tbuckley/cabot-search huggingface dataset:
Pharmacokinetic and pharmacodynamic data of the immunotherapeutic TLR-9 agonist MGN1703 from healthy volunteers and cancer patients.
Authors: Manuel Schmidt, Kerstin Kapp, Detlef Oswald, Matthias Schroff, Burghardt Wittig, Alfredo Zurlo
Journal: Journal of Clinical Oncology (2015)

e14015 Background: The synthetic DNA-based immunomodulator MGN1703 acts as TLR-9 agonist by activating the innate and adaptive immune system. MGN1703 has already shown a good safety profile and a benefit compared to placebo in maintenance therapy of patients with metastatic colorectal carcinoma (mCRC) in a phase 2 clinical trial (MGN1703-C02, IMPACT). Methods: In addition to preclinical studies, a phase 1 trial (MGN1703-C01) including patients with solid tumors and the phase 2 IMPACT trial with mCRC patients, a single dose crossover placebo-controlled phase 1 trial, MGN1703-C04, was performed to assess cardiac and general safety, pharmacokinetics (PK) and pharmacodynamics (PD) in healthy volunteers (HV). Fourteen HV were randomized and 13 subjects completed the study receiving a subcutaneous dose of 60 mg MGN1703 during one treatment period and a single dose of placebo during the other. Results: Standard PK parameters like mean Tmax (14h), AUC0-t (5001 ng•hr/mL) and shape of the curve in the MGN1703-C04 trial were similar to single dose data obtained from cancer patients, with a mean Tmax of 10h and a mean AUC0-t of 5336 ng•hr/mL. Notably, multiple doses resulted in similar levels, but no accumulation of MGN1703. PD was mainly evaluated analyzing levels of the chemokine IP-10 in serum of the HV representing activation of the immune system. In MGN1703-C04 elevated IP-10 levels were detected in the serum of HV peaking at 24-48 hours after dosing with MGN1703. This clearly shows an expected delayed immune activation with respect to appearance of MGN1703 in the serum of the HV. The elevation of IP-10 is in keeping with data from cancer patients, in which an additional activation of innate immune cells – especially the up-regulation of CD169 on monocytes – after dosing with MGN1703 was observed. Conclusions: The data show obvious similarities between HV and cancer patients with respect to PK and PD – with the appearance of the immunomodulatory profile following-up downstream. This supports the twice weekly application scheme of ongoing cancer studies with MGN1703, e.g. the phase 3 IMPALA trial in mCRC patients. Further data will allow for evaluation of a possible association with clinical parameters. Clinical trial information: NCT01982747.
Eyes Wide Open — Examining the Data on Duty-Hour Reform
Authors: Lisa Rosenbaum, Daniela Lamas
Journal: New England Journal of Medicine (2019)

In a world moved by story, medicine — we like to believe — is still moved by measurement. That is why, when resident work-hour limits were implemented in 2003, catalyzed by the tragic death of Libby Zion, many in the medical community pointed out the paucity of evidence to support these sweeping changes.1 Although the harms of excess fatigue were evident,2 there was also concern that the policy conferred new risks, such as those associated with increased handoffs of care or inadequate educational exposure. When the Accreditation Council for Graduate Medical Education (ACGME) enacted even more stringent requirements in 2011, . . .
Abstract 20664: Early and Long-Term Outcomes of Acute Type a Aortic Dissection With Malperfusion According to Affected Organ System
Authors: Yan Li, Qian Chang, Xiangyang Qian, Xiaogang Sun, Cuntao Yu
Journal: Circulation (2016)

Introduction: The management of malperfusion in patients with acute type A aortic dissection (ATAAD) is controversial. We sought to evaluate outcomes, to determine the rate of resolution of malperf...
Prostate Imaging Reporting and Data System Version 2.1: 2019 Update of Prostate Imaging Reporting and Data System Version 2
Authors: Baris Turkbey, Andrew B. Rosenkrantz, Masoom A. Haider, Anwar R. Padhani, Geert Villeirs, Katarzyna J. Macura, Clare M. Tempany, Peter L. Choyke, Francois Cornud, Daniel J. Margolis, Harriet C. Thoeny, Sadhna Verma, Jelle Barentsz, Jeffrey C. Weinreb
Journal: European Urology (2019)
Abstract 18446: Receipt of Implantable Cardioverter-Defibrillator Among HIV+ and HIV- Veterans With Cardiomyopathy
Authors: Omid Fatemi, Pamela Karasik, Steven Singh, Chung-Chou Chang, Janet P Tate, Cynthia Gibert, Debra Benator, Richard Amdur, David Rimland, Stephen Gottlieb, Matthew Budoff, Kathleen McGinnis, Matthew Freiberg
Journal: Circulation (2013)

