Medical Sciences Commons^™

Animal Models Of Delirium: A Narrative Review, Tatiana Barichello, Carla Sasso Simon, Diogo Dominguini, Cristiane Ritter, Tsuyoshi Nishiguchi, Gen Shinozaki, Felipe Dal-Pizzol

Faculty, Staff and Student Publications

Delirium is an acute cognitive failure characterized by an acute onset and psychomotor disturbances. It is associated with poor outcomes in hospitalized patients, resulting in prolonged hospital stays, elevated rates of mortality, and cognitive dysfunctions after hospital discharge. The pathophysiology of delirium remains poorly understood, making the development of animal models a promising avenue for researchers to elucidate the mechanisms underlying human delirium. These models not only aid in understanding the pathophysiology and etiology of the disease but also enhance the efficacy of nonpharmacological interventions and identify pharmacological therapies. This review aims to present the most relevant and translational animal …

Dna Methylation Signatures Associated With Bipolar Disorder In Peripheral Blood Improve Prediction Models, Markos Tesfaye, Anne-Kristin Stavrum, Kira D Höffler, Kevin S O'Connell, Friederike S David, Melanie E Garrett, Sonia Hesam-Shariati, Bronwyn J Overs, Claudia Pisanu, Luana Spano, Oliver J Watkeys, Antoine Weihs, Rafaella Ardau, Allison E Ashley-Koch, Lavinia Athanasiu, Jean C Beckham, Kyle J Bourassa, Caterina Chillotti, Srdjan Djurovic, Ole K Drange, Josef Frank, Anouar Khayachi, Nathan A Kimbrel, Lourdes Martorell, Susanne Meinert, Ingrid Melle, Gunnar Morken, Pasquale Paribello, Marco Pinna, Gloria Roberts, Guy Rouleau, Peter R Schofield, Esteban Sepúlveda, Giovanni Severino, Vidar M Steen, Frederike Stein, Fabian Streit, Va Mid-Atlantic Mirecc Workgroup, Trine Vik Lagerberg, Martin Alda, Udo Dannlowski, Andreas J Forstner, Janice M Fullerton, Hans J Grabe, Melissa J Green, Tilo Kircher, Javier Labad, Mirko Manchia, Philip B Mitchell, Jair C Soares, Alessio Squassina, Alexander Teumer, Leonardo Tondo, Elisabet Vilella, Ole A Andreassen, Boris Chaumette, Gabriel R Fries, Stephanie Le Hellard

Faculty, Staff and Student Publications

Background: Bipolar disorder (BD) is a major mood disorder influenced by both genetic and environmental factors. While DNA methylation from peripheral tissues can reflect both genetic and environmental influences and reveal insights into disease biology, it remains understudied in BD. DNA methylation signatures may complement polygenic scores (PGS) and hold potential as biomarkers. Here, we conducted the largest epigenome-wide association study (EWAS) of BD to date and evaluated the predictive value of polymethylation scores (PMS) in classifying case-control status.

Methods: DNA methylation from peripheral blood of 1729 cases and 1747 controls, comprising twelve cohorts, was obtained. We performed meta-analyses for …

Identifying Novel Gene Dysregulation Associated With Opioid Overdose Death: A Meta-Analysis Of Differential Gene Expression In Human Prefrontal Cortex, Javan K Carter, Bryan C Quach, Caryn Willis, Melyssa S Minto, Dana B Hancock, Janitza Montalvo-Ortiz, Olivia Corradin, Ryan W Logan, Consuelo Walss-Bass, Brion S Maher, Eric Otto Johnson

Faculty, Staff and Student Publications

Only recently have human postmortem brain studies of differential gene expression (DGE) associated with opioid overdose death (OOD) been published; sample sizes from these studies have been modest (N = 40-153). To increase statistical power to identify OOD-associated genes, we leveraged human prefrontal cortex RNA-seq data from four independent OOD studies and conducted a transcriptome-wide DGE meta-analysis (N = 272). Using a unified gene expression data processing and analysis framework across studies, we meta-analyzed 20, 098 genes and found 335 significant differentially expressed genes (DEGs) by OOD status (false discovery rate <  0.05). Of these, 66 DEGs were among the list of 303 genes reported as OOD-associated in prior prefrontal cortex molecular studies (e.g., genes/gene families OPRK1, NPAS4, DUSP, EGR). The remaining 269 DEGs were not previously reported (e.g., NR4A2, SYT1, HCRTR2, BDNF). There was little evidence of genetic drivers for the observed differences in gene expression between opioid addiction cases and controls. Enrichment analyses for the DEGs across molecular pathway and biological process databases highlight an interconnected set of genes and pathways linked to orexin and tyrosine kinase receptors through MEK/ERK/MAPK signaling to affect neuronal plasticity.

