Medical Specialties Commons^™

Impact Of Time Between Diagnosis And Slnb On Outcomes In Cutaneous Melanoma., Daniel W Nelson, Stacey Stern, David E Elashoff, Robert Elashoff, John F Thompson, Nicola Mozzillo, Omgo E Nieweg, Harald J Hoekstra, Alistair J Cochran, Mark B Faries

Articles, Abstracts, and Reports

BACKGROUND: Hypothetically, delay between melanoma diagnosis and SLNB could affect outcomes, either adversely by allowing growth and dissemination of metastases, or beneficially by allowing development of an anti-melanoma immune response. Available data are conflicting about the effect of SLNB delay on patient survival. Our objective was to determine whether delay between initial diagnosis and SLNB affects outcomes in patients with cutaneous melanoma.

STUDY DESIGN: We performed query and analysis of a large prospectively maintained database of patients with primary cutaneous melanomas undergoing SLNB. An independent dataset from MSLT-1 (Multicenter Selective Lymphadenectomy Trial-1) was used for validation. Primary outcomes included disease-free …

Mismatch Repair Deficiency Predicts Response Of Solid Tumors To Pd-1 Blockade., Dung T Le, Jennifer N Durham, Kellie N Smith, Hao Wang, Bjarne R Bartlett, Laveet K Aulakh, Steve Lu, Holly Kemberling, Cara Wilt, Brandon S Luber, Fay Wong, Nilofer S Azad, Agnieszka A Rucki, Dan Laheru, Ross Donehower, Atif Zaheer, George A Fisher, Todd S Crocenzi, James J Lee, Tim F Greten, Austin G Duffy, Kristen K Ciombor, Aleksandra D Eyring, Bao H Lam, Andrew Joe, S Peter Kang, Matthias Holdhoff, Ludmila Danilova, Leslie Cope, Christian Meyer, Shibin Zhou, Richard M Goldberg, Deborah K Armstrong, Katherine M Bever, Amanda N Fader, Janis Taube, Franck Housseau, David Spetzler, Nianqing Xiao, Drew M Pardoll, Nickolas Papadopoulos, Kenneth W Kinzler, James R Eshleman, Bert Vogelstein, Robert A Anders, Luis A Diaz

Articles, Abstracts, and Reports

The genomes of cancers deficient in mismatch repair contain exceptionally high numbers of somatic mutations. In a proof-of-concept study, we previously showed that colorectal cancers with mismatch repair deficiency were sensitive to immune checkpoint blockade with antibodies to programmed death receptor-1 (PD-1). We have now expanded this study to evaluate the efficacy of PD-1 blockade in patients with advanced mismatch repair-deficient cancers across 12 different tumor types. Objective radiographic responses were observed in 53% of patients, and complete responses were achieved in 21% of patients. Responses were durable, with median progression-free survival and overall survival still not reached. Functional analysis …

Variant Prevertebral Muscle: Unique Cadaveric Findings., Jocelyn R Gonzales, Joe Iwanaga, Rod J Oskouian, R Shane Tubbs

Articles, Abstracts, and Reports

The levator scapulae muscle typically runs from the transverse process of the atlas to the superior angle of the scapula. In this paper, we describe a rare finding identified during a dissection of a male cadaver, wherein a continuation of the right levator scapulae ran past its normal attachment to the C1 transverse process, fusing with the inferior attachment of the rectus capitis lateralis muscle. No variants were found on the opposite side, and the innervation of the levator scapulae muscle variant was typical of that of a normal levator scapulae. We also describe other related variants of the cranial …

Multiparametric Immune Profiling In Hpv- Oral Squamous Cell Cancer., Zipei Feng, Daniel Bethmann, Matthias Kappler, Carmen Ballesteros-Merino, Alexander Eckert, R Bryan Bell, Allen Cheng, Tuan Bui, Rom Leidner, Walter Urba, Kent Johnson, Clifford Hoyt, Carlo Bifulco, Juergen Bukur, Claudia Wickenhauser, Barbara Seliger, Bernard A Fox

