Diseases Commons^™

Neuronal Activity-Dependent Gene Dysregulation In C9orf72 I3neuronal Models Of Als/Ftd Pathogenesis, Layla T. Ghaffari, Emily A. Welebob, Sarah E. Bond Newton, Ashley V. Boehringer, Kelly L. Cyliax, Piera Pasinelli, Davide Trotti, Aaron R. Haeusler

Farber Institute for Neuroscience Faculty Papers

The GGGGCC nucleotide repeat expansion (NRE) mutation in the C9ORF72 (C9) gene is the most common cause of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). Neuronal activity plays an essential role in shaping biological processes within both healthy and neurodegenerative disease scenarios. Here, we show that at baseline conditions, C9-NRE-induced pluripotent stem cell-cortical neurons display aberrations in several pathways, including synaptic signaling and transcriptional machinery, potentially priming diseased neurons for an altered response to neuronal stimulation. Indeed, exposure to two pathophysiologically relevant stimulation modes, prolonged membrane depolarization or a blockade of K⁺ channels, followed by RNA sequencing, induces …

Migraine-Related Disability According To Headache Frequency Subclassifications: A Systematic Review And Meta-Analysis, Manjit Singh Matharu, Stephen Silberstein, Hsiangkuo Yuan, Deborah Edgar, Roos Colman, Todd Schwedt, Michel Lanteri-Minet, Mark Obermann

Department of Jefferson Headache Center Papers and Presentations

BackgroundThis systematic review and meta-analysis synthesized migraine-related disability outcomes according to headache frequency subclassifications, including low-frequency episodic migraine (LFEM), high-frequency episodic migraine (HFEM) and chronic migraine (CM).MethodsWe searched the PubMed and Cochrane Library (CENTRAL) up to 16 October 2024 for peer-reviewed non-interventional studies reporting migraine-related disability outcomes in CM and subclassifications of episodic migraine (e.g. LFEM and HFEM). Eligible studies with an HFEM subgroup were grouped by headache frequency measure (monthly migraine days [MMD] or monthly headache days [MHD]), HFEM subgroup, disability parameter and study setting. Random-effects meta-analyses were conducted on groups with three or more studies, with the results …

What Community Members With Chronic Illness Teach Future Healthcare Professionals In A Longitudinal Interprofessional Education Program: A Focus Group Study, Rachel White, Maria Brucato, Amber King, Anne B. Mitchell, Nethra S. Ankam

Department of Medicine Faculty Papers

INTRODUCTION: Nearly 50% of Americans have at least one chronic illness. Preparing future healthcare providers for interprofessional collaborative practice (IPCP) and person-centred care through community-based interprofessional education (IPE) can improve outcomes for this growing population. Partial programme theories predict that patients' participation as teachers in health professions education contributes to students' development of patient-centredness. Role theory asserts that behaviours are shaped by assigned roles; therefore, community members with chronic illness who assume roles of health mentors in an IPE curriculum are predicted to teach students about their patient experiences. Yet, this teaching outcome and the lessons health mentors teach in …

Progress In Progressive Pulmonary Fibrosis, Jesse Roman

Rothman Institute Papers

No abstract provided.

Concurrent Local Therapy Extends Clinical Benefit Of Tebentafusp In Metastatic Uveal Melanoma Patients, Tristan L. Lim, Kamaneh Montazeri, Eric Wehrenberg-Klee, Antoine Desilets, Rino S. Seedor, Marlana Orloff, Takami Sato, Michael Caplan, Mariam El-Ashmawy, Benjamin Izar, Shaheer Khan, Inderjit Mehmi, Aleigha Lawless, Theodore S. Hong, Omid Hamid, Richard D. Carvajal, Alexander Shoushtari, Ryan J. Sullivan

Kimmel Cancer Center Faculty Papers

BACKGROUND: Tebentafusp has significantly improved overall survival in HLA-A*02:01+ metastatic uveal melanoma (mUM) patients even in those with a best objective response of progressive disease. Thus, strategies to maintain tebentafusp therapy are critical. Here, we examine the efficacy and safety of adding concurrent local therapy (CLT) to tebentafusp upon radiological progression with tebentafusp alone.

