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Articles 2881 - 2910 of 8091
Full-Text Articles in Medical Specialties
Decoding Metastatic Microenvironments Through Single-Cell Omics Reveals New Insights Into Niche Dynamics And Tumor Evolution, Fengshuo Liu, Xiang H-F Zhang
Decoding Metastatic Microenvironments Through Single-Cell Omics Reveals New Insights Into Niche Dynamics And Tumor Evolution, Fengshuo Liu, Xiang H-F Zhang
Faculty, Staff and Students Publications
Metastasis is the predominant cause of cancer mortality, primarily driven by complex tumor-host interactions within specialized metastatic niches. Recent advances in single-cell technologies have provided unprecedented insights into metastatic niche formation, evolution and function, including how primary tumors precondition distant organs for metastases and how disseminated tumor cells dynamically interact with host cells to modulate their environments. Integrated single-cell studies across multiple cancer types have also revealed divergent and convergent metastatic adaptation strategies. These findings collectively highlight metastasis as a dynamic, cooperative process shaped by intricate tumor-host interactions, and provide a foundation for novel therapeutic strategies targeting components of the …
Association Of Statin Use On Survival Outcomes Of Patients With Early-Stage Her2-Positive Breast Cancer In The Aphinity Trial, Christian Maurer, Elisa Agostinetto, Lieveke Ameye, Matteo Lambertini, Samuel Martel, Noam Ponde, Mariana Brandão, Francesca Poggio, Arlindo Ferreira, Rachel Schiff, Carmine De Angelis, Richard D Gelber, Susan Dent, Christoph Thomssen, Martine Piccart, Evandro De Azambuja
Association Of Statin Use On Survival Outcomes Of Patients With Early-Stage Her2-Positive Breast Cancer In The Aphinity Trial, Christian Maurer, Elisa Agostinetto, Lieveke Ameye, Matteo Lambertini, Samuel Martel, Noam Ponde, Mariana Brandão, Francesca Poggio, Arlindo Ferreira, Rachel Schiff, Carmine De Angelis, Richard D Gelber, Susan Dent, Christoph Thomssen, Martine Piccart, Evandro De Azambuja
Faculty, Staff and Students Publications
Purpose: There is evidence that statins might improve the outcome of patients with breast cancer. The role of statins in patients with early HER2-positive breast cancer is unknown. Therefore, we explored the association between statin use and survival outcomes in early HER2-positive breast cancer patients in the phase III APHINITY trial (adjuvant pertuzumab/trastuzumab).
Methods: All patients (intent-to-treat population, n = 4804) were included (6.2 years median follow-up database). The primary objective was to investigate the association of statin use on invasive disease-free survival (IDFS), distant relapse-free interval (DRFI), and overall survival (OS). Patients who received statins at baseline, or started …
Comprehensive Genome Analysis And Variant Detection At Scale Using Dragen, Sairam Behera, Severine Catreux, Massimiliano Rossi, Sean Truong, Zhuoyi Huang, Michael Ruehle, Arun Visvanath, Gavin Parnaby, Cooper Roddey, Vitor Onuchic, Andrea Finocchio, Daniel L Cameron, Adam English, Shyamal Mehtalia, James Han, Rami Mehio, Fritz J Sedlazeck
Comprehensive Genome Analysis And Variant Detection At Scale Using Dragen, Sairam Behera, Severine Catreux, Massimiliano Rossi, Sean Truong, Zhuoyi Huang, Michael Ruehle, Arun Visvanath, Gavin Parnaby, Cooper Roddey, Vitor Onuchic, Andrea Finocchio, Daniel L Cameron, Adam English, Shyamal Mehtalia, James Han, Rami Mehio, Fritz J Sedlazeck
Faculty, Staff and Students Publications
Research and medical genomics require comprehensive, scalable methods for the discovery of novel disease targets, evolutionary drivers and genetic markers with clinical significance. This necessitates a framework to identify all types of variants independent of their size or location. Here we present DRAGEN, which uses multigenome mapping with pangenome references, hardware acceleration and machine learning-based variant detection to provide insights into individual genomes, with ~30 min of computation time from raw reads to variant detection. DRAGEN outperforms current state-of-the-art methods in speed and accuracy across all variant types (single-nucleotide variations, insertions or deletions, short tandem repeats, structural variations and copy …
Baseline Cognition And Demographic, Lifestyle, And Cardiovascular Risk Factors In Us Pointer, Kathryn V Papp, Sarah Tomaszewski Farias, Marjorie Howard, Amber Thro, Tiia Ngandu, Brad Caudle, Bonnie C Sachs, Michelle Chan, Kristin R Krueger, Elizabeth R T Hartman, Athene Lee, Michele K York, Marie T Austin, Kathryn E Demos, Thomas M Holland, Xiaoyan Leng, Rema Raman, Heather M Snyder, Maria C Carrillo, Rachel A Whitmer, Mark A Espeland, Laura D Baker
Baseline Cognition And Demographic, Lifestyle, And Cardiovascular Risk Factors In Us Pointer, Kathryn V Papp, Sarah Tomaszewski Farias, Marjorie Howard, Amber Thro, Tiia Ngandu, Brad Caudle, Bonnie C Sachs, Michelle Chan, Kristin R Krueger, Elizabeth R T Hartman, Athene Lee, Michele K York, Marie T Austin, Kathryn E Demos, Thomas M Holland, Xiaoyan Leng, Rema Raman, Heather M Snyder, Maria C Carrillo, Rachel A Whitmer, Mark A Espeland, Laura D Baker
Faculty, Staff and Students Publications
Introduction: Validation of the primary cognitive composite and baseline cognitive characteristics are presented for the US-Study-to-Protect-Brain-Health-Through-Lifestyle-Intervention-to-Reduce-Risk (US POINTER).