Articles, Abstracts, and Reports

Evaluation of T lymphocyte frequency provides prognostic information for patients with oral squamous cell cancer (OSCC). However, the effect of simultaneously evaluating T cell frequency and assessing suppressive elements and defects in antigen-processing machinery (APM) has not been clarified. Simultaneous characterization of CD3+, CD8+, FoxP3+, CD163+, and PD-L1+ cells using multispectral imaging was performed on sections from 119 patients with HPV- OSCC. Expression of β2-microglobulin, MHC class I heavy chain, and large multifunctional peptidase 10 was quantified, and all data were correlated with patient outcome. We found that, consistent with previous reports, high numbers of CD8+ T cells at the …

Protocol Adherence For Continuously Titrated Interventions In Randomized Trials: An Overview Of The Current Methodology And Case Study., F Lauzier, N K Adhikari, A Seely, K K Y Koo, E P Belley-Côté, K E A Burns, D J Cook, F D'Aragon, B Rochwerg, M E Kho, S J W Oczkowksi, E H Duan, M O Meade, A G Day, F Lamontagne

Articles, Abstracts, and Reports

BACKGROUND: The standard definition for protocol adherence is the proportion of all scheduled doses that are delivered. In clinical research, this definition has several limitations when evaluating protocol adherence in trials that study interventions requiring continuous titration.

DISCUSSION: Building upon a specific case study, we analyzed a recent trial of a continuously titrated intervention to assess the impact of different definitions of protocol deviations on the interpretation of protocol adherence. The OVATION pilot trial was an open-label randomized controlled trial of higher (75-80 mmHg) versus lower (60-65 mmHg) mean arterial pressure (MAP) targets for vasopressor therapy in shock. In this …

The Diagnostic Challenge Of Low-Grade Ductal Carcinoma In Situ., Tracy Onega, Donald L Weaver, Paul D Frederick, Kimberly H Allison, Anna N A Tosteson, Patricia A Carney, Berta M Geller, Gary M Longton, Heidi D Nelson, Natalia V Oster, Margaret S Pepe, Joann G Elmore

Articles, Abstracts, and Reports

BACKGROUND: Diagnostic agreement among pathologists is 84% for ductal carcinoma in situ (DCIS). Studies of interpretive variation according to grade are limited.

METHODS: A national sample of 115 pathologists interpreted 240 breast pathology test set cases in the Breast Pathology Study and their interpretations were compared to expert consensus interpretations. We assessed agreement of pathologists' interpretations with a consensus reference diagnosis of DCIS dichotomised into low- and high-grade lesions. Generalised estimating equations were used in logistic regression models of rates of under- and over-interpretation of DCIS by grade.

RESULTS: We evaluated 2097 independent interpretations of DCIS (512 low-grade DCIS and …

