Chemicals and Drugs Commons^™

Quantification Of Illicit And Prescription Drug Residues In Pasteurized Donor Human Milk: A Comprehensive Analytical Approach, Michelle Brenner, Kaytlin Krutsch, Ashlynn Baker, Dhavalkumar Patel, Palika Datta

Department of Pediatrics Faculty Publications

Objective

To assess the risk of infant exposure to illicit and prescription drug residues, from infant-ready, pooled, pasteurized donor human milk (PDHM) provided by healthy, screened, voluntary non-remunerated donors to a not-for-profit milk bank.

Study Design

A total of 150 pooled samples, representing 742 donor contributions, were analyzed for 15 illicit and prescription drug analytes using liquid chromatography-tandem mass spectrometry (LC-MS/MS). Detected concentrations were evaluated for clinical significance.

Result

All 150 PDHM samples tested negative for residues of marijuana, amphetamines, benzodiazepines, fentanyl, hydrocodone, and morphine. Three samples (2%) contained trace amounts of oxycodone (< 0.6 parts per billion), yielding exposures over 455 times lower than established standards for infant safety (Relative Infant Dose: < 0.022%; standard safety threshold 10%).

Conclusion

Comprehensive analysis detected no clinically …

Bortezomib And Vorinostat In Combination With Mitoxantrone, Dexamethasone, And Pegasparaginase During Induction And Reinduction For Infants With Acute Lymphoblastic Leukaemia: A Multicentre Single-Arm Phase 1/2 Study, Tanja A. Gruber, Sima Jeha, Rebecca J. Deyell, Victor Lewis, Bill H. Chang, Eric J. Lowe, Jamie Frediani, Catherine Vezina, Bruno Michon, Michael Richards, Erin H. Breese, Thai-Hoa Tran, Norman Lacayo, Christine Bolen, Sunil Desai, Jennifer L. Pauley, Minxuan Huang, Emily Ashcraft, Cheng Cheng, Kirk R. Schultz, Linda Stork, Krysta Schlis, Van T. Huynh, Nathan Gossai, Yoav H. Messinger, Henrique Bittencourt, Terzah M. Horton, Uma Athale, Duncan Stearns, Deborah Schiff, Paul S. Gaynon

Department of Pediatrics Faculty Publications

Background: Acute lymphoblastic leukaemia in infants remains a therapeutic challenge. In preclinical studies we previously identified bortezomib and vorinostat as active agents against KMT2A rearranged (KMT2Ar) leukaemia. The aim of this study was to determine the tolerability of incorporating bortezomib and vorinostat into an acute lymphoblastic leukaemia-chemotherapy backbone for newly diagnosed infants with acute lymphoblastic leukaemia both with and without KMT2Ar.

Methods: In this single-arm phase 1/2 study conducted at 18 hospitals in the USA and Canada, we enrolled patients aged 1 year or younger at the time of diagnosis with newly diagnosed acute lymphoblastic leukaemia or undifferentiated leukaemia (with …

Estrogen Deprivation During Primate (Papio Anubis) Pregnancy: Impact On Systemic Microvascular Flow And Cardiovascular Development And Function After Birth In Offspring, Sifa Turan, Jeffery S. Babischkin, Graham W. Aberdeen, Gerald J. Pepe, Eugene D. Albrecht

Department of Biomedical and Translational Sciences Faculty Publications

Background

Suppressing estradiol (E₂) during baboon pregnancy lowers offspring skeletal muscle capillary density, vital for insulin-mediated glucose uptake, and induces insulin resistance. We examined whether E₂ deprivation also impairs microvascular flow and cardiac function.

Methods

Offspring of untreated baboons, letrozole-treated baboons, or letrozole plus E₂ (maternal s.c. injections during the second half of gestation) underwent contrast-enhanced microbubble ultrasonography to quantify microvessel flow and echocardiography to assess cardiac performance.

Results

Letrozole reduced maternal serum E₂ by 95% (p <  0.01). In letrozole offspring, microbubble flux rate (β) fell 55% (p <  0.02), replenishment was 5 s slower (p <  0.03), and microvessel flow declined 40% (p = 0.05); all were restored by added E₂. Indices of systolic (isovolumic contraction), diastolic (isovolumic relaxation), global performance (Tei index), and cardiac output were unchanged.

