Medical Specialties Commons^™

Perspectives In Melanoma: Meeting Report From The "Melanoma Bridge" (December 5th-7th, 2019, Naples, Italy)., Paolo A Ascierto, Igor Puzanov, Sanjiv S Agarwala, Christian Blank, Richard D Carvajal, Sandra Demaria, Reinhard Dummer, Marc Ernstoff, Soldano Ferrone, Bernard A Fox, Thomas F Gajewski, Claus Garbe, Patrick Hwu, Roger S Lo, Georgina V Long, Jason J Luke, Iman Osman, Michael A Postow, Ryan J Sullivan, Janis M Taube, Giorgio Trinchieri, Hassane M Zarour, Corrado Caracò, Magdalena Thurin

Articles, Abstracts, and Reports

The melanoma treatment landscape changed in 2011 with the approval of the first anti-cytotoxic T-lymphocyte-associated protein (CTLA)-4 checkpoint inhibitor and of the first BRAF-targeted monoclonal antibody, both of which significantly improved overall survival (OS). Since then, improved understanding of the tumor microenvironment (TME) and tumor immune-evasion mechanisms has resulted in new approaches to targeting and harnessing the host immune response. The approval of new immune and targeted therapies has further improved outcomes for patients with advanced melanoma and other combination modalities are also being explored such as chemotherapy, radiotherapy, electrochemotherapy and surgery. In addition, different strategies of drugs administration including …

Sequential Complications Of Hypercalcemia, Necrotizing Granulomatous Vasculitis, And Aplastic Anemia Occurring In One Patient With Angioimmunoblastic T-Cell Lymphoma., Sriman Swarup, Jonathan Kopel, Kyaw Zin Thein, Kaiser Tarafdar, Khatrina Swarup, Seshadri Thirumala, Donald P Quick

Articles, Abstracts, and Reports

In this case report of a patient with angioimmunoblastic T-cell lymphoma (AITL), we describe the occurrence of three sequential complications that have been reported uncommonly in this disease subtype. Firstly, the patient developed hypercalcemia due to elevated 1,25-didydroxyvitamin D. Although hypercalcemia in AITL is not rare (1-2% incidence), this case was unusual in that the complication developed when disease appeared stable and symptomatically, he was doing well otherwise. Hypercalcemia surprisingly resolved a few months later at a time when his disease appeared to be progressing. A year later, the patient presented with digital ischemia necessitating partial amputation of a finger. …

Efficacy And Safety Of First-Line Avelumab In Patients With Advanced Non-Small Cell Lung Cancer: Results From A Phase Ib Cohort Of The Javelin Solid Tumor Study., Claire F Verschraegen, Guy Jerusalem, Edward F Mcclay, Nicholas Iannotti, Charles H Redfern, Jaafar Bennouna, Franklin L Chen, Karen Kelly, Janice Mehnert, John C Morris, Matthew H Taylor, David Spigel, Ding Wang, Hans Juergen Grote, Dongli Zhou, Neru Munshi, Marcis Bajars, James L Gulley

Articles, Abstracts, and Reports

INTRODUCTION: Avelumab, an antiprogrammed death ligand-1 antibody, is approved as a monotherapy for treatment of metastatic Merkel cell carcinoma and advanced urothelial carcinoma, and in combination with axitinib for advanced renal cell carcinoma. We report the efficacy and safety of first-line avelumab in advanced non-small cell lung cancer (NSCLC).

METHODS: In a phase I expansion cohort of the JAVELIN Solid Tumor trial, patients with treatment-naive, metastatic, or recurrent NSCLC received 10 mg/kg avelumab intravenously every 2 weeks. Endpoints included best overall response, duration of response (DOR), progression-free survival (PFS), overall survival (OS), and safety.

