Hemic and Immune Systems Commons^™

Severe Maternal Morbidity According To Sickle Cell Disease Genotype, Tetsuya Kawakita, Natsume Furukawa, Sora A. Jones, Salimah Navaz Gangji

Department of Obstetrics & Gynecology Faculty Publications

Background

Sickle cell disease (SCD) is a genetic hemoglobinopathy that disproportionately affects individuals of African descent and is associated with elevated risks of maternal complications. However, the contribution of specific SCD genotypes to severe maternal morbidity (SMM) and postpartum readmission remains poorly characterized at the population level.

Objective

We sought to examine the association between SCD genotypes-hemoglobin SS (HbSS) disease, hemoglobin SC (HbSC) disease, sickle thalassemia, and sickle cell trait-and SMM, hospital readmission, and related adverse maternal outcomes.

Study design

This was a retrospective cohort study using the Nationwide Readmissions Database from 2016 through 2022, representing over 20 million weighted …

Chronobiology Of Meal Timing In Early-Stage Hypertension: A Controlled Feeding Pilot Study Investigating The Effects On Renal And Vascular Function, Natalie J. Bohmke, Brittany Barton, Patrice Wiecek, Paula Rodriguez-Miguelez, Dave L. Dixon, Youngdeok Kim, Salvatore Carbone, Danielle L. Kirkman

EVMS School of Health Professions Faculty Publications

Lifestyle intervention is critical for young adults with early-stage hypertension. A Western diet has negative effects on kidney function and blood pressure; however, time-of-day effects are understudied. We hypothesized that consumption of a Western-style meal that is misaligned with the endogenous circadian rhythm would have adverse effects on blood pressure, kidney function, and vascular function. Ten young adults with elevated blood pressure or stage 1 hypertension (means ± SD: 26 ± 8 yr, 50% female) underwent a randomized crossover, isocaloric controlled feeding intervention. Participants were allocated to receive a Western-style meal high in sodium, sugar, and saturated fat in the …

Successful Use Of Chimeric Antigen Receptor T-Cell (Car-T) Therapy With Lisocabtagene Maraleucel In A Renal Transplant Recipient With Refractory/Relapsed Diffuse Large B-Cell Lymphoma (Dlbcl), Waqqas Tai, Fatima Chaudhry, Nesreen Shahrour, Jessica Thomas, Afoma Anyadibe, Anuoluwa Oyetoran, Swathi Gopishetty, Precious Idogun, Dilip Samarapungavan, Jassim H. Sarmad, Ishmael Jaiyesimi

Department of Medicine Faculty Publications

This case describes a 53-year-old male with end-stage renal disease who developed monomorphic post-transplant lymphoproliferative disorder (PTLD) in the form of diffuse large B-cell lymphoma (DLBCL) after kidney transplantation. Despite initial treatment with rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone (R-CHOP), the patient's disease progressed, and he was referred for chimeric antigen receptor (CAR) T-cell therapy with lisocabtagene maraleucel (liso-cel). Given his post-transplant status, his immunosuppressive agents (tacrolimus and mycophenolate) were held, and prednisone was tapered to 5 mg daily to maintain minimal baseline immunosuppression. After lymphodepleting chemotherapy and liso-cel infusion, the patient experienced no significant toxicities, including cytokine release syndrome (CRS) …