Conclusion

Prolonged gestational E₂ deprivation programs a reduction in microvascular flow without altering cardiac function; maternal E₂ prevents this, supporting E₂'s role in …

The Structure Of The Native Cardiac Crossbridge In The Rigor State, Cristina M. Risi, Tyler Nguyen, Betty Belknap, Howard D. White, Jose R. Pinto, Prescott B. Chase, Vitold E. Galkin

Department of Biomedical and Translational Sciences Faculty Publications

Cardiac contraction is driven by double-headed myosin cycling on cardiac thin filaments, where troponin-tropomyosin regulates myosin access to actin. Prior high-resolution structural studies used a single-headed myosin bound to bare actin, thereby limiting insight into coordination between myosin heads and the influence of troponin-tropomyosin on actomyosin interactions. Here, we report a high-resolution structure of the native cardiac rigor cross-bridge formed by heavy meromyosin bound to the thin filament. We show that direct communication between the two bound heads, uneven interactions between the heads and tropomyosin, and spatial constraints imposed by troponin govern myosin placement along the thin filament. Additionally, the …

Microfluidic Encapsulation Of Sorafenib-Loaded Zif-8 Nanoparticles In Ph-Responsive Alginate Microparticles For Oral Chemotherapy Of Hepatocellular Carcinoma, Mojdeh Mirshafiei, Zahra Mahmoudi, Mehdi Mehrpouya, Mahdi Mahmoudi, Masoud Rezaeian, Mona Navaei-Nigjeh, Zahra Katoli, Lobat Tayebi

Electrical & Computer Engineering Faculty Publications

Hepatocellular carcinoma (HCC) remains one of the leading causes of cancer-related mortality. Sorafenib is the current first-line oral therapy; however, its therapeutic efficacy is limited by poor aqueous solubility, low bioavailability, and gastrointestinal instability. This study aimed to develop a pH-responsive nano-in-microparticle delivery system using a single-step droplet-based microfluidic process to protect sorafenib in the gastric environment and achieve controlled release for enhanced oral chemotherapy. Sorafenib-loaded ZIF-8 nanoparticles (SZ NPs) were synthesized and characterized by scanning electron microscopy (SEM), Fourier-transform infrared (FTIR) spectroscopy, Energy-dispersive X-ray (EDX) spectroscopy, and X-ray diffraction (XRD), exhibiting a mean diameter of about 72 nm and …

The Postsynaptic Scaffolding Protein Sapap3 Shapes Mitochondrial Activity: The Case Of Huntington's Disease, Patrícia Coelho, Ildete Luísa Ferreira, Ana Sofia Lourenço, Daniela Marinho, Sandra Isabel Anjo, Zongwei Fang, Lígia Fão, Sandra I. Mota, Philippe J. Mas, Mário Carvalho, Rui Jorge Nobre, Carina Henriques, Joana Fraga, Dongqing Wang, Sandra Macedo Ribeiro, Luís Pereira De Almeida, Patrícia Monteiro, Isaura Simões, Darren J. Hart, Bruno Manadas, João Peça, Pedro Castanheira, A. Cristina Rego

Biological Sciences Faculty Publications

Postsynaptic scaffolding protein SAP90/PSD95-associated protein 3 (SAPAP3) modulates cortico-striatal signalling and regulates the maintenance of synaptic structure. Notably, SAPAP3 defects have been reported in several human psychiatric disorders that share pathophysiological features with Huntington’s disease (HD), a neurodegenerative disorder characterized by the expression of mutant huntingtin (mHTT) and marked dysfunction of cortico-striatal synapses and mitochondria. However, the role of SAPAP3 in mitochondrial function and HD pathophysiology remains unexplored. SAPAP3 was extracted from striatal synaptoneurosomes and analyzed by SWATH-MS proteomics to identify potential interactors, revealing SAPAP3 association with several mitochondrial proteins, particularly Mic60. These data were further complemented with proximity ligation …

Glucagon-Like Peptide-1-Based Therapies And The Intersection Of Metabolic And Skin Disease, Ana Ormaza-Vera, Clinton W. Enos

Department Dermatology Faculty Publications

[Introduction] To the Editor: The development of the glucagon-like peptide-1 (GLP-1) receptor agonists (GLP-1RAs) and the dual glucose-dependent insulinotropic polypeptide/GLP-1RAs is revolutionizing the management of metabolic disease. Perhaps most impressive is that their clinical significance extends far beyond their approved indications and touches seemingly every organ system, even the skin.