RESULTS: Overall, 156 patients were enrolled …

Defining The Proteolytic Landscape During Enterovirus Infection., Mohsan Saeed, Sebastian Kapell, Nicholas T Hertz, Xianfang Wu, Kierstin Bell, Alison W Ashbrook, Milica Tesic Mark, Henry A Zebroski, Maxwell L Neal, Malin Flodström-Tullberg, Margaret R Macdonald, John D Aitchison, Henrik Molina, Charles M Rice

Articles, Abstracts, and Reports

Viruses cleave cellular proteins to remodel the host proteome. The study of these cleavages has revealed mechanisms of immune evasion, resource exploitation, and pathogenesis. However, the full extent of virus-induced proteolysis in infected cells is unknown, mainly because until recently the technology for a global view of proteolysis within cells was lacking. Here, we report the first comprehensive catalog of proteins cleaved upon enterovirus infection and identify the sites within proteins where the cleavages occur. We employed multiple strategies to confirm protein cleavages and assigned them to one of the two enteroviral proteases. Detailed characterization of one substrate, LSM14A, a …

Third-Generation Medium Cross-Linked Polyethylene Demonstrates Very Low Wear In Total Hip Arthroplasty., Omid Jalali, Travis S Scudday, Marie-Claire Fickenscher, Steven L Barnett, Robert S Gorab

Articles, Abstracts, and Reports

Background: Cross-linked polyethylene (XLPE) liners have shown lower wear rates than conventional polyethylene liners in total hip arthroplasty. The primary aim of our study was to report our most recent analysis of wear rates and clinical outcomes of a third-generation XLPE liner. Secondary aims were to investigate the rate of adverse events related to mechanical failure or oxidation of this liner.

Methods: A series of 266 total hip arthroplasties using a specific XLPE liner were retrospectively reviewed. Radiographs were examined to determine linear and volumetric wear rates and presence of osteolysis. Clinical outcomes, revision rates, mechanical failures, and risk factors …

Neoantigen-Specific Cd4(+) T-Cell Response Is Critical For The Therapeutic Efficacy Of Cryo-Thermal Therapy, Peng Peng, Hong-Ming Hu, Ping Liu, Lisa X Xu

Articles, Abstracts, and Reports

Background: Traditional tumor thermal ablations, such as radiofrequency ablation (RFA) and cryoablation, can result in good local control of tumor, but traditional tumor thermal ablations are limited by poor long-term survival due to the failure of control of distal metastasis. Our previous studies developed a novel cryo-thermal therapy to treat the B16F10 melanoma mouse model. Long-term survival and T-cell-mediated durable antitumor immunity were achieved after cryo-thermal therapy, but whether tumor antigen-specific T-cells were augmented by cryo-thermal therapy was not determined.

Methods: The long-term antitumor therapeutic efficacy of cryo-thermal therapy was performed in B16F10 murine melanoma models. Splenocytes derived from mice …

Nonrecurrent Early Post-Transplantation Focal Segmental Glomerulosclerosis., Momina M Ahmed, Massini A Merzkani, Matthew R D'Costa, Muhannad A Leghrouz, Mary E Fidler, Haraldur Bjarnason, Patrick G Dean, Fernando C Fervenza, Sanjit Reddy, Hatem Amer

Articles, Abstracts, and Reports

No abstract provided.

Correction To: Medical Neglect As A Contributor To Poorly Controlled Asthma In Childhood., Barbara L Knox, Francois M Luyet, Debra Esernio-Jenssen

Articles, Abstracts, and Reports

[This corrects the article DOI: 10.1007/s40653-019-00290-0.].

