Digital Commons Network^™

Natural History Of Tango2 Deficiency Disorder: Baseline Assessment Of 73 Patients, Christina Y Miyake, Erica J Lay, Claudia Soler-Alfonso, Kevin E Glinton, Kimberly M Houck, Mustafa Tosur, Nancy E Moran, Sara B Stephens, Fernando Scaglia, Taylor S Howard, Jeffrey J Kim, Tam Dam Pham, Santiago O Valdes, Na Li, Chaya N Murali, Lilei Zhang, Maina Kava, Deane Yim, Cheyenne Beach, Gregory Webster, Leonardo Liberman, Christopher M Janson, Prince J Kannankeril, Samantha Baxter, Moriel Singer-Berk, Jordan Wood, Samuel J Mackenzie, Michael Sacher, Lina Ghaloul-Gonzalez, Claudia Pedroza, Shaine A Morris, Saad A Ehsan, Mahshid S Azamian, Seema R Lalani

Faculty, Staff and Students Publications

PURPOSE: TANGO2 deficiency disorder (TDD), an autosomal recessive disease first reported in 2016, is characterized by neurodevelopmental delay, seizures, intermittent ataxia, hypothyroidism, and life-threatening metabolic and cardiac crises. The purpose of this study was to define the natural history of TDD.

METHODS: Data were collected from an ongoing natural history study of patients with TDD enrolled between February 2019 and May 2022. Data were obtained through phone or video based parent interviews and medical record review.

RESULTS: Data were collected from 73 patients (59% male) from 57 unrelated families living in 16 different countries. The median age of participants at …

Use Of Berlin Excor Cannulas In Both Venovenous And Venoarterial Central Extracorporeal Membrane Oxygenation Configurations Overcomes The Problem Of Cannula Instability While Bridging Infants And Young Children To Lung Transplant, N Adam Stephens, Corey A Chartan, Maria C Gazzaneo, James A Thomas, Shailendra Das, George B Mallory, Ernestina Melicoff, Adam M Vogel, Amanda Parker, Emily Hermes, Jeffrey S Heinle, E Dean Mckenzie, Ryan D Coleman

Faculty, Staff and Students Publications

OBJECTIVES: Infants and young children awaiting lung transplantation present challenges that often preclude successful extracorporeal membrane oxygenation support as a bridge to transplantation. Instability of neck cannulas often results in the need for intubation, mechanical ventilation, and muscle relaxation creating a worse transplant candidate. With the use of Berlin Heart EXCOR cannulas (Berlin Heart, Inc) in both venoarterial and venovenous central cannulation configurations, 5 pediatric patients were successfully bridged to lung transplant.

METHODS: We performed a single-center retrospective case review of central extracorporeal membrane oxygenation cannulation used as a bridge to lung transplantation cases performed at Texas Children's Hospital between …

Interstitial Lung Disease In Veterans: Leveraging Big Data To Bridge Evidence And Practice Gaps, Bhavika Kaul, Laura A Petersen, Ivan O Rosas, Joyce S Lee, Fernando J Martinez, Venkata D Bandi, Drew A Helmer, Paul J Wolters, Harold R Collard, Mary A Whooley

Faculty, Staff and Students Publications

No abstract provided.

Paving The Road For Chimeric Antigen Receptor T Cells: American Society For Transplantation And Cellular Therapy 80/20 Task Force Consensus On Challenges And Solutions To Improving Efficiency Of Clinical Center Certification And Maintenance Of Operations For Commercially Approved Immune Effector Cell Therapies, Sarah Nikiforow, Matthew J Frigault, Noelle V Frey, Rebecca A Gardner, Krishna V Komanduri, Miguel-Angel Perales, Partow Kebriaei, Phyllis Irene Warkentin, Marcelo Pasquini, Joy Lynn Aho, Bruce L Levine, Helen E Heslop, Tracey L Hlucky, Karen Habucky, Mecide Gharibo, Madan Jagasia, Frederick L Locke

Faculty, Staff and Students Publications

As the number and type of regulatory authority-approved cellular therapies grow, clinical treatment centers face a heavy burden of duplicative documentation around initial qualification, ongoing auditing, and reporting, with overlapping requirements from each manufacturer to ensure safe use of their specific product, which in the United States are stipulated under individual Food and Drug Administration (FDA) Biologic License Applications. The American Society for Transplantation and Cellular Therapy (ASTCT) convened the 80/20 Task Force to consider challenges and potential solutions to these issues. The Task Force proposed that 80% of manufacturers' requirements for onboarding and ongoing operations of commercially available products …

