Medicine and Health Sciences Commons^™

Water T2 Could Predict Functional Decline In Patients With Dysferlinopathy, Ursula Moore, Alan Pestronk, Et Al.

2020-Current year OA Pubs

BACKGROUND: Water T2 (T2

METHODS: Patients with genetically confirmed dysferlinopathy were assessed as part of the Jain Foundation Clinical Outcomes Study in dysferlinopathy. The cohort included 18 patients from two sites, both equipped with 3-tesla magnetic resonance imaging (MRI) systems from the same vendor. T2

RESULTS: A higher T2

CONCLUSIONS: In dysferlinopathy, T2

Risk Of Nonalcoholic Fatty Liver Disease And Associations With Gastrointestinal Cancers, Scott Mchenry, Xiaoyu Zong, Mengyao Shi, Cassandra D L Fritz, Katrina S Pedersen, Linda R Peterson, Jeffrey K Lee, Ryan C Fields, Nicholas O Davidson, Yin Cao

2020-Current year OA Pubs

Metabolic syndrome may contribute to the rising incidence of multiple gastrointestinal (GI) cancers in recent birth cohorts. However, other than hepatocellular carcinoma, the association between nonalcoholic fatty liver disease (NAFLD) and risk of non-liver GI cancers is unexplored. We prospectively examined the associations of NAFLD risk with GI cancers among 319,290 participants in the UK Biobank (2006-2019). Baseline risk for NAFLD was estimated using the Dallas Steatosis Index, a validated prediction tool. Multivariable Cox models were used to estimate relative risks (RRs) and 95% confidence intervals (CIs) according to NAFLD risk categories: low (<20%), intermediate (20%-49%), and high (≥50%). We also examined the associations by age of cancer diagnosis (earlier onset [<60] vs. ≥60). A total of 273 incident liver cancer and 4789 non-liver GI cancer cases were diagnosed. Compared with individuals at low risk for NAFLD, those at high risk had 2.41-fold risk of liver cancer (RR = 2.41, 95% CI: 1.73-3.35) and 23% increased risk of non-liver GI cancers (RR = 1.23, 95% CI: 1.14-1.32) (all p

Anxiety Disorders In Children And Adolescents, Alicia Kowalchuk, Sandra J Gonzalez, Roger J Zoorob

Faculty, Staff and Students Publications

Anxiety disorders are the most common psychiatric conditions in children and adolescents, affecting nearly 1 in 12 children and 1 in 4 adolescents. Anxiety disorders include specific phobias, social anxiety disorder, separation anxiety disorder, agoraphobia, panic disorder, and generalized anxiety disorder. Risk factors include parental history of anxiety disorders, socioeconomic stressors, exposure to violence, and trauma. The U.S. Preventive Services Task Force recommends screening for anxiety disorders in children eight years and older; there is insufficient evidence to support screening in children younger than eight years. Symptoms of anxiety disorders in children and adolescents are similar to those in adults …

Association Between Cause Of Kidney Failure And Fracture Incidence In A National Us Dialysis Population Cohort Study, Susan Ziolkowski, Sai Liu, Maria E Montez-Rath, Michelle Denburg, Wolfgang C Winkelmayer, Glenn M Chertow, Michelle M O'Shaughnessy

Faculty, Staff and Students Publications

Background: Bradycardia and asystole events are common among patients treated with maintenance hemodialysis. However, triggers of these events in patients on maintenance hemodialysis (HD), particularly during the long interdialytic period when these events cluster, are uncertain.

