Medical Specialties Commons^™

Editorial Review Of The Validation Of Thoracolumbar Injury Classification And Severity Score In The Management Of Acute And Subacute Osteoporotic Vertebral Compression Fractures, Alex R. Vaccaro

Department of Orthopaedic Surgery Faculty Papers

No abstract provided.

“Ups And Downs, Joys And Sorrows” – Assessment And Clinical Relevance Of Patient Priorities In An Interdisciplinary Parkinson’S Disease Clinic, Esme D. Trahair, Allison M. Allen, Sneha Mantri

Journal of Patient-Centered Research and Reviews

Purpose: Barriers to communication and inaccurate provider assumptions about patient priorities limit the delivery of comprehensive, high-quality, patient-centered care (PCC) to people with Parkinson’s (PWP). This study aimed to analyze priorities of PWP using a qualitative, unstructured single-question survey and to test associations with validated quality of life (QOL) measures.

Methods: During appointments at a subspecialty, interdisciplinary clinic, PWP (n = 139) provided written responses to the prompt: “What is important for your care team to know about you?” Patient Health Questionnaire, Montreal Cognitive Assessment, and Hoehn and Yahr scales were obtained through retrospective chart review. Key qualitative themes were …

Molecular Tumor Testing On Colorectal Adenocarcinoma Specimens In A Large Community-Based Healthcare System, David H. Kruchko, Sareena Ali, Mahbubul Hasan, Madeline Sesselmann, Imad Almanaseer, Eli D. Ehrenpreis

Journal of Patient-Centered Research and Reviews

Purpose: This study aimed to describe the adherence of National Comprehensive Cancer Network guidelines to perform genetic screening for all colorectal cancer (CRC) specimens with molecular tumor testing, eg, immunohistochemical (IHC) testing, in a large community-based healthcare setting. The study also identified trends involving characteristics of CRC, individual reporting physician, and physician location and examined the potential impact of these trends on the performance of molecular tumor testing.

Methods: This was a retrospective, multi-center study using a centralized pathology database to assess molecular testing on CRC specimens. The primary endpoint was whether tumor testing of a CRC specimen was performed. …

Antiplatelet Strategy For Patients With Acute Coronary Syndrome Undergoing Percutaneous Coronary Intervention: A Systematic Review And Network Meta-Analysis, Waqas Ullah, Harigopal Sandhyavenu, Amro Taha, Smitha Narayana Gowda, Maryam Mukhtar, Aravind Reddy Polam, Salman Zahid, David L. Fischman, Michael P. Savage, Sunil V. Rao, Mohamad Alkhouli

Division of Cardiology Faculty Papers

BACKGROUND: Optimal duration and choice of antiplatelet therapy in patients with acute coronary syndrome undergoing percutaneous coronary intervention remain controversial.

METHODS AND RESULTS: Digital databases (PubMed, Cochrane, and Embase) were queried to select all randomized controlled trials on a post-percutaneous coronary intervention population with acute coronary syndrome. Dual-antiplatelet therapy (DAPT) with aspirin and clopidogrel for 12 months was compared with 4 major strategies: high-potency, high- to low-potency, low-dose, and short-duration DAPT. A network meta-analysis was performed to compare the safety and efficacy of different antiplatelet strategies. This study was the second updated manuscript under the International Prospective Register of Systematic …

Yap1 Status Defines Two Intrinsic Subtypes Of Lcnec With Distinct Molecular Features And Therapeutic Vulnerabilities, C Allison Stewart, Lixia Diao, Yuanxin Xi, Runsheng Wang, Kavya Ramkumar, Alejandra G Serrano, Azusa Tanimoto, B Leticia Rodriguez, Benjamin B Morris, Li Shen, Bingnan Zhang, Yan Yang, Samera H Hamad, Robert J Cardnell, Alberto Duarte, Moushumi Sahu, Veronica Y Novegil, Bernard E Weissman, Michael Frumovitz, Neda Kalhor, Luisa Solis Soto, Pedro Da Rocha, Natalie Vokes, Don L Gibbons, Jing Wang, John V Heymach, Bonnie Glisson, Lauren Averett Byers, Carl M Gay

Faculty, Staff and Student Publications

Purpose: Large cell neuroendocrine carcinoma (LCNEC) is a high-grade neuroendocrine malignancy that, like small cell lung cancer (SCLC), is associated with the absence of druggable oncogenic drivers and dismal prognosis. In contrast to SCLC, however, there is little evidence to guide optimal treatment strategies, which are often adapted from SCLC and non-small cell lung cancer approaches.

