Medicine and Health Sciences Commons^™

Effect Of Testosterone Treatment During Puberty In Boys With Klinefelter Syndrome (The Tipy Study): Protocol For A Nationwide Randomised, Double-Blinded, Placebo-Controlled Study, Ida Dyhr Caspersen, Andrés Felipe Østergaard Fritzbøger, Jørgen Holm Petersen, Niels Birkebæk, Ann-Margrethe Rønholt Christensen, Anders Jørgen Schou, Kurt Kristensen, Judith L. Ross, Shanlee Davis, Gary Butler, Sophie Van Rijn, Anders Juul, Lise Aksglaede

Department of Pediatrics Faculty Papers

INTRODUCTION: Klinefelter syndrome (KS) is a genetic condition characterised by the presence of an extra X chromosome in males (47,XXY). KS is associated with various phenotypic characteristics in adult life, including infertility, hypogonadism and increased risk of type II diabetes, cardiovascular disease and osteoporosis. Additionally, individuals with KS often experience mental health challenges and functional impairments that significantly impact their quality of life. Currently, testosterone replacement therapy (TRT) in adolescence is considered the first-line treatment by some physicians for patients with KS and biochemical signs of hypogonadism. However, comprehensive evidence on its effectiveness in preventing typical phenotypic traits associated with …

Inflammation And Gut Barrier Function-Related Genes And Colorectal Cancer Risk In Western European Populations, Hannah B Mandle, Mazda Jenab, Marc J Gunter, Anne Tjønneland, Anja Olsen, Christina C Dahm, Jie Zhang, Pierre-Emmanuel Sugier, Joseph Rothwell, Gianluca Severi, Rudolf Kaaks, Verena A Katzke, Matthias B Schulze, Giovanna Masala, Sabina Sieri, Salvatore Panico, Carlotta Sacerdote, Catalina Bonet, Maria-Jose Sánchez, Pilar Amiano, José María Huerta, Marcela Guevara, Richard Palmqvist, Thyra Löwenmark, Aurora Perez-Cornago, Elisabete Weiderpass, Alicia K Heath, Amanda J Cross, Paolo Vineis, David J Hughes, Veronika Fedirko

Faculty, Staff and Student Publications

Gut barrier dysfunction and related inflammation are known to be associated with the development and progression of colorectal cancer (CRC). We investigated associations of 292 single-nucleotide polymorphisms (SNPs) from 27 genes related to endotoxins/lipopolysaccharide (LPS) sensing and tolerance, mucin synthesis, inflammation, and Crohn's disease with colon and rectal cancer risks. Incident CRC cases (N = 1374; colon = 871, rectum = 503) were matched 1:1 to controls nested within the European Prospective Investigation into Cancer and Nutrition cohort. Previously measured serum concentrations of gut barrier function and inflammation biomarkers (flagellin/LPS-specific immunoglobulins and C-reactive protein [CRP]) were available for a sub-set …

Matrix Metalloproteinases Accelerate Pericellular Matrix Breakdown And Disrupt Mechanotransduction In Osteoarthritis, Jule Nieuwstraten, Rosa Riester, Ulf Krister Hofmann, Farshid Guilak, Marina Danalache

2020-Current year OA Pubs

The pericellular matrix (PCM) is a specialized, narrow matrix surrounding each chondrocyte in articular cartilage, together constituting the chondron - the fundamental metabolic and functional unit of cartilage. The PCM plays a vital role in mediating biomechanical and biochemical signals essential for chondrocyte function. In osteoarthritis (OA), a chronic joint disorder characterized by progressive cartilage degradation, the PCM is one of the earliest sites of catabolic degradation, primarily driven by matrix metalloproteinases (MMPs). This study aims to investigate the functional relationship between PCM degradation and chondrocyte mechanosignaling, with an emphasis on MMP-driven changes in mechanotransduction in osteoarthritic cartilage. Human chondrons …

Precision Phenotyping For Curating Research Cohorts Of Patients With Unexplained Post-Acute Sequelae Of Covid-19, Alaleh Azhir, Jonas Hügel, Jiazi Tian, Jingya Cheng, Ingrid V Bassett, Douglas S Bell, Elmer V Bernstam, Maha R Farhat, Darren W Henderson, Emily S Lau, Michele Morris, Yevgeniy R Semenov, Virginia A Triant, Shyam Visweswaran, Zachary H Strasser, Jeffrey G Klann, Shawn N Murphy, Hossein Estiri

Faculty, Staff and Student Publications

BACKGROUND: Scalable identification of patients with post-acute sequelae of COVID-19 (PASC) is challenging due to a lack of reproducible precision phenotyping algorithms, which has led to suboptimal accuracy, demographic biases, and underestimation of the PASC.

