Digital Commons Network^™

Combined Lenvatinib And Pembrolizumab As Salvage Therapy In Advanced Adrenal Cortical Carcinoma, Sara Bedrose, Kevin Charles Miller, Lina Altameemi, Mohamed S Ali, Sameh Nassar, Naveen Garg, Marilyne Daher, Keith D Eaton, Jeffrey Thomas Yorio, Davey B Daniel, Matthew Campbell, Keith C Bible, Mabel Ryder, Ashish V Chintakuntlawar, Mouhammed Amir Habra

Faculty, Staff and Students Publications

BACKGROUND: There is no effective systemic therapy for metastatic adrenal cortical carcinoma (ACC) after failure of platinum-based chemotherapy. The efficacies of single-agent oral multikinase inhibitors (MKIs) or salvage immune checkpoint inhibitors (CPIs) have been very limited. It is unknown whether combining CPIs, such as pembrolizumab (PEM), with other therapies, such as MKIs, could yield higher response rates in ACC, yet this combination has shown promise in other cancers. Herein, we describe the first case series using PEM in combination with the MKI lenvatinib (LEN) in patients with progressive, metastatic ACC.

METHODS: A retrospective case series describing the use of LEN/PEM …

Association Analysis Of Driver Gene-Related Genetic Variants Identified Novel Lung Cancer Susceptibility Loci With 20,871 Lung Cancer Cases And 15,971 Controls, Yuzhuo Wang, Olga Y Gorlova, Ivan P Gorlov, Meng Zhu, Juncheng Dai, Demetrius Albanes, Stephen Lam, Adonina Tardon, Chu Chen, Gary E Goodman, Stig E Bojesen, Maria Teresa Landi, Mattias Johansson, Angela Risch, Heunz-Erich Wichmann, Heike Bickeboller, David C Christiani, Gad Rennert, Susanne M Arnold, Paul Brennan, John K Field, Sanjay Shete, Loïc Le Marchand, Olle Melander, Hans Brunnstrom, Geoffrey Liu, Rayjean J Hung, Angeline S Andrew, Lambertus A Kiemeney, Shanbeh Zienolddiny, Kjell Grankvist, Mikael Johansson, Neil E Caporaso, Penella J Woll, Philip Lazarus, Matthew B Schabath, Melinda C Aldrich, Victoria L Stevens, Hongxia Ma, Guangfu Jin, Zhibin Hu, Christopher I Amos, Hongbing Shen

Faculty, Staff and Students Publications

BACKGROUND: A substantial proportion of cancer driver genes (CDG) are also cancer predisposition genes. However, the associations between genetic variants in lung CDGs and the susceptibility to lung cancer have rarely been investigated.

METHODS: We selected expression-related single-nucleotide polymorphisms (eSNP) and nonsynonymous variants of lung CDGs, and tested their associations with lung cancer risk in two large-scale genome-wide association studies (20,871 cases and 15,971 controls of European descent). Conditional and joint association analysis was performed to identify independent risk variants. The associations of independent risk variants with somatic alterations in lung CDGs or recurrently altered pathways were investigated using data …

Association Of Interleukin 7 Immunotherapy With Lymphocyte Counts Among Patients With Severe Coronavirus Disease 2019 (Covid-19), Pierre Francois Laterre, Bruno François, Christine Collienne, Philippe Hantson, Robin Jeannet, Kenneth E. Remy, Richard S. Hotchkiss

Open Access Publications

No abstract provided.

The Endosymbiont Wolbachia Rebounds Following Antibiotic Treatment, Emma L. Gunderson, Young-Jun Choi, Makedonka Mitreva, Et Al.

Open Access Publications

Antibiotic treatment has emerged as a promising strategy to sterilize and kill filarial nematodes due to their dependence on their endosymbiotic bacteria, Wolbachia. Several studies have shown that novel and FDA-approved antibiotics are efficacious at depleting the filarial nematodes of their endosymbiont, thus reducing female fecundity. However, it remains unclear if antibiotics can permanently deplete Wolbachia and cause sterility for the lifespan of the adult worms. Concerns about resistance arising from mass drug administration necessitate a careful exploration of potential Wolbachia recrudescence. In the present study, we investigated the long-term effects of the FDA-approved antibiotic, rifampicin, in the Brugia pahangi …

