Pathology Commons^™

Abnormal Urine Drug Screens In Pregnancy- Opportunity For Laboratory Stewardship, Anil K Chokkalla, Sahil Malik, Ridwan Ibrahim, Sridevi Devaraj

Faculty, Staff and Students Publications

Background: Clinical testing for drugs of abuse typically involves initial screening followed by confirmatory testing. Due to limited evidence-based guidelines, the healthcare provider makes the decision to confirm abnormal screens based on the clinical context. This two-step approach proved to be inadequate in scenarios like maternal substance abuse and subsequent fetal/ newborn exposure. The goal of this study is to assess and improve the confirmatory testing rate of abnormal screens among pregnant patients at our women's center.

Methods: A retrospective chart review was conducted to assess the confirmation rates among positively screened pregnant patients, and a lab stewardship initiative was …

Inappropriate Laboratory Testing: Significant Waste Quantified By A Large-Scale Year-Long Study Of Medicare And Commercial Payer Reimbursement, Dave Smart, Jeff Schreier, Ila R Singh

Faculty, Staff and Students Publications

Context.—: Laboratory testing, beyond what is essential for managing health, is considered low-value care, posing patient risks and wasting resources. Measuring excess testing on a national level is crucial to identify waste and optimize healthcare resource allocation for maximum impact.

Objective.—: To measure inappropriate laboratory testing and its cost across Medicare and many US commercial payers.

Design.—: A retrospective analysis on 2019 claims data measured the frequency of 4 commonly used laboratory tests among 64 million individuals with Medicare and 168 million with commercial insurance. Tests included 25-hydroxy vitamin D, prostate-specific antigen, lipid panel, and hemoglobin A1c. Clinical guidelines, medical …

Chronic Hepatitis And Hemophagocytic Lymphohistiocytosis Associated With Systemic Chronic Active Epstein-Barr Virus Disease, Emmanuel Palomera-Tejeda, Lauren Shaffer, Michael Shi, Nagasri Shankar, Roshan Raza, George Cholankeril

Faculty, Staff and Students Publications

Systemic chronic active Epstein-Barr virus (EBV) disease is a rare, delayed, and life-threatening complication of EBV infection. It is characterized by persistent viremia and a mononucleosis-like syndrome with multisystemic involvement because of lymphocytic tissue infiltration. We present the case of an 82-year-old woman without known immunodeficiency who presented with abnormal liver enzymes and interstitial pneumonia. Investigations revealed hyperferritinemia, elevated soluble interleukin-2 receptor levels, hypofibrinogenemia, and hepatosplenomegaly, consistent with hemophagocytic lymphohistiocytosis, as well as a high EBV viral load. Liver biopsy demonstrated portal chronic lymphocytic inflammation and positive EBV in situ hybridization, suggesting systemic chronic active Epstein-Barr virus disease as the …

Supraclavicular Nodal Metastasis At Primary Staging Of Prostate Cancer Using 18f-Psma-1007 Pet/Ct, Samuel Gitau, Jasmit Shah, William Olwit, Saeed Samnakay, Manel Haj Mansour, Khalid Makhdomi

Brain and Mind Institute

Background: The most common sites of metastasis in prostate cancer are bone, pelvic and retroperitoneal lymph nodes, liver and lungs. This study aimed to evaluate the prevalence of supraclavicular nodal metastasis in newly diagnosed prostate cancer using 18F-PSMA-1007 PET/CT which has hitherto been understudied.

Methods: 18F-PSMA-1007 PET/CT examinations performed at our institution between June 2020 and June 2022 for primary staging of prostate cancer were reviewed to identify supraclavicular nodal metastasis from prostate cancer. Data variables included age, stage of disease, PSA level, Gleason score and ISUP/WHO grade group and how these compare with the presence of supraclavicular …

Diagnostic Pearls And Pitfalls In The Interpretation Of Small Biopsies And Frozen Sections Of The Pancreatobiliary Tract, Huamin Wang, Olca Basturk

Faculty, Staff and Student Publications

No abstract provided.

