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Extracorporeal Membrane Oxygenation Utility In Postpartum Patients, Bindu Akkanti, Ismael A Salas De Armas, Ayaaz K Sachedina, Jennifer M Sunny, Mahmoud Samy Ahmed, Avaleen Kaur, Kha T Dinh, Rahat Hussain, Sachin Kumar, Sriram Nathan, Marwan Jumean, Manish K Patel, Mehmet H Akay, Jayeshkumar A Patel, Barbi Witz, John Zaki, Igor Banjac, Lisa Janowiak, Igor D Gregoric, Biswajit Kar Sep 2020

Extracorporeal Membrane Oxygenation Utility In Postpartum Patients, Bindu Akkanti, Ismael A Salas De Armas, Ayaaz K Sachedina, Jennifer M Sunny, Mahmoud Samy Ahmed, Avaleen Kaur, Kha T Dinh, Rahat Hussain, Sachin Kumar, Sriram Nathan, Marwan Jumean, Manish K Patel, Mehmet H Akay, Jayeshkumar A Patel, Barbi Witz, John Zaki, Igor Banjac, Lisa Janowiak, Igor D Gregoric, Biswajit Kar

Faculty, Staff and Student Publications

Although extracorporeal membrane oxygenation (ECMO) has been used in many different populations, its use in pregnant or postpartum patients has not been widely studied. This article reviews the ECMO experience in this population at a large urban hospital. Electronic medical records for all pregnant or postpartum patients who required ECMO between 2012 and 2019 were retrospectively reviewed. Data on clinical characteristics, outcomes, and complications were gathered. Comparisons between survivors and nonsurvivors were completed. Ten postpartum patients were identified. The patients presented as follows: four with cardiac arrest, one with a massive pulmonary embolism, three with acute respiratory distress syndrome (ARDS), …


Dramatic Outcomes In Epilepsy: Depression, Suicide, Injuries, And Mortality, Boulenouar Mesraoua, Dirk Deleu, Al Hail Hassan, Melykian Gayane, Alsheikh Lubna, Musab Abdalhalim Ali, Torbjorn Tomson, Bassel Abou Khalil, J Helen Cross, Ali A Asadi-Pooya Sep 2020

Dramatic Outcomes In Epilepsy: Depression, Suicide, Injuries, And Mortality, Boulenouar Mesraoua, Dirk Deleu, Al Hail Hassan, Melykian Gayane, Alsheikh Lubna, Musab Abdalhalim Ali, Torbjorn Tomson, Bassel Abou Khalil, J Helen Cross, Ali A Asadi-Pooya

Department of Neurology Faculty Papers

In this narrative review, we will discuss some of the significant risks and dramatic consequences that are associated with epilepsy: depression, suicide, seizure-related injuries, and mortality, both in adults and in children. Considering the high prevalence of depression among people with epilepsy (PWE), routine and periodic screening of all PWE for early detection and appropriate management of depression is recommended. PWE should be screened for suicidal ideation regularly and when needed, patients should be referred for a psychiatric evaluation and treatment. When starting an antiepileptic drug (AED) or switching from one to another AED, patients should be advised to report …


Aadc Deficiency From Infancy To Adulthood: Symptoms And Developmental Outcome In An International Cohort Of 63 Patients, Toni S Pearson, Laura Gilbert, Kathleen D Meeks, Et Al. Sep 2020

Aadc Deficiency From Infancy To Adulthood: Symptoms And Developmental Outcome In An International Cohort Of 63 Patients, Toni S Pearson, Laura Gilbert, Kathleen D Meeks, Et Al.

2020-Current year OA Pubs

Aromatic l-amino acid decarboxylase deficiency (AADCD) is a rare, autosomal recessive neurodevelopmental disorder characterized by impaired synthesis of dopamine, noradrenaline, adrenaline and serotonin, leading to a complex syndrome of motor, behavioral, and autonomic symptoms. This retrospective study assessed the symptoms and developmental outcome of a large international cohort of patients with AADCD via physician and/or caregiver responses to a detailed, standardized questionnaire. Sixty-three patients (60% female; ages 6 months-36 years, median 7 years; 58 living) from 23 individual countries participated. Common symptoms at onset (median age 3 months, range 0-12 months) were hypotonia, developmental delay, and/or oculogyric crises. Oculogyric crises …


Nine-Year Prospective Efficacy And Safety Of Brain-Responsive Neurostimulation For Focal Epilepsy, Dileep R Nair, Kenneth D Laxer, Peter B Weber, Anthony M Murro, Yong D Park, Gregory L Barkley, Brien J Smith, Ryder P Gwinn, Michael J Doherty, Katherine H Noe, Richard S Zimmerman, Gregory K Bergey, William S Anderson, Christianne Heck, Charles Y Liu, Ricky W Lee, Toni Sadler, Robert B Duckrow, Lawrence J Hirsch, Robert E Wharen, William Tatum, Shraddha Srinivasan, Guy M Mckhann, Mark A Agostini, Andreas V Alexopoulos, Barbara C Jobst, David W Roberts, Vicenta Salanova, Thomas C Witt, Sydney S Cash, Andrew J Cole, Gregory A Worrell, Brian N Lundstrom, Jonathan C Edwards, Jonathan J Halford, David C Spencer, Lia Ernst, Christopher T Skidmore, Michael R Sperling, Ian Miller, Eric B Geller, Michel J Berg, A James Fessler, Paul Rutecki, Alica M Goldman, Eli M Mizrahi, Robert E Gross, Donald C Shields, Theodore H Schwartz, Douglas R Labar, Nathan B Fountain, W Jeff Elias, Piotr W Olejniczak, Nicole R Villemarette-Pittman, Stephan Eisenschenk, Steven N Roper, Jane G Boggs, Tracy A Courtney, Felice T Sun, Cairn G Seale, Kathy L Miller, Tara L Skarpaas, Martha J Morrell, Rns System Ltt Study Sep 2020