Editor's Choice - International Expert Consensus On The Management Of Acute Aortic Type B Intramural Haematoma And Penetrating Ulcer, Francesco Squizzato, Mario D'Oria, Michele Antonello, Santi Trimarchi, Kevin Mani, Andrew Holden, Tilo Kölbel, Stephan Haulon, Eric Verhoeven, Dittmar Böckler, Tim Resch, Ali Azizzadeh, Joseph Lombardi, Michele Piazza, Aaron Thomas Fargion, Alexander Zimmerman, Ali Azizzadeh, Anders Wanhainen, Andrew Holden, Antonio Freyrie, Adam W. Beck, Adi Bachar, Barend M. E. Mees, Blandine Maurel, Cristoph A. Nienaber, Christos Karkos, Daniela Branzan, Darren Schneider, Randall Demartino, Dittmar Boeckler, Domenico Angiletta, Emanuel J. R. Tenorio, Enrico Gallitto, Eric Verhoeven, Fabio Verzini, Felice Pecoraro, Filippo Benedetto, Firas F. Mussa, Francesco Squizzato, Franco Grego, Gabriele Piffaretti, Emanuele Gatta, Giovanni Pratesi, Giovanni Tinelli, Giuseppe Asciutto, Glenn Wei Leong Tan, Hence Verhagen, Giacomo Isernia, Jean-Paul P. M. De Vries, Jacob Budtz-Lilly, Jorge Fernández-Noya, Jonathan Sobocinski, Joseph Hockley, Kak Khee Yeung, Andrea Kahlberg, Kevin Mani, Joseph V. Lombardi, Luca Bertoglio, Luca Mezzetto, Ludovic Canaud, Manar Khashram, Marcelo Ferreira, Marco Virgilio Usai, Mark G. Davies, Mark Farber, Martin Czerny, Matthew R. Smeds, Mauro Gargiulo, Germano Melissano, Michel Bosiers, Michele Antonello, Michele Piazza, Miranda Witheford, Michel M.P.J. Reijnen, Marc Schermerhorn, Nikolaos Tsilimparis, Nun Dias, Jean Panneton, Kosmas Paraskevas, Gianbattista Parlani, Patrick W.H.E. Vriens, Rafael Malgor, Raffaele Pulli, Ross Milner, Salvatore T. Scali, Sani J. Laukontaus, Santi Trimarchi, Sandro Lepidi, Konstantinos Spanos, Stefano Fazzini, Theodosios Bisdas, Thomas Maldonado, Tilo Koelbel, Tim Resch, Tomasz Jakimowicz, Nicola Troisi, Isabelle Van Herzeele, Vicente Riambau, Wassim Mansour, Wouter Van Den Eynde, Yamume Tshomba

Department Surgery Faculty Publications

Objective

The aim of this study was to achieve an international expert consensus on managing acute type B penetrating aortic ulcers (PAUs) and intramural haematomas (IMHs).

Methods

A modified Delphi consensus process was employed to develop recommendations for the management of acute type B PAU and IMH. Surveys were sent to international experts practicing in high volume aortic centres worldwide. Statements were voted on using a four point Likert scale in a three round Delphi process. Statements achieving grade A (full agreement 75%) or B (overall agreement 80%, full disagreement <  5%) were included as expert recommendations. Consistency of responses was measured using Cohen's κ and the intraclass correlation coefficient.

Results

Eighty three experts were included in the final analysis: …

Peculiarities Of Phosphatidylserine Externalization By Nano- And Microsecond Electric Pulses, Mantas Silkunas, Alayna Enos, Iurii Semenov, Giedre Silkuniene, Eleni Zivla, Olga N. Pakhomova, Andrei G. Pakhomov

Bioelectrics Publications

Phosphatidylserine (PS) externalization is a hallmark of apoptosis but can also be triggered within seconds by pulsed electric fields (PEFs). Whether PS reaches the outer leaflet by lateral migration through electropores or indirectly through Ca²⁺-dependent signaling and scramblase activation remains debated. We used total internal reflection fluorescence (TIRF) microscopy with Annexin V-Alexa Fluor 568 and/or bovine lactadherin-FITC to resolve PS externalization in HEK293 cells placed on an indium tin oxide (ITO) transparent electrode. PEF exposures produced discrete PS-positive puncta ("freckles") within ~ 10 s after a 20-µs pulse (1.2-2.5 kV/cm) or with a ~ 1-min delay after a …

A Comparison Of F/Taf And F/Tdf As Hiv Pre-Exposure Prophylaxis In A Predominantly Cisgender Women Population In East And South Africa: A Randomised, Factorial, Non-Inferiority Trial, Sheena Mccormack, David Dunn, Sylvia Kusemererwa, Patricia Munseri, Nishanta Singh, Wiston William, Gertrude Mutonyi, Henry Bern, Lauriane Goldwirt, Cherry Kingsley, Arne Kkroidl, Christian Holm Hansen, Song Ding, Rachel Kawuma, Mary Amondi, Ubaldo Bahemuka, Deus Buma, Daniel Clutterbuck, Zakir Gaffoor, Angus Jennings, Agricola Joachim, Ayoub Kakande, Berna Kalanzi, Abisai Kisinda, Mabela Matsoso, Thomas Miller, Neetha Mmedsci Morar, Jacqueline Musau, Jane Nabbuto, Ayanda Nzuza, Doreen Pamba, Simona Salomone, Thandiwe Sithole, Edith Tarimo, Kubashni Woeber, Kundai Chinyenze, Glenda Gray, Eligius Lyamuya, Muhammad Bakari, Said Aboud, Lucas Maganga, Gustavo Doncel, Janet Seeley, Jonathan Weber, Pontiano Kaleebu, Julie Fox, Eugene Ruzagira, On Behalf Of The Prepvacc Study Group