Experimental design: To better define the biology of LCNEC, we analyzed cell line and patient genomic data and performed IHC and single-cell RNA sequencing of core needle biopsies from patients with LCNEC and preclinical models.

Results: In this study, we demonstrate that the presence …

Accurate Identification Of Locally Aneuploid Cells By Incorporating Cytogenetic Information In Single Cell Data Analysis, Ziyi Li, Ruoxing Li, Irene Ganan-Gomez, Hussein A Abbas, Guillermo Garcia-Manero, Wei Sun

Faculty, Staff and Student Publications

Single-cell RNA sequencing is a powerful tool to investigate the cellular makeup of tumor samples. However, due to the sparse data and the complex tumor microenvironment, it can be challenging to identify neoplastic cells that play important roles in tumor growth and disease progression. This is especially relevant for blood cancers, where neoplastic cells may be highly similar to normal cells. To address this challenge, we have developed partCNV and partCNVH, two methods for rapid and accurate detection of aneuploid cells with local copy number deletion or amplification. PartCNV uses an expectation-maximization (EM) algorithm with mixtures of Poisson distributions and …

Npm1-Mutated Myeloid Neoplasms Are A Unique Entity Not Defined By Bone Marrow Blast Percentage, Georgina Gener-Ricos, Alex Bataller, Juan Jose Rodriguez-Sevilla, Kelly S Chien, Andres E Quesada, Emmanuel Almanza-Huante, Danielle Hammond, Koji Sasaki, Courtney Dinardo, Tapan Kadia, Naval Daver, Gautam Borthakur, Ghayas C Issa, Nicholas J Short, Rashmi Kanagal-Shamanna, Hagop M Kantarjian, Guillermo Garcia-Manero, Guillermo Montalban-Bravo

Faculty, Staff and Student Publications

Introduction: NPM1-mutated (NPM1mut) myeloid neoplasms (MNs) with < 20% bone marrow (BM) blasts (NPM1mut MNs< 20) are uncommon, and their classification remains inconsistent.

Methods: The clinicopathologic features of 54 patients with NPM1mut MNs < 20 were evaluated and compared with wild-type NPM1 MNs < 20 and NPM1mut MNs≥20, respectively.

Results: NPM1mut MNs had similar features regardless of blast percentage, except for higher IDH2 (29% vs 7%, p = .023) and FLT3 (70% vs 11%, p < .001) frequency in patients with ≥20% BM blasts. Thirty-three (61%) patients with NPM1mut MNs < 20 received low-intensity chemotherapy (LIC) and 12 (22%) received intensive chemotherapy (IC). Higher complete remission rates (75% vs 27%, p = .006) and median overall survival (mOS) (not reached vs 30.4 months, p = .06) were observed with IC compared to LIC. Young patients (age < 60 years) did not reach mOS either when treated with LIC or IC. Stem cell transplant was associated with increased survival only in patients treated with LIC (HR, 0.24; p = .025). No differences in mOS were observed by BM blast strata (32.2 months, not reached and 46.9 months for < 10%, 10%-19%, and ≥20% blasts, p = .700) regardless of treatment modality (LIC: p = .900; IC: p = .360). Twenty-three patients (43%) with NPM1mut MNs < 20 had marrow blast progression to ≥20%.

Conclusions: Overall, NPM1mut MNs define a unique entity independent of BM blast percentage.

