Digital Commons Network^™

Sickle Cell Disease Induces Chromatin Introversion And Ferroptosis In Cd8+ T Cells To Suppress Anti-Tumor Immunity, Zilong Zhao, Benxia Hu, Yalan Deng, Melinda Soeung, Jun Yao, Lanxin Bei, Yaohua Zhang, Pengju Gong, Lisa A Huang, Zhou Jiang, Jian Gao, Shuang Peng, Tina K Nguyen, Menuka Karki, Bora Lim, Cassian Yee, Jared K Burks, Qing Zhang, Li Ma, Jianjun Gao, Nizar M Tannir, Leng Han, Dihua Yu, Linghua Wang, Michael A Curran, Maria A Gubbiotti, Giannicola Genovese, Boyi Gan, Wenbo Li, Pavlos Msaouel, Liuqing Yang, Chunru Lin

Faculty, Staff and Student Publications

Understanding how genetic disorders affect CD8+ T cells in the tumor microenvironment is key to improving cancer immunotherapy. Individuals with sickle cell disease (SCD), the most prevalent inherited blood disorder, have a higher risk of developing certain cancers than the general population, but the mechanisms driving this increased risk remain unclear. Our study revealed that SCD altered CD8+ T cell 3D genome architecture, triggering ferroptosis and weakening anti-tumor immunity, thereby promoting tumor growth. Using murine and humanized SCD models, we found that disrupted chromosomal interactions in CD8+ T cells reduced the expression of anti-ferroptotic genes, including SLC7A11 and hydrogen sulfide …

Application Of Claims-Based Frailty Index To A Structured Electronic Health Record Data, Min Ji Kwak, Caroline Schaefer, Youngran Kim, Sunyang Fu, Chan Mi Park, Abhijeet Dhoble, Nahid Rianon, Holly M Holmes, Dae Hyun Kim

Faculty, Staff and Student Publications

Background: The Claims-based Frailty Index (CFI) has been developed and validated using Medicare claims data. However, whether CFI can be applied to structured electronic health record data has not been studied.

Methods: We applied the CFI to a structured electronic health record dataset (Explorys dataset) and a Medicare fee-for-service 5% sample data and compared the prevalence of frailty from each dataset, using the cohort of older adults. Then, we assessed the odds ratio and area under the curve of the frailty predicting adverse clinical outcomes, any hospital or emergency room visit, or any adverse drug events related encounter within 1 …

Radiotherapy Promotes Cuproptosis And Synergizes With Cuproptosis Inducers To Overcome Tumor Radioresistance, Guang Lei, Mingchuang Sun, Jun Cheng, Rui Ye, Zhengze Lu, Amber Horbath, David Huo, Shengrong Wu, Anagha Alapati, Sadhna Aggarwal, Zhihao Xu, Chao Mao, Yuelong Yan, Jun Yao, Qidong Li, Xiong Chen, Hyemin Lee, Li Zhuang, Dadi Jiang, Apar Pataer, Jack A Roth, Nicholas Navin, Albert C Koong, Mingjian James You, Steven H Lin, Boyi Gan

Faculty, Staff and Student Publications

Cuproptosis is a recently identified form of copper-dependent cell death. Here, we reveal that radiotherapy (RT) induces cuproptosis in cancer cells, independent of apoptosis and ferroptosis, and depletes lipoylated proteins and iron-sulfur (Fe-S) cluster proteins-both hallmarks of cuproptosis-in patient tumors. Mechanistically, RT elevates mitochondrial copper levels by upregulating copper transporter 1 (CTR1) and depleting mitochondrial glutathione, a copper chelator, thereby triggering cuproptosis. Integrated analyses of RNA sequencing (RNA-seq) from radioresistant esophageal cancer cells and single-cell RNA-seq from esophageal tumors of patients unresponsive to RT link radioresistance to the downregulation of BTB and CNC homology 1 (BACH1). This downregulation de-represses the …

Role Of Interventional Pulmonology In Intensive Care Units: A Scoping Review, Abdul Rahman R Halawa, Saad Farooq, Mohammad Asim Amjad, Pushan P Jani, Sujith V Cherian

