Medical Specialties Commons^™

Dose Accumulation Of Daily Adaptive Plans To Decide Optimal Plan Adaptation Strategy For Head-And-Neck Patients Treated With Mr-Linac, Shin Yun Lim, Alan Tran, Anh Ngoc Kieu Tran, Angela Sobremonte, Clifton D Fuller, Lori Simmons, Jinzhong Yang

Faculty, Staff and Student Publications

Advances in magnetic resonance linear accelerators (MR-Linacs) allow for superior visualization of soft tissue to guide online adaptive replanning for precise radiotherapy delivery. Elekta Unity MR-Linacs (Elekta AB, Stockholm, Sweden) provides 2 plan adaptation approaches, adapt-to-position (ATP), plan reoptimization based on the reference CT with the iso-shift measured from daily MR scans, and adapt-to-shape (ATS), full plan reoptimization based on the re-contoured daily MR scans. Our study aims to close the gap in knowledge regarding the use of the ATP technique in the treatment of head and neck (HN) cancers through the analysis of accumulated dose of daily ATP plans …

Influenza Clinical Testing And Oseltamivir Treatment In Hospitalized Children With Acute Respiratory Illness, 2015-2016., Lubna Hamdan, Varvara Probst, Zaid Haddadin, Herdi Rahman, Andrew J. Spieker, Simon Vandekar, Laura S. Stewart, John V. Williams, Julie A. Boom, Flor Munoz, Janet A. Englund, Rangaraj Selvarangan, Mary A. Staat, Geoffrey A. Weinberg, Parvin H. Azimi, Eileen J. Klein, Monica Mcneal, Leila C. Sahni, Monica N. Singer, Peter G. Szilagyi, Christopher J. Harrison, Manish Patel, Angela P. Campbell, Natasha B. Halasa

Manuscripts, Articles, Book Chapters and Other Papers

BACKGROUND: Antiviral treatment is recommended for all hospitalized children with suspected or confirmed influenza, regardless of their risk profile. Few data exist on adherence to these recommendations, so we sought to determine factors associated with influenza testing and antiviral treatment in children.

METHODS: Hospitalized children(ARI) were enrolled through active surveillance at pediatric medical centers in seven cities between 11/1/2015 and 6/30/2016; clinical information was obtained from parent interview and chart review. We used generalized linear mixed-effects models to identify factors associated with influenza testing and antiviral treatment.

RESULTS: Of the 2299 hospitalized children with ARI enrolled during one influenza season, …

Interleukin-6 Blockade Abrogates Immunotherapy Toxicity And Promotes Tumor Immunity, Ahmed Omar Kaseb, Elshad Hasanov, Hop Sanderson Tran Cao, Lianchun Xiao, Jean-Nicolas Vauthey, Sunyoung S Lee, Betul Gok Yavuz, Yehia I Mohamed, Aliya Qayyum, Sonali Jindal, Fei Duan, Sreyashi Basu, Shalini S Yadav, Courtney Nicholas, Jing Jing Sun, Kanwal Pratap Singh Raghav, Asif Rashid, Kristen Carter, Yun Shin Chun, Ching-Wei David Tzeng, Divya Sakamuri, Li Xu, Ryan Sun, Vittorio Cristini, Laura Beretta, James C Yao, Robert A Wolff, James Patrick Allison, Padmanee Sharma

Faculty, Staff and Student Publications

BACKGROUND: Hepatocellular carcinoma has high recurrence rates after surgery; however, there are no approved standard-of-care neoadjuvant or adjuvant therapies. Immunotherapy has been shown to improve survival in advanced hepatocellular carcinoma; we therefore aimed to evaluate the safety and tolerability of perioperative immunotherapy in resectable hepatocellular carcinoma.

