Biological Phenomena, Cell Phenomena, and Immunity Commons^™

Surgical Outcomes Of Hidradenitis Suppurativa Excision: Factors Impacting Wound Healing Time, Christina Huang, Scott H. Koeneman, Sherry Yang, Sami Tannour

Department of Surgery Faculty Papers

Hidradenitis suppurativa (HS) can be treated surgically to excise recurrent and recalcitrant regions of disease activity. However, surgical outcomes are highly variable depending on closure method, concomitant medical management and area of excision. In this study, we aim to characterise the healing courses from HS excision in a case series. To reduce operator variability, we opted to conduct a case series from a single surgeon. Surgeries conducted from June 2024-December 2025 by surgeon S.T. were included, and the postoperative course was followed until February 2026. Surgical details and postoperative course for 34 sites of HS across 20 patients were analysed. …

Soluble C5b-9 (Sc5b-9) In Pediatrics-A Clinical Assessment, Ridwan B Ibrahim, Radwa Almamoun, Sarah E Sartain, Sridevi Devaraj

Faculty, Staff and Students Publications

Background: The soluble C5b-9 (sC5b-9) is a soluble form of the Terminal Complement Complex (TCC) that is released into the circulation with elevated levels, associated with increased morbidity and mortality in patients with complement-mediated inflammatory conditions. With the advent of eculizumab and ravulizumab, proper testing for diagnoses and therapeutic monitoring is warranted.

Methods: We evaluated both the analytical and clinical performance of the Quidel Microvue sC5b-9 Plus enzyme immunoassay. Analytical performance was evaluated with precision, linearity, interference studies, and correlation with a reference laboratory. Reference intervals were established using control donor samples [n = 26; median age 18.5 years (range …

Fibroblasts Are The Primary Contributors To A Disrupted Micro-Environment In End-Stage Pediatric Hypertrophic Cardiomyopathy, Hanna J Tadros, Diwakar Turaga, Yi Zhao, Chang-Ru Tsai, Iki A Adachi, Xiao Li, James F Martin

Faculty, Staff and Students Publications

Background: Hypertrophic cardiomyopathy (HCM) is a relatively rare but debilitating diagnosis in the pediatric population, and patients with end-stage HCM require heart transplantation. Here, we have examined the transcriptome in ventricular tissue from this patient group to identify cell states and underlying cellular processes unique to pediatric HCM.

Methods: We performed single-nucleus RNA sequencing (snRNA-seq) on explanted hearts at transplant in 3 pediatric patients with end-stage HCM and compared findings to pediatric control and adult HCM.

Results: We identified distinct underlying cellular processes in cardiomyocytes, fibroblasts, endothelial cells, and myeloid cells compared with controls. Pediatric HCM was enriched in cardiomyocytes …

Insights From A Survey Of School Nurses: Assessing The Challenges Of Constipation In Schools, Andrew S Chu, Eric H Chiou

Faculty, Staff and Students Publications

Objectives: School nurses are key responders to students with constipation, yet their experiences are underreported. This study surveyed their observations regarding constipation, identified barriers to student restroom access, and assessed educational needs.

Methods: In this descriptive, cross-sectional survey study, an anonymous online survey was distributed to school nurses participating in a virtual education series. The survey assessed nurse demographics, frequency of encounters with constipation and encopresis, school restroom policies, barriers to restroom use, accommodation requests, and training in constipation management.

Findings: Of 125 respondents, 95% encountered students with constipation at least monthly and 55% reported ≥ 6 encounters monthly. Commonly …

Real-World Outcomes Of Infections Following Tisagenlecleucel In Patients With B-Cell All: A Cibmtr Analysis, Hemalatha G Rangarajan, Prakash Satwani, Megan M Herr, Min Chen, Michael J Martens, Kitsada Wudhikarn, Samuel John, Vanessa A Fabrizio, Emily M Hsieh, Amar H Kelkar, Erin Doherty, David I Marks, Olle Ringden, Brian Friend, Matthew S Kelly, Nosha Farhadfar, Tim Prestidge, Nasheed M Hossain, Hongtao Liu, Shahrukh Hashmi, Dipenkumar Modi, Lena E Winestone, Zeinab El Boghdadly, Hemant S Murthy, Miguel-Angel Perales, Roy F Chemaly, Christopher E Dandoy, Joshua A Hill, Anna Huppler, Marcie Riches, Jeffery J Auletta

