Medicine and Health Sciences Commons^™

Electronically Available Patient Claims Data Improve Models For Comparing Antibiotic Use Across Hospitals: Results From 576 Us Facilities, Katherine E Goodman, Lisa Pineles, Laurence S Magder, Deverick J Anderson, Elizabeth Dodds Ashley, Ronald E Polk, Hude Quan, William E Trick, Keith F Woeltje, Surbhi Leekha, Sara E Cosgrove, Anthony D Harris

2020-Current year OA Pubs

BACKGROUND: The Centers for Disease Control and Prevention (CDC) uses standardized antimicrobial administration ratios (SAARs)-that is, observed-to-predicted ratios-to compare antibiotic use across facilities. CDC models adjust for facility characteristics when predicting antibiotic use but do not include patient diagnoses and comorbidities that may also affect utilization. This study aimed to identify comorbidities causally related to appropriate antibiotic use and to compare models that include these comorbidities and other patient-level claims variables to a facility model for risk-adjusting inpatient antibiotic utilization.

METHODS: The study included adults discharged from Premier Database hospitals in 2016-2017. For each admission, we extracted facility, claims, and …

Enhancing Dopamine Tone Modulates Global And Local Cortical Perfusion As A Function Of Comt Val158met Genotype, Daniella J Furman, Ioannis Pappas, Robert L White 3rd, Andrew S Kayser, Mark D'Esposito

2020-Current year OA Pubs

The cognitive effects of pharmacologically enhancing cortical dopamine (DA) tone are variable across healthy human adults. It has been postulated that individual differences in drug responses are linked to baseline cortical DA activity according to an inverted-U-shaped function. To better understand the effect of divergent starting points along this curve on DA drug responses, researchers have leveraged a common polymorphism (rs4680) in the gene encoding the enzyme catechol-O-methyltransferase (COMT) that gives rise to greater (Met allele) or lesser (Val allele) extracellular levels of cortical DA. Here we examined the extent to which changes in resting cortical perfusion following the administration …

Development And Immunogenicity Of A Prototype Multivalent Group B Streptococcus Bioconjugate Vaccine, Jeremy A Duke, Amy V Paschall, Lloyd S Robinson, Cory J Knoot, Evgeny Vinogradov, Nichollas E Scott, Mario F Feldman, Fikri Y Avci, Christian M Harding

2020-Current year OA Pubs

Group B

Physical Activity And Fat-Free Mass During Growth And In Later Life, Klaas R Westerterp, Susan B Racette, Et Al.

2020-Current year OA Pubs

BACKGROUND: Physical activity may be a way to increase and maintain fat-free mass (FFM) in later life, similar to the prevention of fractures by increasing peak bone mass.

OBJECTIVES: A study is presented of the association between FFM and physical activity in relation to age.

METHODS: In a cross-sectional study, FFM was analyzed in relation to physical activity in a large participant group as compiled in the International Atomic Energy Agency Doubly Labeled Water database. The database included 2000 participants, age 3-96 y, with measurements of total energy expenditure (TEE) and resting energy expenditure (REE) to allow calculation of physical …

Influential Periods In Longitudinal Clinical Cardiovascular Health Scores, Amy E Krefman, Vito M R Muggeo, Et Al.

2020-Current year OA Pubs

The prevalence of ideal cardiovascular health (CVH) among adults in the United States is low and decreases with age. Our objective was to identify specific age windows when the loss of CVH accelerates, to ascertain preventive opportunities for intervention. Data were pooled from 5 longitudinal cohorts (Project Heartbeat!, Cardiovascular Risk in Young Finns Study, The Bogalusa Heart Study, Coronary Artery Risk Development in Young Adults, Special Turku Coronary Risk Factor Intervention Project) from the United States and Finland from 1973 to 2012. Individuals with clinical CVH factors (i.e., body mass index, blood pressure, cholesterol, blood glucose) measured from ages 8 …