METHODS: In this single-centre, randomised, open-label, phase 2 trial, patients with resectable hepatocellular carcinoma were randomly assigned (1:1) to receive 240 mg of nivolumab intravenously every 2 weeks (for up to three doses before surgery at 6 weeks) followed in the adjuvant phase by 480 mg of nivolumab intravenously every 4 weeks for 2 …

Metabolic Stress Induces Gd2+ Cancer Stem Cell-Like Phenotype In Triple-Negative Breast Cancer, Appalaraju Jaggupilli, Stanley Ly, Khoa Nguyen, Vivek Anand, Bin Yuan, Fouad El-Dana, Yuanqing Yan, Zoe Arvanitis, Danthasinghe Waduge Badrajee Piyarathna, Nagireddy Putluri, Helen Piwnica-Worms, Henry Charles Manning, Michael Andreeff, V Lokesh Battula

Faculty, Staff and Student Publications

Background: Metabolic stress resulting from nutrient deficiency is one of the hallmarks of a growing tumour. Here, we tested the hypothesis that metabolic stress induces breast cancer stem-like cell (BCSC) phenotype in triple-negative breast cancer (TNBC).

Methods: Flow cytometry for GD2 expression, mass spectrometry and Ingenuity Pathway Analysis for metabolomics, bioinformatics, in vitro tumorigenesis and in vivo models were used.

Results: Serum/glucose deprivation not only increased stress markers but also enhanced GD2+ BCSC phenotype and function in TNBC cells. Global metabolomics profiling identified upregulation of glutathione biosynthesis in GD2high cells, suggesting a role of glutamine in the BCSC phenotype. Cueing …

Stem Cell Architecture Drives Myelodysplastic Syndrome Progression And Predicts Response To Venetoclax-Based Therapy, Irene Ganan-Gomez, Hui Yang, Feiyang Ma, Guillermo Montalban-Bravo, Natthakan Thongon, Valentina Marchica, Guillaume Richard-Carpentier, Kelly Chien, Ganiraju Manyam, Feng Wang, Ana Alfonso, Shuaitong Chen, Caleb Class, Rashmi Kanagal-Shamanna, Justin P Ingram, Yamini Ogoti, Ashley Rose, Sanam Loghavi, Pamela Lockyer, Benedetta Cambo, Muharrem Muftuoglu, Sarah Schneider, Vera Adema, Michael Mclellan, John Garza, Matteo Marchesini, Nicola Giuliani, Matteo Pellegrini, Jing Wang, Jason Walker, Ziyi Li, Koichi Takahashi, Joel D Leverson, Carlos Bueso-Ramos, Michael Andreeff, Karen Clise-Dwyer, Guillermo Garcia-Manero, Simona Colla

Faculty, Staff and Student Publications

Myelodysplastic syndromes (MDS) are heterogeneous neoplastic disorders of hematopoietic stem cells (HSCs). The current standard of care for patients with MDS is hypomethylating agent (HMA)-based therapy; however, almost 50% of MDS patients fail HMA therapy and progress to acute myeloid leukemia, facing a dismal prognosis due to lack of approved second-line treatment options. As cancer stem cells are the seeds of disease progression, we investigated the biological properties of the MDS HSCs that drive disease evolution, seeking to uncover vulnerabilities that could be therapeutically exploited. Through integrative molecular profiling of HSCs and progenitor cells in large patient cohorts, we found …

Underutilization Of Endovascular Therapy In Black Patients With Ischemic Stroke: An Analysis Of State And Nationwide Cohorts, Youngran Kim, Anjail Sharrief, Min Ji Kwak, Swapnil Khose, Rania Abdelkhaleq, Sergio Salazar-Marioni, Guo-Qiang Zhang, Sunil A Sheth

Faculty, Staff and Student Publications

BACKGROUND AND PURPOSE: Endovascular therapy (EVT) is a very effective treatment but relies on specialized capabilities that are not available in every hospital where acute ischemic stroke is treated. Here, we assess whether access to and utilization of this therapy has extended uniformly across racial and ethnic groups.

METHODS: We conducted a retrospective, population-based study using the 2019 Texas Inpatient Public Use Data File. Acute ischemic stroke cases and EVT use were identified using the

RESULTS: Among 40 814 acute ischemic stroke cases in Texas in 2019, 54% were White, 17% Black, and 21% Hispanic. Black patients had similar admissions …

Chronic Estrus Disrupts Uterine Gland Development And Homeostasis, C Allison Stewart, M David Stewart, Ying Wang, Rachel D Mullen, Bonnie K Kircher, Rui Liang, Yu Liu, Richard R Behringer