Faculty, Staff and Students Publications

Tisagenlecleucel (tisa-cel) is a CD19-directed chimeric antigen receptor T-cell therapy for relapsed/refractory precursor B-cell acute lymphoblastic leukemia (R/R B-ALL). We report infectious complications for 100 days (D100) following tisa-cel therapy in 471 pediatric and young adults (median age 13.8 years) with R/R B-ALL reported from September 2017 to June 2022. By D100, 137 (29%) patients had an infectious event, with an infection density of 0.542 per 100 person-days at risk. D100 cumulative incidences of bacterial, viral, and fungal infections were 14.1%, 11.6%, and 1.3%, corresponding to infection density scores of 0.296, 0.213, and 0.033 per 100 person-days at risk, respectively. …

Infection After Cd19 Chimeric Antigen Receptor T-Cell Therapy For Large B-Cell Lymphoma: Real-World Analysis From Cibmtr, Kitsada Wudhikarn, Megan M Herr, Min Chen, Michael J Martens, John H Baird, Lohith Gowda, Hemalatha G Rangarajan, Muhammad Bilal Abid, Mohamed A Kharfan-Dabaja, Kirsten M Williams, Siddhartha Ganguly, Jo-Anne H Young, Akshay Sharma, Giancarlo Fatobene, Tania Jain, Christopher G Kanakry, Dipenkumar Modi, Natalie S Grover, Baheyeldin Salem, Marjorie Vieira Batista, Paschalis Vergidis, Dwight E Yin, Amer M Beitinjaneh, Amar H Kelkar, Taiga Nishihori, Jennifer Holter Chakrabarty, Usama Gergis, Melody Smith, Zeinab El Boghdadly, Christopher E Dandoy, Hemant S Murthy, Anna R Huppler, Miguel-Angel Perales, Roy F Chemaly, Joshua A Hill, Marcie Riches, Jeffery J Auletta

Faculty, Staff and Students Publications

Infection is increasingly recognized as a significant cause of morbidity and mortality in patients with relapsed/refractory (R/R) large B-cell lymphoma (LBCL) receiving CD19 chimeric antigen receptor (CAR) T-cell therapy. The current study analyzed the natural history, risk factors, and outcomes of infection in 3350 patients with R/R LBCL receiving commercial CD19 CAR T-cell therapy (n = 2804 axicabtagene ciloleucel [axi-cel], n = 546 tisagenlecleucel) from December 2017 to June 2022. Infection developed in 834 patients (24.9%) within 100 days after infusion, resulting in an infection density of 0.43 per 100 patient days and a 100-day cumulative incidence of 22%. Bacterial, …

Optimising Drowning Prevention Counselling Through A Physician Maintenance Of Certification (Moc) Quality Improvement (Qi) Initiative, Tracy E Mccallin, Anthony R Arredondo, Elizabeth A Camp, Shabana Yusuf

Faculty, Staff and Students Publications

Drowning is the leading cause of death in children 1–4 years old in the USA. Paediatricians play an important role in giving anticipatory guidance on drowning prevention. This quality improvement initiative aimed to increase the rate of drowning prevention counselling with provision of educational materials to caregivers of children aged 0–10 years during clinical encounters in an outpatient setting.

We refined a previously published Texas state educational programme that included evidence-based counselling strategies across three Plan Do Study Act (PDSA) cycles, with the addition of preintervention baseline counselling phase during expansion of the programme nationally to 17 and 21 states …

Acute Loss Of Tactile Input Leads To General Compensatory Changes In Eye-Hand Coordination During Object Manipulation, Kevin Ung, John F Magnotti, Brandon Kim, Jeffrey M Yau, Per F Nordmark

Faculty, Staff and Students Publications

Current models of motor control emphasize the critical role of sensory feedback, as demonstrated by movement coordination deficits following sensory impairment. When both vision and touch are available for object-oriented manual behaviors, they serve distinct roles; vision guides the execution of planned movements, while touch provides more direct feedback on hand-object interactions. The impact of losing somatosensory feedback on eye-hand coordination during dexterous object manipulation tasks has not been thoroughly studied. Conceivably, vision is recruited to compensate for the feedback lost when touch is abolished based on the dexterity demands of the behavior. To investigate this, we tested healthy participants …