Introduction: Those with HIV infection (HIV+) are at increased risk for AMI, CHF, and sudden cardiac death compared to uninfected individuals (HIV-). HIV+ people also receive fewer cardiac procedures for AMI than HIV- people. Whether those with HIV with cardiomyopathy (CM) and low ejection fraction (EF) receive fewer implantable cardioverter defibrillators (ICD) compared to HIV- people with CM is not known. Hypothesis: We hypothesized (1) that HIV+ veterans with CM who qualify for an ICD (EF≤ 35%, NYHA II-III) will receive proportionally fewer ICDs than uninfected people with CM and (2) among those not receiving an ICD, mortality rates will be the highest for those with HIV infection. Methods: We analyzed data on 626 participants (44% HIV+) from the Veterans Aging Cohort Study Virtual Cohort, a prospective longitudinal of HIV+ and 1:2 matched HIV- Veterans, who were free of prevalent cardiovascular disease at study enrollment (n=97,685) and experienced an incident CM event with an associated EF ≤35% and/or left ventricular EF described as moderately to severely reduced between 2003-2009. Chi square testing was used to determine difference in the proportion of receipt of an ICD by HIV status. We calculated age and race adjusted mortality rates by HIV and ICD status. Results: Of the 626 participants with CM and low EF, 8.7% of HIV+ and 14.3% of HIV- patients received an ICD (p=0.04). Mortality rates (per 1000 person years) were: HIV+ no ICD (134, 95% CI=101-183), HIV+ with ICD (100, 95% CI=59-171), HIV- no ICD (73, 95% CI=53-103), HIV- with ICD (55, 95% CI=32-95). Among HIV+ and HIV-, there was no difference in mortality by ICD placement, p=0.66 and p=0.27, respectively. Mortality rates by HIV and ICD status over time are presented in Figure 1. Conclusions: Among Veterans with cardiomyopathy and low EF, receipt of ICD was lower among HIV+ compared to HIV- Veterans. Although not statistically significant, mortality rates were higher among those not receiving ICD, regardless of HIV status.
Abstract P170: Etiologies and Characteristics of Heart Failure for Human Immunodeficiency Virus (HIV)-Infected Persons and Uninfected Controls
Authors: Abdul A Abutaleb, Alexandra B Steverson, Faraz S Ahmad, Donald M Lloyd-Jones, Matthew J Feinstein
Journal: Circulation (2019)