Methods: US POINTER is a multicenter, randomized clinical trial of two lifestyle interventions testing cognitive benefit in older adults without significant cognitive impairment but at-risk for decline due to well-established factors. Cognition is measured using a global cognitive composite (US POINTER modified Neuropsychological Test Battery-PmNTB).
Results: The PmNTB is a valid cognitive composite, exhibiting good psychometric properties and tracking with other established outcomes. Among the 2111 enrolled participants (mean age = 68.2 years, 69% women, 31% from race and ethnic minoritized groups), …
Integrative Analysis Reveals The Prognostic Effects Of Epigenetic Regulators In Bladder Cancer, Venugopalareddy Mekala, Yupei Lin, Xiang Wang, Naail Chowdhury, Jianrong Li, Chao Cheng
Integrative Analysis Reveals The Prognostic Effects Of Epigenetic Regulators In Bladder Cancer, Venugopalareddy Mekala, Yupei Lin, Xiang Wang, Naail Chowdhury, Jianrong Li, Chao Cheng
Faculty, Staff and Students Publications
Background: Epigenetic regulatory genes (epiRG) are pivotal in the epigenetic regulation of the human genome, primarily through DNA and histone modifications. These genes are frequently mutated in human cancers, particularly bladder cancer (BC). However, the functional impact of epiRG mutations on patient outcomes remains poorly understood.
Methods: In this study, we developed gene signatures for the most frequent genomic aberrations of epiRG using The Cancer Genome Atlas Bladder Carcinoma (TCGA-BLCA) dataset and validated these signatures with independent tumor expression profiles for prognostic relevance. Furthermore, we evaluated the role of these signature scores in the immune system within the tumor microenvironment …
Crispr-Cas9 Mediated Proteinase 3 Autoantigen Deletion As A Treatment Strategy For Anti-Neutrophil Cytoplasmic Autoantibody-Associated Vasculitis, Uwe Jerke, Claudia Eulenberg-Gustavus, Dimitrios Laurin Wagner, Adrian Schreiber, Ralph Kettritz
Crispr-Cas9 Mediated Proteinase 3 Autoantigen Deletion As A Treatment Strategy For Anti-Neutrophil Cytoplasmic Autoantibody-Associated Vasculitis, Uwe Jerke, Claudia Eulenberg-Gustavus, Dimitrios Laurin Wagner, Adrian Schreiber, Ralph Kettritz
Faculty, Staff and Students Publications
Introduction: Proteinase 3 (PR3) is a major autoantigen in patients with anti-neutrophil cytoplasmic autoantibody (ANCA)-associated vasculitis (AAV). Here, we performed a proof-of-principle study using ex vivo CRISPR-Cas9 guided gene editing to eliminate the PR3 autoantigen as an alternative to suppressing the autoimmune response to PR3.
Methods: A ribonucleoprotein (RNP) complex of Cas9 protein and a PR3-specific single guide-RNA was transfected into human CD34+ hematopoietic stem and progenitor cells (HSPC) by electroporation. Effects on PR3 protein abundance, neutrophil differentiation, and ANCA-dependent and -independent neutrophil responses were assessed.
Results: Gene editing introduced a frame shift in exon 2 of PRTN3. Consequently, PR3 …
Functional Assays In Drosophila Facilitate Classification Of Variants Of Uncertain Significance Associated With Rare Diseases, Jung-Wan Mok, Shelley B Gibson, Haley A Dostalik, Shinya Yamamoto
Functional Assays In Drosophila Facilitate Classification Of Variants Of Uncertain Significance Associated With Rare Diseases, Jung-Wan Mok, Shelley B Gibson, Haley A Dostalik, Shinya Yamamoto
Faculty, Staff and Students Publications
Individuals living with rare diseases often undergo a frustrating and expensive diagnostic odyssey. Clinical geneticists who analyze exome or genome sequencing data from rare disease patients often encounter a list of variants of uncertain significance (VUS) in known disease-causing genes or rare variants in genes of uncertain significance (GUS) that are difficult to interpret, even with the integration of the latest bioinformatic tools. In this Perspective, we review how studies using the fruit fly Drosophila melanogaster have facilitated rare disease diagnosis by uncovering the clinical relevance of GUS and classifying rare variants into specific allelic categories (loss-of-function or gain-of-function, Muller's …
Development And Diversity Of Astrocytes, Michael R Williamson, Sanjana Murali, Benjamin Deneen
Development And Diversity Of Astrocytes, Michael R Williamson, Sanjana Murali, Benjamin Deneen
Faculty, Staff and Students Publications
Proper development of the central nervous system (CNS) depends on astrocytes, which are the most abundant glial cells in the CNS. Here, we provide an overview of astrocyte ontogeny and morphogenesis, highlighting mechanisms that regulate astrocyte development. In addition, we describe the roles of astrocytes in regulating the development of other CNS cell types, with emphasis on neural circuits and vascular networks. We also discuss evidence for astrocyte diversity and its implications for CNS development. Finally, we pose open questions related to astrocyte development and its intersection with astrocyte diversity.