Identification Of Distinct Biological Groups Of Patients With Cryptogenic Norse Via Inflammatory Profiling, Martin Guillemaud, Mario Chavez, Firas Kobeissy, Annamaria Vezzani, Anthony D Jimenez, Maysaa Merhi Basha, Ayush Batra, Sophie Demeret, Onome Eka, Krista Eschbach, Brandon Foreman, Nicolas Gaspard, Elizabeth E Gerard, Teneille Emma Gofton, Hiba A Haider, Stephen T Hantus, Charles L Howe, Amy Jongeling, Mariel Kalkach-Aparicio, Padmaja Kandula, Karnig Kazazian, Minjee Kim, Yi-Chen Lai, Clémence Marois, Andrew Mellor, Wazim Mohamed, Mikaela Morales, Cederic M Pimentel, Alexandra M Ramirez, Claude Steriade, Aaron F Struck, Olga Taraschenko, Nathan Torcida Sedano, Mark S Wainwright, Ji Yeoun Yoo, Kevin K W Wang, Vincent Navarro, Lawrence J Hirsch, Aurélie Hanin

Faculty, Staff and Students Publications

Background and objectives: Emerging evidence suggests that immune dysregulation plays a pivotal role in triggering cryptogenic new-onset refractory status epilepticus (c-NORSE), prompting a consensus on early initiation of immunotherapy. However, despite similar timing of administration, responses to immunotherapies have been varied and unpredictable, suggesting the presence of heterogeneous underlying mechanisms. The aim of this study was to identify distinct inflammatory response subtypes in patients with c-NORSE by analyzing their cytokine profiles. Insights into underlying mechanisms were sought to understand the pathophysiology and guide personalized therapies to improve patient outcomes.

Methods: Sixty-two patients with c-NORSE were included. A comprehensive panel …

Modeling Reemergence Of Vaccine-Eliminated Infectious Diseases Under Declining Vaccination In The Us, Mathew V Kiang, Kate M Bubar, Yvonne Maldonado, Peter J Hotez, Nathan C Lo

Faculty, Staff and Students Publications

Importance: Widespread childhood vaccination has eliminated many infectious diseases in the US. However, vaccination rates are declining, and there are ongoing policy debates to reduce the childhood vaccine schedule, which may risk reemergence of previously eliminated infectious diseases.

Objective: To estimate the number of cases and complications in the US under scenarios of declining childhood vaccination for measles, rubella, poliomyelitis, and diphtheria.

Design, setting, and participants: A simulation model was used to assess the importation and dynamic spread of vaccine-preventable infectious diseases across 50 US states and the District of Columbia. The model was parameterized with data on area-specific estimates …

Recovery Potential In Patients After Cardiac Arrest Who Die After Limitations Or Withdrawal Of Life Support, Jonathan Elmer, Patrick J Coppler, Cecelia Ratay, Alexis Steinberg, Sara Difiore-Sprouse, Nicholas Case, Baruch Fischhoff, Maria De-Arteaga, Alain Cariou, Alejandro A Rabinstein, Andrea O Rossetti, Ankur A Doshi, Bradley J Molyneaux, Cameron Dezfulian, Carolina B Maciel, Christoph Leithner, Cindy H Hsu, Claudio Sandroni, David M Greer, David B Seder, Francis X Guyette, Fabio Silvio Taccone, Hiromichi Naito, Jasmeet Soar, Jean-Baptiste Lascarrou, Jerry P Nolan, Karen G Hirsch, Katherine M Berg, Marion Moseby-Knappe, Markus B Skrifvars, Michael C Kurz, Min Jung Kathy Chae, Mypinder S Sekhon, Nicholas J Johnson, Pedro Kurtz, Romergryko G Geocadin, Sachin Agarwal, Teresa L May, Theresa M Olasveengen, Clifton W Callaway, Optimizing Recovery Prediction After Cardiac Arrest (Orca) Study Group

Faculty, Staff and Students Publications

Importance: Understanding the relationship between patients' clinical characteristics and outcomes is fundamental to medicine. When critically ill patients die after withdrawal of life-sustaining therapy (WLST), the inability to observe the potential for recovery with continued aggressive care could bias future clinical decisions and research.

Objective: To quantify the frequency with which experts consider patients who died after WLST following resuscitated cardiac arrest to have had recovery potential if life-sustaining therapy had been continued.