Phase 1b Study Of Avb-500 In Combination With Paclitaxel Or Pegylated Liposomal Doxorubicin Platinum-Resistant Recurrent Ovarian Cancer, Katherine C Fuh, Michael A Bookman, Joyce F Liu, Robert L Coleman, Thomas J Herzog, Premal H Thaker, Bradley J Monk, Randy Anderson, Gail Mcintyre, Reshma Rangwala, Kathleen N Moore

2020-Current year OA Pubs

OBJECTIVE: GAS6 and AXL are expressed in high-grade serous ovarian cancer but not in normal ovarian tissue. AVB-500, a novel high affinity Fc-sAXL fusion protein, binds GAS6 preventing AXL signaling. This Phase 1b study (NCT03639246) evaluated safety, efficacy, and exploratory predictive markers of AVB-500 combined with paclitaxel (PAC) or pegylated liposomal doxorubicin (PLD) in patients with platinum-resistant ovarian cancer (PROC), and used a model informed drug development (MIDD) approach for identification of the recommended phase 2 dose (RP2D).

METHODS: Eligible patients received AVB-500 at 10, 15, or 20 mg/kg IV q2wk combined with PAC (n = 23) or PLD (n …

Risk Factors For Progression Or Death After First-Line Platinum-Based Chemotherapy In Real-World Patients In The Usa With Ovarian Cancer From 2011 To 2018, Shannon N Westin, Melinda Louie-Gao, Divya Gupta, Premal H Thaker

2020-Current year OA Pubs

No abstract provided.

Riociguat For The Treatment Of Phe508del Homozygous Adults With Cystic Fibrosis, Nico Derichs, Daniel Rosenbluth, Et Al.

2020-Current year OA Pubs

BACKGROUND: Riociguat is a first-in-class soluble guanylate cyclase stimulator for which preclinical data suggested improvements in cystic fibrosis transmembrane conductance regulator (CFTR) function.

METHODS: This international, multicenter, two-part, Phase II study of riociguat enrolled adults with cystic fibrosis (CF) homozygous for Phe508del CFTR. Part 1 was a 28-day, randomized, double-blind, placebo-controlled study in participants not receiving CFTR modulator therapy. Twenty-one participants were randomized 1:2 to placebo or oral riociguat (0.5 mg three times daily [tid] for 14 days, increased to 1.0 mg tid for the subsequent 14 days). The primary and secondary efficacy endpoints were change in sweat chloride concentration …

Modulation In Cortical Excitability Disrupts Information Transfer In Perceptual-Level Stimulus Processing, Ladan Moheimanian, Sivylla E Paraskevopoulou, Markus Adamek, Gerwin Schalk, Peter Brunner

2020-Current year OA Pubs

Despite significant interest in the neural underpinnings of behavioral variability, little light has been shed on the cortical mechanism underlying the failure to respond to perceptual-level stimuli. We hypothesized that cortical activity resulting from perceptual-level stimuli is sensitive to the moment-to-moment fluctuations in cortical excitability, and thus may not suffice to produce a behavioral response. We tested this hypothesis using electrocorticographic recordings to follow the propagation of cortical activity in six human subjects that responded to perceptual-level auditory stimuli. Here we show that for presentations that did not result in a behavioral response, the likelihood of cortical activity decreased from …

Phase I Study Of Single Agent Niz985, A Recombinant Heterodimeric Il-15 Agonist, In Adult Patients With Metastatic Or Unresectable Solid Tumors, Kevin Conlon, Andrea Wang-Gillam, Et Al

2020-Current year OA Pubs

BACKGROUND: NIZ985 is a recombinant heterodimer of physiologically active interleukin (IL-)15 and IL-15 receptor alpha. In preclinical models, NIZ985 promotes cytotoxic lymphocyte proliferation, killing function, and organ/tumor infiltration, with resultant anticancer effects. In this first-in-human study, we assessed the safety, pharmacokinetics, and immune effects of NIZ985 in patients with metastatic or unresectable solid tumors.