Maternal Knowledge Of The Risk Of Vertical Transmission And Offspring Acquisition Of Hepatitis B., Mauricio Lisker-Melman, Mandana Khalili, Steven H Belle, Norah A Terrault, Hsing-Hua S Lin, Coleman I Smith, Raymond T Chung, Naoky Tsai, Natalie H Bzowej, Tram T Tran, Sarah Jane Schwarzenberg, Hepatitis B Research Network (Hbrn)

Open Access Publications

INTRODUCTION AND OBJECTIVES: Universal vaccination at birth and in infancy is key to the elimination of chronic hepatitis B infection. We aimed to assess hepatitis B immune-prophylaxis and perinatal transmission knowledge, in a large and ethnically diverse cohort of previously pregnant North American women, chronically infected with hepatitis B.

MATERIALS AND METHODS: The Hepatitis B Research Network (HBRN) is comprised of 28 Clinical Centers in the United States and Canada. Female cohort participants were administered a questionnaire to assess: (1) their assertion of knowledge regarding HBV prophylaxis at birth, testing, and diagnosis of hepatitis B in their children, and (2) …

Test-Retest Reliability Of Fmri-Measured Brain Activity During Decision Making Under Risk, Ozlem Korucuoglu, Michael P. Harms, Serguei V. Astafiev, James T. Kennedy, Semyon Golosheykin, Deanna M. Barch, Andrey P. Anokhin

2020-Current year OA Pubs

Neural correlates of decision making under risk are being increasingly utilized as biomarkers of risk for substance abuse and other psychiatric disorders, treatment outcomes, and brain development. This research relies on the basic assumption that fMRI measures of decision making represent stable, trait-like individual differences. However, reliability needs to be established for each individual construct. Here we assessed long-term test-retest reliability (TRR) of regional brain activations related to decision making under risk using the Balloon Analogue Risk Taking task (BART) and identified regions with good TRRs and familial influences, an important prerequisite for the use of fMRI measures in genetic …

A Domain-General Cognitive Core Defined In Multimodally Parcellated Human Cortex, Moataz Assem, Matthew F Glasser, David C Van Essen, John Duncan

2020-Current year OA Pubs

Numerous brain imaging studies identified a domain-general or "multiple-demand" (MD) activation pattern accompanying many tasks and may play a core role in cognitive control. Though this finding is well established, the limited spatial localization provided by traditional imaging methods precluded a consensus regarding the precise anatomy, functional differentiation, and connectivity of the MD system. To address these limitations, we used data from 449 subjects from the Human Connectome Project, with the cortex of each individual parcellated using neurobiologically grounded multimodal MRI features. The conjunction of three cognitive contrasts reveals a core of 10 widely distributed MD parcels per hemisphere that …

Robust Principal Component Analysis For Accurate Outlier Sample Detection In Rna-Seq Data, Xiaoying Chen, Bo Zhang, Ting Wang, Azad Bonni, Guoyan Zhao

Open Access Publications

BACKGROUND: High throughput RNA sequencing is a powerful approach to study gene expression. Due to the complex multiple-steps protocols in data acquisition, extreme deviation of a sample from samples of the same treatment group may occur due to technical variation or true biological differences. The high-dimensionality of the data with few biological replicates make it challenging to accurately detect those samples, and this issue is not well studied in the literature currently. Robust statistics is a family of theories and techniques aim to detect the outliers by first fitting the majority of the data and then flagging data points that …

Systemic Inflammatory Response Syndrome In Patients With Acute Obstructive Upper Tract Urinary Stone: A Risk Factor For Urgent Renal Drainage And Revisit To The Emergency Department, Spencer Larkin, Jeremy Johnson, Trisha Venkatesh, Joel Vetter, Ramakrishna Venkatesh

Open Access Publications

BACKGROUND: In patients seen in the emergency department (ED) with acute stone obstruction many risk factors that indicate need for urgent renal drainage are known. However, in patients discharged from ED without renal drainage factors that can minimize revisit to the emergency department are not fully identified. We evaluated SIRS (systemic inflammatory response syndrome) as a risk factor for urgent renal drainage and revisit to the ED in patients with acute stone colic during their ED visit.