Interim Estimates Of 2024-2025 Seasonal Influenza Vaccine Effectiveness - Four Vaccine Effectiveness Networks, United States, October 2024-February 2025., Aaron M. Frutos, Seana Cleary, Emily L. Reeves, Haris M. Ahmad, Ashley M. Price, Wesley H. Self, Yuwei Zhu, Basmah Safdar, Ithan D. Peltan, Kevin W. Gibbs, Matthew C. Exline, Adam S. Lauring, Sarah W. Ball, Malini Desilva, Sara Y. Tartof, Kristin Dascomb, Stephanie A. Irving, Nicola P. Klein, Brian E. Dixon, Toan C. Ong, Ivana A. Vaughn, Stacey L. House, Kiran A. Faryar, Mary Patricia Nowalk, Manjusha Gaglani, Karen J. Wernli, Vel Murugan, Olivia L. Williams, Rangaraj Selvarangan, Geoffrey A. Weinberg, Mary A. Staat, Natasha B. Halasa, Leila C. Sahni, Marian G. Michaels, Janet A. Englund, Marie K. Kirby, Diya Surie, Fatimah S. Dawood, Benjamin R. Clopper, Heidi L Moline, Ruth Link-Gelles, Amanda B. Payne, Elizabeth Harker, Kristina Wielgosz, Zachary A. Weber, Duck-Hye Yang, Nathaniel M. Lewis, Jennifer Decuir, Samantha M. Olson, Jessie R. Chung, Brendan Flannery, Lisa A. Grohskopf, Carrie Reed, Shikha Garg, Sascha Ellington, Cdc Influenza Vaccine Effectiveness Collaborators

Manuscripts, Articles, Book Chapters and Other Papers

Annual influenza vaccination is recommended for all persons aged ≥6 months in the United States. Interim influenza vaccine effectiveness (VE) was calculated among patients with acute respiratory illness-associated outpatient visits and hospitalizations from four VE networks during the 2024-25 influenza season (October 2024-February 2025). Among children and adolescents agedyears, VE against any influenza was 32%, 59%, and 60% in the outpatient setting in three networks, and against influenza-associated hospitalization was 63% and 78% in two networks. Among adults aged ≥18 years, VE in the outpatient setting was 36% and 54% in two networks and was 41% and 55% against hospitalization …

Clostridioides Difficile Colonization Is Not Mediated By Bile Salts And Utilizes Stickland Fermentation Of Proline In An In Vitro Model, Xiaoyun Huang, April E Johnson, Joshua N Brehm, Thi Van Thanh Do, Thomas A Auchtung, Hugh C Mccullough, Armando I Lerma, Sigmund J Haidacher, Kathleen M Hoch, Thomas D Horvath, Joseph A Sorg, Anthony M Haag, Jennifer M Auchtung

Faculty, Staff and Students Publications

Treatment with antibiotics is a major risk factor for Clostridioides difficile infection, likely due to depletion of the gastrointestinal microbiota. Two microbiota-mediated mechanisms thought to limit C. difficile colonization include the conversion of conjugated primary bile salts into secondary bile salts toxic to C. difficile growth and competition between the microbiota and C. difficile for limiting nutrients. Using a continuous flow model that simulates the nutrient conditions of the distal colon, we investigated how treatment with 6 clinically used antibiotics influenced susceptibility to C. difficile infection in 12 different microbial communities cultivated from healthy individuals. Antibiotic treatment reduced microbial richness; …

Pulmonopoly: A Game-Based Approach To Teach And Reinforce Basic Concepts Of Pulmonary Medicine To Medical Students, Michael Dong, James Uricheck, Urvashi Vaid

Division of Pulmonary, Allergy, and Critical Care Medicine Faculty Papers

INTRODUCTION: Pulmonopoly is an innovative active-learning medical board game addressses core pulmonary concepts in an engaging, competitive style. The strength of Pulmonopoly lies in its ability to combine ease of setup and play with comprehensive content coverage that comprises a significant proportion of national board examinations, offering a gamification experience that can be readily applied in different settings and modified for learner levels.

METHODS: We created an instructional game, Pulmonopoly, based on pulmonary content delivered to preclinical medical students and required for national board examinations. We invited first-year medical students to participate in 60-minute small-group sessions. Content addressed pulmonary subject …

Mage-A4 Induces Non-Small Cell Lung Cancer And Tumor-Promoting Plasma Cell Accumulation, Dominique Armstrong, Cheng-Yen Chang, Monica J Hong, Linda Green, Yichao Shen, William Hudson, Kelsey E Mauk, Li-Zhen Song, Sheetal Jammi, Benjamin Casal, Brianna Burns, Chad J Creighton, Alexandre Carisey, Xiang H-F Zhang, Neil J Mckenna, Sung Wook Kang, Hyun-Sung Lee, William Decker, David B Corry, Farrah Kheradmand