European Society Of Paediatric Radiology Artificial Intelligence Taskforce: A New Taskforce For The Digital Age, Lene Bjerke Laborie, Jaishree Naidoo, Erika Pace, Pierluigi Ciet, Christine Eade, Matthias W Wagner, Thierry A G M Huisman, Susan C Shelmerdine

Faculty, Staff and Students Publications

A new task force dedicated to artificial intelligence (AI) with respect to paediatric radiology was created in 2021 at the International Paediatric Radiology (IPR) meeting in Rome, Italy (a joint society meeting by the European Society of Pediatric Radiology [ESPR] and the Society for Pediatric Radiology [SPR]). The concept of a separate task force dedicated to AI was borne from an ESPR-led international survey of health care professionals' opinions, expectations and concerns regarding AI integration within children's imaging departments. In this survey, the majority (> 80%) of ESPR respondents supported the creation of a task force and helped define our …

Lobar Pneumonia Presenting As Fever, Headaches, And A Negative Chest Radiograph, David R Rendon, Jason Shiau, Stephanie V Sherman

Faculty, Staff and Students Publications

No abstract provided.

Impact Of Covid-19 On Outcomes Of Patients Hospitalized With Stemi: A Nationwide Propensity-Matched Analysis, Akshay Goel, Aaqib H Malik, Dhrubajyoti Bandyopadhyay, Ameesh Isath, Rahul Gupta, Adrija Hajra, Rishi Shrivastav, Salim S Virani, Gregg C Fonarow, Carl J Lavie, Srihari S Naidu

Faculty, Staff and Students Publications

Patients with ST-segment elevation myocardial infarction (STEMI) and concurrent coronavirus disease 2019 (COVID-19) have been reported to have poor outcomes. However, previous studies are small and limited. The National Inpatient Sample database for the year 2020 was queried to identify all adult hospitalizations with a primary diagnosis of STEMI, with and without concurrent COVID-19. A 1:1 propensity score matching was performed. A total of 159,890 hospitalizations with a primary diagnosis of STEMI were identified. Of these, 2210 (1.38%) had concurrent COVID-19. After propensity matching, STEMI patients with concurrent COVID-19 had a significantly higher mortality (17.8% vs 9.1%, OR 1.96, P< 0.001), lower likelihood to receive same-day percutaneous coronary intervention (PCI) (63.6% vs 70.6%, P = 0.019), with a trend towards lower overall PCI (74.9% vs 80.2%, P = 0.057) and significantly lower coronary artery bypass grafting) (3.0% vs 6.8%, P = 0.008) prior to discharge, compared with STEMI patients without COVID-19. The prevalence of cardiogenic shock, need for mechanical circulatory support, extracorporeal membrane oxygenation, cardiac arrest, acute kidney injury (AKI), dialysis, major bleeding and stroke were not significantly different between the groups. COVID-19-positive STEMI patients who received same-day PCI had significantly lower odds of in-hospital mortality (adjusted OR 0.42, 95% CI 0.20-0.85, P = 0.017). STEMI patients with concurrent COVID-19 infection had a significantly higher (almost 2 times) in-hospital mortality, and lower likelihood of receiving same-day PCI, overall (any-day) PCI, and CABG during their admission, compared with STEMI patients without COVID-19.

The Risk Of Hepatocellular Carcinoma In Entecavir Versus Tenofovir Treated Us Cohort With Chronic Hepatitis B Virus, Jennifer R Kramer, Peter A Richardson, Hyunseok Kim, Yao-Chun Hsu, Fasiha Kanwal, Hashem B El-Serag

Faculty, Staff and Students Publications

The comparative effectiveness of tenofovir (TDF) versus entecavir (ETV) in reducing the risk of hepatocellular carcinoma (HCC) in patients with chronic hepatitis B (HBV) remains unclear. Data from a retrospective Korean cohort study published by Choi et al. initially suggested lower than expected incidence of HCC in patients on long-term TDF. However, additional studies from Korea did not show a statistically significant difference in HCC incidence rate between TDF and ETV groups, and subsequent studies reported mixed results ranging from no association or a slight advantage for TDF⁴. Most of these studies examined Asian patients from Korea, Taiwan, …

Pilot Clinical Trial Of Macimorelin To Assess Safety And Efficacy In Patients With Cancer Cachexia, Megan Herodes, Lindsey J Anderson, Samuel Shober, Ellen A Schur, Solomon A Graf, Nicola Ammer, Ramiro Salas, Marco Marcelli, Jose M Garcia

Faculty, Staff and Students Publications

BACKGROUND: Cancer cachexia is associated with reduced body weight, appetite and quality of life (QOL) with no approved treatments. Growth hormone secretagogues like macimorelin have potential to mitigate these effects.