Large-Scale Association Analysis Identifies New Lung Cancer Susceptibility Loci And Heterogeneity In Genetic Susceptibility Across Histological Subtypes., James D Mckay, Rayjean J Hung, Younghun Han, Xuchen Zong, Robert Carreras-Torres, David C Christiani, Neil E Caporaso, Mattias Johansson, Xiangjun Xiao, Yafang Li, Jinyoung Byun, Alison Dunning, Karen A Pooley, David C Qian, Xuemei Ji, Geoffrey Liu, Maria N Timofeeva, Stig E Bojesen, Xifeng Wu, Loic Le Marchand, Demetrios Albanes, Heike Bickeböller, Melinda C Aldrich, William S Bush, Adonina Tardon, Gad Rennert, M Dawn Teare, John K Field, Lambertus A Kiemeney, Philip Lazarus, Aage Haugen, Stephen Lam, Matthew B Schabath, Angeline S Andrew, Hongbing Shen, Yun-Chul Hong, Jian-Min Yuan, Pier Alberto Bertazzi, Angela C Pesatori, Yuanqing Ye, Nancy Diao, Li Su, Ruyang Zhang, Yonathan Brhane, Natasha Leighl, Jakob S Johansen, Anders Mellemgaard, Walid Saliba, Christopher A Haiman, Lynne R Wilkens, Ana Fernandez-Somoano, Guillermo Fernandez-Tardon, Henricus F M Van Der Heijden, Jin Hee Kim, Juncheng Dai, Zhibin Hu, Michael P A Davies, Michael W Marcus, Hans Brunnström, Jonas Manjer, Olle Melander, David C Muller, Kim Overvad, Antonia Trichopoulou, Rosario Tumino, Jennifer A Doherty, Matt P Barnett, Chu Chen, Gary E Goodman, Angela Cox, Fiona Taylor, Penella Woll, Irene Brüske, H-Erich Wichmann, Judith Manz, Thomas R Muley, Angela Risch, Albert Rosenberger, Kjell Grankvist, Mikael Johansson, Frances A 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, Shanbeh Zienolddiny, Eric J Duell, Lesley M Butler, Woon-Puay Koh, Yu-Tang Gao, Richard S Houlston, John Mclaughlin, Victoria L Stevens, Philippe Joubert, Maxime Lamontagne, David C Nickle, Ma'en Obeidat, Wim Timens, Bin Zhu, Lei Song, Linda Kachuri, María Soler Artigas, Martin D Tobin, Louise V Wain, Thorunn Rafnar, Thorgeir E Thorgeirsson, Gunnar W Reginsson, Kari Stefansson, Dana B Hancock, Laura J Bierut, Margaret R Spitz, Nathan C Gaddis, Sharon M Lutz, Fangyi Gu, Eric O Johnson, Ahsan Kamal, Claudio Pikielny, Dakai Zhu, Sara Lindströem, Xia Jiang, Rachel F Tyndale, Georgia Chenevix-Trench, Jonathan Beesley, Yohan Bossé, Stephen Chanock, Paul Brennan, Maria Teresa Landi, Christopher I Amos

Articles, Abstracts, and Reports

Although several lung cancer susceptibility loci have been identified, much of the heritability for lung cancer remains unexplained. Here 14,803 cases and 12,262 controls of European descent were genotyped on the OncoArray and combined with existing data for an aggregated genome-wide association study (GWAS) analysis of lung cancer in 29,266 cases and 56,450 controls. We identified 18 susceptibility loci achieving genome-wide significance, including 10 new loci. The new loci highlight the striking heterogeneity in genetic susceptibility across the histological subtypes of lung cancer, with four loci associated with lung cancer overall and six loci associated with lung adenocarcinoma. Gene expression …

Is Pregnancy-Associated Melanoma Associated With Adverse Outcomes?, Maris S Jones, Jihey Lee, Stacey L Stern, Mark Faries

Articles, Abstracts, and Reports

BACKGROUND: Melanoma is the most common malignancy encountered during pregnancy. Conflicting data have led to ongoing confusion regarding pregnancy-associated melanoma (PAM) in the media and among the public. The objective of this study was to better characterize both the clinical presentation of PAM and its prognostic implications.

STUDY DESIGN: Female patients of reproductive age, with stage 0 to IV cutaneous melanoma, were identified from our prospectively maintained database. Clinical and histopathologic factors were analyzed with appropriate statistical methods. Univariable and then multivariable analysis were used on matched data to compare disease-free survival (DFS), overall survival (OS), and melanoma-specific survival (MSS) …

Meta-Analysis Of Five Genome-Wide Association Studies Identifies Multiple New Loci Associated With Testicular Germ Cell Tumor., Zhaoming Wang, Katherine A Mcglynn, Ewa Rajpert-De Meyts, D Timothy Bishop, Charles C Chung, Marlene D Dalgaard, Mark H Greene, Ramneek Gupta, Tom Grotmol, Trine B Haugen, Robert Karlsson, Kevin Litchfield, Nandita Mitra, Kasper Nielsen, Louise C Pyle, Stephen M Schwartz, Vésteinn Thorsson, Saran Vardhanabhuti, Fredrik Wiklund, Clare Turnbull, Stephen J Chanock, Peter A Kanetsky, Katherine L Nathanson