Faculty, Staff and Students Publications

Adaptive immunity is critical in eliminating tumors, but cancer-intrinsic factors can subvert this function. Melanoma antigen-A4 (MAGE-A4), a cancer-testis antigen, is expressed in solid tumors and correlates with poor survival, but its role in tumorigenesis and antitumor immunity remains unclear. We found that expression of MAGE-A4 was highly associated with the loss of PTEN, a tumor suppressor, in human non–small cell lung cancers (NSCLC). Here, we show that constitutive expression of human MAGE-A4 with Pten loss in mouse airway epithelia results in metastatic adenocarcinoma. Tumors showed distinct enrichment in IgA+ CD138+ CXCR4+ plasma cells (PCs) and increased expression of …

Prediction Of Cognitive Conversion Within The Alzheimer’S Disease Continuum Using Deep Learning, Siyu Yang, Xintong Zhang, Xinyu Du, Peng Yan, Jing Zhang, Wei Wang, Jing Wang, Lei Zhang, Huaiqing Sun, Yin Liu, Xinran Xu, Yaxuan Di, Jin Zhong, Caiyun Wu, Jan D Reinhardt, Yu Zheng, Ting Wu

Faculty, Staff and Students Publications

Background: Early diagnosis and accurate prognosis of cognitive decline in Alzheimer's disease (AD) is important to timely assignment to optimal treatment modes. We aimed to develop a deep learning model to predict cognitive conversion to guide re-assignment decisions to more intensive therapies where needed.

Methods: Longitudinal data including five variable sets, i.e. demographics, medical history, neuropsychological outcomes, laboratory and neuroimaging results, from the Alzheimer's Disease Neuroimaging Initiative (ADNI) cohort were analyzed. We first developed a deep learning model to predicted cognitive conversion using all five variable sets. We then gradually removed variable sets to obtained parsimonious models for four different …

Neutralizing Antibody Immune Correlates For A Recombinant Protein Vaccine In The Covail Trial, Youyi Fong, Lauren Dang, Bo Zhang, Jonathan Fintzi, Shiyu Chen, Jing Wang, Nadine G Rouphael, Angela R Branche, David J Diemert, Ann R Falsey, Cecilia Losada, Lindsey R Baden, Sharon E Frey, Jennifer A Whitaker, Susan J Little, Satoshi Kamidani, Emmanuel B Walter, Richard M Novak, Richard Rupp, Lisa A Jackson, Chenchen Yu, Craig A Magaret, Cindy Molitor, Bhavesh Borate, Tara M Babu, Angelica C Kottkamp, Anne F Luetkemeyer, Lilly C Immergluck, Rachel M Presti, Martín Bäcker, Patricia L Winokur, Siham M Mahgoub, Paul A Goepfert, Dahlene N Fusco, Robert L Atmar, Christine M Posavad, Jinjian Mu, Mat Makowski, Mamodikoe K Makhene, Seema U Nayak, Paul C Roberts, Dean Follmann, Peter B Gilbert

Faculty, Staff and Students Publications

For COVAIL recipients of a coronavirus disease 2019 (COVID-19) Sanofi booster vaccine, neutralizing antibody titers were assessed as a correlate of risk (CoR) of COVID-19. Peak and exposure-proximal titers were inverse CoRs with covariate-adjusted hazard ratios (95% confidence intervals) 0.30 (0.11, 0.78) and 0.25 (0.07, 0.85) per 10-fold increase in weighted average titer.

Global Guideline For The Diagnosis And Management Of Candidiasis: An Initiative Of The Ecmm In Cooperation With Isham And Asm, Oliver A. Cornely, Rosanne Sprute, Matteo Bassetti, Sharon C-A Chen, Andreas H. Groll, Oliver Kurzai, Cornelia Lass Flörl, Luis Ostrosky Zeichner, Riina Rautemaa Richardson, Gunturu Revathi

Pathology, East Africa

Candida species are the predominant cause of fungal infections in patients treated in hospital, contributing substantially to morbidity and mortality. Candidaemia and other forms of invasive candidiasis primarily affect patients who are immunocompromised or critically ill. In contrast, mucocutaneous forms of candidiasis, such as oral thrush and vulvovaginal candidiasis, can occur in otherwise healthy individuals. Although mucocutaneous candidiasis is generally not life-threatening, it can cause considerable discomfort, recurrent infections, and complications, particularly in patients with underlying conditions such as diabetes or in those taking immunosuppressive therapies. The rise of difficult-to-treat Candida infections is driven by new host factors and antifungal …