Nine-Year Prospective Efficacy And Safety Of Brain-Responsive Neurostimulation For Focal Epilepsy, Dileep R Nair, Kenneth D Laxer, Peter B Weber, Anthony M Murro, Yong D Park, Gregory L Barkley, Brien J Smith, Ryder P Gwinn, Michael J Doherty, Katherine H Noe, Richard S Zimmerman, Gregory K Bergey, William S Anderson, Christianne Heck, Charles Y Liu, Ricky W Lee, Toni Sadler, Robert B Duckrow, Lawrence J Hirsch, Robert E Wharen, William Tatum, Shraddha Srinivasan, Guy M Mckhann, Mark A Agostini, Andreas V Alexopoulos, Barbara C Jobst, David W Roberts, Vicenta Salanova, Thomas C Witt, Sydney S Cash, Andrew J Cole, Gregory A Worrell, Brian N Lundstrom, Jonathan C Edwards, Jonathan J Halford, David C Spencer, Lia Ernst, Christopher T Skidmore, Michael R Sperling, Ian Miller, Eric B Geller, Michel J Berg, A James Fessler, Paul Rutecki, Alica M Goldman, Eli M Mizrahi, Robert E Gross, Donald C Shields, Theodore H Schwartz, Douglas R Labar, Nathan B Fountain, W Jeff Elias, Piotr W Olejniczak, Nicole R Villemarette-Pittman, Stephan Eisenschenk, Steven N Roper, Jane G Boggs, Tracy A Courtney, Felice T Sun, Cairn G Seale, Kathy L Miller, Tara L Skarpaas, Martha J Morrell, Rns System Ltt Study

Faculty, Staff and Students Publications

OBJECTIVE: To prospectively evaluate safety and efficacy of brain-responsive neurostimulation in adults with medically intractable focal onset seizures (FOS) over 9 years.

METHODS: Adults treated with brain-responsive neurostimulation in 2-year feasibility or randomized controlled trials were enrolled in a long-term prospective open label trial (LTT) to assess safety, efficacy, and quality of life (QOL) over an additional 7 years. Safety was assessed as adverse events (AEs), efficacy as median percent change in seizure frequency and responder rate, and QOL with the Quality of Life in Epilepsy (QOLIE-89) inventory.

RESULTS: Of 256 patients treated in the initial trials, 230 participated in …


The De Winter Ecg Pattern: Distribution And Morphology Of St Depression, Zhong-Qun Zhan, Yang Li, Li-Hong Han, Kjell C Nikus, Yochai Birnbaum, Adrian Baranchuk Sep 2020

The De Winter Ecg Pattern: Distribution And Morphology Of St Depression, Zhong-Qun Zhan, Yang Li, Li-Hong Han, Kjell C Nikus, Yochai Birnbaum, Adrian Baranchuk

Faculty, Staff and Students Publications

BACKGROUND: The reported positive predictive value (PPV) for the "de Winter ECG pattern" to predict an acute left anterior descending artery (LAD) lesion is inconsistent. Besides, the morphology of upsloping or nonupsloping ST depression (STD) may have different significance of severity and prognostication.

METHODS: We searched the MEDLINE database using "de Winter" or "junctional ST-depression with tall symmetrical T-waves" or "tall T wave" or "STEMI equivalent" as the item up to March 2020. We compared the ECG differences between the different culprit arteries and various morphological STD.

RESULTS: A total of 70 patients with analyzable ECGs were included. In 60 …


Complete Chemical Structures Of Human Mitochondrial Trnas, Takeo Suzuki, Yuka Yashiro, Ittoku Kikuchi, Yuma Ishigami, Hironori Saito, Ikuya Matsuzawa, Shunpei Okada, Mari Mito, Shintaro Iwasaki, Ding Ma, Xuewei Zhao, Kana Asano, Huan Lin, Yohei Kirino, Yuriko Sakaguchi, Tsutomu Suzuki Aug 2020

Complete Chemical Structures Of Human Mitochondrial Trnas, Takeo Suzuki, Yuka Yashiro, Ittoku Kikuchi, Yuma Ishigami, Hironori Saito, Ikuya Matsuzawa, Shunpei Okada, Mari Mito, Shintaro Iwasaki, Ding Ma, Xuewei Zhao, Kana Asano, Huan Lin, Yohei Kirino, Yuriko Sakaguchi, Tsutomu Suzuki

Computational Medicine Center Faculty Papers

Mitochondria generate most cellular energy via oxidative phosphorylation. Twenty-two species of mitochondrial (mt-)tRNAs encoded in mtDNA translate essential subunits of the respiratory chain complexes. mt-tRNAs contain post-transcriptional modifications introduced by nuclear-encoded tRNA-modifying enzymes. They are required for deciphering genetic code accurately, as well as stabilizing tRNA. Loss of tRNA modifications frequently results in severe pathological consequences. Here, we perform a comprehensive analysis of post-transcriptional modifications of all human mt-tRNAs, including 14 previously-uncharacterized species. In total, we find 18 kinds of RNA modifications at 137 positions (8.7% in 1575 nucleobases) in 22 species of human mt-tRNAs. An up-to-date list of 34 …