METHODS: This pilot study assessed the safety and efficacy of macimorelin for 1 week. Efficacy was defined a priori as 1-week change in body weight (≥0.8 kg), plasma insulin-like growth factor (IGF)-1 (≥50 ng/mL) or QOL (≥15%). Secondary outcomes included food intake, appetite, functional performance, energy expenditure and safety laboratory parameters. Patients with cancer cachexia were randomized to 0.5 or 1.0 mg/kg macimorelin or placebo; outcomes were assessed non-parametrically.

RESULTS: …

Commentary: Through Thick And Thin, Jonathan C Hong, Joseph S Coselli

Faculty, Staff and Students Publications

No abstract provided.

Reclassification Of Pre-Heart Failure Stages Using Cardiac Biomarkers: The Aric Study, Xiaoming Jia, Mahmoud Al Rifai, Chiadi E Ndumele, Salim S Virani, James A De Lemos, Emmanuel Lee, Amil M Shah, Justin B Echouffo-Tcheugui, Biykem Bozkurt, Ron Hoogeveen, Elizabeth Selvin, Christie M Ballantyne, Vijay Nambi

Faculty, Staff and Students Publications

BACKGROUND: The recent heart failure (HF) guideline recommends the inclusion of cardiac biomarkers in defining Stage B HF.

OBJECTIVES: The authors evaluated the impact of incorporating cardiac biomarkers to reclassify HF in 5,324 participants (mean age: 75.8 years) without prevalent HF enrolled in the ARIC (Atherosclerosis Risk In Communities) study and assessed prognosis of Stage B using cardiac biomarkers.

METHODS: Using N-terminal pro-B-type natriuretic peptide (/mL or ≥125 pg/mL), high-sensitivity troponin T (/L or ≥14 ng/L), and abnormal cardiac structure/function by echocardiography, individuals were classified as Stage A

RESULTS: Overall, 4,326 (81.3%) individuals were classified as Stage B

CONCLUSIONS: Incorporating …

Naive T Cells Inhibit The Outgrowth Of Intractable Antigen-Activated Memory T Cells: Implications For T-Cell Immunotherapy, Sandhya Sharma, Mae Woods, Naren U Mehta, Tim Sauer, Kathan S Parikh, Michael Schmuck-Henneresse, Huimin Zhang, Birju Mehta, Malcolm K Brenner, Helen E Heslop, Cliona M Rooney

Faculty, Staff and Students Publications

BACKGROUND: The wider application of T cells targeting viral tumor-antigens via their native receptors is hampered by the failure to expand potent tumor-specific T cells from patients. Here, we examine reasons for and solutions to this failure, taking as our model the preparation of Epstein-Barr virus (EBV)-specific T cells (EBVSTs) for the treatment of EBV-positive lymphoma. EBVSTs could not be manufactured from almost one-third of patients, either because they failed to expand, or they expanded, but lacked EBV specificity. We identified an underlying cause of this problem and established a clinically feasible approach to overcome it.

METHODS: CD45RO+CD45RA- memory compartment …

Contribution Of Adaptive Immunity To Human Copd And Experimental Models Of Emphysema, Farrah Kheradmand, Yun Zhang, David B Corry

Faculty, Staff and Students Publications

The pathophysiology of chronic obstructive pulmonary disease (COPD) and the undisputed role of innate immune cells in this condition have dominated the field in the basic research arena for many years. Recently, however, compelling data suggesting that adaptive immune cells may also contribute to the progressive nature of lung destruction associated with COPD in smokers have gained considerable attention. The histopathological changes in the lungs of smokers can be limited to the large or small airways, but alveolar loss leading to emphysema, which occurs in some individuals, remains its most significant and irreversible outcome. Critically, however, the question of why …