Diagnostic Accuracy Prior To Congenital Heart Defect Surgery: A Multicenter Collaboration, Shobha S Natarajan, Kasey Chaszczewski, Chris Penney, Steve Ampah, Douglas Ryba, Andrea T Kennedy, Robert Olsen, Shubhika Srivastava, Matthew J Campbell, Mya Carney, Carol Prospero, Lisa Elliott, Carlie Brewer, Michael Dimaria, Nitin Madan, Seda Tierney, Meaghan Beattie, Ritu Sachdeva, Joan Lipinski, Kenan W D Stern, Grace Kong, Preeta Dhanantwari, Elena N Kwon, Hari Rajagopal, Carolyn Taylor, Tammy Churchill, Aura A Sanchez Mejia, Deidra Abenlah Ansah, Anitha Parthiban, Hasti Sanandajifar, Sowmya Balasubramanian, David A Parra, Kimberly Crum, Corey Stiver, Aarti H Bhat, Pei-Ni Jone, Stefani Samples, Kathleen Van't Hof, Curt Degroff, Dalia Lopez-Colon, Meryl S Cohen

Faculty, Staff and Students Publications

Background: Echocardiography is the mainstay for diagnosing congenital heart disease (CHD). Diagnostic errors can lead to suboptimal surgical outcomes.

Objectives: This multicenter pediatric echocardiography collaborative learning initiative explores reasons for diagnostic errors, investigates associations between patient- and center-specific factors and errors, and relays the benefits of a multicenter approach to decrease these errors as a first step to improve CHD surgical outcomes.

Methods: Participating centers submitted diagnostic evaluations on patients prior to 2-ventricle repair into a central database. We held virtual meetings to revise variables and discuss cases to learn from each other.

Results: Fourteen pediatric echocardiography laboratories entered data …

Inflammatory Hyperplastic Mass Mimicking Local Recurrence Following Endoscopic Submucosal Dissection Of A Colonic Adenoma, Isiah Gonzalez, Linda K Green, Salmaan Jawaid, Wasseem Skef

Faculty, Staff and Students Publications

This case presents a hyperplastic inflammatory mass at the resection site of a colorectal tubular adenoma. A 65-year-old man with a history of alcohol-associated liver cirrhosis, >10 lifetime polyps, and a CHEK2 mutation underwent hybrid endoscopic submucosal dissection of a 3 cm lateral spreading tumor, nongranular, Paris 0-IIa polyp in the ascending colon. Postresection pathology confirmed tubular adenoma with negative margins (R0). Six-month surveillance colonoscopy in the community identified a mass at the resection site, initially suspected to be local recurrence. Repeat colonoscopy demonstrated a mass which appeared inflammatory, with a Kudo type II hyperplastic pit pattern on narrow-band imaging …

Podoplanin And Microthrombi In Lung Injury, Jahnavi Gollamudi, Ricardo Gonzalez Delgado, Min Soon Cho, Brianne Wharton, Hani Lee, Animesh Vadaparti, Swapan K Dasgupta, Miguel A Cruz, Perumal Thiagarajan, Vahid Afshar-Kharghan

Faculty, Staff and Students Publications

No abstract provided.

Advancing Diagnostic Accuracy And Quality Of Patient Care Through The Implementation Of A Flow Cytometry Quality Assurance Program, Dylan Wang, Hong Fang, Chi Young Ok, Jeffrey L Jorgensen, L Jeffrey Medeiros, Wei Wang, Sa A Wang

Faculty, Staff and Student Publications

Context.—: Flow cytometry immunophenotypic analysis plays an important role in the diagnosis, classification, and disease monitoring of hematologic neoplasms. The interpretation of flow cytometry testing can be challenging.

Objective.—: To explore ways to improve diagnostic accuracy and in turn enhance the quality of patient care.

Design.—: A flow cytometry quality assurance (QA) program was developed. Cases from various complex flow cytometry panels were randomly selected and cross-reviewed. The outcomes of the QA review were categorized into 3 groups: complete agreement, minor discrepancy, and major discrepancy. Each discrepancy underwent a process of documentation, discussion, and resolution. Here we summarize our 3 …

Atypical Presentation Of Non-Small Cell Lung Carcinoma With Metastasis To Breast Tissue, Tylar P. Seckman, Diane Krutzler-Berry, Mohamed Ashal, Waqas Mahmud, Krista L. Denning, Logan M. Lawrence

Marshall Journal of Medicine

Malignant neoplasms of the lung commonly metastasize to lymph nodes, bone, brain, and liver via hematogenous and lymphatic routes. Much less commonly, metastasis occurs in the breast. Secondary metastatic disease of the breast is very rare, with a reported incidence ranging from 0.4-1.3%­­—with primary lung cancer being one of the most anomalous sources. This case details non-small cell lung cancer metastasis to the breast with proven primary contralateral lung origination. This atypical finding prompts medical professionals to consider these malignant cells' immunologic, histologic, and pathologic makeup to understand further and treat the neoplasm.