Figo Position Statement: Gamete Donations, Laurie Henry, Aris Antsaklis, Dov Feldberg, Jaideep Malhotra, Suchitra Pandit, Carlos Salazar, Alex Vidaeff, Rafal Zadykowicz, M Louise Hull, Nikhil Purandare
Figo Position Statement: Gamete Donations, Laurie Henry, Aris Antsaklis, Dov Feldberg, Jaideep Malhotra, Suchitra Pandit, Carlos Salazar, Alex Vidaeff, Rafal Zadykowicz, M Louise Hull, Nikhil Purandare
Faculty, Staff and Students Publications
Gamete donation has become a crucial part of Assisted Reproductive Technologies (ARTs), providing hope to individuals, including those who may have no other option for parenthood. This process comes with a wide range of ethical, medical, and legal challenges that need to be carefully addressed to protect the well-being and rights of all parties involved: donors, recipients, and offspring. Navigating these complexities requires strict ethical standards, robust regulatory frameworks, and international collaboration. By standardizing these, the field of gamete donation can continue to develop while ensuring that all parties are well informed and safeguarded. This paper explores the ethical concerns …
Deficits In Mitochondrial Dynamics And Iron Balance Result In Templated Insertions, Jordan Fox, Yang Yu, Yang Yu, Pilendra Thakre, Chloe Fox, Qian Li, Yunxia Wang, Adam Hughes, Xin Wang, Kaifu Chen, Grzegorz Ira
Deficits In Mitochondrial Dynamics And Iron Balance Result In Templated Insertions, Jordan Fox, Yang Yu, Yang Yu, Pilendra Thakre, Chloe Fox, Qian Li, Yunxia Wang, Adam Hughes, Xin Wang, Kaifu Chen, Grzegorz Ira
Faculty, Staff and Students Publications
Mitochondrial membrane dynamics control the shape, number, and distribution of mitochondria and regulate energy production and cell health. In a screen for yeast mutants with increased levels of templated insertions (~10-1000 bp) in the nuclear genome, we identified mitochondrial fusion deficient mutants (mgm1Δ, ugo1Δ, fzo1Δ). We found that fusion mutants activate the iron regulon, have decreased iron-sulfur clusters (ISCs), and increased DNA damage, suggesting a role of iron homeostasis in preventing insertions. Consistently, a secondary screen found mutants affecting iron-sulfur cluster production (yfh1Δ, grx5Δ), vacuolar iron storage (ccc1Δ) or general iron homeostasis (aft1Δ) to exhibit high insertion levels. Treatment with …
Defining Lipedema’S Molecular Hallmarks By Multi-Omics Approach For Disease Prediction In Women, Leon G Straub, Jan-Bernd Funcke, Nolwenn Joffin, Chanmin Joung, Sara Al-Ghadban, Shangang Zhao, Qingzhang Zhu, Ilja L Kruglikov, Yi Zhu, Paul R Langlais, Ruth Gordillo, Karen L Herbst, Philipp E Scherer
Defining Lipedema’S Molecular Hallmarks By Multi-Omics Approach For Disease Prediction In Women, Leon G Straub, Jan-Bernd Funcke, Nolwenn Joffin, Chanmin Joung, Sara Al-Ghadban, Shangang Zhao, Qingzhang Zhu, Ilja L Kruglikov, Yi Zhu, Paul R Langlais, Ruth Gordillo, Karen L Herbst, Philipp E Scherer
Children’s Nutrition Research Center Staff Publications
Lipedema is a chronic disease in females characterized by pathologic subcutaneous adipose tissue expansion and hitherto remains without druggable targets. In this observational study, we investigated the molecular hallmarks of lipedema using an unbiased multi-omics approach. We found adipokine dysregulation in lipedema patients participating in a cross-sectional clinical study (ClinicalTrial.gov, NCT02838277), pointing towards the adipocyte as a key player. Analyses of newly generated transcriptomic (SRA, PRJNA940039) and proteomic (ProteomeXchange, PXD058489) datasets of early- and late-stage lipedema samples revealed a local downregulation of factors involved in inflammation. Concomitantly, factors involved in cellular respiration, oxidative phosphorylation, as well as in mitochondrial …
Definition And Classification Of Dystonia, Alberto Albanese, Kailash P Bhatia, Victor S C Fung, Mark Hallett, Joseph Jankovic, Christine Klein, Joachim K Krauss, Anthony E Lang, Jonathan W Mink, Sanjay Pandey, Jan K Teller, Marina A J Tijssen, Marie Vidailhet, H A Jinnah
Definition And Classification Of Dystonia, Alberto Albanese, Kailash P Bhatia, Victor S C Fung, Mark Hallett, Joseph Jankovic, Christine Klein, Joachim K Krauss, Anthony E Lang, Jonathan W Mink, Sanjay Pandey, Jan K Teller, Marina A J Tijssen, Marie Vidailhet, H A Jinnah
Faculty, Staff and Students Publications