Background: Human immunodeficiency virus (HIV) is associated with elevated risks for heart failure (HF). No studies to our knowledge have evaluated physician-adjudicated etiologies of HF (e.g., ischemic vs. non-ischemic) for HIV-infected persons in the modern ART era. Hypothesis: We hypothesize that non-ischemic etiologies of HF will comprise a greater proportion of overall HF for HIV-infected than uninfected persons. Methods: We performed a nested study of a cohort of HIV-infected and uninfected persons frequency-matched on age, sex, race, zip code of residence, and clinic location receiving care at an urban medical center between 1/1/2000 and 1/1/2018. Two trained MDs independently reviewed clinical notes, imaging and laboratory studies to determine contributing etiologies of HF for 128 patients (75 HIV-infected, 53 uninfected) with physician-adjudicated HF. Laboratory and imaging data as well as clinical notes from clinical care were used to classify etiologies of HF. HF was considered ischemic in etiology based on any prior angiogram demonstrating ≥70% epicardial coronary stenosis, stress testing consistent with ischemia, and/or documented previous myocardial infarction. Non-ischemic heart failure etiologies were subtyped based on pre-specified criteria as valvular, inflammatory, drug induced, hypertensive, infiltrative, hypertrophic, dilated, tachycardia induced, pulmonary hypertension, acute pulmonary embolism, stress cardiomyopathy (Takotsubo), renal volume overload, cirrhotic volume overload, or unspecified. More than one etiology of HF was possible if criteria were met for multiple etiologies. Results: Age at HF onset, sex, and race of HIV-infected vs. uninfected persons with HF were similar. Diabetes was less common among HIV-infected (30.7%) vs. uninfected (54.7%; p = 0.01) persons with HF. There were no significant differences in the proportion of HIV-infected vs. uninfected persons with ischemic vs. non-ischemic etiology of HF. Within non-ischemic HF, drug/toxin-induced cardiomyopathy was more common among HIV-infected (17.3%) than uninfected (5.7%) persons (p= 0.049). The left ventricular ejection fraction (LVEF) at HF diagnosis was significantly lower for HIV-infected (37.6% ± 16.4%) than uninfected (44.9% ± 18.3%; p =0.02) persons. The difference was apparent among persons with non-ischemic etiologies (38.0% ± 16.7% vs. 47.9% ± 17.8% for HIV-infected vs. uninfected; p=0.01), but not for those with ischemic etiologies of HF (37.1% ± 15.9% vs. 38.3% ± 18.3% for HIV-infected vs. uninfected; p=0.83). Conclusions: HIV-infected persons with HF had lower LVEF at HF diagnosis and were more likely to have toxin/drug-induced HF etiology than uninfected persons with HF. Future studies are needed to understand etiologies of and prognosis HF among HIV-infected persons to inform prevention and treatment.
Commensal Candida albicans Positively Calibrates Systemic Th17 Immunological Responses
Authors: Tzu-Yu Shao, W.X. Gladys Ang, Tony T. Jiang, Felicia Scaggs Huang, Heidi Andersen, Jeremy M. Kinder, Giang Pham, Ashley R. Burg, Brandy Ruff, Tammy Gonzalez, Gurjit K. Khurana Hershey, David B. Haslam, Sing Sing Way
Journal: Cell Host & Microbe (2019)
Pattern of neurological diseases at the Jimma University Medical Center neurology clinic, Jimma, Ethiopia, 2015–17: a survey of newly enrolled patients
Authors: A A Mldie
Journal: The Lancet Global Health (2019)

BackgroundThe burden of neurological diseases is higher in low-income and middle-income countries than in high-income countries. However, there is a paucity of literature on neurological diseases in sub-Saharan Africa, including Ethiopia. This study aims to describe the pattern of neurological diseases in newly enrolled patients at the neurology clinic of Jimma University Medical Center, Ethiopia.MethodsI collected data from records for newly enrolled neurological patients at Jimma University Medical Center neurology clinic between June 30, 2015, and June 30, 2017. I used a sampling technique to calculate the required sample size and I used SPSS version 24.0 for analysis.FindingsI accessed data from 2347 medical patients, 639 (27·2%) of whom were diagnosed with a neurological disorder, and data from 226 of these were included in final analysis. Most patients were male (143 [63·3%]). Mean age was 38·17 years (SD 17·75, range 15–80 years); 131 patients (57·9%) were aged between 15 and 40 years. The most common reasons for attending were: convulsion (96, 42·5%); hemiparesis (62, 27·4%); and pain, paraesthesia, and tingling sensation (24, 10·6%). Most patients (92, 40·7%) reported that they had had symptoms for more than 1 month; however, 43 (19%) presented within 24 h of symptom onset and 17 (7·5%) within 3 h. The most common conditions in the study group were epilepsy (95 patients, 42%), cerebrovascular disease (67, 29·6%), peripheral neuropathy (26, 11·5%), and Parkinson's disease (10, 4·4%). ICD-10 classification episodic and paroxysmal disorders were observed in 165 patients (72·9%); polyneuropathies and other disorders of the peripheral nervous system, and extrapyramidal and movement disorders were noted in 36 patients (15·9%).InterpretationThe causes of neurological morbidity in this low-resource setting are highly disabling but easily preventable and treatable. Hypertension was the most common comorbidity, especially in patients with stroke and peripheral neuropathy, so patients should be advised on lifestyle modification and be managed appropriately. Importantly, health-care policy makers should focus on planning for disease prevention and better management of common neurological disorders.FundingNone.
Prognostic value of genomic alterations in DNA damage response (DDR) genes in relapsed/advanced bladder cancer (BCa).
Authors: Ming Yin, Petros Grivas, Edmund Folefac, Steven K. Clinton, Hamid Emamekhoo, Sheldon L. Holder, Joseph J. Drabick, Michele Sue-Ann Woo, Monali K. Vasekar, Sumanta K. Pal, Monika Joshi
Journal: Journal of Clinical Oncology (2019)