Faculty, Staff and Student Publications

Interventional pulmonology (IP) represents a rapidly growing and developing subspecialty within pulmonary medicine. To the intensivist, given the elaborate undertakings with respect to airway, lung and pleural disease management-IP has shown an increasing presence and remain a major ally in the care of these patients. Thus, an understanding of the different roles that IP could offer to the intensivist is of prime importance in the multi-disciplinary care of the complex patients within the intensive care units, particularly in relation to lung, airway and pleural diseases. This review article will explore the different intersections of IP in critical care and discuss …

Forum Of Esrd Networks: 50 Years Of Collaboration, Innovation, And Education To Promote Equitable And Optimal Kidney-Patient Centered Care, David Henner, Daniel Landry, Donald A Molony, Andrew Howard, Mary Albin, Mary Baliker, Dawn P Edwards, Dee Leduc, Ramin Sam, Preethi Yerram, Kamyar Kalantar-Zadeh

Faculty, Staff and Student Publications

No abstract provided.

Omitting Regional Nodal Irradiation After Response To Neoadjuvant Chemotherapy, Eleftherios P Mamounas, Hanna Bandos, Julia R White, Thomas B Julian, Atif J Khan, Simona F Shaitelman, Mylin A Torres, Frank A Vicini, Patricia A Ganz, Susan A Mccloskey, Peter C Lucas, Nilendu Gupta, X Allen Li, Beryl Mccormick, Benjamin Smith, Rahul D Tendulkar, Vivek S Kavadi, Koji Matsumoto, Samantha Andrews Seaward, William J Irvin, Jolinta Y Lin, Robert W Mutter, Thierry M Muanza, Jannifer Stromberg, Reshma Jagsi, Anna C Weiss, Walter J Curran, Norman Wolmark

Faculty, Staff and Student Publications

Background: The benefit of regional nodal irradiation in the treatment of breast cancer is well established for patients with pathologically positive axillary nodes, but whether it is also beneficial for patients whose nodes become pathologically tumor free (ypN0) after neoadjuvant chemotherapy remains unclear.

Methods: We evaluated whether regional nodal irradiation improves outcomes in patients with biopsy-proven, node-positive breast cancer who reach ypN0 status after neoadjuvant chemotherapy. Patients with breast cancer with a clinical stage of T1 to T3 (tumor size, ≤2 cm to >5 cm), N1, and M0 (indicating spread to one to three axillary lymph nodes but no distant …

Eph Receptors Activate Myeloid Checkpoint Receptor Lilrb5 To Support Tumor Development, Yubo He, Chengcheng Zhang, Lingxiao Tan, Mi Deng, Xiaoye Liu, Ryan Huang, Xing Yang, Jingjing Xie, Qi Lou, Meng Fang, Caroline Smith, Samuel John, Wei Xiong, Xin Li, Cheryl Lewis, Jade Homsi, Ankit Gupta, Ningyan Zhang, Zhiqiang An, Cheng Cheng Zhang

Faculty, Staff and Student Publications

Immunosuppressive myeloid cells are critical obstacles to T cell-centered immune checkpoint blockade therapies, which have been successful in treating a fraction of patients with cancer. How tumor cells interact with myeloid cells to regulate immune responses and tumor development is unclear. In this study, we report that certain membrane tyrosine kinase Eph receptors, including EphA7 and EphB1, specifically bind the immune inhibitory receptors leukocyte Ig-like receptor family B 5 (LILRB5) and LILRB2. These Eph receptors induce LILRB5-mediated signaling activation, and LILRB5 also activates Eph receptor signaling. Activation of LILRB5 promoted immunosuppressive marker expression and inhibited activating marker expression on myeloid …

The Present And Future Of Precision Oncology And Tumor-Agnostic Therapeutic Approaches, Nakul M Shah, Funda Meric-Bernstam

Faculty, Staff and Student Publications

Precision oncology has transformed the treatment landscape for patients with advanced solid tumors. Tumor-agnostic therapies, those that have been approved based on genetic mutations or biomarkers across tumor histology types, are important examples of how the implementation of precision oncology can expand therapeutic options for patients, especially those with rare cancer types and treatment-refractory disease. In this review, we first discuss how advances in next-generation sequencing and molecular profiling have enabled the identification of shared actionable alterations. Subsequently, we explore the current landscape of tumor-agnostic therapies that have received approval from the Food and Drug Administration. We discuss the strengths …

