Digital Commons Network^™

The Burden Of Unintentional Drowning: Global, Regional And National Estimates Of Mortality From The Global Burden Of Disease 2017 Study, Richard Charles Franklin, Amy E. Peden, Erin B. Hamilton, Catherine Bisignano, Chris D. Castle, Zachary V. Dingels, Simon I. Hay, Zichen Liu, Ali H. Mokdad, Zulfiqar Ahmed Bhutta

Woman and Child Health

Background: Drowning is a leading cause of injury-related mortality globally. Unintentional drowning (International Classification of Diseases (ICD) 10 codes W65-74 and ICD9 E910) is one of the 30 mutually exclusive and collectively exhaustive causes of injury-related mortality in the Global Burden of Disease (GBD) study. This study's objective is to describe unintentional drowning using GBD estimates from 1990 to 2017.
Methods: Unintentional drowning from GBD 2017 was estimated for cause-specific mortality and years of life lost (YLLs), age, sex, country, region, Socio-demographic Index (SDI) quintile, and trends from 1990 to 2017. GBD 2017 used standard GBD methods for estimating mortality …

The Impact Of Delayed Treatment Of Uncomplicated P. Falciparum Malaria On Progression To Severe Malaria: A Systematic Review And A Pooled Multicenter Individual-Patient Meta-Analysis, Andria Mousa, Abdullah Al-Taiar, Nicholas Anstey, Cyril Badaut, Bridget Barber, Quique Bassat, Joseph Challenger, Aubrey Cunnington, Dibyadyuti Datta, Robert Opoka

Paediatrics and Child Health, East Africa

Background: Delay in receiving treatment for uncomplicated malaria (UM) is often reported to increase the risk of developing severe malaria (SM), but access to treatment remains low in most high-burden areas. Understanding the contribution of treatment delay on progression to severe disease is critical to determine how quickly patients need to receive treatment and to quantify the impact of widely implemented treatment interventions, such as 'test-and-treat' policies administered by community health workers (CHWs). We conducted a pooled individual-participant meta-analysis to estimate the association between treatment delay and presenting with SM.

Methods and findings: A search using Ovid MEDLINE and …

Sod2 Deficiency In Cardiomyocytes Defines Defective Mitochondrial Bioenergetics As A Cause Of Lethal Dilated Cardiomyopathy, Sudha Sharma, Susmita Bhattarai, Hosne Ara, Grace Sun, Daret K. St. Clair, Md Shenuarin Bhuiyan, Christopher Kevil, Megan N. Watts, Paari Dominic, Takahiko Shimizu, Kevin J. Mccarthy, Hong Sun, Manikandan Panchatcharam, Sumitra Miriyala

Toxicology and Cancer Biology Faculty Publications

Electrophilic aldehyde (4-hydroxynonenal; 4-HNE), formed after lipid peroxidation, is a mediator of mitochondrial dysfunction and implicated in both the pathogenesis and the progression of cardiovascular disease. Manganese superoxide dismutase (MnSOD), a nuclear-encoded antioxidant enzyme, catalyzes the dismutation of superoxide radicals (O2^•-) in mitochondria. To study the role of MnSOD in the myocardium, we generated a cardiomyocyte-specific SOD2 (SOD2Δ) deficient mouse strain. Unlike global SOD2 knockout mice, SOD2Δ mice reached adolescence; however, they die at ~4 months of age due to heart failure. Ultrastructural analysis of SOD2Δ hearts revealed altered mitochondrial architecture, with prominent disruption of the …

The Write Stuff - Autumn 2020 (Vol. 17, No. 4), Research Medical Library

Write Stuff 2020

• New NIH training module: Vertebrate Animals Section
• When a journal requests English-language editing
• CRediT aims to clarify contributions to scientific publications
• The Assisted Referral Tool (ART): A resource for selecting the best NIH study sections for your grant proposal
• Unusual terms used in scientific writing and publishing: Cascading peer review