Design, setting, and participants: This prospective cohort study included comatose adult patients (aged ≥18 years) treated following resuscitation from cardiac arrest at a single academic medical center …

Impact Of Measurable Residual Disease Clearance Kinetics In Patients With Aml Undergoing Intensive Chemotherapy, Wei-Ying Jen, Koji Sasaki, Farhad Ravandi, Tapan M Kadia, Sa A Wang, Wei Wang, Sanam Loghavi, Naval G Daver, Courtney D Dinardo, Ghayas C Issa, Hussein A Abbas, Cedric Nasnas, Alex Bataller, Samuel Urrutia, Omer S Karrar, Sherry Pierce, Hagop M Kantarjian, Nicholas J Short

Faculty, Staff and Student Publications

The prognostic impact of measurable residual disease (MRD) in acute myeloid leukemia (AML) is unequivocal; however, the optimal time point for achieving undetectable MRD is unclear. We retrospectively studied patients with newly diagnosed (ND) AML who achieved remission with frontline intensive chemotherapy and had MRD assessed by flow cytometry after induction (time point 1 [TP1]) and after cycles 2 or 3 (TP2). Cases were grouped into MRD negative (Neg)/Neg, positive (Pos)/Neg, or Pos/Pos at TP1 and TP2, respectively. Of 1980 patients with ND AML, 277 met the inclusion criteria and were included in this analysis. The median relapse-free survival (RFS) …

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

Faculty, Staff and Students Publications

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

Atm Expression And Activation In Ataxia Telangiectasia Patients With And Without Class Switch Recombination Defects, Fereshte Salami, Tannaz Moeini Shad, Nazanin Fathi, Hanieh Mojtahedi, Marzie Esmaeili, Sepideh Shahkarami, Ladan Gol Mohammad Pour Afrakoti, Parisa Amirifar, Samaneh Delavari, Hassan Nosrati, Azadehsadat Razavi, Mohammad Reza Ranjouri, Mahsa Yousefpour, Zahra Hamidi Esfahani, Gholamreza Azizi, Mahmoudreza Ashrafi, Nima Rezaei, Reza Yazdani, Hassan Abolhassani

Department of Neurology Faculty Papers

BACKGROUND: Ataxia telangiectasia mutated (ATM) kinase plays a critical role in DNA double-strand break (DSB) repair. Ataxia telangiectasia (A-T) patients exhibit abnormalities in immunoglobulin isotype expression and class switch recombination (CSR). This study investigates the role of residual ATM kinase expression and activity in the severity of A-T disease.

METHODS: A-T patients with defined genetic diagnoses were classified based on CSR and based on the severity of their medical complications. Isolated peripheral blood mononuclear cells from any patient were evaluated before and after exposure to 0.5 Gy ionizing radiation for one minute. Western blotting was performed to identify the expression …

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

Faculty, Staff and Students Publications

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

Longitudinal Host Transcriptional Responses To Sars-Cov-2 Infection In Adults With Extremely High Viral Load, Vasanthi Avadhanula, Chad J Creighton, Laura Ferlic-Stark, Divya Nagaraj, Yiqun Zhang, Richard Sucgang, Erin G Nicholson, Anubama Rajan, Vipin Kumar Menon, Harshavardhan Doddapaneni, Donna Marie Muzny, Ginger A Metcalf, Sara Joan Javornik Cregeen, Kristi Louise Hoffman, Richard A Gibbs, Joseph F Petrosino, Pedro A Piedra

Faculty, Staff and Students Publications

Current understanding of viral dynamics of SARS-CoV-2 and host responses driving the pathogenic mechanisms in COVID-19 is rapidly evolving. Here, we conducted a longitudinal study to investigate gene expression patterns during acute SARS-CoV-2 illness. Cases included SARS-CoV-2 infected individuals with extremely high viral loads early in their illness, individuals having low SARS-CoV-2 viral loads early in their infection, and individuals testing negative for SARS-CoV-2. We could identify widespread transcriptional host responses to SARS-CoV-2 infection that were initially most strongly manifested in patients with extremely high initial viral loads, then attenuating within the patient over time as viral loads decreased. Genes …

Diabetter Together: Clinical Trial Protocol For A Strengths-Based Peer Mentor Intervention For Young Adults With Type 1 Diabetes Transitioning To Adult Care, Samantha A Carreon, Charles G Minard, Sarah K Lyons, Wendy Levy, Stephanie Camey, Kishan Desai, Brenda Duran, Randi Streisand, Barbara J Anderson, Siripoom V Mckay, Tricia S Tang, Sridevi Devaraj, Ryan Ramphul, Marisa E Hilliard