Investigating The Role Of Traditional Chinese Herbal Medicine For Cancer Symptom Management In Older Adults: A Rapid Review, Isabelle C. Karshner

Honors Undergraduate Theses

Background: Patients with cancer often experience symptoms related to disease, complications, and treatment. One potential method of alleviating these symptoms is traditional Chinese herbal medications (TCHM). This rapid review explores the role of traditional Chinese herbal medications in treating cancer-related symptoms in older adults.

Purpose: The purpose of this rapid review is to gain and provide a better understanding of the effects of TCHM on cancer-symptom management in the older adult population. This review explores the association between TCHM and effects on cancer symptoms in older adults, including interactions, toxicity, and signs/symptoms of TCHM use that may be useful information …

Synthesis And Characterization Of Succinate Dehydrogenase Inhibitors H2/Z14 And C6/Z96 In Order To Combat Small Cell Lung Cancer, Lauren M. Graves

Honors Undergraduate Theses

The use of ubiquinone inhibitors to combat cancer is a recent development in medicinal science and procedures to efficiently synthesize these drugs remain limited. C6/Z96 and H2/Z14, two succinate dehydrogenase inhibitors, have been previously tested in vitro against NSCLC with positive results. Their similarity to ubiquinone is what makes them a strong candidate for a succinate dehydrogenase inhibitor at the ubiquinone binding site. The heterocyclic scaffolds and substituents are proposed to bind strongly through a combination of electronics, hydrogen-bonding, and fit, allowing them to bind well and prove to be more favorable than ubiquinone when competing for the Q-site. By …

From Controversy To Comeback: The Renewed Role Of Pralidoxime In Op Poisoning, Dr Sanaa Jain, Dr Savitha V, Dr . Shashidhara K C

Digital Journal of Clinical Medicine

Organophosphorus compounds are commonly used as pesticides in agriculture, but they are responsible for approximately one-third of suicide deaths in Asian countries.The symptoms of organophosphate (OP) poisoning vary over time and are categorized into three phases: Acute Cholinergic Crisis (minutes to 24 hours), Delayed Phase (24 hours to 2 weeks), which may include intermediate syndrome, coma, and extrapyramidal symptoms, and Late Phase (OPIDP). Treatment typically involves Atropine, Pralidoxime, and symptomatic management, including airway support and mechanical ventilation.

Does The Serum Salicylate Need To Be Checked On Every Patient With An Overdose? Could A Toxic Salicylate Concentration Be Ruled Out With The Absence Of An Elevated Anion Gap?, Ibrahim Al-Saadi, William Lopez Jr, Hedaya Othman, Nicholas Connors

South Atlantic Division GME Research Days 2026

No abstract provided.

Gastrointestinal Symptoms Associated With Sodium Bicarbonate Supplementation Protocols: A Systematic Review, Ian P. Winter, Paul Sarac, Patrick B. Wilson

Exercise Science Faculty Publications

Sodium bicarbonate positively impacts performance, but its associated gastrointestinal symptoms (GIS) may limit use. This systematic review synthesized literature that has evaluated GIS with sodium bicarbonate supplementation. Literature searches were performed from February 2024-March 2026. Eligible studies provided ≥ 5 g of sodium bicarbonate within a 24-h period or, if a multi-day protocol, at least one day involving ≥ 5 g. Included studies had a placebo group/condition or a comparison group/condition that created a contrast related to delivery method, form, or dose. In total, 101 investigations were summarized in six categories: acute single dosing (n = 35); acute spread dosing …

Recognizing Early Serotonin Syndrome From Ssri-Buspirone Combination: A Case Report, Jacob Moore, Barbara Gracious

South Atlantic Division GME Research Days 2026

No abstract provided.