PATIENTS AND METHODS: This multicenter retrospective study included mUM patients treated with tebentafusp and CLT, consisting of extrahepatic soft tissue irradiation and liver-directed therapies (LDTs). Efficacy of target and nontarget sites were assessed per RECIST version 1.1. PFS with tebentafusp alone (PFS1) was compared to that …

A Case-Based Video Review Of Arteriovenous Fistulae, Jonathan J. Russin, Stavropoula Tjoumakaris, Mika Niemela, Erez Nossek, Jeffrey Steinberg, Sepideh Amin-Hanjani

Department of Neurosurgery Faculty Papers

No abstract provided.

A Comparative Evaluation Of Two Subharmonic-Aided Pressure Estimation (Shape) Analysis Methods, Hailee Mayer, Priscilla Machado, Trang Vu, Annalisa Berzigotti, Jaume Bosch, Elton Dajti, Antonina Antonenko, Kirk Wallace, Flemming Forsberg

Department of Radiology Faculty Papers

Pressure measurement in clinical practice is a valuable tool for diagnostic evaluation, especially in diseases such as portal hypertension. Currently, portal pressures are measured by invasive hepatic vein catheterization, posing risks to patients, and limiting how often measurements can be obtained. Subharmonic-aided pressure estimation (SHAPE) is an ultrasound-based technique that leverages ultrasound contrast agents (UCAs) to estimate changes in hydrostatic pressure. UCAs act as nonlinear oscillators when exposed to high enough acoustic pressures (typically > 200 kPa) and produce significant energy components ranging from subharmonics to higher harmonics. Tissues do not generate significant subharmonic components, thus making it the optimal component …

Three-Dimensional Human Mucopolysaccharidosis Iva Chondrocyte Culture Reveals Significant Impairments In The Lysosomal-Mitochondrial Crosstalk, Andrés Felipe Leal, Sampurna Saikia, Shaukat A. Khan, Shunji Tomatsu

Department of Pediatrics Faculty Papers

Mucopolysaccharidosis IVA (MPS IVA) is a lysosomal storage disorder (LSD) caused by a deficiency of N-acetylgalactosamine-6-sulfate sulfatase enzyme. MPS IVA patients suffer from skeletal dysplasia due to the abnormal function of chondrocytes. Given the interactions of lysosomes with various intracellular organelles, it is not surprising that lysosomal dysfunction can lead to improper functioning of lysosome-interacting organelles such as mitochondria. Mitochondrial alterations have been evaluated in several LSDs; nevertheless, they have not been fully addressed in MPS IVA. In this study, we assessed the mitochondrial alterations in MPS IVA chondrocytes using a three-dimensional culture approach. Our findings revealed that MPS IVA …

Ketorolac Use Following Operative Clavicle Fracture Fixation Is Not Associated With Increased Nonunion Or Surgical Complications: A Propensity-Matched Analysis, Tuckerman Jones, Tej Joshi, Akhil Katakam, Daniella Ogilvie, Sefy Paulose, Balazs Galdi

Wills Eye Hospital Papers

OBJECTIVES: Nonsteroidal anti-inflammatory drugs (NSAIDs), including ketorolac, are commonly used for postoperative pain management. Concerns about their potential impact on bone healing have been raised. This study investigated the relationship between ketorolac use and postoperative complications following clavicle surgery, including nonunion rates.

METHODS: This retrospective cohort study used the TriNetX Research Database to identify patients who underwent surgical fixation of clavicle fractures between 2002 and 2022. Two propensity-matched cohorts were created: patients who received postoperative ketorolac and those who did not. Primary outcomes included nonunion diagnosis and revision surgery; secondary outcomes included opioid use, wound disruption, surgical site infection, and …

Economics Of Corneal Cross-Linking For Keratoconus Treatment, Christopher J. Rapuano, Richard L. Lindstrom, Eric Donnenfeld, John P. Berdahl, Vance Thompson, David Kratochvil, John Carter

Wills Eye Hospital Papers

AIM: To optimize the real-world applicability of a health economic model estimating the cost-effectiveness of corneal cross-linking for the treatment of keratoconus in the United States.