Articles, Abstracts, and Reports

The international Testicular Cancer Consortium (TECAC) combined five published genome-wide association studies of testicular germ cell tumor (TGCT; 3,558 cases and 13,970 controls) to identify new susceptibility loci. We conducted a fixed-effects meta-analysis, including, to our knowledge, the first analysis of the X chromosome. Eight new loci mapping to 2q14.2, 3q26.2, 4q35.2, 7q36.3, 10q26.13, 15q21.3, 15q22.31, and Xq28 achieved genome-wide significance (P < 5 × 10

The Rhoj-Bad Signaling Network: An Achilles' Heel For Braf Mutant Melanomas., Rolando Ruiz, Sohail Jahid, Melissa Harris, Diego M Marzese, Francisco Espitia, Priya Vasudeva, Chi-Fen Chen, Sebastien De Feraudy, Jie Wu, Daniel L Gillen, Tatiana B Krasieva, Bruce J Tromberg, William J Pavan, Dave S B Hoon, Anand K Ganesan

Articles, Abstracts, and Reports

Genes and pathways that allow cells to cope with oncogene-induced stress represent selective cancer therapeutic targets that remain largely undiscovered. In this study, we identify a RhoJ signaling pathway that is a selective therapeutic target for BRAF mutant cells. RhoJ deletion in BRAF mutant melanocytes modulates the expression of the pro-apoptotic protein BAD as well as genes involved in cellular metabolism, impairing nevus formation, cellular transformation, and metastasis. Short-term treatment of nascent melanoma tumors with PAK inhibitors that block RhoJ signaling halts the growth of BRAF mutant melanoma tumors in vivo and induces apoptosis in melanoma cells in vitro via …

Tumor-Treating Fields Plus Chemotherapy Versus Chemotherapy Alone For Glioblastoma At First Recurrence: A Post Hoc Analysis Of The Ef-14 Trial., Santosh Kesari, Zvi Ram

Articles, Abstracts, and Reports

BACKGROUND: This post hoc analysis of the EF-14 trial (NCT00916409) of tumor-treating fields (TTFields) plus temozolomide versus temozolomide alone in newly diagnosed glioblastoma compared the efficacy of TTFields plus chemotherapy (physician's choice) versus chemotherapy alone after first recurrence.

METHODS: Patients on TTFields plus temozolomide continued TTFields plus second-line chemotherapy after first recurrence. Some patients on temozolomide alone crossed over after approval of TTFields for recurrent GBM. The primary efficacy outcome was overall survival (OS).

RESULTS: After disease progression, 131 patients received TTFields plus chemotherapy and 73 chemotherapy alone. Thirteen patients in the original temozolomide-alone group crossed over to receive TTFields …

Clinical Anatomy Of The Frenulum Of The Oral Vestibule., Joe Iwanaga, Naoshi Takeuchi, Rod J Oskouian, R Shane Tubbs

Articles, Abstracts, and Reports

Introduction The frenula of the oral vestibule include the labial and buccal frenula. Abnormal labial and buccal frenula can affect facial esthetics and oral cavity function by retracting the gingival margin, creating a median diastema, and limiting lip movement. Because of the lack of information on these structures, we aimed to clarify their anatomy. Methods A total of 34 sides from 17 fresh frozen cadaveric Caucasian heads were used in the present study. The specimens were derived from 11 male and 6 female adult cadavers. The relationships between the frenulum of the mucosa and the tissue underneath the mucosa was …

Pathologists' Diagnosis Of Invasive Melanoma And Melanocytic Proliferations: Observer Accuracy And Reproducibility Study., Joann G Elmore, Raymond L Barnhill, David E Elder, Gary M Longton, Margaret S Pepe, Lisa M Reisch, Patricia A Carney, Linda J Titus, Heidi D Nelson, Tracy Onega, Anna N A Tosteson, Martin A Weinstock, Stevan R Knezevich, Michael W Piepkorn

Articles, Abstracts, and Reports

No abstract provided.