METHODS: Single agent NIZ985 dose escalation data are reported from a phase I dose escalation/expansion study of NIZ985 as monotherapy. Adult patients (N=14) received 0.25, 0.5, 1, 2 or 4 µg/kg subcutaneous NIZ985 three times weekly (TIW) for the first 2 weeks of each 28-day cycle, …

Coffee, Tea, And Mammographic Breast Density In Premenopausal Women, Adashi Margaret Odama, Valerie Otti, Shuai Xu, Olamide Adebayo, Adetunji T Toriola

2020-Current year OA Pubs

Studies have investigated the associations of coffee and tea with mammographic breast density (MBD) in premenopausal women with inconsistent results. We analyzed data from 375 premenopausal women who attended a screening mammogram at Washington University School of Medicine, St. Louis, MO in 2016, and stratified the analyses by race (non-Hispanic White (NHW) vs. Black/African American). Participants self-reported the number of servings of coffee, caffeinated tea, and decaffeinated tea they consumed. Volpara software was used to determine volumetric percent density (VPD), dense volume (DV), and non-dense volume (NDV). We used generalized linear regression models to quantify the associations of coffee and …

Patient-Reported Reasons For Stopping Care Or Switching Clinics In Zambia: A Multisite, Regionally Representative Estimate Using A Multistage Sampling-Based Approach In Zambia, Izukanji Sikazwe, Ingrid Eshun-Wilson, Kombatende Sikombe, Laura K Beres, Paul Somwe, Aaloke Mody, Sandra Simbeza, Chama Bukankala, David V Glidden, Lloyd B Mulenga, Nancy Padian, Peter Ehrenkranz, Carolyn Bolton-Moore, Charles B Holmes, Elvin H Geng

2020-Current year OA Pubs

BACKGROUND: Understanding patient-reported reasons for lapses of retention in human immunodeficiency virus (HIV) treatment can drive improvements in the care cascade. A systematic assessment of outcomes among a random sample of patients lost to follow-up (LTFU) from 32 clinics in Zambia to understand the reasons for silent transfers and disengagement from care was undertaken.

METHODS: We traced a simple random sample of LTFU patients (>90 days from last scheduled visit) as determined from clinic-based electronic medical records from a probability sample of facilities. Among patients found in person, we solicited reasons for either stopping or switching care and predictors …

Ceftolozane/Tazobactam Probability Of Target Attainment And Outcomes In Participants With Augmented Renal Clearance From The Randomized Phase 3 Aspect-Np Trial, Andrew F Shorr, Christopher J Bruno, Zufei Zhang, Erin Jensen, Wei Gao, Hwa-Ping Feng, Jennifer A Huntington, Brian Yu, Elizabeth G Rhee, Carisa De Anda, Sumit Basu, Marin H Kollef

2020-Current year OA Pubs

BACKGROUND: The randomized, double-blind, phase 3 ASPECT-NP trial evaluated the efficacy of 3 g of ceftolozane/tazobactam (C/T) versus 1 g of meropenem infused every 8 h for 8 to 14 days for treatment of adults with hospital-acquired bacterial pneumonia (HABP) or ventilator-associated bacterial pneumonia (VABP). We assessed the probability of target attainment and compared efficacy outcomes from ASPECT-NP in participants with augmented renal clearance (ARC) versus those with normal renal function.

METHODS: Baseline renal function was categorized as normal renal function (creatinine clearance 80-130 mL/min) or ARC (creatinine clearance > 130 mL/min). Population pharmacokinetic models informed Monte Carlo simulations to assess …

Ct Findings And Patterns Of E-Cigarette Or Vaping Product Use-Associated Lung Injury: A Multicenter Cohort Of 160 Cases, Seth J Kligerman, Constantine A Raptis, Kaitlin M Marquis, Et Al.

2020-Current year OA Pubs

BACKGROUND: e-Cigarette or vaping-induced lung injury (EVALI) causes a spectrum of CT lung injury patterns. Relative frequencies and associations with vaping behavior are unknown.

RESEARCH QUESTION: What are the frequencies of imaging findings and CT patterns in EVALI and what is the relationship to vaping behavior?