MATERIALS AND METHODS: A previously reported discrete-event simulation (DES) model was adapted to reassess the cost-effectiveness of corneal cross-linking (CXL) from the US payer perspective. The simulation of keratoconus progression, which is a key driver of model outcomes, was remodeled to more accurately reflect the real-world relationship between age and the rate of disease progression. All costs were updated to reflect 2025 values. We simulated 4,000 eyes of 2,000 patients diagnosed with keratoconus to …

Uncovering The Pml::Rara Fusion In Cytogenetically Cryptic And Fish-Negative Acute Promyelocytic Leukemia-A Case Report And Comprehensive Literature Review, Busra Delikkaya, Jaime Eberle-Singh, Arianna Morton, Jerald Gong, Jinglan Liu

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

The PML::RARA fusion resulting from t(15;17) is the genetic hallmark of acute promyelocytic leukemia (APL), typically detected by cytogenetics and/or fluorescence in situ hybridization (FISH) studies. Rarely, APL patients present with normal cytogenetics and FISH findings, complicating diagnosis and delaying life-saving therapy. We report a 23-year-old male with clinical, morphologic and immunophenotypic features consistent with APL but negative for FISH studies. Despite prompt initiation of all-trans retinoic acid (ATRA) based on clinical suspicion, the patient succumbed to intracranial hemorrhage. Quantitative reverse transcriptase PCR (qRT-PCR) confirmed a long isoform PML::RARA fusion. A review of 34 published cytogenetics- and FISH-negative cases since …

Association Of Estimated Plasma Volume Status With Invasive Hemodynamics And Adverse Clinical Outcomes In Patients With Pulmonary Hypertension And Chronic Kidney Disease, Andrew Geller, Jose Manuel Martinez Manzano, Esteban Kosak Lopez, Phuuwadith Wattanachayakul, John Malin, Raul Leguizamon, Tara John, Rasha Khan, Ian Mclaren, Alexander Prendergast, Simone Jarrett, Kevin Bryan Lo, Christian Witzke

Einstein Health Papers

Identifying noninvasive measures to assess intravascular volume status and risk stratify patients with pulmonary hypertension (PH) and chronic kidney disease (CKD) is needed. We assessed the predictive value of estimated plasma volume status (ePVS) using the Strauss-derived Duarte formula in PH-CKD patients. This single-center retrospective cohort analysis included patients with PH and CKD Stage 3b (CKD3b), Stage 4 (CKD4), or Stage 5 (CKD5) who underwent right heart catheterization from 2018 to 2023. Patients were categorized into low ePVS (< 6.2) and high ePVS (≥ 6.2) using Youden's J statistics. We used the Cox-proportional hazards model, adjusting for age, sex, and body mass index, to investigate the association between …

Trajectory Of Iron And Red Cell Parameters In Moderately Anemic Iron-Deficient Pregnant Women Receiving Daily Iron-Folic Acid Supplementation: A Prospective Cohort Study, J. P. Akshaykirthan, Manjunath S. Somannavar, S. Yogeshkumar, M. S. Deepthy, Umesh Charantimath, Amaresh Patil, Mrutyunjaya B. Bellad, Richard Derman, Shivaprasad S. Goudar

Global Health Articles

Background/Objectives: The objective is to study the trajectories of hematologic and biochemical markers in moderately anemic pregnant women receiving oral iron supplementation throughout pregnancy. Methods: This prospective cohort study was conducted from August 2021 to September 2023 involving 315 pregnant women from rural areas of Belgaum, Karnataka, India, with hemoglobin levels between 7.0 and 9.9 g/dL and serum ferritin < 30 ng/mL and/or TSAT < 20%. Participants received iron-folic acid supplementation (IFAS) as per Anaemia Mukt Bharat guidelines. Blood samples were collected to measure various hematologic and iron markers and compared across each visits. Results: We report a complete adherence rate of 95.3% for iron and 97.8% for folic acid supplementation throughout pregnancy and also observed significant improvements in hemoglobin (9.36 (8.55, 9.74) to 12.03 (11.49, 12.72)) g/dL, hematocrit (29.93 ± 2.87 to …