Biochemical And Structural Insights Into A 5′ To 3′ Rna Ligase Reveal A Potential Role In Trna Ligation, Yingjie Hu, Victor A Lopez, Hengyi Xu, James P Pfister, Bing Song, Kelly A Servage, Masahiro Sakurai, Benjamin T Jones, Joshua T Mendell, Tao Wang, Jun Wu, Alan M Lambowitz, Diana R Tomchick, Krzysztof Pawłowski, Vincent S Tagliabracci

Faculty, Staff and Student Publications

ATP-grasp superfamily enzymes contain a hand-like ATP-binding fold and catalyze a variety of reactions using a similar catalytic mechanism. More than 30 protein families are categorized in this superfamily, and they are involved in a plethora of cellular processes and human diseases. Here, we identify C12orf29 (RLIG1) as an atypical ATP-grasp enzyme that ligates RNA. Human RLIG1 and its homologs autoadenylate on an active site Lys residue as part of a reaction intermediate that specifically ligates RNA halves containing a 5’-phosphate and a 3’-hydroxyl. RLIG1 binds tRNA in cells and can ligate tRNA within the anticodon loop in vitro. Transcriptomic …

Proportional Hazards Violations In Phase Iii Cancer Clinical Trials: A Potential Source Of Trial Misinterpretation, Timothy A Lin, Zachary R Mccaw, Alex Koong, Christine Lin, Joseph Abi Jaoude, Roshal Patel, Ramez Kouzy, Molly B El Alam, Alexander D Sherry, Sonal S Noticewala, Clifton D Fuller, Charles R Thomas, Ryan Sun, J Jack Lee, Ruitao Lin, Ying Yuan, Yu Shyr, Tomer Meirson, Ethan B Ludmir

Faculty, Staff and Student Publications

Purpose: Survival analyses of novel agents with long-term responders often exhibit differential hazard rates over time. Such proportional hazards violations (PHV) may reduce the power of the log-rank test and lead to misinterpretation of trial results. We aimed to characterize the incidence and study attributes associated with PHVs in phase III oncology trials and assess the utility of restricted mean survival time and maximum combination test as additional analyses.

Experimental design: Clinicaltrials.gov and PubMed were searched to identify two-arm, randomized, phase III superiority-design cancer trials with time-to-event primary endpoints and published results through 2020. Patient-level data were reconstructed from published …

Evaluating Debio 1347 In Patients With Fgfr Fusion-Positive Advanced Solid Tumors From The Fuze Multicenter, Open-Label, Phase Ii Basket Trial, Petros Grivas, Elena Garralda, Funda Meric-Bernstam, Ingo K Mellinghoff, Lipika Goyal, James J Harding, E Claire Dees, Rastislav Bahleda, Nilofer S Azad, Asha Karippot, Razelle Kurzrock, Josep Tabernero, Juha Kononen, Matthew C H Ng, Rutika Mehta, Nataliya V Uboha, Frédéric Bigot, Valentina Boni, Samantha E Bowyer, Valeriy Breder, Andrés Cervantes, Nancy Chan, James M Cleary, Mallika Dhawan, Rikke L Eefsen, James Ewing, Donna M Graham, Tormod K Guren, Jin Won Kim, Krassimir Koynov, Do-Youn Oh, Rebecca Redman, Chia-Jui Yen, David Spetzler, Marie-Claude Roubaudi-Fraschini, Valerie Nicolas-Metral, Rafik Ait-Sarkouh, Claudio Zanna, Abdallah Ennaji, Anna Pokorska-Bocci, Keith T Flaherty

Faculty, Staff and Student Publications

Purpose: This multicenter phase II basket trial investigated the efficacy, safety, and pharmacokinetics of Debio 1347, an investigational, oral, highly selective, ATP-competitive, small molecule inhibitor of FGFR1-3, in patients with solid tumors harboring a functional FGFR1-3 fusion.

Patients and methods: Eligible adults had a previously treated locally advanced (unresectable) or metastatic biliary tract (cohort 1), urothelial (cohort 2), or another histologic cancer type (cohort 3). Debio 1347 was administered at 80 mg once daily, continuously, in 28-day cycles. The primary endpoint was the objective response rate. Secondary endpoints included duration of response, progression-free survival, overall survival, pharmacokinetics, and incidence of …

First-In-Human Clinical Outcomes With Ng-350a, An Anti-Cd40 Expressing Tumor-Selective Vector Designed To Remodel Immunosuppressive Tumor Microenvironments, Aung Naing, Danny Khalil, Oliver Rosen, D Ross Camidge, Tom Lillie, Rui-Ru Ji, Andrea Stacey, Matthew Thomas, Lee Rosen

Faculty, Staff and Student Publications

Background: Tumor-selective oncolytic viral vectors are promising anticancer therapeutics; however, challenges with dosing and potency in advanced/metastatic cancers have limited efficacy and usage. NG-350A is a next-generation blood-stable adenoviral vector engineered to express an agonist anti-cluster of differentiation (CD)40 antibody without affecting tumor-selectivity and oncolytic potency.