Methods: The Monitoring in Dialysis Study (MiD) enrolled 66 patients on maintenance HD who were implanted with loop recorders and followed for 6 months. We analyzed associations of predialysis laboratory values with clinically significant bradyarrhythmia or asystole (CSBA) during the 12 hours before an HD session. Associations with CSBA were analyzed with mixed-effect models. Adjusted negative binomial mixed-effect regression was used to estimate incidence …

Assessment Of Donor Quality And Risk Of Graft Failure After Liver Transplantation: The Id2eal Score, Sumeet K Asrani, Giovanna Saracino, Anji Wall, James F Trotter, Giuliano Testa, Ruben Hernaez, Pratima Sharma, Allison Kwong, Srikanta Banerjee, Gregory Mckenna

Faculty, Staff and Students Publications

Accurate assessment of donor quality at the time of organ offer for liver transplantation candidates may be inadequately captured by the donor risk index (DRI). We sought to develop and validate a novel objective and simple model to assess donor risk using donor level variables available at the time of organ offer. We utilized national data from candidates undergoing primary LT (2013-2019) and assessed the prediction of graft failure 1 year after LT. The final components were donor Insulin-dependent diabetes mellitus, Donor type (DCD or DBD), cause of Death = CVA, serum creatinine, Age, height, and weight (length). The ID

Human Islet Amyloid Polypeptide (Hiapp) Protofibril-Specific Antibodies For Detection And Treatment Of Type 2 Diabetes, Angelina S Bortoletto, W Vallen Graham, Gabriella Trout, Alessandra Bonito-Oliva, Manija A Kazmi, Jing Gong, Emily Weyburne, Brandy L Houser, Thomas P Sakmar, Ronald J Parchem

Faculty, Staff and Students Publications

Type 2 diabetes mellitus (T2D) is a major public health concern and is characterized by sustained hyperglycemia due to insulin resistance and destruction of insulin-producing β cells. One pathological hallmark of T2D is the toxic accumulation of human islet amyloid polypeptide (hIAPP) aggregates. Monomeric hIAPP is a hormone normally co-secreted with insulin. However, increased levels of hIAPP in prediabetic and diabetic patients can lead to the formation of hIAPP protofibrils, which are toxic to β cells. Current therapies fail to address hIAPP aggregation and current screening modalities do not detect it. Using a stabilizing capping protein, monoclonal antibodies (mAbs) can …

Effects Of Α And Β-Adrenergic Signaling On Innate Immunity And Porphyromonas Gingivalis Virulence In An Invertebrate Model, Renata Mendonça Moraes, Maíra Terra Garcia, Fabio Stossi, Patrícia Pimentel De Barros, Juliana Campos Junqueira, Ana Lia Anbinder

Faculty, Staff and Students Publications

To investigate the role of adrenergic signalling (AS) in the host immune response and Porphyromonas gingivalis virulence, we compared norepinephrine (NE) and isoproterenol (ISO) responses in Galleria mellonella. P. gingivalis infection was evaluated by survival; humoral immune responses (i.e. melanization and cecropin and gloverin mRNA expression); cellular immune responses (i.e. haemocyte count, nodulation by histology); and P. gingivalis recovery (CFU/mL). P. gingivalis was cultivated in the presence of ISO (PgISO) or NE and injected into the larvae for survival evaluation. Finally, we co-injected ISO and PgISO to evaluate the concomitant effects on the immune response and bacterial virulence. None …

A Recurrent Single-Exon Deletion In Tbck Might Be Under-Recognized In Patients With Infantile Hypotonia And Psychomotor Delay, Hongzheng Dai, Wenmiao Zhu, Bo Yuan, Nicole Walley, Kelly Schoch, Yong-Hui Jiang, John A Phillips, Melissa S Jones, Pengfei Liu, David R Murdock, Lindsay C Burrage, Brendan Lee, Jill A Rosenfeld, Rui Xiao