Immune And Microrna Responses To Infection And Indole-3-Carbinol During Colitis, Rasha Raheem Alkarkoushi, Yvonne Hui, Abbas S. Tavakoli, Udai Singh, Prakash Nagarkatti, Mitzi Nagarkatti, Ioulia Chatzistamou, Marpe Bam, Traci L. Testerman Aug 2020

Immune And Microrna Responses To Infection And Indole-3-Carbinol During Colitis, Rasha Raheem Alkarkoushi, Yvonne Hui, Abbas S. Tavakoli, Udai Singh, Prakash Nagarkatti, Mitzi Nagarkatti, Ioulia Chatzistamou, Marpe Bam, Traci L. Testerman

Faculty Publications

BACKGROUND: Indole-3-carbinol (I3C) and other aryl hydrocarbon receptor agonists are known to modulate the immune system and ameliorate various inflammatory and autoimmune diseases in animal models, including colitis induced by dextran sulfate sodium (DSS). MicroRNAs (miRNAs) are also gaining traction as potential therapeutic agents or diagnostic elements. Enterohepatic (EHH) species are associated with an increased risk of inflammatory bowel disease, but little is known about how these species affect the immune system or response to treatment. AIM: To determine whether infection with an EHH species alters the response to I3C and how the immune and miRNA responses of an EHH …


Regional Correlation Of Biochemical Measures Of Amyloid And Tau Phosphorylation In The Brain, Kanta Horie, Nicolas R Barthélemy, Nipun Mallipeddi, Yan Li, Erin E Franklin, Richard J Perrin, Randall J Bateman, Chihiro Sato Aug 2020

Regional Correlation Of Biochemical Measures Of Amyloid And Tau Phosphorylation In The Brain, Kanta Horie, Nicolas R Barthélemy, Nipun Mallipeddi, Yan Li, Erin E Franklin, Richard J Perrin, Randall J Bateman, Chihiro Sato

2020-Current year OA Pubs

Alzheimer's disease (AD) neuropathologic change is characterized by amyloid plaques and neurofibrillary tangles (NFTs) that consist of aggregated amyloid beta (Abeta) and hyperphosphorylated tau proteins (p-tau), respectively. Although the global relationship between Abeta and p-tau has been studied for decades, it is still unclear whether a regional correlation exists between Abeta and p-tau in the human brain. Recent studies in cerebrospinal fluid (CSF) have suggested that tau phosphorylation at specific sites such as T217 is modified at an early stage of AD when amyloid plaques become detectable. We applied biochemical and mass spectrometry methods in human brain samples with and …


Teaching Diagnostic Reasoning To Faculty Using An Assessment For Learning Tool: Training The Trainer, Adam Cohen, Moushumi Sur, Martin Weisse, Kathryn Moffett, Jeffrey Lancaster, Renee Saggio, Geeta Singhal, Satid Thammasitboon Aug 2020

Teaching Diagnostic Reasoning To Faculty Using An Assessment For Learning Tool: Training The Trainer, Adam Cohen, Moushumi Sur, Martin Weisse, Kathryn Moffett, Jeffrey Lancaster, Renee Saggio, Geeta Singhal, Satid Thammasitboon

Faculty, Staff and Students Publications

INTRODUCTION: There is a need for a standardized approach to understand and assess clinical reasoning in medical learners. The Assessment of Reasoning Tool was developed based on prevalent theories and frameworks using a multidisciplinary expert panel. As the tool provides a standardized rubric for assessing clinical reasoning, we designed an interactive train-the-trainer workshop for clinical educators and education leaders interested in improving their teaching skills and/or introducing curricula surrounding diagnostic reasoning.

METHODS: In this workshop, participants were exposed to the major domains of diagnostic reasoning and how to apply it to the assessment of a learner's skills. Kolb's experiential learning …


Structure And Mechanism Of A Unique Diiron Center In Mammalian Stearoyl-Coa Desaturase, Jiemin Shen, Gang Wu, Ah-Lim Tsai, Ming Zhou Aug 2020

Structure And Mechanism Of A Unique Diiron Center In Mammalian Stearoyl-Coa Desaturase, Jiemin Shen, Gang Wu, Ah-Lim Tsai, Ming Zhou

Faculty, Staff and Students Publications

Stearoyl-CoA desaturase 1 (SCD1) is a membrane-embedded metalloenzyme that catalyzes formation of a double-bond on a saturated acyl-CoA. SCD1 has a diiron center and its proper function requires an electron transport chain composed of NADH (or NADPH), cytochrome b5 reductase (b5R), and cytochrome b5 (cyt b5). Since SCD1 is a key regulator in fat metabolism and is required for survival of cancer cells, there is intense interest in targeting SCD1 for various metabolic diseases and cancers. Crystal structures of human and mouse SCD1 were reported recently, however, both proteins have two zinc ions instead of two iron ions in the …


Saturated Fats And Health: A Reassessment And Proposal For Food-Based Recommendations: Jacc State-Of-The-Art Review, Arne Astrup, Faidon Magkos, Dennis M Bier, J Thomas Brenna, Marcia C De Oliveira Otto, James O Hill, Janet C King, Andrew Mente, Jose M Ordovas, Jeff S Volek, Salim Yusuf, Ronald M Krauss Aug 2020

