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Full-Text Articles in Medical Specialties

Are You Still On The Fence About Wearing A Mask?, Richard Davis Jul 2020

Are You Still On The Fence About Wearing A Mask?, Richard Davis

Articles, Abstracts, and Reports

Microbe-containing droplets are produced by coughing, talking, singing and sneezing. Masks are effective at blocking most of these droplets, even when up close.


A Phase Ii Single-Arm Study Of Pembrolizumab With Enzalutamide In Men With Metastatic Castration-Resistant Prostate Cancer Progressing On Enzalutamide Alone., Julie N Graff, Tomasz M Beer, Joshi J Alumkal, Rachel E Slottke, William L. Redmond, George V Thomas, Reid F Thompson, Mary A Wood, Yoshinobu Koguchi, Yiyi Chen, Emile Latour, Raymond C Bergan, Charles G Drake, Amy E Moran Jul 2020

A Phase Ii Single-Arm Study Of Pembrolizumab With Enzalutamide In Men With Metastatic Castration-Resistant Prostate Cancer Progressing On Enzalutamide Alone., Julie N Graff, Tomasz M Beer, Joshi J Alumkal, Rachel E Slottke, William L. Redmond, George V Thomas, Reid F Thompson, Mary A Wood, Yoshinobu Koguchi, Yiyi Chen, Emile Latour, Raymond C Bergan, Charles G Drake, Amy E Moran

Articles, Abstracts, and Reports

BACKGROUND: Checkpoint inhibitors can induce profound anticancer responses, but programmed cell death protein-1 (PD-1) inhibition monotherapy has shown minimal activity in prostate cancer. A published report showed that men with prostate cancer who were resistant to the second-generation androgen receptor inhibitor enzalutamide had increased programmed death-ligand 1 (PD-L1) expression on circulating antigen-presenting cells. We hypothesized that the addition of PD-1 inhibition in these patients could induce a meaningful cancer response.

METHODS: We evaluated enzalutamide plus the PD-1 inhibitor pembrolizumab in a single-arm phase II study of 28 men with metastatic castration-resistant prostate cancer (mprogressing on enzalutamide alone. Pembrolizumab 200 mg …


Perianal Basal Cell Carcinoma: A Common Cancer In An Uncommon Location., Ed Hagen, Nathan Hite, John A Griffin, Rodney Kratz Jul 2020

Perianal Basal Cell Carcinoma: A Common Cancer In An Uncommon Location., Ed Hagen, Nathan Hite, John A Griffin, Rodney Kratz

Articles, Abstracts, and Reports

This is a case of a perianal basal cell carcinoma, a common skin cancer in an unusual location. Our patient is a 67-year-old male with a perianal lesion. He first noticed this painless lesion 5 years prior to presentation and was having fecal incontinence and weight loss. He had a fully encompassing ulcerated lesion involving the entirety of the anal margin. We performed a biopsy that returned on pathology as a basal cell carcinoma. Due to the size of the lesion and his current nutritional status, it was determined to be unresectable. We were able to provide him with a …


Characterization Of Patients With Axial Spondyloarthritis By Enthesitis Presence: Data From The Corrona Psoriatic Arthritis/Spondyloarthritis Registry., Philip Mease, Mei Liu, Sabrina Rebello, Winnie Hua, Robert R Mclean, Esther Yi, Yujin Park, Alexis Ogdie Jul 2020

Characterization Of Patients With Axial Spondyloarthritis By Enthesitis Presence: Data From The Corrona Psoriatic Arthritis/Spondyloarthritis Registry., Philip Mease, Mei Liu, Sabrina Rebello, Winnie Hua, Robert R Mclean, Esther Yi, Yujin Park, Alexis Ogdie

Articles, Abstracts, and Reports

OBJECTIVE: To compare the characteristics of patients with axial spondyloarthritis (axSpA) who had enthesitis versus those without enthesitis.

METHODS: This study included adult patients with axSpA enrolled in the Corrona Psoriatic Arthritis/Spondyloarthritis Registry (March 2013 to August 2018). Enthesitis was assessed at enrollment via the Spondyloarthritis Research Consortium of Canada Enthesitis Index. Characteristics were compared between patients with and without enthesitis using t tests or Wilcoxon rank-sum tests for continuous variables and χ

RESULTS: Of 477 patients with axSpA, 121 (25.4%) had enthesitis (mean, 3.9 sites) at enrollment. Higher proportions of patients with enthesitis were female and had nonradiographic axSpA …


Crack Cocaine Induced Upper Airway Injury., N D Vandjelovic, A K Larson, E M Sugihara, N A Stern Jun 2020

Crack Cocaine Induced Upper Airway Injury., N D Vandjelovic, A K Larson, E M Sugihara, N A Stern

Articles, Abstracts, and Reports

The paper describes the presentation and management of patients presenting with crack cocaine induced upper airway injury. The study involved a retrospective clinical series of six patients with crack cocaine induced upper airway injury. Demographics, symptoms, physical exam, flexible laryngoscopy findings, treatment and intervention were recorded. All patients with crack cocaine induced thermal injury presented with mouth or throat pain plus at least one other laryngeal symptom, such as globus sensation, dysphagia or throat tightness. On physical exam, the supraglottis was the most common subsite of endolaryngeal injury. The only statistically significant finding was the number of subsites on initial …


Working With People With Disabilities: An Interactive Video/Lecture Session For First- And Second-Year Medical Students., Sandra L Hearn, Pamela J Hearn Jun 2020

Working With People With Disabilities: An Interactive Video/Lecture Session For First- And Second-Year Medical Students., Sandra L Hearn, Pamela J Hearn

Articles, Abstracts, and Reports

Introduction: Negative physician attitudes toward people with disabilities create barriers to health care for these individuals. Barriers can include withholding of standard medical and preventive care, provision of inferior treatment, and patient mistrust of the health care system. Thus, preparing medical students to care for people with disabilities is especially important. Educating health care providers early in their careers can shape their interactions while their approach to patients is still deliberate.