Degenerative Changes Of The Canine Cervical Spine After Discectomy Procedures, An In Vivo Study., Peter Grunert, Yu Moriguchi, Brian P Grossbard, Rodolfo J Ricart Arbona, Lawrence J Bonassar, Roger Härtl

Articles, Abstracts, and Reports

BACKGROUND: Discectomies are a common surgical treatment for disc herniations in the canine spine. However, the effect of these procedures on intervertebral disc tissue is not fully understood. The objective of this study was to assess degenerative changes of cervical spinal segments undergoing discectomy procedures, in vivo.

RESULTS: Discectomies led to a 60% drop in disc height and 24% drop in foraminal height. Segments did not fuse but showed osteophyte formation as well as endplate sclerosis. MR imaging revealed terminal degenerative changes with collapse of the disc space and loss of T2 signal intensity. The endplates showed degenerative type II …

Igf2 Mrna Binding Protein 3 (Imp3) Promotes Glioma Cell Migration By Enhancing The Translation Of Rela/P65., Shruti Bhargava, Abhirami Visvanathan, Vikas Patil, Anuj Kumar, Santosh Kesari, Saumitra Das, Alangar S Hegde, Arimappamagan Arivazhagan, Vani Santosh, Kumaravel Somasundaram

Articles, Abstracts, and Reports

The diffusely infiltrative nature of glioblastoma (GBM) makes them highly recurrent. IGF2 mRNA-binding protein 3 (IMP3), a GBM upregulated RNA binding protein, promotes glioma cell migration. An integrative bioinformatics analysis identified p65 (RELA), a subunit of NF-κB heterodimer as a target and an important mediator of IMP3 promoted glioma cell migration. IMP3 increased p65 protein levels without any change in p65 transcript levels, but promoted its polysome association. RIP-PCR demonstrated the binding of IMP3 to p65 transcript. UV crosslinking experiments with in vitro transcribed RNA confirmed the specific and direct binding of IMP3 to sites on p65 3'UTR. Further, IMP3 …

More Than Meets The Eye: The Contributions Of John Dalrymple (1803-1852)., Joy Mh Wang, Bryan Edwards, Gabrielle G Tardieu, Marios Loukas, Rod J Oskouian, R Shane Tubbs

Articles, Abstracts, and Reports

Having authored two major ophthalmology textbooks and honored with the eponym, the "Dalrymple sign," many are familiar with the works of Dr. John Dalrymple when it comes to the eye. However, few are aware of his other, numerous and wide-ranging contributions to the fields of science and medicine. In this article, we discuss the life and work of a man dedicated to the pursuit and advancement of knowledge and education.

Xenon In The Treatment Of Panic Disorder: An Open Label Study., Alexander Dobrovolsky, Thomas E Ichim, Daqing Ma, Santosh Kesari, Vladimir Bogin

Articles, Abstracts, and Reports

BACKGROUND: Current treatments of panic disorder (PD) are limited by adverse effects, poor efficacy, and need for chronic administration. The established safety profile of subanesthetic concentrations of xenon gas, which is known to act as a glutamate subtype NMDA receptor antagonist, coupled with preclinical studies demonstrating its effects in other anxiety related conditions, prompted us to evaluate its feasibility and efficacy in treatment of patients with PD.

METHODS: An open-label clinical trial of xenon-oxygen mixture was conducted in 81 patients with PD; group 1 consisting of patients only with PD (N = 42); and group 2 patients with PD and …

Hiding Within The Cracks: Case Report Of Rare Sutural Bone Found At The Nasion., Bryan Edwards, Joy Mh Wang, Joe Iwanaga, Jennifer Luviano, Marios Loukas, Rod J Oskouian, R Shane Tubbs

Articles, Abstracts, and Reports

Pathology such as skull fractures can be misdiagnosed in the presence of anatomical variations. One variant that has had little description in the literature are the sutural bones associated with the nasal bones. Herein, we describe a case of a rare sutural bone at the nasion, between the bones of the right nasal, frontal, and maxillary frontal process. To our knowledge, this is the first report of such a variant bone in this location, and such it should be considered by clinicians when evaluating patients for pathology in this region.