Faculty, Staff and Student Publications

Female mice homozygous for an engineered Gnrhr E90K mutation have reduced gonadotropin-releasing hormone signaling, leading to infertility. Their ovaries have numerous antral follicles but no corpora lutea, indicating a block to ovulation. These mutants have high levels of circulating estradiol and low progesterone, indicating a state of persistent estrus. This mouse model provided a unique opportunity to examine the lack of cyclic levels of ovarian hormones on uterine gland biology. Although uterine gland development appeared similar to controls during prepubertal development, it was compromised during adolescence in the mutants. By age 20 weeks, uterine gland development was comparable to controls, …

Naked (N) Mutant Mice Carry A Nonsense Mutation In The Homeobox Of Hoxc13, Carlos J Perez, Lars Mecklenburg, Almudena Fernandez, Marta Cantero, Tiago Antonio De Souza, Kevin Lin, Sharon Y R Dent, Lluis Montoliu, Alexander Awgulewitsch, Fernando Benavides

Faculty, Staff and Student Publications

Loss of function mutations in HOXC13 have been associated with Ectodermal Dysplasia-9, Hair/Nail Type (ECTD9) in consanguineous families, characterized by sparse to complete absence of hair and nail dystrophy. Here we characterize the spontaneous mouse mutation Naked (N) as a terminal truncation in the Hoxc13 (homeobox C13) gene. Similar to previous reports for homozygous Hoxc13 knock-out (KO) mice, homozygous N/N mice exhibit generalized alopecia with abnormal nails and a short lifespan. However, in contrast to Hoxc13 heterozygous KO mice, N/+ mice show generalized or partial alopecia, associated with loss of hair fibres, along with normal lifespan and fertility. Our data …

Perioperative Nivolumab Monotherapy Versus Nivolumab Plus Ipilimumab In Resectable Hepatocellular Carcinoma: A Randomised, Open-Label, Phase 2 Trial, Ahmed Omar Kaseb, Elshad Hasanov, Hop Sanderson Tran Cao, Lianchun Xiao, Jean-Nicolas Vauthey, Sunyoung S Lee, Betul Gok Yavuz, Yehia I Mohamed, Aliya Qayyum, Sonali Jindal, Fei Duan, Sreyashi Basu, Shalini S Yadav, Courtney Nicholas, Jing Jing Sun, Kanwal Pratap Singh Raghav, Asif Rashid, Kristen Carter, Yun Shin Chun, Ching-Wei David Tzeng, Divya Sakamuri, Li Xu, Ryan Sun, Vittorio Cristini, Laura Beretta, James C Yao, Robert A Wolff, James Patrick Allison, Padmanee Sharma

Faculty, Staff and Student Publications

BACKGROUND: Hepatocellular carcinoma has high recurrence rates after surgery; however, there are no approved standard-of-care neoadjuvant or adjuvant therapies. Immunotherapy has been shown to improve survival in advanced hepatocellular carcinoma; we therefore aimed to evaluate the safety and tolerability of perioperative immunotherapy in resectable hepatocellular carcinoma.

METHODS: In this single-centre, randomised, open-label, phase 2 trial, patients with resectable hepatocellular carcinoma were randomly assigned (1:1) to receive 240 mg of nivolumab intravenously every 2 weeks (for up to three doses before surgery at 6 weeks) followed in the adjuvant phase by 480 mg of nivolumab intravenously every 4 weeks for 2 …

Accounting For Egfr Mutations In Epidemiologic Analyses Of Non-Small Cell Lung Cancers: Examples Based On The International Lung Cancer Consortium Data, Sabine Schmid, Mei Jiang, M Catherine Brown, Aline Fares, Miguel Garcia, Joelle Soriano, Mei Dong, Sera Thomas, Takashi Kohno, Leticia Ferro Leal, Nancy Diao, Juntao Xie, Zhichao Wang, David Zaridze, Ivana Holcatova, Jolanta Lissowska, Beata Świątkowska, Dana Mates, Milan Savic, Angela S Wenzlaff, Curtis C Harris, Neil E Caporaso, Hongxia Ma, Guillermo Fernandez-Tardon, Matthew J Barnett, Gary Goodman, Michael P A Davies, Mónica Pérez-Ríos, Fiona Taylor, Eric J Duell, Ben Schoettker, Hermann Brenner, Angeline Andrew, Angela Cox, Alberto Ruano-Ravina, John K Field, Loic Le Marchand, Ying Wang, Chu Chen, Adonina Tardon, Sanjay Shete, Matthew B Schabath, Hongbing Shen, Maria Teresa Landi, Brid M Ryan, Ann G Schwartz, Lihong Qi, Lori C Sakoda, Paul Brennan, Ping Yang, Jie Zhang, David C Christiani, Rui Manuel Reis, Kouya Shiraishi, Rayjean J Hung, Wei Xu, Geoffrey Liu