METHODS: In a retrospective case-control study, we developed a precision phenotyping algorithm for identifying cohorts of patients with PASC. We used longitudinal electronic health records data from over 295,000 patients from 14 hospitals and 20 community health centers in Massachusetts. The algorithm employs an attention mechanism to simultaneously exclude sequelae that prior conditions can explain and include infection-associated chronic conditions. We performed independent chart reviews …

Should Proximal Fixation Be At C2 Or C3-C4? An Application Of The Operative Value Index For Elective Posterior Cervical Decompression And Fusion, Advith Sarikonda, D. Mitchell Self, Danyal Quraishi, Ashmal Sami, Emily L. Isch, Steven Glener, Joshua Heller, Srinivas Prasad, Ashwini Sharan, Jack Jallo, Alex R. Vaccaro, James Harrop, Ahilan Sivaganesan

Department of Neurosurgery Faculty Papers

BACKGROUND: There is clinical equipoise regarding the ideal upper instrumented vertebrae (UIV) for elective posterior cervical decompression and fusion (PCDF). Instrumentation may be performed at the axial C2 level, or at the subaxial C3/C4 vertebrae. To our knowledge, a true "value" (outcomes per dollar spent) comparison axial versus subaxial UIV for PCDF has never been performed.

METHODS: We retrospectively identified 275 long-segment (≥3-levels fused) PCDFs with available Neck Disability Index (NDI) scores at baseline and at 3 months postoperatively. C2 UIV (n = 67) was compared to C3/C4 UIV (n = 208). Time-driven activity-based costing was applied to identify the …

Tunneling Nanotube-Like Structures Regulate Distant Cellular Interactions During Heart Formation, Lianjie Miao, Yangyang Lu, Anika Nusrat, Guizhen Fan, Shaohua Zhang, Luqi Zhao, Chia-Ling Wu, Hongyan Guo, Trang Le Nu Huyen, Yi Zheng, Zhen-Chuan Fan, Weinian Shou, Robert J Schwartz, Yu Liu, Ashok Kumar, Haixin Sui, Irina I Serysheva, Alan R Burns, Leo Q Wan, Bin Zhou, Sylvia M Evans, Mingfu Wu

Faculty, Staff and Student Publications

In the developing mammalian heart, the endocardium and the myocardium are separated by so-called cardiac jelly. Communication between the endocardium and the myocardium is essential for cardiac morphogenesis. How membrane-localized receptors and ligands achieve interaction across the cardiac jelly is not understood. Working in developing mouse cardiac morphogenesis models, we used a variety of cellular, imaging, and genetic approaches to elucidate this question. We found that myocardium and endocardium interacted directly through microstructures termed tunneling nanotube-like structures (TNTLs). TNTLs extended from cardiomyocytes (CMs) to contact endocardial cells (ECs) directly. TNTLs transported cytoplasmic proteins, transduced signals between CMs and ECs, and …

Preoperative Brain Volume Loss Is Associated With Postoperative Delirium In Advanced Heart Failure Patients Supported By Left Ventricular Assist Device, Iván Murrieta-Álvarez, Jacob P Scioscia, José M Benítez-Salazar, Jason Uwaeze, Zicheng Xu, Guangyao Zheng, Shiyi Li, Vladimir Braverman, Carl P Walther, Alexis E Shafii, Camila Hochman-Mendez, Todd K Rosengart, Kenneth K Liao, Nandan K Mondal