Posterior Predictive Design For Phase I Clinical Trials, Chenqi Fu, Shouhao Zhou, J Jack Lee

Faculty, Staff and Student Publications

Interval-based designs represent cutting-edge adaptive methodologies for phase I clinical trials to identify the maximum tolerated dose (MTD). These designs exhibit robust performance comparable to more intricate, model-based designs, and their pretabulated decision rule enables them to be implemented as simply as the conventional algorithm-based designs. In this paper, we introduce the posterior predictive (PoP) design, a novel interval-based design that leverages advanced Bayesian predictive hypothesis testing techniques for dose escalation and de-escalation. Our work moves beyond the existing model-assisted interval-based designs by achieving global optimality in dose transition. Theoretically, the global optimality ensures that the proposed design can consistently …

Mutant P53 Gain Of Function: Why Many See It, Why Some Do Not, Guillermina Lozano, Carol Prives, Kanaga Sabapathy

Faculty, Staff and Student Publications

Mutations in the TP53 tumor-suppressor gene in human cancer are unique in that 60% to 70% are of the missense variety, resulting in a full-length protein that is often highly expressed in patients' tumors. These missense mutant proteins often exhibit pro-oncogenic activities (referred to as gain of function) in mouse models and human cell lines and correlate with poor cancer prognosis in some cases.

Suppression Of Brca1 Facilitates Kidney Regeneration, Kaira A Church, Xunian Zhou, Raghu Kalluri

Faculty, Staff and Student Publications

Maladaptive repair following kidney injury leads to the development of kidney disease. In this issue of JEM, Ajay et al. (https://doi.org/10.1084/jem.20231107) uncover the role of breast cancer susceptibility gene 1 (BRCA1) in cell cycle arrest, DNA damage, and cell senescence, preventing maladaptive repair.

Harnessing Electrophiles In Vivo: A Pilot Study In Swine Using A Hydrophobic Radiopaque Formulation Of 2-Propylpentanoyl Chloride, Erik Cressman, Danielle Stolley, Natalie Fowlkes, Edd Felix, Waldemar Priebe, Steve Parrish, David Fuentes

Faculty, Staff and Student Publications

Manipulating biology through chemistry is older than the discipline of chemistry itself. Traditionally, selectivity of oral or intravenous drugs relied on preferential drug-receptor binding. A novel approach exploiting image-guided techniques to impart spatial selectivity opens up a wide range of new possibilities for study and manipulation of biology. Motivated initially by the poor prognosis for solid tumors such as liver cancer, we demonstrate the use of an extreme form of in vivo chemistry for targeted delivery of 2-propylpentanoyl chloride in a swine model. The ensuing reaction in tissue devitalizes it by multiple mechanisms with lasting effects and, critically, demonstrates very …

Switching On The Evolutionary Potential Of Pancreatic Cancer: The Tumor Suppressor Functions Of Pbrm1, Luigi Perelli, Giannicola Genovese

Faculty, Staff and Student Publications

Cell plasticity is a hallmark of cancer, enabling tumor cells to acquire multiple phenotypes responsible for tumor progression, metastasis, and therapy resistance. In this issue of the JCI, Kawai and colleagues leveraged genetically engineered mouse models (GEMM) of pancreatic ductal adenocarcinoma (PDAC) to demonstrate that loss of Pbrm1, a member of the SWI/SNF complex, drives dedifferentiation and aggressive tumor features. Pbrm1 loss activated a program of epithelial-to-mesenchymal transition (EMT) and allowed the emergence of poorly differentiated histologies that are commonly associated with high recurrence rate and dismal prognosis. These findings reveal the role of the SWI/SNF complex during PDAC evolution …

Hyaluronan Network Remodeling By Zeb1 And Itih2 Enhances The Motility And Invasiveness Of Cancer Cells, Sieun Lee, Jihye Park, Seongran Cho, Eun Ju Kim, Seonyeong Oh, Younseo Lee, Sungsoo Park, Keunsoo Kang, Dong Hoon Shin, Song Yi Ko, Jonathan M Kurie, Young-Ho Ahn