Faculty, Staff and Student Publications

Background: Somatic EGFR mutations define a subset of non-small cell lung cancers (NSCLC) that have clinical impact on NSCLC risk and outcome. However, EGFR-mutation-status is often missing in epidemiologic datasets. We developed and tested pragmatic approaches to account for EGFR-mutation-status based on variables commonly included in epidemiologic datasets and evaluated the clinical utility of these approaches.

Methods: Through analysis of the International Lung Cancer Consortium (ILCCO) epidemiologic datasets, we developed a regression model for EGFR-status; we then applied a clinical-restriction approach using the optimal cut-point, and a second epidemiologic, multiple imputation approach to ILCCO survival analyses that did and did …

Subtype-Specific And Co-Occurring Genetic Alterations In B-Cell Non-Hodgkin Lymphoma, Man Chun John Ma, Saber Tadros, Alyssa Bouska, Tayla Heavican, Haopeng Yang, Qing Deng, Dalia Moore, Ariz Akhter, Keenan Hartert, Neeraj Jain, Jordan Showell, Sreejoyee Ghosh, Lesley Street, Marta Davidson, Christopher Carey, Joshua Tobin, Deepak Perumal, Julie M Vose, Matthew A Lunning, Aliyah R Sohani, Benjamin J Chen, Shannon Buckley, Loretta J Nastoupil, R Eric Davis, Jason R Westin, Nathan H Fowler, Samir Parekh, Maher Gandhi, Sattva Neelapu, Douglas Stewart, Kapil Bhalla, Javeed Iqbal, Timothy Greiner, Scott J Rodig, Adnan Mansoor, Michael R Green

Faculty, Staff and Student Publications

B-cell non-Hodgkin lymphoma (B-NHL) encompasses multiple clinically and phenotypically distinct subtypes of malignancy with unique molecular etiologies. Common subtypes of B-NHL, such as diffuse large B-cell lymphoma, have been comprehensively interrogated at the genomic level, but rarer subtypes, such as mantle cell lymphoma, remain less extensively characterized. Furthermore, multiple B-NHL subtypes have thus far not been comprehensively compared using the same methodology to identify conserved or subtype-specific patterns of genomic alterations. Here, we employed a large targeted hybrid-capture sequencing approach encompassing 380 genes to interrogate the genomic landscapes of 685 B-NHL tumors at high depth, including diffuse large B-cell lymphoma, …

Intracardiac Thrombus In Coronavirus Disease-2019, Suganya Karikalan, Munish Sharma, Megha Chandna, Manju Sachdev, Ajay Gaalla, Farah Yasmin, Reena Shah, Iqbal Ratnani

Internal Medicine, East Africa

Intracardiac thrombus is often seen as a complication of ischemic heart disease (IHD) and non-ischemia cardiomyopathies (NICM). The advancements in imaging modalities and therapeutic options have helped reduce the complications arising from ventricular thrombi, such as systemic embolization. Here we present two cases of intracardiac thrombus associated with coronavirus disease (COVID) 19, one with an apical thrombus in the left ventricle and the other with a thrombus in the right ventricle adjacent to chordae tendinae. The effects of covid-19 on the cardiovascular system are yet to be thoroughly evaluated. Venous and arterial thrombosis is commonly associated with COVID-19 but in …

Secondary Infections In Patients With Covid-19 Pneumonia Treated With Tocilizumab Compared To Those Not Treated With Tocilizumab: A Retrospective Study At A Tertiary Hospital In Kenya, Reena Shah, Jasmit Shah, Jaimini Gohil, Gunturu Revathi, Salim Surani

