Medicine and Health Sciences Commons^™

Episodes Of Acute Methotrexate-Related Neurotoxicity Linked To Compromised Long-Term Neurocognitive Function, Rachel D Harris, Olga A Taylor, Kimberly P Raghubar, Mariana Matheus Gonzalez, Mark Zobeck, M Monica Gramatges, Karen R Rabin, Michael E Scheurer, Austin L Brown

Faculty, Staff and Students Publications

Methotrexate is a critical component of curative chemotherapy for pediatric acute lymphoblastic leukemia (ALL), but is associated with neurotoxicity. Information on long-term outcomes following an acute neurotoxic event is limited. Therefore, this report compares neurocognitive performance more than 12 months post diagnosis (mean = 4 years) between ALL patients with (n = 25) and without (n = 146) a history of acute neurotoxicity. Compared to children with no documented on-treatment neurotoxic event, children who experienced a neurotoxic event during treatment exhibited poorer performance on measures of fine motor function (p = .02) and attention (p = .02). Children with ALL …

Women’S Health And Kidney Protective Medications, Mythri Shankar, Sehrish Ali, Silvi Shah

Faculty, Staff and Students Publications

Purpose of review: We discuss the sex-based differences in the pharmacokinetics and pharmacodynamics of kidney protective medications and their implications on women's health.

Recent findings: A critical examination of adverse drug reactions highlights the underrepresentation of women in clinical trials for kidney and cardiovascular protective drugs, such as SGLT2 inhibitors, ACE inhibitors, and endothelin receptor antagonists. This underscores the need for sex-specific analyses in clinical studies to accurately assess medication efficacy and safety.

Summary: The research demonstrates that women are more likely to experience adverse events and less likely to benefit from certain treatments, emphasizing the urgent need for healthcare …

Disruption Of Fuz In Mouse Embryos Generates Hypoplastic Hindbrain Development And Reduced Cranial Nerve Ganglia, Carlo Donato Caiaffa, Yogeshwari S Ambekar, Manmohan Singh, Ying Linda Lin, Bogdan Wlodarczyk, Salavat R Aglyamov, Giuliano Scarcelli, Kirill V Larin, Richard H Finnell

Faculty, Staff and Students Publications

Background: The brain and spinal cord formation is initiated in the earliest stages of mammalian pregnancy in a highly organized process known as neurulation. Environmental or genetic interferences can impair neurulation, resulting in clinically significant birth defects known collectively as neural tube defects. The Fuz gene encodes a subunit of the CPLANE complex, a macromolecular planar polarity effector required for ciliogenesis. Ablation of Fuz in mouse embryos results in exencephaly and spina bifida, including dysmorphic craniofacial structures due to defective cilia formation and impaired Sonic Hedgehog signaling.

Results: We demonstrate that knocking Fuz out during embryonic mouse development results in …

Phase Ii Study Of Samotolisib In Children And Young Adults With Tumors Harboring Phosphoinositide 3-Kinase/Mammalian Target Of Rapamycin Pathway Alterations: Pediatric Match Apec1621d, Theodore W Laetsch, Kathleen Ludwig, P Mickey Williams, Sinchita Roy-Chowdhuri, David R Patton, Brent Coffey, Joel M Reid, Jin Piao, Lauren Saguilig, Todd A Alonzo, Stacey L Berg, Joyce Mhlanga, Elizabeth Fox, Brenda J Weigel, Douglas S Hawkins, Margaret M Mooney, Naoko Takebe, James V Tricoli, Katherine A Janeway, Nita L Seibel, Donald Williams Parsons

Faculty, Staff and Students Publications

Purpose: Patients age 1-21 years with relapsed or refractory solid and CNS tumors were assigned to phase II studies of molecularly targeted therapies on the National Cancer Institute-Children's Oncology Group (NCI-COG) Pediatric Molecular Analysis for Therapy Choice (MATCH) trial. Patients whose tumors harbored predefined genetic alterations in the phosphoinositide 3-kinase (PI3K)/mammalian target of rapamycin (mTOR) pathway and lacked mitogen-activated protein kinase pathway activating alterations were treated with the PI3K/mTOR inhibitor samotolisib.