Methods: Intravenous and intratumoral (IT) administration of NG-350A was assessed in a phase Ia/Ib study in patients with metastatic/advanced epithelial tumors (NCT03852511). Dose-escalation was performed separately for intravenous (four dose levels available, each with infusions on Days 1, 3 and 5 of a 57-day treatment period) and IT (single injection on D1 …

Cdk12 Loss Drives Prostate Cancer Progression, Transcription-Replication Conflicts, And Synthetic Lethality With Paralog Cdk13, Jean Ching-Yi Tien, Jie Luo, Yu Chang, Yuping Zhang, Yunhui Cheng, Xiaoju Wang, Jianzhang Yang, Rahul Mannan, Somnath Mahapatra, Palak Shah, Xiao-Ming Wang, Abigail J Todd, Sanjana Eyunni, Caleb Cheng, Ryan J Rebernick, Lanbo Xiao, Yi Bao, James Neiswender, Rachel Brough, Stephen J Pettitt, Xuhong Cao, Stephanie J Miner, Licheng Zhou, Yi-Mi Wu, Estefania Labanca, Yuzhuo Wang, Abhijit Parolia, Marcin Cieslik, Dan R Robinson, Zhen Wang, Felix Y Feng, Jonathan Chou, Christopher J Lord, Ke Ding, Arul M Chinnaiyan

Faculty, Staff and Student Publications

Biallelic loss of cyclin-dependent kinase 12 (CDK12) defines a metastatic castration-resistant prostate cancer (mCRPC) subtype. It remains unclear, however, whether CDK12 loss drives prostate cancer (PCa) development or uncovers pharmacologic vulnerabilities. Here, we show Cdk12 ablation in murine prostate epithelium is sufficient to induce preneoplastic lesions with lymphocytic infiltration. In allograft-based CRISPR screening, Cdk12 loss associates positively with Trp53 inactivation but negatively with Pten inactivation. Moreover, concurrent Cdk12/Trp53 ablation promotes proliferation of prostate-derived organoids, while Cdk12 knockout in Pten-null mice abrogates prostate tumor growth. In syngeneic systems, Cdk12/Trp53-null allografts exhibit luminal morphology and immune checkpoint blockade sensitivity. Mechanistically, Cdk12 inactivation …

A Phase Ib/Ii Randomized Clinical Trial Of Oleclumab With Or Without Durvalumab Plus Chemotherapy In Patients With Metastatic Pancreatic Ductal Adenocarcinoma, Andrew L Coveler, Matthew J Reilley, Mark Zalupski, Teresa Macarulla, Christos Fountzilas, Mariano Ponz-Sarvisé, Adnan Nagrial, Nataliya V Uboha, Sophia Frentzas, Michael Overman, Anne Noonan, Wells A Messersmith, Nick Pavlakis, Niharika B Mettu, Ina Bisha, Ying Wang, Paul Smith, Elina Murtomaki, Agata A Bielska, Veronique Bragulat, Zachary A Cooper, Rakesh Kumar, David R Spigel

Faculty, Staff and Student Publications

Purpose: Pancreatic ductal adenocarcinoma upregulates CD73, potentially contributing to immune surveillance evasion. Combining oleclumab (CD73 inhibitor) and durvalumab with chemotherapy may identify an effective treatment option.

Patients and methods: We describe a multicenter phase Ib/II randomized clinical trial in patients with metastatic pancreatic ductal adenocarcinoma, untreated (cohort A) or previously received gemcitabine-based chemotherapy (cohort B; NCT03611556). During escalation, patients received oleclumab 1,500 or 3,000 mg, durvalumab 1,500 mg, and gemcitabine plus nab-paclitaxel (GnP; cohort A; n = 14) or modified FOLFOX (cohort B; n = 11). During expansion, cohort A patients (n = 170) were randomized to GnP (arm …

Development And Validation Of A Machine Learning Model To Predict Myocardial Blood Flow And Clinical Outcomes From Patients’ Electrocardiogram, Fares Alahdab, Maliazurina Binti Saad, Ahmed Ibrahim Ahmed, Qasem Al Tashi, Muhammad Aminu, Yushui Han, Jonathan B Moody, Venkatesh L Murthy, Jia Wu, Mouaz H Al-Mallah