Methods: We developed an interactive introductory session for first- and second-year medical students on how to approach individuals with observable disability in clinical settings. In the session, we explored-through …


Integrated Assessment Of Circulating Cell-Free Microrna Signatures In Plasma Of Patients With Melanoma Brain Metastasis., Matias Bustos, Kevin Tran, Negin Rahimzadeh, Rebecca Gross, Selena Y Lin, Yoshiaki Shoji, Tomohiro Murakami, Christine L Boley, Linh T Tran, Hunter Cole, Daniel F Kelly, Steven J O'Day, Dave Hoon Jun 2020

Integrated Assessment Of Circulating Cell-Free Microrna Signatures In Plasma Of Patients With Melanoma Brain Metastasis., Matias Bustos, Kevin Tran, Negin Rahimzadeh, Rebecca Gross, Selena Y Lin, Yoshiaki Shoji, Tomohiro Murakami, Christine L Boley, Linh T Tran, Hunter Cole, Daniel F Kelly, Steven J O'Day, Dave Hoon

Articles, Abstracts, and Reports

Primary cutaneous melanoma frequently metastasizes to distant organs including the brain. Identification of cell-free microRNAs (cfmiRs) found in the blood can be used as potential body fluid biomarkers for detecting and monitoring patients with melanoma brain metastasis (MBM). In this pilot study, we initially aimed to identify cfmiRs in the blood of MBM patients. Normal donors plasma (healthy, n = 48) and pre-operative MBM patients' plasma samples (n = 36) were compared for differences in >2000 microRNAs (miRs) using a next generation sequencing (NGS) probe-based assay. A 74 cfmiR signature was identified in an initial cohort of MBM plasma …


Advancing Human Health In The Decade Ahead: Pregnancy As A Key Window For Discovery: A Burroughs Wellcome Fund Pregnancy Think Tank., Yoel Sadovsky, Sam Mesiano, Graham J Burton, Michelle Lampl, Jeffrey C Murray, Rachel M Freathy, Anita Mahadevan-Jansen, Ashley Moffett, Nathan D Price, Paul H Wise, Derek E Wildman, Ralph Snyderman, Nigel Paneth, John Anthony Capra, Marcelo A Nobrega, Yaacov Barak, Louis J Muglia Jun 2020

Advancing Human Health In The Decade Ahead: Pregnancy As A Key Window For Discovery: A Burroughs Wellcome Fund Pregnancy Think Tank., Yoel Sadovsky, Sam Mesiano, Graham J Burton, Michelle Lampl, Jeffrey C Murray, Rachel M Freathy, Anita Mahadevan-Jansen, Ashley Moffett, Nathan D Price, Paul H Wise, Derek E Wildman, Ralph Snyderman, Nigel Paneth, John Anthony Capra, Marcelo A Nobrega, Yaacov Barak, Louis J Muglia

Articles, Abstracts, and Reports

Recent revolutionary advances at the intersection of medicine, omics, data sciences, computing, epidemiology, and related technologies inspire us to ponder their impact on health. Their potential impact is particularly germane to the biology of pregnancy and perinatal medicine, where limited improvement in health outcomes for women and children has remained a global challenge. We assembled a group of experts to establish a Pregnancy Think Tank to discuss a broad spectrum of major gestational disorders and adverse pregnancy outcomes that affect maternal-infant lifelong health and should serve as targets for leveraging the many recent advances. This report reflects avenues for future …


Longitudinal Analysis Reveals Transition Barriers Between Dominant Ecological States In The Gut Microbiome., Roie Levy, Andrew T Magis, John C Earls, Ohad Manor, Tomasz Wilmanski, Jennifer Lovejoy, Sean M Gibbons, Gilbert S Omenn, Leroy Hood, Nathan D Price Jun 2020

Longitudinal Analysis Reveals Transition Barriers Between Dominant Ecological States In The Gut Microbiome., Roie Levy, Andrew T Magis, John C Earls, Ohad Manor, Tomasz Wilmanski, Jennifer Lovejoy, Sean M Gibbons, Gilbert S Omenn, Leroy Hood, Nathan D Price

Articles, Abstracts, and Reports

The Pioneer 100 Wellness Project involved quantitatively profiling 108 participants' molecular physiology over time, including genomes, gut microbiomes, blood metabolomes, blood proteomes, clinical chemistries, and data from wearable devices. Here, we present a longitudinal analysis focused specifically around the Pioneer 100 gut microbiomes. We distinguished a subpopulation of individuals with reduced gut diversity, elevated relative abundance of the genus Prevotella, and reduced levels of the genus Bacteroides We found that the relative abundances of Bacteroides and Prevotella were significantly correlated with certain serum metabolites, including omega-6 fatty acids. Primary dimensions in distance-based redundancy analysis of clinical chemistries explained 18.5% …