Completion Dissection Or Observation For Sentinel-Node Metastasis In Melanoma., Mark Faries, John F Thompson, Alistair J Cochran, Robert H Andtbacka, Nicola Mozzillo, Jonathan S Zager, Tiina Jahkola, Tawnya L Bowles, Alessandro Testori, Peter D Beitsch, Harald J Hoekstra, Marc Moncrieff, Christian Ingvar, Michel W J M Wouters, Michael S Sabel, Edward A Levine, Doreen Agnese, Michael Henderson, Reinhard Dummer, Carlo R Rossi, Rogerio I Neves, Steven D Trocha, Frances Wright, David R Byrd, Maurice Matter, Eddy Hsueh, Alastair Mackenzie-Ross, Douglas B Johnson, Patrick Terheyden, Adam C Berger, Tara L Huston, Jeffrey D Wayne, B Mark Smithers, Heather B Neuman, Schlomo Schneebaum, Jeffrey E Gershenwald, Charlotte E Ariyan, Darius C Desai, Lisa Jacobs, Kelly M Mcmasters, Anja Gesierich, Peter Hersey, Steven D Bines, John M Kane, Richard J Barth, Gregory Mckinnon, Jeffrey M Farma, Erwin Schultz, Sergi Vidal-Sicart, Richard A Hoefer, James M Lewis, Randall Scheri, Mark C Kelley, Omgo E Nieweg, R Dirk Noyes, Dave S B Hoon, He-Jing Wang, David A Elashoff, Robert M Elashoff

Articles, Abstracts, and Reports

BACKGROUND: Sentinel-lymph-node biopsy is associated with increased melanoma-specific survival (i.e., survival until death from melanoma) among patients with node-positive intermediate-thickness melanomas (1.2 to 3.5 mm). The value of completion lymph-node dissection for patients with sentinel-node metastases is not clear.

METHODS: In an international trial, we randomly assigned patients with sentinel-node metastases detected by means of standard pathological assessment or a multimarker molecular assay to immediate completion lymph-node dissection (dissection group) or nodal observation with ultrasonography (observation group). The primary end point was melanoma-specific survival. Secondary end points included disease-free survival and the cumulative rate of nonsentinel-node metastasis.

RESULTS: Immediate completion …

Pineal Gland Agenesis: Review And Case Illustration., Marcus A Cox, Michele Davis, Vlad Voin, Mohammadali Shoja, Rod J Oskouian, Marios Loukas, R Shane Tubbs

Articles, Abstracts, and Reports

Agenesis of the pineal gland has rarely been reported in the medical literature. Herein, we report a cadaveric specimen found to have agenesis of the pineal gland. The remaining gross examination of the brain was normal. A review of the literature was performed on this unusual finding.

Genome-Wide Chromatin Accessibility, Dna Methylation And Gene Expression Analysis Of Histone Deacetylase Inhibition In Triple-Negative Breast Cancer., Matias A Bustos, Matthew P Salomon, Nellie Nelson, Sandy C Hsu, Maggie L Dinome, Dave S B Hoon, Diego M Marzese

Articles, Abstracts, and Reports

Triple-negative breast cancer (TNBC), especially the subset with a basal phenotype, represents the most aggressive subtype of breast cancer. Unlike other solid tumors, TNBCs harbor a low number of driver mutations. Conversely, we and others have demonstrated a significant impact of epigenetic alterations, including DNA methylation and histone post-translational modifications, affecting TNBCs. Due to the promising results in pre-clinical studies, histone deacetylase inhibitors (HDACi) are currently being tested in several clinical trials for breast cancer and other solid tumors. However, the genome-wide epigenetic and transcriptomic implications of HDAC inhibition are still poorly understood. Here, we provide detailed information about the …