Faculty, Staff and Students Publications

Background: Type 1 diabetes (T1D) management is challenging for young adults, who are expected to transfer from the pediatric to adult T1D healthcare system while also managing typical developmental demands (e.g., social, financial, work/school, residential). Many young adults have extended gaps in care before following up in adult care, increasing risk for poor health outcomes. There are few evidence-based programs to support young adults with T1D to promote a timelier transition during this period. This paper reports on the design of DiaBetter Together, a randomized controlled trial to evaluate a 12-month Peer Mentor-delivered intervention compared to usual care among young …

Randomized, Observer-Blind, Controlled Phase 1 Study Of The Safety And Immunogenicity Of The Na-Gst-1/Alhydrogel Hookworm Vaccine With Or Without A Cpg Odn Adjuvant In Hookworm-Naïve Adults, David J Diemert, Maria Zumer, Mark Bova, Christina Gibbs-Tewary, Elissa M Malkin, Doreen Campbell, Lara Hoeweler, Guangzhao Li, Maria Elena Bottazzi, Peter J Hotez, Jeffrey M Bethony

Faculty, Staff and Students Publications

BACKGROUND: Recombinant Necator americanus Glutathione-S-Transferase-1 (Na-GST-1) formulated on Alhydrogel (Na-GST-1/Alhydrogel) is being developed to prevent anemia and other complications of N. americanus infection. Antibodies induced by vaccination with recombinant Na-GST-1 are hypothesized to interfere with the blood digestion pathway of adult hookworms in the host. Phase 1 trials have demonstrated the safety of Na-GST-1 formulated on Alhydrogel, but further optimization of the vaccine adjuvant formulation may improve humoral immune responses, thereby increasing the likelihood of vaccine efficacy.

METHODS: A randomized, observer-blind, dose escalation Phase 1 trial was conducted in 24 healthy, hookworm-naïve adults. In each cohort of 12 participants, 4 …

A Proteogenomic Analysis Of Cervical Cancer Reveals Therapeutic And Biological Insights, Jing Yu, Xiuqi Gui, Yunhao Zou, Qian Liu, Zhicheng Yang, Jusheng An, Xuan Guo, Kaihua Wang, Jiaming Guo, Manni Huang, Shuhan Zhou, Jing Zuo, Yimin Chen, Lu Deng, Guangwen Yuan, Ning Li, Yan Song, Jia Jia, Jia Zeng, Yuxi Zhao, Xianming Liu, Xiaoxian Du, Yansheng Liu, Pei Wang, Bing Zhang, Li Ding, Ana I Robles, Henry Rodriguez, Hu Zhou, Zhen Shao, Lingying Wu, Daming Gao

Faculty, Staff and Students Publications

Although the incidence of cervical cancer (CC) has been reduced in high-income countries due to human papillomavirus (HPV) vaccination and screening strategies, it remains a significant public health issue that poses a threat to women's health in low-income countries. Here, we perform a comprehensive proteogenomic profiling of CC tumors obtained from 139 Chinese women. Integrated proteogenomic analysis links genetic aberrations to downstream pathogenesis-related pathways and reveals the landscape of HPV-associated multi-omic changes. EP300 is found to enhance the acetylation of FOSL2-K222, consequently accelerating the malignant proliferation of CC cells. Proteomic stratification identifies three patient subgroups with distinct features in prognosis, …

Genotype-Specific Effects Of Elamipretide In Patients With Primary Mitochondrial Myopathy: A Post Hoc Analysis Of The Mmpower-3 Trial, Amel Karaa, Enrico Bertini, Valerio Carelli, Bruce Cohen, Gregory M Ennes, Marni J Falk, Amy Goldstein, Gráinne Gorman, Richard Haas, Michio Hirano, Thomas Klopstock, Mary Kay Koenig, Cornelia Kornblum, Costanza Lamperti, Anna Lehman, Nicola Longo, Maria Judit Molnar, Sumit Parikh, Han Phan, Robert D S Pitceathly, Russekk Saneto, Fernando Scaglia, Serenella Servidei, Mark Tarnopolsky, Antonio Toscano, Johan L K Van Hove, John Vissing, Jerry Vockley, Jeffrey S Finman, Anthony Abbruscato, David A Brown, Alana Sullivan, James A Shiffer, Michelango Mancuso, Mmpower-3 Trial Investigators