The Central Melanocortin System And Human Obesity, Yongjie Yang, Yong Xu

Children’s Nutrition Research Center Staff Publications

The prevalence of obesity and the associated comorbidities highlight the importance of understanding the regulation of energy homeostasis. The central melanocortin system plays a critical role in controlling body weight balance. Melanocortin neurons sense and integrate the neuronal and hormonal signals, and then send regulatory projections, releasing anorexigenic or orexigenic melanocortin neuropeptides, to downstream neurons to regulate the food intake and energy expenditure. This review summarizes the latest progress in our understanding of the role of the melanocortin pathway in energy homeostasis. We also review the advances in the identification of human genetic variants that cause obesity via mechanisms that …

Virtual Connectivity During Quarantine: The Role Of Social Media For Radiation Oncology During Covid-19, Miriam A Knoll, Mudit Chowdhary, Adam Dicker, Thomas Eichler

Kimmel Cancer Center Faculty Papers

No abstract provided.

Type Iii Gastric Neuroendocrine Tumor: Case Report Of A Rare Gastric Carcinoma, Christopher L. Orpiano, Michael Quinn, Gurjeet Kang, Aric Tucker, Aric Tucker, Lakshminarasimhan Venu, Joseph Staffetti

Gastroenterology

No abstract provided.

Progress In The Therapy Of Myasthenia Gravis: Getting Closer To Effective Targeted Immunotherapies, Marinos Dalakas

Department of Neurology Faculty Papers

PURPOSE OF REVIEW: To provide an update on immunomodulating and immunosuppressive therapies in myasthenia gravis and highlight newly approved, or pending approval, therapies with new biologics.

RECENT FINDINGS: Preoperative IVIg is not needed to prevent myasthenic crisis in stable myasthenia gravis patients scheduled for surgery under general anesthesia, based on controlled data. Rituximab, if initiated early in new-onset myasthenia gravis, can lead to faster and more sustained remission even without immunotherapies in 35% of patients at 2 years. Biomarkers determining the timing for follow-up infusions in Rituximab-responding AChR-positive patients are discussed. Most patients with MuSK-positive myasthenia gravis treated with Rituximab …

Assessment Of Surgical Procedural Time, Pedicle Screw Accuracy, And Clinician Radiation Exposure Of A Novel Robotic Navigation System Compared With Conventional Open And Percutaneous Freehand Techniques: A Cadaveric Investigation, Alex R. Vaccaro, Jonathan A Harris, Mir M Hussain, Rishi Wadhwa, Victor W Chang, Samuel R Schroerlucke, Walter P Samora, Peter G Passias, Rakesh D Patel, Ripul R Panchal, Sabino D'Agostino, Nathaniel L Whitney, Neil R Crawford, Brandon S Bucklen

Rothman Institute Papers

STUDY DESIGN: Cadaveric study.

OBJECTIVE: To evaluate accuracy, radiation exposure, and surgical time of a new robotic-assisted navigation (RAN) platform compared with freehand techniques in conventional open and percutaneous procedures.

METHODS: Ten board-certified surgeons inserted 16 pedicle screws at T10-L5 (n = 40 per technique) in 10 human cadaveric torsos. Pedicle screws were inserted with (1) conventional MIS technique (L2-L5, patient left pedicles), (2) MIS RAN (L2-L5, patient right pedicles), (3) conventional open technique (T10-L1, patient left pedicles), and (4) open RAN (T10-L1, patient right pedicles). Output included (1) operative time, (2) number of fluoroscopic images, and (3) screw accuracy. …

The Society For Immunotherapy Of Cancer (Sitc) Clinical Practice Guideline On Immunotherapy For The Treatment Of Acute Leukemia., Michael M Boyiadzis, Ivan Aksentijevich, Daniel A Arber, John Barrett, Renier J Brentjens, Jill Brufsky, Jorge Cortes, Marcos De Lima, Stephen J Forman, Ephraim J Fuchs, Linda J Fukas, Steven D Gore, Mark R Litzow, Jeffrey S Miller, John M Pagel, Edmund K Waller, Martin S Tallman