Faculty, Staff and Students Publications

Advanced bioinformatics algorithms allow detection of multiple-exon copy-number variations (CNVs) from exome sequencing (ES) data, while detection of single-exon CNVs remains challenging. A retrospective review of Baylor Genetics' clinical ES patient cohort identified four individuals with homozygous single-exon deletions of TBCK (exon 23, NM_001163435.2), a gene associated with an autosomal recessive neurodevelopmental phenotype. To evaluate the prevalence of this deletion and its contribution to disease, we retrospectively analyzed single nucleotide polymorphism (SNP) array data for 8194 individuals undergoing ES, followed by PCR confirmation and RT-PCR on individuals carrying homozygous or heterozygous exon 23 TBCK deletions. A fifth individual was diagnosed …

An Open-Access, Interactive Decision-Support Tool To Facilitate Guideline-Driven Care For Hepatocellular Carcinoma, Robert J Wong, Channa Jayasekera, Patricia Jones, Fasiha Kanwal, Amit G Singal, Aijaz Ahmed, Robert Taglienti, Zobair Younossi, Laura Kulik, Neil Mehta

Faculty, Staff and Students Publications

Hepatocellular carcinoma (HCC) is increasing in incidence and is a leading cause of cancer-related mortality worldwide. Adherence to HCC surveillance guidelines and appropriate treatment triage of liver lesions may improve receipt of curative-intent treatment and improved survival. Late-stage HCC diagnosis reflects sub-optimal implementation of effective HCC surveillance, whereas inappropriate treatment triage or linkage to care accounts for the non-receipt of curative-intent in close to half of early-stage HCC in the USA. A free, open-access decision-support tool for liver lesions that incorporates current guideline recommendations in a user-friendly interface could improve appropriate and timely triage of patients to appropriate care. This …

Long Read Sequencing And Expression Studies Of Ahdc1 Deletions In Xia-Gibbs Syndrome Reveal A Novel Genetic Regulatory Mechanism, Varuna Chander, Medhat Mahmoud, Jianhong Hu, Zain Dardas, Christopher M Grochowski, Moez Dawood, Michael M Khayat, He Li, Shoudong Li, Shalini Jhangiani, Viktoriya Korchina, Hua Shen, George Weissenberger, Qingchang Meng, Marie-Claude Gingras, Donna M Muzny, Harsha Doddapaneni, Jennifer E Posey, James R Lupski, Aniko Sabo, David R Murdock, Fritz J Sedlazeck, Richard A Gibbs

Faculty, Staff and Students Publications

Xia-Gibbs syndrome (XGS; MIM# 615829) is a rare mendelian disorder characterized by Development Delay (DD), intellectual disability (ID), and hypotonia. Individuals with XGS typically harbor de novo protein-truncating mutations in the AT-Hook DNA binding motif containing 1 (AHDC1) gene, although some missense mutations can also cause XGS. Large de novo heterozygous deletions that encompass the AHDC1 gene have also been ascribed as diagnostic for the disorder, without substantial evidence to support their pathogenicity. We analyzed 19 individuals with large contiguous deletions involving AHDC1, along with other genes. One individual bore the smallest known contiguous AHDC1 deletion (∼350 Kb), encompassing eight …

Highlights Of Cardiovascular Disease Prevention Studies Presented At The 2022 European Society Of Cardiology Congress, Melody Hermel, Megan Pelter, Timothy Jordan, Azka Latif, Mohamed M Gad, Leandro Slipczuk, Dinesh Kalra, Salim S Virani

Faculty, Staff and Students Publications

Purpose of review: Focused review of select studies presented at the 2022 European Society of Cardiology Congress.

Recent findings: Included studies assessed the effects of aspirin and omega-3 fatty acid supplements on heart failure (ASCEND study); the impact of icosapent ethyl on ST-elevation MI incidence (REDUCE-IT); air temperature's effect on cardiovascular mortality (EXHAUSTION project); LVEF outcomes after troponin-guided neurohormonal blockade for the prevention of anthracycline toxicity; efficacy of routine stress testing after high-risk PCI (POST-PCI trial); influenza vaccine among patients with acute coronary syndromes (VIP-ACS trial); empagliflozin in patients with acute myocardial infarction (EMMY); effects of comprehensive imaging-based cardiovascular screening …