Complex Oncological Decision-Making Utilizing Fast-And-Frugal Trees In A Community Setting-Role Of Academic And Hybrid Modeling., Ravi Salgia, Isa Mambetsariev, Tingting Tan, Amanda Schwer, Daryl Pearlstein, Hazem Chehabi, Angel Baroz, Jeremy Fricke, Rebecca Pharaon, Hannah Romo, Thomas Waddington, Razmig Babikian, Linda Buck, Prakash Kulkarni, Mary Cianfrocca, Benjamin Djulbegovic, Sumanta K Pal Jun 2020

Complex Oncological Decision-Making Utilizing Fast-And-Frugal Trees In A Community Setting-Role Of Academic And Hybrid Modeling., Ravi Salgia, Isa Mambetsariev, Tingting Tan, Amanda Schwer, Daryl Pearlstein, Hazem Chehabi, Angel Baroz, Jeremy Fricke, Rebecca Pharaon, Hannah Romo, Thomas Waddington, Razmig Babikian, Linda Buck, Prakash Kulkarni, Mary Cianfrocca, Benjamin Djulbegovic, Sumanta K Pal

Articles, Abstracts, and Reports

Non-small cell lung cancer is a devastating disease and with the advent of targeted therapies and molecular testing, the decision-making process has become complex. While established guidelines and pathways offer some guidance, they are difficult to utilize in a busy community practice and are not always implemented in the community. The rationale of the study was to identify a cohort of patients with lung adenocarcinoma at a City of Hope community site (n = 11) and utilize their case studies to develop a decision-making framework utilizing fast-and-frugal tree (FFT) heuristics. Most patients had stage IV (N = 9, 81.8%) disease …


Discrimination Of Benign From Malignant Breast Lesions In Dense Breasts With Model-Based Analysis Of Regions-Of-Interest Using Directional Diffusion-Weighted Images., Alan I Penn, Milica Medved, Vandana Dialani, Etta D Pisano, Elodia B Cole, David Brousseau, Gregory S Karczmar, Guimin Gao, Barry D Reich, Hiroyuki Abe Jun 2020

Discrimination Of Benign From Malignant Breast Lesions In Dense Breasts With Model-Based Analysis Of Regions-Of-Interest Using Directional Diffusion-Weighted Images., Alan I Penn, Milica Medved, Vandana Dialani, Etta D Pisano, Elodia B Cole, David Brousseau, Gregory S Karczmar, Guimin Gao, Barry D Reich, Hiroyuki Abe

Articles, Abstracts, and Reports

BACKGROUND: There is an increasing interest in non-contrast-enhanced magnetic resonance imaging (MRI) for detecting and evaluating breast lesions. We present a methodology utilizing lesion core and periphery region of interest (ROI) features derived from directional diffusion-weighted imaging (DWI) data to evaluate performance in discriminating benign from malignant lesions in dense breasts.

METHODS: We accrued 55 dense-breast cases with 69 lesions (31 benign; 38 cancer) at a single institution in a prospective study; cases with ROIs exceeding 7.50 cm

RESULTS: The region-growing algorithm for 3D lesion model generation improved inter-observer variability over hand drawn ROIs (DSC: 0.66 vs 0.56 (p < 0.001) with substantial agreement (DSC > 0.8) …


Psjh Telehealth Covid-19 Repsonse, Todd Czartoski Jun 2020

Psjh Telehealth Covid-19 Repsonse, Todd Czartoski

Articles, Abstracts, and Reports

No abstract provided.


Medial Femoral Condyle Vascularized Bone Graft For Treatment Of Midshaft Clavicle Recalcitrant Nonunion With Use Of The Transverse Cervical Artery As An Anastomosis., Christopher M Belyea, Jefferson L Lansford, Joseph B Golden, Emily H Shin, Rey D L Gumboc Jun 2020

Medial Femoral Condyle Vascularized Bone Graft For Treatment Of Midshaft Clavicle Recalcitrant Nonunion With Use Of The Transverse Cervical Artery As An Anastomosis., Christopher M Belyea, Jefferson L Lansford, Joseph B Golden, Emily H Shin, Rey D L Gumboc

Articles, Abstracts, and Reports

Vascularized medial femoral condyle bone grafts have been reported to be a reliable treatment for recalcitrant bony nonunions of the extremities. Although clavicle fracture nonunions are rare after treatment with open reduction internal fixation, symptomatic nonunions can be a challenge. The medial femoral condyle vascularized bone graft has been described as a treatment option for clavicle nonunions with the thoracoacromial trunk as the recipient anastomosis site. This case illustrates how the transverse cervical artery and accompanying veins can be used as an anastomosis when the thoracoacromial trunk is inaccessible because of previous surgical- and infection-related scaring. At the final follow-up, …


Robotic Surgery For Gynecologic Cancers: Indications, Techniques And Controversies., Kiran H Clair, Krishnansu S Tewari Jun 2020

Robotic Surgery For Gynecologic Cancers: Indications, Techniques And Controversies., Kiran H Clair, Krishnansu S Tewari