STUDY DESIGN AND METHODS: CT scans of 160 subjects with EVALI from 15 institutions were retrospectively reviewed. CT findings and patterns were defined and agreed on via consensus. The parenchymal organizing pneumonia (OP) pattern was defined as regional or diffuse ground-glass opacity (GGO) ± consolidation without centrilobular nodules (CNs). An airway-centered OP pattern was …

Multicenter, Double-Blind, Placebo-Controlled Trial Of Seviprotimut-L Polyvalent Melanoma Vaccine In Patients With Post-Resection Melanoma At High Risk Of Recurrence, Craig L Slingluff, Leonel Hernandez-Aya, Et Al

2020-Current year OA Pubs

BACKGROUND: Most patients with advanced melanomas relapse after checkpoint blockade therapy. Thus, immunotherapies are needed that can be applied safely early, in the adjuvant setting. Seviprotimut-L is a vaccine containing human melanoma antigens, plus alum. To assess the efficacy of seviprotimut-L, the Melanoma Antigen Vaccine Immunotherapy Study (MAVIS) was initiated as a three-part multicenter, double-blind, placebo-controlled phase III trial. Results from part B1 are reported here.

METHODS: Patients with AJCC V.7 stage IIB-III cutaneous melanoma after resection were randomized 2:1, with stage stratification (IIB/C, IIIA, IIIB/C), to seviprotimut-L 40 mcg or placebo. Recurrence-free survival (RFS) was the primary endpoint. For …

Quality Of Life Analyses In Patients With Multiple Myeloma: Results From The Selinexor (Kpt-330) Treatment Of Refractory Myeloma (Storm) Phase 2b Study, Gabriel Tremblay, Ravi Vij, Et Al.

2020-Current year OA Pubs

BACKGROUND: Selinexor is an oral, selective nuclear export inhibitor. STORM was a phase 2b, single-arm, open-label, multicenter trial of selinexor with low dose dexamethasone in patients with penta-exposed relapsed/refractory multiple myeloma (RRMM) that met its primary endpoint, with overall response of 26% (95% confidence interval [CI], 19 to 35%). Health-related quality of life (HRQoL) was a secondary endpoint measured using the Functional Assessment of Cancer Therapy - Multiple Myeloma (FACT-MM). This study examines impact of selinexor treatment on HRQoL of patients treated in STORM and reports two approaches to calculate minimal clinically important differences for the FACT-MM.

METHODS: FACT-MM data …

American Society Of Transplantation And Cellular Therapy, Center Of International Blood And Marrow Transplant Research, And European Society For Blood And Marrow Transplantation Clinical Practice Recommendations For Transplantation And Cellular Therapies In Mantle Cell Lymphoma, Pashna N Munshi, Brad Kahl, Amanda F Cashen, Et Al.

2020-Current year OA Pubs

Autologous (auto-) and allogeneic (allo-) hematopoietic cell transplantation (HCT) are accepted treatment modalities in contemporary treatment algorithms for mantle cell lymphoma (MCL). Chimeric antigen receptor (CAR) T cell therapy recently received approval for MCL; however, its exact place and sequence in relation to HCT remain unclear. The American Society of Transplantation and Cellular Therapy, Center of International Blood and Marrow Transplant Research, and the European Society for Blood and Marrow Transplantation jointly convened an expert panel to formulate consensus recommendations for role, timing, and sequencing of auto-HCT, allo-HCT, and CAR T cell therapy for patients with newly diagnosed and relapsed/refractory …

Differential Classification Of States Of Consciousness Using Envelope- And Phase-Based Functional Connectivity, Catherine Duclos, Michael S Avidan, Et Al.

