported Toxin-Producing Cutaneous Diphtheria — Minnesota, Washington, and New Mexico, 2015–2018
Authors: Jayne Griffith, Catherine H. Bozio, Amy J. Poel, Kelly Fitzpatrick, Chas A. DeBolt, Pamela Cassiday, Cynthia Kenyon, Chad Smelser, Paula Snippes Vagnone, Karissa Culbreath, Anna M. Acosta
Journal: MMWR Morbidity and Mortality Weekly Report (2019)

From September 2015 to March 2018, CDC confirmed four cases of cutaneous diphtheria caused by toxin-producing Corynebacterium diphtheriae in patients from Minnesota (two), Washington (one), and New Mexico (one). All patients had recently returned to the United States after travel to countries where diphtheria is endemic. C. diphtheriae infection was not clinically suspected in any of the patients; treating institutions detected the organism through matrix-assisted laser desorption/ionization-time-of-flight mass spectrometry (MALDI-TOF) testing of wound-derived coryneform isolates. MALDI-TOF is a rapid screening platform that uses mass spectrometry to identify bacterial pathogens. State public health laboratories confirmed C. diphtheriae through culture and sent isolates to CDC's Pertussis and Diphtheria Laboratory for biotyping, polymerase chain reaction (PCR) testing, and toxin production testing. All isolates were identified as toxin-producing C. diphtheriae. The recommended public health response for cutaneous diphtheria is similar to that for respiratory diphtheria and includes treating the index patient with antibiotics, identifying close contacts and observing them for development of diphtheria, providing chemoprophylaxis to close contacts, testing patients and close contacts for C. diphtheriae carriage in the nose and throat, and providing diphtheria toxoid-containing vaccine to incompletely immunized patients and close contacts. This report summarizes the patient clinical information and response efforts conducted by the Minnesota, Washington, and New Mexico state health departments and CDC and emphasizes that health care providers should consider cutaneous diphtheria as a diagnosis in travelers with wound infections who have returned from countries with endemic diphtheria.
Inadvertent Injection of a Breast Implant During Lymphoscintigraphy
Authors: Mark S. Manganaro, John D. Millet, Matthew S. Manganaro
Journal: Clinical Nuclear Medicine (2019)

A 34-year-old woman with history of bilateral saline implants, invasive ductal carcinoma of the right breast, and suspicious left breast calcifications was referred for left breast lymphoscintigraphy before bilateral mastectomy. A total of 3.2 mCi of Tc-filtered sulfur colloid was administered with 3 subdermal injections in the superior, lateral, and inferior periareolar left breast in the late afternoon preceding the day of surgery. Imaging identified radiotracer uptake within a dense, circular area deep to the injection sites within the left breast, compatible with implant puncture and radiotracer administration within the indwelling breast implant.
HSR19-078: Human Papillomavirus Status and Survival Among Patients With Oropharyngeal Cancer: Analyses of a United States Health System
Authors: Himani Aggarwal, Li Li, Gebra Cuyun Carter, Kathy Fraeman, Ariel Berger
Journal: Journal of the National Comprehensive Cancer Network (2019)