METHODS: Retrospective review was performed of patients presenting to a tertiary academic emergency department (ED) from an obstructing ureteral or UPJ stone with …

Transient Hyponatremia Of Prematurity Caused By Mild Bartter Syndrome Type Ii: A Case Report., Subhrata Verma, Rahul Chanchlani, Victoria Mok Siu, Guido Filler

Paediatrics Publications

BACKGROUND: Bartter syndrome subtypes are a group of rare renal tubular diseases characterized by impaired salt reabsorption in the tubule, specifically the thick ascending limb of Henle's loop. Clinically, they are characterized by the association of hypokalemic metabolic alkalosis, hypercalciuria, nephrocalcinosis, increased levels of plasma renin and aldosterone, low blood pressure and vascular resistance to angiotensin II. Bartter syndrome type II is caused by mutations in the renal outer medullary potassium channel (ROMK) gene (KCNJ1), can present in the newborn period and typically requires lifelong therapy.

CASE PRESENTATION: We describe a case of a prematurely born female infant presenting with …

Nuclear Localization Of A Novel Calpain-2 Mediated Junctophilin-2 C-Terminal Cleavage Peptide Promotes Cardiomyocyte Remodeling, Satadru K Lahiri, Ann P Quick, Benoit Samson-Couterie, Mohit Hulsurkar, Ies Elzenaar, Ralph J Van Oort, Xander H T Wehrens

Faculty, Staff and Students Publications

Heart failure (HF) is a leading cause of morbidity and mortality worldwide. Patients with HF exhibit a loss of junctophilin-2 (JPH2), a structural protein critical in forming junctional membrane complexes in which excitation-contraction takes place. Several mechanisms have been proposed to mediate the loss of JPH2, one being cleavage by the calcium-dependent protease calpain. The downstream mechanisms underlying HF progression after JPH2 cleavage are presently poorly understood. In this study, we used Labcas to bioinformatically predict putative calpain cleavage sites on JPH2. We identified a cleavage site that produces a novel C-terminal JPH2 peptide (JPH2-CTP) using several domain-specific antibodies. Western …

Vitamin A And Fish Oils For Preventing The Progression Of Retinitis Pigmentosa., Stephen G. Schwartz, Xue Wang, Pamela Chavis, Ajay E. Kuriyan, Samuel A. Abariga

Wills Eye Hospital Papers

BACKGROUND: Retinitis pigmentosa (RP) comprises a group of hereditary eye diseases characterized by progressive degeneration of retinal photoreceptors. It results in severe visual loss that may lead to blindness. Symptoms may become manifest during childhood or adulthood which include poor night vision (nyctalopia) and constriction of peripheral vision (visual field loss). Visual field loss is progressive and affects central vision later in the disease course. The worldwide prevalence of RP is approximately 1 in 4000, with 100,000 individuals affected in the USA. At this time, there is no proven therapy for RP.

OBJECTIVES: The objective of this review was to …

Effect Of Continuous Glucose Monitoring On Hypoglycemia In Older Adults With Type 1 Diabetes: A Randomized Clinical Trial, Richard E. Pratley, Lauren G. Kanapka, Michael R. Rickels, Andrew Ahmann, Grazia Aleppo, Roy Beck, Anuj Bhargava, Bruce W. Bode, Anders Carlson, Naomi S. Chaytor, D Steven Fox, Robin Goland, Irl B. Hirsch, Davida F. Kruger, Yogish C. Kudva, Carol Levy, Janet B. Mcgill, Anne Peters, Louis Philipson, Athena Philis-Tsimikas, Rodica Pop-Busui, Viral N. Shah, Michael Thompson, Francesco Vendrame, Alandra Verdejo, Ruth S. Weinstock, Laura Young, Kellee M. Miller

Endocrinology Articles

Importance: Continuous glucose monitoring (CGM) provides real-time assessment of glucose levels and may be beneficial in reducing hypoglycemia in older adults with type 1 diabetes.

Objective: To determine whether CGM is effective in reducing hypoglycemia compared with standard blood glucose monitoring (BGM) in older adults with type 1 diabetes.

Design, Setting, and Participants: Randomized clinical trial conducted at 22 endocrinology practices in the United States among 203 adults at least 60 years of age with type 1 diabetes.

Interventions: Participants were randomly assigned in a 1:1 ratio to use CGM (n = 103) or standard BGM (n = 100).