Long Term Survival And Local Control Outcomes From Single Dose Targeted Intraoperative Radiotherapy During Lumpectomy (Targit-Iort) For Early Breast Cancer: Targit-A Randomised Clinical Trial., Jayant S Vaidya, Max Bulsara, Michael Baum, Frederik Wenz, Samuele Massarut, Steffi Pigorsch, Michael Alvarado, Michael Douek, Christobel Saunders, Henrik L Flyger, Wolfgang Eiermann, Chris Brew-Graves, Norman R Williams, Ingrid Potyka, Nicholas Roberts, Marcelle Bernstein, Douglas Brown, Elena Sperk, Siobhan Laws, Marc Sütterlin, Tammy Corica, Steinar Lundgren, Dennis R Holmes, Lorenzo Vinante, Fernando Bozza, Montserrat Pazos, Magali Le Blanc-Onfroy, Günther Gruber, Wojciech Polkowski, Konstantin J Dedes, Marcus Niewald, Jens Blohmer, David Mccready, Richard Hoefer, Pond Kelemen, Gloria Petralia, Mary Falzon, David J Joseph, Jeffrey S Tobias

Articles, Abstracts, and Reports

OBJECTIVE: To determine whether risk adapted intraoperative radiotherapy, delivered as a single dose during lumpectomy, can effectively replace postoperative whole breast external beam radiotherapy for early breast cancer.

DESIGN: Prospective, open label, randomised controlled clinical trial.

SETTING: 32 centres in 10 countries in the United Kingdom, Europe, Australia, the United States, and Canada.

PARTICIPANTS: 2298 women aged 45 years and older with invasive ductal carcinoma up to 3.5 cm in size, cN0-N1, eligible for breast conservation and randomised before lumpectomy (1:1 ratio, blocks stratified by centre) to either risk adapted targeted intraoperative radiotherapy (TARGIT-IORT) or external beam radiotherapy (EBRT).

INTERVENTIONS: …

Molecular Profiling Of Melanoma Brain Metastases Compared To Primary Cutaneous Melanoma And To Extracranial Metastases., Gino K In, Kelsey Poorman, Michelle Saul, Steven O'Day, Jeffrey M Farma, Anthony J Olszanski, Michael S Gordon, Jacob S Thomas, Burton Eisenberg, Lawrence Flaherty, Amy Weise, Steven Daveluy, Geoffrey Gibney, Michael B Atkins, Ari Vanderwalde

Articles, Abstracts, and Reports

BACKGROUND: Brain metastases are a significant cause of mortality and morbidity for patients with melanoma. We hypothesize that the development of brain metastases may be explained by molecular heterogeneity between primary cutaneous melanoma (PCM) or extracranial (ECM) and brain (MBM) melanoma metastases.

MATERIALS AND METHODS: We compared next-generation sequencing, tumor mutational burden (TMB), and immunohistochemical staining for PD-L1 expression, among 132 MBM, 745 PCM, and 1190 ECM.

RESULTS: The most common genetic alterations among MBM included: BRAF (52.4%), NRAS (26.6%), CDKN2A (23.3%), NF1 (18.9%), TP53 (18%), ARID2 (13.8%), SETD2 (11.9%), and PBRM1 (7.5%). Four genes were found with higher frequency …

Incorporating Breast Cancer Recurrence Events Into Population-Based Cancer Registries Using Medical Claims: Cohort Study., Teresa A'Mar, J David Beatty, Catherine Fedorenko, Daniel Markowitz, Thomas Corey, Jane Lange, Stephen M Schwartz, Bin Huang, Jessica Chubak, Ruth Etzioni

Articles, Abstracts, and Reports

BACKGROUND: There is a need for automated approaches to incorporate information on cancer recurrence events into population-based cancer registries.

OBJECTIVE: The aim of this study is to determine the accuracy of a novel data mining algorithm to extract information from linked registry and medical claims data on the occurrence and timing of second breast cancer events (SBCE).