Modulation Of Bax And Mtor For Cancer Therapeutics., Rui Li, Chunyong Ding, Jun Zhang, Maohua Xie, Dongkyoo Park, Ye Ding, Guo Chen, Guojing Zhang, Melissa Gilbert-Ross, Wei Zhou, Adam I Marcus, Shi-Yong Sun, Zhuo G Chen, Gabriel L Sica, Suresh S Ramalingam, Andrew T Magis, Haian Fu, Fadlo R Khuri, Walter J Curran, Taofeek K Owonikoko, Dong M Shin, Jia Zhou, Xingming Deng

Articles, Abstracts, and Reports

A rationale exists for pharmacologic manipulation of the serine (S)184 phosphorylation site of the proapoptotic Bcl2 family member Bax as an anticancer strategy. Here, we report the refinement of the Bax agonist SMBA1 to generate CYD-2-11, which has characteristics of a suitable clinical lead compound. CYD-2-11 targeted the structural pocket proximal to S184 in the C-terminal region of Bax, directly activating its proapoptotic activity by inducing a conformational change enabling formation of Bax homooligomers in mitochondrial membranes. In murine models of small-cell and non-small cell lung cancers, including patient-derived xenograft and the genetically engineered mutant KRAS-driven lung cancer models, CYD-2-11 …

The Quest For Sustained Multiple Morbidity Reduction In Very Low-Birth-Weight Infants: The Antifragility Project., Joseph Kaempf, N M Schmidt, S Rogers, C Novack, M Friant, L Wang, N Tipping

Articles, Abstracts, and Reports

OBJECTIVE: Can a comprehensive, explicitly directive evidence-based guideline for all therapies that might affect the major morbidities of very low-birth-weight (VLBW) infants help a neonatal intensive care unit (NICU) further improve generally favorable morbidity rates? Can Antifragility principles of provider adaptive growth from stressors, enhanced infant risk assessment and adherence to effective therapies minimize unproven treatments and reduce all morbidities?

STUDY DESIGN: Prospectively planned observational trial in VLBW infants: control group born October 2011 to September 2013 and study group October 2013 to September 2015. Multi-disciplinary evidence-based review assigned all NICU treatments into one of four distinct categories: (1) always …

The First Histological Analysis Of The Tissues Lining The Fossa Navicularis: Insights To Its Etiology., Sarvenaz Sheikh, Joe Iwanaga, Steven Rostad, Tarush Rustagi, Rod J Oskouian, R Shane Tubbs

Articles, Abstracts, and Reports

The fossa navicularis (FN) is an anatomical variant on the ventral surface of the basilar part of the occipital bone that, to date, has only been investigated in bone specimens. We aim to clarify the structure of the fossa navicularis by gross anatomical, radiological, and histological methods. The FN was found in the occipital bone of the Caucasian male cadaver. There was no bony or histological continuity between the FN and posterior cranial fossa. The histological analysis found that the overlying tissue was composed of loose connective tissue with a mixture of collagen and elastic fibers and a vascular matrix …

Internal Hernia Of The Greater Omentum: Cadaveric Findings Of A Previously Unreported Variant., Andrea Andrea, Vy Tran, Cameron K Schmidt, Christian Fisahn, Joe Iwanaga, Rod J Oskouian, R Shane Tubbs

Articles, Abstracts, and Reports

Transomental hernias (TOHs) are a rare finding, constituting a fraction of all intestinal hernias. Here, we report the cadaveric discovery of a spontaneous TOH involving the sigmoid colon in an 82-year-old female and discuss the relevant literature. To our knowledge, a TOH involving the sigmoid colon has not been previously reported.

Johann Gaspar Spurzheim: A Life Dedicated To Phrenology., Mohammad Bilal, Bryan Edwards, Marios Loukas, Rod J Oskouian, R Shane Tubbs

Articles, Abstracts, and Reports

Loved for his empathetic nature but admired for his analytical mind, Gaspar Spurzheim (1776-1832) was a prominent contributor to phrenology, a field of neuroscience focused on studying the shapes of the skulls in relation to the activity levels of certain functional areas of the brain. This curiosity about the connection between physical characteristics and brain function was seeded in the young mind of Spurzheim when he observed that classmates with seemingly superb memories also appeared to have bright eyes. It launched Spurzheim on a journey to study the shape and function of the brain, which eventually led him to his …