Faculty, Staff and Student Publications

We develop a machine learning (ML) model using electrocardiography (ECG) to predict myocardial blood flow reserve (MFR) and assess its prognostic value for major adverse cardiovascular events (MACEs). Using 3,639 ECG-positron emission tomography (PET) and 17,649 ECG-single-photon emission computed tomography (SPECT) data pairs, the ML model is trained with a swarm intelligence approach and support vector regression (SVR). The model achieves a receiver-operator curve (ROC) area under the curve (AUC) of 0.83, with a sensitivity and specificity of 0.75. An ECG-MFR value below 2 is significantly associated with MACE, with hazard ratios (HRs) of 3.85 and 3.70 in the discovery …

Interleukin-15 And High-Intensity Exercise: Relationship With Inflammation, Body Composition And Fitness In Cancer Survivors, Morgan J. Farley, Alexander N. Boytar, Kirsten N. Adlard, Chloe E. Salisbury, Nicolas H. Hart, Mia A. Schaumberg, David G. Jenkins, Tina L. Skinner

Research outputs 2022 to 2026

Pre-clinical murine and in vitro models have demonstrated that exercise suppresses tumour and cancer cell growth. These anti-oncogenic effects of exercise were associated with the exercise-mediated release of myokines such as interleukin (IL)-15. However, no study has quantified the acute IL-15 response in human cancer survivors, and whether physiological adaptations to exercise training (i.e. body composition and cardiorespiratory fitness) influence this response. In the present study breast, prostate and colorectal cancer survivors (n = 14) completed a single bout of high-intensity interval exercise (HIIE) [4×4 min at 85–95% heart rate (HR) peak, 3 min at 50–70% HR peak] before and …

Intraindividual Discordance Between Remnant Cholesterol And Low-Density Lipoprotein Cholesterol Associated With Incident Stroke: Results From 2 National Cohorts, Cancan Cui, Pingan Li, Yitian Qi, Jiayin Song, Tianjiao Han, Xinyun Shang, Lois Balmer, Chen Sheng, Yining Zha, Zhonghang Xu, Xu Wang, Zhiyuan Wu

Research outputs 2022 to 2026

BACKGROUND: The atherogenic effect of remnant cholesterol is being increasingly acknowledged. This study aimed to explore the association of discordance between remnant cholesterol and low-density lipoprotein cholesterol with stroke onset using 2 Chinese national cohorts. METHODS AND RESULTS: We studied 11 139 participants from CHARLS (China Health and Retirement Longitudinal Study) and 5993 participants from CHNS (China Health and Nutrition Survey) aged 45 years or older. The discordance between remnant cholesterol and low-density lipoprotein cholesterol was defined using the difference in percentile units (>15 units). There were 988 (8.9%) and 128 (2.1%) stroke events reported during follow-up in the …

Exposure To Per- And Polyfluoroalkyl Substances And Alterations In Plasma Microrna Profiles In Children, Yijie Li, Brittney O Baumert, Nikos Stratakis, Jesse A Goodrich, Haotian Wu, Shelley H Liu, Hongxu Wang, Emily Beglarian, Scott M Bartell, Sandrah Proctor Eckel, Douglas Walker, Damaskini Valvi, Michele Andrea La Merrill, Thomas H Inge, Todd Jenkins, Justin R Ryder, Stephanie Sisley, Rohit Kohli, Stavra A Xanthakos, Marina Vafeiadi, Aikaterini Margetaki, Theano Roumeliotaki, Max Aung, Rob Mcconnell, Andrea Baccarelli, David Conti, Lida Chatzi

Faculty, Staff and Students Publications

BACKGROUND: Per- and polyfluoroalkyl substances (PFAS) are synthetic chemicals that persist in the environment and can accumulate in humans, leading to adverse health effects. MicroRNAs (miRNAs) are emerging biomarkers that can advance the understanding of the mechanisms of PFAS effects on human health. However, little is known about the associations between PFAS exposures and miRNA alterations in humans.

OBJECTIVE: To investigate associations between PFAS concentrations and miRNA levels in children.