METHODS: We used supervised data from 3092 stage I and II breast cancer cases (with 394 recurrences), diagnosed between 1993 and 2006 inclusive, of patients at Kaiser Permanente Washington and cases in the Puget Sound Cancer Surveillance System. Our goal was to classify …

The Great Debate At 'Immunotherapy Bridge', Naples, December 5, 2019., Paolo A Ascierto, Carlo Bifulco, Jerome Galon, Claus Garbe, Samir N Khleif, Jennifer Mcquade, Kunle Odunsi, Hideho Okada, Chrystal M Paulos, Sergio A Quezada, Hussein A Tawbi, John Timmerman, Giorgio Trinchieri, Lisa H Butterfield, Igor Puzanov

Articles, Abstracts, and Reports

As part of the 2019 Immunotherapy Bridge congress (December 4-5, Naples, Italy), the Great Debate session featured counterpoint views from leading experts on six topical issues in immunotherapy today. These were the use of chimeric antigen receptor T cell therapy in solid tumors, whether the Immunoscore should be more widely used in clinical practice, whether antibody-dependent cellular cytotoxicity is important in the mode of action of anticytotoxic T-lymphocyte-associated protein 4 antibodies, whether the brain is immunologically unique or just another organ, the role of microbiome versus nutrition in affecting responses to immunotherapy, and whether chemotherapy is immunostimulatory or immunosuppressive. Discussion …

Perioperative Anticoagulation Management In Spine Surgery: Initial Findings From The Ao Spine Anticoagulation Global Survey., Philip Louie, Garrett Harada, James Harrop, Thomas Mroz, Khalid Al-Saleh, Giovanni Barbanti Brodano, Jens R Chapman, Michael Fehlings, Serena Hu, Yoshiharu Kawaguchi, Michael Mayer, Venugopal Menon, Jong-Beom Park, Sheeraz Qureshi, Shanmuganathan Rajasekaran, Marcelo Valacco, Luiz Vialle, Jeffrey C Wang, Karsten Wiechert, K Daniel Riew, Dino Samartzis

Articles, Abstracts, and Reports

STUDY DESIGN: Cross-sectional, international survey.

OBJECTIVES: This study addressed the global perspectives concerning perioperative use of pharmacologic thromboprophylaxis during spine surgery along with its risks and benefits.

METHODS: A questionnaire was designed and implemented by expert members in the AO Spine community. The survey was distributed to AO Spine's spine surgeon members (N = 3805). Data included surgeon demographic information, type and region of practice, anticoagulation principles, different patient scenarios, and comorbidities.

RESULTS: A total of 316 (8.3% response rate) spine surgeons completed the survey, representing 64 different countries. Completed surveys were primarily from Europe (31.7%), South/Latin America (19.9%), and …

Life Experiences Associated With Change In Perpetration Of Domestic Violence., Avanti Adhia, Vivian H Lyons, Hannah Cohen-Cline, Ali Rowhani-Rahbar

Articles, Abstracts, and Reports

BACKGROUND: This study assessed whether several adult life experiences, including loss of support, loss of food security, loss of housing, and substance use cessation, are associated with change in domestic violence (DV) perpetration from early to later adulthood. Using 2015 to 2016 cross-sectional, self-report survey data from Medicaid enrollees in Oregon (N = 1620), we assessed change in DV perpetration from early adulthood (19-30 years) to later adulthood (≥ 31 years of age), cut points determined by existing survey questions. Multinomial logistic regression models were constructed to estimate the association between life experiences and physical DV perpetration using odds ratios …

Supervised Exercise Intervention And Overall Activity In Ckd., Mindy M Pike, Aseel Alsouqi, Samuel A E Headley, Katherine Tuttle, Elizabeth Elspeth Evans, Charles M Milch, Kelsey Anne Moody, Michael Germain, Thomas G Stewart, Loren Lipworth, Jonathan Himmelfarb, T Alp Ikizler, Cassianne Robinson-Cohen

Articles, Abstracts, and Reports

Introduction: Patients are often instructed to engage in multiple weekly sessions of exercise to increase physical activity. We aimed to determine whether assignment to a supervised exercise regimen increases overall weekly activity in individuals with chronic kidney disease (CKD).