Internal Medicine, East Africa

Introduction: From the first case of SARS-Co-2 in Wuhan, China, to the virus being declared as a pandemic in March 2020, the world has witnessed morbidity and mortality on a global scale. Scientists have worked at a record pace to deliver a vaccine for the prevention of this deadly disease. Tocilizumab, an interleukin-6 (IL-6) blocker, received an emergency use authorization (EUA) by the Federal Drug Agency (FDA) in June 2021.
Methods: This retrospective observational cohort study was conducted at the Aga Khan University Hospital, Nairobi, from March 8, 2020, to December 31, 2020. All patients with PCR confirmed …

Clinical Spectrum Of Celiac Disease In Adults At A Tertiary Care Hospital In Karachi, Pakistan, Verda Arshad, Maha Inam, Safia Awan, Faisal Wasim Ismail

Medical College Documents

Objectives: Celiac Disease (CD) is a disorder that impacts physical, social and emotional health. Requiring life-long treatment, it poses a major economic burden on the healthcare system. Our objective was to study CD in patients from initial presentation to diagnosis and to ascertain the effect of a low resource setting on improvement in disease process.
Methods: This is a retrospective cross-sectional study conducted at a Aga Khan University Hospital (AKUH), a tertiary care center in Karachi, Pakistan. Medical records of patients (≥ 18 years) from 2008 to 2018 with a diagnosis of CD were reviewed. Data on demographics, presenting complaints, …

The Mesencephalic Locomotor Region Recruits V2a Reticulospinal Neurons To Drive Forward Locomotion In Larval Zebrafish, Nicole Ilonzo, Ella Taubenfeld, Maisoon D Yousif, Claudine Henoud, Jake Howitt, Max Wohlauer, Mario D'Oria, Gretchen Maccarrick

Faculty, Staff and Student Publications

Although the topics of surgical techniques and medical therapies have been widely studied in aortic dissection (AD), studies examining the short- and long-term impact of this event on mental health are largely lacking. Many of the studies have used the 36-Item Short Form Survey at variable time points after the event. However, AD as medical trauma has a complex impact on a person's identity. Its implications for emotional, mental, social, existential, and self-concept could be explored more robustly. This topic was identified as a topic of interest by the AD Collaborative. The AD Collaborative Mental Health Working Group was formed …

Of Vascular Defense, Hemostasis, Cancer, And Platelet Biology: An Evolutionary Perspective, David G Menter, Vahid Afshar-Kharghan, John Paul Shen, Stephanie L Martch, Anirban Maitra, Scott Kopetz, Kenneth V Honn, Anil K Sood

Faculty, Staff and Student Publications

We have established considerable expertise in studying the role of platelets in cancer biology. From this expertise, we were keen to recognize the numerous venous-, arterial-, microvascular-, and macrovascular thrombotic events and immunologic disorders are caused by severe, acute-respiratory-syndrome coronavirus 2 (SARS-CoV-2) infections. With this offering, we explore the evolutionary connections that place platelets at the center of hemostasis, immunity, and adaptive phylogeny. Coevolutionary changes have also occurred in vertebrate viruses and their vertebrate hosts that reflect their respective evolutionary interactions. As mammals adapted from aquatic to terrestrial life and the heavy blood loss associated with placentalization-based live birth, platelets …

Inhibition Of Calcium-Triggered Secretion By Hydrocarbon-Stapled Peptides, Ying Lai, Giorgio Fois, Jose R Flores, Michael J Tuvim, Qiangjun Zhou, Kailu Yang, Jeremy Leitz, John Peters, Yunxiang Zhang, Richard A Pfuetzner, Luis Esquivies, Philip Jones, Manfred Frick, Burton F Dickey, Axel T Brunger

Faculty, Staff and Student Publications

Membrane fusion triggered by Ca2+ is orchestrated by a conserved set of proteins to mediate synaptic neurotransmitter release, mucin secretion and other regulated exocytic processes1-4. For neurotransmitter release, the Ca2+ sensitivity is introduced by interactions between the Ca2+ sensor synaptotagmin and the SNARE complex5, and sequence conservation and functional studies suggest that this mechanism is also conserved for mucin secretion6. Disruption of Ca2+-triggered membrane fusion by a pharmacological agent would have therapeutic value for mucus hypersecretion as it is the major cause of airway obstruction in the pathophysiology of respiratory viral infection, asthma, chronic obstructive pulmonary disease and cystic fibrosis7-11. …