E-Cigarette Aerosols Of Propylene Glycol Impair Bk Channel Activity And Parameters Of Mucociliary Function, Michael D Kim, Samuel Chung, Nathalie Baumlin, Liang Sun, Neerupma Silswal, John S Dennis, Makoto Yoshida, Juan Sabater, Frank T Horrigan, Matthias Salathe

Faculty, Staff and Students Publications

Propylene glycol (PG) is a common delivery vehicle for nicotine and flavorings in e-cigarette (e-cig) liquids and is largely considered safe for ingestion. However, little is known about its effects as an e-cig aerosol on the airway. Here, we investigated whether pure PG e-cig aerosols in realistic daily amounts impact parameters of mucociliary function and airway inflammation in a large animal model (sheep) in vivo and primary human bronchial epithelial cells (HBECs) in vitro. Five-day exposure of sheep to e-cig aerosols of 100% PG increased mucus concentrations (% mucus solids) of tracheal secretions. PG e-cig aerosols further increased the activity …

Heart Failure-Type Symptom Score Trajectories In Ckd: Findings From The Chronic Renal Insufficiency Cohort (Cric) Study, Carl P Walther, Julia S Benoit, Nisha Bansal, Vijay Nambi, Sankar D Navaneethan, Cric Study Investigators

Faculty, Staff and Students Publications

RATIONALE & OBJECTIVE: Quality of life in chronic kidney disease (CKD) is impaired by a large burden of symptoms including some that overlap with the symptoms of heart failure (HF). We studied a group of individuals with CKD to understand the patterns and trajectories of HF-type symptoms in this setting.

STUDY DESIGN: Prospective cohort study.

SETTING & PARTICIPANTS: 3,044 participants in the Chronic Renal Insufficiency Cohort (CRIC) without prior diagnosis of HF.

PREDICTORS: Sociodemographics, medical history, medications, vital signs, laboratory values, echocardiographic and electrocardiographic parameters.

OUTCOME: Trajectory over 5.5 years of a HF-type symptom score (modified Kansas City Cardiomyopathy Questionnaire …

Machine Learning And Health Care: Potential Benefits And Issues, J Graham Atkinson, Elizabeth G Atkinson

Faculty, Staff and Students Publications

We discuss the potential for machine learning (ML) and artificial intelligence (AI) to improve health care, while detailing caveats and important considerations to ensure unbiased and equitable implementation. If disparities exist in the data used to train ML algorithms, they must be recognized and accounted for, so they do not bias performance accuracy or are not interpreted by the algorithm as simply a lack of need. We pay particular attention to an area in which bias in data composition is particularly striking, that is in large-scale genetics databases, as people of European descent are vastly overrepresented in the existing resources.

Construction Of Semi-Supervised Spatial Projections To Identify The Source Of Beta- And High Frequency Oscillations In Parkinson’S Disease, Luciano R F Branco, Ashwin Viswanathan, Arjun Tarakad, Nuri F Ince

Faculty, Staff and Students Publications

Traditional deep brain stimulation (DBS) treatment for Parkinson's disease (PD) targets the placement of DBS leads into subthalamic nucleus (STN). Extraction of neurobiomarkers from STN local field potential activity can be used for the optimization of DBS. Beta (12-30 Hz) and high frequency oscillations (200-450 Hz, HFO) of STN and their phase-amplitude coupling have been previously correlated with symptom severity in PD. The typical approach is to take bipolar derivations of electrode contacts in order to enhance recordings of local brain activity and suppress noise levels. This approach can often cancel the signals in correlated neighboring contacts and create ambiguity …

Interactive Mobile Application For Parkinson’S Disease Deep Brain Stimulation (Map Dbs): An Open-Label, Multicenter, Randomized, Controlled Clinical Trial, Gordon Duffley, Aniko Szabo, Barbara J Lutz, Emily C Mahoney-Rafferty, Christopher W Hess, Adolfo Ramirez-Zamora, Pamela Zeilman, Kelly D Foote, Shannon Chiu, Michael H Pourfar, Clarisse Goas Cnp, Jennifer L Wood, Ihtsham U Haq, Mustafa S Siddiqui, Mitra Afshari, Melissa Heiry, Jennifer Choi, Monica Volz, Jill L Ostrem, Marta San Luciano, Nicki Niemann, Andrew Billnitzer, Daniel Savitt, Arjun Tarakad, Joohi Jimenez-Shahed, Camila C Aquino, Michael S Okun, Christopher R Butson

Faculty, Staff and Students Publications

INTRODUCTION: Deep brain stimulation (DBS) is an effective treatment for Parkinson's disease (PD), but its efficacy is tied to DBS programming, which is often time consuming and burdensome for patients, caregivers, and clinicians. Our aim is to test whether the Mobile Application for PD DBS (MAP DBS), a clinical decision support system, can improve programming.