Mechanisms Of Cancer Metastasis, Maria Castaneda, Petra Den Hollander, Nick A Kuburich, Jeffrey M Rosen, Sendurai A Mani

Faculty, Staff and Students Publications

Metastatic cancer is almost always terminal, and more than 90% of cancer deaths result from metastatic disease. Combating cancer metastasis and post-therapeutic recurrence successfully requires understanding each step of metastatic progression. This review describes the current state of knowledge of the etiology and mechanism of cancer progression from primary tumor growth to the formation of new tumors in other parts of the body. Open questions, avenues for future research, and therapeutic approaches with the potential to prevent or inhibit metastasis through personalization to each patient's mutation and/or immune profile are also highlighted.

Role Of Bacteriophage Therapy For Resistant Infections In Transplant Recipients, Paul Nicholls, Saima Aslam

Faculty, Staff and Students Publications

Purpose of review: Multidrug-resistant organisms (MDROs) are prevalent in transplant recipients and associated with poor outcomes. We review recent cases of phage therapy used to treat recalcitrant infections in transplant recipients and explore the future role of such therapy in this setting.

Recent findings: Individual case reports and small case series suggest possible efficacy of phage therapy for the treatment of MDRO infections in pre and posttransplant patients. Importantly, there have been no serious safety concerns in the reported cases that we reviewed. There are no applicable randomized controlled trials (RCTs) to better guide phage therapy at this time.

Summary: …

Association Between Cause Of Kidney Failure And Fracture Incidence In A National Us Dialysis Population Cohort Study, Susan Ziolkowski, Sai Liu, Maria E Montez-Rath, Michelle Denburg, Wolfgang C Winkelmayer, Glenn M Chertow, Michelle M O'Shaughnessy

Faculty, Staff and Students Publications

Background: Whether fracture rates, overall and by fracture site, vary by cause of kidney failure in patients receiving dialysis is unknown.

Methods: Using the US Renal Data System, we compared fracture rates across seven causes of kidney failure in patients who started dialysis between 1997 and 2014. We computed unadjusted and multivariable adjusted proportional sub-distribution hazard models, with fracture events (overall, and by site) as the outcome and immunoglobulin A nephropathy as the reference group. Kidney transplantation and death were competing events.

Results: Among 491 496 individuals, with a median follow-up of 2.0 (25%, 75% range 0.9-3.9) years, 62 954 …

Renal Osteodystrophy: A Historical Review Of Its Origins And Conceptual Evolution, Garabed Eknoyan, Sharon M Moe

Faculty, Staff and Students Publications

Long considered an inert supporting framework, bone studies went neglected until the 17th century when they began as descriptive microscopic studies of structure which over time progressed into that of chemistry and physiology. It was in the mid-19th century that studies evolved into an inquisitive discipline which matured into the experimental investigation of bone in health and disease in the 20th century, and ultimately that of molecular studies now deciphering the genetic language of bone biology. These fundamental studies were catalyzed by increasing clinical interest in bone disease. The first bone disease to be identified was rickets in 1645. Its …

A Narrative Review Of Sex And Gender Differences In Sleep Disordered Breathing: Gaps And Opportunities, Margaret Bublitz, Nour Adra, Leen Hijazi, Fidaa Shaib, Hrayr Attarian, Ghada Bourjeily

Faculty, Staff and Students Publications

Introduction: Sleep disordered breathing (SDB) is a common condition, associated with multiple comorbidities including cardiovascular and metabolic disease. It has been previously established that SDB is more prevalent in men than women, shifting the literature's focus away from the latter population. As such, underdiagnosis, and thus undertreatment, of SDB in women exists.

Methods: To establish the differences in prevalence, clinical presentation, and pathophysiology of SDB between the two sexes, a narrative review of the current literature was performed.