Faculty, Staff and Students Publications

Delirium is a common neurological complication in patients with advanced heart failure (ADHF) following left ventricular assist device (LVAD) implantation, significantly impacting recovery. This study aimed to analyze non-contrast computed tomography (CT) scans of the brain in ADHF patients undergoing LVAD implantation to determine the association between pre-existing brain atrophy and postoperative delirium. A study involving 166 ADHF patients was conducted from March 2020 to July 2023. Non-contrast CT scans were analyzed using advanced quantitative neuroimaging techniques before implantation. The primary marker assessed was the lateral ventricle fraction (LVF), with secondary markers including cortical gray matter fraction (cGMF), white matter …

Exploration Of Working Memory Retrieval Stage For Mild Cognitive Impairment: Time-Varying Causality Analysis Of Electroencephalogram Based On Dynamic Brain Networks, Yi Jiang, Zhiwei Guo, Xiaobo Zhou, Ning Jiang, Jiayuan He

Faculty, Staff and Student Publications

Background: Mild Cognitive Impairment (MCI) is an intermediate stage between the expected cognitive decline of normal aging and Alzheimer's disease (AD). Its management is crucial for it helps intervene and slow the progression of cognitive decline to AD. However, the understanding of the MCI mechanism is not completely clear. As working memory (WM) damage is a common symptom of MCI, this study focused on the core stage of WM, i.e., the memory retrieval stage, to investigate information processing and the causality relationships among brain regions based on electroencephalogram (EEG) signals.

Method: 21 MCI and 20 normal cognitive control (NC) participants …

Developing A Novel Index For Individual-Level Social Determinants And Cardiovascular Diseases In The Coronary Artery Risk Development In Young Adults (Cardia) Study, Tao Gao, Yinan Zheng, Brian Joyce, Lei Liu, Lili Liu, Catarina Kiefe, Sarah Forrester, Bing Yu, Ankeet Bhatt, Penny Gordon-Larsen, Donald Lloyd-Jones, Kai Zhang, Lifang Hou

Faculty, Staff and Student Publications

Background: Social determinants of health (SDH) have been found to contribute to cardiovascular risk and the development of cardiovascular disease (CVD). However, few studies have examined early-life exposure to SDH and the combined effect of multiple SDH measures on CVD. There is an urgent need to develop an SDH index for use in practice and clinical settings.

Methods: A total of 3189 participants from the CARDIA Study who had chest CT scans at the year-25 (Y25) visit were included in this study. Personal and parental SDH measures, including education, occupation, income, financial strain, and childhood family environment, were obtained through …

Youtube User Traffic To Paired Epilepsy Education Videos In English And Spanish: Comparative Study., Luna Kimahri Varela, Stephanie Horton, Ahmed Abdelmoity, Jean-Baptist Lepichon, Mark A. Hoffman

Manuscripts, Articles, Book Chapters and Other Papers

BACKGROUND: Effectively managing epilepsy in children necessitates the active engagement of parents, a factor that is reliant on their understanding of this neurological disorder. Widely available, high-quality, patient-focused, bilingual videos describing topics important for managing epilepsy are limited. YouTube Analytics is a helpful resource for gaining insights into how users of differing backgrounds consume video content.

OBJECTIVE: This study analyzes traffic to paired educational videos of English and Spanish versions of the same content. By examining the use patterns and preferences of individuals seeking information in different languages, we gained valuable insights into how language influences the use of clinical …

Efficacy And Safety Of Venetoclax Plus Azacitidine For Patients With Treatment-Naive High-Risk Myelodysplastic Syndromes, Jacqueline S Garcia, Uwe Platzbecker, Olatoyosi Odenike, Shaun Fleming, Chun Yew Fong, Uma Borate, Meagan A Jacoby, Daniel Nowak, Maria R Baer, Pierre Peterlin, Brenda Chyla, Huipei Wang, Grace Ku, David Hoffman, Jalaja Potluri, Guillermo Garcia-Manero

Faculty, Staff and Student Publications

Outcomes are poor in patients with higher-risk myelodysplastic syndromes (HR MDS) and frontline treatment options are limited. This phase 1b study investigated safety and efficacy of venetoclax, a selective B-cell lymphoma 2 inhibitor, at the recommended phase 2 dose (RP2D; 400 mg for 14 days per 28-day cycle), in combination with azacitidine (75 mg/m2 for 7 days per 28-day cycle) for treatment-naive HR MDS. Safety was the primary outcome, and complete remission (CR) rate was the primary efficacy outcome. Secondary outcomes included rates of modified overall response (mOR), hematologic improvement (HI), overall survival (OS), and time to next treatment (TTNT). …