Methods: Patients received samotolisib twice daily in 28-day cycles until disease progression or unacceptable toxicity. A rolling 6 limited dose escalation was performed as, to our knowledge, this was …

Treatment Response To Onabotulinumtoxina In Cervical Dystonia Patients With Anterocollis And Retrocollis, Khashayar Dashtipour, Marjan Sadeghi, David Charles, Shyamal Mehta, Hubert H Fernandez, Marc Schwartz, Joseph Jankovic

Faculty, Staff and Students Publications

Anterocollis (AC) and retrocollis (RC) are less common cervical dystonia (CD) subtypes that are often under-represented in CD clinical trials. Herein we describe real-world demographics, disease characteristics, and treatment response to onabotulinumtoxinA (onabotA) in AC or RC patients from an observational, multicenter, prospective registry, CD PROBE. After three onabotA treatments, outcomes (CDIP-58, PGIC, CGIC, CD severity, TWSTRS) in patients with predominant AC or RC were compared to torticollis (TC) and all CD subtypes combined. The mean dosages at each treatment ranged from 153.5 to 195.4 U (AC) to 184.0-213.4 U (RC). After treatment, AC and RC patients reported improvements in …

High-Sensitivity Troponin T, Nt-Probnp, And Cognitive Outcomes In Sprint, Devin Haney, Yuan Ma, Djhenne Dalmacy, Nicholas M Pajewski, Ihab Hajjar, James A De Lemos, Wenxin Zhang, Elsayed Z Soliman, Christie M Ballantyne, Vijay Nambi, Naveed Sattar, Anthony A Killeen, Joachim H Ix, Michael G Shlipak, Jarett D Berry, Simon B Ascher

Faculty, Staff and Students Publications

Background: Hs-cTnT (cardiac troponin T measured with a highly sensitive assay) and NT-proBNP (N-terminal pro-B-type natriuretic peptide) may identify adults with hypertension who derive greater cognitive benefits from lower systolic blood pressure targets.

Methods: In the SPRINT (Systolic Blood Pressure Intervention Trial) MIND study, participants were categorized as having both hs-cTnT and NT-proBNP in the lower 2 tertiles (n=4226), one in the highest tertile (n=2379), and both in the highest tertile (n=1506). We assessed the effect of intensive versus standard treatment on the composite of mild cognitive impairment (MCI) or probable dementia (PD) across biomarker categories.

Results: Over a median …

X-Linked Genetic Associations In Sporadic Thoracic Aortic Dissection, Fadi I Musfee, Goo Jun, Laura E Mitchell, Han Chen, Dongchuan Guo, Siddharth K Prakash, Shaunak Sanjay Adkar, Megan L Grove, Ryan Bohyun Choi, Derek Klarin, Million Veteran Program, Eric Boerwinkle, Dianna M Milewicz

Faculty, Staff and Students Publications

The male predominance in sporadic thoracic aortic aneurysm and dissection (TAD) suggests that the X chromosome contributes to TAD, but this has not been tested. We investigated whether X-linked variation-common (minor allele frequency [MAF] ≥0.01) and rare (MAF < 0.01)-was associated with sporadic TAD in three cohorts of European descent (Discovery: 364 cases, 874 controls; Replication: 516 cases, 440,131 controls, and ARIC [Atherosclerosis Risk in Communities study]: 753 cases, 2247 controls). For analysis of common variants, we applied a sex-stratified logistic regression model followed by a meta-analysis of sex-specific odds ratios. Furthermore, we conducted a meta-analysis of overlapping common variants between the Discovery and Replication cohorts. For analysis of rare variants, we used a sex-stratified optimized sequence kernel association test model. Common variants results showed no statistically significant findings in the Discovery cohort. An intergenic common variant near SPANXN1 was statistically significant in the Replication cohort (p = 1.81 × 10-8). The highest signal from the meta-analysis of the Discovery and Replication cohorts was a ZNF182 intronic common variant (p = 3.5 × 10-6). In rare variants results, RTL9 reached statistical significance (p = 5.15 × 10-5). Although most of our results were statistically insignificant, our analysis is the most comprehensive X-chromosome association analysis of sporadic TAD to date.