Results: Rates of SDB are higher among men, likely driven by differences in symptom presentation between men and women, with women presenting …

Loss Of Wnt4 In The Gubernaculum Causes Unilateral Cryptorchidism And Fertility Defects, Abhishek Seth, Juan C Bournat, Olga Medina-Martinez, Armando Rivera, Joshua Moore, Hunter Flores, Jill A Rosenfeld, Liya Hu, Carolina J Jorgez

Faculty, Staff and Students Publications

Undescended testis (UDT) affects 6% of male births. Despite surgical correction, some men with unilateral UDT may experience infertility with the contralateral descended testis (CDT) showing no A-dark spermatogonia. To improve our understanding of the etiology of infertility in UDT, we generated a novel murine model of left unilateral UDT. Gubernaculum-specific Wnt4 knockout (KO) mice (Wnt4-cKO) were generated using retinoic acid receptor β2-cre mice and were found to have a smaller left-unilateral UDT. Wnt4-cKO mice with abdominal UDT had an increase in serum follicle-stimulating hormone and luteinizing hormone and an absence of germ cells in the undescended testicle. Wnt4-cKO mice …

Cancer Evaluations During The Covid-19 Pandemic: An Observational Study Using National Veterans Affairs Data, Ashley N D Meyer, Hardeep Singh, Andrew J Zimolzak, Li Wei, Debra T Choi, Abigail D Marinez, Daniel R Murphy

Faculty, Staff and Students Publications

INTRODUCTION: Fewer cancer diagnoses have been made during the COVID-19 pandemic. Pandemic-related delays in cancer diagnosis could occur from limited access to care or patient evaluation delays (e.g., delayed testing after abnormal results). Follow-up of abnormal test results warranting evaluation for cancer was examined before and during the pandemic.

METHODS: Electronic trigger algorithms were applied to the Department of Veterans Affairs electronic health record data to assess follow-up of abnormal test results before (March 10, 2019-March 7, 2020) and during (March 8, 2020-March 6, 2021) the pandemic.

RESULTS: Electronic triggers were applied to 8,021,406 veterans' electronic health records to identify …

Baseline Microperimetry And Oct In The Rush2a Study: Structure-Function Association And Correlation With Disease Severity, Eleonora M Lad, Jacque L Duncan, Wendi Liang, Maureen G Maguire, Allison R Ayala, Isabelle Audo, David G Birch, Joseph Carroll, Janet K Cheetham, Todd A Durham, Abigail T Fahim, Jessica Loo, Zengtian Deng, Dibyendu Mukherjee, Elise Heon, Robert B Hufnagel, Bin Guan, Alessandro Iannaccone, Glenn J Jaffe, Christine N Kay, Michel Michaelides, Mark E Pennesi, Ajoy Vincent, Christina Y Weng, Sina Farsiu

Faculty, Staff and Students Publications

PURPOSE: To investigate baseline mesopic microperimetry (MP) and spectral domain optical coherence tomography (OCT) in the Rate of Progression in USH2A-related Retinal Degeneration (RUSH2A) study.

DESIGN: Natural history study METHODS: Setting: 16 clinical sites in Europe and North AmericaStudy Population: Participants with Usher syndrome type 2 (USH2) (N = 80) or autosomal recessive nonsyndromic RP (ARRP) (N = 47) associated with biallelic disease-causing sequence variants in USH2AObservation Procedures: General linear models were used to assess characteristics including disease duration, MP mean sensitivity and OCT intact ellipsoid zone (EZ) area. The associations between mean sensitivity and EZ area with other measures, …

Chronic Kidney Disease, Risk Of Readmission, And Progression To End-Stage Renal Disease In 519,387 Patients Undergoing Coronary Artery Bypass Grafting, Ryan Nowrouzi, Christopher B Sylvester, John A Treffalls, Qianzi Zhang, Todd K Rosengart, Joseph S Coselli, Marc R Moon, Ravi K Ghanta, Subhasis Chatterjee

Faculty, Staff and Students Publications

Objective: The association between chronic kidney disease and adverse outcomes after coronary artery bypass grafting is well established; in contrast, the association between chronic kidney disease and readmission has been less thoroughly investigated. We hypothesized that patients at higher chronic kidney disease stages have greater risk of readmission, poorer operative outcomes, and greater hospitalization cost.