Faculty, Staff and Students Publications

BACKGROUND: As previously published, the MMPOWER-3 clinical trial did not demonstrate a significant benefit of elamipretide treatment in a genotypically diverse population of adults with primary mitochondrial myopathy (PMM). However, the prespecified subgroup of subjects with disease-causing nuclear DNA (nDNA) pathogenic variants receiving elamipretide experienced an improvement in the six-minute walk test (6MWT), while the cohort of subjects with mitochondrial DNA (mtDNA) pathogenic variants showed no difference versus placebo. These published findings prompted additional genotype-specific post hoc analyses of the MMPOWER-3 trial. Here, we present these analyses to further investigate the findings and to seek trends and commonalities among those …

Nepali Oral Microbiomes Reflect A Gradient Of Lifestyles From Traditional To Industrialized, Erica Ryu, Yoshina Gautam, Diana Proctor, Dinesh Bhandari, Sarmila Tandukar, Meera Gupta, Guru Prasad Gautam, David Relman, Ahmed Shibl, Jeevan Bahadur Sherchand, Aashish Jha, Emily Davenport

SKMC Student Presentations and Publications

BACKGROUND: Lifestyle plays an important role in shaping the gut microbiome. However, its contributions to the oral microbiome remain less clear, due to the confounding effects of geography and methodology in investigations of populations studied to date. Furthermore, while the oral microbiome seems to differ between foraging and industrialized populations, we lack insight into whether transitions to and away from agrarian lifestyles shape the oral microbiota. Given the growing interest in so-called "vanishing microbiomes" potentially being a risk factor for increased disease prevalence in industrialized populations, it is important that we distinguish lifestyle from geography in the study of microbiomes …

Pharmacogenomic Insights In Psychiatric Care: Uncovering Novel Actionability, Allele-Specific Cyp2d6 Copy Number Variation, And Phenoconversion In 15,000 Patients, Jai N Patel, Sarah A Morris, Raul Torres, Brooke Rhead, Chris Vlangos, Daniel J Mueller, Lisa C Brown, Hailey Lefkofsky, Muneer Ali, Francisco M De La Vega, Kathleen C Barnes, Anthony Zoghbi, Joseph D Stanton, Marcus A Badgeley

Faculty, Staff and Students Publications

Pharmacogenomic testing has emerged as an aid in clinical decision making for psychiatric providers, but more data is needed regarding its utility in clinical practice and potential impact on patient care. In this cross-sectional study, we determined the real-world prevalence of pharmacogenomic actionability in patients receiving psychiatric care. Potential actionability was based on the prevalence of CYP2C19 and CYP2D6 phenotypes, including CYP2D6 allele-specific copy number variations (CNVs). Combined actionability additionally incorporated CYP2D6 phenoconversion and the novel CYP2C-TG haplotype in patients with available medication data. Across 15,000 patients receiving clinical pharmacogenomic testing, 65% had potentially actionable CYP2D6 and CYP2C19 phenotypes, and …

Perivascular Epithelioid Cell-Family Tumors In Children, Adolescents, And Young Adults: Clinicopathologic Features In 70 Cases, Phoebe M Hammer, Angus Toland, Muhammad Shaheen, Archana Shenoy, Ashwini Esnakula, M John Hicks, Mikako Warran, Alyaa Al-Ibraheemi, Jessica L Davis, Serena Y Tan

Faculty, Staff and Students Publications

Context.—: Perivascular epithelioid cell tumors (PEComas) are rare mesenchymal tumors of uncertain histogenesis expressing smooth muscle and melanocytic markers. The clinicopathologic spectrum in young patients is not well documented.

Objective.—: To describe a multi-institutional series of PEComas in children, adolescents, and young adults.

Design.—: PEComas, not otherwise specified (NOS); angiomyolipomas (AMLs); lymphangioleiomyomatosis; and clear cell sugar tumors were retrospectively identified from 6 institutions and the authors' files.