Background: The incidence of oropharyngeal cancer (OPC) due to tobacco and alcohol, respectively, has been declining, while that linked to human papilloma virus (HPV) has been rising. Epidemiologic, biologic, and prognostic characteristics of OPC differ by HPV-status. This study compared overall survival (OS) among HPV-positive and -negative patients with OPC in a real-world setting. Methods: This retrospective observational study used electronic medical records data from the Geisinger Health System to select patients diagnosed with OPC between January 1, 2010 and September 30, 2015. Patients were designated as HPV-positive if the HPV or P16 test closest to the diagnosis date was positive. All other patients were deemed HPV-negative. Descriptive statistics and relevant statistical tests were used to compare baseline characteristics by HPV status; survival by HPV status was examined using Kaplan–Meier methods and multivariable Cox models. Results: In this study, 152 patients met all selection criteria; 110 (72.4%) were HPV-positive. HPV-positive patients were more likely to be men (89.1% vs 73.8%; P =.019) and to have lymph node involvement (88.2% vs 59.5%; P =.0008); they were less likely to have cerebrovascular disease (6.9% vs. 23.5%; P =.01), or distant metastases (1.8% vs 9.5%; P =.029) vs HPV-negative patients. Among HPV-positive patients, 75.5%, 12.7%, and 10.9% had squamous cell carcinoma NOS, basaloid squamous cell carcinoma, and squamous cell carcinoma large cell non-keratinizing, respectively; corresponding values for HPV-negative patients were 85.7%, 0.0%, and 2.4%, respectively ( P =.0013). HPV-positive patients were nominally younger than HPV-negative patients (median: 58 vs 61 years; P =.085). Log-rank test showed OS of HPV-positive patients (median OS from treatment initiation: not reached) is higher than of HPV-negative patients (median OS: 3.7 years; P =.002). In multivariable analyses, HPV-negative status was associated with increased mortality risk ( P =.0035); other significant risk factors included alcohol use, diabetes, and distant metastases. Conclusions: HPV-positive status was associated with a decreased risk of mortality among OPC patients in this study. Despite the small sample size and potential violation of assumption of proportional hazard rate, this study underscores the prognostic implication of HPV status in OPC, which may have important ramifications in optimizing treatment decisions among this patient population.
Pharmacy services at the PyeongChang 2018 Olympic and Paralympic Winter Games
Authors: Mark Stuart, Young In Kwon, Sandy Jeong Rhie
Journal: British Journal of Sports Medicine (2019)

Pharmacy services at large multisport events support safe and effective medication use. Our aim is to describe the contribution of pharmacists and to share the pharmacy experiences at the 2018 PyeongChang Olympic and Paralympic Games.The data collected included the accreditation details of patients and prescribers indicating: sport, country, athlete or non-athlete status, and prescription details including: medication, strength, frequency, length of treatment, for the period of the Olympic Games (1-26 February 2018) and the Paralympic Games (5-20 March 2018). The numbers of prescriptions dispensed were analysed by medication category, sports and country of the patient.A total of 5313 medication items were dispensed over the course of the Olympic and Paralympic Games (athletes: 670; non-athletes: 4615; unknown: 28), for a total of 2360 patients. 72 of 82 countries (87.8%) had fewer than 20 patient visits. The first high peak (Olympic: 5.0%; Paralympic: 7.3%) of daily volume of prescriptions were dispensed in the 2 days prior to the Olympic and the 1 day prior to Paralympic opening ceremonies. Therapeutic Use Exemption (TUE) and International Olympic Committee NeedlePolicy were well managed and compliant with the regulations.Pharmacy services at major multisport games include dispensing over 5000 prescriptions, supporting the TUE and IOC Needle Policy processes and providing clinical information to athletes and prescribers on drugs in sports and the World Anti-Doping Agency regulations of drugs prohibited in sport. During the PyeongChang 2018 Olympic and Paralympic Winter Games, pharmacists played a crucial role in delivering safe and effective pharmacy service based on their expert knowledge in antidoping and the clinical use of drugs in sport.
Targeting Multiple Myeloma with AMG 424, a Novel Anti-CD38/CD3 Bispecific T-cell–recruiting Antibody Optimized for Cytotoxicity and Cytokine Release
Authors: Christina L. Zuch de Zafra, Flordeliza Fajardo, Wendy Zhong, Matthew J. Bernett, Umesh S. Muchhal, Gregory L. Moore, Jennitte Stevens, Ryan Case, Joshua T. Pearson, Siyuan Liu, Patricia L. McElroy, Jude Canon, John R. Desjarlais, Angela Coxon, Mercedesz Balazs, Olivier Nolan-Stevaux
Journal: Clinical Cancer Research (2019)