Main …

Linking Activity, Nutrition, And Child Health (Launch): Protocol For A Longitudinal Cohort Study Of Children As They Develop From Infancy To Preschool Age, Russell R. Pate, Edward A. Frongillo Jr., Kerry Cordan, Marsha Dowda, Alexander C. Mclain, Myriam E. Torres, William H. Brown, Agnes Bucko, Emily R. Shull

Faculty Publications

Background

Physical activity is known to provide important health benefits in children ages 3 years and above, but little is known about the effects of physical activity on health in very young children under age 3. LAUNCH (Linking Activity, Nutrition, and Child Health) is a study designed to expand the body of knowledge on development of physical activity behavior and associations between physical activity and other health characteristics as children transition from infancy to preschool age.

Methods

Physical activity and sedentary behavior will be measured objectively in young children over a period of 30 months. Each child will complete a …

Covid-19 Medical Papers Have Fewer Women First Authors Than Expected., Jens Peter Andersen, Mathias Wullum Nielsen, Nicole L Simone, Resa E Lewiss, Reshma Jagsi

Department of Radiation Oncology Faculty Papers

The COVID-19 pandemic has resulted in school closures and distancing requirements that have disrupted both work and family life for many. Concerns exist that these disruptions caused by the pandemic may not have influenced men and women researchers equally. Many medical journals have published papers on the pandemic, which were generated by researchers facing the challenges of these disruptions. Here we report the results of an analysis that compared the gender distribution of authors on 1893 medical papers related to the pandemic with that on papers published in the same journals in 2019, for papers with first authors and last …

A Genome-Wide Association Study Identifies Two Novel Susceptible Regions For Squamous Cell Carcinoma Of The Head And Neck, Sanjay Shete, Hongliang Liu, Jian Wang, Robert Yu, Erich M Sturgis, Guojun Li, Kristina R Dahlstrom, Zhensheng Liu, Christopher I Amos, Qingyi Wei

Faculty, Staff and Students Publications

To identify genetic variants for risk of squamous cell carcinoma of the head and neck (SCCHN), we conducted a two-phase genome-wide association study consisting of 7,858,089 SNPs in 2,171 cases and 4,493 controls of non-Hispanic white, of which 434,839 typed and 7,423,250 imputed SNPs as the discovery. SNPs with P <1×10–3 were further validated in the OncoArray study of oral and pharynx cancer (5,205 cases and 3,232 controls of European ancestry) from dbGaP. Meta-analysis of the discovery and replication studies identified one novel locus 6p22.1 (P = 2.96×10–9 for the leading rs259919) and two cancer susceptibility loci 6p21.32 (rs3135001, HLA-DQB1) and 6p21.33 (rs1265081, CCHCR1) associated with SCCHN risk. Further stratification by tumor site revealed four known cancer loci (5p15.33, 6p21.32, 6p21.33, and 2p23.1) associated with oral cavity cancer risk and oropharyngeal cancer risk, respectively. In addition, one novel locus 18q22.2 (P = 2.54×10–9 for the leading SNP rs142021700) was identified for hypo-pharynx and larynx cancer risk. For SNPs in those reported or novel loci, we also performed functional annotations by bioinformatics prediction and eQTL analysis. Collectively, our identification of four reported loci (2p23.1, 5p15.33, 6p21.32, and 6p21.33) and two novel loci (6p22.1 and 18q22.2) for SCCHN risk highlight the importance of HLA loci for oropharyngeal cancer risk, suggesting that immunologic mechanisms are implicated in the etiology of this subset of SCCHN.

Multidimensional Imaging Of Liver Injury Repair In Mice Reveals Fundamental Role Of The Ductular Reaction, Kenji Kamimoto, Yasuhiro Nakano, Kota Kaneko, Atsushi Miyajima, Tohru Itoh

Open Access Publications

Upon severe and/or chronic liver injury, ectopic emergence and expansion of atypical biliary epithelial-like cells in the liver parenchyma, known as the ductular reaction, is typically induced and implicated in organ regeneration. Although this phenomenon has long been postulated to represent activation of facultative liver stem/progenitor cells that give rise to new hepatocytes, recent lineage-tracing analyses have challenged this notion, thereby leaving the pro-regenerative role of the ductular reaction enigmatic. Here, we show that the expanded and remodelled intrahepatic biliary epithelia in the ductular reaction constituted functional and complementary bile-excreting conduit systems in injured parenchyma where hepatocyte bile canalicular networks …

Posterior Cortical Atrophy: Characteristics From A Clinical Data Registry., Jennifer J Olds, William L Hills, Judith Warner, Julie Falardeau, Lori Haase Alasantro, Mark L Moster, Robert A Egan, Wayne T Cornblath, Andrew G Lee, Benjamin M Frishberg, Roger E Turbin, David M Katz, John A Charley, Victoria S Pelak

Department of Neurology Faculty Papers

No abstract provided.