Immediate Nerve And Tendon Transfers After Wide Resection Of A Radial Nerve Malignant Peripheral Nerve Sheath Tumor: A Case Report And Surgical Technique, Joanne Zhou, Sai Shreya Kambham, Andrew Fang, Christopher Frey, Michael Macavoy

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The authors have reported on immediate nerve and tendon transfers postresection of a radial nerve-based malignant peripheral nerve sheath tumor in a 15-year-old female with neurofibromatosis. The median nerve branch to flexor carpi radialis was transferred to the posterior interosseous nerve, the median nerve branch to flexor digitorum superficialis was transferred to the nerve to extensor carpi radialis brevis, and the pronator teres tendon was transferred to the extensor carpi radialis brevis tendon, with 3-year outcomes reported. Tumor excision, tendon, and nerve transfer yielded negative margins and remission. Functional wrist/finger extension appeared at 6 months and increased until 3 years …

Large-Scale Genetic Characterization Of Parkinson’S Disease In The African And African Admixed Populations, Fulya Akçimen, Kimberly Paquette, Peter Wild Crea, Kathryn Step, Emily Waldo, Mathew J Koretsky, Paula Saffie-Awad, Charles Achoru, Funmilola Taiwo, Simon Ozomma, Gerald Onwuegbuzie, Marzieh Khani, Spencer Grant, Lukman Owolabi, Chiamaka Okereke, Olajumoke Oshinaike, Emmanuel Iwuozo, Suleyman Can Akerman, Paul Suhwan Lee, Shyngle Oyakhire, Nosakhare Osemwegie, Kensuke Daida, Sani Abubakar, Adedunni Olusanya, Mariam Isayan, Christiane Alvarez, Rami Traurig, Adebimpe Ogunmodede, Sarah Samuel, Mary B Makarious, Fadimatu Sa'ad, Rashidat Olanigan, Kristin Levine, Ewere Marie Ogbimi, Dan Vitale, Francis Odiase, Francis Ojini, Olanike Odeniyi, Zih-Hua Fang, Nkechi Obianozie, Deborah A Hall, Ernest Nwazor, Tao Xie, Francesca Nwaokorie, Mahesh Padmanaban, Paul Nwani, Ejaz A Shamim, Alero Nnama, David Standaert, Morenikeji Komolafe, Marissa Dean, Godwin Osaigbovo, Elizabeth Disbrow, Ismaila Ishola, Ashley Rawls, Frank Imarhiagbe, Shivika Chandra, Cyril Erameh, Vanessa Hinson, Naomi Louie, Ahmed Idowu, J Solle, Scott A Norris, Abdullahi Ibrahim, Camilla Kilbane, Gauthaman Sukumar, Lisa M Shulman, Daniel Ezuduemoih, Julia Staisch, Sarah Breaux, Clifton Dalgard, Erin R Foster, Abiodun Bello, Andrew Ameri, Raquel Real, Erica Ikwenu, Huw R Morris, Roosevelt Anyanwu, Erin Furr Stimming, Kimberley Billingsley, Wemimo Alaofin, Pilar Alvarez Jerez, Osigwe Agabi, Dena G Hernandez, Rufus Akinyemi, Sampath Arepalli, Laksh Malik, Raymond Owolabi, Yakub Nyandaiti, Hampton L Leonard, Kolawole Wahab, Oladunni Abiodun, Carlos F Hernandez, Fatima Abdulai, Hirotaka Iwaki, Soraya Bardien, Christine Klein, John Hardy, Henry Houlden, Kamalini Ghosh Galvelis, Mike A Nalls, Nabila Dahodwala, Whitley Aamodt, Emily Hill, Alberto Espay, Stewart Factor, Chantale Branson, Cornelis Blauwendraat, Andrew B Singleton, Oluwadamilola Ojo, Lana M Chahine, Njideka Okubadejo, Sara Bandres-Ciga