427 Background: DDR defects play an important role in tumorigenesis, progression, treatment response and outcomes of BCa. We previously showed DDR mutations were associated with better prognosis in relapsed/advanced (TxN 2-3 M 0-1 ) BCa. In this study, we aimed to update and validate our findings in 3 independent datasets. Methods: 81 BCa patients (pts) who had FoundationOne tumor tissue genomic sequencing (315 cancer-related genes) were used as discovery dataset. Validation dataset 1 consisted of additional 91 pts with FoundationOne test. Validation dataset 2 consisted of 129 relapsed/advanced pts from TCGA BCa cohort. Overall survival (OS) was measured from time of initial BCa diagnosis to death or last follow-up. Cox proportional hazard regression analysis was performed to calculate the hazard ratio (HR) and 95% confidence interval (CI). Logistic regression analysis was performed to calculate odds ratio (OR) and 95% CI. A panel of 32 DDR genes (excluding ATM) were used for analyses because ATM mutation was a negative prognostic factor in our prior study. Results: DDR mutations were present in 76.5% (62/81), 40.7% (37/91) and 51.2% (66/129) pts of the 3 datasets. They were associated with longer OS (adjHR = 0.39, 95% CI 0.21–0.73, p = 0.003) in the discovery dataset, which were confirmed in two validation datasets (Validation 1: adjHR = 0.51, 95% CI 0.26–1.03, p = 0.059; Validation 2: adjHR = 0.62, 95% CI 0.39–0.97, p = 0.038). There was a trend for longer OS with increased number of DDR mutations in individual pts. Pts carrying ≥3 DDR mutations had the best prognosis (data not shown). In 144 cisplatin or carboplatin-treated pts pooled from the 3 cohorts, pts with DDR mutations were more likely to have objective response (OR = 1.81, 95% CI 0.85–3.92 for any DDR mutations; OR = 3.65, 95% CI 0.91–14.7 for ≥3 DDR mutations) and longer overall survival (HR = 0.61, 95% CI 0.38–0.98 for any DDR mutations; HR = 0.49, 95% CI 0.19–1.27 for ≥3 DDR mutations). Conclusions: DDR mutations (excluding ATM gene and especially ≥3) correlated with better outcomes in relapsed/advanced BCa. Further exploration of the deleterious nature and functional impact of alterations is critical along with prospective validation in ongoing trials.
Concentrations of Ustekinumab During Induction Therapy Associate With Remission in Patients With Crohn’s Disease
Authors: Ninon Soufflet, Gilles Boschetti, Xavier Roblin, Charlotte Cuercq, Nicolas Williet, Anne-Laure Charlois, Remi Duclaux-Loras, Pauline Danion, Anne Mialon, Mathias Faure, Stéphane Paul, Bernard Flourie, Stéphane Nancey
Journal: Clinical Gastroenterology and Hepatology (2019)
Abstract P090: Oculus/PlayStation IV VR Game for Youth to Build Food and Drink Selection Skills
Authors: Bradley Tanner
Journal: Circulation (2019)