Articles, Abstracts, and Reports

Acute leukemia is a constellation of rapidly progressing diseases that affect a wide range of patients regardless of age or gender. Traditional treatment options for patients with acute leukemia include chemotherapy and hematopoietic cell transplantation. The advent of cancer immunotherapy has had a significant impact on acute leukemia treatment. Novel immunotherapeutic agents including antibody-drug conjugates, bispecific T cell engagers, and chimeric antigen receptor T cell therapies have efficacy and have recently been approved by the US Food and Drug Administration (FDA) for the treatment of patients with acute leukemia. The Society for Immunotherapy of Cancer (SITC) convened a panel of …

Untargeted Longitudinal Analysis Of A Wellness Cohort Identifies Markers Of Metastatic Cancer Years Prior To Diagnosis., Andrew T Magis, Noa Rappaport, Matthew P Conomos, Gilbert S Omenn, Jennifer C Lovejoy, Leroy Hood, Nathan D Price

Articles, Abstracts, and Reports

We analyzed 1196 proteins in longitudinal plasma samples from participants in a commercial wellness program, including samples collected pre-diagnosis from ten cancer patients and 69 controls. For three individuals ultimately diagnosed with metastatic breast, lung, or pancreatic cancer, CEACAM5 was a persistent longitudinal outlier as early as 26.5 months pre-diagnosis. CALCA, a biomarker for medullary thyroid cancer, was hypersecreted in metastatic pancreatic cancer at least 16.5 months pre-diagnosis. ERBB2 levels spiked in metastatic breast cancer between 10.0 and 4.0 months pre-diagnosis. Our results support the value of deep phenotyping seemingly healthy individuals in prospectively inferring disease transitions.

Announcing The Isev2020 Special Achievement Award Recipients: Andrew Hill And Edit Buzás; And The Recipient Of The Isev2020 Special Education Award: Carolina Soekmadji., Kenneth W Witwer, Lucia R Languino, Alissa M Weaver, Marca H Wauben

Kimmel Cancer Center Faculty Papers

No abstract provided.

Improving Data For Decision-Making: A Toolkit For Cervical Cancer Prevention And Control Programmes, Elkanah Omenge, Edwin Were, Oliver Rode, Kapten Muthoka, Michael Byczkowski, Heike Sartor, Davy Vanden Broeck, Dietmar Schmidt, Miriam Reuschenbach, Magnus Von Knebel Doeberitz

Obstetrics and Gynaecology, East Africa

Background: Screening of unvaccinated women remains essential to mitigate the high morbidity/mortality of cervical cancer. Here, we compared visual inspection with acetic acid (VIA), recommended by WHO as the most cost-effective screening approach in LMICs, with HPV-based screening, and usage of p16INK4a/Ki-67 dual stain cytology.

Methods: We prospectively enrolled women participating in a VIA-based cervical cancer screening program in two peri-urban health centers of Kenya. Consenting women had a VIA examination preceded by collection of a liquid-based cytology sample from the cervix stored in PreservCyt medium (Hologic®). Analysis of all samples included a hrHPV DNA test and evaluation of a …

Role Of Fine Needle Aspiration Cytology In The Diagnosis Of Parotid Gland Tumors: Analysis Of 193 Cases, Rahim Dhanani, Haissan Iftikhar, Mohammad Sohail Awan, Nida Zahid, Sehrish Nizar Ali Momin

Section of Otolaryngology, Head & Neck Surgery

Introduction: Parotid gland tumors include a wide variety of inflammatory and neoplastic diseases. The majority of these tumors are benign (80%), which usually require superficial parotidectomy, while the incidence of malignant tumors is lower (20%), requiring more radical surgery with or without neck dissection. The diagnosis cannot be established on the basis of clinical history and simple physical examination and requires complementary diagnostic methods. Fine needle aspiration cytology (FNAC) guided by ultrasound is a widely used diagnostic tool to evaluate parotid swellings.
Objective: To determine the sensitivity, specificity, positive and negative predictive values and diagnostic accuracy of FNAC in the …