Faculty, Staff and Student Publications

Elucidating the genetic contributions to Parkinson's disease aetiology across diverse ancestries is a critical priority for the development of targeted therapies in a global context. We conducted the largest sequencing characterization of potentially disease-causing, protein-altering and splicing mutations in 710 cases and 11 827 controls from genetically predicted African or African admixed ancestries. We explored copy number variants (CNVs) and runs of homozygosity in prioritized early onset and familial cases. Our study identified rare GBA1 coding variants to be the most frequent mutations among patients with Parkinson's disease, with a frequency of 4% in our case cohort. Of the 18 …

Randomised Controlled Trial Comparing Antibiotic Cement Bead Pouch Versus Negative Pressure Wound Therapy For The Management Of Severe Open Tibia Fracture Wounds: Beads Versus Vac (Bvv) Protocol, Lucas S Marchand, Gerard Slobogean, Nathan N O'Hara, Anthony D Harris, David W Grainger, Lehana Thabane, Mohit Bhandari, Gregory J Della Rocca, Patrick J Kellam, Robert D Zura, Debra Marvel, Jeffrey L Wells, I Leah Gitajn, Kyle J Jeray, Robert V O'Toole, Zachary M Working, Roman M Natoli, Patrick F Bergin, Jennifer E Hagen, Ashley E Levack, Ernesto Guerra-Farfan, Gregory M Schrank, Joan N Hebden, Franca Mossuto, Cassandra Tsoutsounakis, David Pogorzelski, Hailey Pineda, Sofia Bzovsky, Sheila Sprague, Bvv Investigators

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Introduction: Early open fracture management aims to minimise the risk of complications. For the most severe open fracture wounds, multiple irrigation and debridement surgeries are required to overcome severe wound contamination, to reassess the evolving tissue injury or to temporise and plan further surgery. When multiple irrigation and debridement surgeries are needed, uncertainty remains about how the open fracture wound should be managed to best minimise complications. The primary aim of this trial is to compare the antibiotic cement bead pouch vs negative pressure wound therapy in the management of patients with severe open tibia fracture wounds.

Methods and analysis: …

Minimal Change Disease Following B-Cell Maturation Antigen-Directed Chimeric Antigen Receptor T-Cell Therapy, Kiran Shivaraj, Omar Mamlouk, Amanda Tchakarov, Krina Patel, Ala Abudayyeh

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Acute kidney injury (AKI) is a well-recognized complication of chimeric antigen receptor (CAR) T-cell therapy, typically attributed to cytokine release syndrome and acute tubular injury. However, glomerular disease post CAR-T cell is rare. We report a case of minimal change disease presenting with AKI and nephrotic-range proteinuria 3 weeks after B-cell maturation antigen-directed CAR-T cell therapy, ciltacabtagene autoleucel, in a patient with relapsed refractory multiple myeloma. The kidney biopsy revealed diffuse podocyte foot process effacement and a predominance of CD4+ T cells with potential on-target, off-tumor effect of B-cell maturation antigen-directed CAR-T cell therapy, leading to podocyte injury. The patient …

Race To Mitigate Aortic Dissection: Exercise, Pde5a, And The Dissecting Aorta, Siddharth K Prakash

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No abstract provided.

Severe, Non-Apneic Respiratory Dysfunction And Hypoxia Following Generalized Convulsive Seizures, Haley E Pysick, Rup K Sainju, Roshni Nair, Deidre N Dragon, Eduardo Bravo, Laura Vilella, Xiaojin Li, Samden D Lhatoo, George B Richerson, Brian K Gehlbach

Faculty, Staff and Student Publications

Objective: Sudden unexpected death in epilepsy (SUDEP) is a devastating consequence of some generalized convulsive seizures (GCS). Recent work has focused on seizure related apnea as a biomarker of SUDEP risk, frequently without characterizing the adequacy of non-apneic ventilation or identifying other dysfunctional breathing patterns. We hypothesized that GCS frequently induce immediate, severe, non-apneic respiratory dysfunction that can induce critical hypoxia and bradycardia and sought to characterize breathing patterns after GCS.