Methods: We performed a secondary analysis of a pilot randomized 2 × 2 factorial design trial examining the effects of diet and exercise (10%-15% reduction in caloric intake, 3 supervised exercise sessions/wk, combined diet restriction/exercise, and control). Activity was measured as counts detected by accelerometer. Counts data were collected on all days for which an accelerometer was worn at baseline, month …

Brainstem Ischemic Syndrome In Juvenile Nf2., John W Henson, Tara Benkers, Connor Mccormick

Articles, Abstracts, and Reports

Objective: A new case of brainstem ischemic necrosis in a young woman with de novo neurofibromatosis type 2 (NF2) is reported, and given notable similarities to 7 prior cases of brainstem stroke in the literature, features defining a possible syndrome were sought.

Methods: Case review including detailed clinical assessment, neuroimaging analysis, genetic testing, and brain biopsy, followed by a multicase analysis.

Results: Brainstem ischemia in juvenile NF2 typically occurs in teenagers without previously known NF2 as an acute, monophasic presentation with restricted diffusion in the midbrain or pons following a recent hypoperfusion event, normal vascular imaging, obvious intracranial imaging features …

Congenital Myasthenic Syndrome Caused By A Frameshift Insertion Mutation In, Szabolcs Szelinger, Jonida Krate, Keri Ramsey, Samuel P Strom, Perry B Shieh, Hane Lee, Newell Belnap, Chris Balak, Ashley L Siniard, Megan Russell, Ryan Richholt, Matt De Both, Ana M Claasen, Isabelle Schrauwen, Stanley F Nelson, Matthew J Huentelman, David W Craig, Samuel Yang, Steven A Moore, Kumaraswamy Sivakumar, Vinodh Narayanan, Sampathkumar Rangasamy, Ucla Clinical Genomics Center

Articles, Abstracts, and Reports

Objective: Description of a new variant of the glutamine-fructose-6-phosphate transaminase 1 (GFPT1) gene causing congenital myasthenic syndrome (CMS) in 3 children from 2 unrelated families.

Methods: Muscle biopsies, EMG, and whole-exome sequencing were performed.

Results: All 3 patients presented with congenital hypotonia, muscle weakness, respiratory insufficiency, head lag, areflexia, and gastrointestinal dysfunction. Genetic analysis identified a homozygous frameshift insertion in the GFPT1 gene (NM_001244710.1: c.686dupC; p.Arg230Ter) that was shared by all 3 patients. In one of the patients, inheritance of the variant was through uniparental disomy (UPD) with maternal origin. Repetitive nerve stimulation and single-fiber EMG was consistent …

Respiratory Failure Due To A Large Mediastinal Mass In A 4-Year-Old Female With Blast Cell Crisis: A Case Report., Christian I Wade, Cody J Couperus-Mashewske, Mia E Geurts, Nicholas Derfler, John Ngo, Kyle S Couperus

Articles, Abstracts, and Reports

INTRODUCTION: Symptomatic leukostasis is an exceptionally atypical presentation of blast crisis; and when coupled with an enlarged neoplastic mediastinal mass in a four-year-old female, an extremely rare and challenging pediatric emergency arises.

CASE REPORT: We present a unique case of a four-year-old female who arrived via emergency medical services in cardiopulmonary arrest with clinical and radiographic evidence suggestive of bilateral pneumothoraces, prompting bilateral chest tube placement. Further evaluation revealed a large mediastinal mass and a concurrent white blood cell count of 428,400 per milliliter (/mL) (4,400-12,900/mL), with a 96% blast differential, consistent with complications of T-cell acute lymphoblastic leukemia.