Results.—: Seventy PEComas in 64 patients (median age, 15 years) were identified. They were more common in females (45 of 64 patients), occurring predominantly in the kidney (53 of 70), followed by the …

Multicenter Pivotal Study Of The Alterra Adaptive Prestent For The Treatment Of Pulmonary Regurgitation, V Vivian Dimas, Vasilis Babaliaros, Dennis Kim, D Scott Lim, Gareth Morgan, Thomas K Jones, Aimee K Armstrong, Darren Berman, Jamil Aboulhosn, Vaikom S Mahadevan, Matthew J Gillespie, David Balzer, Thomas Zellers, Xiao Yu, Girish Shirali, Anitha Parthiban, Jonathan Leipsic, Philipp Blanke, Evan Zahn, Shabana Shahanavaz

Faculty, Staff and Students Publications

Background: A dilated native right ventricular outflow tract (RVOT) presents unique challenges for transcatheter management using balloon-expandable valves. The Alterra Adaptive Prestent was designed to expand transcatheter therapy to treat patients with dilated RVOTs.

Objectives: The aim of this study was to report 2-year outcomes of the main cohort of the ALTERRA (Multicenter Study of Congenital Pulmonic Valve Dysfunction Studying the SAPIEN 3 THV With the Alterra Adaptive Prestent) pivotal trial using the prestent with transcatheter pulmonary valve replacement.

Methods: The prestent device used with the 29 mm SAPIEN 3 transcatheter heart valve (THV) was evaluated for the management of …

Larp1 Haploinsufficiency Is Associated With An Autosomal Dominant Neurodevelopmental Disorder, James Chettle, Raymond J Louie, Olivia Larner, Robert Best, Kevin Chen, Josephine Morris, Zinaida Dedeic, Anna Childers, R Curtis Rogers, Barbara R Dupont, Cindy Skinner, Sébastien Küry, Kevin Uguen, Marc Planes, Danielle Monteil, Megan Li, Aviva Eliyahu, Lior Greenbaum, Nofar Mor, Thomas Besnard, Bertrand Isidor, Benjamin Cogné, Alyssa Blesson, Anne Comi, Ingrid M Wentzensen, Blake Vuocolo, Seema R Lalani, Roberta Sierra, Lori Berry, Kent Carter, Stephan J Sanders, Sarah P Blagden

Faculty, Staff and Students Publications

Autism spectrum disorder (ASD) is a neurodevelopmental disorder (NDD) that affects approximately 4% of males and 1% of females in the United States. While causes of ASD are multi-factorial, single rare genetic variants contribute to around 20% of cases. Here, we report a case series of seven unrelated probands (6 males, 1 female) with ASD or another variable NDD phenotype attributed to de novo heterozygous loss of function or missense variants in the gene LARP1 (La ribonucleoprotein 1). LARP1 encodes an RNA-binding protein that post-transcriptionally regulates the stability and translation of thousands of mRNAs, including those regulating cellular metabolism and …

Psychological Distress Among Ethnically Diverse Participants From Eastern And Southern Africa, Kester B B Tindi, Allan Kalungi, Eugene Kinyanda, Bizu Gelaye, Alicia R Martin, Ronald Galiwango, Wilber Ssembajjwe, Fred Kirumira, Adele Pretorius, Anne Stevenson, Charles R J C Newton, Dan J Stein, Elizabeth G Atkinson, Emanuel K Mwesiga, Joseph Kyebuzibwa, Lori B Chibnik, Lukoye Atwoli, Mark Baker, Melkam Alemayehu, Rehema M Mwende, Rocky E Stroud, Solomon Teferra, Stella Gichuru, Symon M Kariuki, Zukiswa Zingela, Moffat Nyirenda, Segun Fatumo, Dickens H Akena

Faculty, Staff and Students Publications

IMPORTANCE: Psychological distress is characterized by anxiety and depressive symptoms. Although prior research has investigated the occurrence and factors associated with psychological distress in low- and middle-income countries, including those in Africa, these studies' findings are not very generalizable and have focused on different kinds of population groups.

OBJECTIVE: To investigate the prevalence and characteristics (sociodemographic, psychosocial, and clinical) associated with psychological distress among African participants.