Non-Invasive Detection Of Choroidal Melanoma Via Tear-Derived Protein Corona On Gold Nanoparticles: A Machine Learning Approach, Hakimeh Rakhshandeh, Ahmad Nasiraei, Hamid Riazi-Esfahani, Babak Masoomian, Fariba Ghassemi, Mojtaba Arjmand, Saeed Heidari Keshel, Fatemeh Atyabi, Rassoul Dinarvand

Wills Eye Hospital Papers

This study investigates the feasibility of using tear sample analysis, based on protein corona formation on gold nanoparticles combined with electrospray ionization mass spectrometry (ESI-MS) and machine learning techniques, as a non-invasive approach for the detection of choroidal melanoma. The aim is to assess whether protein-nanoparticle interactions can support early and reliable identification of this ocular condition. Tear samples were collected using Schirmer strips from six healthy individuals and six patients diagnosed with choroidal melanoma, with subsequent augmentation to 18 samples per group. Gold nanoparticles (AuNPs, ~ 20 nm) were synthesized via citrate reduction and incubated with tear samples to …

The Impact Of Myopia On Regional Visual Field Loss And Progression In Glaucoma, Anagha Lokhande, Luo Song, Yueyin Pang, Yan Luo, Louis R. Pasquale, Sarah R. Wellik, Carlos G. De Moraes, Jonathan S. Myers, Mohammad Eslami, Tobias Elze, Lucy Q. Shen, Nazlee Zebardast, David S. Friedman, Michael V. Boland, Mengyu Wang

Wills Eye Hospital Papers

PURPOSE: The purpose of this study was to investigate the impact of myopia on regional visual field (VF) loss and progression in glaucoma.

METHODS: We included 112,633 24-2 VFs; longitudinal analyses comprised patients with at least 5 reliable VFs over 4 years. The degree of myopia was measured by spherical equivalent (SE) extracted from VF testing. Linear and Cox regressions determined the impact of myopia on regional VF loss and progression, respectively. We calculated three VF progression outcomes: (1) mean deviation (MD) progression: MD slope < 0; (2) total deviation (TD) pointwise progression: at least 3 TD locations with TD slope ≤-1 decibels (dB)/year; (3) MD fast progression: MD slope ≤-1 dB/year (P value < 0.05). Longitudinal analyses were conducted for all subjects and with exclusion of patients with high myopia (SE ≤-6.00 diopters [D]).

RESULTS: More negative SE values were associated with worse TD values in the paracentral VF …

Practice Patterns In Management Of Low- To Intermediate-Grade Salivary Gland Carcinoma: A Multi-Institutional Study, Mirabelle Sajisevi, Kenny Nguyen, Peter Callas, Andrew Holcomb, Emre Vural, Kyle Davis, Carissa Thomas, John Stein, Ameya Asarkar, Ricardo Aulet, Rebecca Bell, Michael Blasco, Vanessa Bowmaster, Clayton Burruss, Jeffson Chung, Kimberly Chan, Brent Chang, Charles Coffey, David Cognetti, Dylan Cooper, Joehassin Cordero, John Donovan, Yue Jennifer Du, Yusuf Dundar, Rogerio Dedivitis, Heather Edwards, Boban Erovic, Antoine Eskander, Philip Feinberg, Emily Garvey, David Goldstein, Joseph Goodman, Rafael Goulart, Neerav Goyal, Stefan Grasl, Jonathan Giurintano, Nikita Gupta, Andy Habib, Trevor Hackman, Jared Hara, Christina Henson, Michael Hinni, Nadia Hua, Stephanie Johnson-Obaseki, Aditya Juloori, Noah Kalman, Alexandra Kejner, Sobia Khaja, Jamie Ku, Arnaud Lambert, Bao Luu, Kelly Magliocca, Luiz Medina Dos Santos, Cara Michael, Brett Miles, Giulianno De Melo, Michael Moore, Gregoire Morand, Kauê Moura, Hesameddin Noroozi, Rusha Patel, Joseph Paydarfar, Karolina Plonowska-Hirschfeld, Nader Sadeghi, Fabrice Savaria, Nicole Schmitt, Justin Shapiro, Timothy Shaver, Sandro Stoeckli, William Stokes, Anita Sulibhavi, Jason Tasoulas, Varun Vendra, Daniel Vinh, Celina Virgen, Neil Woody, Geoffrey Young, Kiran Kakarala, Danny Enepekides, Michael Hier, Louise Davies, William Ryan