CONRAD Publications

Background:

F/TAF was shown to be non-inferior to F/TDF as pre-exposure prophylaxis (PrEP) in men, but approval was not extended to cisgender women. We report the results of PrEPVacc, in which a predominantly female population was randomly allocated to receive daily oral F/TDF or F/TAF for ∼6 months within a HIV-1 prophylactic vaccine trial.

Setting:

Five study sites in three African countries (Uganda, Tanzania, South Africa).

Methods:

The two regimens were compared by the averted infections ratio (AIR) - the proportion of infections averted by F/TAF relative to F/TDF. The counterfactual HIV incidence, an essential component of this metric, was …

Stat4-Dependent Regulation Of Neuroinflammation In Atherosclerosis, Natalie Stahr, Alina K. Moriarty, Shelby D. Ma, W. Coles Keeter, Woong-Ki Kim, Larry D. Sanford, Elena V. Galkina

Department of Biomedical and Translational Sciences Faculty Publications

Atherosclerosis is linked to an increased risk of cognitive decline, with chronic inflammation being a common feature of both pathologies. IL-12 activates STAT4 to regulate myeloid cell functions, and blockade of this pathway alleviates cognitive impairment in Alzheimer's models. However, the mechanisms connecting vascular pathology to neuroinflammation remain unclear. Here, we examine whether STAT4 functions as a common mediator of neuroinflammation in atherosclerosis. We demonstrate that LysM^Cre-specific STAT4 deficiency ameliorates deficits in long-term memory in low-density lipoprotein-deficient (Ldlr^-/-) mice fed a high-fat diet (HFD-C). STAT4 deficiency moderately reduces Ser199-phosphorylated Tau burden. Atherosclerosis alters brain immune …

Cervicovaginal Lavage Fluid Iron And Manganese Levels In Women With And Without Vaginitis, Barbara Kozma, David Ratonyi, Bence Kozma, Peter Takacs, Attila G. Sipos

Department of Obstetrics & Gynecology Faculty Publications

Transition metals such as iron and manganese are critical for cellular metabolism, redox balance, and immune function, and they also influence host–pathogen interactions. Vaginitis is characterized by mucosal inflammation that may alter local trace-element homeostasis. We hypothesize that inflammatory conditions such as vaginitis may be associated with altered cervicovaginal iron and manganese levels. We performed a prospective, single-center cohort study at the University of Debrecen (Hungary) between April 2023 and April 2024, enrolling 80 women ≥ 18 years with vulvovaginal complaints. Participants were assessed at baseline and at weeks 4, 8, and 12 with clinical evaluation and cervicovaginal lavage (CVL) …

Nanofibrous Materials And Nanoparticles For Combating Antimicrobial Resistance: Synthesis, Integration, And Translational Perspectives, Rewati Raman Ujjwal, Ashish Dilip Sutar, Rahul Shukla, Gymama Slaughter

Center for Bioelectronics Publications

Antimicrobial resistance (AMR) is a major global health challenge driven by mechanisms such as biofilm formation, efflux pumps, and genetic mutations. Nanoparticulate and fibrous materials have emerged as promising strategies to overcome these limitations through multimodal antimicrobial action and controlled drug delivery. This review highlights recent advances in electrospun nanofibrous systems, including natural and synthetic polymer-based scaffolds, stimuli-responsive nanofibers, and functionalized patches. Nanoparticle-loaded nanofiber systems demonstrate enhanced performance, including bacterial eradication, sustained drug release, and significant biofilm disruption. Multifunctional systems combining antimicrobial, antioxidant, and immunomodulatory properties further show synergism. Emerging innovations, such as piezoelectric and smart sensing systems, enable self-powered …