Median Nerve Palsies Due To Injections: A Review., Andrea Andrea, Jocelyn R Gonzales, Joe Iwanaga, Rod J Oskouian, R Shane Tubbs

Articles, Abstracts, and Reports

Injection nerve palsy (INP) in the median nerve is an iatrogenic peripheral nerve injury that can be inflicted by a faulty intramuscular injection in the median nerve area. The literature reports a 2% incidence of INP among all peripheral nerve injuries. The incidence of INP in developed countries has decreased significantly during the past decade, but the injury appears to remain prevalent in developing countries. A deep understanding of the anatomy of the peripheral nerves, and a precise intramuscular injection technique, have been shown to be vital for preventing INP in the median nerve. Debates continue regarding what, if any, …

A Cell-Surface Membrane Protein Signature For Glioblastoma., Dhimankrishna Ghosh, Cory C Funk, Juan Caballero, Nameeta Shah, Katherine Rouleau, John C Earls, Liliana Soroceanu, Greg Foltz, Charles Cobbs, Nathan D Price, Leroy Hood

Articles, Abstracts, and Reports

We present a systems strategy that facilitated the development of a molecular signature for glioblastoma (GBM), composed of 33 cell-surface transmembrane proteins. This molecular signature, GBMSig, was developed through the integration of cell-surface proteomics and transcriptomics from patient tumors in the REMBRANDT (n = 228) and TCGA datasets (n = 547) and can separate GBM patients from control individuals with a Matthew's correlation coefficient value of 0.87 in a lock-down test. Functionally, 17/33 GBMSig proteins are associated with transforming growth factor β signaling pathways, including CD47, SLC16A1, HMOX1, and MRC2. Knockdown of these genes impaired GBM invasion, reflecting their role …

Impact Of Ibrutinib Dose Adherence On Therapeutic Efficacy In Patients With Previously Treated Cll/Sll., Paul M Barr, Jennifer R Brown, Peter Hillmen, Susan O'Brien, Jacqueline C Barrientos, Nishitha M Reddy, Steven Coutre, Stephen P Mulligan, Ulrich Jaeger, Richard R Furman, Florence Cymbalista, Marco Montillo, Claire Dearden, Tadeusz Robak, Carol Moreno, John M Pagel, Jan A Burger, Samuel Suzuki, Juthamas Sukbuntherng, George Cole, Danelle F James, John C Byrd

Articles, Abstracts, and Reports

Ibrutinib, an oral inhibitor of Bruton's tyrosine kinase (BTK), at a once-daily dose of 420 mg achieved BTK active-site occupancy in patients with chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL) that was maintained at 24 hours. It is unknown if intermittent interruption of ibrutinib therapy contributes to altered clinical outcomes. We therefore evaluated the effect of ibrutinib dose adherence on patient outcomes in the phase 3 RESONATE trial. The overall mean dose intensity (DI) was 95% with median treatment duration of ∼9 months. Pharmacokinetic assessment of ibrutinib exposure at 420-mg dose suggested similar exposure regardless of patient weight or age. …

Ccr4 Is A Determinant Of Melanoma Brain Metastasis., Anat Klein, Orit Sagi-Assif, Tsipi Meshel, Alona Telerman, Sivan Izraely, Shlomit Ben-Menachem, Jagadeesh Bayry, Diego M Marzese, Shuichi Ohe, Dave S B Hoon, Neta Erez, Isaac P Witz

Articles, Abstracts, and Reports

We previously identified the chemokine receptor CCR4 as part of the molecular signature of melanoma brain metastasis. The aim of this study was to determine the functional significance of CCR4 in melanoma brain metastasis. We show that CCR4 is more highly expressed by brain metastasizing melanoma cells than by local cutaneous cells from the same melanoma. Moreover, we found that the expression of CCR4 is significantly higher in paired clinical specimens of melanoma metastases than in samples of primary tumors from the same patients. Notably, the expression of the CCR4 ligands, Ccl22 and Ccl17 is upregulated at the earliest stages …