Methods: Adult patients admitted to an epilepsy monitoring unit were studied. The effects of GCS on breathing and heart rate were analyzed using nasal pressure transducers, chest and abdominal …

Donor Sex And Platelet Storage Change The Therapeutic Effects Of Platelet-Derived Extracellular Vesicles On Endothelium, Mandeep Kaur, Malvika Gupta, Sowmya Shree Gopal, Charles E Wade, Jessica C Cardenas, Amit K Srivastava

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Platelet-derived extracellular vesicles (PEVs) play an active role in vascular protection and repair and are being explored as a viable alternative to platelet therapy. Because platelet function and stability are shaped by donor sex and storage conditions, these same factors are likely to influence the PEVs they release. Understanding these influences is key to developing PEVs into a safe and dependable therapeutic option. In this study, we investigated how donor sex and platelet storage affect the therapeutic properties of PEVs. To address this, PEVs were isolated from platelets of healthy male and female donors. Platelets were either processed immediately after …

Are Drains After Trauma Splenectomy Associated With Organ Space Surgical Site Infections?, Stephanie Martinez Ugarte, Mokunfayo O Fajemisin, Seokhun Kim, William D Rieger, Renee W Green, Gabrielle E Hatton, Lillian S Kao

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Introduction: Left upper quadrant (LUQ) drain use after trauma splenectomy varies, with minimal existing data to guide practice. We aimed to investigate the association of LUQ drains with organ space surgical site infection (OS-SSI) after splenectomy. We hypothesized that LUQ drains after trauma splenectomy are associated with increased odds of OS-SSI.

Patients and methods: A retrospective study of adult blunt trauma patients who underwent splenectomy from 7/2018 to 6/2024 was performed. We excluded patients who survived < 5 days after operation, and those with an intraoperatively identified pancreatic injury. Demographics, surgical details, and drain information were abstracted from the medical record. Inverse probability of treatment weighting (IPTW) was used to balance variables between patients who did and did not receive an LUQ drain after splenectomy. Multivariable logistic regression with IPTW was performed to estimate the association of LUQ drains with OS-SSI.

Results: Of 179 patients, 68% (n = 121) were male, the median age was 38 years (interquartile range 28, 55), and 27% (n = …

Structural Brain Differences Associated With Panic Disorder: An Enigma-Anxiety Working Group Mega-Analysis Of 4924 Individuals Worldwide, Laura K M Han, Willem B Bruin, Janna Marie Bas-Hoogendam, Nynke A Groenewold, Kevin Hilbert, Anderson M Winkler, Andre Zugman, Takeshi Asami, Jacques P Barber, Francesco Benedetti, Robert J R Blair, Joscha Böhnlein, Paolo Brambilla, Fabian Breuer, Randy L Buckner, Robin Bülow, Monica E Calkins, Natalia Chechko, Udo Dannlowski, Katharina Dohm, Katharina Domschke, Thomas Dresler, Angelika Erhardt-Lehmann, Gregory A Fonzo, Andreas J Forstner, Hans J Grabe, Dominik Grotegerd, Raquel E Gur, Ruben C Gur, Catherine Harmer, David Hofmann, Odile A Van Den Heuvel, Neda Jahanshad, Tilo T J Kircher, Katharina Koch, Max A Laansma, Till Langhammer, Sang-Hyuk Lee, Elisabeth J Leehr, Eleonora Maggioni, Claire E Marino, Susanne Meinert, Hannah Meinert, Barbara Milrod, Benson Mwangi, Jared A Nielsen, Patricia Ohrmann, Spiro P Pantazatos, Martin P Paulus, Brenda W J H Penninx, Sara Poletti, Andrea Reinecke, Isabelle C Ridderbusch, Pavel Rjabtsenkov, Philipp G Sämann, Theodore D Satterthwaite, Lianne Schmaal, Elisabeth Schrammen, Jair C Soares, Nili Solomonov, Murray B Stein, Benjamin Straube, Thomas Straube, Benjamin Suarez-Jimenez, Jordan W Smoller, Ardesheer Talati, Sophia I Thomopoulos, Carlos E Vazquez, Henry Völzke, Katharina Wittfeld, Mon-Ju Wu, Yunbo Yang, Giovana B Zunta Soares, Ulrike Lueken, Paul M Thompson, Daniel S Pine, Dan J Stein, Nic J A Van Der Wee, Dick J Veltman, Moji Aghajani

Faculty, Staff and Student Publications

Neuroanatomical findings on panic disorder (PD) are typically difficult to replicate, with inconsistent effects. These concerns prompted a paradigm shift towards large-scale collaborations, focused on harmonized data extraction and processing for robust examination of PD brain correlates. Hence, leveraging the largest-ever multi-site neuroimaging database on PD (Age: 10–66 years; global sites: 28), compiled by the ENIGMA-Anxiety Working Group, we report on cortical and subcortical differences in individuals with PD (N = 1146) versus healthy controls (HC: N = 3778). The analyses revealed lower thickness and smaller cortical surface area within fronto-temporo-parietal regions in PD (Cohen’s ds: −0.08–0.13), along with lower …