Dystonia is a movement disorder with varied clinical features and diverse etiologies. Here we present a revision of the 2013 consensus definition and classification of dystonia in light of subsequent publications and experience with its application during the last decade. A panel of movement disorder specialists with expertise in dystonia reviewed the original document and proposed some revision. There was broad consensus to retain the definition of dystonia with only minor clarifications to the wording. Dystonia is defined as a movement disorder characterized by sustained or intermittent abnormal movements, postures, or both. Dystonic movements and postures are typically patterned and …
C-Terminal Frameshift Variants In Gpkow Are Associated With A Multisystemic X-Linked Disorder, Jung-Wan Mok, Laura Mackay, Maria Blazo, Elizabeth Mizerik, Jozef Gecz, Renee Carroll, Mathilde Nizon, Sophie Rondeau, Madeleine Joubert, Silvestre Cuinat, Wallid Deb, Fernanda Valle Sirias, Monika Weisz-Hubshman, Shamika Ketkar, Urszula Polak, Alyssa A Tran, Debra Kearney, Neil A Hanchard, Oguz Kanca, Michael F Wangler, Hugo J Bellen, Brendan H Lee, Shinya Yamamoto, Keren Machol
C-Terminal Frameshift Variants In Gpkow Are Associated With A Multisystemic X-Linked Disorder, Jung-Wan Mok, Laura Mackay, Maria Blazo, Elizabeth Mizerik, Jozef Gecz, Renee Carroll, Mathilde Nizon, Sophie Rondeau, Madeleine Joubert, Silvestre Cuinat, Wallid Deb, Fernanda Valle Sirias, Monika Weisz-Hubshman, Shamika Ketkar, Urszula Polak, Alyssa A Tran, Debra Kearney, Neil A Hanchard, Oguz Kanca, Michael F Wangler, Hugo J Bellen, Brendan H Lee, Shinya Yamamoto, Keren Machol
Duncan NRI Faculty and Staff Publications
Purpose: GPKOW, a gene on the X-chromosome, encodes a nuclear RNA-binding protein important in messenger RNA (mRNA) processing as a spliceosome subunit. This work aims to establish GPKOW as a disease-associated gene.
Methods: We describe 3 males from 2 unrelated families with hemizygous frameshift variants affecting the last exon of GPKOW p.(Arg441SerfsTer30) and p.(Ser444GlufsTer28). The effect of p.(Ser444GlufsTer28) on gene expression was evaluated in patient's fibroblasts. In vivo studies in Drosophila melanogaster targeting the sole GPKOW fly ortholog, CG10324 (Gpkow) were performed.
Results: Clinical presentations included intrauterine growth restriction, microcephaly/microencephaly, and eye, brain, skin, and skeletal abnormalities. Heterozygote females presented …
Enzyme-Independent Functions Of Hdac3 In The Adult Hear, Sichong Qian, Chen Zhang, Wenbo Li, Shiyang Song, Guanqiao Lin, Zixiu Cheng, Wenjun Zhou, Huiqi Yin, Yueli Wang, Haiyang Li, Ying H Shen, Zheng Sun
Enzyme-Independent Functions Of Hdac3 In The Adult Hear, Sichong Qian, Chen Zhang, Wenbo Li, Shiyang Song, Guanqiao Lin, Zixiu Cheng, Wenjun Zhou, Huiqi Yin, Yueli Wang, Haiyang Li, Ying H Shen, Zheng Sun
Center on Aging Staff Publications
The cardioprotective effects of histone deacetylase (HDAC) inhibitors (HDIs) are at odds with the deleterious effects of HDAC depletion. Here, we use HDAC3 as a prototype HDAC to address this contradiction. We show that adult-onset cardiac-specific depletion of HDAC3 in mice causes cardiac hypertrophy and contractile dysfunction on a high-fat diet (HFD), excluding developmental disruption as a major reason for the contradiction. Genetically abolishing HDAC3 enzymatic activity without affecting its protein level does not cause cardiac dysfunction on HFD. HDAC3 depletion causes robust downregulation of lipid oxidation/bioenergetic genes and upregulation of antioxidant/anti-apoptotic genes. In contrast, HDAC3 enzyme activity abolishment causes …
The Somatic Mosaicism Across Human Tissues Network, Tim H H Coorens, Ji Won Oh, Yujin Angelina Choi, Nam Seop Lim, Boxun Zhao, Adam Voshall, Alexej Abyzov, Lucinda Antonacci-Fulton, Samuel Aparicio, Kristin G Ardlie, Thomas J Bell, James T Bennett, Bradley E Bernstein, Thomas G Blanchard, Alan P Boyle, Jason D Buenrostro, Kathleen H Burns, Fei Chen, Rui Chen, Sangita Choudhury, Harsha V Doddapaneni, Evan E Eichler, Gilad D Evrony, Melissa A Faith, Thomas G Fazzio, Robert S Fulton, Manuel Garber, Nils Gehlenborg, Soren Germer, Gad Getz, Richard A Gibbs, Raquel G Hernandez, Fulai Jin, Jan O Korbel, Dan A Landau, Heather A Lawson, Niall J Lennon, Heng Li, Yan Li, Po-Ru Loh, Gabor Marth, Michael J Mcconnell, Ryan E Mills, Stephen B Montgomery, Pradeep Natarajan, Peter J Park, Rahul Satija, Fritz J Sedlazeck, Diane D Shao, Hui Shen, Andrew B Stergachis, Hunter R Underhill, Alexander E Urban, Melissa W Vondran, Christopher A Walsh, Ting Wang, Tao P Wu, Chenghang Zong, Eunjung Alice Lee, Flora M Vaccarino