CONCLUSION: …

Lower Rates Of Heart Failure And All-Cause Hospitalizations During Pulmonary Artery Pressure-Guided Therapy For Ambulatory Heart Failure: One-Year Outcomes From The Cardiomems Post-Approval Study., David M Shavelle, Akshay S Desai, William T Abraham, Robert C Bourge, Nirav Raval, Lisa D Rathman, J Thomas Heywood, Rita A Jermyn, Jamie Pelzel, Orvar T Jonsson, Maria Rosa Costanzo, John D Henderson, Marie-Elena Brett, Philip B Adamson, Lynne W Stevenson, Cardiomems Post-Approval Study Investigators, Jacob Abraham (Cardiomems Post-Approval Study Investigator)

Articles, Abstracts, and Reports

BACKGROUND: Ambulatory hemodynamic monitoring with an implantable pulmonary artery (PA) sensor is approved for patients with New York Heart Association Class III heart failure (HF) and a prior HF hospitalization (HFH) within 12 months. The objective of this study was to assess the efficacy and safety of PA pressure-guided therapy in routine clinical practice with special focus on subgroups defined by sex, race, and ejection fraction.

METHODS: This multi-center, prospective, open-label, observational, single-arm trial of 1200 patients across 104 centers within the United States with New York Heart Association class III HF and a prior HFH within 12 months evaluated …

Management Of Failed Uka To Tka: Conventional Versus Robotic-Assisted Conversion Technique., Andrew G Yun, Marilena Qutami, Mary Chang-Hwa Chen, Kory B Dylan Pasko

Articles, Abstracts, and Reports

BACKGROUND: Failure of unicompartmental knee arthroplasty (UKA) is a distressing and technically challenging complication. Conventional conversion techniques (CCT) with rods and jigs have produced varying results. A robotic-assisted conversion technique (RCT) is an unexplored, though possibly advantageous, alternative. We compare our reconstructive outcomes between conventional and robotic methods in the management of failed UKA.

METHODS: Thirty-four patients with a failed UKA were retrospectively reviewed. Patients underwent conversion total knee arthroplasty (TKA) with either a CCT or RCT. Seventeen patients were included in each group. All procedures were done by a single surgeon at a single institution, with a mean time …

Long-Term Safety And Tolerability Of Apremilast Versus Placebo In Psoriatic Arthritis: A Pooled Safety Analysis Of Three Phase Iii, Randomized, Controlled Trials., Philip Mease, Dafna D Gladman, Juan J Gomez-Reino, Stephen Hall, Arthur Kavanaugh, Eric Lespessailles, Georg Schett, Maria Paris, Nikolay Delev, Lichen Teng, Jürgen Wollenhaupt

Articles, Abstracts, and Reports

OBJECTIVE: Psoriatic arthritis (PsA) requires long-term treatment, yet safety concerns and monitoring requirements make maintenance a challenge. This analysis of pooled Psoriatic Arthritis Long-term Assessment of Clinical Efficacy (PALACE) 1, 2, and 3 data describes 3-year apremilast safety and tolerability in PsA.

METHODS: Patients with active PsA were randomized (1:1:1) to placebo, apremilast 30 mg twice daily, or apremilast 20 mg twice daily. Placebo patients were re-randomized to apremilast 30 mg twice daily or 20 mg twice daily at week 16 (early escape) or 24. Double-blind treatment continued to week 52; patients could continue apremilast during an open-label, long-term treatment …

Assessing The Effect Of Interventions For Axial Spondyloarthritis According To The Endorsed Asas/Omeract Core Outcome Set: A Meta-Research Study Of Trials Included In Cochrane Reviews., Rikke A Andreasen, Lars E Kristensen, Xenofon Baraliakos, Vibeke Strand, Philip Mease, Maarten De Wit, Torkell Ellingsen, Inger Marie J Hansen, Jamie Kirkham, George A Wells, Peter Tugwell, Lara Maxwell, Maarten Boers, Kenneth Egstrup, Robin Christensen