Efficacy And Safety Of Venetoclax Plus Azacitidine For Patients With Treatment-Naive High-Risk Myelodysplastic Syndromes, Jacqueline S Garcia, Uwe Platzbecker, Olatoyosi Odenike, Shaun Fleming, Chun Yew Fong, Uma Borate, Meagan A Jacoby, Daniel Nowak, Maria R Baer, Pierre Peterlin, Brenda Chyla, Huipei Wang, Grace Ku, David Hoffman, Jalaja Potluri, Guillermo Garcia-Manero

Faculty, Staff and Student Publications

Outcomes are poor in patients with higher-risk myelodysplastic syndromes (HR MDS) and frontline treatment options are limited. This phase 1b study investigated safety and efficacy of venetoclax, a selective B-cell lymphoma 2 inhibitor, at the recommended phase 2 dose (RP2D; 400 mg for 14 days per 28-day cycle), in combination with azacitidine (75 mg/m2 for 7 days per 28-day cycle) for treatment-naive HR MDS. Safety was the primary outcome, and complete remission (CR) rate was the primary efficacy outcome. Secondary outcomes included rates of modified overall response (mOR), hematologic improvement (HI), overall survival (OS), and time to next treatment (TTNT). …

Cranial Radiation Disrupts Dopaminergic Signaling And Connectivity In The Mammalian Brain, Die Zhang, Riya Thomas, Thanh Thai Lam, Ines Veselinovic, David R Grosshans

Faculty, Staff and Student Publications

Cognitive impairment is a common and challenging side effect of cranial radiation therapy for brain tumors, though its precise mechanisms remain unclear. The mesocortical dopaminergic pathway, known to play a key role in cognitive function, is implicated in several neuropsychiatric disorders, yet its involvement in radiation-induced cognitive dysfunction is unexplored. Here, with using in vivo multi-electrode array recordings of both anesthetized and free-moving rats to monitor the firing activities of dopamine neurons in the ventral tegmental area (VTA) and local field potentials in both the prefrontal cortex (PFC) and VTA, as well as the immunofluorescence assays and western blotting, we …

Structure-Guided Design Of Partial Agonists At An Opioid Receptor, Balazs R Varga, Sarah M Bernhard, Amal El Daibani, Jhoan Aguilar, Kevin Appourchaux, Alexa Kouvelis, Amynah Pradhan, Susruta Majumdar, Tao Che, Et Al.

2020-Current year OA Pubs

Chronic pain and opioid overdose deaths highlight the need for non-addictive analgesics with novel mechanisms. The δ opioid receptor (δOR) is a promising target, as it lacks the respiratory depression associated with µ opioid receptor (µOR) agonists. However, early δOR full agonists caused seizures, limiting their clinical use. Partial δOR agonists may offer more controlled receptor activation than full agonists, but their development has been hindered by uncertainty regarding the molecular mechanism of partial agonism. Here we show that C6-Quino, a bitopic ligand developed through structure-based design, acts as a selective δOR partial agonist. Functional studies reveal that C6-Quino shows …

Developing A Novel Index For Individual-Level Social Determinants And Cardiovascular Diseases In The Coronary Artery Risk Development In Young Adults (Cardia) Study, Tao Gao, Yinan Zheng, Brian Joyce, Lei Liu, Lili Liu, Catarina Kiefe, Sarah Forrester, Bing Yu, Ankeet Bhatt, Penny Gordon-Larsen, Donald Lloyd-Jones, Kai Zhang, Lifang Hou

2020-Current year OA Pubs

BACKGROUND: Social determinants of health (SDH) have been found to contribute to cardiovascular risk and the development of cardiovascular disease (CVD). However, few studies have examined early-life exposure to SDH and the combined effect of multiple SDH measures on CVD. There is an urgent need to develop an SDH index for use in practice and clinical settings.