2020-Current year OA Pubs

The development of sophisticated computational tools to quantify changes in the brain's oscillatory dynamics across states of consciousness have included both envelope- and phase-based measures of functional connectivity (FC), but there are very few direct comparisons of these techniques using the same dataset. The goal of this study was to compare an envelope-based (i.e. Amplitude Envelope Correlation, AEC) and a phase-based (i.e. weighted Phase Lag Index, wPLI) measure of FC in their classification of states of consciousness. Nine healthy participants underwent a three-hour experimental anesthetic protocol with propofol induction and isoflurane maintenance, in which five minutes of 128-channel electroencephalography were …

Das181 Treatment Of Severe Lower Respiratory Tract Parainfluenza Virus Infection In Immunocompromised Patients: A Phase 2 Randomized, Placebo-Controlled Study, Roy F Chemaly, Francisco M Marty, Cameron R Wolfe, Steven J Lawrence, Sanjeet Dadwal, Rosemary Soave, Jason Farthing, Stephen Hawley, Paul Montanez, Jimmy Hwang, Jennifer Hui-Chun Ho, Stanley Lewis, George Wang, Michael Boeckh

2020-Current year OA Pubs

BACKGROUND: There are no antiviral therapies for parainfluenza virus (PIV) infections. DAS181, a sialidase fusion protein, has demonstrated activity in in vitro and in animal models of PIV.

METHODS: Adult immunocompromised patients diagnosed with PIV lower respiratory tract infection (LRTI) who required oxygen supplementation were randomized 2:1 to nebulized DAS181 (4.5 mg/day) or matching placebo for up to 10 days. Randomization was stratified by need for mechanical ventilation (MV) or supplemental oxygen (SO). The primary endpoint was the proportion of patients reaching clinical stability survival (CSS) defined as returning to room air (RTRA), normalization of vital signs for at least …

De-Identification Procedures For Magnetic Resonance Images And The Impact On Structural Brain Measures At Different Ages, Elizabeth E L Buimer, Hugo G Schnack, Yaron Caspi, Neeltje E M Van Haren, Mikhail Milchenko, Pascal Pas, Alzheimer's Disease Neuroimaging Initiative, Hilleke E Hulshoff Pol, Rachel M Brouwer

2020-Current year OA Pubs

Surface rendering of MRI brain scans may lead to identification of the participant through facial characteristics. In this study, we evaluate three methods that overwrite voxels containing privacy-sensitive information: Face Masking, FreeSurfer defacing, and FSL defacing. We included structural T1-weighted MRI scans of children, young adults and older adults. For the young adults, test-retest data were included with a 1-week interval. The effects of the de-identification methods were quantified using different statistics to capture random variation and systematic noise in measures obtained through the FreeSurfer processing pipeline. Face Masking and FSL defacing impacted brain voxels in some scans especially in …

Integrated Analysis Of A Phase 2 Study Of Cemiplimab In Advanced Cutaneous Squamous Cell Carcinoma: Extended Follow-Up Of Outcomes And Quality Of Life Analysis, Danny Rischin, Leonel Hernandez-Aya, Et Al

2020-Current year OA Pubs

BACKGROUND: To provide pooled longer term data from three groups of a phase 2 study of cemiplimab in patients with advanced cutaneous squamous cell carcinoma (CSCC), and to determine duration of response (DOR) and impact on quality of life (QoL).

METHODS: Patients received cemiplimab 3 mg/kg every 2 weeks (group 1, metastatic CSCC [mCSCC], n=59; group 2, locally advanced CSCC, n=78) or cemiplimab 350 mg every 3 weeks (group 3, mCSCC, n=56). Primary endpoint was objective response rate (ORR) per independent central review (ICR). QoL was repeatedly measured at day 1 of each treatment cycle (groups 1 and 2: 8 …

Standardizing Definitions Of Hematopoietic Recovery, Graft Rejection, Graft Failure, Poor Graft Function, And Donor Chimerism In Allogeneic Hematopoietic Cell Transplantation: A Report On Behalf Of The American Society For Transplantation And Cellular Therapy, Mohamed A Kharfan-Dabaja, Iskra Pusic, Shalini Shenoy, Et Al.