The Somatic Mosaicism Across Human Tissues Network, Tim H H Coorens, Ji Won Oh, Yujin Angelina Choi, Nam Seop Lim, Boxun Zhao, Adam Voshall, Alexej Abyzov, Lucinda Antonacci-Fulton, Samuel Aparicio, Kristin G Ardlie, Thomas J Bell, James T Bennett, Bradley E Bernstein, Thomas G Blanchard, Alan P Boyle, Jason D Buenrostro, Kathleen H Burns, Fei Chen, Rui Chen, Sangita Choudhury, Harsha V Doddapaneni, Evan E Eichler, Gilad D Evrony, Melissa A Faith, Thomas G Fazzio, Robert S Fulton, Manuel Garber, Nils Gehlenborg, Soren Germer, Gad Getz, Richard A Gibbs, Raquel G Hernandez, Fulai Jin, Jan O Korbel, Dan A Landau, Heather A Lawson, Niall J Lennon, Heng Li, Yan Li, Po-Ru Loh, Gabor Marth, Michael J Mcconnell, Ryan E Mills, Stephen B Montgomery, Pradeep Natarajan, Peter J Park, Rahul Satija, Fritz J Sedlazeck, Diane D Shao, Hui Shen, Andrew B Stergachis, Hunter R Underhill, Alexander E Urban, Melissa W Vondran, Christopher A Walsh, Ting Wang, Tao P Wu, Chenghang Zong, Eunjung Alice Lee, Flora M Vaccarino
Center on Aging Staff Publications
From fertilization onwards, the cells of the human body acquire variations in their DNA sequence, known as somatic mutations. These postzygotic mutations arise from intrinsic errors in DNA replication and repair, as well as from exposure to mutagens. Somatic mutations have been implicated in some diseases, but a fundamental understanding of the frequency, type and patterns of mutations across healthy human tissues has been limited. This is primarily due to the small proportion of cells harbouring specific somatic variants within an individual, making them more challenging to detect than inherited variants. Here we describe the Somatic Mosaicism across Human Tissues …
Clonal Evolution Of Hematopoietic Stem Cells After Autologous Stem Cell Transplantation, Hidetaka Uryu, Koichi Saeki, Hiroshi Haeno, Chiraag Deepak Kapadia, Ken Furudate, Jyoti Nangalia, Michael Spencer Chapman, Linda Zhang, Jennifer Padilla, Li Zhao, Joanne I Hsu, Chong Zhao, Shujuan Chen, Tomoyuki Tanaka, Zongrui Li, Satoko Ogata, Sarah Hanache, Hui Yang, Courtney Dinardo, Naval Daver, Naveen Pemmaraju, Nitin Jain, Farhad Ravandi, Jianhua Zhang, Xingzhi Song, Erika Thompson, Hongli Tang, Latasha Little, Curtis Gumbs, Robert Z Orlowski, Muzaffar Qazilbash, Kapil Bhalla, Simona Colla, Hagop Kantarjian, Rashmi Kanagal-Shamanna, Carlos Bueso-Ramos, Daisuke Nakada, Gheath Al-Atrash, Jeffery Molldrem, P Andrew Futreal, Elizabeth Shpall, Margaret Goodell, Guillermo Garcia-Manero, Koichi Takahashi
Clonal Evolution Of Hematopoietic Stem Cells After Autologous Stem Cell Transplantation, Hidetaka Uryu, Koichi Saeki, Hiroshi Haeno, Chiraag Deepak Kapadia, Ken Furudate, Jyoti Nangalia, Michael Spencer Chapman, Linda Zhang, Jennifer Padilla, Li Zhao, Joanne I Hsu, Chong Zhao, Shujuan Chen, Tomoyuki Tanaka, Zongrui Li, Satoko Ogata, Sarah Hanache, Hui Yang, Courtney Dinardo, Naval Daver, Naveen Pemmaraju, Nitin Jain, Farhad Ravandi, Jianhua Zhang, Xingzhi Song, Erika Thompson, Hongli Tang, Latasha Little, Curtis Gumbs, Robert Z Orlowski, Muzaffar Qazilbash, Kapil Bhalla, Simona Colla, Hagop Kantarjian, Rashmi Kanagal-Shamanna, Carlos Bueso-Ramos, Daisuke Nakada, Gheath Al-Atrash, Jeffery Molldrem, P Andrew Futreal, Elizabeth Shpall, Margaret Goodell, Guillermo Garcia-Manero, Koichi Takahashi
Faculty, Staff and Student Publications
The impact of exogenous stressors, such as cancer chemotherapies, on the genomic integrity and clonal dynamics of normal hematopoiesis is not well defined. We conducted whole-genome sequencing on 1,276 single-cell-derived hematopoietic stem and progenitor cell (HSPC) colonies from ten patients with multiple myeloma treated with chemotherapies and six normal donors. Melphalan treatment significantly increased the mutational burden, producing a distinctive mutation signature, whereas other chemotherapeutic agents had minimal effects. Consequently, the clonal diversity and architecture of post-treatment HSPCs resemble those observed in normal elderly individuals, particularly through the progression of oligoclonal hematopoiesis, thereby suggesting that chemotherapy accelerates clonal aging. Integrated …
The Commonly Uncommon Presentation Of Cerebral Venous Thrombosis: A Case Report, Elizabeth Piwowarski, Kalyan Mantha, Martin Wegman