Age Modifies The Association Between Severe Sleep Apnea And All-Cause Mortality, Amin Ramezani, Mehrnaz Azarian, Amir Sharafkhaneh, Arash Maghsoudi, Melissa B Jones, Thomas Penzel, Javad Razjouyan

Faculty, Staff and Students Publications

Purpose: While sleep apnea (SA) gets more prevalent with advancing age, the impact of age on the association between SA and health outcomes is not well known. We assessed the association between the severity of SA and all-cause mortality in different age groups using large longitudinal data.

Method: We applied a Natural Language Processing pipeline to extract the apnea-hypopnea index (AHI) from the physicians' interpretation of sleep studies performed at the Veteran Health Administration (FY 1999-2022). We categorized the participants as no SA (n-SA, AHI< 5) and severe SA (s-SA, AHI≥30). We grouped the cohort based on age: Young≤40; Middle-aged:40-65; and Older adults≥65; and calculated the odds ratio (aOR) of mortality adjusted for age, sex, race, ethnicity, BMI, and Charlson-Comorbidity Index (CCI) using n-SA as the reference.

Results: We identified 146,148 participants (age 52.23 ± 15.02; BMI 32.11 ± 6.05; male 86.7 …

Molecular Detection Of Intestinal Parasites In A Rural Community Of Colombia: A One Health Approach To Explore Potential Environmental-Zoonotic Transmission, Sergio Castañeda, Claudia Patricia Acosta, Luis Reinel Vasquez-A, Luz H Patiño, Rojelio Mejía, Juan David Ramírez

Faculty, Staff and Students Publications

Aims: Protozoan and helminth parasitic infections pose significant public health challenges, especially in developing countries with rural populations marked by suboptimal hygiene practices and socio-economic constraints. The parasites are the etiological agents of these infections and have a notably elevated global prevalence. Therefore, this study focuses on estimating the frequency and transmission dynamics of several parasitic species, including Blastocystis, Giardia, Cryptosporidium spp., Entamoeba histolytica, Ascaris lumbricoides, Trichuris trichiura, Taenia spp. and hookworms, within a rural community in southwest Colombia with a particular emphasis on the One Health framework, considering environmental and zoonotic transmission potentials.

Methods and results: This study involved …

Older And Better: A Narrative Review Of Successful Aging And Adaptation To Pain In Late Life, Emanuel Narcis Husu

Faculty, Staff and Students Publications

"Invariably, the self-assessed QoL was far better than I, as a physician, would have anticipated from the diseases and disabilities that you reported." -Ben Eiseman, MD, based on a survey of his octogenarian Yale University classmates.

Background: Chronic pain control is a high priority for the elderly; it is one of the most frequently encountered medical problems in this group. Chronic pain affects 60%-75% of people aged 65 years and older. Chronic pain's prevalence is even higher in those living in assisted living or nursing homes. Based on epidemiological data, the prevalence of chronic pain is directly proportional to age …

Physician Infertility: A Structured Literature Review, Jordan G Kassab, Angelica Garcia Keeme-Sayre, Larry I Lipshultz

Faculty, Staff and Students Publications

Physician infertility has become a growing concern because of the increasingly high rates of infertility physicians experience associated with their strenuous work schedules, environmental exposures, and delayed family planning due to their necessitated years of training. Fortunately, there has been an increase in awareness, advocacy, and urgency for institutional support alongside this suboptimal association. This awareness is reflected in the vast existing literature regarding physician infertility; in this scoping review, we aggregated and assessed the current data as well as identified gaps in the available research. Including 56 articles regarding various aspects of the current state of physician infertility, we …