Circulating Biomarker Results From A Phase 2 Study Of Seralutinib In Pulmonary Arterial Hypertension, Robin Osterhout, Athénaïs Boucly, Raymond L. Benza, Richard N. Channick, Kelly M. Chin, Robert P. Frantz, Anna R. Hemnes, Luke S. Howard, Vallerie V. Mclaughlin, Olivier Sitbon, Jean-Luc Vachiéry, Rotham T. Zamanian, Richard Aranda, Matt Cravets, Zhaoqing Ding, Thao Duong-Verlé, David Mattola, Robert F. Roscigno, Ravikumar Sitapara, Lawrence S. Zisman, Jean-Marie Bruey, Hossein-Ardeschir Ghofrani

Department of Medicine Faculty Publications

[Introduction] To the Editor: Pulmonary arterial hypertension (PAH) is a progressive disease characterized by obstructive pulmonary arterial remodeling (1). Seralutinib, an investigational inhaled tyrosine kinase inhibitor, potently and selectively targets kinases relevant to PAH pathobiology including platelet-derived growth factor receptors (PDGFR) α and β, colony stimulating factor 1 receptor (CSF1R), and mast/stem cell growth factor receptor kit (c-KIT) (2). In preclinical models, seralutinib improved cardiopulmonary hemodynamics, reversed pulmonary vascular pathology and decreased right ventricular hypertrophy (3). In TORREY, a phase 2, multicenter, double-blind, randomized, placebo-controlled trial in PAH, seralutinib significantly reduced pulmonary vascular resistance (PVR) after 24 weeks with good …

Baseline Lymphopenia Predicts Survival In Ici-Naïve Solid Tumor Patients Receiving Immune Checkpoint Inhibitors: A Propensity-Matched Real-World Pan-Cancer Analysis, Ahmed Ismail, Nina Balanchivadze, George R. Simon, Yanis Boumber

Department of Medicine Faculty Publications

Background: Baseline lymphopenia is common among advanced solid tumors and may influence the efficacy/safety of immune checkpoint inhibitors (ICIs), but large real-world evidence is limited. We evaluated the association between baseline absolute lymphocyte count (ALC) and clinical outcomes in adults with solid tumors treated with ICIs in routine practice. Methods: We performed a retrospective cohort study using TriNetX. Adults with solid tumors who received pembrolizumab, nivolumab, or atezolizumab (ICI-Naïve) between January 2015 and June 2026 were included. Baseline ALC was measured within 30 days before first treatment and was classified as lymphopenic (ALC < 1.5 × 10⁹/L) or non-lymphopenic (ALC ≥ 1.5 × 10⁹/L). Propensity score matching (1:1) yielded 5249 patients per group. The index date was the first immunotherapy date, and outcomes were assessed at 6, 12, 24, 36 months, and 5 years. The primary outcome was 24-month overall survival (OS); secondary outcomes were OS at 6 and 12 months and 6-month risks of healthcare utilization, immune-related adverse events (irAEs), and serious infections; and exploratory outcomes included OS at 36 months and 5 years. All outcomes were analyzed using Kaplan–Meier analysis, Cox proportional hazards models, and risk ratios. Subgroup analysis included OS stratified by solid tumor subtypes and prior lines of therapy. Results: After matching, patients with baseline lymphopenia …

Microarray Analysis Of Human Abdominal Aortic Aneurysm With Emphasis On Cardiovascular Genes Revealed Differentially Expressed Genes, Song Lu, Li Ping Li, John V. White, Xiaoying Zhang, Ifeyinwa Nwaneshiudu, Adaobi Nwaneshiudu, Nectaria Ntaoula, John Gaughan, Dimitri S. Monos, Wan-Lu Lin, Charalambos C. Solomides, Emilia L. Oleszak, Chris D. Platsoucas

Biological Sciences Faculty Publications

Background/Aim: We examined gene expression profiles in abdominal aortic aneurysm (AAA) lesions vs. normal aortas by cDNA microarray and real-time quantitative reverse-transcriptase polymerase chain reaction (qRT-PCR).

Materials and Methods: Phosphorus (32P)-labeled cDNA from AAA specimens (mean AAA size 6.65 cm) and normal aortas were hybridized with a 588-gene microarray primarily of the cardiovascular system. The results were validated by qRT-PCR.