Despite advances in the treatment of multiple myeloma, new therapies are needed to induce more profound clinical responses. T-cell-redirected lysis triggered by bispecific antibodies recruiting T cells to cancer cells is a clinically validated mechanism of action against hematologic malignancies and CD38 is a tumor-associated antigen with near-universal expression in multiple myeloma. Thus, an anti-CD38/CD3 bispecific T-cell-recruiting antibody has the potential to be an effective new therapeutic for multiple myeloma.Anti-CD38/CD3 XmAb T-cell-recruiting antibodies with different affinities for CD38 and CD3 were assessed in vitro and in vivo for their redirected T-cell lysis activity against cancer cell lines, their lower levels of cytokine release, and their potency in the presence of high levels of soluble CD38. Select candidates were further tested in cynomolgus monkeys for B-cell depletion and cytokine release properties.AMG 424 was selected on the basis of its ability to kill cancer cells expressing high and low levels of CD38 in vitro and trigger T-cell proliferation, but with attenuated cytokine release. In vivo, AMG 424 induces tumor growth inhibition in bone marrow-invasive mouse cancer models and the depletion of peripheral B cells in cynomolgus monkeys, without triggering excessive cytokine release. The activity of AMG 424 against normal immune cells expressing CD38 is also presented.These findings support the clinical development of AMG 424, an affinity-optimized T-cell-recruiting antibody with the potential to elicit significant clinical activity in patients with multiple myeloma.
Mitochondrial Transfer from Bone Marrow Mesenchymal Stem Cells to Motor Neurons in Spinal Cord Injury Rats via Gap Junction
Authors: Heyangzi Li, Chao Wang, Teng He, Tengfei Zhao, Ying-Ying Chen, Yue-Liang Shen, Xiaoming Zhang, Lin-Lin Wang
Journal: Theranostics (2019)

Recent studies have demonstrated that bone marrow mesenchymal stem cells (BMSCs) protect the injured neurons of spinal cord injury (SCI) from apoptosis while the underlying mechanism of the protective effect of BMSCs remains unclear. In this study, we found the transfer of mitochondria from BMSCs to injured motor neurons and detected the functional improvement after transplanting. Methods: Primary rat BMSCs were co-cultured with oxygen-glucose deprivation (OGD) injured VSC4.1 motor neurons or primary cortical neurons. FACS analysis was used to detect the transfer of mitochondria from BMSCs to neurons. The bioenergetics profiling of neurons was detected by Extracellular Flux Analysis. Cell viability and apoptosis were also measured. BMSCs and isolated mitochondria were transplanted into SCI rats. TdT-mediated dUTP nick end labelling staining was used to detect apoptotic neurons in the ventral horn. Immunohistochemistry and Western blotting were used to measure protein expression. Re-myelination was examined by transmission electron microscope. BBB scores were used to assess locomotor function. Results: MitoTracker-Red labelled mitochondria of BMSCs could be transferred to the OGD injured neurons. The gap junction intercellular communication (GJIC) potentiator retinoid acid increased the quantity of mitochondria transfer from BMSCs to neurons, while GJIC inhibitor 18β glycyrrhetinic acid decreased mitochondria transfer. Internalization of mitochondria improved the bioenergetics profile, decreased apoptosis and promoted cell survival in post-OGD motor neurons. Furthermore, both transplantation of mitochondria and BMSCs to the injured spinal cord improved locomotor functional recovery in SCI rats. Conclusions: To our knowledge, this is the first evidence that BMSCs protect against SCI through GJIC to transfer mitochondrial to the injured neurons. Our findings suggested a new therapy strategy of mitochondria transfer for the patients with SCI.
QIM19-115: Barriers and Trends in Cancer Patients` Pain Management in Qatar: A Randomized Cohort Prospective Study
Authors: Rehab Abdelwahab, Anas Hamad, Randa Al Okka, Mohd A. Wahid, Khalil Ullah Shibli, Wael Saleem, Ahmed El Geziry, Fathi Saleh, Kakil Rasul, Shereen Elazzazy
Journal: Journal of the National Comprehensive Cancer Network (2019)