Mortality In Recipients Of Durable Left Ventricular Assist Devices Undergoing Ventricular Tachycardia Ablation, Patrick T Lynch, Alexandra Maloof, Anish Badjatiya, Payam Safavi-Naeini, Matthew W Segar, Jitae A Kim, Qussay Marashly, Joanna E Molina-Razavi, Leo Simpson, Selby B Oberton, Lola X Xie, Andrew Civitello, Nilesh Mathuria, Jie Cheng, Abdi Rasekh, Mohammad Saeed, Mehdi Razavi, Ajith Nair, Mihail G Chelu

Faculty, Staff and Students Publications

Background: Left ventricular assist device (LVAD) recipients have a higher incidence of ventricular tachycardia (VT). However, the role of VT ablation in this population is not well-established.

Objectives: This single-center retrospective cohort study sought to examine the impact of post-LVAD implant VT ablation on survival.

Methods: This retrospective study examined a cohort of patients that underwent LVAD implantation at Baylor St. Luke's Medical Center and Texas Heart Institute between January 2011 and January 2021. All-cause estimated mortality was compared across LVAD recipients based on the incidence of VT, timing of VT onset, and the occurrence and timing of VT ablation …

Contributions Of White Adipose Tissue To Energy Requirements For Female Reproduction, Elizabeth S Anaya, Evelyn L De Groot, John P Lydon, Stephanie A Pangas, Sean M Hartig

Faculty, Staff and Students Publications

Body composition impacts female fertility and there are established relationships between adipose tissue and the reproductive system. Maintaining functional adipose tissue is vital for meeting the energetic demands during the reproductive process, from ovulation to delivery and lactation. White adipose tissue (WAT) shows plastic responses to daily physiology and secretes diverse adipokines that affect the hypothalamic-pituitary-ovarian axis, but many other interorgan interactions remain to be determined. This review summarizes the current state of research on the dialogue between WAT and the female reproductive system, focusing on the impact of this crosstalk on ovarian and endometrial factors essential for fecundity.

Leveraging Preclinical Models Of Metastatic Breast Cancer, Diego A Pedroza, Yang Gao, Xiang H-F Zhang, Jeffrey M Rosen

Faculty, Staff and Students Publications

Women that present to the clinic with established breast cancer metastases have limited treatment options. Yet, the majority of preclinical studies are actually not directed at developing treatment regimens for established metastatic disease. In this review we will discuss the current state of preclinical macro-metastatic breast cancer models, including, but not limited to syngeneic GEMM, PDX and xenografts. Challenges within these models which are often overlooked include fluorophore-immunogenic neoantigens, differences in experimental vs spontaneous metastasis and tumor heterogeneity. Furthermore, due to cell plasticity in the tumor immune microenvironment (TIME) of the metastatic landscape, the treatment efficacy of newly approved immune …

Optimal Timing Of Delivery For Pregnant Individuals With Mild Chronic Hypertension, Torri D Metz, Hui-Chien Kuo, Lorie Harper, Baha Sibai, Sherri Longo, George R Saade, Lorraine Dugoff, Kjersti Aagaard, Kim Boggess, Kirsten Lawrence, Brenna L Hughes, Joseph Bell, Rodney K Edwards, Kelly S Gibson, David M Haas, Lauren Plante, Brian Casey, Sean Esplin, Matthew K Hoffman, Kara K Hoppe, Janelle Foroutan, Methodius Tuuli, Michelle Y Owens, Hyagriv N Simhan, Heather Frey, Todd Rosen, Anna Palatnik, Susan Baker, Phyllis August, Uma M Reddy, Wendy Kinzler, Emily J Su, Iris Krishna, Nguyet A Nguyen, Mary E Norton, Daniel Skupski, Yasser Y El-Sayed, Dotun Ogunyemi, Ronald Librizzi, Leonardo Pereira, Everett F Magann, Mounira Habli, Shauna Williams, Giancarlo Mari, Gabriella Pridjian, David S Mckenna, Marc Parrish, Eugene Chang, Joanne Quiñones, Zorina S Galis, Namasivayam Ambalavanan, Rachel G Sinkey, Jeff M Szychowski, Alan T N Tita