Results: A total of 35 out of the 588 genes were differentially expressed, with either log2 ratio of AAAs/controls ≥1 (upregulated; 20 genes) or ≤−1 (downregulated; 15 genes) in AAA lesions vs. normal aorta, and 25 of these were significantly …

Presentation, Diagnosis, And Acute Treatment Of Secondary Hemophagocytic Lymphohistiocytosis: A Case Report, Alexandra Bartholomew, Michael Connick, Catherine Loehr, Shane Sanne

School of Medicine Faculty Publications

Secondary hemophagocytic lymphohistiocytosis (HLH) is a rare, immunologically driven disorder with a high mortality rate. It is typically diagnosed on the basis of clinical and laboratory criteria. We present the case of a 53-year-old woman with multiple previous hospitalizations for fever of unknown origin and fatigue. Her workup ultimately led to a diagnosis of HLH. We discuss the presentation, diagnostic criteria, and clinical treatment of secondary HLH to guide workup and management for future patients affected by this rare disease.

Imaging Hallmarks Of Idiopathic Intracranial Hypertension And Insights Into Pathogenesis, Albalooshy Basimah, Scott Faro, Hsiangkuo Yuan, Kiran Talekar, Prabath Mondel, Enchao Qiu, Joga Chaganti

Department of Radiology Faculty Papers

Idiopathic Intracranial hypertension (IIH), also referred to as pseudotumor cerebri, is a term used to describe increased intracranial pressure in the absence of a known identifiable secondary cause. Despite advancements of neuroimaging techniques, imaging of the pathological underpinnings in the diagnosis of IIH has been limited. Although the causation of IIH has been ascribed to increased Cerebrospinal Fluid production and disordered drainage through the dural sinuses, new evidence shows that the glymphatic system which is an alternate pathway of drainage is likely to play a pivotal role. In this review, we address the pathophysiological underpinnings in the causation of IIH …

Excess Fructose In High-Fructose Corn Syrup Reduces Cell Viability & Promotes Nitric Oxide Release In Raw 264.7 Macrophages, Renzo F. Galarza, Edward L. Villegas

Research and Creativity Symposium

High-fructose corn syrup (HFCS) is an artificial sweetener that contains slightly higher concentrations of fructose compared to standard sucrose. It has been linked to an increased risk of obesity, type 2 diabetes, cardiovascular disease, and fatty liver disease. While both HFCS and sucrose are widely used sweeteners, growing evidence suggests they may differ in their inflammatory potential. We sought to understand the effects of elevated fructose on RAW 264.7 macrophages. To investigate these effects, we treated the cells with either a sucrose solution or a
solution designed to mimic high-fructose corn syrup. Lipopolysaccharide (LPS) stimulation was used to model innate …

Transcription Factor Runx1 Regulates Coagulation Factor Xiii-A (F13a1): Decreased Platelet-Megakaryocyte F13a1 Expression And Clot Contraction In Runx1 Haplodeficiency, Fabiola Del Carpio-Cano, Natthapol Songdej, Liying Guan, Guangfen Mao, Lawrence E. Goldfinger, Jeremy G.T. Wurtzel, Kiwon Lee, Michele P. Lambert, Mortimer Poncz, A. Koneti Rao

Cardeza Foundation for Hematologic Research

BACKGROUND: Germline RUNX1 haplodeficiency (RHD) is associated with thrombocy- topenia, platelet dysfunction, and predisposition to myeloid malignancies. Platelet expression profiling of an RHD patient showed decreased F13A1, encoding for the A subunit of factor (F)XIII, a transglutaminase that cross-links fibrin and induces clot stabilization. FXIII-A is synthesized by hematopoietic cells, megakaryocytes, and monocytes.

OBJECTIVES: o understand RUNX1 regulation of F13A1 expression in platelets/mega- karyocytes and the mechanisms and consequences of decreased F13A1 in RHD.

METHODS: We performed studies in platelets, human erythroleukemia (HEL) cells, and human CD34+ cell-derived megakaryocytes including on clot contraction in cells following small inhibitor RNA knockdown …

Neuroinflammatory Signaling And Immune Cell Infiltration Differ In Brains Of Rats Exposed To Space Radiation And Social Isolation, Austin M. Adkins, Zachary N. M. Luyo, Alea F. Boden, Riley S. Heerbrandt, Richard A. Britten, Laurie L. Wellman, Larry D. Sanford

Center for Integrative Neuroscience and Inflammatory Diseases (CINID) Faculty Publications

Astronauts on the proposed Mars missions will be exposed to extended periods of social isolation (SI) and space radiation (SR). SI and SR-induced immune dysregulation can result in persistent neuroinflammation and neuronal damage which could negatively impact an astronaut’s health and ability to maintain adequate levels of performance. The synergistic effects of combined SI and SR on immune system functionality and the brain remain unknown. Determining how single and combined inflight stressors modulate the immune system is crucial for fully understanding pathways impacting astronaut health and performance. We used ground-based analogs of SI and SR in rodent models to investigate …