Articles, Abstracts, and Reports

Minimally invasive surgery for gynecologic cancers is associated with fewer postoperative complications including less blood loss and quicker recovery time compared to traditional laparotomy. The robotic platform has allowed patients access to minimally invasive surgery due to its increased utilization by gynecologic oncologists. Many surgeons have embraced the robotic platform due to its technological advances over traditional laparoscopy including high-definition 3D optics, wristed instrumentation, camera stability and improved ergonomics. While robotic surgery continues as a mainstay in the management of gynecologic cancers, it remains controversial in regards to its cost effectiveness and more recently, its long-term impact on clinical and …


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 Jun 2020

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 …


Novel Application Of Vinylpolysiloxane Hearing Aid Impression Mold As Patient-Specific Bolus For Head And Neck Cancer Radiotherapy., Anne Elizabeth Gunter, John Burgoyne, Min Park, Namou Kim, Daliang Cao, Vivek Mehta Jun 2020

Novel Application Of Vinylpolysiloxane Hearing Aid Impression Mold As Patient-Specific Bolus For Head And Neck Cancer Radiotherapy., Anne Elizabeth Gunter, John Burgoyne, Min Park, Namou Kim, Daliang Cao, Vivek Mehta

Articles, Abstracts, and Reports

Hearing aid impression material composed of vinylpolysiloxane is an ideal bolus material which may be used to aid in delivery of adjuvant radiation to complex surgical defects of the head and neck. It is affordable, easily accessed, and efficient.


Bilateral Pulmonary Metastases Of Papillary Thyroid Carcinoma In A 12-Year-Old Child-A Case Report And Review Of The Literature., V Thirumala, C O'Souji, S Thirumala Jun 2020

Bilateral Pulmonary Metastases Of Papillary Thyroid Carcinoma In A 12-Year-Old Child-A Case Report And Review Of The Literature., V Thirumala, C O'Souji, S Thirumala

Articles, Abstracts, and Reports

Metastatic disease of the lung has been extensively documented in the adult patient population. The most common primary sources for pulmonary metastases include breast, colon gastrointestinal including pancreas and urinary bladder. Malignant lung tumors in pediatric population is extremely rare. However, like in adult patient population, metastases are more common than primary tumors in lung in pediatric patients. Metastatic spread of tumors can occur both by way of hematogenous spread and lymphatic pathways. We present a rare case of biopsy proven metastatic thyroid carcinoma in the lung in a 12-year-old male child masquerading as bilateral miliary nodules on imaging studies. …


Progress In The Seasonal Variations Of Blood Lipids: A Mini-Review., Xiaochun Ma, Haichen Yan, Haizhou Zhang, Mansen Wang, Qunye Zhang, Xiaoming Zhou May 2020

Progress In The Seasonal Variations Of Blood Lipids: A Mini-Review., Xiaochun Ma, Haichen Yan, Haizhou Zhang, Mansen Wang, Qunye Zhang, Xiaoming Zhou

Articles, Abstracts, and Reports

The seasonal variations of blood lipids have recently gained increasing interest in this field of lipid metabolism. Elucidating the seasonal patterns of blood lipids is particularly helpful for the prevention and treatment of cardiovascular and cerebrovascular diseases. However, the previous results remain controversial and the underlying mechanisms are still unclear. This mini-review is focused on summarizing the literature relevant to the seasonal variability of blood lipid parameters, as well as on discussing its significance in clinical diagnoses and management decisions.


Correction To: Small Molecule Kras Agonist For Mutant Kras Cancer Therapy., Ke Xu, Dongkyoo Park, Andrew T Magis, Jun Zhang, Wei Zhou, Gabriel L Sica, Suresh S Ramalingam, Walter J Curran, Xingming Deng May 2020

Correction To: Small Molecule Kras Agonist For Mutant Kras Cancer Therapy., Ke Xu, Dongkyoo Park, Andrew T Magis, Jun Zhang, Wei Zhou, Gabriel L Sica, Suresh S Ramalingam, Walter J Curran, Xingming Deng

Articles, Abstracts, and Reports

An amendment to this paper has been published and can be accessed via the original article.


Ire1Α And Igf Signaling Predict Resistance To An Endoplasmic Reticulum Stress-Inducing Drug In Glioblastoma Cells., Jeffrey J Rodvold, Su Xian, Julia Nussbacher, Brian Tsui, T Cameron Waller, Stephen C Searles, Alyssa Lew, Pengfei Jiang, Ivan Babic, Natsuko Nomura, Jonathan H Lin, Santosh Kesari, Hannah Carter, Maurizio Zanetti May 2020

Ire1Α And Igf Signaling Predict Resistance To An Endoplasmic Reticulum Stress-Inducing Drug In Glioblastoma Cells., Jeffrey J Rodvold, Su Xian, Julia Nussbacher, Brian Tsui, T Cameron Waller, Stephen C Searles, Alyssa Lew, Pengfei Jiang, Ivan Babic, Natsuko Nomura, Jonathan H Lin, Santosh Kesari, Hannah Carter, Maurizio Zanetti