Current State And Future Directions Of Genomic Medicine In Aortic Dissection: A Path To Prevention And Personalized Care, Alana C Cecchi, Madeline Drake, Chrisanne Campos, Jake Howitt, Jonathan Medina, Scott M Damrauer, Sherene Shalhub, Dianna M Milewicz, Aortic Dissection Collaborative

Faculty, Staff and Student Publications

Aortic dissection confers high mortality and morbidity rates despite advances in treatment, impacts quality of life, and contributes immense burden to the healthcare system globally. Efforts to prevent aortic dissection through screening and management of modifiable risk factors and early detection of aneurysms should incorporate genomic information, as it is integral to stratifying risk. However, effective integration of genomic-guided risk assessment into clinical practice will require addressing implementation barriers that currently permeate our healthcare systems. The Aortic Dissection Collaborative was established to define aortic dissection research priorities through patient engagement. Using a collaborative patient-centered feedback model, our Genomic Medicine Working …

Methyl-Lysine Readers Phf20 And Phf20l1 Define Two Distinct Gene Expression-Regulating Nsl Complexes, Hieu T Van, Peter R Harkins, Avni Patel, Abhinav K Jain, Yue Lu, Mark T Bedford, Margarida A Santos

Faculty, Staff and Student Publications

The methyl-lysine readers plant homeodomain finger protein 20 (PHF20) and its homolog PHF20-like protein 1 (PHF20L1) are known components of the nonspecific lethal (NSL) complex that regulates gene expression through its histone acetyltransferase activity. In the current model, both PHF homologs coexist in the same NSL complex, although this was not formally tested; nor have the functions of PHF20 and PHF20L1 regarding NSL complex integrity and transcriptional regulation been investigated. Here, we perform an in-depth biochemical and functional characterization of PHF20 and PHF20L1 in the context of the NSL complex. Using mass spectrometry, genome-wide chromatin analysis, and protein-domain mapping, we …

Value Of Measurable Residual Disease Monitoring In Patients With Acute Promyelocytic Leukemia In The Era Of Frontline ‘Chemotherapy-Free’ Therapy, Jorge M Ramos Perez, Keyur P Patel, Sanam Loghavi, Guillermo Garcia-Manero, Gautam Borthakur, Elias Jabbour, William Wierda, Sherry Pierce, Mark Brandt, Steven Kornblau, Tapan Kadia, Naval Daver, Courtney D Dinardo, Nitin Jain, Musa Yilmaz, Nicholas Short, Srdan Verstovsek, Alessandra Ferrajoli, Michael Andreeff, Marina Konopleva, Daniel Rivera, David Mccue, Hagop M Kantarjian, Farhad Ravandi

Faculty, Staff and Student Publications

Acute promyelocytic leukemia (APL) is characterized by the chromosomal translocation t(15;17) and the resulting gene PML-RARA, used for measurable residual disease (MRD) monitoring. Despite highly effective therapy for APL, MRD monitoring practices are not fully established. We aimed to assess the value of MRD monitoring by RT-qPCR in patients with APL treated with ATRA and arsenic trioxide +/- GO. We reviewed 223 patients with APL treated with this regimen. RT-qPCR for PML-RARA was measured every 3 months, and at 12, 18, and 24 months after therapy. Seven patients relapsed. Time to relapse was 7.9-12.4 months in 6 patients, and …

Long-Term Survival Following Definitive Radiation Therapy For Recurrence Or Oligometastases In Gynecological Malignancies: A Landmark Analysis, Kelsey L Corrigan, Alison Yoder, Brian De, Lilie Lin, Anuja Jhingran, Melissa M Joyner, Patricia J Eifel, Lauren E Colbert, Karen H Lu, Ann H Klopp

Faculty, Staff and Student Publications

Objective: Radiation therapy (RT) may improve outcomes for patients with oligometastatic cancer. We sought to determine if there are long-term survivors treated with definitive RT for recurrent or oligometastatic gynecological cancer (ROMGC), and to evaluate the clinical and disease characteristics of these patients.

Methods: We performed a landmark analysis in 48 patients with ROMGC who survived for ≥5 years following definitive RT of their metastasis. Patient characteristics were extracted from the medical record. DFS was modeled using the Kaplan-Meier method.