Saturated Fats And Health: A Reassessment And Proposal For Food-Based Recommendations: Jacc State-Of-The-Art Review, Arne Astrup, Faidon Magkos, Dennis M Bier, J Thomas Brenna, Marcia C De Oliveira Otto, James O Hill, Janet C King, Andrew Mente, Jose M Ordovas, Jeff S Volek, Salim Yusuf, Ronald M Krauss

Children’s Nutrition Research Center Staff Publications

The recommendation to limit dietary saturated fatty acid (SFA) intake has persisted despite mounting evidence to the contrary. Most recent meta-analyses of randomized trials and observational studies found no beneficial effects of reducing SFA intake on cardiovascular disease (CVD) and total mortality, and instead found protective effects against stroke. Although SFAs increase low-density lipoprotein (LDL) cholesterol, in most individuals, this is not due to increasing levels of small, dense LDL particles, but rather larger LDL particles, which are much less strongly related to CVD risk. It is also apparent that the health effects of foods cannot be predicted by their …


The Ubiquitin Ligase Cullin-1 Associates With Chromatin And Regulates Transcription Of Specific C-Myc Target Genes, Melanie A Sweeney, Polina Iakova, Laure Maneix, Fu-Yuan Shih, Hannah E Cho, Ergun Sahin, Andre Catic Aug 2020

The Ubiquitin Ligase Cullin-1 Associates With Chromatin And Regulates Transcription Of Specific C-Myc Target Genes, Melanie A Sweeney, Polina Iakova, Laure Maneix, Fu-Yuan Shih, Hannah E Cho, Ergun Sahin, Andre Catic

Faculty, Staff and Students Publications

Transcription is regulated through a dynamic interplay of DNA-associated proteins, and the composition of gene-regulatory complexes is subject to continuous adjustments. Protein alterations include post-translational modifications and elimination of individual polypeptides. Spatially and temporally controlled protein removal is, therefore, essential for gene regulation and accounts for the short half-life of many transcription factors. The ubiquitin-proteasome system is responsible for site- and target-specific ubiquitination and protein degradation. Specificity of ubiquitination is conferred by ubiquitin ligases. Cullin-RING complexes, the largest family of ligases, require multi-unit assembly around one of seven cullin proteins. To investigate the direct role of cullins in ubiquitination of …


Genomic Characterization Of Malignant Progression In Neoplastic Pancreatic Cysts, Michaël Noë, Noushin Niknafs, Catherine G Fischer, Wenzel M Hackeng, Violeta Beleva Guthrie, Waki Hosoda, Marija Debeljak, Eniko Papp, Vilmos Adleff, James R White, Claudio Luchini, Antonio Pea, Aldo Scarpa, Giovanni Butturini, Giuseppe Zamboni, Paola Castelli, Seung-Mo Hong, Shinichi Yachida, Nobuyoshi Hiraoka, Anthony J Gill, Jaswinder S Samra, G Johan A Offerhaus, Anne Hoorens, Joanne Verheij, Casper Jansen, N Volkan Adsay, Wei Jiang, Jordan Winter, Jorge Albores-Saavedra, Benoit Terris, Elizabeth D Thompson, Nicholas J Roberts, Ralph H Hruban, Rachel Karchin, Robert B Scharpf, Lodewijk A A Brosens, Victor E Velculescu, Laura D Wood Aug 2020

Genomic Characterization Of Malignant Progression In Neoplastic Pancreatic Cysts, Michaël Noë, Noushin Niknafs, Catherine G Fischer, Wenzel M Hackeng, Violeta Beleva Guthrie, Waki Hosoda, Marija Debeljak, Eniko Papp, Vilmos Adleff, James R White, Claudio Luchini, Antonio Pea, Aldo Scarpa, Giovanni Butturini, Giuseppe Zamboni, Paola Castelli, Seung-Mo Hong, Shinichi Yachida, Nobuyoshi Hiraoka, Anthony J Gill, Jaswinder S Samra, G Johan A Offerhaus, Anne Hoorens, Joanne Verheij, Casper Jansen, N Volkan Adsay, Wei Jiang, Jordan Winter, Jorge Albores-Saavedra, Benoit Terris, Elizabeth D Thompson, Nicholas J Roberts, Ralph H Hruban, Rachel Karchin, Robert B Scharpf, Lodewijk A A Brosens, Victor E Velculescu, Laura D Wood

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Intraductal papillary mucinous neoplasms (IPMNs) and mucinous cystic neoplasms (MCNs) are non-invasive neoplasms that are often observed in association with invasive pancreatic cancers, but their origins and evolutionary relationships are poorly understood. In this study, we analyze 148 samples from IPMNs, MCNs, and small associated invasive carcinomas from 18 patients using whole exome or targeted sequencing. Using evolutionary analyses, we establish that both IPMNs and MCNs are direct precursors to pancreatic cancer. Mutations in SMAD4 and TGFBR2 are frequently restricted to invasive carcinoma, while RNF43 alterations are largely in non-invasive lesions. Genomic analyses suggest an average window of over three …


The Effect Of Neighborhood Social Environment On Prostate Cancer Development In Black And White Men At High Risk For Prostate Cancer, Shannon M Lynch, Elizabeth Handorf, Kristen A Sorice, Elizabeth Blackman, Lisa Bealin, Veda N. Giri, Elias Obeid, Camille Ragin, Mary Daly Aug 2020

The Effect Of Neighborhood Social Environment On Prostate Cancer Development In Black And White Men At High Risk For Prostate Cancer, Shannon M Lynch, Elizabeth Handorf, Kristen A Sorice, Elizabeth Blackman, Lisa Bealin, Veda N. Giri, Elias Obeid, Camille Ragin, Mary Daly

Department of Medical Oncology Faculty Papers

INTRODUCTION: Neighborhood socioeconomic (nSES) factors have been implicated in prostate cancer (PCa) disparities. In line with the Precision Medicine Initiative that suggests clinical and socioenvironmental factors can impact PCa outcomes, we determined whether nSES variables are associated with time to PCa diagnosis and could inform PCa clinical risk assessment.