Mepolizumab Improves Outcomes In Patients With Crswnp With One Or More Prior Nasal Polyp Surgeries, Joseph K. Han, Joaquim Mullol, Martin Wagenmann, Laura Walrave, Lingjiao Zhang, Ana R. Sousa, Peter Howarth, Claire Hopkins

Department of Otolaryngology (ENT) Faculty Publications

BACKGROUND: Patients with chronic rhinosinusitis with nasal polyps (CRSwNP) often undergo multiple nasal surgeries. The Phase III SYNAPSE study (GSK ID:205687; NCT0308579) demonstrated that mepolizumab reduces the need for repeat surgery. We explored whether outcomes differed based on the number of prior surgeries. METHODOLOGY: This post hoc analysis of SYNAPSE stratified patients by history of 1 or more than 1 prior surgery. Patients were randomised to receive mepolizumab or placebo every 4 weeks, alongside standard of care, for 52 weeks. Outcomes included change from baseline in endoscopic nasal polyp (NP) score, visual analogue scale (VAS) scores for nasal obstruction, loss …

Cold-Sensitive Acral Hand Lesions, Avery H. Seward, Jocelyn H. Larocque

Department of Medicine Faculty Publications

[Case description] An otherwise healthy woman in her 60s presented with a 2-year history of a persistent, itchy, and tender rash on the dorsal hands. The rash fluctuated in severity with the seasons, worsening during the colder months. The patient denied joint pain and fatigue, or lesions elsewhere.

Examination revealed partially blanchable violaceous plaques on the dorsal hands with partial sparing of the proximal and distal interphalangeal joints (Fig 1). A few punctate, crusted erosions and purpuric macules were present on the dorsal and volar distal phalanges (Figs 2 and 3).

Drug-Induced Lichen Planus Associated With Ocrelizumab, Avery Seward, John D. Strickley, Jeffrey P. Callen

Department of Medicine Faculty Publications

This case report highlights recurrent cutaneous lichen planus as a rare adverse effect of ocrelizumab, with flares occurring after each infusion and improving with prophylactic prednisone. Recognizing this association may help clinicians diagnose and manage similar cases while allowing patients to continue an otherwise effective therapy.

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) …

Acute Fatty Liver Of Pregnancy And Fetal Fatty Acid Oxidation Disorders: A Systematic Review, Dante Varotsis, Sarah Araji, Rebecca Horgan, Jennifer E. Powel, Rodney Mclaren Jr., Brian Kirmse, Mona Makhamreh, Huda B. Al-Kouatly

Department of Obstetrics & Gynecology Faculty Publications

OBJECTIVE:

To evaluate the association between maternal acute fatty liver of pregnancy (AFLP) and fetal fatty acid oxidation (FAO) disorders and to define the clinical and genetic characteristics of mothers with AFLP and their fetuses affected by FAO disorders, we performed a systematic literature review of all reported cases of AFLP that underwent genetic testing for FAO disorders.

DATA SOURCES:

We searched PubMed, Ovid MEDLINE, Cochrane Library, CINAHL (EBSCO), Scopus, and ClinicalTrials.gov. Terms included were related to AFLP and FAO testing.

METHODS OF STUDY SELECTION:

We conducted a systematic literature review from inception through May 18, 2025, to evaluate the …

Longitudinal Patterns Of Urinary Biomarkers Of Placental And Renal Function In Pregnancy And Associations With Early Pregnancy Exposure To Phthalates And Replacements, Erin E. Mcnell, Danielle R. Stevens, Barrett M. Welch, Suzanne Fenton, Antonia M. Calafat, Julianne Cook Botelho, Elena Sinkovskaya, Ann Przybylska, George Saade, Alfred Abuhamad, Kelly K. Ferguson

Department of Obstetrics & Gynecology Faculty Publications

Phthalates and replacements are endocrine-disrupting chemicals that may interfere with early pregnancy processes such as placentation and renal adaptation. Placental and renal biomarkers may help examine these toxicologic mechanisms. This study aims to characterize longitudinal changes in urinary protein biomarkers of placental angiogenesis (sFlt-1, PlGF, sEng) and renal function (KIM-1, NGAL, nephrin), and investigate associations with early pregnancy exposure to phthalates and replacements. Among 291 participants from the Human Placenta and Phthalates prospective cohort, urinary metabolites of eight phthalates and two replacements were quantified at up to 2 time points from 12 to 15 weeks gestation. Repeated measures were averaged …