Serially Assessed Bisphenol A And Phthalate Exposure And Association With Kidney Function In Children With Chronic Kidney Disease In The Us And Canada: A Longitudinal Cohort Study., Melanie H. Jacobson, Yinxiang Wu, Mengling Liu, Teresa M. Attina, Mrudula Naidu, Rajendiran Karthikraj, Kurunthachalam Kannan, Bradley A. Warady, Susan Furth, Suzanne Vento, Howard Trachtman, Leonardo Trasande

Manuscripts, Articles, Book Chapters and Other Papers

BACKGROUND: Exposure to environmental chemicals may be a modifiable risk factor for progression of chronic kidney disease (CKD). The purpose of this study was to examine the impact of serially assessed exposure to bisphenol A (BPA) and phthalates on measures of kidney function, tubular injury, and oxidative stress over time in a cohort of children with CKD.

METHODS AND FINDINGS: Samples were collected between 2005 and 2015 from 618 children and adolescents enrolled in the Chronic Kidney Disease in Children study, an observational cohort study of pediatric CKD patients from the US and Canada. Most study participants were male (63.8%) …

Versatile Phenotype-Activated Cell Sorting, John F Ahrens, Shujuan Lai, Xiaoyu Lu, Sihui Guan, François St-Pierre

Faculty, Staff and Students Publications

Unraveling the genetic and epigenetic determinants of phenotypes is critical for understanding and re-engineering biology and would benefit from improved methods to separate cells based on phenotypes. Here, we report SPOTlight, a versatile high-throughput technique to isolate individual yeast or human cells with unique spatiotemporal profiles from heterogeneous populations. SPOTlight relies on imaging visual phenotypes by microscopy, precise optical tagging of single target cells, and retrieval of tagged cells by fluorescence-activated cell sorting. To illustrate SPOTlight's ability to screen cells based on temporal properties, we chose to develop a photostable yellow fluorescent protein for extended imaging experiments. We screened 3 …

An Autism-Linked Missense Mutation In Shank3 Reveals The Modularity Of Shank3 Function, Carolyn J Adamski, Wei Wang, Lingjie He, Jason K Lai, Vitaliy V Bondar, Joseph G Duman, Ronald Richman, Kimberley F Tolias, Patrick Barth, Timothy Palzkill, Zhandong Liu, J Lloyd Holder, Huda Y Zoghbi

Faculty, Staff and Students Publications

Genome sequencing has revealed an increasing number of genetic variations that are associated with neuropsychiatric disorders. Frequently, studies limit their focus to likely gene-disrupting mutations because they are relatively easy to interpret. Missense variants, instead, have often been undervalued. However, some missense variants can be informative for developing a more profound understanding of disease pathogenesis and ultimately targeted therapies. Here we present an example of this by studying a missense variant in a well-known autism spectrum disorder (ASD) causing gene SHANK3. We analyzed Shank3's in vivo phosphorylation profile and identified S685 as one phosphorylation site where one ASD-linked variant has …

Ampk Regulation Of Raptor And Tsc2 Mediate Metformin Effects On Transcriptional Control Of Anabolism And Inflammation, Eric L Van Nostrand, Alina Dayn, Jingting Yu, Maxim N Shokhirev, Yelena Dayn, Gene W Yeo, Reuben J Shaw

Faculty, Staff and Students Publications

Despite being the frontline therapy for type 2 diabetes, the mechanisms of action of the biguanide drug metformin are still being discovered. In particular, the detailed molecular interplays between the AMPK and the mTORC1 pathway in the hepatic benefits of metformin are still ill defined. Metformin-dependent activation of AMPK classically inhibits mTORC1 via TSC/RHEB, but several lines of evidence suggest additional mechanisms at play in metformin inhibition of mTORC1. Here we investigated the role of direct AMPK-mediated serine phosphorylation of RAPTOR in a new