METHODS: A total of 3189 participants from the CARDIA Study who had chest CT scans at the year-25 (Y25) visit were included in this study. Personal and parental SDH measures, including education, occupation, income, financial strain, and childhood family environment, were obtained through …

Respiratory Muscle Training Reduces Painful Swallowing And Opioid Use During Radiation Therapy For Head And Neck Cancer: A Matched Pair Analysis, Andrew D. Ray, Chi-Chen Hong, Nicolas F. Schlecht, Han Yu, Kristopher Attwood, Kent L. Nastiuk, Bryan A. Spinelli, Ann Marie Flores, Hillary Jacobson, Julia Fulfaro, M. Jeffrey Mador, Austin J. Iovoli, Mark K. Farrugia, Anurag K. Singh

Department of Physical Therapy Faculty Papers

BACKGROUND: Patients with head and neck cancer (HNC) receiving radiation therapy (RT) are at increased risk for symptoms of oral mucositis (OM), opioid use, and declines in physical function, outcomes that contribute to increased morbidity and mortality. The study objective was to determine the effects of respiratory muscle training (RMT) on OM and opioid use, as well as functional performance in patients with HNC receiving RT with or without concurrent chemotherapy (CCRT).

METHODS: Patients aged ≥ 18 years of age with stage I to IV HNC being treated with RT or CCRT receiving a home-based respiratory muscle training (RMT) (n …

Identifying Distinct Prognostic And Predictive Contributions Of Tumor Epithelium Versus Tumor Microenvironment In Colorectal Cancer, Mingli Yang, Moh'd Khushman, Et Al.

2020-Current year OA Pubs

BACKGROUND: Accumulating evidence has suggested that cancer progression and therapeutic response depend on both tumor epithelium (EPI) and tumor microenvironment (TME). However, the dependency of clinical outcomes on the tumor EPI vs. the TME has neither been clearly defined nor quantified.

METHODS: We classified 2373 colorectal cancer (CRC) tumors into the consensus molecular subtypes (CMS1-4) and generated the 10-gene TME

RESULTS: The TME

CONCLUSIONS: Here we identified a pair of new, distinct 10-gene signatures (the EPI

Associations Of Sociodemographic, Clinical Factors And Hla-B Alleles With Enthesitis And Peripheral Arthritis In Patients With Ankylosing Spondylitis, Benjamin Sornrung Naovarat, Lianne Gensler, Michael Ward, Mark Hwang, Amirali Tahanan, Mohammad Hossein Rahbar, Mariko Ishimori, Minjae Lee, Matthew A Brown, Michael H Weisman, John D Reveille

Faculty, Staff and Student Publications

Objectives: Factors associated with peripheral arthritis and enthesitis, especially Achilles tendonitis and plantar fasciitis, were examined in a longitudinal cohort of 1075 patients with ankylosing spondylitis (AS) (also known as radiographic axial spondyloarthritis).

Methods: Patients were derived from the Prospective Study of Outcomes in Ankylosing Spondylitis cohort. Disease activity and functional indices, as well as physical examination and medications used, were measured at every study visit. Univariable and multivariable analyses of the association of peripheral arthritis and enthesitis with clinical, sociodemographic factors were performed. Human leucocyte antigen (HLA)-B alleles were analysed by single-stranded conformational polymorphism analysis.

Results: Those with peripheral …

The Role Of Electrophysiologic Study In Device Selection For Leadless Atrial Pacing, Joshua R Hirsch, Jordan M Gales, Irakli Giorgberidze, Hamid Afshar

The Texas Heart Institute Journal

The AVEIR DR (Abbott Medical) was the first dual-chamber leadless pacing system approved by the US Food and Drug Administration. Many patients with sinus node dysfunction have physiologically normal atrioventricular conduction, so an atrial-only pacing system may be appropriate for them. Three patients with symptomatic sinus node dysfunction underwent device implantation with electrophysiologic study, including incremental atrial pacing until loss of 1:1 atrioventricular conduction (atrioventricular Wenckebach cycle length) and His-ventricular interval measurement. If the atrioventricular Wenckebach cycle length was no more than 400 milliseconds and the His-ventricular interval measurement was no more than 55 milliseconds, single-chamber atrial implantation was deemed …

Factors Influencing Cyanoacrylate Tissue Adhesive Outcomes For Corneal Thinning And Perforation, Anjali Om, Anjali Badami, Yuqing Wang, Xiangqin Cui, Soroosh Behshad, Joung Kim, Praneetha Thulasi

2020-Current year OA Pubs

No abstract provided.