METHODS: We conducted an open-label, 1:1 randomized, controlled, multicenter clinical trial comparing six months of SOC standard of care (SOC) to six months of MAP DBS-aided programming. We enrolled patients between 30 and 80 years old who received DBS to treat idiopathic PD at six …

Approaching Object Acceleration Differentially Affects The Predictions Of Neuronal Collision Avoidance Models, Fabrizio Gabbiani, Thomas Preuss, Richard B Dewell

Faculty, Staff and Students Publications

The processing of visual information for collision avoidance has been investigated at the biophysical level in several model systems. In grasshoppers, the (so-called) [Formula: see text] model captures reasonably well the visual processing performed by an identified neuron called the lobular giant movement detector as it tracks approaching objects. Similar phenomenological models have been used to describe either the firing rate or the membrane potential of neurons responsible for visually guided collision avoidance in other animals. Specifically, in goldfish, the [Formula: see text] model has been proposed to describe the Mauthner cell, an identified neuron involved in startle escape responses. …

Ichthyosis Uteri: A Keratinizing Squamous Metaplasia Of The Endometrium With Premalignant Potential, Yingao Zhang, Sarah Tounsi, Ghanshyam Yadav, Ramya P Masand, Anthony B Costales

Faculty, Staff and Students Publications

• Ichthyosis uteri is a rare condition describing extensive endometrial keratinization.

• There may be an association with squamous cell carcinoma of the endometrium.

• Endometrial extension of cervical malignancy may closely resemble ichthyosis.

• A hysterectomy should be considered in patients who have completed childbearing.

Light Responses And Amacrine Cell Modulation Of Morphologically-Identified Retinal Ganglion Cells In The Mouse Retina, Ji-Jie Pang, Fan Gao, Samuel M Wu

Faculty, Staff and Students Publications

By analyzing light-evoked spike responses, cation currents (ΔIC) and chloride currents (ΔICl) of over 100 morphologically-identified retinal ganglion cells (GCs) in dark-adapted mouse retina, we found there are at least 14 functionally- and morphologically-distinct types of RGCs. These cells can be divided into 5 groups based on their patterns of spike response to whole field light steps (SRWFLS), a GC identification scheme commonly used in studies with extracellular recording techniques. We also found that all GCs in the mouse retina express strychnine-sensitive glycine receptors, and receive light-elicited chloride current (ΔICl) accompanied by a conductance increase from narrow-field, glycinergic amacrine cells. …

Kcna1 Gain-Of-Function Epileptic Encephalopathy Treated With 4-Aminopyridine, Peter Müller, Danielle S Takacs, Ulrike B S Hedrich, Rohini Coorg, Laura Masters, Kevin E Glinton, Hongzheng Dai, Jon A Cokley, James J Riviello, Holger Lerche, Edward C Cooper

Faculty, Staff and Students Publications

Precision medicine for Mendelian epilepsy is rapidly developing. We describe an early infant with severely pharmacoresistant multifocal epilepsy. Exome sequencing revealed the de novo variant p.(Leu296Phe) in the gene KCNA1, encoding the voltage‐gated K+ channel subunit KV1.1. So far, loss‐of‐function variants in KCNA1 have been associated with episodic ataxia type 1 or epilepsy. Functional studies of the mutated subunit in oocytes revealed a gain‐of‐function caused by a hyperpolarizing shift of voltage dependence. Leu296Phe channels are sensitive to block by 4‐aminopyridine. Clinical use of 4‐aminopyridine was associated with reduced seizure burden, enabled simplification of co‐medication and prevented rehospitalization.