MATERIALS AND METHODS: The study sample included 358 high risk men (PCa family history and/or Black race), aged 35-69 years, enrolled in an early detection program. Patient variables were linked to 78 nSES variables (employment, income, etc.) from previous literature via geocoding. Patient-level models, including baseline age, prostate specific antigen (PSA), …


Low Anterior Resection Syndrome, Theresa H Nguyen, Reena V Chokshi Aug 2020

Low Anterior Resection Syndrome, Theresa H Nguyen, Reena V Chokshi

Faculty, Staff and Students Publications

PURPOSE OF REVIEW: Low anterior resection syndrome is a highly prevalent condition that can develop after anal sphincter-sparing surgery for rectal cancer and impair quality of life. In this review, we summarize the major features and pathophysiology of this syndrome and discuss treatment approaches.

RECENT FINDINGS: Quality of life correlates significantly with severity of low anterior resection syndrome. Prompt assessment and initiation of therapy are essential to rehabilitating damaged mechanical and neural structures. Anorectal manometry demonstrates a global decrease in sphincteric function postoperatively, though in many patients, function does recover. Transanal irrigation, pelvic floor rehabilitation, and biofeedback are the mainstays …


Metabolism Of Jq1, An Inhibitor Of Bromodomain And Extra Terminal Bromodomain Proteins, In Human And Mouse Liver Microsomes†, Feng Li, Kevin R Mackenzie, Prashi Jain, Conrad Santini, Damian W Young, Martin M Matzuk Aug 2020

Metabolism Of Jq1, An Inhibitor Of Bromodomain And Extra Terminal Bromodomain Proteins, In Human And Mouse Liver Microsomes†, Feng Li, Kevin R Mackenzie, Prashi Jain, Conrad Santini, Damian W Young, Martin M Matzuk

Faculty, Staff and Students Publications

JQ1 is a small-molecule inhibitor of the bromodomain and extra terminal (BET) protein family that potently inhibits the bromodomain testis-specific protein (BRDT), which is essential for spermatogenesis. JQ1 treatment produces a reversible contraceptive effect by targeting the activity of BRDT in mouse male germ cells, validating BRDT as a male contraceptive target. Although JQ1 possesses favourable physical properties, it exhibits a short half-life. Because the details of xenobiotic metabolism play important roles in the optimization of drug candidates and in determining the role of metabolism in drug efficacy, we investigated the metabolism of JQ1 in human and mouse liver microsomes. …


A Global Slc7a7 Knockout Mouse Model Demonstrates Characteristic Phenotypes Of Human Lysinuric Protein Intolerance, Bridget M Stroup, Ronit Marom, Xiaohui Li, Chih-Wei Hsu, Cheng-Yen Chang, Luan D Truong, Brian Dawson, Ingo Grafe, Yuqing Chen, Ming-Ming Jiang, Denise Lanza, Jennie Rose Green, Qin Sun, J P Barrish, Safa Ani, Audrey E Christiansen, John R Seavitt, Mary E Dickinson, Farrah Kheradmand, Jason D Heaney, Brendan Lee, Lindsay C Burrage Aug 2020

A Global Slc7a7 Knockout Mouse Model Demonstrates Characteristic Phenotypes Of Human Lysinuric Protein Intolerance, Bridget M Stroup, Ronit Marom, Xiaohui Li, Chih-Wei Hsu, Cheng-Yen Chang, Luan D Truong, Brian Dawson, Ingo Grafe, Yuqing Chen, Ming-Ming Jiang, Denise Lanza, Jennie Rose Green, Qin Sun, J P Barrish, Safa Ani, Audrey E Christiansen, John R Seavitt, Mary E Dickinson, Farrah Kheradmand, Jason D Heaney, Brendan Lee, Lindsay C Burrage

Faculty, Staff and Students Publications

Lysinuric protein intolerance (LPI) is an inborn error of cationic amino acid (arginine, lysine, ornithine) transport caused by biallelic pathogenic variants in SLC7A7, which encodes the light subunit of the y+LAT1 transporter. Treatments for the complications of LPI, including growth failure, renal disease, pulmonary alveolar proteinosis, autoimmune disorders and osteoporosis, are limited. Given the early lethality of the only published global Slc7a7 knockout mouse model, a viable animal model to investigate global SLC7A7 deficiency is needed. Hence, we generated two mouse models with global Slc7a7 deficiency (Slc7a7em1Lbu/em1Lbu; Slc7a7Lbu/Lbu and Slc7a7em1(IMPC)Bay/em1(IMPC)Bay; Slc7a7Bay/Bay) using CRISPR/Cas9 technology by introducing a deletion of exons …


A Systematic Review Of Interventions For Family Caregivers Who Care For Patients With Advanced Cancer At Home., Soojung Ahn, Rafael D. Romo, Cathy L. Campbell Aug 2020

A Systematic Review Of Interventions For Family Caregivers Who Care For Patients With Advanced Cancer At Home., Soojung Ahn, Rafael D. Romo, Cathy L. Campbell

Nursing | Faculty Scholarship

OBJECTIVE: To examine the characteristics of interventions to support family caregivers of patients with advanced cancer.