Comprehensive Cross-Sectional And Longitudinal Comparisons Of Plasma Glial Fibrillary Acidic Protein And Neurofilament Light Across Ftd Spectrum Disorders, Udit Sheth, Nupur Ghoshal, Et Al.

2020-Current year OA Pubs

BACKGROUND: Therapeutic development for frontotemporal dementia (FTD) is hindered by the lack of biomarkers that inform susceptibility/risk, prognosis, and the underlying causative pathology. Blood glial fibrillary acidic protein (GFAP) has garnered attention as a FTD biomarker. However, investigations of GFAP in FTD have been hampered by symptomatic and histopathologic heterogeneity and small cohort sizes contributing to inconsistent findings. Therefore, we evaluated plasma GFAP as a FTD biomarker and compared its performance to that of neurofilament light (NfL) protein, a leading FTD biomarker.

METHODS: We availed ARTFL LEFFTDS Longitudinal Frontotemporal Lobar Degeneration (ALLFTD) study resources to conduct a comprehensive cross-sectional and …

Exploratory Co-Design On Electronic Health Record Nursing Summaries: Case Study, Suhyun Park, Jenna L Marquard, Robin R Austin, Christie L Martin, David S Pieczkiewicz, Connie W Delaney

The Brown Foundation: Institute of Molecular Medicine

Background: Although electronic health record nursing summaries aim to provide a concise overview of patient data, they often fall short of meeting nurses' information needs, leading to underutilization. This gap arises from a lack of involvement of nurses in the design of health information technologies.

Objective: The purpose of this exploratory co-design case study was to solicit insights from nurses regarding nursing summary design considerations, including key information types and the preferred design prototype.

Methods: We recruited clinical nurses (N=33) from 7 inpatient units at a university hospital in the Midwestern United States using a purposive sampling method. We used …

Treatment Patterns And Outcomes In Follicular Lymphoma With Pod24: An Analysis From The Leo Consortium, Jonathan R Day, Brad S Kahl, Et Al.

2020-Current year OA Pubs

Progression of disease within 24 months of initial immunochemotherapy (POD24) is a negative prognostic factor for patients with follicular lymphoma (FL). There is no standard treatment after POD24. Assembling an academic-based cohort from the Lymphoma Epidemiology of Outcomes Consortium for Real World Evidence, we evaluated patterns of care and outcomes for 220 patients with FL with POD24 and retained FL histology. Therapy after POD24 was heterogeneous, with no treatment category accounting for >25% of the total. Among patients initially treated with bendamustine-rituximab, rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone (R-CHOP) was the predominant second-line choice (48%). Among patients initially treated with R-CHOP, …

Vdac2 And Bak Scarcity In Liver Mitochondria Enables Targeting Hepatocarcinoma While Sparing Hepatocytes, Shamim Naghdi, Piyush Mishra, Soumya S. Roy, David Weaver, Ludivine Walter, Erika Davies, Anil N. Antony, Xuena Lin, Gisela Moehren, Mark A. Feitelson, Christopher A. Reed, Tullia Lindsten, Craig B. Thompson, Hien T. Dang, Jan B. Hoek, Erik S. Knudsen, György Hajnóczky

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Differences between normal tissues and invading tumors that allow tumor targeting while saving normal tissue are much sought after. Here we show that scarcity of VDAC2, and the consequent lack of Bak recruitment to mitochondria, renders hepatocyte mitochondria resistant to permeabilization by truncated Bid (tBid), a Bcl-2 Homology 3 (BH3)-only, Bcl-2 family protein. Increased VDAC2 and Bak is found in most human liver cancers and mitochondria from tumors and hepatic cancer cell lines exhibit VDAC2- and Bak-dependent tBid sensitivity. Exploring potential therapeutic targeting, we find that combinations of activators of the tBid pathway with inhibitors of the Bcl-2 family proteins …