METHODS: Data from two distinct cohorts were utilized: 176 participants (average age 17.1 years; 75.6% female) from the Teen-Longitudinal Assessment of Bariatric Surgery (Teen-LABS) cohort in the United States, and …

Magnetoelectrics For Implantable Bioelectronics: Progress To Date, Fatima Alrashdan, Kaiyuan Yang, Jacob T Robinson

Faculty, Staff and Students Publications

The coupling of magnetic and electric properties manifested in magnetoelectric (ME) materials has unlocked numerous possibilities for advancing technologies like energy harvesting, memory devices, and medical technologies. Due to this unique coupling, the magnetic properties of these materials can be tuned by an electric field; conversely, their electric polarization can be manipulated through a magnetic field. Over the past seven years, our lab work has focused on leveraging these materials to engineer implantable bioelectronics for various neuromodulation applications. One of the main challenges for bioelectronics is to design miniaturized solutions that can be delivered with minimally invasive procedures and yet …

Sall4 And Gata4 Induce Cardiac Fibroblast Transition Towards A Partially Multipotent State With Cardiogenic Potential, Hong Gao, Saliha Pathan, Beverly R E A Dixon, Aarthi Pugazenthi, Megumi Mathison, Tamer M A Mohamed, Todd K Rosengart, Jianchang Yang

Faculty, Staff and Students Publications

Cardiac cellular fate transition holds remarkable promise for the treatment of ischemic heart disease. We report that overexpressing two transcription factors, Sall4 and Gata4, which play distinct and overlapping roles in both pluripotent stem cell reprogramming and embryonic heart development, induces a fraction of stem-like cells in rodent cardiac fibroblasts that exhibit unlimited ex vivo expandability with clonogenicity. Transcriptomic and phenotypic analyses reveal that around 32 ± 6.4% of the expanding cells express Nkx2.5, while 13 ± 3.6% express Oct4. Activated signaling pathways like PI3K/Akt, Hippo, Wnt, and multiple epigenetic modification enzymes are also detected. Under suitable conditions, these cells …

Pathological Fractures And The Perils Of Purchasing Steroids Online, Danielle C Thor, Valerie Rome

Rowan-Virtua School of Osteopathic Medicine Departmental Research

Exogenous steroids are a staple of modern medicine, with utility in a variety of direct and supplemental treatment modalities. However, all pharmaceuticals are undoubtedly coupled with unique side effect profiles, and steroids are no exception. In the case presented, the assessment and management of a 36-year-old male who inappropriately self-administered high-dose steroids for prolonged periods of time is reviewed. In doing so, attention is drawn to both the impact of glucocorticoid-induced osteoporosis and the greater risk of online availability of these powerful medications.

Memory Modulation: Dominance Of Negative Visual Context Over Neutral Verbal Memory, Stas Kozak, Noa Herz, Maya Tocker, Yair Bar-Haim, Nitzan Censor

Department of Neurology Faculty Papers

Neutral memories can be modulated via intentional memory control paradigms such as directed forgetting. In addition, previous studies have shown that neutral visual memories can be modulated indirectly, via remember and forget instructions towards competing verbal memories. Here we show that direct modulation of neutral verbal memory strength is impaired by negative visual context, and that negative visual context is resistant to indirect memory modulation. Participants were directly instructed to intentionally remember or forget newly encoded neutral verbal information. Importantly, this verbal information was interleaved with embedded negative visual context. Results showed that negative visual context eliminated the well-documented effect …

Simulated Resections And Responsive Neurostimulator Placement Can Optimize Postoperative Seizure Outcomes When Guided By Fast Ripple Networks, Shennan Aibel Weiss, Michael R Sperling, Jerome Engel, Anli Liu, Itzhak Fried, Chengyuan Wu, Werner Doyle, Charles Mikell, Sima Mofakham, Noriko Salamon, Myung Shin Sim, Anatol Bragin, Richard Staba

Department of Neurology Faculty Papers

In medication-resistant epilepsy, the goal of epilepsy surgery is to make a patient seizure free with a resection/ablation that is as small as possible to minimize morbidity. The standard of care in planning the margins of epilepsy surgery involves electroclinical delineation of the seizure-onset zone and incorporation of neuroimaging findings from MRI, PET, single-photon emission CT and magnetoencephalography modalities. Resecting cortical tissue generating high-frequency oscillations has been investigated as a more efficacious alternative to targeting the seizure-onset zone. In this study, we used a support vector machine (SVM), with four distinct fast ripple (FR: 350-600 Hz on oscillations, 200-600 Hz …