Methods: Using the 2016-2018 Nationwide Readmissions Database, we identified 519,387 patients who underwent isolated coronary artery bypass grafting. Patients were stratified by chronic kidney disease stage based on International Classification of Diseases 10th Revision classification. Multivariable logistic regression was used to assess risk factors for …

The Us Department Of Veterans Affairs Science And Health Initiative To Combat Infectious And Emerging Life-Threatening Diseases (Va Shield): A Biorepository Addressing National Health Threats, John B Harley, Saiju Pyarajan, Elizabeth S Partan, Lauren Epstein, Jason A Wertheim, Abhinav Diwan, Christopher W Woods, Victoria Davey, Sharlene Blair, Dennis H Clark, Kenneth M Kaufman, Shagufta Khan, Iouri Chepelev, Alexander Devine, Perry Cameron, Monica F Mccann, Mary Cloud B Ammons, Devin D Bolz, Jane K Battles, Jeffrey L Curtis, Mark Holodniy, Vincent C Marconi, Charles D Searles, David O Beenhouwer, Sheldon T Brown, Jonathan P Moorman, Zhi Q Yao, Maria C Rodriguez-Barradas, Shyam Mohapatra, Osmara Y Molina De Rodriguez, Emerson B Padiernos, Eric R Mcindoo, Emily Price, Hailey M Burgoyne, Ian Robey, Dawn C Schwenke, Carey L Shive, Ronald M Przygodzki, Rachel B Ramoni, Holly K Krull, Robert A Bonomo

Faculty, Staff and Students Publications

Background: The coronavirus disease 2019 (COVID-19) pandemic, caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has demonstrated the need to share data and biospecimens broadly to optimize clinical outcomes for US military Veterans.

Methods: In response, the Veterans Health Administration established VA SHIELD (Science and Health Initiative to Combat Infectious and Emerging Life-threatening Diseases), a comprehensive biorepository of specimens and clinical data from affected Veterans to advance research and public health surveillance and to improve diagnostic and therapeutic capabilities.

Results: VA SHIELD now comprises 12 sites collecting de-identified biospecimens from US Veterans affected by SARS-CoV-2. In addition, 2 …

Pharmacogenomics Translation In A Community Medical Context Using A Diffusion Of Innovations Framework: Provider Perspectives And Evaluation Implications, Sabrina Ewald Holley

Dissertations

Translation, in the context of medical research, is a process that describes how knowledge and innovation move and change into real world applications and outcomes. This study explores the translation of a medical innovation, pharmacogenomics (PGx), from research into clinical practice using the perspectives of medical providers in a community setting. PGx is the influence of a person’s genetics on drug response. Despite being available for over a decade, PGx testing is not widely adopted. Prior research primarily examined PGx translation in large academic medical centers, but not much is known about it in community practice settings. A better understanding …

Targeting The Mtor Pathway For The Prevention Of Er-Negative Breast Cancer, Abhijit Mazumdar, William M Tahaney, Jamal L Hill, Yun Zhang, Sumankalai Ramachandran, Jitesh Kawedia, Jing Qian, Alejandro Contreras, Michelle I Savage, Lana A Vornik, Shizuko Sei, Altaf Mohammed, Powel H Brown

Faculty, Staff and Student Publications

Our results show that everolimus delays mammary tumor formation in multiple mouse models, suggesting that mTOR inhibitors will be useful for the prevention of ER-negative and triple-negative breast cancer in humans. See related Spotlight, p. 787.