Ancestry-Dependent Immunologic And Prognostic Effects Characterize The Prostate Cancer Urinary Proteome, Annie Ha, Jaron Arbet, Zhuyu Qiu, Amanda Khoo, Brian P. Main, Meinusha Govindarajan, Matthew Waas, Stanley K. Liu, O. John Semmes, Julius O. Nyalwidhe, Paul C. Boutros, Thomas Kislinger

Leroy T. Canoles Jr. Cancer Research Center Faculty Publications

Urine is an attractive biomarker analyte for non-invasive longitudinal monitoring of health and disease, particularly for diseases of the genitourinary tract, like prostate and bladder cancer. The composition of an individual's urine reflects both genetic and lifestyle characteristics that differ across geographies and populations, like diet, hydration and other socio-economic factors. While men of African ancestry have elevated prostate cancer risk, it is unclear to what extent this influences urinary biomarkers. We therefore quantified the urinary proteomes of 329 localized prostate cancer patients: 135 self-identifying as White and 194 self-identifying as Black. We identified 110 proteins that significantly differed between …

Large-Bore Mechanical Thrombectomy Versus Catheter-Directed Thrombolysis In The Management Of Intermediate-Risk Pulmonary Embolism: Primary Results Of The Peerless Randomized Controlled Trial, Wissam A. Jaber, Carin F. Gonsalves Md, Stefan Stortecky, Samuel Horr, Ripal T. Gandhi, Keith Pereira, Jay Giri, Sameer J. Khandhar, Khawaja Afzal Ammar, David M. Lasorda, Brian Stegman, Lucas Busch, David J. Dexter, Ezana M. Azene, Nikhil Daga, Fakhir Elmasri, Chandra R. Kunavarapu, Mark E. Rea, Joseph S. Rossi, Joseph Campbell, Jonathan Lindquist, Adam Raskin, Jason C. Smith, Thomas M. Tamlyn, Gabriel A. Hernandez, Parth Rali, Torrey R. Schmidt, Jeffrey T. Bruckel, Juan C. Camacho, Jun Li, Samy Selim, Catalin Toma, Sukhdeep Singh Basra, Brian A. Bergmark, Bhavraj Khalsa, David M. Zlotnick, Jordan Castle, David J. O'Connor, C. Michael Gibson, For The Peerless Committees And Investigators

Department Surgery Faculty Publications

BACKGROUND: There are a lack of randomized controlled trial data comparing outcomes of different catheter-based interventions for intermediate-risk pulmonary embolism.

METHODS: PEERLESS is a prospective, multicenter, randomized controlled trial that enrolled 550 patients with intermediate-risk pulmonary embolism with right ventricular dilatation and additional clinical risk factors randomized 1:1 to treatment with large-bore mechanical thrombectomy (LBMT) or catheter-directed thrombolysis (CDT). The primary end point was a hierarchal win ratio composite of the following (assessed at the sooner of hospital discharge or 7 days after the procedure): (1) all-cause mortality, (2) intracranial hemorrhage, (3) major bleeding, (4) clinical deterioration and/or escalation …

Anaplastic Large Cell Lymphoma In Children And Adolescents, Eric J. Lowe, Wilhelm Woessmann

Department of Pediatrics Faculty Publications

Anaplastic lymphoma kinase (ALK)-positive anaplastic large-cell lymphoma (ALCL) accounts for >95% of ALCL cases in children and adolescents. The first description of ALCL as a CD30-positive lymphoma in 1985 was followed by the detection of chromosomal translocations involving the ALK gene at chromosome 2p23. The pathogenesis of ALK-positive ALCL is based on signalling from the constitutive active ALK kinase. The clinical characteristics, therapy regimens and outcome data were reported in the 1990s and 2000s. Different chemotherapy regimens led to astonishingly similar long-term event-free survival rates of 70%, independent of the drugs, doses and duration of therapy. Additionally, patients with relapsed …

A Linear Presentation Of Cutaneous Rosai Dorfman Disease, Emily Sheetz, Ryan C. Saal, Molly K. Smith, Rachel Chikowski Byrd

Department of Medicine Faculty Publications

[Case description] A 53-year-old female with type II diabetes and hypertension presented to the dermatology clinic with a 3-month history of an asymptomatic linear eruption along the right knee that extended distally along the shin. Initial biopsy showed an atypical lymphohistiocytic infiltrate (Fig 1), which was found to be polyclonal. At her 3-month follow up visit, the eruption demonstrated significant clinical progression with numerous indurated papules and papulonodules, some of which were tender, along the right knee and pretibial surface (Fig 2). No improvement was noted with topical triamcinolone prescribed at her initial visit.