Department of Otolaryngology - Head and Neck Surgery Faculty Papers

OBJECTIVES: To characterize practice patterns and outcomes in the management of low- and intermediate-grade salivary gland carcinoma prior to the existence of treatment guidelines.

METHODS: Analysis of a registry of patients who underwent parotid and submandibular gland resections for low-and intermediate-grade carcinomas between 2010 and 2019.

RESULTS: Of all 786 patients included in the study, 726 (92%) had preoperative imaging and 653 (83%) had preoperative biopsy. Of the 729 patients with parotid gland cancer, the majority underwent superficial (n = 384, 53%) or total (n = 254, 35%) parotidectomy. In patients with facial nerve preservation, total parotidectomy was …

Neurofilament Light (Nfl) Chain Levels Predict Clinical Decline In Alzheimer’S Disease: A Systematic Review And Meta-Analysis, Kim Thomas, Paul Spin, Nikita Sir, Kevin Hou, Nicholas J. Ashton, Henrik Zetterberg, Sonya Miller, Carol Pringle, Richard G. Stefanacci, Claude M. Wischik, Serge Gauthier

College of Population Health Faculty Papers

BACKGROUND: Regulatory approval of new investigational Alzheimer's disease (AD) therapies could be accelerated if reasonably likely surrogate endpoints could be used. Neurofilament light chain (NfL) has potential utility as a prognostic biomarker of neurodegeneration in AD.

OBJECTIVE: To synthesize available evidence on the relationship between baseline NfL levels and longitudinal clinical decline.

METHODS: A systematic literature review identified 19 eligible studies, contributing 37 longitudinal statistical models evaluating the association between baseline NfL (plasma or cerebrospinal fluid [CSF]) with subsequent clinical decline based on validated clinical scales including Mini-Mental State Examination (MMSE), Alzheimer's Disease Assessment Scale-Cognitive Subscale, and Clinical Dementia Rating. …

Immunotherapy For Precision Medicine In Colorectal Cancer, Miao Cao, Michael Xu, Zinah Bairmani, Babar Bashir, Scott A. Waldman, Adam E. Snook

Department of Pharmacology, Physiology, and Cancer Biology Faculty Papers

INTRODUCTION: Colorectal cancer (CRC) is the fourth most common cancer and second leading cause of cancer-related death in the United States. The implementation of CRC screening has decreased CRC incidence in adults older than 65 years. However, among young adults who experience more aggressive disease progression, CRC incidence has been increasing for decades. Immunotherapy represents a collection of innovative and promising approaches with greater efficacy and safety. In this review, we discuss modalities and selected targets of immunotherapies for CRCs that are guided by precision medicine.

AREAS COVERED: The following review focuses on immunological approaches for CRCs, including therapeutic monoclonal …

Medical Guidelines For Fibrodysplasia Ossificans Progressiva, Frederick S. Kaplan, Mona Al Mukaddam, Genevieve Baujat, Alberto Hidalgo Bravo, Matthew Brown, Amanda Cali, Tae-Joon Cho, Corrie Crowe, Carmen L. De Cunto, Patricia L. R. Delai, Robert J. Diecidue, Elisabeth Marelise W Eekhoff, Lisa Friedlander, Clive S. Friedman, Zvi Grunwald, Nobuhiko Haga, Edward C. Hsiao, Richard Keen, Joseph A. Kitterman, Charles Levy, Vrisha Madhuri, Rolf Morhart, J. Coen Netelenbos, Christiaan Scott, Eileen M. Shore, Michael Zasloff, Keqin Zhang, Robert J. Pignolo