Low-quality food and drink selection by today’s youth is well documented despite their ability to distinguish between low and high-quality foods. In addition, attention spans are short and youth are drawn to screens and gaming technology in our technology-focused culture. We are addressing the need to instill food and drink selection skills using a game-based behavioral intervention utilizing headset virtual reality (VR) technology. As a part of our Obesity Prevention project, we created Food Fight in VR. The virtual reality experience uses current PlayStation VR and Oculus headsets to offer an experience with high ecological validity by presenting high quality and accurate visual and auditory stimuli in a proper social and environmental context. In a realistic virtual world, the game immerses the young player in a believable world with altered game mechanics that control success and failure parameters. VR offers the young player an opportunity to experiment, try out new behaviors, fail, and build confidence. VR success then translates to real-world skills, feelings of empowerment, and improved selection behaviors. In our FoodFight Oculus or Playstation VR game, food cues bombard a young player wearing a virtual reality headset. They inspect each food or drink tossed at them. They quickly decide if the item is unhealthy (based on a diet they have chosen) and thus should be blocked (using a virtual tray), caught and thrown back, discarded, or hit away. Or, if they deem the food to be healthy, they grab it or pull it in with a food magnet and store it in the pantry or fridge for later. Visual cues, points, and active involvement make the process of selecting healthy foods and resisting unhealthy foods easy and fun. The game provides appropriate feedback for saving unhealthy food or rejecting healthy food. Eventually, they have collected enough food to build a healthy meal, win the game level, and proceed to the next level; winning and leveling up are strong motivators for this audience. In the long term, we seek to enhance internal control over the food selection process. Our short-term objectives are for the player to: 1) recognize healthy and unhealthy food, 2) reject unhealthy food/drink, 3) build confidence in rejecting unhealthy foods, and 4) recognize the foods required to build a balanced healthy meal consistent with a dietary guideline. Our future work involves expanding the game to highlight specific dietary requirements beyond the preparation of a single meal and include a wide range of diets such as Dash, Mediterranean, gluten-free, vegan, plant-based whole food, and vegetarian. Initial usability studies show a positive response and innovative use of game mechanics. A more robust evaluation is ongoing.
Burden of Morbidity Borne By Survivors of Multiple Myeloma (MM) Treated with Autologous Blood or Marrow Transplant (BMT) — Results of the BMT Survivor Study (BMTSS)
Authors: Mukta Arora, Yanjun Chen, Lindsey Hageman, Jessica Wu, Liton F. Francisco, Michelle Kung, Emily Ness, Mariel Parman, Daniel J. Weisdorf, Stephen J Forman, Saro H. Armenian, Smita Bhatia
Journal: Blood (2018)
Disparities in time to care for pancreatic cancer.
Authors: Marcus Smith Noel, Megan Herr, Kevin Fiscella
Journal: Journal of Clinical Oncology (2015)

e17587 Background: Pancreatic cancer affects more than 48,000 individuals each year and currently is the fourth leading cause of cancer death in the United States. Dismal outcomes are in large part due to advanced disease at the time of presentation; thus early detection and expedited specialty referrals are crucial for effective symptom management and treatment. Research is lacking on the challenges that arise in seeking a specialty referral, particularly in those patients who are poor and potentially underinsured. Methods: We conducted a single institutional retrospective analysis of all patients who were seen at our academic cancer center with a diagnosis of pancreatic adenocarcinoma from March 2011- July 2014. 75 charts were randomly selected and relevant data were extracted and divided into private versus Medicaid insurance. Medicare patients were distributed into one of these categories based upon presence or absence of dual Medicaid eligibility. Time to specialty care was defined as time of symptom onset to date patient was initially evaluated by a surgical or medical oncologist at the cancer center. Analyses were conducted using Kaplan-Meier methods and statistically significant differences were tested for using the Wilcoxon test. Results: 48 patients were classified as private insurance and 27 as Medicaid. Median age in each group was 60. Baseline sociodemographic characteristics for each group were; (the private group) 60% male, 92% white and 63% unresectable; (the Medicaid) 52% male, 81% white, and 60% unresectable. The most common presenting symptoms in the private group were pain 73%, weight loss 56%, and jaundice 38%, in the Medicaid group pain 70%, weight loss 37% and jaundice 41%. The median time to care in the private group was 9.8 weeks and in the Medicaid group 19 weeks, p = 0.0188. Conclusions: At our institution Medicaid patients with pancreatic cancer were faced with a significantly longer delay from symptom onset to oncologic evaluation compared to those with private insurance. Our next step is to expand this analysis using available national cancer registries to validate our findings and examine reasons for this difference. Findings could potentially inform design of an intervention to reduce delay in care with the ultimate goal of impacting survival.
Transmission of CMV, HTLV-1, and HIV through breastmilk
Authors: Andrew J Prendergast, Ameena E Goga, Catriona Waitt, Antoine Gessain, Graham P Taylor, Nigel Rollins, Elaine J Abrams, E. Hermione Lyall, Philippe Van de Perre
Journal: The Lancet Child & Adolescent Health (2019)
Bearing Witness and Finding Meaning
Authors: Emily J. Martin
Journal: JAMA (2019)

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