Antidepressant-Like Effects Of Extinction Learning As An Animal Model Of Behavioral Therapy, Jing Liu, Sarah E Bulin, David A Morilak

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Exposure-based behavioral therapy, the most effective treatment for posttraumatic stress disorder (PTSD), also reduces depressive symptoms. However, neurobiological mechanisms underlying the beneficial effects of exposure-based behavioral therapy on depression remain unknown. Our lab has established fear extinction as a rat model of exposure therapy to investigate the mechanisms underlying its therapeutic behavioral effects in chronically stressed rats. In this study, we demonstrated that extinction learning reduced immobility in the forced-swim test and reversed chronic stress-induced reduction in sucrose preference. Chemogenetic inactivation of pyramidal neurons in the ventral medial prefrontal cortex (vmPFC) prevented these antidepressant-like effects of extinction. Extinction learning enhanced …

Plasma Constituents Promote Endothelial Thromboinflammatory Dysfunction After Hemorrhagic Shock, Kelly E Sanders, Marissa D Pokharel, Baron K Osborn, Yao-Wei Wang, Charles E Wade, Lucy Z Kornblith, Mitchell J Cohen, Jessica C Cardenas

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Background: Hemorrhagic shock (HS) following traumatic injury is hallmarked by innate immune activation, hypercoagulability, and thromboinflammatory complications. To date, the direct link between HS, injury severity, and endothelial cell (EC) contributions to thromboinflammation remains poorly understood. The goals of this study were to determine the impact of injury severity and HS on endothelial-mediated thromboinflammation and examine whether these changes increase the propensity for thrombosis.

Methods: Plasma from 89 male trauma patients, stratified by HS and injury severity, and 10 healthy subjects were assessed for inflammatory mediators by BioPlex. Human lung microvascular endothelial cells were exposed to patient plasma for 4 …

Neurointerventional Advances In 2025, Amol Mehta, Sunil A Sheth, Ashutosh P Jadhav

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No abstract provided.

Multidisciplinary Approach To Complex Lower Extremity Limb Salvage In Pyogenic Arthritis, Pyoderma Gangrenosum, And Acne (Papa) Syndrome: A Case Report, Michael M Talanker, Anthony V Basta, Tien Do, Robert Tung, Addison Allen, Morgan Martin, Bryan L Ruygrok, Patrick J Kellam, Jeffrey G Trost, Mohin A Bhadkamkar

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Limb salvage using free tissue transfer in patients with rare autoinflammatory syndromes is poorly described, and the safety of microvascular reconstruction in this population remains uncertain. Hereditary pyogenic arthritis, pyoderma gangrenosum, and acne (PAPA) syndrome is characterized by dysregulated inflammation, pathergy, and impaired wound healing, raising concern for flap compromise and postoperative complications. We report a rare case of lower extremity free tissue transfer in a patient with PAPA syndrome. A 66-year-old woman with rheumatoid arthritis and PAPA syndrome presented with rapid wound breakdown, violaceous ulceration, exposed hardware, and periprosthetic joint infection following left total knee arthroplasty (TKA). Examination revealed …

Assessment Of Skin In Patients With Systemic Sclerosis Using High-Frequency Ultrasound And Shear Wave Elastography: A Comparative Study With Histology, Molecular, And Clinical Parameters, Ruhani Desai, Filemon Tan, Minghua Wu, Jeffery L Browning, Samuel Theodore, Meng Zhang, Brian Skaug, Harshdeep Singh Chawla, Manmohan Singh, Salavat Aglyamov, Kirill V Larin, Maureen Mayes, Shervin Assassi

Faculty, Staff and Student Publications

Objective: Ultrasound (US) has been proposed as a potential tool for assessing skin fibrosis in systemic sclerosis (SSc). However, a large-scale comparison of US-based assessment with histologic markers of skin fibrosis has not been reported. We evaluated US-based skin assessments for their face validity (differentiation between involved SSc and healthy control [HC] skin), construct validity (comparison to modified Rodnan skin score [mRSS]), and criterion validity (comparison to histologic and gene expression fibrosis markers).

Methods: Twenty HCs and 52 patients with SSc underwent clinical and US assessment followed by a forearm skin biopsy. Predefined areas were assessed on the finger, hand, …

Creating Space For New Ideas And Advancing Gender Equity In Physical Activity And Health Research: Reflections On The Nature Portfolio Physical Activity Series, Andrea Ramírez Varela, Deborah Salvo, Pedro C Hallal, Erica Hinckson

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No abstract provided.