Department of Oral and Maxillofacial Surgery Faculty Papers

Fibrodysplasia ossificans progressiva (FOP) is an ultra-rare genetic condition characterized by congenital malformations of the great toes and progressive heterotopic ossification (HO) in specific anatomic patterns. Present management summarized here is focused on early diagnosis, assiduous avoidance of injury and iatrogenic harm, symptomatic amelioration of painful flare-ups, and optimization of residual function. Twenty-one members of the International Clinical Council on FOP (ICC) and seven consultants from 15 countries, chosen for their clinical expertise in FOP, developed this summary statement. Further advances in therapeutics will be based on rigorous clinical trials to assess novel and emerging treatment and prevention strategies. A …

Chronic Poppers Maculopathy: Case Report And Literature Comparison Of Chronic And Acute Use, Francesco Cappellani, Caterina Gagliano, Jose S. Pulido

Wills Eye Hospital Papers

RATIONALE: Alkyl nitrites ("poppers") are recreational substances known for their vasodilatory and euphoric effects. Increasing evidence links them to a vision-threatening condition termed poppers maculopathy, characterized by foveal yellow spots and outer retinal changes on optical coherence tomography. While most reports describe acute exposure, little is known about long-term consequences. This case describes one of the longest documented durations of chronic poppers use, combined with a literature review to contextualize the clinical spectrum.

PATIENT CONCERNS: A 68-year-old man with human immunodeficiency virus, type 2 diabetes, hypertension, and depression presented with progressive central vision loss in both eyes persisting for at …

Trends And Disparities In Acute Coronary Syndrome-Related Mortality In The United States: Implications For Healthcare, Muhammad Khuzzaim Khan, Ibrahim Ahmed Khan, Abdul Moiz Javed, Arslan Wazir, Hira Saleem, Muhammad Zohaib, Faisal Rasheed, Priyanka Mohan Lal, Syeda Laiba Sherazi, Amiaz Karim, Nikhil Duseja, Hussam Al Hennawi

Abington Jefferson Health Papers

Acute coronary syndrome (ACS) is a major cause of morbidity and mortality in the United States (US). However, the trends and disparities in ACS mortality are not well understood. This study aimed to analyze the ACS mortality in the US from 1999 to 2020 using the Centers for Disease Control and Prevention Wide-Ranging Online Data for Epidemiologic Research database. The age-adjusted mortality rates (AAMR) due to ACS were calculated for each year from 1999 to 2020, stratified by sex, race, urbanization, and state. The trends and disparities in AAMR were examined using descriptive statistics and graphical methods. The AAMR due …

Rapid Mapping Of Spinal And Supraspinal Connectome Via Self-Targeting Glucose-Based Carbon Dots, Yasin B. Seven, Elif S. Seven, Emel Kirbas Cilingir, Komal Parikh, Mehmet Aydin, Edward K. Luca, Jayakrishnan Nair, Roger M. Leblanc

Department of Physical Therapy Faculty Papers

The spinal cord is a highly dynamic network, playing significant roles in the vital functions of the brain. Disorders of the spinal cord, such as spinal cord injury and amyotrophic lateral sclerosis (ALS), are associated with neurodegeneration, often resulting in morbidity and mortality. The blood-brain barrier (BBB) poses a major challenge to imaging and therapeutic agents because less than 2% of small-molecule drugs and almost no large-molecule drugs can cross the BBB. Furthermore, spatial spectroscopy studies have shown highly heterogeneous BBB crossing with significant accumulation at the unintended brain regions. Thus, targeting systems that can cross the BBB at the …

Early Blood Pressure Targets In Acute Spinal Cord Injury: A Randomized Clinical Trial, Ruba Sajdeya, N. David Yanez, Michael Kampp, Michael D. Goodman, David Zonies, Brandon Togioka, Andrew Nunn, Robert D. Winfield, Niels D. Martin, Anirudh Kohli, Toan T. Huynh, David O. Okonkwo, Roy A. Poblete, Emily J. Gilmore, Randall M. Chesnut, Aaron E. Bunnell, Tetsu Ohnuma, Mona Hashemaghaie, Miriam M. Treggiari

Department of Surgery Faculty Papers

IMPORTANCE: Early blood pressure management is central to neurologic resuscitation of spinal cord injury; however, the role of augmented blood pressure is unclear.