DESIGN, SETTING, AND PARTICIPANTS: This case-control study analyzed data of participants in the Neuropsychiatric Genetics in African Populations-Psychosis (NeuroGAP-Psychosis) study, which recruited from general outpatient clinics in Eastern (Uganda, Kenya, and Ethiopia) and Southern …

Prognostic Impact Of Notch1 Intracellular Domain, P63, And C-Myc In Lacrimal Gland Adenoid Cystic Carcinoma, Jiawei Zhao, Michelle D Williams, Mike Hernandez, Grace Kuang, Hila Goldberg, Janet Fan, Jing Ning, Renata Ferrarotto, Bita Esmaeli

Faculty, Staff and Student Publications

PURPOSE: We assessed whether NICD1 expression, c-MYC expression, and P63 expression by immunohistochemistry (IHC) correlate with prognosis and high-risk clinicopathological features in lacrimal gland adenoid cystic carcinoma (ACC).

METHODS: Records of patients with lacrimal gland ACC who underwent surgery between 1998 to 2018 were reviewed. Clinicopathologic and treatment data were collected. Tumor tissues were subjected to light microscopy and IHC.

RESULTS: Of 43 patients treated during the study period, 21 had archived tumor tissue available and were included. The median age at diagnosis was 47 years, and 13 patients (62%) were male. Thirteen patients (62%) had T2 disease, and none …

Setrusumab For The Treatment Of Osteogenesis Imperfecta: 12-Month Results From The Phase 2b Asteroid Study, Francis H Glorieux, Bente Langdahl, Roland Chapurlat, Suzanne Jan De Beur, Vernon Reid Sutton, Kenneth E S Poole, Kathryn M Dahir, Eric S Orwoll, Bettina M Willie, Nicholas Mikolajewicz, Elizabeth Zimmermann, Seyedmahdi Hosseinitabatabaei, Michael S Ominsky, Chris Saville, James Clancy, Alastair Mackinnon, Arun Mistry, Muhammad K Javaid

Faculty, Staff and Students Publications

Osteogenesis imperfecta (OI) is a rare genetic disorder commonly caused by variants of the type I collagen genes COL1A1 and COL1A2. OI is associated with increased bone fragility, bone deformities, bone pain, and reduced growth. Setrusumab, a neutralizing antibody to sclerostin, increased areal bone mineral density (aBMD) in a 21-week phase 2a dose escalation study. The phase 2b Asteroid (NCT03118570) study evaluated the efficacy and safety of setrusumab in adults. Adults with a clinical diagnosis of OI type I, III, or IV, a pathogenic variant in COL1A1/A2, and a recent fragility fracture were randomized 1:1:1:1 to receive 2, 8, or …

Psychosocial Outcomes Of Pain And Pain Management In Adults With Osteogenesis Imperfecta: A Qualitative Study, Whitney S Shepherd, Andrew D Wiese, Hannah E Cho, W Conor Rork, M Usman Baig, Kristin M Kostick, Dianne Nguyen, Erin M Carter, Members Of The Bbdc, Chaya N Murali, Marie-Eve Robinson, Sophie C Schneider, Brendan Lee, V Reid Sutton, Eric A Storch

Faculty, Staff and Students Publications

Objectives

Osteogenesis imperfecta (OI) is a genetic disorder characterized by bone fragility and fractures, short stature, dental abnormalities, hearing loss, scoliosis, and chronic pain. Despite a growing literature on the functional outcomes of OI, limited research has explicitly examined the psychosocial outcomes of pain within OI.

Methods

Adults with OI (N=15) were interviewed to understand pain-related experiences through a thematic analysis of semi-structured interview data. Research team members, genetic research experts, and OI clinicians developed an interview guide focused on topics related to pain and mental health challenges. Participants’ transcripts were coded by two independent coders; codes were then merged …

Determining Predictors Of Actual Living Kidney Donation Based On Potential Donor Characteristics, Andrea M Meinders, Edward A Graviss, Duc T Nguyen, Jonathan Daw, Krista L Lentine, John Devin Peipert, Ahmed Osama Gaber, David A Axelrod, Francis L Weng, Amy D Waterman

Faculty, Staff and Students Publications

Background: Living donor kidney transplantation is the optimal treatment for end-stage kidney disease; however, few living donor candidates (LDCs) who begin evaluation actually donate. While some LDCs are deemed medically ineligible, others discontinue for potentially modifiable reasons.

Methods: At five transplant centers, we conducted a prospective cohort study measuring LDCs' clinical and psychosocial characteristics, educational preparation, readiness to donate, and social determinants of health. We followed LDCs for 12 months after evaluation to determine whether they donated a kidney, opted to discontinue, had modifiable reasons for discontinuing, were medically ineligible, or had other recipient-related reasons for discontinuing.

Results: Among 2184 …