Surgical Timing After Acromioclavicular Joint Separation: Association With Clinical Outcomes, Mallory B Lane, Jacob Siahaan, James M Gregory

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Background: Treatment of acromioclavicular joint (ACJ) separations continually lacks consensus between providers, and while low-grade injuries generally respond well to conservative management, high-grade injury management is more complex. For patients requiring surgery, the effect of the timing of surgery with respect to the original injury on clinical outcomes remains unclear.

Hypothesis: Clinical outcome measures would worsen as the time between ACJ dislocation injury and surgery increased.

Study design: Cohort study; Level of evidence, 3.

Methods: A large nationwide insurance claims database was queried for patients who had an ACJ dislocation injury using International Classification of Diseases, Ninth and Tenth Revision …

A Rare Case Of Gastric Ascariasis, Sharon Pan, Kevin Yu, Blaine A Mathison, Yan Gao, Marc Roger Couturier, Salem Muayad, Violeta Chávez, Ranya Selim

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Background: Ascariasis, caused by the parasitic roundworm Ascaris lumbricoides, is one of the most common helminthic infections globally. Spread by contaminated soil through the fecal-oral route, A. lumbricoides typically infects the small intestine and has rarely been reported to infect the stomach.

Case summary: We describe an unusual case of a male in his 30s with a history of neuroendocrine tumor (NET) who immigrated from Colombia and who underwent esophagogastroduodenoscopy (EGD) and colonoscopy for further evaluation of abdominal pain. He was incidentally found to have a female Ascaris worm in his stomach that was retrieved during the EGD.

Conclusion: …

An Assessment Of Green Plasma: The In Vitro Hemostatic Superiority Of A Currently Discarded Blood Product, Samantha C Redden, David J Sun, Yao-Wei W Wang, Elizabeth Hartwell, Jessica C Cardenas, Scott D Olson, Bryan A Cotton

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Introduction: Recent studies have linked trauma patient outcomes to the plasma donor's sex, with premenopausal females associated with improved survival and lower organ failure. Currently, green-colored plasma (due to oral contraceptive use) is removed from the donor pool. We set out to evaluate the hemostatic potential of green plasma.

Study design & methods: We obtained 90 units of plasma from our regional blood center: 30 units of visible green plasma and 60 units of standard-color plasma divided between male and female donors. We collected clinical data such as age, sex, ethnicity, and number of pregnancies. We then assessed the hemostatic …

Computational Modeling Meets 3d Bioprinting: Emerging Synergies In Cardiovascular Disease Modeling, Tanmay Mukherjee, Mehdi Salar Amoli, Sarah Rezapourdamanab, Lama Rita El Shammas, Martin L Tomov, Emilio A Mendiola, Vahid Serpooshan, Reza Avazmohammadi

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Cardiovascular diseases (CVDs) remain the leading cause of death worldwide, underscoring the need for improved strategies in diagnosis, treatment, and disease modeling. Traditional in vitro models often fall short in replicating human CV physiology, prompting efforts to advance cardiac tissue engineering and computational modeling. Among these, three-dimensional (3D) bioprinting has emerged as a transformative tool, enabling the creation of biomimetic CV constructs that more faithfully replicate native tissue structure and function. However, challenges persist in achieving appropriate mechanical properties and long-term performance of engineered CV constructs. Computational modeling offers powerful solutions to assist with these challenges, providing predictive insights into …