OBJECTIVE: To compare the efficacy and safety of augmented vs conventional blood pressure on 6-month neurologic outcomes after acute spinal cord injury.

DESIGN, SETTING, AND PARTICIPANTS: This multicenter randomized clinical trial took place from October 3, 2017, to July 26, 2023, and assessed patients 18 years or older with spinal cord injury followed up for 6 months at 13 large US trauma centers.

INTERVENTIONS: Patients were equally randomized to augmented (>85-90 mm Hg) or conventional ( …

Efficacy And Safety Of Rigosertib In Patients With Recessive Dystrophic Epidermolysis Bullosa-Associated Advanced/Metastatic Cutaneous Squamous Cell Carcinoma, Martin Laimer, Andrew P. South, Elisabeth Mayr, Sophie Kitzmueller, Lauren Banner, Michael Alexander, Linda Hosler, Henry Yang, Matthew Parris, Meena Arora, Georg Zimmermann, Gregor Schweighofer-Zwink, Johann Bauer, Neda Nikbakht

Department of Dermatology and Cutaneous Biology Faculty Papers

BACKGROUND: Recessive dystrophic epidermolysis bullosa (RDEB) is an epithelial fragility disease primarily affecting the skin and is caused by variants in the COL7A1 gene. Individuals with RDEB are predisposed to develop highly aggressive cutaneous squamous cell carcinomas (SCCs) which are the most common cause of premature death. There is a lack of effective prevention or treatment options for patients with RDEB-SCC.

OBJECTIVES: To evaluate the antitumour activity and safety of the polo-like kinase-1 (PLK1) inhibitor, rigosertib, two investigator-initiated open-label, single-arm phase II studies were opened in Europe and the USA and enrolled five patients with RDEB diagnosed with locally advanced …

Predictors Of All-Cause In-Hospital Mortality In Patients With Malignant Well-Differentiated Gastroenteropancreatic Neuroendocrine Tumors, Elvis Obomanu, Tarfa Verinumbe, Tinsae Anebo, Colton Jones, Claudia Dourado

Einstein Health Papers

BACKGROUND: Factors influencing in-hospital mortality in patients with well-differentiated gastroenteropancreatic neuroendocrine tumors (GEP-NETs) remain understudied, highlighting gaps in optimizing acute clinical outcomes. This study aimed to identify sociodemographic and clinical predictors of all-cause in-hospital mortality in this population.

METHODS: Using 2016 - 2020 data from the National Inpatient Sample (NIS), patients with malignant well-differentiated GEP-NETs were identified via the International Classification of Diseases, 10th Revision (ICD-10) codes. The primary outcome was in-hospital mortality. Sociodemographic and clinical variables (heart failure (HF), malnutrition, Charlson Comorbidity Index (CCI), and tumor site) were analyzed using multivariable logistic regression.

RESULTS: Among 5,642 patients (mean age …

Impact Of Tricuspid Regurgitation On The Clinical Outcomes Of Patients With Heart Failure, Muhammad U. Almani, Rasha Khan, Noor Fatima, Muhammad Yousuf, Aman Amanullah

Einstein Health Papers

BACKGROUND: Tricuspid regurgitation (TR) is a common occurrence in patients with heart failure (HF), and its role in disease progression has gained attention in recent years. Although TR can worsen clinical outcomes in HF patients, the impact of gender, racial, and socioeconomic factors remains largely unexplored. With growing evidence supporting the role of percutaneous interventions for the treatment of significant TR, understanding these disparities is more crucial than ever.