Evaluation Of Mavacamten In Symptomatic Patients With Nonobstructive Hypertrophic Cardiomyopathy, Carolyn Y Ho, Richard G Bach, Et Al.

2020-Current year OA Pubs

BACKGROUND: Patients with nonobstructive hypertrophic cardiomyopathy (nHCM) often experience a high burden of symptoms; however, there are no proven pharmacological therapies. By altering the contractile mechanics of the cardiomyocyte, myosin inhibitors have the potential to modify pathophysiology and improve symptoms associated with HCM.

OBJECTIVES: MAVERICK-HCM (Mavacamten in Adults With Symptomatic Non-Obstructive Hypertrophic Cardiomyopathy) explored the safety and efficacy of mavacamten, a first-in-class reversible inhibitor of cardiac-specific myosin, in nHCM.

METHODS: The MAVERICK-HCM trial was a multicenter, double-blind, placebo-controlled, dose-ranging phase II study in adults with symptomatic nHCM (New York Heart Association functional class II/III), left ventricular ejection fraction (LVEF) ≥55%, …

Does Empathy Decline In The Clinical Phase Of Medical Education? A Nationwide, Multi-Institutional, Cross-Sectional Study Of Students At Do-Granting Medical Schools, Mohammadreza Hojat, Stephen C. Shannon, Jennifer Desantis, Mark R. Speicher, Lynn Bragan, Leonard H. Calabrese

CRMEHC Faculty Papers

PURPOSE: To examine differences in students' empathy in different years of medical school in a nationwide study of students of U.S. DO-granting medical schools.

METHOD: Participants in this cross-sectional study included 10,751 students enrolled in 41 of 48 campuses of DO-granting medical schools in the United States (3,616 first-year, 2,764 second-year, 2,413 third-year, and 1,958 fourth-year students). They completed a web-based survey at the end of the 2017-2018 academic year that included the Jefferson Scale of Empathy and the Infrequency Scale of the Zuckerman-Kuhlman Personality Questionnaire for measuring "good impression" response bias. Comparisons were made on empathy scores among students …

Relationships Of P16 Immunohistochemistry And Other Biomarkers With Diagnoses Of Cervical Abnormalities: Implications For Last Terminology, Philip E. Castle, Rachael Adcock, Jack Cuzick, Nicolas Wentzensen, Norah E. Torrez-Martinez, Salina M. Torres, Mark H. Stoler, Brigitte M. Ronnett, Nancy E. Joste, Teresa M. Darragh, Patti E. Gravitt, Mark Schiffman, William C. Hunt, Walter K. Kinney, Cosette M. Wheeler

Pathology Research and Scholarship

CONTEXT.—: Lower Anogenital Squamous Terminology (LAST) standardization recommended p16

OBJECTIVE.—: To describe the relationships of p16 IHC and other biomarkers associated with cervical cancer risk with biopsy diagnoses.

DESIGN.—: A statewide, stratified sample of cervical biopsies diagnosed by community pathologists (CPs), including 1512 CIN2, underwent a consensus, expert pathologist panel (EP) review (without p16 IHC results), p16 IHC interpretation by a third pathology group, and human papillomavirus (HPV) genotyping, results of which were grouped hierarchically according to cancer risk. Antecedent cytologic interpretations were also available.

RESULTS.—: Biopsies were more likely to test p16 IHC positive with increasing severity of CP …

Secukinumab Provides Sustained Low Rates Of Radiographic Progression In Psoriatic Arthritis: 52-Week Results From A Phase 3 Study, Future 5., Désirée Van Der Heijde, Philip Mease, Robert B M Landewé, Proton Rahman, Hasan Tahir, Atul Singhal, Elke Boettcher, Sandra Navarra, Xuan Zhu, Gregory Ligozio, Aimee Readie, Shephard Mpofu, Luminita Pricop

Articles, Abstracts, and Reports

OBJECTIVE: To evaluate the effect of secukinumab on radiographic progression through 52 weeks in patients with PsA from the FUTURE 5 study.