Background: Up to 70% of cancer patients experience pain during the course of illness (Fallon, Support Care Cancer 2008). Studies showed that 40%–50% of patients with cancer pain receive insufficient analgesia due to different factors. Physicians are facing different challenges to accurately assess pain which might affect drug selection and pain control (Beyeler et al, Support Care Cancer 2008; Salminen et al, Support Cancer Care 2008; Stewart, Ulster Med J 2014). In NCCCR, treating physicians may prescribe analgesics to their patients or refer them to the Pain Management Service (PMS) based on their evaluation or as requested by patients. This study explored the factors which might lead to undertreatment of cancer pain in Qatar. In addition, focused on cancer patients’ pain management satisfaction and PMS awareness. Objectives: To assess the existing PMS at NCCCR from patients' perspective. Methods: In this study, we evaluated patients’ pain management perception via a validated written (Arabic and English) questionnaire (SF-MPQ-2; available at https://eprovide.mapi-trust.org/instruments/short-form-mcgill-pain-questionnaire#DESCRIPTIVE_INFORMATION ; Gauthier et al, J Pain 2014) and a structured interview by outpatient pharmacists at a single point of time, to assess patients` awareness towards the PMS, if they are receiving pain medications or not, if they are experiencing any pain regardless on pain medications or not, pain severity, and patients’ level of satisfaction towards their medications. A sample of 400 patients was randomly selected amongst the total cancer population visiting NCCCR Pharmacy over a specific period of time. Participants were consented and interviewed. Results: 400 patients agreed to participate; the median age was 50. Male to female ratio was 3 to 7. Data showed that 61% (245/400) of participants were not aware of the existence of the PMS. Only 20% (78/400) were aware and followed by PMS, with a satisfaction rate of 76% (59/78). Although 69% (276/400) of the patients were on pain medications, only 70% (191/276) were satisfied with their current medications. However from the satisfied patients, 57% (109/191) rated their pain as 4–10 at the time of interview (ATI). In the 31% (124/400) that were not taking any pain medications; 77% (96/124) didn’t know about the PMS, and 44% (55/124) had 4–10 pain severity (ATI). Conclusion: These findings provide clear evidence that factors leading to undertreating of cancer pain in Qatar might be unawareness of the PMS existence, pain treatment by unspecialized physicians, and patients’ reluctance to express their pain. Thus, raising patients’ awareness and standardizing the referral criteria can improve pain control and quality of life amongst cancer patients.
Dicer1 Phosphomimetic Promotes Tumor Progression and Dissemination
Authors: Neeraj K. Aryal, Vinod Pant, Amanda R. Wasylishen, Bobbie J. Rimel, Laura Baseler, Adel K. El-Naggar, David G. Mutch, Paul J. Goodfellow, Swathi Arur, Guillermina Lozano
Journal: Cancer Research (2019)

Dicer1 functions as a tumor suppressor in mouse models. In humans, somatic mutations are associated with many cancers in adults, and patients with DICER1 syndrome with DICER1 germline mutations are susceptible to childhood cancers. Dicer is phosphorylated by the ERK-MAP kinase pathway and because this pathway is activated in human cancers, we asked whether phosphorylated Dicer1 contributed to tumor development. In human endometrioid cancers, we discovered that phosphorylated DICER1 is significantly associated with invasive disease. To test a direct involvement of Dicer1 phosphorylation in tumor development, we studied mice with phosphomimetic alterations at the two conserved serines phosphorylated by ERK and discovered that a phosphomimetic Dicer1 drives tumor development and dissemination in two independent murine cancer models (KRas+/LA1 and p53+/- ). Our findings demonstrate that phosphomimetic Dicer1 promotes tumor development and invasion. SIGNIFICANCE: This work highlights the relevance of Dicer1 phosphorylation in mammalian tumor development and dissemination.