Estetrol (E4) For The Treatment Of Moderate To Severe Vasomotor Symptoms In Postmenopausal Women - Efficacy And Safety Results From The Phase 3 E4comfort I Multicenter, Placebo-Controlled Study, Tommaso Simoncini, Céline Bouchard, Marie Cloes, Mélanie Taziaux, Santiago Palacios, Sebastião Freitas De Medeiros, Valeriu Vrabii, David F. Archer, Nick Panay

Department of Obstetrics & Gynecology Faculty Publications

Objective

To evaluate the efficacy and safety of estetrol in reducing moderate to severe vasomotor symptoms in postmenopausal women.

Methods

Multicenter, randomized, parallel group (1:1:1), placebo-controlled, double-blind, phase 3 study in hysterectomized and non-hysterectomized participants aged 40-65 years. A total of 640 participants with seven or more moderate to severe hot flashes daily or 50 weekly received estetrol 15 mg, estetrol 20 mg, or placebo for 12 weeks. Co-primary endpoints were the change in frequency and severity of moderate to severe vasomotor symptoms from baseline to weeks 4 and 12. Comparisons versus placebo were made using a mixed-effects model for …

Vaginal Pra1 Identifies Clinically Relevant Candida Albicans Vaginitis And Excludes Asymptomatic Colonization: An Exploratory Study, Elena Roselletti, Barbara Kozma, David Ratonyi, Alexandra Kunkli, Bence Kozma, Peter Takacs, Duncan Wilson

Department of Obstetrics & Gynecology Faculty Publications

Background

Accurate interpretation of Candida detection in women with vulvovaginal symptoms remains difficult, because organism recovery may reflect either clinically relevant infection or nonpathogenic colonization. We have recently demonstrated that the secreted fungal zinc-binding protein, Pra1 is responsible for driving the inflammatory immunopathology of VVC. We therefore reasoned that PRA1 expression by Candida albicans in the vagina may act as a diagnostic tool to discriminate between commensal colonisation and active disease.

Methods

We conducted a 12-week prospective, single-center exploratory biomarker analysis nested within a registered parent clinical trial. Nine women with vulvovaginal symptoms provided cervicovaginal lavage samples and clinical data …

Trends In Glp-1 Based Therapy Use Before And After Pregnancy, Nansi S. Boghossain, Lauren Mcabee, Antonio F. Saad, Maged M. Costantine, Marwan Ma'ayeh, Joseph A. Ewing

Department of Obstetrics & Gynecology Faculty Publications

[Introduction] Glucagon-like peptide-1 (GLP-1)-based therapies are increasingly prescribed for the treatment of type 2 diabetes and obesity, with rapid uptake of newer agents such as semaglutide and tirzepatide [1, 2]. These medications improve glycemic control and promote weight loss and are now widely used among reproductive-aged individuals [2, 3]. However, GLP-1-based therapies are typically discontinued prior to pregnancy because of limited safety data and potential fetal risks, and current guidance recommends avoiding use during pregnancy [3]. As prescribing expands, a growing number of individuals entering pregnancy may have recent exposure to GLP-1-based …

Antibody-Drug Conjugates Beyond Her2 In Non-Small Cell Lung Cancer (Nsclc): Mechanisms, Emerging Targets, And Future Directions, Ahmed Ismail, Akash Desai, George R. Simon, Yanis Boumber

Department of Medicine Faculty Publications

Antibody–drug conjugates (ADCs) are a rapidly evolving class of oncology therapeutics that enable precise delivery of potent cytotoxic agents to tumor cells while minimizing systemic toxicity. While HER2-targeted ADCs such as trastuzumab deruxtecan (T-DXd) in HER2-mutant, Datopotamab deruxtecan (Dato-Dxd) in EGFR-mutant, and telisotumumab vedotin (Teliso-V) in MET IHC 3+ expressing lung cancer have already established a clinical role in non-small cell lung cancer (NSCLC), multiple ADCs targeting alternative antigens, including additional TROP2 ADCs, HER3, MET, CEACAM5, B7-H3, Nectin-4, and others, are now in advanced clinical development. This review synthesizes the current evidence for non-HER2 ADCs in NSCLC, highlighting mechanisms of …