Articles, Abstracts, and Reports

To date current therapies of glioblastoma multiforme (GBM) are largely ineffective. The induction of apoptosis by an unresolvable unfolded protein response (UPR) represents a potential new therapeutic strategy. Here we tested 12ADT, a sarcoendoplasmic reticulum Ca2+ ATPase (SERCA) inhibitor, on a panel of unselected patient-derived neurosphere-forming cells and found that GBM cells can be distinguished into "responder" and "non-responder". By RNASeq analysis we found that the non-responder phenotype is significantly linked with the expression of UPR genes, and in particular ERN1 (IRE1) and ATF4. We also identified two additional genes selectively overexpressed among non-responders, IGFBP3 and IGFBP5. CRISPR-mediated deletion of …


Allosteric Inhibitor Of Β-Catenin Selectively Targets Oncogenic Wnt Signaling In Colon Cancer., Anton Cheltsov, Natsuko Nomura, Venkata Mahidhar Yenugonda, Jatin Roper, Rajesh Mukthavaram, Pengfei Jiang, Nam-Gu Her, Ivan Babic, Santosh Kesari, Elmar Nurmemmedov May 2020

Allosteric Inhibitor Of Β-Catenin Selectively Targets Oncogenic Wnt Signaling In Colon Cancer., Anton Cheltsov, Natsuko Nomura, Venkata Mahidhar Yenugonda, Jatin Roper, Rajesh Mukthavaram, Pengfei Jiang, Nam-Gu Her, Ivan Babic, Santosh Kesari, Elmar Nurmemmedov

Articles, Abstracts, and Reports

Abnormal regulation of β-catenin initiates an oncogenic program that serves as a main driver of many cancers. Albeit challenging, β-catenin is an attractive drug target due to its role in maintenance of cancer stem cells and potential to eliminate cancer relapse. We have identified C2, a novel β-catenin inhibitor, which is a small molecule that binds to a novel allosteric site on the surface of β-catenin. C2 selectively inhibits β-catenin, lowers its cellular load and significantly reduces viability of β-catenin-driven cancer cells. Through direct binding to β-catenin, C2 renders the target inactive that eventually activates proteasome system for its removal. …


Abstract 219: Use Of Machine Learning Models To Identify Atherosclerotic Cardiovascular Disease Patients At Very High Risk For Future Events In A Multi-State Health Care System, Hsin-Fang Li, Amir Ali, Kateri Spinelli, A Sajja, Ss Virani, Ss Martin, Tyler J Gluckman May 2020

Abstract 219: Use Of Machine Learning Models To Identify Atherosclerotic Cardiovascular Disease Patients At Very High Risk For Future Events In A Multi-State Health Care System, Hsin-Fang Li, Amir Ali, Kateri Spinelli, A Sajja, Ss Virani, Ss Martin, Tyler J Gluckman

Articles, Abstracts, and Reports

Background: In the 2018 AHA/ACC Blood Cholesterol Guideline, it is recommended that ASCVD patients be classified as very high-risk (VHR) vs not-VHR (NVHR) to guide treatment decisions. This has important implications for ezetimibe and PCSK9 inhibitor eligibility. We aimed to develop a tool that could assist in more easily identifying VHR patients based on machine learning (ML) techniques. This approach offers a powerful, assumption-free alternative to conventional methods, such as logistic regression, to identify potential interactions among risk factors while incorporating the hierarchy of interaction among variables.

Method: We used EHR-derived ICD-10 codes to identify patients within our health system …


Safety And Activity Of Varlilumab, A Novel And First-In-Class Agonist Anti-Cd27 Antibody, For Hematologic Malignancies., Stephen M Ansell, Ian Flinn, Matthew H Taylor, Branimir I Sikic, Joshua Brody, John Nemunaitis, Andrew Feldman, Thomas R Hawthorne, Tracey Rawls, Tibor Keler, Michael J Yellin May 2020

Safety And Activity Of Varlilumab, A Novel And First-In-Class Agonist Anti-Cd27 Antibody, For Hematologic Malignancies., Stephen M Ansell, Ian Flinn, Matthew H Taylor, Branimir I Sikic, Joshua Brody, John Nemunaitis, Andrew Feldman, Thomas R Hawthorne, Tracey Rawls, Tibor Keler, Michael J Yellin

Articles, Abstracts, and Reports

CD27, a costimulatory molecule on T cells, induces intracellular signals mediating cellular activation, proliferation, effector function, and cell survival on binding to its ligand, CD70. Varlilumab, a novel, first-in-class, agonist immunoglobulin G1 anti-CD27 antibody, mediates antitumor immunity and direct killing of CD27+ tumor cells in animal models. This first-in-human, dose-escalation, and expansion study evaluated varlilumab in patients with hematologic malignancies. Primary objectives were to assess safety and the maximum tolerated and optimal biologic doses of varlilumab. Secondary objectives were to evaluate pharmacokinetics, pharmacodynamics, immunogenicity, and antitumor activity. In a 3 + 3 dose-escalation design, 30 patients with B-cell (n = …