METHODS: Five databases (CINAHL, Medline, PsycINFO, Web of Science, and the Cochrane Library) were searched for English language articles of intervention studies utilizing randomized controlled trials or quasi-experimental designs, reporting caregiver-related outcomes of interventions for family caregivers caring for patients with advanced cancer at home.

RESULTS: A total of 11 studies met the inclusion criteria. Based on these studies, the types of interventions were categorized into psychosocial, educational, or both. The characteristics of interventions varied. Most interventions demonstrated statistically significant results of reducing psychological …


Characterization Of Initial North American Pediatric Surgical Response To The Covid-19 Pandemic, Martha-Conley E Ingram, Mehul V Raval, Christopher Newton, Monica E Lopez, Loren Berman, Md Aug 2020

Characterization Of Initial North American Pediatric Surgical Response To The Covid-19 Pandemic, Martha-Conley E Ingram, Mehul V Raval, Christopher Newton, Monica E Lopez, Loren Berman, Md

Department of Surgery Faculty Papers

INTRODUCTION: The impact of COVID-19 pandemic on pediatric surgical care systems is unknown. We present an initial evaluation of self-reported pediatric surgical policy changes from hospitals across North America.

METHODS: On March 30, 2020, an online open access, data gathering spreadsheet was made available to pediatric surgeons through the American Pediatric Surgical Association (APSA) website, which captured information surrounding COVID-19 related policy changes. Responses from the first month of the pandemic were collected. Open-ended responses were evaluated and categorized into themes and descriptive statistics were performed to identify areas of consensus.

RESULTS: Responses from 38 hospitals were evaluated. Policy changes …


Low-Dose Versus High-Dose Carfilzomib With Dexamethasone (S1304) In Patients With Relapsed-Refractory Multiple Myeloma, Sikander Ailawadhi, Rachael Sexton, Suzanne Lentzsch, Muneer H Abidi, Peter M Voorhees, Adam D Cohen, Eric M Rohren, Stephen Heitner, Kevin Kelly, Niklas J Mackler, David M Baer, Antje Hoering, Brian Durie, Robert Z Orlowski Aug 2020

Low-Dose Versus High-Dose Carfilzomib With Dexamethasone (S1304) In Patients With Relapsed-Refractory Multiple Myeloma, Sikander Ailawadhi, Rachael Sexton, Suzanne Lentzsch, Muneer H Abidi, Peter M Voorhees, Adam D Cohen, Eric M Rohren, Stephen Heitner, Kevin Kelly, Niklas J Mackler, David M Baer, Antje Hoering, Brian Durie, Robert Z Orlowski

Faculty, Staff and Students Publications

PURPOSE: Treatment of multiple myeloma has evolved tremendously and optimal utilization of available therapies will ensure maximal patient benefits.

PATIENTS AND METHODS: We report the Southwest Oncology Group randomized phase II trial (S1304) comparing twice weekly low-dose (27 mg/m

RESULTS: Among 143 enrolled patients, of whom 121 were eligible and analyzable, the overall response rate was 42.8%, with no significant difference between the arms (

CONCLUSIONS: This randomized trial did not support a benefit of fixed duration, twice weekly 56 mg/m


Molecular Mechanisms And Epidemiology Of Covid-19 From An Allergist’S Perspective, Koa Hosoki, Abhijit Chakraborty, Sanjiv Sur Aug 2020

Molecular Mechanisms And Epidemiology Of Covid-19 From An Allergist’S Perspective, Koa Hosoki, Abhijit Chakraborty, Sanjiv Sur

Faculty, Staff and Students Publications

The global pandemic caused by the newly described severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused worldwide suffering and death of unimaginable magnitude from coronavirus disease 2019 (COVID-19). The virus is transmitted through aerosol droplets, and causes severe acute respiratory syndrome. SARS-CoV-2 uses the receptor-binding domain of its spike protein S1 to attach to the host angiotensin-converting enzyme 2 receptor in lung and airway cells. Binding requires the help of another host protein, transmembrane protease serine S1 member 2. Several factors likely contribute to the efficient transmission of SARS-CoV-2. The receptor-binding domain of SARS-CoV-2 has a 10- to 20-fold …


Post-Registration Experience Of Nivolumab In Advanced Hepatocellular Carcinoma: An International Study, Petros Fessas, Ahmed Kaseb, Yinghong Wang, Anwaar Saeed, David Szafron, Tomi Jun, Sirish Dharmapuri, Abdul Rafeh Naqash, Mahvish Muzaffar, Musharraf Navaid, Uqba Khan, Chiehju Lee, Anushi Bulumulle, Bo Yu, Sonal Paul, Neil Nimkar, Dominik Bettinger, Francesca Benevento, Hannah Hildebrand, Tiziana Pressiani, Yehia I Abugabal, Nicola Personeni, Yi-Hsiang Huang, Lorenza Rimassa, Celina Ang, Thomas Marron, David J Pinato Aug 2020

Post-Registration Experience Of Nivolumab In Advanced Hepatocellular Carcinoma: An International Study, Petros Fessas, Ahmed Kaseb, Yinghong Wang, Anwaar Saeed, David Szafron, Tomi Jun, Sirish Dharmapuri, Abdul Rafeh Naqash, Mahvish Muzaffar, Musharraf Navaid, Uqba Khan, Chiehju Lee, Anushi Bulumulle, Bo Yu, Sonal Paul, Neil Nimkar, Dominik Bettinger, Francesca Benevento, Hannah Hildebrand, Tiziana Pressiani, Yehia I Abugabal, Nicola Personeni, Yi-Hsiang Huang, Lorenza Rimassa, Celina Ang, Thomas Marron, David J Pinato

Faculty, Staff and Students Publications

BACKGROUND: Nivolumab is Food and Drug Administration approved in sorafenib-experienced, advanced hepatocellular carcinoma (HCC). Post-registration data of treatment in a real-world setting is lacking.