Faculty, Staff and Students Publications

Objective: To investigate the optimal gestational age to deliver pregnant people with chronic hypertension to improve perinatal outcomes.

Methods: We conducted a planned secondary analysis of a randomized controlled trial of chronic hypertension treatment to different blood pressure goals. Participants with term, singleton gestations were included. Those with fetal anomalies and those with a diagnosis of preeclampsia before 37 weeks of gestation were excluded. The primary maternal composite outcome included death, serious morbidity (heart failure, stroke, encephalopathy, myocardial infarction, pulmonary edema, intensive care unit admission, intubation, renal failure), preeclampsia with severe features, hemorrhage requiring blood transfusion, or abruption. The primary …

Potentially Functional Variants Of Chmp4a And Panx1 In The Pyroptosis-Related Pathway Predict Survival Of Patients With Non-Oropharyngeal Head And Neck Squamous Cell Carcinoma, Xiaozhun Tang, Huiling Wang, Hongliang Liu, Guojun Li, Erich M Sturgis, Sanjay Shete, Qingyi Wei

Faculty, Staff and Students Publications

Background: Pyroptosis has been implicated in the advancement of various cancers. Triggering pyroptosis within tumors amplifies the immune response, thereby fostering an antitumor immune environment. Nonetheless, few published studies have evaluated associations between functional variants in the pyroptosis-related genes and clinical outcomes of patients with non-oropharyngeal head and neck squamous cell carcinoma (NON-ORO HNSCC).

Methods: We conducted an association study of 985 NON-ORO HNSCC patients who were randomly divided into two groups: the discovery group of 492 patients and the replication group of 493 patients. We used Cox proportional hazards regression analysis to examine associations between genetic variants of the …

Initiation Of Metformin In Early Pregnancy Results In Fetal Bioaccumulation, Growth Restriction, And Renal Dysmorphology In A Primate Model, Erin Bolte, Tyler Dean, Brandon Garcia, Maxim D Seferovic, Kristin Sauter, Gwendolynn Hummel, Matthew Bucher, Feng Li, John Hicks, Xuan Qin, Melissa A Suter, Enrico R Barrozo, Michael Jochum, Cynthia Shope, Jacob E Friedman, Maureen Gannon, Stephanie R Wesolowski, Carrie E Mccurdy, Paul Kievit, Kjersti M Aagaard

Faculty, Staff and Students Publications

Background: In recent years, pragmatic metformin use in pregnancy has stretched to include prediabetes mellitus, type 2 diabetes mellitus, gestational diabetes mellitus, and (most recently) preeclampsia. However, with its expanded use, concerns of unintended harm have been raised.

Objective: This study developed an experimental primate model and applied ultrahigh performance liquid chromatography coupled to triple-quadrupole mass spectrometry for direct quantitation of maternal and fetal tissue metformin levels with detailed fetal biometry and histopathology.

Study design: Within 30 days of confirmed conception (defined as early pregnancy), 13 time-bred (timed-mated breeding) Rhesus dams with pregnancies designated for fetal necropsy were initiated on …

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 …

Prolonged Cytopenias After Immune Effector Cell Therapy And Lymphodepletion In Patients With Leukemia, Lymphoma And Solid Tumors, Anne Miller, Rachel Daum, Tao Wang, Mengfen Wu, Candise Tat, Thomas Pfeiffer, Shoba Navai, Andras Heczey, Meenakshi Hegde, Nabil Ahmed, Sarah B Whittle, Laquisa Hill, Caridad Martinez, Robert Krance, Carlos A Ramos, Rayne H Rouce, Premal Lulla, Helen E Heslop, Bilal Omer, Meghan Shekar