Protein-Altering Germline Mutations Implicate Novel Genes Related To Lung Cancer Development., Xuemei Ji, Semanti Mukherjee, Maria Teresa Landi, Yohan Bosse, Philippe Joubert, Dakai Zhu, Ivan Gorlov, Xiangjun Xiao, Younghun Han, Olga Gorlova, Rayjean J Hung, Yonathan Brhane, Robert Carreras-Torres, David C Christiani, Neil Caporaso, Mattias Johansson, Geoffrey Liu, Stig E Bojesen, Loic Le Marchand, Demetrios Albanes, Heike Bickeböller, Melinda C Aldrich, William S Bush, Adonina Tardon, Gad Rennert, Chu Chen, Jinyoung Byun, Konstantin H Dragnev, John K Field, Lambertus Fa Kiemeney, Philip Lazarus, Shan Zienolddiny, Stephen Lam, Matthew B Schabath, Angeline S Andrew, Pier A Bertazzi, Angela C Pesatori, Nancy Diao, Li Su, Lei Song, Ruyang Zhang, Natasha Leighl, Jakob S Johansen, Anders Mellemgaard, Walid Saliba, Christopher Haiman, Lynne Wilkens, Ana Fernandez-Somoano, Guillermo Fernandez-Tardon, Erik H F M Van Der Heijden, Jin Hee Kim, Michael P A Davies, Michael W Marcus, Hans Brunnström, Jonas Manjer, Olle Melander, David C Muller, Kim Overvad, Antonia Trichopoulou, Rosario Tumino, Gary E Goodman, Angela Cox, Fiona Taylor, Penella Woll, Erich Wichmann, Thomas Muley, Angela Risch, Albert Rosenberger, Kjell Grankvist, Mikael Johansson, Frances Shepherd, Ming-Sound Tsao, Susanne M Arnold, Eric B Haura, Ciprian Bolca, Ivana Holcatova, Vladimir Janout, Milica Kontic, Jolanta Lissowska, Anush Mukeria, Simona Ognjanovic, Tadeusz M Orlowski, Ghislaine Scelo, Beata Swiatkowska, David Zaridze, Per Bakke, Vidar Skaug, Lesley M Butler, Kenneth Offit, Preethi Srinivasan, Chaitanya Bandlamudi, Matthew D Hellmann, David B Solit, Mark E Robson, Charles M Rudin, Zsofia K Stadler, Barry S Taylor, Michael F Berger, Richard Houlston, John Mclaughlin, Victoria Stevens, David C Nickle, Ma'en Obeidat, Wim Timens, María Soler Artigas, Sanjay Shete, Hermann Brenner, Stephen Chanock, Paul Brennan, James D Mckay, Christopher I Amos May 2020

Protein-Altering Germline Mutations Implicate Novel Genes Related To Lung Cancer Development., Xuemei Ji, Semanti Mukherjee, Maria Teresa Landi, Yohan Bosse, Philippe Joubert, Dakai Zhu, Ivan Gorlov, Xiangjun Xiao, Younghun Han, Olga Gorlova, Rayjean J Hung, Yonathan Brhane, Robert Carreras-Torres, David C Christiani, Neil Caporaso, Mattias Johansson, Geoffrey Liu, Stig E Bojesen, Loic Le Marchand, Demetrios Albanes, Heike Bickeböller, Melinda C Aldrich, William S Bush, Adonina Tardon, Gad Rennert, Chu Chen, Jinyoung Byun, Konstantin H Dragnev, John K Field, Lambertus Fa Kiemeney, Philip Lazarus, Shan Zienolddiny, Stephen Lam, Matthew B Schabath, Angeline S Andrew, Pier A Bertazzi, Angela C Pesatori, Nancy Diao, Li Su, Lei Song, Ruyang Zhang, Natasha Leighl, Jakob S Johansen, Anders Mellemgaard, Walid Saliba, Christopher Haiman, Lynne Wilkens, Ana Fernandez-Somoano, Guillermo Fernandez-Tardon, Erik H F M Van Der Heijden, Jin Hee Kim, Michael P A Davies, Michael W Marcus, Hans Brunnström, Jonas Manjer, Olle Melander, David C Muller, Kim Overvad, Antonia Trichopoulou, Rosario Tumino, Gary E Goodman, Angela Cox, Fiona Taylor, Penella Woll, Erich Wichmann, Thomas Muley, Angela Risch, Albert Rosenberger, Kjell Grankvist, Mikael Johansson, Frances Shepherd, Ming-Sound Tsao, Susanne M Arnold, Eric B Haura, Ciprian Bolca, Ivana Holcatova, Vladimir Janout, Milica Kontic, Jolanta Lissowska, Anush Mukeria, Simona Ognjanovic, Tadeusz M Orlowski, Ghislaine Scelo, Beata Swiatkowska, David Zaridze, Per Bakke, Vidar Skaug, Lesley M Butler, Kenneth Offit, Preethi Srinivasan, Chaitanya Bandlamudi, Matthew D Hellmann, David B Solit, Mark E Robson, Charles M Rudin, Zsofia K Stadler, Barry S Taylor, Michael F Berger, Richard Houlston, John Mclaughlin, Victoria Stevens, David C Nickle, Ma'en Obeidat, Wim Timens, María Soler Artigas, Sanjay Shete, Hermann Brenner, Stephen Chanock, Paul Brennan, James D Mckay, Christopher I Amos

Articles, Abstracts, and Reports

Few germline mutations are known to affect lung cancer risk. We performed analyses of rare variants from 39,146 individuals of European ancestry and investigated gene expression levels in 7,773 samples. We find a large-effect association with an ATM L2307F (rs56009889) mutation in adenocarcinoma for discovery (adjusted Odds Ratio = 8.82, P = 1.18 × 10-15) and replication (adjusted OR = 2.93, P = 2.22 × 10-3) that is more pronounced in females (adjusted OR = 6.81 and 3.19 and for discovery and replication). We observe an excess loss of heterozygosity in lung tumors among ATM L2307F allele carriers. L2307F is …