Metabolic Signatures In Adipose Tissue Linking Lipophilic Persistent Organic Pollutant Mixtures To Blood Pressure Five Years After Bariatric Surgery Among Adolescents, Shudi Pan, Zhenjiang Li, Douglas I Walker, Brittney O Baumert, Hongxu Wang, Jesse A Goodrich, Sarah Rock, Thomas H Inge, Todd M Jenkins, Stephanie Sisley, Scott M Bartell, Stavra Xanthakos, Xiangping Lin, Brooklynn Mcneil, Anna R Robuck, Catherine E Mullins, Michele A La Merill, Erika Garcia, Max T Aung, Sandrah P Eckel, Rob Mcconnell, David V Conti, Justin R Ryder, Lida Chatzi

Faculty, Staff and Students Publications

Persistent organic pollutants (POPs) are lipophilic environmental contaminants accumulated in the adipose tissue. Weight loss interventions, such as bariatric surgery, can mobilize POPs from adipose tissue into the bloodstream. We hypothesized that this mobilization could contribute to increases in blood pressure among 57 adolescents with severe obesity undergoing bariatric surgery. POPs and metabolic features were measured from visceral adipose tissue collected during surgery using gas and liquid chromatography, coupled with high-resolution mass spectrometry. Blood pressure was assessed at baseline, 6 months, and 5 years post-surgery. We used quantile g-computation to estimate associations of POP mixtures with blood pressure changes. With …

Simvastatin And Rifaximin In Decompensated Cirrhosis: A Randomized Clinical Trial, Elisa Pose, César Jiménez, Giacomo Zaccherini, Daniela Campion, Salvatore Piano, Frank Erhard Uschner, Koos De Wit, Olivier Roux, Kohilan Gananandan, Wim Laleman, Cristina Solé, Sonia Alonso, Berta Cuyàs, Xavier Ariza, Adrià Juanola, Ann T Ma, Laura Napoleone, Jordi Gratacós-Ginès, Marta Tonon, Enrico Pompili, Jordi Sánchez-Delgado, Andrew S Allegretti, Manuel Morales-Ruiz, Marta Carol, Martina Pérez-Guasch, Núria Fabrellas, Judit Pich, Claudia Martell, María Joyera, Gemma Domenech, José Ríos, Ferrán Torres, Miquel Serra-Burriel, Rubén Hernáez, Elsa Solà, Isabel Graupera, Hugh Watson, Germán Soriano, Rafael Bañares, Rajeshwar P Mookerjee, Claire Francoz, Ulrich Beuers, Jonel Trebicka, Paolo Angeli, Carlo Alessandria, Paolo Caraceni, Víctor M Vargas, Juan G Abraldes, Patrick S Kamath, Pere Ginès

Faculty, Staff and Students Publications

Importance: There are no useful treatments to prevent the development of severe complications of liver cirrhosis. Simvastatin and rifaximin have shown beneficial effects in liver cirrhosis.

Objective: To assess whether simvastatin combined with rifaximin improves outcomes in patients with decompensated cirrhosis.

Design, setting, and participants: Double-blind, placebo-controlled, phase 3 trial conducted among patients with decompensated cirrhosis in 14 European hospitals between January 2019 and December 2022. The last date of follow-up was December 2022.

Interventions: Patients were randomly assigned to receive simvastatin, 20 mg/d, plus rifaximin, 1200 mg/d (n = 117), or identical-appearing placebo (n = 120) for 12 months …

Hematopoietic Cell Transplant Compared With Standard Care In Adolescents And Young Adults With Sickle Cell Disease, Mark C Walters, Mary Eapen, Yiwen Liu, Fuad El Rassi, Edmund K Waller, John E Levine, John J Strouse, Joseph H Antin, Suhag H Parikh, Nitya Bakshi, Carlton Dampier, Jennifer J Jaroscak, Shayla Bergmann, Trisha Wong, Vamsi Kota, Betty Pace, Lazaros J Lekakis, Premal Lulla, Robert S Nickel, Kimberly A Kasow, Uday Popat, Wally Smith, Lolie Yu, Nancy Difronzo, Nancy Geller, Naynesh Kamani, Elizabeth S Klings, Kathryn Hassell, Adam Mendizabal, Keith Sullivan, Donna Neuberg, Lakshmanan Krishnamurti