Mir-30a Targets Gene Networks That Promote Browning Of Human And Mouse Adipocytes, Vasanta Putluri, Jessica B Felix, Peter Masschelin, Aaron R Cox, Mandeep Bajaj, Nagireddy Putluri, Cristian Coarfa, Sean M Hartig

Faculty, Staff and Students Publications

MicroRNA-30a (miR-30a) impacts adipocyte function, and its expression in white adipose tissue (WAT) correlates with insulin sensitivity in obesity. Bioinformatic analysis demonstrates that miR-30a expression contributes to 2% of all miRNA expression in human tissues. However, molecular mechanisms of miR-30a function in fat cells remain unclear. Here, we expanded our understanding of how miR-30a expression contributes to antidiabetic peroxisome proliferator-activated receptor-γ (PPARγ) agonist activity and metabolic functions in adipocytes. We found that WAT isolated from diabetic patients shows reduced miR-30a levels and diminished expression of the canonical PPARγ target genes ADIPOQ and FABP4 relative to lean counterparts. In human adipocytes, …

Nipple Sparing Mastectomy: A Review Of Outcomes At A 1 Single Institution, Steven Woodward, Md, Alliric Willis, Melissa Lazar, Adam C. Berger, Theodore Tsangaris

Department of Surgery Faculty Papers

Introduction

Nipple sparing mastectomy (NSM) offers patients who are not candidates for breast conserving treatment an aesthetically pleasing alternative to traditional mastectomy. Some studies have demonstrated its oncologic safety while others have demonstrated residual occult tumor cells at the nipple areolar complex (NAC). These data prompt further review of oncologic outcomes after NSM.

Methods

A single institution retrospective chart review of all NSMs performed by 4 breast surgeons at Thomas Jefferson University Hospital over a span of 2012-2019. In this cohort we review the reconstruction performed, axillary lymph node status, surgical margins, final pathology, loss of the NAC, recurrence rates, …

Orthopedic Principles To Facilitate Enhanced Recovery After Cardiac Surgery, Marc W Gerdisch, Keith B Allen, Yoshifumi Naka, Mark R Bonnell, Kevin P Landolfo, John Grehan, Kendra J Grubb, David J Cohen, T. Sloane Guy, Nirav C Patel, Vinod H Thourani

Department of Surgery Faculty Papers

Enhanced recovery after surgery (ERAS) protocols recognize early postoperative mobilization as a driver of faster postoperative recovery, return to normal activities, and improved long-term patient outcomes. For patients undergoing open cardiac surgery, an opportunity for facilitating earlier mobilization and a return to normal activity lies in the use of improved techniques to stabilize the sternal osteotomy. By following the key orthopedic principles of approximation, compression, and rigid fixation, a more nuanced approach to sternal precaution protocols is possible, which may enable earlier patient mobilization, physical rehabilitation, and recovery.

Canakinumab To Reduce Deterioration Of Cardiac And Respiratory Function In Sars-Cov-2 Associated Myocardial Injury With Heightened Inflammation (Canakinumab In Covid-19 Cardiac Injury: The Three C Study), Tom Kai Ming Wang, Prabalini Rajendram, Abhijit Duggal, A Michael Lincoff, Steven E Nissen, Venu Menon, Paul C Cremer

Faculty, Staff and Student Publications

BACKGROUND: In patients with Covid-19, myocardial injury and increased inflammation are associated with morbidity and mortality. We designed a proof-of-concept randomized controlled trial to evaluate whether treatment with canakinumab prevents progressive respiratory failure and worsening cardiac dysfunction in patients with SARS-CoV2 infection, myocardial injury, and high levels of inflammation.

HYPOTHESIS: The primary hypothesis is that canakiumab will shorten time to recovery.