Articles, Abstracts, and Reports

The Assessment of SpondyloArthritis international Society (ASAS) has defined core sets for (i) symptom-modifying anti-rheumatic drugs (SM-ARD), (ii) clinical record keeping, and (iii) disease-controlling anti-rheumatic therapy (DC-ART). These include the following domains for all three core sets: "physical function," "pain," "spinal mobility," "spinal stiffness," and "patient's global assessment" (PGA). The core set for clinical record keeping further includes the domains "peripheral joints/entheses" and "acute phase reactants," and the core set for DC-ART further includes the domains "fatigue" and "spine radiographs/hip radiographs." The Outcome Measures in Rheumatology (OMERACT) endorsed the core sets in 1998.Using empirical evidence from axSpA trials, we investigated …

Meta-Analysis Of The Alzheimer's Disease Human Brain Transcriptome And Functional Dissection In Mouse Models., Ying-Wooi Wan, Rami Al-Ouran, Carl G Mangleburg, Thanneer M Perumal, Tom V Lee, Katherine Allison, Vivek Swarup, Cory C Funk, Chris Gaiteri, Mariet Allen, Minghui Wang, Sarah M Neuner, Catherine C Kaczorowski, Vivek M Philip, Gareth R Howell, Heidi Martini-Stoica, Hui Zheng, Hongkang Mei, Xiaoyan Zhong, Jungwoo Wren Kim, Valina L Dawson, Ted M Dawson, Ping-Chieh Pao, Li-Huei Tsai, Jean-Vianney Haure-Mirande, Michelle E Ehrlich, Paramita Chakrabarty, Yona Levites, Xue Wang, Eric B Dammer, Gyan Srivastava, Sumit Mukherjee, Solveig K Sieberts, Larsson Omberg, Kristen D Dang, James A Eddy, Phil Snyder, Yooree Chae, Sandeep Amberkar, Wenbin Wei, Winston Hide, Christoph Preuss, Ayla Ergun, Phillip J Ebert, David C Airey, Sara Mostafavi, Lei Yu, Hans-Ulrich Klein, Accelerating Medicines Partnership, Alzheimer’S Disease Consortium, Gregory W Carter, David A Collier, Todd E Golde, Allan I Levey, David A Bennett, Karol Estrada, T Matthew Townsend, Bin Zhang, Eric Schadt, Philip L De Jager, Nathan D Price, Nilüfer Ertekin-Taner, Zhandong Liu, Joshua M Shulman, Lara M Mangravite, Benjamin A Logsdon

Articles, Abstracts, and Reports

We present a consensus atlas of the human brain transcriptome in Alzheimer's disease (AD), based on meta-analysis of differential gene expression in 2,114 postmortem samples. We discover 30 brain coexpression modules from seven regions as the major source of AD transcriptional perturbations. We next examine overlap with 251 brain differentially expressed gene sets from mouse models of AD and other neurodegenerative disorders. Human-mouse overlaps highlight responses to amyloid versus tau pathology and reveal age- and sex-dependent expression signatures for disease progression. Human coexpression modules enriched for neuronal and/or microglial genes broadly overlap with mouse models of AD, Huntington's disease, amyotrophic …

Inter-Tumor Heterogeneity-Melanomas Respond Differently To Gm-Csf-Mediated Activation., Adi Moshe, Sivan Izraely, Orit Sagi-Assif, Sapir Malka, Shlomit Ben-Menachem, Tsipi Meshel, Metsada Pasmanik-Chor, Dave Hoon, Isaac P Witz

Articles, Abstracts, and Reports

Granulocyte-monocyte colony stimulating factor (GM-CSF) is used as an adjuvant in various clinical and preclinical studies with contradictory results. These were attributed to opposing effects of GM-CSF on the immune or myeloid systems of the treated patients or to lack of optimal dosing regimens. The results of the present study point to inter-tumor heterogeneity as a possible mechanism accounting for the contrasting responses to GM-CSF incorporating therapies. Employing xenograft models of human melanomas in nude mice developed in our lab, we detected differential functional responses of melanomas from different patients to GM-CSF both in vitro as well as in vivo. …

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

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

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

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

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

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 …