The Commonly Uncommon Presentation Of Cerebral Venous Thrombosis: A Case Report, Elizabeth Piwowarski, Kalyan Mantha, Martin Wegman
HCA Healthcare Journal of Medicine
Introduction
Cerebral venous thrombosis (CVT) is notoriously misdiagnosed as more benign etiologies during the initial examination owing to its relative rarity, its wide variety of presenting symptoms and onset and progression patterns, and its frequent requirement for less commonly utilized imaging techniques in its diagnosis. Accordingly, most cases are identified only after repeated evaluations for symptom persistence or progression, or in cases involving prothrombotic states linked to the disease, such as pregnancy, puerperium, genetic or acquired thrombophilia, and infection.
Case Presentation
We present the case of a 29-year-old woman with a history of obesity and oral contraceptive use who was …
Persistent Lichenoid Reaction And Eruptive Keratoacanthomas Following Pd-1 Inhibitor Therapy, Paul Vance, Michael Hohnadel
Persistent Lichenoid Reaction And Eruptive Keratoacanthomas Following Pd-1 Inhibitor Therapy, Paul Vance, Michael Hohnadel
HCA Healthcare Journal of Medicine
Background
Immune checkpoint inhibitors, such as nivolumab, have become integral in treating metastatic malignancies by enhancing immune responses against tumors. However, they are associated with immune-related adverse events (irAEs), including cutaneous reactions. We report a case of persistent lichenoid dermatitis during therapy and eruptive keratoacanthomas (KAs) following the cessation of nivolumab.
Case Presentation
A 77-year-old Caucasian man presented with a subcutaneous melanoma on the left lateral chest, treated with excision followed by adjuvant nivolumab. Seven weeks into therapy, he developed pruritic erythematous macules, forming patches on his forearms, later spreading to his trunk. Biopsy confirmed lichenoid dermatitis. Treatment with triamcinolone …
Unraveling The Threads: A Case Report On Confusional Migraine And The Intricate Dance Between Psychiatry And Neurology, Mabit C. Gonzalez, Manjula Kottapalli
Unraveling The Threads: A Case Report On Confusional Migraine And The Intricate Dance Between Psychiatry And Neurology, Mabit C. Gonzalez, Manjula Kottapalli
HCA Healthcare Journal of Medicine
Background
Migraine affects about 1 billion people worldwide and is associated with a significant negative impact on personal and occupational functioning. Migraine accompanied by aura is seen in about 15% of migraineurs. Visual aura is the most common type of aura. Much less common though are auras that involve higher mental function, such as confusional state. The confusional state may manifest with a wide variety of cortical dysfunction, such as speech impairment, increased alertness, agitation, and amnesia, often lasting longer than a typical migraine aura.
Case Presentation
The authors present the unique case of a 29-year-old patient with episodic and …
Unique Presentation Of Vertebral Artery Dissection: A Case Report, Rossen I. Kirkov, Daniel Fisher
Unique Presentation Of Vertebral Artery Dissection: A Case Report, Rossen I. Kirkov, Daniel Fisher
HCA Healthcare Journal of Medicine
Background
Vertebral artery dissection (VAD) is a common cause of stroke within the younger patient population. It is usually associated with headache or neck pain, as well as signs and symptoms of a posterior circulation stroke, such as vertigo, dysarthria, and ataxia. However, there are very scarce reports of patients with this pathology presenting with focal neurologic deficits, which are more indicative of a cerebral stroke.
Case Presentation
This case involves a 46-year-old woman who presented to the emergency department (ED) with complaints of right-sided headache and neck pain, which had been ongoing for 1 week, with newly developed right …
Complications And Management Of Idiopathic Multicentric Castleman Disease, Kavanya Feustel, Jacob W. Keeling, Olivia Makos, Dmitriy Scherbak
Complications And Management Of Idiopathic Multicentric Castleman Disease, Kavanya Feustel, Jacob W. Keeling, Olivia Makos, Dmitriy Scherbak
HCA Healthcare Journal of Medicine
Background
The pathophysiology of idiopathic multicentric Castleman disease (iMCD) is poorly understood compared to the other subtypes of MCD, which has contributed to limited treatment options and poor prognosis for iMCD patients. The pathogenesis of iMCD is thought to be mediated in part by dysregulation of interleukin (IL)-6.