Faculty, Staff and Students Publications

Disease-modifying therapies are standard of care (SOC) for sickle cell disease (SCD), but hematopoietic cell transplantation (HCT) has curative potential. We compared outcomes prospectively through 2 years after biologic assignment to a donor or no donor (SOC) arm based on the availability of an HLA-matched sibling or unrelated donor (BMT CTN 1503). A donor search was commenced after eligibility confirmation. The primary end point was a comparison of survival between the treatment arms 2 years after biologic assignment. Power calculations required 60 participants in the donor arm and 140 in the no donor arm to determine if early transplant-related mortality …

Ibrutinib For Therapy Of Steroid-Refractory Chronic Graft-Versus-Host Disease: A Multicenter Real-World Analysis, Joseph Pidala, Iskra Pusic, Et Al.

2020-Current year OA Pubs

To examine the activity of ibrutinib in steroid-refractory chronic graft-versus-host disease (SR-cGVHD) after the US Food and Drug Administration approval, we conducted a multicenter retrospective study. Data were standardly collected (N = 270 from 19 centers). Involved organs included skin (75%), eye (61%), mouth (54%), joint/fascia (47%), gastrointestinal (GI) (26%), lung (27%), liver (19%), genital (7%), and others (4.4%). The National Institutes of Health (NIH) severity was mild in 5.7%, moderate 42%, and severe 53%. Thirty-nine percent had overlap subtype. Karnofsky performance status (KPS) was ≥80% in 72%. The median prednisone was 0.21 mg/kg (0-2.27). Ibrutinib was started at a …

Recessive Genetic Contribution To Congenital Heart Disease In 5,424 Probands, Weilai Dong, Sheng Chih Jin, Et Al.

2020-Current year OA Pubs

Variants with large effect contribute to congenital heart disease (CHD). To date, recessive genotypes (RGs) have commonly been implicated through anecdotal ascertainment of consanguineous families and candidate gene-based analysis; the recessive contribution to the broad range of CHD phenotypes has been limited. We analyzed whole exome sequences of 5,424 CHD probands. Rare damaging RGs were estimated to contribute to at least 2.2% of CHD, with greater enrichment among laterality phenotypes (5.4%) versus other subsets (1.4%). Among 108 curated human recessive CHD genes, there were 66 RGs, with 54 in 11 genes with >1 RG, 12 genes with 1 RG, and …

Improved Patient-Reported Outcomes With Post-Transplant Cyclophosphamide: A Quality-Of-Life Evaluation And 2-Year Outcomes Of Bmt Ctn 1703., Shernan G Holtan, Javier Bolaños-Meade, Monzr M Al Malki, Juan Wu, Carrie L Kitko, Ran Reshef, Andrew R Rezvani, Brian C Shaffer, Melhem M Solh, Janny M Yao, Lyndsey Runaas, Hany Elmariah, Karilyn T Larkin, Najla El Jurdi, Mahasweta Gooptu, Alison W Loren, Aric C Hall, Amin M Alousi, Omer Jamy, William Clark, Leslie Kean, Ami S Bhatt, Miguel-Angel Perales, Kristy Applegate, Yvonne Adeduni Efebera, Eric Leifer, Richard J Jones, Mary M Horowitz, Deborah Mattila, Wael Saber, Mehdi Hamadani, Michael J Martens

Oncology Articles

The BMT CTN 1703 phase III trial confirmed that graft-versus-host disease (GVHD) prophylaxis with post-transplantation cyclophosphamide (PTCy), tacrolimus (Tac), and mycophenolate mofetil (MMF) results in superior GVHD-free, relapse-free survival (GRFS) compared with Tac/methotrexate (MTX) prophylaxis. This companion study assesses the effect of these regimens on patient-reported outcomes (PROs). Using the Lee Chronic GVHD Symptom Score and PROMIS subscales (physical function, GI symptoms, social role satisfaction) as primary end points and hemorrhagic cystitis symptoms and Lee subscales as secondary end points, responses from English and Spanish speakers were analyzed at baseline and days 100, 180, and 365 after transplant. PRO scores …