2020-Current year OA Pubs

Allogeneic hematopoietic cell transplantation (allo-HCT) is potentially curative for certain hematologic malignancies and nonmalignant diseases. The field of allo-HCT has witnessed significant advances, including broadening indications for transplantation, availability of alternative donor sources, less toxic preparative regimens, new cell manipulation techniques, and novel GVHD prevention methods, all of which have expanded the applicability of the procedure. These advances have led to clinical practice conundrums when applying traditional definitions of hematopoietic recovery, graft rejection, graft failure, poor graft function, and donor chimerism, because these may vary based on donor type, cell source, cell dose, primary disease, graft-versus-host disease (GVHD) prophylaxis, and …

Exploring Perceptions Of Healthcare Technologies Enabled By Artificial Intelligence: An Online, Scenario-Based Survey, Alison L Antes, Sara Burrous, Bryan A Sisk, Matthew J Schuelke, Jason D Keune, James M Dubois

2020-Current year OA Pubs

BACKGROUND: Healthcare is expected to increasingly integrate technologies enabled by artificial intelligence (AI) into patient care. Understanding perceptions of these tools is essential to successful development and adoption. This exploratory study gauged participants' level of openness, concern, and perceived benefit associated with AI-driven healthcare technologies. We also explored socio-demographic, health-related, and psychosocial correlates of these perceptions.

METHODS: We developed a measure depicting six AI-driven technologies that either diagnose, predict, or suggest treatment. We administered the measure via an online survey to adults (N = 936) in the United States using MTurk, a crowdsourcing platform. Participants indicated their level of openness …

Significant Regional Differences In Antibiotic Use Across 576 Us Hospitals And 11 701 326 Adult Admissions, 2016-2017, Katherine E Goodman, Sara E Cosgrove, Lisa Pineles, Laurence S Magder, Deverick J Anderson, Elizabeth Dodds Ashley, Ronald E Polk, Hude Quan, William E Trick, Keith F Woeltje, Surbhi Leekha, Anthony D Harris

2020-Current year OA Pubs

BACKGROUND: Quantifying the amount and diversity of antibiotic use in United States hospitals assists antibiotic stewardship efforts but is hampered by limited national surveillance. Our study aimed to address this knowledge gap by examining adult antibiotic use across 576 hospitals and nearly 12 million encounters in 2016-2017.

METHODS: We conducted a retrospective study of patients aged ≥ 18 years discharged from hospitals in the Premier Healthcare Database between 1 January 2016 and 31 December 2017. Using daily antibiotic charge data, we mapped antibiotics to mutually exclusive classes and to spectrum of activity categories. We evaluated relationships between facility and case-mix …

Current State Of Scientific Evidence On Internet-Based Interventions For The Treatment Of Depression, Anxiety, Eating Disorders And Substance Abuse: An Overview Of Systematic Reviews And Meta-Analyses, C Barr Taylor, Andrea K Graham, Rachael E Flatt, Karin Waldherr, Ellen E Fitzsimmons-Craft

2020-Current year OA Pubs

BACKGROUND: ICare represents a consortium of European Investigators examining the effects of online mental health care for a variety of common mental health disorders provided in a variety of settings. This article provides an overview of the evidence of effectiveness for Internet-based treatment for four common mental health disorders that are the focus of much of this work: depression, anxiety, substance abuse and eating disorders.

METHODS: The overview focused primarily on systematic reviews and meta-analyses identified through PubMed (Ovid) and other databases and published in English. Given the large number of reviews specific to depression, anxiety, substance abuse and/or eating …

Oral Once-Daily Berotralstat For The Prevention Of Hereditary Angioedema Attacks: A Randomized, Double-Blind, Placebo-Controlled Phase 3 Trial, Bruce Zuraw, H James Wedner, Et Al.

2020-Current year OA Pubs

BACKGROUND: Berotralstat (BCX7353) is an oral, once-daily inhibitor of plasma kallikrein in development for the prophylaxis of hereditary angioedema (HAE) attacks.

OBJECTIVE: Our aim was to determine the efficacy, safety, and tolerability of berotralstat in patients with HAE over a 24-week treatment period (the phase 3 APeX-2 trial).