METHODS: Patients with active PsA, stratified by prior anti-TNF use (naïve or inadequate response), were randomized to s.c. secukinumab 300 mg load (300 mg), 150 mg load (150 mg), 150 mg no load regimens or placebo at baseline, at weeks 1, 2 and 3 and every 4 weeks starting at week 4. Radiographic progression was assessed by change in van der Heijde-modified total Sharp score (vdH-mTSS; mean of two readers). Statistical analysis used a linear mixed-effects model (random …

Wolff-Parkinson-White Syndrome: De Novo Variants And Evidence For Mutational Burden In Genes Associated With Atrial Fibrillation, Zeynep H Coban-Akdemir, Wu-Lin Charng, Mahshid Azamian, Ingrid S Paine, Jaya Punetha, Christopher M Grochowski, Tomasz Gambin, Santiago O Valdes, Bryan Cannon, Gladys Zapata, Patricia P Hernandez, Shalini Jhangiani, Harsha Doddapaneni, Jianhong Hu, Fatima Boricha, Donna M Muzny, Eric Boerwinkle, Yaping Yang, Richard A Gibbs, Jennifer E Posey, Xander H T Wehrens, John W Belmont, Jeffrey J Kim, Christina Y Miyake, James R Lupski, Seema R Lalani

Faculty, Staff and Student Publications

BACKGROUND: Wolff-Parkinson-White (WPW) syndrome is a relatively common arrhythmia affecting ~1-3/1,000 individuals. Mutations in PRKAG2 have been described in rare patients in association with cardiomyopathy. However, the genetic basis of WPW in individuals with a structurally normal heart remains poorly understood. Sudden death due to atrial fibrillation (AF) can also occur in these individuals. Several studies have indicated that despite ablation of an accessory pathway, the risk of AF remains high in patients compared to general population.

METHODS: We applied exome sequencing in 305 subjects, including 65 trios, 80 singletons, and 6 multiple affected families. We used de novo analysis, …

Epigenomic Programming In Early Fetal Brain Development, Luolan Li, Ting Wang, Et Al

2020-Current year OA Pubs

No abstract provided.

Natural History Of Geographic Atrophy Secondary To Age-Related Macular Degeneration: Results From The Prospective Proxima A And B Clinical Trials, Nancy Holekamp, Charles C Wykoff, Steffen Schmitz-Valckenberg, Jordi Monés, Eric H Souied, Hugh Lin, Melvin D Rabena, Ronald A Cantrell, Erin C Henry, Fan Tang, Balakumar Swaminathan, Jillian Martin, Daniela Ferrara, Giovanni Staurenghi

2020-Current year OA Pubs

PURPOSE: To better characterize visual function decline and geographic atrophy (GA) progression secondary to age-related macular degeneration (AMD).

DESIGN: Proxima A (NCT02479386)/Proxima B (NCT02399072) were global, prospective, noninterventional, observational clinical trials.

PARTICIPANTS: Eligible patients were aged ≥50 years. Patients in Proxima A had bilateral GA without choroidal neovascularization (CNV) in either eye (N = 295). Patients in Proxima B had GA without CNV in the study eye and CNV±GA in the fellow eye (fellow eye CNV cohort, n = 168) or GA without CNV in the study eye, no CNV/GA in the fellow eye (fellow eye intermediate AMD cohort, n …

Effects Of Ruxolitinib Cream On Pruritus And Quality Of Life In Atopic Dermatitis: Results From A Phase 2, Randomized, Dose-Ranging, Vehicle- And Active-Controlled Study, Brian S Kim, Kang Sun, Kim Papp, May Venturanza, Adnan Nasir, Michael E. Kuligowski

2020-Current year OA Pubs

BACKGROUND: Atopic dermatitis (AD), a chronic, highly pruritic skin disorder, impairs quality of life (QoL). Janus kinase inhibitors suppress inflammatory and pruritus-associated cytokine signaling in AD.

OBJECTIVE: To report the effects of ruxolitinib (RUX) cream on itch and QoL in AD.