METHODS: The three C study (canakinumab in Covid-19 Cardiac Injury, NCT04365153) is a double-blind, randomized controlled trial comparing canakinumab 300 mg IV, 600 mg IV, or placebo in a 1:1:1 ratio in hospitalized Covid-19 patients with elevations in troponin …

Yebc Regulates Variable Surface Antigen Vlse Expression And Is Required For Host Immune Evasion In Borrelia Burgdorferi, Jing Yang, X Frank Yang, Yongliang Lou

Faculty, Staff and Student Publications

Borrelia burgdorferi, the Lyme disease pathogen causes persistent infection by evading the host immune response. Differential expression of the surface-exposed lipoprotein VlsE that undergoes antigenic variation is a key immune evasion strategy employed by B. burgdorferi. Most studies focused on the mechanism of VlsE antigen variation, but little is known about VlsE regulation and factor(s) that regulates differential vlsE expression. In this study, we investigated BB0025, a putative YebC family transcriptional regulator (and hence designated BB0025 as YebC of B. burgdorferi herein). We constructed yebC mutant and complemented strain in an infectious strain of B. burgdorferi. The yebC mutant could …

Low-Shot Deep Learning Of Diabetic Retinopathy With Potential Applications To Address Artificial Intelligence Bias In Retinal Diagnostics And Rare Ophthalmic Diseases, Neil Joshi, Katia D Pacheco, Neil M Bressler

Faculty, Staff and Students Publications

IMPORTANCE: Recent studies have demonstrated the successful application of artificial intelligence (AI) for automated retinal disease diagnostics but have not addressed a fundamental challenge for deep learning systems: the current need for large, criterion standard-annotated retinal data sets for training. Low-shot learning algorithms, aiming to learn from a relatively low number of training data, may be beneficial for clinical situations involving rare retinal diseases or when addressing potential bias resulting from data that may not adequately represent certain groups for training, such as individuals older than 85 years.

OBJECTIVE: To evaluate whether low-shot deep learning methods are beneficial when using …

Human Genes Differ By Their Uv Sensitivity Estimated Through Analysis Of Uv-Induced Silent Mutations In Melanoma, Colin Begg, Eva Hernando, Chao Cheng, Ronglai Shen, Irene Orlow, Li Luo, Marc S Ernstoff, Joel Parker, Nancy E Thomas, Olga Y Gorlova, Marianne Berwick

Faculty, Staff and Students Publications

We hypothesized that human genes differ by their sensitivity to ultraviolet (UV) exposure. We used somatic mutations detected by genome-wide screens in melanoma and reported in the Catalog Of Somatic Mutations In Cancer. As a measure of UV sensitivity, we used the number of silent mutations generated by C>T transitions in pyrimidine dimers of a given transcript divided by the number of potential sites for this type of mutations in the transcript. We found that human genes varied by UV sensitivity by two orders of magnitude. We noted that the melanoma-associated tumor suppressor gene CDKN2A was among the top …

Prognosic Factors Related To The Complete Hematologic Response (Chr) In 3 Months In Leukemia Granulositic Patients Administered With Imatinib Mesylate, Ikhwan Rinaldi, Arry H. Reksodiputro

Jurnal Penyakit Dalam Indonesia

Introduction. The complete hematologic response is an integral part to achieve the complete cytogenetic response target and the major molecular response of imatinib mesylate therapy, although it does not determine the prognosis. The complete hematologic response in Indonesia is lower than in the world (74% vs. 95%). Sixty percent of chronic myeloid leukemia patients in Indonesia were administered hydroxyurea before imatinib mesylate. Chronic myeloid leukaemia (CML) patients in Indonesia are younger than in other countries. This study aimed to determine what prognostic factors which affect the complete hematological response of chronic phase CML patients who received imatinib mesylate in Indonesia. …