In-Hospital Mortality Risk Stratification In Children Aged Under 5 Years With Pneumonia With Or Without Pulse Oximetry: A Secondary Analysis Of The Pneumonia Research Partnership To Assess Who Recommendations (Prepare) Dataset, Shubhada Hooli, Carina King, Eric D Mccollum, Tim Colbourn, Norman Lufesi, Charles Mwansambo, Christopher J Gregory, Somsak Thamthitiwat, Clare Cutland, Shabir Ahmed Madhi, Marta C Nunes, Bradford D Gessner, Tabish Hazir, Joseph L Mathew, Emmanuel Addo-Yobo, Noel Chisaka, Mumtaz Hassan, Patricia L Hibberd, Prakash Jeena, Juan M Lozano, William B Macleod, Archana Patel, Donald M Thea, Ngoc Tuong Vy Nguyen, Syed Ma Zaman, Raul O Ruvinsky, Marilla Lucero, Cissy B Kartasasmita, Claudia Turner, Rai Asghar, Salem Banajeh, Imran Iqbal, Irene Maulen-Radovan, Greta Mino-Leon, Samir K Saha, Mathuram Santosham, Sunit Singhi, Shally Awasthi, Ashish Bavdekar, Monidarin Chou, Pagbajabyn Nymadawa, Jean-William Pape, Glaucia Paranhos-Baccala, Valentina Sanchez Picot, Mala Rakoto-Andrianarivelo, Vanessa Rouzier, Graciela Russomando, Mariam Sylla, Philippe Vanhems, Jianwei Wang, Sudha Basnet, Tor A Strand, Mark I Neuman, Luis Martinez Arroyo, Marcela Echavarria, Shinjini Bhatnagar, Nitya Wadhwa, Rakesh Lodha, Satinder Aneja, Angela Gentile, Mandeep Chadha, Siddhivinayak Hirve, Kerry-Ann F O'Grady, Alexey W Clara, Chris A Rees, Harry Campbell, Harish Nair, Jennifer Falconer, Linda J Williams, Margaret Horne, Shamim A Qazi, Yasir Bin Nisar, Pneumonia Research Partnership To Assess Who Recommendations (Prepare) Study Group

Faculty, Staff and Students Publications

OBJECTIVES: We determined the pulse oximetry benefit in pediatric pneumonia mortality risk stratification and chest-indrawing pneumonia in-hospital mortality risk factors.

METHODS: We report the characteristics and in-hospital pneumonia-related mortality of children aged 2-59 months who were included in the Pneumonia Research Partnership to Assess WHO Recommendations dataset. We developed multivariable logistic regression models of chest-indrawing pneumonia to identify mortality risk factors.

RESULTS: Among 285,839 children, 164,244 (57.5%) from hospital-based studies were included. Pneumonia case fatality risk (CFR) without pulse oximetry measurement was higher than with measurement (5.8%, 95% confidence interval [CI] 5.6-5.9% vs 2.1%, 95% CI 1.9-2.4%). One in five …

Insulin-Like Growth Factor-1 Supplementation Promotes Brain Maturation In Preterm Pigs, Line I Christiansen, Bo Holmqvist, Xiaoyu Pan, Kristine Holgersen, Sandy E H Lindholm, Nicole L Henriksen, Douglas G Burrin, David Ley, Thomas Thymann, Per Torp Sangild, Stanislava Pankratova

Faculty, Staff and Students Publications

Very preterm infants show low levels of insulin-like growth factor-1 (IGF-1), which is associated with postnatal growth restriction and poor neurologic outcomes. It remains unknown whether supplemental IGF-1 may stimulate neurodevelopment in preterm neonates. Using cesarean-delivered preterm pigs as a model of preterm infants, we investigated the effects of supplemental IGF-1 on motor function and on regional and cellular brain development. Pigs were treated with 2.25 mg/kg/d recombinant human IGF-1/IGF binding protein-3 complex from birth until day 5 or 9 before the collection of brain samples for quantitative immunohistochemistry (IHC), RNA sequencing, and quantitative PCR analyses. Brain protein synthesis was …

Clinical Implications Of Molecular Drug Resistance Testing For Mycobacterium Tuberculosis: A 2023 Tbnet/Resist-Tb Consensus Statement, José Domínguez, Martin J Boeree, Emmanuelle Cambau, Dumitru Chesov, Francesca Conradie, Vivian Cox, Keertan Dheda, Andrii Dudnyk, Maha R Farhat, Sebastien Gagneux, Martin P Grobusch, Matthias I Gröschel, Lorenzo Guglielmetti, Irina Kontsevaya, Berit Lange, Frank Van Leth, Christian Lienhardt, Anna M Mandalakas, Florian P Maurer, Matthias Merker, Paolo Miotto, Barbara Molina-Moya, Florence Morel, Stefan Niemann, Nicolas Veziris, Andrew Whitelaw, Charles R Horsburgh, Christoph Lange