METHODS: A total of 307 adult patients with an Investigator's Global Assessment (score of 2 or 3) and 3% to 20% affected body surface area were randomly assigned for 8 weeks to receive double-blind treatment with RUX (1.5% twice daily, 1.5% once daily, 0.5% once daily, or 0.15% once daily), vehicle twice daily, or triamcinolone cream (0.1% twice daily …

Phase 2 Study Of Cemiplimab In Patients With Metastatic Cutaneous Squamous Cell Carcinoma: Primary Analysis Of Fixed-Dosing, Long-Term Outcome Of Weight-Based Dosing, Danny Rischin, Leonel Hernandez-Aya, Et Al

2020-Current year OA Pubs

BACKGROUND: Cemiplimab, a high-affinity, potent human immunoglobulin G4 monoclonal antibody to programmed cell death-1 demonstrated antitumor activity in a Phase 1 advanced cutaneous squamous cell carcinoma (CSCC) expansion cohort (NCT02383212) and the pivotal Phase 2 study (NCT02760498). Here we report the primary analysis of fixed dose cemiplimab 350 mg intravenously every 3 weeks (Q3W) (Group 3) and provide a longer-term update after the primary analysis of weight-based cemiplimab 3 mg/kg intravenously every 2 weeks (Q2W) (Group 1) among metastatic CSCC (mCSCC) patients in the pivotal study (NCT02760498).

METHODS: The primary objective for each group was objective response rate (ORR) per …

Growth Velocity In Children With Environmental Enteric Dysfunction Is Associated With Specific Bacterial And Viral Taxa Of The Gastrointestinal Tract In Malawian Children, Chandni Desai, Scott A. Handley, Rachel Rodgers, Cynthia Rodriguez, Maria I. Ordiz, Mark J. Manary, Lori R. Holtz

Open Access Publications

Environmental enteric dysfunction (EED) is characterized by diffuse villous atrophy of the small bowel. EED is strongly associated with stunting, a major public health problem linked to increased childhood morbidity and mortality. EED and subsequent stunting of linear growth are surmised to have microbial origins. To interrogate this relationship, we defined the comprehensive virome (eukaryotic virus and bacteriophage) and bacterial microbiome of a longitudinal cohort of rural Malawian children with extensive metadata and intestinal permeability testing at each time point. We found thirty bacterial taxa differentially associated with linear growth. We detected many eukaryotic viruses. Neither the total number of …

The Impact Of Four Years Of Semiannual Treatments With Albendazole Alone On Lymphatic Filariasis And Soil-Transmitted Helminth Infections: A Community-Based Study In The Democratic Republic Of The Congo, Sébastien D. S. Pion, Cédric B. Chesnais, Naomi P. Awaca-Uvon, Johnny Vlaminck, Anlimou Abdou, Billy Kunyu-Shako, Godefroy Kuyangisa Simuna, Jean-Paul Tambwe, Gary J. Weil, Michel Boussinesq

Open Access Publications

BACKGROUND: The World Health Organization now recommends semiannual mass drug administration (MDA) of albendazole with integrated vector management as an option for eliminating lymphatic filariasis (LF) in areas of loiasis-endemic countries where it may not be safe to use diethylcarbamazine or ivermectin in MDA programs. However, the published evidence base to support this policy is thin, and uptake by national programs has been slow.

METHODOLOGY/PRINCIPAL FINDINGS: We conducted a community trial to assess the impact of semiannual MDA on lymphatic filariasis and soil-transmitted helminth infections (STH) in two villages in the Bandundu province of the Democratic Republic of the Congo …

Bosutinib For Pretreated Patients With Chronic Phase Chronic Myeloid Leukemia: Primary Results Of The Phase 4 Byond Study, Andreas Hochhaus, Camille Abboud, Et Al

Open Access Publications

Bosutinib is approved for newly diagnosed Philadelphia chromosome-positive (Ph+) chronic phase (CP) chronic myeloid leukemia (CML) and for Ph+ CP, accelerated (AP), or blast (BP) phase CML after prior treatment with tyrosine kinase inhibitors (TKIs). In the ongoing phase 4 BYOND study (NCT02228382), 163 CML patients resistant/intolerant to prior TKIs (n = 156 Ph+ CP CML, n = 4 Ph+ AP CML, n = 3 Ph-negative/BCR-ABL1+ CML) received bosutinib 500 mg once daily (starting dose). As of ≥1 year after last enrolled patient (median treatment duration 23.7 months), 56.4% of Ph+ CP CML patients remained on bosutinib. Primary endpoint of …