Psychotropic Medications And Their Interactions With Subcortical Brain Volume In Bipolar Disorder: An Enigma Mega-Analysis, Sinead King, John O'Connor, Emma Corley, Giulia Tronchin, Elisa Fontana, Leila Nabulsi, Melody J Y Kang, Joaquim Radua, Brian Hallahan, Christoph Abé, Martin Alda, Dag Alnæs, Silvia Alonso-Lana, Silvia Amoretti, Jochen Bauer, Francesco Benedetti, Klaus Berger, Michael Berk, Erlend Bøen, Joscha Böhnlein, Birgitte Boye, Beatrice Bravi, Erick J Canales-Rodríguez, Udo Dannlowski, Caroline Demro, Annabella Di Giorgio, Ana M Diaz-Zuluaga, Torbjørn Elvsåshagen, Pauline Favre, Tracy Erwin-Grabner, María Florencia Forte, Janice M Fullerton, Lisa S Furlong, Susan L Rossell, David C Glahn, Benjamin I Goldstein, Ian H Gotlib, Roberto Goya-Maldonado, Melissa J Green, Dominik Grotegerd, Oliver Gruber, Bartholomeus C M Haarman, Tim Hahn, Tomas Hajek, Leonie Hater, Marco Hermesdorf, Josselin Houenou, Fleur M Howells, James A Karantonis, Kody G Kennedy, Tilo Kircher, Anna Luisa Klahn, Maximilian Konowski, Bernd Krämer, Elijah Lahud, Rayus Kuplicki, Mikael Landén, Carlos López-Jaramillo, Bradley J Macintosh, Hannah Meinert, Susanne Meinert, Elisa M T Melloni, Philip B Mitchell, Benson Mwangi, Igor Nenadić, Bronwyn J Overs, Nadine Parker, Godfrey Pearlson, Edith Pomarol-Clotet, James J Prisciandaro, Yann Quidé, Gloria Roberts, Amanda Rodrigue, Elena Rodríguez-Cano, Lisa Rauer, Matthew D Sacchet, Raymond Salvador, Fabio Sambataro, Theodore D Satterthwaite, Jonathan Savitz, Freda Scheffler, Navid Schürmeyer, Chen Shen, Kang Sim, Jair C Soares, Aleix Solanes, Márcio Gerhardt Soeiro-De-Souza, Scott R Sponheim, Dan J Stein, Frederike Stein, Henk S Temmingh, Lea Teutenberg, Sophia I Thomopoulos, Snezana Urosevic, Tamsyn E Van Rheenen, Eduard Vieta, Lars T Westlye, Daniel H Wolf, Mon-Ju Wu, Lakshmi N Yatham, Giovana B Zunta-Soares, Dara M Cannon, Paul M Thompson, Ole A Andreassen, Christopher R K Ching, Colm Mcdonald

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MRI studies in bipolar disorder (BD) have yielded inconsistent findings, partly due to the varied use of psychotropic medications. This study utilised a mega-analysis approach, accounting for concurrent medication status (syndrome-based and Neuroscience-based Nomenclature (NbN) classifications), in order to assess the association of medication status with subcortical brain volumes in BD. Data from 2,664 BD patients and 4,065 controls (CN) were pooled from 34 research groups as part of the ENIGMA Bipolar Disorder Working Group. Standardized ENIGMA protocols were used to measure subcortical brain volumes. Linear-mixed-effects regression evaluated the association between psychotropic medications and subcortical volumes, and moderation analyses explored …

Intravenous Buprenorphine Reversed Opioid-Induced Respiratory Depression Without Precipitating Withdrawal In Emergency Department Patients, Anthony Spadaro, Nicholas Imperato, Jaclyn Scalgione, Cynthia Santos

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Objective: Buprenorphine is a high-affinity partial agonist that can displace full opioid agonists and could be used to reverse opioid-induced respiratory depression. There is scant evidence to support the use of buprenorphine in an acute opioid overdose to reverse respiratory depression in the era of high fentanyl prevalence in the drug supply. This is a case series of four patients with signs and symptoms of an opioid overdose who showed clinical improvement after receiving intravenous buprenorphine.

Method: A case series of adult emergency department patients treated at a single urban academic medical center was reviewed by the authors, who determined …

The Impact Of Rapid Infusers On The Hemostatic Potential Of Cryoprecipitate Products, Connor D Purvis, Samantha Redden, Andrew Jacobson, Yao-Wei Wang, Julie Campbell, Jessica Cardenas, Jan-Michael Van Gent, Bryan A Cotton

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Background: In cases of massive transfusion, intravenous access can be limited. Additionally, delivering different products through separate lines and infusion methods adds unnecessary steps. RBC, plasma, and whole blood (WB) are delivered via rapid infusers; cryoprecipitate (CRYO) is infused through separate access and is not approved with these devices.