Sarcoidosis With Isolated Osseous Manifestations Mimicking Metastatic Malignancy, Ahmed Ismail, Ahmed Saleh, Yanis Boumber

Department of Medicine Faculty Publications

Sarcoidosis is an inflammatory disease of unknown etiology that commonly involves multiple organ systems, with the lungs and lymph nodes most frequently affected. Osseous involvement, although recognized, is considered uncommon and often overlooked due to its nonspecific clinical and radiographic features. Patients may be asymptomatic or present with pain, swelling, and functional limitations of the affected limb. Imaging can reveal findings such as bone lesions that mimic malignancy, including lytic or sclerotic changes. Diagnosis relies on histopathological confirmation of non-caseating granulomas. Treatment is directed at symptom relief and preservation of limb function. Here, we present a rare case of isolated …

Sars-Cov-2 Infection Induces Human Milk Antibodies Capable Of Mediating Multiple Functional Activities, Jared Sheehan, Aline Andres, Laxmi Yeruva, Alistair J. Ramsay

School of Medicine Faculty Publications

Background and Aims: Passive transfer of antibodies through breastfeeding is a potential mode of protection for newborns and infants following maternal SARS-CoV-2 infection. The primary goal of this study was to evaluate and characterize SARS-CoV-2 Spike (S)-specific antibodies in human milk samples collected longitudinally from a cohort of convalescent mothers. Methods: SARS-CoV-2 infected participants enrolled in this study were lactating women aged 29–36 years with a confirmed COVID-19 diagnosis who donated milk samples at intervals over the six-month study period. Samples were evaluated for antibody subclass SARS-Cov-2 S glycoprotein binding activity by ELISA, and for the capacity of antibodies purified …

Hyperbaric Oxygen Therapy In The Atls/Acls Resuscitative Management Of Acutely Ill Or Severely Injured Patients With Severe Anemia: A Review, Keith W. Van Meter

School of Medicine Faculty Publications

For short periods, even without the presence of red blood cells, hyperbaric oxygen can safely allow plasma to meet the oxygen delivery requirements of a human at rest. By this means, hyperbaric oxygen, in special instances, may be used as a bridge to lessen blood transfusion requirements. Hyperbaric oxygen, applied intermittently, can readily avert oxygen toxicity while meeting the body's oxygen requirements. In acute injury or illness, accumulated oxygen debt is shadowed by adenosine triphosphate debt. Hyperbaric oxygen efficiently provides superior diffusion distances of oxygen in tissue compared to those provided by breathing normobaric oxygen. Intermittent application of hyperbaric oxygen …

Mouse Monocytes Express Cd127 By Immune Cells, Not Lps, Reza Yazdani, Mozhde Askari, Amir Moghadam-Ahmadi, Gholamreza Azizi, Bogoljub Ciric, Alexandra Boehm, Guang-Xian Zhang, Mohamad Rostami

Department of Neurology Faculty Papers

The essential role of interleukin 7 (IL-7) signaling via its receptor (IL-7Rα; CD127) in T cell development and function has been well documented. However, CD127 expression and function in myeloid cells, including monocytes, are less clear, especially in mice. In the present study we report an inducible CD127 expression in mouse monocytes/macrophages. This induction is dependent on the presence of other immune cells, highlighting that regulation of CD127 expression on monocytes differs in mice and humans. We demonstrate that CD127 is functional, as IL-7 downregulated its expression. We also saw decreased CD127 expression during inflammation in vivo. Overall, upregulation …

Csf1r Inhibition Depletes Brain Macrophages And Reduces Brain Virus Burden In Siv-Infected Macaques, Diana G. Bohannon, Laurent D. Zablocki-Thomas, Evan S. Leung, Jinbum K. Dupont, Julian B. Hattler, Jolanta Kowalewska, Miaoyun Zhao, Jiangtao Luo, Marco Salemi, Angela M. Amedee, Qingsheng Li, Marcelo J. Kuroda, Woong-Ki Kim