Will They Be More Honest With An (External) Proctor? Evaluating Ufc Match Performance Before And After The Adoption Of The Usada Doping Program, Moonsup Hyun, Wonsok (Frank) Jee, Sehwon Kang, Yohan Lee

Human Movement Studies & Special Education Faculty Publications

Over the eight years from 2015 to 2023, the Ultimate Fighting Championship (UFC) partnered with the United States Anti-Doping Agency (USADA) to institute comprehensive external oversight of doping controls. This study investigates the effects of transitioning from internally administered anti-doping protocols to exclusive external governance by comparing UFC performance metrics before and during the USADA partnership. Using a Difference-in-Differences (DiD) approach with data from 2012 to 2018, we find that match duration significantly increased, while the likelihood of extreme outcomes, knockouts (KO), technical knockouts (TKO), and submissions, decreased during the USADA period. These results suggest that performance-enhancing drugs (PEDs) could …

Inflammatory Co-Regulation Of Voltage-Gated Sodium Channels And Na,K-Atpase In Metastatic Breast Cancer, Steven D. Scahill, Kelly Jean Sherman, Dennis Paul

School of Graduate Studies Faculty Publications

Sodium regulation is a potentially major driver of cancer metastasis. Voltage-gated sodium channels (VGSCs) and Na,K-ATPase are sodium transporters that are upregulated in many advanced carcinomas and are implicated as metastatic drivers. However, little is known about what drives this overexpression, how these proteins influence metastatic behavior, or whether these complementary sodium transporters are co-regulated in cancer. Using sodium transporter regulation in healthy neurons as a model, the present study demonstrated that the inflammatory mediator tumor necrosis factor alpha (TNFα) affects the expression of VGSCs and Na,K-ATPase in an in vitro model of metastatic breast cancer. Acute TNFα challenge increased …

The Effect Of Glp-1 Receptor Agonists On Reoperation Following Anterior Cervical Discectomy And Fusion, Nicholas C. Bank, Daniel Whittingslow, Sam Duggan, Joshua L. Morningstar, Douglas S. Weinberg

Student Papers, Posters & Projects

BACKGROUND: Pseudarthrosis remains a significant complication of ACDF, contributing to patient morbidity and increased healthcare costs. Glucagon-like peptide-1 receptor agonists (GLP-1RA), widely prescribed for diabetes and obesity, have been shown to reduced odds of pseudoarthrosis after ACDF. However, it remains unclear whether these reductions meaningfully translate to reduced odds of subsequent cervical surgery.

METHODS: The TriNetX United States Collaborative Network was queried for patients who underwent single- or multi-level ACDF between 2013-2023. Patients with perioperative GLP-1RA use and propensity-score-matched controls without GLP-1RA use were compared for subsequent rates of pseudoarthrosis and cervical reoperation at 6-, 12-, and 24-month intervals. Odds …

Radiogenomic Profiling Of Prostate Tumors Prior To External Beam Radiotherapy Converges On A Transcriptomic Signature Of Tgf-Β Activity Driving Tumor Recurrence, Anson T. Ku, Uma Shankavaram, Shana Y. Trostel, Hong Zhang, Sumeyra Kartal, Houssein A. Sater, Stephanie A. Harmon, Nicole V. Carrabba, Yang Liu, Hyunnam Ryu, James A. Proudfoot, Boon Hao Hong, Bradford J. Wood, Peter A. Pinto, Peter L. Choyke, Mack Roach, Howard M. Sandler, Stephanie L. Pugh, Kenneth L. Zeitzer, Lucas C. Mendez, Nirav S. Kapadia, William A. Hall, Anand B. Desai, Radka S. Stoyanova, Alan Pollack, Elai Davicioni, Melvin L. K. Chua, Baris Turkbey, Adam G. Sowalsky, Deborah E. Citrin

Einstein Health Papers

PURPOSE: Clinical risk grouping based on PSA, tumor grade, and disease extent guides treatment intensity for localized prostate cancer. However, many patients with intermediate- or high-risk disease treated with external beam radiotherapy (EBRT) and androgen deprivation therapy (ADT) still develop biochemical recurrence (BCR). Early identification of patients at high risk for BCR could enable personalized treatment strategies.