Faculty, Staff and Students Publications

Drug-resistant tuberculosis is a substantial health-care concern worldwide. Despite culture-based methods being considered the gold standard for drug susceptibility testing, molecular methods provide rapid information about the Mycobacterium tuberculosis mutations associated with resistance to anti-tuberculosis drugs. This consensus document was developed on the basis of a comprehensive literature search, by the TBnet and RESIST-TB networks, about reporting standards for the clinical use of molecular drug susceptibility testing. Review and the search for evidence included hand-searching journals and searching electronic databases. The panel identified studies that linked mutations in genomic regions of M tuberculosis with treatment outcome data. Implementation of molecular …

Monogenic Early-Onset Lymphoproliferation And Autoimmunity: Natural History Of Stat3 Gain-Of-Function Syndrome, Jennifer W Leiding, Tiphanie P Vogel, Valentine G J Santarlas, Rahul Mhaskar, Madison R Smith, Alexandre Carisey, Alexander Vargas-Hernández, Manuel Silva-Carmona, Maximilian Heeg, Anne Rensing-Ehl, Bénédicte Neven, Jérôme Hadjadj, Sophie Hambleton, Timothy Ronan Leahy, Kornvalee Meesilpavikai, Charlotte Cunningham-Rundles, Cullen M Dutmer, Svetlana O Sharapova, Mervi Taskinen, Ignatius Chua, Rosie Hague, Christian Klemann, Larysa Kostyuchenko, Tomohiro Morio, Akaluck Thatayatikom, Ahmet Ozen, Anna Scherbina, Cindy S Bauer, Sarah E Flanagan, Eleonora Gambineri, Lisa Giovannini-Chami, Jennifer Heimall, Kathleen E Sullivan, Eric Allenspach, Neil Romberg, Sean G Deane, Benjamin T Prince, Melissa J Rose, John Bohnsack, Talal Mousallem, Rohith Jesudas, Maria Marluce Dos Santos Vilela, Michael O'Sullivan, Jana Pachlopnik Schmid, Štěpánka Průhová, Adam Klocperk, Matthew Rees, Helen Su, Sami Bahna, Safa Baris, Lisa M Bartnikas, Amy Chang Berger, Tracy A Briggs, Shannon Brothers, Vanessa Bundy, Alice Y Chan, Shanmuganathan Chandrakasan, Mette Christiansen, Theresa Cole, Matthew C Cook, Mukesh M Desai, Ute Fischer, David A Fulcher, Silvanna Gallo, Amelie Gauthier, Andrew R Gennery, José Gonçalo Marques, Frédéric Gottrand, Bodo Grimbacher, Eyal Grunebaum, Emma Haapaniemi, Sari Hämäläinen, Kaarina Heiskanen, Tarja Heiskanen-Kosma, Hal M Hoffman, Luis Ignacio Gonzalez-Granado, Anthony L Guerrerio, Leena Kainulainen, Ashish Kumar, Monica G Lawrence, Carina Levin, Timi Martelius, Olaf Neth, Peter Olbrich, Alejandro Palma, Niraj C Patel, Tamara Pozos, Kahn Preece, Saúl Oswaldo Lugo Reyes, Mark A Russell, Yael Schejter, Christine Seroogy, Jan Sinclair, Effie Skevofilax, Daniel Suan, Daniel Suez, Paul Szabolcs, Helena Velasco, Klaus Warnatz, Kelly Walkovich, Austen Worth, Stat3 Gof Working Group Members, Mikko R J Seppänen, Troy R Torgerson, Georgios Sogkas, Stephan Ehl, Stuart G Tangye, Megan A Cooper, Joshua D Milner, Lisa R Forbes Satter

Faculty, Staff and Students Publications

BACKGROUND: In 2014, germline signal transducer and activator of transcription (STAT) 3 gain-of-function (GOF) mutations were first described to cause a novel multisystem disease of early-onset lymphoproliferation and autoimmunity.

OBJECTIVE: This pivotal cohort study defines the scope, natural history, treatment, and overall survival of a large global cohort of patients with pathogenic STAT3 GOF variants.

METHODS: We identified 191 patients from 33 countries with 72 unique mutations. Inclusion criteria included symptoms of immune dysregulation and a biochemically confirmed germline heterozygous GOF variant in STAT3.