Identification Of Plasma Glycosphingolipids As Potential Biomarkers For Prostate Cancer (Pca) Status, Ashley J. Snider, Michael C. Seeds, Laurel Johnstone, Justin M. Snider, Brian Hallmark, Rahul Dutta, Cristina Moraga Franco, John S. Parks, Jeannette T. Bensen, Corey D. Broeckling, James L. Mohler, Gary J. Smith, Elizabeth T.H. Fontham, Hui Kuan Lin, William Bresette, Susan Sergeant, Floyd H. Chilton

School of Public Health Faculty Publications

Prostate cancer (PCa) is the most common male cancer and the second leading cause of cancer death in United States men. Controversy continues over the effectiveness of prostate-specific antigen (PSA) for distinguishing aggressive from indolent PCa. There is a critical need for more specific and sensitive biomarkers to detect and distinguish low-versus high-risk PCa cases. Discovery metabolomics were performed utilizing ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS) on plasma samples from 159 men with treatment naïve prostate cancer participating in the North Carolina-Louisiana PCa Project to determine if there were metabolites associated with aggressive PCa. Thirty-five identifiable plasma small molecules were …

Five Year Survival Of Active Multiple Myeloma Patients Based On Durie-Salmon And International Myeloma Working Group 2003 Diagnostic Criteria, Sri Agustini Kurniawati, Ary Harryanto Reksodiputro, Tubagus Djumhana Atmakusuma

Jurnal Penyakit Dalam Indonesia

Introduction. Survival of active multiple myeloma (MM) patients is determined by early diagnosis and various prognostic factors. The development of MM diagnostic criteria from Durie-Salmon (DS) criteria to International Myeloma Working Group (IMWG) 2003 is an attempt to diagnose active MM earlier. However, due to limited resources, these diagnostic criteria cannot be fulfilled consistently in Indonesia. Based on this reason, it is necessary to know the proportion of MM based on DS and IMWG 2003 diagnostic criteria and also their impact on the survival of MM patients in Indonesia. Methods. This was a retrospective cohort study with survival analysis. Subjects …

Effects Of Germline And Somatic Events In Candidate Brca-Like Genes On Breast-Tumor Signatures, Weston R. Bodily, Brian H. Shirts, Tom Walsh, Suleyman Gulsuner, Mary-Claire King, Alyssa Parker, Moom Roosan, Stephen R. Piccolo

Pharmacy Faculty Articles and Research

Mutations in BRCA1 and BRCA2 cause deficiencies in homologous recombination repair (HR), resulting in repair of DNA double-strand breaks by the alternative non-homologous end-joining pathway, which is more error prone. HR deficiency of breast tumors is important because it is associated with better responses to platinum salt therapies and PARP inhibitors. Among other consequences of HR deficiency are characteristic somatic-mutation signatures and gene-expression patterns. The term “BRCA-like” (or “BRCAness”) describes tumors that harbor an HR defect but have no detectable germline mutation in BRCA1 or BRCA2. A better understanding of the genes and molecular events associated with tumors being …

Laryngeal Histoplasmosis In Patients With Crohn’S Disease Undergoing Treatment With Humira (Adalimumab): A Case Series, Jenna Berg, Jonathan Blecha, Chris Bingcang, Justin Oltman, Jayme Dowdall, Subodh M. Lele

Graduate Medical Education Research Journal

The FDA has advocated for increasing awareness of histoplasmosis for patients undergoing TNF blockers as delay in diagnosis can lead to a poor outcome.¹ Laryngeal histoplasmosis is a rare entity that should be part of the differential diagnosis in patients receiving immune suppression for Crohn’s disease. Patients with laryngeal histoplasmosis often report hoarseness, mucosal ulcerations, dysphagia, and odynophagia. We present a series of two cases of laryngeal histoplasmosis in patients with Crohn’s. These cases illustrate the high index of suspicion required to make the diagnosis of laryngeal histoplasmosis, especially in the Midwestern United States. Diagnosis is made quickly and …