EXPERIMENTAL DESIGN: We prospectively enrolled 29 patients with intermediate- or high-risk prostate cancer undergoing EBRT and ADT. Pretreatment biopsies (n = 60) underwent whole-transcriptome microarray and whole-exome sequencing. Patients received multiparametric MRI at baseline and 6 months after treatment, with a median follow-up …

Vasoactive Drug Use In Children With Community Acquired Septic Shock In Australia And New Zealand, Elliot Long, Stephen Hearps, Amanda Williams, Ben Gelbart, Warwick Butt, Thomas Rozen, Sarah Mcnab, Meredith Borland, Simon Erickson, Shefali Jani, Marino Festa, Eunicia Tan, Natalie Phillips, Sainath Raman, Amit Kochar, Subodh Ganu, Simon Craig, Anna Lithgow, Arjun Rao, Emma Whyte, Stuart Dalziel, Shane George, Fran Balamuth, Scott Weiss, Nathan Kuppermann, Franz Babl

Department of Medicine Faculty Papers

BACKGROUND: Vasoactive agents are a critical supportive therapy for children with sepsis. We describe the choice and use patterns of vasoactive agents in children with sepsis.

METHODS: Prospective observational study conducted in 11 hospitals in Australia and New Zealand through the Paediatric Research in Emergency Departments International Collaborative (PREDICT) Network from April 2021 to December 2023. Children aged 0-< 18 years with suspected sepsis were included. Children admitted to hospital and treated with parenteral antibiotics and either 1) a provisional diagnosis of sepsis, and/or 2) treatment for suspected sepsis (fluid bolus to treat poor perfusion). The frequency and sequence of use of vasoactive agents, and contributors to the choice of initial vasoactive were collected.

FINDINGS: 6232 children with suspected sepsis were included; median age of 2.1 years (IQR 0.3-7.1 years), in-hospital mortality of 60 (1.0%), in whom a subset of 306 (4.9%) met Phoenix sepsis criteria. Vasoactive agents were used in 179 (2.9%) children overall …

Discovery Of A Small Molecule Tlr3 Agonist Adjuvant, Branden Lee, Danica Dong, Etsuro Nanishi, John Mark Awad, Kimia Abedi, Yoshine Saito, Francesco Borriello, Soumik Barman, Byron Brook, Aisling Kelly, Manisha Menon, Constance Marques-Mourlet, Maansi Gupta, Ida Lister, Chiwoo Oh, Kevin Lyskawa, Morgan Goetz, Kristina Walker, Wing Ki Cheng, Spencer Brightman, Pankaj Sharma, Timothy O'Meara, Katherine Chew, Daniel Vieira, Kevin Ryff, Cali Sweitzer, Sanya Thomas, Simon Van Haren, Matthew Pettengill, Hyuk-Soo Seo, Sirano Dhe-Paganon, Wei Zhang, Ofer Levy, David Dowling

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Pattern-recognition receptor (PRR) agonists are valuable agents across multiple medical applications, from vaccinology to immune-oncology. However, well-defined and potent small molecule agonists for many PRRs still await discovery and development. Screening of chemical libraries of ~200,000 small molecules for maturation of human monocytic cells by quantifying NF-κB activation and cell adherence was completed. From this screen, we selected a thiazole benzamide derivative, PVP-057, for its robust immunomodulatory properties, low toxicity profile, and concentration-dependent activity. In vitro investigation of pathway and receptor activation reveals that PVP-057 is a Toll-like receptor 3 (TLR3) agonist. As a single-component adjuvant, administered intramuscularly or intradermally …

Breastfeeding Safety Following Maternal Anesthesia: A Guideline Development, Megan Honea, Mary Johnson

Doctoral Projects

Recommendations regarding breastfeeding following maternal anesthesia are inconsistent and often not up to date with current best practice guidelines. Previous recommendations have led to mothers unnecessarily “pumping and dumping” breast milk has benefits for both mother and baby. These benefits include (a) increasing the infant’s access to colostrum, (b) encouraging mother-baby bonding, (c) improving the mother’s breastfeeding experience, (d) and providing significant health benefits to the infant. The purpose of this scholarly project was to develop a set of evidence-based recommendations that focus on mothers who desire to breastfeed following general anesthesia. These recommendations will highlight maternal- fetal transfer of …