Results: This cohort included 20 patients (42%) with ovarian cancer, 16 (33%) with endometrial cancer, 11 (23%) with cervical cancer, …

Peripheral And Central Kynurenine Pathway Abnormalities In Major Depression, Elisabeth R Paul, Lilly Schwieler, Sophie Erhardt, Sandra Boda, Ada Trepci, Robin Kämpe, Anna Asratian, Lovisa Holm, Adam Yngve, Robert Dantzer, Markus Heilig, J Paul Hamilton, Martin Samuelsson

Faculty, Staff and Student Publications

Considerable data relate major depressive disorder (MDD) with aberrant immune system functioning. Pro-inflammatory cytokines facilitate metabolism of tryptophan along the kynurenine pathway (KP) putatively resulting in reduced neuroprotective and increased neurotoxic KP metabolites in MDD, in addition to modulating metabolic and immune function. This central nervous system hypothesis has, however, only been tested in the periphery. Here, we measured KP-metabolite levels in both plasma and cerebrospinal fluid (CSF) of depressed patients (n = 63/36 respectively) and healthy controls (n = 48/33). Further, we assessed the relation between KP abnormalities and brain-structure volumes, as well as body mass index (BMI), an …

Sleep Challenges And Interventions In Children With Visual Impairment., David G. Ingram Md, Jose M. Cruz, Erin Stahl, Nicole M. Carr, Lisa J. Lind, Carla C. Keirns

Manuscripts, Articles, Book Chapters and Other Papers

PURPOSE: To examine sleep patterns in a large and heterogeneous group of children with visual impairment.

METHODS: A cross-sectional survey of parents of children with visual impairment was offered via the National Federation of the Blind and the National Organization for Albinism and Hypopigmentation.

RESULTS: Complete survey results were available for 72 participants, aged 1 to 16 years. Parents of 52 (72%) children reported that their child had cycles of good sleep and bad sleep, and 50 (69%) reported that their child's sleep patterns caused significant stress for them or their family. Scores on the Childhood Sleep Habits Questionnaire (CSHQ) …

Characterization Of Patient-Derived Bone Marrow Human Mesenchymal Stem Cells As Oncolytic Virus Carriers For The Treatment Of Glioblastoma, Yuzaburo Shimizu, Joy Gumin, Feng Gao, Anwar Hossain, Elizabeth J Shpall, Akihide Kondo, Brittany C Parker Kerrigan, Jing Yang, Daniel Ledbetter, Juan Fueyo, Candelaria Gomez-Manzano, Frederick F Lang

Faculty, Staff and Student Publications

Objective: Delta-24-RGD is an oncolytic adenovirus that is capable of replicating in and killing human glioma cells. Although intratumoral delivery of Delta-24-RGD can be effective, systemic delivery would improve its clinical application. Bone marrow-derived human mesenchymal stem cells (BM-hMSCs) obtained from healthy donors have been investigated as virus carriers. However, it is unclear whether BM-hMSCs can be derived from glioma patients previously treated with marrow-toxic chemotherapy or whether such BM-hMSCs can deliver oncolytic viruses effectively. Herein, the authors undertook a prospective clinical trial to determine the feasibility of obtaining BM-hMSCs from patients with recurrent malignant glioma who were previously exposed …

Local Treatment Of A Pediatric Osteosarcoma Model With A 4-1bbl Armed Oncolytic Adenovirus Results In An Antitumor Effect And Leads To Immune Memory, Naiara Martinez-Velez, Virginia Laspidea, Marta Zalacain, Sara Labiano, Marc García-Moure, Montse Puigdelloses, Lucía Marrodan, Marisol Gonzalez-Huarriz, Guillermo Herrador, Daniel De La Nava, Iker Ausejo-Mauleon, Juan Fueyo, Candelaria Gomez-Manzano, Ana Patiño-García, Marta M Alonso

Faculty, Staff and Student Publications

Osteosarcoma is an aggressive bone tumor occurring primarily in pediatric patients. Despite years of intensive research, the outcomes of patients with metastatic disease or those who do not respond to therapy have remained poor and have not changed in the last 30 years. Oncolytic virotherapy is becoming a reality to treat local and metastatic tumors while maintaining a favorable safety profile. Delta-24-ACT is a replicative oncolytic adenovirus engineered to selectively target cancer cells and to potentiate immune responses through expression of the immune costimulatory ligand 4-1BB. This work aimed to assess the antisarcoma effect of Delta-24-ACT. MTS and replication assays …