Faculty, Staff and Students Publications

Background aims: The success of chimeric antigen receptor (CAR) T-cell therapy in treating B-cell malignancies has led to the evaluation of CAR T-cells targeting a variety of other malignancies. Although the efficacy of CAR T-cells is enhanced when administered post-lymphodepleting chemotherapy, this can trigger bone marrow suppression and sustained cytopenia after CD19.CAR T-cell therapy. Additionally, systemic inflammation associated with CAR T-cell activity may contribute to myelosuppression. Cytopenias, such as neutropenia and thrombocytopenia, elevate the risk of severe infections and bleeding, respectively. However, data on the incidence of prolonged cytopenias after immune effector therapy in the solid tumor context remain limited. …

A Prospective Cohort Study Of Pregnancy Outcomes Following Antepartum Infection With Sars-Cov-2, James D Doss, Emily Diveley, Fan Zhang, Amy Scheffer, Ruizhi Huang, Daniel Jackson, Nandini Raghuraman, Ebony B Carter, Indira U Mysorekar, Jeannie C Kelly

Faculty, Staff and Students Publications

Objectives: Our study aimed to explore the impact of COVID-19 infection on pregnancy outcomes, accounting for the progression of variants, vaccines, and treatment modalities.

Study design: We performed a prospective longitudinal cohort study at two urban tertiary centers enrolling patients with a confirmed intrauterine singleton pregnancy from December 23, 2020 to July 18, 2022. Patients were evaluated for SARS-CoV-2 infection at enrollment and every trimester using serum antibody testing. The primary outcome was preterm birth. Symptom and treatment data were collected from pregnant patients with COVID-19 infections. Variant strain infection status was determined from local wastewater analysis.

Results: 448 patients …

Altered Extracellular Matrix-Related Pathways Accelerate The Transition From Normal To Prefibroid Myometrium In Black Women, Maria Victoria Bariani, Sandra L Grimm, Cristian Coarfa, Digna R Velez Edwards, Qiwei Yang, Cheryl L Walker, Mohamed Ali, Ayman Al-Hendy

Faculty, Staff and Students Publications

Background: Black women experience a disproportionate impact of uterine fibroids compared to White women, including earlier diagnosis, higher frequency, and more severe symptoms. The etiology underlying this racial disparity remains elusive.

Objective: The aim of this study was to evaluate the molecular differences in normal myometrium (fibroid-free uteri) and at-risk myometrium (fibroid-containing uteri) tissues in Black and White women.

Study design: We conducted whole-genome RNA-seq on normal and at-risk myometrium tissues obtained from both self-identified Black and White women (not Hispanic or Latino) to determine global gene expression profiles and to conduct enriched pathway analyses (n=3 per group). We initially …

Satisfaction With Mode Of Delivery Of Genomic Sequencing Results In A Diverse National Sample Of Research Participants Through The Clinical Sequencing Evidence-Generating Research Consortium, Sarah Scollon, Jill O Robinson, Eunji Jo, Sabrina A Suckiel, Laura M Amendola, Ann Katherine M Foreman, Gail P Jarvik, Christine Rini, Tao Wang, Anne Slavotinek

Faculty, Staff and Students Publications

Purpose: Research that includes diverse patient populations is necessary to optimize implementation of telehealth.

Methods: As part of a Clinical Sequencing Evidence-Generating Research Consortium cross-site study, we assessed satisfaction with mode of return of results (RoR) delivery across a diverse sample of participants receiving genetic testing results in person vs telemedicine (TM).