Study design and methods: We examined the impact of different transfusion methods on hemostatic performance and factor activity using two available CRYO products. Ten bags of CRYO, ten bags pathogen-reduced CRYO (Intercept® Fibrinogen Complex, IFC), and 20 units of WB were obtained. Each CRYO bag was infused with one unit of …

Estrogen As A Therapeutic Agent: Targeting Endotheliopathy And Coagulopathy In Trauma, Niruktha Raghavan, Mira Patel, Bryan A Cotton, Julia Coleman, Donald Jenkins

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Background: Traumatic injury remains a leading cause of death, often due to uncontrolled hemorrhage and trauma-induced coagulopathy (TIC). TIC is critically triggered by the endotheliopathy of trauma, involving endothelial cell injury and glycocalyx degradation. Despite conventional advances, the stable casualty rate underscores the urgent need for new precision resuscitation strategies that acknowledge factors like biological sex.

Design: The central hypothesis is that estrogen confers a survival advantage in hormonally active females through a dual action: endothelial cell stabilization (halting glycocalyx shedding) and its inherent procoagulant effect. The analysis assesses the therapeutic potential of both exogenous estrogen and female-derived blood products …

Declaring Futility After Traumatic Injury And The Burden Of Failure On The Surgeon, Jan-Michael Van Gent, Bryan A Cotton

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In this edition of the THOR supplement in Transfusion, there are two articles that deal with resuscitation futility and transfusion. In one article, Yazer et al. delve into the details of the studies outlined in this editorial and summarize the literature on the topic of transfusion and futility. The second article by Dr. Jay Malone discusses the ethical issues surrounding massive transfusion and resuscitation. Taken together, these articles address the clinical and ethical issues surrounding this very emotive and difficult topic.

Brief Report: Hepatitis B Vaccination Histories In Persons With Hiv Needing Revaccination, Minhee Kang, Triin Umbleja, Anchalee Avihingsanon, Sandra W Cardoso, Josphat Kosgei, Karen J Vigil, Ta Thi Dieu Ngan, Unoda Chakalisa, Stephanie Caruso, Kenneth E Sherman, Kristen M Marks

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Introduction: Past studies of hepatitis B vaccines in people with HIV (PWH) have shown mixed results about improving responses with increases in dose or dose frequency, leading to inconsistent guidelines and practice. We examined vaccine series completion and revaccinations in PWH lacking a seroprotective response.

Methods: Hepatitis B vaccination histories were evaluated as a retrospective study in 561 participants of A5379 trial (NCT04193189). Individuals in 41 sites in Africa, Asia, South America, and the United States qualified for the trial with antibody titers below the seroprotective level (< 10 mIU/mL) despite past hepatitis B vaccinations. The primary measure of interest was the number of vaccines in the past vaccination records.

Results: Of the 1098 trial candidates, 561 (51%) did not …

Quantitative Muscle Magnetic Resonance Imaging Demonstrates Resolution Of Muscle Edema In Refractory Dermatomyositis: A Post Hoc Analysis Of A Proof-Of-Concept Clinical Trial Of Tofacitinib, Mona Dabiri, Anshula Nallapati, Marwin Groener, Patrick Debs, Jemima Albayda, Eleni Tiniakou, Lisa Christopher-Stine, Laura Fayad, Julie J Paik

Faculty, Staff and Student Publications

Objective: To evaluate changes in muscle edema using short-tau inversion recovery (STIR) imaging and quantitative diffusion-weighted imaging (DWI) with apparent diffusion coefficient (ADC) mapping in patients with refractory dermatomyositis (DM) treated with tofacitinib.

Methods: This post hoc imaging analysis included patients from a 12-week, open-label trial of tofacitinib 11 mg daily in refractory DM. Bilateral thigh magnetic resonance imaging was obtained at baseline and week 12 using standardized STIR, T1-weighted, and DWI sequences. Muscle edema (ME) and fascial edema were assessed qualitatively on STIR imaging. ADC values were measured in muscles demonstrating baseline STIR hyperintensity using three nonoverlapping regions of …

Gender Disparities Among General Surgeons: A Comprehensive Review, Julie Holihan, Devi Bavishi, Kush Brahmbhatt, Rebecca Franks, Zuhair Ali, Karla Bernardi, Christine Castillo, Mike Liang, Rachel Wong, Michele Loor

Faculty, Staff and Student Publications

Background: Unlike in-house call, the Accreditation Council for Graduate Medical Education (ACGME) does not require a postcall day for "home call" shifts. Despite this, we hypothesize that on-call residents are still in the hospital for the majority of their shift despite having the luxury of home call and, thus, are not protected by ACGME postcall duty hour regulations.

Methods: A prospective single center survey study was conducted by surveying junior and senior residents who completed overnight call shifts from January 2023 to April 2023 at one of the busiest level 1 trauma centers in the United States. Data include number …