Clean Intermittent Catheterisation Determinants And Caregiver Adherence In Paediatric Patients With Spinal Dysraphism And Spinal Cord Injury In A Paediatric Spinal Differences Clinic: A Mixed Methods Study Protocol., Azadeh Wickham, Cynthia L. Russell, John Gatti

Manuscripts, Articles, Book Chapters and Other Papers

INTRODUCTION: Clean intermittent catheterisation (CIC) is the standard of care for treating neurogenic lower urinary tract dysfunction (NLUTD), the most common bladder dysfunction in children diagnosed with spinal dysraphism (SD) and spinal cord injury (SCI). Failure to follow the prescribed CIC regimen results in urinary tract infections, incontinence and renal insufficiency. Adherence to CIC is suboptimal, with reported non-adherence rates of 18%-66%. Despite the efficacy of CIC, the research on CIC adherence is not well defined in the literature and even less for caregivers of children on CIC protocols.

METHODS: This proposed study aims to identify caregiver CIC adherence and …

Ovarian Cancer Metastasis: Looking Beyond The Surface, Emine Bayraktar, Sisy Chen, Sara Corvigno, Jinsong Liu, Anil K Sood

Faculty, Staff and Student Publications

Historically, ovarian cancer (OC) was thought to metastasize by surface-to-surface spread, but recent developments have yielded a new understanding of the paths of metastatic spread. Given the histologic and molecular heterogeneity of OC, we will focus on high-grade serous carcinoma (HGSC). Here, we provide a critical and more holistic view of the evidence supporting various routes of metastasis, including peritoneal, hematogenous, lymphatic, and nerve-related. Understanding the underlying mechanisms is necessary to improve treatment strategies for this challenging disease.

Left Ventricular Diastolic Dysfunction With Elevated Filling Pressures Is Associated With Embolic Stroke Of Undetermined Source And Atrial Fibrillation, Zubair Bashir, Liqi Shu, Yuqian Guo, Edward W Chen, Shuyuan Wang, Eric D Goldstein, Maheen Rana, Narendra Kala, Xing Dai, Daniel Mandel, Shadi Yaghi, Phinnara Has, Mingxing Xie, Tao Wang, James Simmons, Christopher Song, Philip Haines

Faculty, Staff and Student Publications

Background/Objectives: Left ventricular diastolic dysfunction (LVDD) and elevated left ventricular filling pressure (LVFP) are strong predictors of clinical outcomes across various populations. However, their diagnostic utility in embolic stroke of undetermined source (ESUS) remains unclear. We hypothesized that LVDD with elevated LVFP (based on echocardiography) was more likely to be prevalent in ESUS compared to non-cardioembolic stroke (NCE) and to be associated with atrial fibrillation (AF) on follow-up monitoring.

Methods: This is a single-center retrospective study that included adult patients with a diagnosis of acute ischemic stroke between January 2016 and June 2017. LV function was assessed by …

High-Sensitivity Cardiac Troponin [Hs-Ctn] As A Valuable Biomarker For Pulmonary Hypertension Risk Stratification: A Contemporary Review Of The Literature, Vijay Durga Pradeep Ganipineni, Sahas Reddy Jitta, Mohan Chandra Vinay Bharadwaj Gudiwada, Jaswanth Rao Jasti, Chaitra Janga, Bhavyasri Merugu, Revanth Reddy Bandaru, Srikanth Puli, Vikramaditya Samala Venkata, Advait Vasavada, Rupak Desai

Abington Jefferson Health Papers

Background: Pulmonary hypertension (PH) can lead to cardiac failure, thereby signif- icantly affecting life expectancy and quality of life. Due to inadequate disease surveillance and risk assessment, clinical challenges persist despite advances in diagnosis and treatment. We aimed to review the potential of high-sensitivity cardiac troponin (hs-cTn) as a biomarker for predicting outcomes in PH patients. Methods: A thorough examination of the PubMed and Google Scholar databases was conducted through March 2023. Studies involving adult PH patients and hsTn as a prognostic indicator of outcomes such as mortality, hospitalization, and disease progression were included, after screening their titles and abstracts. …