METHODS: APeX-2 was a double-blind, parallel-group study that randomized patients at 40 sites in 11 countries 1:1:1 to receive once-daily berotralstat in a dose of 110 mg or 150 mg or placebo (Clinicaltrials.gov identifier NCT03485911). Patients aged 12 years or older with HAE due to C1 inhibitor deficiency and at least 2 …

Outcomes For Continuous Subcutaneous Insulin Infusion Users In Young Adults From Lower Socioeconomic Backgrounds, Alexis M Mckee, Stewart G Albert, Noor Al-Hammadi, Leslie J Hinyard

2020-Current year OA Pubs

OBJECTIVE: Diabetes technology is available and its efficacy and safety have been demonstrated; however, there is little evidence as to how this technology is being utilized and its effectiveness in vulnerable populations. This study evaluated differences in outcomes for young adults in the United States (U.S.) from lower socioeconomic (SES) backgrounds with type 1 diabetes (T1D) managed on continuous subcutaneous insulin infusion (CSII) versus multiple daily injections (MDI) or fixed-dose insulin (FDI).

RESEARCH DESIGN METHODS AND PARTICIPANTS: Utilizing the Optum® de-identified Electronic Health Record data set between 2008 and 2018 to perform a retrospective, cohort study, we identified 805 subjects …

Riociguat: Clinical Research And Evolving Role In Therapy, James R Klinger, Murali M Chakinala, David Langleben, Stephan Rosenkranz, Olivier Sitbon

2020-Current year OA Pubs

Riociguat is a first-in-class soluble guanylate cyclase stimulator, approved for the treatment of adults with pulmonary arterial hypertension (PAH), inoperable chronic thromboembolic pulmonary hypertension (CTEPH), or persistent or recurrent CTEPH after pulmonary endarterectomy. Approval was based on the results of the phase III PATENT-1 (PAH) and CHEST-1 (CTEPH) studies, with significant improvements in the primary endpoint of 6-minute walk distance vs placebo of +36 m and +46 m, respectively, as well as improvements in secondary endpoints such as pulmonary vascular resistance and World Health Organization functional class. Riociguat acts as a stimulator of cyclic guanosine monophosphate synthesis rather than as …

Bintrafusp Alfa, A Bifunctional Fusion Protein Targeting Tgf-Β And Pd-L1, In Patients With Esophageal Adenocarcinoma: Results From A Phase 1 Cohort, Benjamin Tan, Adnan Khattak, Enriqueta Felip, Karen Kelly, Patricia Rich, Ding Wang, Christoph Helwig, Isabelle Dussault, Laureen S Ojalvo, Nicolas Isambert

2020-Current year OA Pubs

BACKGROUND: Esophageal adenocarcinoma patients have limited treatment options. TGF-β can be upregulated in esophageal adenocarcinoma, and blocking this pathway may enhance clinical response to PD-(L)1 inhibitors. Bintrafusp alfa is a first-in-class bifunctional fusion protein composed of the extracellular domain of the TGF-βRII receptor (a TGF-β "trap") fused to a human IgG1 mAb blocking PD-L1.

OBJECTIVE: The objective of this study was to investigate the efficacy and safety of bintrafusp alfa in patients with advanced, post-platinum esophageal adenocarcinoma, unselected for PD-L1 expression.

PATIENTS AND METHODS: In this phase 1 study, patients with post-platinum, PD-L1-unselected esophageal adenocarcinoma received bintrafusp alfa 1200 mg …

Dietary Fiber Intake, The Gut Microbiome, And Chronic Systemic Inflammation In A Cohort Of Adult Men, Wenjie Ma, Yin Cao, Et Al.

2020-Current year OA Pubs

BACKGROUND: A higher intake of dietary fiber is associated with a decreased risk of chronic inflammatory diseases such as cardiovascular disease and inflammatory bowel disease. This may function in part due to abrogation of chronic systemic inflammation induced by factors such as dysbiotic gut communities. Data regarding the detailed influences of long-term and recent intake of differing dietary fiber sources on the human gut microbiome are lacking.

METHODS: In a cohort of 307 generally healthy men, we examined gut microbiomes, profiled by shotgun metagenomic and metatranscriptomic sequencing, and long-term and recent dietary fiber intake in relation to plasma levels of …