PATIENTS AND METHODS: We performed an international, multicenter observational study to confirm safety and efficacy of nivolumab in 233 patients treated outside clinical trials from eight centers in North America, Europe and Asia.

RESULTS: Patients received nivolumab for Barcelona Clinic Liver Cancer stage C (n=191, 92.0%) and Child-Pugh (CP) A (n=158, 67.8%) or B (n=75, 32.2%) HCC as first (n=85, 36.5%) or second to fourth systemic therapy line …


Platypnea-Orthodeoxia Syndrome Caused By An Intracardiac Shunt, Sanket P Borgaonkar, Wilson W Lam, Mehdi Razavi, Dhaval R Parekh Aug 2020

Platypnea-Orthodeoxia Syndrome Caused By An Intracardiac Shunt, Sanket P Borgaonkar, Wilson W Lam, Mehdi Razavi, Dhaval R Parekh

Faculty, Staff and Students Publications

Platypnea-orthodeoxia syndrome, a rare condition characterized by posture-related dyspnea, is usually caused by an intracardiac shunt, hepatopulmonary syndrome, or shunting resulting from severe pulmonary disease. We report the case of a 33-year-old woman who presented with increasing dyspnea and oxygen desaturation when she sat up or arose. Our diagnosis was platypnea-orthodeoxia syndrome. A lead of a previously implanted pacemaker exacerbated a severe tricuspid regurgitant jet that was directed toward the patient's intra-atrial septum. Percutaneous closure of a small secundum atrial septal defect eliminated right-to-left shunting and substantially improved the patient's functional status. In addition to this case, we discuss this …


Longitudinal Effects Of A Novel Advanced Pneumatic Compression Device On Patient-Reported Outcomes In The Management Of Cancer-Related Head And Neck Lymphedema: A Preliminary Report, Carolina Gutiérrez, Harvey N Mayrovitz, Syed Hassan Shiraz Naqvi, Ron J Karni Aug 2020

Longitudinal Effects Of A Novel Advanced Pneumatic Compression Device On Patient-Reported Outcomes In The Management Of Cancer-Related Head And Neck Lymphedema: A Preliminary Report, Carolina Gutiérrez, Harvey N Mayrovitz, Syed Hassan Shiraz Naqvi, Ron J Karni

Faculty, Staff and Student Publications

BACKGROUND: Head and neck cancer (HNC) survivors experience head and neck lymphedema (HNL), which requires treatment to prevent morbidity. We explore the self-reported outcomes and satisfaction of patients with HNC receiving treatment for HNL with an advanced pneumatic compression device (APCD).

METHODS: HNC survivors (n = 205) prescribed with an at-home Flexitouch head and neck APCD completed pretreatment and posttreatment self-reported assessments addressing efficacy, function, and symptoms. Participant average age was 60 years with 74% male. Pre-post responses for ≥25 days of use were assessed via the non-parametric Wilcoxon Signed Rank test.

RESULTS: Analysis revealed statistically significant improvement in all …


Transcatheter Mitral Valve Replacement For Treating Native Mitral Valve Disease: Current Status, Yan Chen, Junjie Hu, Shunqiang Wu, San Zhang, Kaiqin Wu, Wenli Wang, Yongxin Zhou Aug 2020

Transcatheter Mitral Valve Replacement For Treating Native Mitral Valve Disease: Current Status, Yan Chen, Junjie Hu, Shunqiang Wu, San Zhang, Kaiqin Wu, Wenli Wang, Yongxin Zhou

The Texas Heart Institute Journal

Transcatheter mitral valve replacement is increasingly being used as a treatment for high-risk patients who have native mitral valve disease; however, no comprehensive studies on its effectiveness have been reported. We therefore searched the literature for reports on patients with native mitral valve disease who underwent transcatheter access treatment. We found 40 reports, published from September 2013 through April 2017, that described the cases of 66 patients (mean age, 71 ± 12 yr; 30 women; 30 patients with mitral stenosis, 34 with mitral regurgitation, and 2 mixed) who underwent transcatheter mitral valve replacement. We documented their baseline clinical characteristics, comorbidities, …


Interventricular Septal Rupture In A 62-Year-Old Man With Familial Amyloid Polyneuropathy, Stefano Pidello, Erika Simonato, Fulvio Orzan, Simone Frea, Antonella Barreca, Mauro Rinaldi, Massimo Boffini Aug 2020

Interventricular Septal Rupture In A 62-Year-Old Man With Familial Amyloid Polyneuropathy, Stefano Pidello, Erika Simonato, Fulvio Orzan, Simone Frea, Antonella Barreca, Mauro Rinaldi, Massimo Boffini

The Texas Heart Institute Journal

Cardiac involvement in familial amyloid polyneuropathy consists of arrhythmias, conduction disturbances, and heart failure. To our knowledge, heart rupture has never been described in association with this condition. We report the case of a 62-year-old man with a 6-year history of refractory familial amyloid polyneuropathy who underwent liver transplantation. The operation was complicated by severe hypotension because the neuropathy involved the autonomic system. Perioperatively, the patient had a myocardial infarction, and during the next 10 days, a complete interventricular septal rupture developed, resulting in a systemic-to-pulmonary shunt. Coronary angiographic findings were normal. However, the shunt caused unstable hemodynamics, resulting in …