Cervical Osteomyelitis In The Setting Of Multiple Comorbidities: A Complex Anatomical Approach. Illustrative Case, Jack A. Leoni, Michelle E. Veillon-Bradshaw, Kaleb J. Derouen, John M. Wilson, Wesley M. Shoap

School of Medicine Faculty Publications

BACKGROUND Vertebral osteomyelitis (VO), also known as spinal osteomyelitis or spondylodiscitis, is a rather rare yet serious disease comprising 3%–5% of all osteomyelitis cases, with only 3%–6% of this subset affecting the cervical spine. Risk factors include an advanced age, diabetes, immunosuppression, and intravenous (IV) drug use. The incidence of VO has increased over recent decades, with high-risk patients experiencing higher mortality rates. Treatment guidelines for VO are not standardized and rely on physician preference, often starting with IV antibiotics and progressing to surgery, if necessary. OBSERVATIONS A 54-year-old female with tracheostomy-dependent obesity hypoventilation syndrome, hypertension, and morbid obesity presented …

Transjugular Random Renal Biopsy: A Review, Katelyn Gill, Dan F. Laney Iv, Hector Ferral

School of Medicine Faculty Publications

Random renal biopsy is considered the gold standard for the diagnosis of systemic renal disorders. Percutaneous biopsy remains a safe option for most patients; however, the percutaneous approach may be considered too risky in approximately 5-10% of patients. In these high-risk patients, transjugular renal biopsy (TJRB) may represent an underutilized alternative. TJRB is a technically difficult procedure with a learning curve of approximately 10 cases. When performed properly, TJRB is a safe alternative to percutaneous biopsy in patients with renal failure or who are at high risk of bleeding. This article aims to provide a comprehensive review of the indications, …

Integrated Electrophysiological And Genomic Profiles Of Single Cells Reveal Spiking Tumor Cells In Human Glioma, Rachel N Curry, Qianqian Ma, Malcolm F Mcdonald, Yeunjung Ko, Snigdha Srivastava, Pey-Shyuan Chin, Peihao He, Brittney Lozzi, Prazwal Athukuri, Junzhan Jing, Su Wang, Arif O Harmanci, Benjamin Arenkiel, Xiaolong Jiang, Benjamin Deneen, Ganesh Rao, Akdes Serin Harmanci

Faculty, Staff and Students Publications

Prior studies have described the complex interplay that exists between glioma cells and neurons, however, the electrophysiological properties endogenous to tumor cells remain obscure. To address this, we employed Patch-sequencing on human glioma specimens and found that one third of patched cells in IDH mutant (IDHmut) tumors demonstrate properties of both neurons and glia by firing single, short action potentials. To define these hybrid cells (HCs) and discern if they are of tumoral origin, we developed a computational tool, Single Cell Rule Association Mining (SCRAM), to annotate each cell individually. SCRAM revealed that HCs represent tumor and non-tumor cells that …

Sdeper: A Hybrid Machine Learning And Regression Method For Cell-Type Deconvolution Of Spatial Barcoding-Based Transcriptomic Data, Yunqing Liu, Ningshan Li, Ji Qi, Gang Xu, Jiayi Zhao, Nating Wang, Xiayuan Huang, Wenhao Jiang, Huanhuan Wei, Aurélien Justet, Taylor S Adams, Robert Homer, Amei Amei, Ivan O Rosas, Naftali Kaminski, Zuoheng Wang, Xiting Yan

Faculty, Staff and Students Publications

Spatial barcoding-based transcriptomic (ST) data require deconvolution for cellular-level downstream analysis. Here we present SDePER, a hybrid machine learning and regression method to deconvolve ST data using reference single-cell RNA sequencing (scRNA-seq) data. SDePER tackles platform effects between ST and scRNA-seq data, ensuring a linear relationship between them while addressing sparsity and spatial correlations in cell types across capture spots. SDePER estimates cell-type proportions, enabling enhanced resolution tissue mapping by imputing cell-type compositions and gene expressions at unmeasured locations. Applications to simulated data and four real datasets showed SDePER's superior accuracy and robustness over existing methods.