Projected Deaths Of Despair From Covid-19, Stephen Petterson, John M. Westfall, Benjamin F. Miller May 2020

Projected Deaths Of Despair From Covid-19, Stephen Petterson, John M. Westfall, Benjamin F. Miller

Articles, Abstracts, and Reports

More Americans could lose their lives to deaths of despair, deaths due to drug, alcohol, and suicide, if we do not do something immediately. Deaths of despair have been on the rise for the last decade, and in the context of COVID-19, deaths of despair should be seen as the epidemic within the pandemic. The goal of this report is to predict what deaths of despair we might see based on three assumptions during COVID-19: economic recovery, relationship between deaths of despair and unemployment, and geography. Across nine different scenarios, additional deaths of despair range from 27,644 (quick recovery, smallest …


The Society For Immunotherapy Of Cancer Perspective On Regulation Of Interleukin-6 Signaling In Covid-19-Related Systemic Inflammatory Response, Fernanda I. Arnaldez, Steven J. O'Day, Charles G. Drake, Bernard A Fox, Bingqing Fu, Walter Urba, Vincenzo Montesarchio, Jeffrey S. Weber, Haiming Wei, Jon M. Wigginton, Paolo Antonio Ascierto May 2020

The Society For Immunotherapy Of Cancer Perspective On Regulation Of Interleukin-6 Signaling In Covid-19-Related Systemic Inflammatory Response, Fernanda I. Arnaldez, Steven J. O'Day, Charles G. Drake, Bernard A Fox, Bingqing Fu, Walter Urba, Vincenzo Montesarchio, Jeffrey S. Weber, Haiming Wei, Jon M. Wigginton, Paolo Antonio Ascierto

Articles, Abstracts, and Reports

The pandemic caused by the novel coronavirus SARS-CoV-2 has placed an unprecedented burden on healthcare systems around the world. In patients who experience severe disease, acute respiratory distress is often accompanied by a pathological immune reaction, sometimes referred to as ‘cytokine storm’. One hallmark feature of the profound inflammatory state seen in patients with COVID-19 who succumb to pneumonia and hypoxia is marked elevation of serum cytokines, especially interferon gamma, tumor necrosis factor alpha, interleukin 17 (IL-17), interleukin 8 (IL-8) and interleukin 6 (IL-6). Initial experience from the outbreaks in Italy, China and the USA has anecdotally demonstrated improved outcomes …


The Society For Immunotherapy Of Cancer Statement On Best Practices For Multiplex Immunohistochemistry (Ihc) And Immunofluorescence (If) Staining And Validation., Janis M Taube, Guray Akturk, Michael Angelo, Elizabeth L Engle, Sacha Gnjatic, Shirley Greenbaum, Noah F Greenwald, Cyrus V Hedvat, Travis J Hollmann, Jonathan Juco, Edwin R Parra, Marlon C Rebelatto, David L Rimm, Jaime Rodriguez-Canales, Kurt A Schalper, Edward C Stack, Cláudia S Ferreira, Konstanty Korski, Ana Lako, Scott J Rodig, Emanuel Schenck, Keith E Steele, Michael J Surace, Michael T Tetzlaff, Katharina Von Loga, Ignacio I Wistuba, Carlo Bifulco, Society For Immunotherapy Of Cancer (Sitc) Pathology Task Force. May 2020

The Society For Immunotherapy Of Cancer Statement On Best Practices For Multiplex Immunohistochemistry (Ihc) And Immunofluorescence (If) Staining And Validation., Janis M Taube, Guray Akturk, Michael Angelo, Elizabeth L Engle, Sacha Gnjatic, Shirley Greenbaum, Noah F Greenwald, Cyrus V Hedvat, Travis J Hollmann, Jonathan Juco, Edwin R Parra, Marlon C Rebelatto, David L Rimm, Jaime Rodriguez-Canales, Kurt A Schalper, Edward C Stack, Cláudia S Ferreira, Konstanty Korski, Ana Lako, Scott J Rodig, Emanuel Schenck, Keith E Steele, Michael J Surace, Michael T Tetzlaff, Katharina Von Loga, Ignacio I Wistuba, Carlo Bifulco, Society For Immunotherapy Of Cancer (Sitc) Pathology Task Force.

Articles, Abstracts, and Reports

OBJECTIVES: The interaction between the immune system and tumor cells is an important feature for the prognosis and treatment of cancer. Multiplex immunohistochemistry (mIHC) and multiplex immunofluorescence (mIF) analyses are emerging technologies that can be used to help quantify immune cell subsets, their functional state, and their spatial arrangement within the tumor microenvironment.

METHODS: The Society for Immunotherapy of Cancer (SITC) convened a task force of pathologists and laboratory leaders from academic centers as well as experts from pharmaceutical and diagnostic companies to develop best practice guidelines for the optimization and validation of mIHC/mIF assays across platforms.