School of Graduate Studies Faculty Publications

Perivascular macrophages (PVMs) and, to a lesser degree, microglia are targets and reservoirs of HIV and simian immunodeficiency virus (SIV) in the brain. Previously, we demonstrated that colony-stimulating factor 1 receptor (CSF1R) in PVMs was upregulated and activated in chronically SIV-infected rhesus macaques with encephalitis, correlating with SIV infection of PVMs. Herein, we investigated the role of CSF1R in the brain during acute SIV infection using BLZ945, a brain-penetrant CSF1R kinase inhibitor. Apart from three uninfected historic controls, nine Indian rhesus macaques were infected acutely with SIVmac251 and divided into three groups (n = 3 each): an untreated control and …

Ikaros Expression Drives The Aberrant Metabolic Phenotype Of Macrophages In Chronic Hiv Infection, Cecilia Vittori, Celeste Faia, Dorota Wyczechowska, Amber Trauth, Karlie Plaisance-Bonstaff, Mary Meyaski-Schluter, Krzysztof Reiss, Francesca Peruzzi

School of Medicine Faculty Publications

The increased risk for acquiring secondary illnesses in people living with HIV (PLWH) has been associated with immune dysfunction. We have previously found that circulating monocytes from PLWH display a trained phenotype. Here, we evaluated the metabolic profile of these cells and found increased mitochondrial respiration and glycolysis of monocyte-derived macrophages (MDMs) from PLWH. We additionally found that cART shifted the energy metabolism of MDMs from controls toward increased utilization of mitochondrial respiration. Importantly, both downregulation of IKAROS expression and inhibition of the mTOR pathway reversed the metabolic profile of MDMs from PLWH and cART-treated control-MDMs. Altogether, this study reveals …

Predicting Radiation-Induced Immune Suppression In Lung Cancer Patients Treated With Stereotactic Body Radiation Therapy, Jonathan Colen, Cam Nguyen, Seth W. Liyanage, Eric Aliotta, Joe Chen, Clayton Alonso, Kara Romano, Sean Peach, Timothy Showalter, Paul Read, James Larner, Krishni Wijesooriya

Data Science Faculty Publications

BACKGROUND: Stereotactic body radiation therapy (SBRT) is known to modulate the immune system and contribute to the generation of anti-tumor T cells and stimulate T cell infiltration into tumors. Radiation-induced immune suppression (RIIS) is a side effect of radiation therapy that can decrease immunological function by killing naive T cells as well as SBRT-induced newly created effector T cells, suppressing the immune response to tumors and increasing susceptibility to infections.

PURPOSE: RIIS varies substantially among patients and it is currently unclear what drives this variability. Models that can accurately predict RIIS in near real time based on treatment plan characteristics …

St-Elevation In Avr With Diffuse St-Segment Depression: Need For Urgent Catheterization?, Bruce M. Lo, Megyn K. Christensen, Katherine E. Schaffer, Theodore J. Tzavaras

Department of Emergency Medicine Faculty Publications

Case Presentation: A 33 year old female with a history of antiphospholipid syndrome presented with exertional chest pain and ST-elevation in aVR with diffuse ST-depression. An emergent catheterization was performed which showed an isolated 99% stenosis in the left main coronary artery. The remaining coronary arteries were without any stenosis. Successful stent placement was performed, and the patient was discharged without complications.

Discussion: Previous guidelines suggested that ST-elevation with diffuse ST-depression should be treated as a STEMI-equivalent involving the left-main or proximal left anterior descending coronary artery. However recent data suggests that the majority of these cases may not involve …

Triphlapan: Predicting Hla Molecules Binding Peptides Based On Triple Coding Matrix And Transfer Learning, Meng Wang, Chuqi Lei, Jianxin Wang, Yaohang Li, Min Li

Computer Science Faculty Publications

Human leukocyte antigen (HLA) recognizes foreign threats and triggers immune responses by presenting peptides to T cells. Computationally modeling the binding patterns between peptide and HLA is very important for the development of tumor vaccines. However, it is still a big challenge to accurately predict HLA molecules binding peptides. In this paper, we develop a new model TripHLApan for predicting HLA molecules binding peptides by integrating triple coding matrix, BiGRU + Attention models, and transfer learning strategy. We have found the main interaction site regions between HLA molecules and peptides, as well as the correlation between HLA encoding and binding …