Clinical Characteristics Of Patients With Copd And Comorbid Depression And Anxiety: Data From A National Multicenter Cohort Study, Jing Gennie Wang, Sonali Bose, Janet T Holbrook, Lin Nan, Michelle N Eakin, Abebaw M Yohannes, Robert A Wise, Nicola A Hanania

Faculty, Staff and Students Publications

Background: Most studies on mental health among individuals with chronic obstructive pulmonary disease (COPD) utilize screening questionnaires, which detect psychiatric symptoms, but cannot be used to diagnose depression/anxiety disorders. We utilized the Mini-International Neuropsychiatric Interview (MINI) to identify depression/anxiety disorders meeting the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition diagnostic criteria and described associated disease burden in people with COPD.

Methods: This is a cross-sectional, secondary analysis of a multicenter study designed to evaluate anxiety questionnaires in COPD patients. Research coordinators administered both the MINI and screening questionnaires to determine participants who met diagnostic criteria for depression/anxiety …

Co-Option Of Mitochondrial Nucleic Acid-Sensing Pathways By Hsv-1 Ul12.5 For Reactivation From Latent Infection, Patryk A. Krakowiak, Matthew E. Flores, Sean R. Cuddy, Abigail L. Whitford, Sara A. Dochnal, Aleksandra Babnis, Tsuyoshi Miyake, Marco Tigano, Daniel A. Engel, Anna R. Cliffe

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Although viruses subvert innate immune pathways for their replication, there is evidence they can also co-opt antiviral responses for their benefit. The ubiquitous human pathogen, Herpes simplex virus-1 (HSV-1), encodes a protein (UL12.5) that induces the release of mitochondrial nucleic acid into the cytosol, which activates immune-sensing pathways and reduces productive replication in nonneuronal cells. HSV-1 establishes latency in neurons and can reactivate to cause disease. We found that UL12.5 is required for HSV-1 reactivation in neurons and acts to directly promote viral lytic gene expression during initial exit from latency. Further, the direct activation of innate immune-sensing pathways triggered …

Neutralizing Antibody Immune Correlates In Covail Trial Recipients Of An Mrna Second Covid-19 Vaccine Boost, Bo Zhang, Youyi Fong, Lauren Dang, Jonathan Fintzi, Shiyu Chen, Jing Wang, Nadine G Rouphael, Angela R Branche, David J Diemert, Ann R Falsey, Daniel S Graciaa, Lindsey R Baden, Sharon E Frey, Jennifer A Whitaker, Susan J Little, Satoshi Kamidani, Emmanuel B Walter, Richard M Novak, Richard Rupp, Lisa A Jackson, Chenchen Yu, Craig A Magaret, Cindy Molitor, Bhavesh Borate, Sydney Busch, David Benkeser, Antonia Netzl, Derek J Smith, Tara M Babu, Angelica C Kottkamp, Anne F Luetkemeyer, Lilly C Immergluck, Rachel M Presti, Martín Bäcker, Patricia L Winokur, Siham M Mahgoub, Paul A Goepfert, Dahlene N Fusco, Robert L Atmar, Christine M Posavad, Jinjian Mu, Mat Makowski, Mamodikoe K Makhene, Seema U Nayak, Paul C Roberts, Peter B Gilbert, Dean Follmann

Faculty, Staff and Students Publications

Neutralizing antibody titer has been a surrogate endpoint for guiding COVID-19 vaccine approval and use, although the pandemic's evolution and the introduction of variant-adapted vaccine boosters raise questions as to this surrogate's contemporary performance. For 985 recipients of an mRNA second bivalent or monovalent booster containing various Spike inserts [Prototype (Ancestral), Beta, Delta, and/or Omicron BA.1 or BA.4/5] in the COVAIL trial (NCT05289037), titers against 5 strains were assessed as correlates of risk of symptomatic COVID-19 ("COVID-19") and as correlates of relative (Pfizer-BioNTech Omicron vs. Prototype) booster protection against COVID-19 over 6 months of follow-up during the BA.2-BA.5 Omicron-dominant period. …