Association Of Tph1 And Serotonin Transporter Genotypes With Treatment Response For Suicidal Ideation: A Preliminary Study, David A Nielsen, Huiqiong Deng, Michelle A Patriquin, Mark J Harding, John Oldham, Ramiro Salas, J Christopher Fowler, B Christopher Frueh Aug 2020

Association Of Tph1 And Serotonin Transporter Genotypes With Treatment Response For Suicidal Ideation: A Preliminary Study, David A Nielsen, Huiqiong Deng, Michelle A Patriquin, Mark J Harding, John Oldham, Ramiro Salas, J Christopher Fowler, B Christopher Frueh

Staff and Researcher Publications

Variants in three genes coding for components of the serotonergic system, the tryptophan hydroxylase 1 (TPH1) rs1799913, serotonin transporter (SLC6A4) 5-HTTLPR, and serotonin receptor 2A (HTR2A) rs6311, were evaluated for association with suicidal ideation (SI) and with recovery from SI in a psychiatric inpatient population. Five hundred and eighty-two adult inpatients, including 390 patients who had SI, collected from December 2012 to April 2016 were assessed. SI recovery, calculated as change in SI between the first two-week period after admission and weeks 5 and 6, was appraised for association with the three variants. In this preliminary study, both TPH1 and …


Importance Of Persistent Right-To-Left Shunt After Patent Foramen Ovale Closure In Cryptogenic Stroke Patients, Lu He, Gesheng Cheng, Yajuan Du, Yushun Zhang Aug 2020

Importance Of Persistent Right-To-Left Shunt After Patent Foramen Ovale Closure In Cryptogenic Stroke Patients, Lu He, Gesheng Cheng, Yajuan Du, Yushun Zhang

The Texas Heart Institute Journal

Percutaneous closure of patent foramen ovale (PFO) is widely performed to prevent recurrent stroke or transient ischemic attack in patients with cryptogenic stroke. However, the influence of different degrees of right-to-left shunting (RLS) has rarely been reported.

We retrospectively evaluated the cases of 268 patients with cryptogenic stroke who underwent PFO closure at our hospital from April 2012 through April 2015. In accordance with RLS severity, we divided the patients into 2 groups: persistent RLS during normal breathing and the Valsalva maneuver (n=112) and RLS only during the Valsalva maneuver (n=156). Baseline characteristics, morphologic features, and procedural and follow-up data …


Modulation Of Hedgehog Signaling By Kappa Opioids To Attenuate Osteoarthritis, Alexander E Weber, Omid Jalali, Sean Limfat, Ruzanna Shkhyan, Robert Van Der Horst, Siyoung Lee, Yucheng Lin, Liangliang Li, Erik N Mayer, Liming Wang, Nancy Q Liu, Frank A Petrigliano, Jay R Lieberman, Denis Evseenko Aug 2020

Modulation Of Hedgehog Signaling By Kappa Opioids To Attenuate Osteoarthritis, Alexander E Weber, Omid Jalali, Sean Limfat, Ruzanna Shkhyan, Robert Van Der Horst, Siyoung Lee, Yucheng Lin, Liangliang Li, Erik N Mayer, Liming Wang, Nancy Q Liu, Frank A Petrigliano, Jay R Lieberman, Denis Evseenko

Faculty, Staff and Students Publications

OBJECTIVE: Inhibition of hedgehog (HH) signaling prevents cartilage degeneration and promotes repair in animal models of osteoarthritis (OA). This study, undertaken in OA models and in human OA articular cartilage, was designed to explore whether kappa opioid receptor (KOR) modulation via the inhibition of HH signaling may have therapeutic potential for achieving disease-modifying activity in OA.

METHODS: Primary human articular cartilage and synovial tissue samples from patients with knee OA undergoing total joint replacement and from healthy human subjects were obtained from the National Disease Research Interchange. For in vivo animal studies, a partial medial meniscectomy (PMM) model of knee …


Prevalence Of Helicobacter Pylori Positive Non-Cardia Gastric Adenocarcinoma Is Low And Decreasing In A Us Population, Theresa H Nguyen, Niharika Mallepally, Tariq Hammad, Yan Liu, Aaron P Thrift, Hashem B El-Serag, Mimi C Tan Aug 2020

Prevalence Of Helicobacter Pylori Positive Non-Cardia Gastric Adenocarcinoma Is Low And Decreasing In A Us Population, Theresa H Nguyen, Niharika Mallepally, Tariq Hammad, Yan Liu, Aaron P Thrift, Hashem B El-Serag, Mimi C Tan

Faculty, Staff and Students Publications

BACKGROUND: Helicobacter pylori infection is an established causal factor for non-cardia gastric cancer. H. pylori negative gastric cancer prevalence among US patients is unclear.

METHODS: This retrospective cohort study examined H. pylori prevalence among consecutive patients with incident non-cardia gastric adenocarcinoma at the Houston VA Hospital (11/2007-10/2018). H. pylori positivity was defined by H. pylori on histopathology, positive antibody serology, stool antigen, or urea breath testing. We examined for trends in H. pylori negative gastric cancer based on year of diagnosis. Associations between histopathologic and cancer-related outcomes with H. pylori positivity were determined using regression models.

RESULTS: Of 91 patients …