Case Presentation
We present a case report of a 39-year-old Caucasian man with siltuximab-refractory iMCD. He presented with severe lower extremity lymphedema and wounds. His disease progressed through standard-of-care siltuximab. Due to his severe disease-related morbidity, he contracted recurrent infections, often complicated by sepsis. Ultimately, he required a left lower extremity amputation. …
Covid-19 Vaccine-Induced Rhabdomyolysis In A 53-Year-Old Woman, Akash Hazari, Jack Chien, Daniel Nunez
Covid-19 Vaccine-Induced Rhabdomyolysis In A 53-Year-Old Woman, Akash Hazari, Jack Chien, Daniel Nunez
HCA Healthcare Journal of Medicine
Introduction
COVID-19-induced rhabdomyolysis is a common complication in COVID-19 infection. However, only a handful of cases have been reported showing links between COVID-19 vaccine and rhabdomyolysis.
Case Presentation
We present the case of a 53-year-old woman, who recently received COVID-19 vaccine and presented to the hospital with progressive extremity weakness. Common reasons for rhabdomyolysis were ruled out as possibility and the patient was found to have rhabdomyolysis induced from COVID-19 vaccine.
Conclusion
Even though COVID-19 vaccine-induced rhabdomyolysis is rare, it should be considered in the differential diagnosis with patients presenting with neuromuscular complaints and a recent COVID-19 vaccine.
Clinical Outcomes After Hospitalization For Acute Coronary Syndrome In Patients Treated With Semaglutide Versus Bariatric Surgery: A Retrospective Multicenter Analysis, Nameer Ascandar, Charles Boadu, Gauthier Stepman, George Skaf, Olugbenga Oyesanmi, Sabry Omar, Rias Ali, Michael Schandorf-Lartey
Clinical Outcomes After Hospitalization For Acute Coronary Syndrome In Patients Treated With Semaglutide Versus Bariatric Surgery: A Retrospective Multicenter Analysis, Nameer Ascandar, Charles Boadu, Gauthier Stepman, George Skaf, Olugbenga Oyesanmi, Sabry Omar, Rias Ali, Michael Schandorf-Lartey
HCA Healthcare Journal of Medicine
Background
Obesity is a chronic medical condition with a rising prevalence in the United States. A wide range of morbidity and mortality is associated with obesity, with coronary artery disease being among the most common. Ischemic heart disease continues to be the primary cause of death in the United States. Taken together, interventions to minimize the detrimental effects of obesity on patients at risk of heart disease will not only benefit the patient, but the health care system as well.
Methods
In this retrospective study, we used the HCA Healthcare enterprise data warehouse to identify all adult patients who were …
The Prevalence Of Abdominal Compartment Syndrome In The State Of Florida, Jason M. Clark, Laura Mena-Albors, Huazhi Liu, Darwin Ang
The Prevalence Of Abdominal Compartment Syndrome In The State Of Florida, Jason M. Clark, Laura Mena-Albors, Huazhi Liu, Darwin Ang
HCA Healthcare Journal of Medicine
Introduction
Abdominal compartment syndrome (ACS) is associated with significant mortality. Multiple studies have evaluated the prevalence of ACS at individual institutions and/or for short durations. No study has looked at the change of prevalence over an extended time or included nonresearch institutions. This study aims to evaluate the trend in the prevalence of ACS over time within the state of Florida.
Methods
This is a population-based retrospective study using deidentified data from the Florida’s Agency of Healthcare Database between 2006 and 2021. A total of 16 217 617 patients were evaluated within the intensive care unit (ICU), with 4002 developing …
Care Alert Program In Chronic Emergency Department Using Patients: Expanded Study, Jonathan Leggett, Kaitlyn Phelps, David Nuñez, Brent Wright, Erica Gibbons, Jonathan Bryan, Brian Griggs
Care Alert Program In Chronic Emergency Department Using Patients: Expanded Study, Jonathan Leggett, Kaitlyn Phelps, David Nuñez, Brent Wright, Erica Gibbons, Jonathan Bryan, Brian Griggs
HCA Healthcare Journal of Medicine
Introduction
The Care Alert Program (CAP) is designed to help navigate encounters with patients who are high utilizers of Emergency Department (ED) resources. The CAP intends to address the needs of this challenging patient population by designing individualized care plans that are approved by a multidisciplinary committee. The patient populations that frequently use ED resources often have chronic medical conditions, a poor understanding of their conditions, unrealistic expectations regarding treatment, a lack of outpatient resources, and present with multiple complaints when using ED resources.