Lack Of Consensus Among Healthcare Professionals At A Large Academic Medical Center On The Use Of Exome Sequencing For Prenatal Diagnosis, Kylie Johnson, Hadi Erfani, Mohamad Ali Maktabi, Ignatia Van Den Veyver, Salma Nassef

Center for Medical Ethics and Health Policy Staff Publications

Prenatal exome sequencing (ES) is increasingly used for prenatal diagnosis because emerging data indicate it has incremental diagnostic benefit in pregnancies with fetal anomalies without identified genetic abnormalities by karyotyping and chromosomal microarray analysis. The aim of this study was to evaluate the medical community's attitude toward the clinical utility and use of exome sequencing for prenatal diagnosis and to address differences in attitudes and responses by type of practitioner, level of training, and years passed since last full-time training. We analyzed the answers of 109 trainees and professionals in the fields of genetic counseling, laboratory science, and medicine to …

Prenatal Phenotyping Of Fetal Tubulinopathies: A Multicenter Retrospective Case Series, Bobby K Brar, Marisa Gilstrop Thompson, Neeta L Vora, Kelly Gilmore, Karin Blakemore, Kristen A Miller, Jessica Giordano, Andreas Dufke, Beatrix Wong, Samantha Stover, Billie Lianoglou, Ignatia Van Den Veyver, Esther Dempsey, Mara Rosner, Karen Chong, David Chitayat, Teresa N Sparks, Mary E Norton, Ronald Wapner, Kristin Baranano, Angie C Jelin, Fetal Sequencing Consortium

Center for Medical Ethics and Health Policy Staff Publications

Objective: Tubulinopathies refer to conditions caused by genetic variants in isotypes of tubulin resulting in defective neuronal migration. Historically, diagnosis was primarily via postnatal imaging. Our objective was to establish the prenatal phenotype/genotype correlations of tubulinopathies identified by fetal imaging.

Methods: A large, multicenter retrospective case series was performed across nine institutions in the Fetal Sequencing Consortium. Demographics, fetal imaging reports, genetic screening and diagnostic testing results, delivery reports, and neonatal imaging reports were extracted for pregnancies with a confirmed molecular diagnosis of a tubulinopathy.

Results: Nineteen pregnancies with a fetal tubulinopathy were identified. The most common prenatal imaging findings …

Effect Of Problem-Solving Treatment On Self-Reported Disability Among Veterans With Gulf War Illness: A Randomized Clinical Trial, Lisa M Mcandrew, Karen S Quigley, Shou-En Lu, David Litke, Joseph F Rath, Gudrun Lange, Susan L Santos, Nicole Anastasides, Beth Ann Petrakis, Lauren Greenberg, Drew A Helmer, Wilfred R Pigeon

Center for Medical Ethics and Health Policy Staff Publications

Importance: Few evidence-based treatments are available for Gulf War illness (GWI). Behavioral treatments that target factors known to maintain the disability from GWI, such as problem-solving impairment, may be beneficial. Problem-solving treatment (PST) targets problem-solving impairment and is an evidence-based treatment for other conditions.

Objective: To examine the efficacy of PST to reduce disability, problem-solving impairment, and physical symptoms in GWI.

Design, setting, and participants: This multicenter randomized clinical trial conducted in the US Department of Veterans Affairs compared PST with health education in a volunteer sample of 511 Gulf War veterans with GWI and disability (January 1, 2015, to …

A Toddler With New Seizures, Progressive White Matter Lesions, And Multifocal Microhemorrhages, Dana Tlais, Stephanie Fetzko, Nitya Gulati, Huy Brandon D Tran, Sarah Risen, Yi-Chen Lai