Results: Ninety-eight percent of participants were satisfied with their mode of results delivery. Participants receiving results by TM were more likely to report a preference for receiving results in a different way and challenges with providers noticing difficulties with understanding. More than 90% reported satisfaction across all items …

Pnpla3, Obesity, And Heavy Alcohol Use In Cirrhosis Patients May Exert A Synergistic Increase Hepatocellular Carcinoma Risk, Aaron P Thrift, Fasiha Kanwal, Hyeyeun Lim, Hao Duong, Yanhong Liu, Amit G Singal, Saira Khaderi, Sumeet K Asrani, Christopher I Amos, Hashem B El-Serag

Faculty, Staff and Students Publications

BACKGROUND & AIMS: In patients with cirrhosis, continued heavy alcohol consumption and obesity may increase risk of hepatocellular carcinoma (HCC). We examined whether germline susceptibility to hepatic steatosis not only independently predisposes to HCC but may also act synergistically with other risk factors.

METHODS: We analyzed data from 1911 patients in 2 multicenter prospective cohort studies in the United States. We classified patients according to alcohol consumption (current heavy vs not current heavy), obesity (body mass index ≥30 vs/m2), and PNPLA3 I148M variant status (carrier of at least one G risk allele vs noncarrier). We examined the independent and joint …

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 …

Methicillin-Resistant Staphylococcus Aureus In Diabetic And Non-Diabetic Foot Infections, Lawrence A Lavery, Mario C Reyes, Mehmet Suludere, Bijan Najafi, Matthew Sideman, Michael C Siah, Arthur N Tarricone

Center on Aging Staff Publications

To identify the incidence of methicillin-resistant Staphylococcus aureus (MRSA) infection, reinfection and clinical outcomes. Four hundred forty-six patients that were admitted to the hospital with moderate or severe foot infections were retrospectively reviewed. Tissue and bone cultures were obtained from the index hospital admission. Conversion was defined as methicillin susceptible Staphylococcus aureus in the first culture and subsequently MRSA when there was a reinfection. The incidence of MRSA was 7.8% (n = 35), with no significant difference between soft tissue infections (7.7%) and osteomyelitis (8.0%). MRSA incidence was 9.4 times higher in non-diabetics (23.8% vs. 3.2%, p = < 0.01). The incidence of reinfection was 40.8% (n = 182). Conversion to MRSA was seen in 2.2% (n = 4) total, occurring in 5.4%. Non-diabetics were 20.1 times more likely to have MRSA reinfection than people with diabetes (28.6% vs. 1.9%, p <  0.001). MRSA patients had a higher proportion of healed wounds (82.4% vs. 69.3%, p = 0.02). There were no differences in other clinical outcomes in MRSA vs. other infections in reinfection (28.6% vs. 24.3%, p = 0.11), amputation (48.6% vs. 52.0%, p = 0.69) or hospitalization (28.6% vs. 42.6, p = 0.11). The incidence of MRSA for the first infection (7.8%), reinfection (6.0%) and conversion to MRSA (2.2%) was low. MRSA was 9.4 times more common in people without diabetes.

The Impact Of Margins And Re-Resection In Pediatric Synovial Sarcoma, Andres F Espinoza, Priya B Shetty, Jillian C Jacobson, Hannah Todd, Kelley Harrell, Alfred F Trappey, John Doski, Eumenia C Castro, Nicole I Montgomery, M Fatih Okcu, Rajkumar Venkatramani, Dai H Chung, Sanjeev A Vasudevan

Faculty, Staff and Students Publications

INTRODUCTION: Synovial sarcoma is one of the most common soft tissue sarcomas in children. Guidelines regarding the adequate extent of resection margins and the role of re-resection are lacking. We sought to evaluate the adequate resection margin and the role of re-resection in predicting outcomes in children with synovial sarcomas.