RESULTS: Representative outputs …


Effect Of Pembrolizumab Plus Neoadjuvant Chemotherapy On Pathologic Complete Response In Women With Early-Stage Breast Cancer: An Analysis Of The Ongoing Phase 2 Adaptively Randomized I-Spy2 Trial., Rita Nanda, Minetta C Liu, Christina Yau, Rebecca Shatsky, Lajos Pusztai, Anne Wallace, A Jo Chien, Andres Forero-Torres, Erin D Ellis, Heather Han, Amy Clark, Kathy Albain, Judy C Boughey, Nora T Jaskowiak, Anthony Elias, Claudine Isaacs, Kathleen Kemmer, Teresa Helsten, Melanie Majure, Erica Stringer-Reasor, Catherine Parker, Marie C Lee, Tufia Haddad, Ronald N Cohen, Smita Asare, Amy Wilson, Gillian L Hirst, Ruby Singhrao, Katherine Steeg, Adam Asare, Jeffrey B Matthews, Scott Berry, Ashish Sanil, Richard Schwab, W Fraser Symmans, Laura Van 'T Veer, Douglas Yee, Angela Demichele, Nola M Hylton, Michelle Melisko, Jane Perlmutter, Hope S Rugo, Donald A Berry, Laura J Esserman May 2020

Effect Of Pembrolizumab Plus Neoadjuvant Chemotherapy On Pathologic Complete Response In Women With Early-Stage Breast Cancer: An Analysis Of The Ongoing Phase 2 Adaptively Randomized I-Spy2 Trial., Rita Nanda, Minetta C Liu, Christina Yau, Rebecca Shatsky, Lajos Pusztai, Anne Wallace, A Jo Chien, Andres Forero-Torres, Erin D Ellis, Heather Han, Amy Clark, Kathy Albain, Judy C Boughey, Nora T Jaskowiak, Anthony Elias, Claudine Isaacs, Kathleen Kemmer, Teresa Helsten, Melanie Majure, Erica Stringer-Reasor, Catherine Parker, Marie C Lee, Tufia Haddad, Ronald N Cohen, Smita Asare, Amy Wilson, Gillian L Hirst, Ruby Singhrao, Katherine Steeg, Adam Asare, Jeffrey B Matthews, Scott Berry, Ashish Sanil, Richard Schwab, W Fraser Symmans, Laura Van 'T Veer, Douglas Yee, Angela Demichele, Nola M Hylton, Michelle Melisko, Jane Perlmutter, Hope S Rugo, Donald A Berry, Laura J Esserman

Articles, Abstracts, and Reports

Importance: Approximately 25% of patients with early-stage breast cancer who receive (neo)adjuvant chemotherapy experience a recurrence within 5 years. Improvements in therapy are greatly needed.

Objective: To determine if pembrolizumab plus neoadjuvant chemotherapy (NACT) in early-stage breast cancer is likely to be successful in a 300-patient, confirmatory randomized phase 3 neoadjuvant clinical trial.

Design, Setting, and Participants: The I-SPY2 study is an ongoing open-label, multicenter, adaptively randomized phase 2 platform trial for high-risk, stage II/III breast cancer, evaluating multiple investigational arms in parallel. Standard NACT serves as the common control arm; investigational agent(s) are added to this backbone. Patients with …


Heterodimeric Il-15 Delays Tumor Growth And Promotes Intratumoral Ctl And Dendritic Cell Accumulation By A Cytokine Network Involving Xcl1, Ifn-Γ, Cxcl9 And Cxcl10., Cristina Bergamaschi, Hrishikesh Pandit, Bethany A Nagy, Dimitris Stellas, Shawn M. Jensen, Jenifer Bear, Maggie Cam, Antonio Valentin, Bernard A Fox, Barbara K Felber, George N Pavlakis May 2020

Heterodimeric Il-15 Delays Tumor Growth And Promotes Intratumoral Ctl And Dendritic Cell Accumulation By A Cytokine Network Involving Xcl1, Ifn-Γ, Cxcl9 And Cxcl10., Cristina Bergamaschi, Hrishikesh Pandit, Bethany A Nagy, Dimitris Stellas, Shawn M. Jensen, Jenifer Bear, Maggie Cam, Antonio Valentin, Bernard A Fox, Barbara K Felber, George N Pavlakis

Articles, Abstracts, and Reports

BACKGROUND: Interleukin-15 (IL-15) promotes growth and activation of cytotoxic CD8

METHODS: The antitumor activity of hetIL-15 produced from mammalian cells was tested in mouse tumor models (MC38 colon carcinoma and TC-1 epithelial carcinoma). The functional diversity of the immune infiltrate and the cytokine/chemokine network within the tumor was evaluated by flow cytometry, multicolor immunohistochemistry (IHC), gene expression profiling by Nanostring Technologies, and protein analysis by electrochemiluminescence and ELISA assays.

RESULTS: hetIL-15 treatment resulted in delayed primary tumor growth. Increased NK and CD8

CONCLUSIONS: Our results show that hetIL-15 administration enhances T cell entry into tumors, increasing the success rate of …


Are "Replicants" The Spine Surgeons Of The Future?, Jens R Chapman, Jeffrey C Wang, Karsten Wiechert May 2020

Are "Replicants" The Spine Surgeons Of The Future?, Jens R Chapman, Jeffrey C Wang, Karsten Wiechert

Articles, Abstracts, and Reports

No abstract provided.