Determinant Of Repeat Revascularization Within 5 Years Of Percutaneous Coronary Lntervention At A Tertiary Care Hospital, Karachi: A Matched Case-Control Study, Komal Valliani, Azmina Artani, Iqbal Azam, Javed Tai, M. Masood Kadir

Community Health Sciences

Objective: To determine factors associated with repeat revascularization among adults aged 25 years and above within 5 years of first Percutaneous Coronary Intervention (PCI) at a tertiary care hospital.
Methods: A matched case-control study was conducted through a hospital records review. A total of 90 cases with repeat revascularization and 180 controls without repeat revascularization were included. Data was analyzed using Multiple Conditional Logistic Regression.
Results: The mean age was similar in cases and controls (60.05 ± 10.01 vs 62.20 ± 10.43 years) and sex (male: 77.8% vs. 76.1%). History of being an ever-smoker (40% vs. 25%), overweight (36.3% vs. …

The Corkscrew Technique For Removing A Fibular Strut Allograft From The Proximal Humerus., Brian Skura, Matthew T Glazier, Hayden B Schuette, Braden J Passias, Iou-Ren Chang, John Verre, Sanjay Mehta, Benjamin C Taylor

Surgery Articles

A fibular strut allograft is a reliable option for augmentation in open reduction internal fixation (ORIF) of proximal humerus fractures, but techniques to remove a fibular strut during revision shoulder arthroplasty are limited. Currently published techniques on extracting fibular strut grafts from humeral shafts include using a Midas burr, flexible osteotomes, humeral shaft osteotomy, and reaming. To our knowledge there has not been a technique that uses a corkscrew to remove the fibular strut from the proximal humerus in preparation for revision shoulder arthroplasty. This is a case report and description of a simple and reproducible technique that can be …

The Correlation Of D-Dimer To Stroke Diagnosis Within 24 Hours: A Meta-Analysis, Adeel Ahmad, Zara Islam, Saad Manzoor Ahmad, Zouina Sarfraz, Azza Sarfraz, Miguel Felix, Ivan Cherrez-Ojeda

Department of Paediatrics and Child Health

Background: Diagnosing D-Dimer early is essential to optimize clinical treatment and quality of life and reduce mortality. This study aims to identify the difference of D-Dimer levels (ng/ml) in patients with stroke within the 6- and 24-h period compared to patients that mimic stroke.
Methods: An electronic database search across PubMed/MEDLINE, Cochrane, Web of Science, CINAHL, EMBASE, and Scopus was conducted until December 10, 2021. Studies were eligible if they included adult patients with stroke compared to stroke mimics or controls reporting D-Dimer values. Quality assessment was conducted using GRADE. The standardized mean difference and 95% confidence intervals were calculated …

Optimizing Prevention And Community-Based Management Of Severe Malnutrition In Children, Zulfiqar Ahmed Bhutta

Department of Paediatrics and Child Health

Zulfiqar A. Bhutta discusses prevention and treatment strategies for optimization of community-based management of severe acute malnutrition in children

Factors Associated With Penicillin Allergy Labels In Electronic Health Records Of Children In 2 Large Us Pediatric Primary Care Networks, Margaret G Taylor, Torsten Joerger, Yun Li, Michael E Scheurer, Michael E Russo, Jeffrey S Gerber, Debra L Palazzi

Faculty, Staff and Students Publications

IMPORTANCE: Penicillin allergy labels influence clinical decision-making, yet most children who are labeled do not have type 1 hypersensitivity allergic reactions and instead have a history of predictable adverse reactions or unspecified illness symptoms while receiving penicillin for viral infections. Studies describing penicillin allergy labeling in the pediatric outpatient setting are lacking.

OBJECTIVE: To describe the epidemiology and factors associated with penicillin allergy labels across 2 large US pediatric primary care networks.

DESIGN, SETTING, AND PARTICIPANTS: This retrospective, longitudinal birth cohort study was conducted in 90 primary care pediatric practices serving a diverse population of children across Houston, Texas, Austin, …