METHODS: A cohort of 36 patients less than 18 years of age at diagnosis who were treated for localized synovial sarcoma at three tertiary pediatric hospitals between January 2004 and December 2020 were included in this study. Patient and tumor demographics, treatment information, and margin status after surgical resection were …

Quantitative Gradient Recalled Echo (Qgre) Mri Enables In Vivo Measurement Of Pre-Atrophic Neurodegeneration In A Mouse Model Of Alzheimer's Disease, Michal R Tomaszewski, Alexander L Sukstanskii, Hyking Haley, Xiangjun Meng, Corin O Miller, Dmitriy A Yablonskiy

2020-Current year OA Pubs

Robust methods are needed for preclinical evaluation of novel Alzheimer Disease (AD) therapies to accelerate drug discovery. Quantitative Gradient Recalled Echo (qGRE) MRI has shown promise to provide insight into neurodegeneration in AD prior to atrophy development in humans, highlighting areas of low neuronal density. In this study a novel qGRE method (20 echoes, TE=2-40ms) is shown to non-invasively measure the longitudinal neuronal loss in the hippocampus of a mouse model of AD tauopathy Tg4510. Tg4510 (n=10) and wild type (WT, n=6) mice underwent MRI (7T field strength) at 3-7 months old. 3D qGRE approach was used to generate brain-specific …

Low-Dose Ondansetron: A Candidate Prospective Precision Medicine To Treat Alcohol Use Disorder Endophenotypes, Bankole Johnson, Hannu Alho, Giovanni Addolorato, Otto Michael Lesch, Jonathan Chick, Lei Liu, Vinzant Schuyler

2020-Current year OA Pubs

BACKGROUND: Alcohol use disorder (AUD) is among the leading causes of morbidity and mortality worldwide, and over 95 million people live with alcohol dependence globally. The estimated heritability of AUD is 50-60 %, and multiple genes are thought to contribute to various endophenotypes of the disease. Previous clinical trials support a precision medicine approach using ondansetron (AD04, a 5-HT3 antagonist) by segregating AUD populations by the bio-genetic endophenotype of specific serotonergic genotypes and the bio-psychosocial endophenotype of the severity of drinking or both. By targeting the modulation of biogenetic signaling within the biopsychosocial context of AUD, low-dose AD04 holds promise …

Utility Of Eosinophil Peroxidase As A Biomarker Of Eosinophilic Inflammation In Asthma, Monica Tang, Kaharu Sumino, Et Al.

2020-Current year OA Pubs

BACKGROUND: The relative utility of eosinophil peroxidase (EPX) and blood and sputum eosinophil counts as disease biomarkers in asthma is uncertain.

OBJECTIVE: We sought to determine the utility of EPX as a biomarker of systemic and airway eosinophilic inflammation in asthma.

METHODS: EPX protein was measured by immunoassay in serum and sputum in 110 healthy controls to establish a normal reference range and in repeated samples of serum and sputum collected during 3 years of observation in 480 participants in the Severe Asthma Research Program 3.

RESULTS: Over 3 years, EPX levels in patients with asthma were higher than normal …

Evaluating The Psychometric Structure Of The Hamilton Rating Scale For Depression Pre- And Post-Treatment In Antidepressant Randomised Trials: Secondary Analysis Of 6843 Individual Participants From 20 Trials, David Byrne, Frank Doyle, Susan Brannick, Robert M Carney, Pim Cuijpers, Alexandra L Dima, Kenneth Freedland, Suzanne Guerin, David Hevey, Bishember Kathuria, Emma Wallace, Fiona Boland

2020-Current year OA Pubs

BACKGROUND: The 17-item Hamilton Rating Scale for Depression (HRSD-17) is the most popular depression measure in antidepressant clinical trials. Prior evidence indicates poor replicability and inconsistent factorial structure. This has not been studied in pooled randomised trial data, nor has a psychometrically optimal model been developed.

AIMS: To examine the psychometric properties of the HRSD-17 for pre-treatment and post-treatment clinical trial data in a large pooled database of antidepressant randomised controlled trial participants, and to determine an optimal abbreviated version.

METHOD: Data for 6843 participants were obtained from the data repository Vivli.org and randomly split into groups for exploratory (n …