RESULTS: Overall survival was 88%, median age at onset of symptoms was 2.3 years, and median …

Admixture Mapping In African Americans Identifies New Risk Loci For Hcv-Related Cirrhosis, Hyun-Seok Kim, Priya B Shetty, Spiridon Tsavachidis, Jing Dong, Christopher I Amos, Hashem B El-Serag, Aaron P Thrift

Faculty, Staff and Students Publications

BACKGROUND & AIMS: Cirrhosis is the main predisposing condition for hepatocellular carcinoma. Host genetic risk factors have been reported for cirrhosis; however, whether there is a genetic contribution to racial disparities in cirrhosis requires further investigation.

METHODS: We used an affected-only mapping by admixture linkage disequilibrium analysis to characterize the genetic risk of cirrhosis in 227 African American patients with cirrhosis genotyped at 19,804 ancestry-informative marker single nucleotide polymorphisms. We additionally performed analyses stratified by hepatitis C virus (HCV) infection status. To replicate our findings, we conducted a case-control analysis in an external study population (452 cases and 196 controls). …

Incidence Rates Of Medically Attended Covid-19 In Infants Less Than 6 Months Of Age, Isabel Griffin, Stephanie A Irving, Carmen Sofia Arriola, Angela P Campbell, De-Kun Li, Fatimah S Dawood, Caroline Doughty-Skierski, Jeannette R Ferber, Nickolas Ferguson, Louise Hadden, Jillian T Henderson, Mary Juergens, Venkatesh Kancharla, Allison L Naleway, Gabriella Newes-Adeyi, Erin Nicholson, Roxana Odouli, Lawrence Reichle, Mo Sanyang, Kate Woodworth, Flor M Munoz

Faculty, Staff and Students Publications

BACKGROUND: Studies suggest infants may be at increased risk of severe coronavirus disease 2019 (COVID-19) relative to older children, but few data exist regarding the incidence of COVID-19 episodes and associated risk factors. We estimate incidence rates and describe characteristics associated with medically attended COVID-19 episodes among infants younger than 6 months of age.

METHODS: We analyzed electronic medical record data from a cohort of infants born March 1, 2020-February 28, 2021. Data from 3 health care delivery systems included demographic characteristics, maternal and infant outpatient visit and hospitalization diagnoses and severe acute respiratory syndrome coronavirus syndrome 2 (SARS-CoV-2) test …

Association Of Clinical Outcomes And Connectivity In Awake Versus Asleep Deep Brain Stimulation For Parkinson Disease, Ron Gadot, Nora Vanegas Arroyave, Huy Dang, Adrish Anand, Ricardo A Najera, Lisa Yutong Taneff, Steven Bellows, Arjun Tarakad, Joseph Jankovic, Andreas Horn, Ben Shofty, Ashwin Viswanathan, Sameer A Sheth

Faculty, Staff and Students Publications

OBJECTIVE: Deep brain stimulation (DBS) for Parkinson disease (PD) is traditionally performed with awake intraoperative testing and/or microelectrode recording. Recently, however, the procedure has been increasingly performed under general anesthesia with image-based verification. The authors sought to compare structural and functional networks engaged by awake and asleep PD-DBS of the subthalamic nucleus (STN) and correlate them with clinical outcomes.

METHODS: Levodopa equivalent daily dose (LEDD), pre- and postoperative motor scores on the Movement Disorders Society-Unified Parkinson's Disease Rating Scale part III (MDS-UPDRS III), and total electrical energy delivered (TEED) at 6 months were retroactively assessed in patients with PD who …

Cigarette Smoke Condensate Induces Centrosome Clustering In Normal Lung Epithelial Cells, Jose Thaiparambil, Chandra S Amara, Subrata Sen, Nagireddy Putluri, Randa El-Zein

Faculty, Staff and Students Publications

BACKGROUND: Unlike normal cells, cancer cells frequently have multiple centrosomes that can cluster to form bipolar mitotic spindles and allow for successful cell division. Inhibiting centrosome clustering, therefore, holds therapeutic promise to promote cancer cell-specific cell death.

METHODS: We used confocal microscopy, real-time PCR, siRNA knockdown, and western blot to analyze centrosome clustering and declustering using normal lung bronchial epithelial and nonsmall-cell lung cancer (NSCLC) cell lines. Also, we used Ingenuity Pathway Analysis software to identify novel pathways associated with centrosome clustering.

RESULTS: In this study, we found that exposure to cigarette smoke condensate induces centrosome amplification and clustering in …