Methods
The CAP was adopted by our facility in the spring of 2020. The present study …
Efficacy And Safety Of Lotilaner Ophthalmic Solution 0.25% In Demodex Blepharitis: A Systematic Review, Stephanie P. Fabara, Thalia Fabara, Akankcha Alok, Nausheen Khuddus
Efficacy And Safety Of Lotilaner Ophthalmic Solution 0.25% In Demodex Blepharitis: A Systematic Review, Stephanie P. Fabara, Thalia Fabara, Akankcha Alok, Nausheen Khuddus
HCA Healthcare Journal of Medicine
Demodex blepharitis is a chronic eyelid inflammation caused by Demodex mites, which are ubiquitous skin parasites. Lotilaner, a newly United States Food and Drug Administration (FDA)-approved drug, is an antiparasitic agent that selectively inhibits parasite-specific γ-aminobutyric acid chloride channels, inducing spastic paralysis and death of Demodex mites. It is applied as an ophthalmic solution, 0.25%, twice a day for 6 weeks, and it has a long half-life and high lipophilicity, facilitating the penetration of the drug into the eyelash follicles and meibomian glands where the mites reside. This study systematically reviewed 6 clinical trials that compared lotilaner with placebo for …
Mortalitas Pada Pasien Hemodialisis: Masih Menjadi Tantangan Globa, Anandhara Indriani Indriani Khumaedi, Dina Elita
Mortalitas Pada Pasien Hemodialisis: Masih Menjadi Tantangan Globa, Anandhara Indriani Indriani Khumaedi, Dina Elita
Jurnal Penyakit Dalam Indonesia
No abstract provided.
Faktor-Faktor Yang Berhubungan Dengan Massa Otot, Kekuatan Otot, Dan Performa Fisik Pada Lansia, Nur Riviati, Taufik Indrajaya, Rukiah Chodilawati, Ridzqie Dibyantari, Bima Indra
Faktor-Faktor Yang Berhubungan Dengan Massa Otot, Kekuatan Otot, Dan Performa Fisik Pada Lansia, Nur Riviati, Taufik Indrajaya, Rukiah Chodilawati, Ridzqie Dibyantari, Bima Indra
Jurnal Penyakit Dalam Indonesia
Introduction. Despite its high prevalence and significant impact on health, comprehensive studies are still needed to explore the factors affecting sarcopenia parameters, such as muscle mass, muscle strength, and physical performance. This study aimed to identify the factors influencing sarcopenia parameters in the elderly, including muscle mass, muscle strength, and physical performance.
Methods. A cross-sectional study was conducted from July to December 2022 on elderly individuals (>60 years old) at the Geriatric Polyclinic, Moh. Hoesin General Hospital, Palembang, selected through consecutive sampling. Muscle mass was measured using bioimpedance analysis, expressed in ASMI values; muscle strength was measured …
Faktor Risiko Yang Berhubungan Dengan Kematian Pasien Penyakit Ginjal Kronis Pada Usia Dewasa Yang Menjalani Hemodialisis Reguler Di Provinsi Lampung, Joue Abraham Trixie Latupeirissa, Mondastri Korib Sudaryo, Muhamad Zulfikar Hadiaturahman, Steven Sapta Putra Sinaga
Faktor Risiko Yang Berhubungan Dengan Kematian Pasien Penyakit Ginjal Kronis Pada Usia Dewasa Yang Menjalani Hemodialisis Reguler Di Provinsi Lampung, Joue Abraham Trixie Latupeirissa, Mondastri Korib Sudaryo, Muhamad Zulfikar Hadiaturahman, Steven Sapta Putra Sinaga
Jurnal Penyakit Dalam Indonesia
Introduction. Although mortality among adult chronic kidney disease (CKD) patients on regular hemodialysis remains infrequent within the first three months, it is still a potential outcome. Given that hemodialysis is required for life, identifying risk factors for mortality is critical. This study aims to examine risk factors associated with mortality in adult CKD patients undergoing regular hemodialysis.
Methods. A case-control study, without matching, was conducted using medical record data from adult CKD patients (≥18 years) receiving regular hemodialysis between 2022 and 2024 at three hospitals (types A, B, and C) in Lampung Province. The case group consisted of …
Gejala Neuropsikiatri Pasien Hiv Setelah Menjalani Transisi Antiretrovirus Nevirapin Ke Dolutegravir Di Rumah Sakit Cipto Mangunkusumo, Jakarta, Metra Adi Pratama, Rudi Putranto, Herqutanto Herqutanto, Aisyah Syahrani, Aljira Fitya Hapsari, Veritea Natali, Meivina Ramadhani Pane, Evy Yunihastuti
Gejala Neuropsikiatri Pasien Hiv Setelah Menjalani Transisi Antiretrovirus Nevirapin Ke Dolutegravir Di Rumah Sakit Cipto Mangunkusumo, Jakarta, Metra Adi Pratama, Rudi Putranto, Herqutanto Herqutanto, Aisyah Syahrani, Aljira Fitya Hapsari, Veritea Natali, Meivina Ramadhani Pane, Evy Yunihastuti
Jurnal Penyakit Dalam Indonesia
Introduction. Dolutegravir (DTG) is one of the effective antiretroviral therapies (ART) for suppressing HIV replication and has a favorable safety profile. However, reports regarding neuropsychiatric side effects, especially in patients transitioning from a nevirapine (NVP) regimen to dolutegravir, have started to emerge. This study aimed to describe the changes in neuropsychiatric symptoms before and after the transition from a NVP-based ARV regimen to DTG in HIV patients at Cipto Mangunkusumo Hospital (RSCM), Jakarta.
Methods. This study employed a prospective cohort design involving 292 HIV patients at Cipto Mangunkusumo Hospital who were transitioning from NVP to DTG regimen. Participants …