Faculty, Staff and Students Publications

A 16-month-old, previously healthy male is hospitalized for new onset seizures. Initial investigation is significant for enterovirus/rhinovirus respiratory infection, abnormal T2 signal predominantly in the white matter and scattered microhemorrhages on brain MRI, transaminitis, and thrombocytopenia. His symptoms initially improve on steroid therapy and he is discharged from the hospital. During the ensuing month with the tapering of the steroids, he develops new motor deficits for which he is rehospitalized. His laboratory investigation on readmission is unremarkable. However, there is significant progression of white matter lesions and microhemorrhages on repeat MRI. While in the hospital, he becomes febrile and has …

Wide Range Of Phenotypic Severity In Individuals With Late Truncations Unique To The Predominant Cdkl5 Transcript In The Brain, Laura Keehan, Isabel Haviland, Yoel Gofin, Lindsay C Swanson, Christelle Moufawad El Achkar, John Schreiber, Grace E Vannoy, Emily O'Heir, Anne O'Donnell-Luria, Richard Alan Lewis, Pilar Magoulas, Alyssa Tran, Mahshid S Azamian, Hsiao-Tuan Chao, Lisa Pham, Rodney C Samaco, Sarah Elsea, Erin Thorpe, Akanchha Kesari, Denise Perry, Brendan Lee, Seema R Lalani, Jill A Rosenfeld, Heather E Olson, Lindsay C Burrage

Faculty, Staff and Students Publications

Cyclin-dependent kinase-like 5 (CDKL5) deficiency disorder (CDD) is caused by heterozygous or hemizygous variants in CDKL5 and is characterized by refractory epilepsy, cognitive and motor impairments, and cerebral visual impairment. CDKL5 has multiple transcripts, of which the longest transcripts, NM_003159 and NM_001037343, have been used historically in clinical laboratory testing. However, the transcript NM_001323289 is the most highly expressed in brain and contains 170 nucleotides at the 3' end of its last exon that are noncoding in other transcripts. Two truncating variants in this region have been reported in association with a CDD phenotype. To clarify the significance and range …

Fulminant Lung Fibrosis In Non-Resolvable Covid-19 Requiring Transplantation, Soma S K Jyothula, Andrew Peters, Yafen Liang, Weizhen Bi, Pooja Shivshankar, Simon Yau, Puneet S Garcha, Xiaoyi Yuan, Bindu Akkanti, Scott Collum, Nancy Wareing, Rajarajan A Thandavarayan, Fernando Poli De Frias, Ivan O Rosas, Bihong Zhao, L Maximilian Buja, Holger K Eltzschig, Howard J Huang, Harry Karmouty-Quintana

Faculty, Staff and Student Publications

BACKGROUND: Coronavirus Disease 2019 (COVID-19) can lead to the development of acute respiratory distress syndrome (ARDS). In some patients with non-resolvable (NR) COVID-19, lung injury can progress rapidly to the point that lung transplantation is the only viable option for survival. This fatal progression of lung injury involves a rapid fibroproliferative response and takes on average 15 weeks from initial symptom presentation. Little is known about the mechanisms that lead to this fulminant lung fibrosis (FLF) in NR-COVID-19.

METHODS: Using a pre-designed unbiased PCR array for fibrotic markers, we analyzed the fibrotic signature in a subset of NR-COVID-19 lungs. We …

Stellate Ganglion Block For Long Covid Symptom Management: A Case Report, Mashfee H Khan, Kennedy P Kirkpatrick, Yi Deng, Krishna B Shah

Faculty, Staff and Students Publications

Stellate ganglion block (SGB) is gaining increasing acceptance as a treatment modality for various medical conditions. It works by blocking neuronal transmissions which in turn alleviates sympathetically-driven disease processes. Many of the prolonged sequelae of long COVID are thought to be mediated by dysregulation of the autonomic nervous system, and SGB is being investigated as a potential option for symptomatic management of long COVID. This case report demonstrates the efficacy of SGB in a previously healthy patient for the management of long COVID symptoms including fatigue, post-exertional malaise, shortness of breath, and gastrointestinal symptoms.