METHODS: Data were extracted from the National Inpatient and National Readmission 2016-2020 Databases. We used ICD-10 code I50 to identify the patients primarily admitted for HF and subdivided the cohort into …

Bard1: A Friend Or Foe In Pancreatic Ductal Adenocarcinoma?, Lily Zekavat, Aditi Jain

Department of Surgery Faculty Papers

Pancreatic ductal adenocarcinoma (PDAC) is an aggressive solid malignancy with poor overall prognosis and limited response to standard treatments. Growing interest in the modulation of DNA repair mechanisms, including the homologous recombination (HR) repair pathway, has opened new avenues for therapeutic development. BARD1 (BRCA1-Associated RING Domain 1) plays a complex role in tumor biology, functioning either as a tumor suppressor or as an oncogenic driver, depending on isoform expression, cellular context, and regulatory environment. In this review, we examine the dual roles of BARD1, focusing on its regulation and paradoxical activities in PDAC. We summarize evidence that BARD1 and BARD1 …

The Predilection Of Specific Diseases To Affect Different Sections Of The Esophagus, Monjur Ahmed

Division of Gastroenterology and Hepatology Faculty Papers

Certain esophageal diseases have a predilection for affecting different parts of the esophagus. This predilection is noted in our clinical practice as we investigate various esophageal diseases using multiple imaging and motility studies, as well as endoscopic procedures with biopsies. Clinical presentations vary with the stage and location of the disease. Clinicians can suspect certain diseases when a particular part of the esophagus is involved and then can perform appropriate investigations. Esophageal diseases with section involvement, with their symptomatology, diagnostic tests, and management, have been discussed in this narrative review. This review aims to revisit those diseases with a current …

Reaching International Consensus On The Definition Of Refractory Migraine Using The Delphi Method, Jennifer Robblee, Fawad A. Khan, Michael J. Marmura, Hope L. O'Brien, Lawrence D. Robbins, Marielle K. Samaha, Morris Levin, Simona Sacco, Raffaele Ornello, Stephanie J. Nahas, Heike Hesse, Annika Ehrlich, Adam S. Sprouse-Blum, Christina Sun-Edelstein, Bronwyn Jenkins, Elizabeth K, Seng, Shivang Joshi, Meredith J. Barad, Mi Ji Lee, Sheena K. Aurora, Mario Fernando Prieto Peres

Department of Neurology Faculty Papers

Aim: Despite its frequency in tertiary headache centers, the International Classification of Headache Disorders, 3rd edition (ICHD-3) does not include refractory migraine. Multiple definitions have been proposed with a recent 2020 proposal for both refractory migraine and resistant migraine by the European Headache Federation (EHF). The aim is to reach an international consensus on the definition of refractory migraine.

Methods: This study is a Delphi consensus carried out by a group of international experts in headache medicine. Following a focus group, a panel of 20 experts and one facilitator reviewed the EHF proposed criteria to build upon their definitions. The …

A Novel Sialylation Pathway Mediated By Extracellular Vesicles In Aggressive Prostate Cancer, Camila A. Bach, Md Niamat Hossain, Ishan J. Chaudhari, Cecilia E. Verrillo, Nicole M. Naranjo, Isabella Amoroso, Anna Testa, Samuel Sey, W. Kevin Kelly, Susan L. Bellis, Aurelio Lorico, Ada G. Blidner, Gabriel A. Rabinovich, Lucia R. Languino

Department of Pharmacology, Physiology, and Cancer Biology Faculty Papers

Altered cell surface glycosylation is a hallmark of cancer; among aberrant glycan structures, hypersialylated proteins contribute to disease progression. The enzyme ST6 β-galactoside α2,6-sialyltransferase 1 (ST6GAL1) mediates α2,6-linked sialylation of N-glycosylated proteins and is upregulated in many cancers, including prostate cancer (PrCa). We propose that ST6GAL1 may be released by cancer cells in small extracellular vesicles (sEVs) in the PrCa tumor microenvironment to potentially modulate cell surface sialylation in recipient cells. We isolated sEVs from PrCa cells by density gradient separation and characterized them by nanoparticle tracking analysis using ZetaView and immunoblotting analysis. We identified ST6GAL1 in both its membrane-bound …