Faculty, Staff and Student Publications

Hyaluronan (HA) in the extracellular matrix promotes epithelial-mesenchymal transition (EMT) and metastasis; however, the mechanism by which the HA network constructed by cancer cells regulates cancer progression and metastasis in the tumor microenvironment (TME) remains largely unknown. In this study, inter-α-trypsin inhibitor heavy chain 2 (ITIH2), an HA-binding protein, was confirmed to be secreted from mesenchymal-like lung cancer cells when cocultured with cancer-associated fibroblasts. ITIH2 expression is transcriptionally upregulated by the EMT-inducing transcription factor ZEB1, along with HA synthase 2 (HAS2), which positively correlates with ZEB1 expression. Depletion of ITIH2 and HAS2 reduced HA matrix formation and the migration and …

Externally Validated Digital Decision Support Tool For Time-To-Osteoradionecrosis Risk-Stratification Using Right-Censored Multi-Institutional Observational Cohorts, Laia Humbert-Vidan, Serageldin Kamel, Andrew Wentzel, Zaphanlene Kaffey, Moamen Abdelaal, Kyle B Spier, Natalie A West, G Elisabeta Marai, Guadalupe Canahuate, Xinhua Zhang, Melissa M Chen, Kareem A Wahid, Jillian Rigert, Seyedmohammadhossein Hosseinian, Andrew J Schaefer, Kristy K Brock, Mark Chambers, Adegbenga O Otun, Ruth Aponte-Wesson, Vinod Patel, Andrew Hope, Jack Phan, Adam S Garden, Steven J Frank, William H Morrison, Michael T Spiotto, David Rosenthal, Anna Lee, Renjie He, Mohamed A Naser, Erin Watson, Katherine A Hutcheson, Abdallah S R Mohamed, Vlad C Sandulache, Lisanne V Van Dijk, Amy C Moreno, Teresa Guerrero Urbano, Clifton D Fuller, Stephen Y Lai

Faculty, Staff and Student Publications

Background: Existing studies on osteoradionecrosis of the jaw (ORNJ) have primarily used cross-sectional data, assessing risk factors at a single time point. Determining the time-to-event profile of ORNJ has important implications to monitor oral health in head and neck cancer (HNC) long-term survivors.

Methods: Data were retrospectively obtained for a clinical observational cohort of 1129 patients (198 ORNJ cases) with HNC treated with radiotherapy (RT) at The University of Texas MD Anderson Cancer Center. A Weibull Accelerated Failure Time model was trained on previously identified dosimetric, clinical and demographic predictors. External validation was performed using an independent cohort of 265 …

Early Life Exposure To Fine Particulate Matter And Fine Motor Function, Attentional Function, And Working Memory Among Spanish School-Aged Children, Kristina W Whitworth, Aitana Lertxundi, Mingze Yuan, Alison Rector-Houze, Wei-Jen Chen, Mònica Guxens, Jordi Julvez, Michael Swartz, Elaine Symanski, Antonia Valentin, Carmen Iniguez, Llúcia L González-Safont, Jesús Ibarluzea

Faculty, Staff and Student Publications

Background: Evidence of the association between fine particulate matter (PM2.5) exposure and child neuropsychological function is equivocal. We examined early life PM2.5 exposure in relation to fine motor function, attention, and working memory in early childhood.

Methods: We used data from the Spanish INfancia y Medio Ambiente Project, 2003-2008. Exposure to PM2.5 (μg/m3) was assessed using spatiotemporal land-use random forest models and assigned based on residential address histories. Around age six, children completed the finger tapping test, attentional network test (ANT), and n-back task to evaluate fine motor speed, attention, and working memory, respectively. A total of 1,310 children had …

The Association Of Vision And Hearing Impairment On Cognitive Function And Loneliness: Evidence From The Mexican Health And Aging Study, Kimberly Hreha, Rafael Samper-Ternent, Heather E Whitson, L P Downer, Jessica S West, Brian Downer

Faculty, Staff and Student Publications

Objectives: We investigated whether self-reported vision and hearing were associated with cognitive function and loneliness among Mexican adults aged 50 and older.

Methods: Mexican Health and Aging Study data. Vision/hearing status was self-reported (excellent-very good, good, fair-poor). Cognition was measured using nine tasks. Loneliness was measured using the UCLA Loneliness Scale. Analyses controlled for demographic and health characteristics.

Results: Among 12,353 participants (mean age = 67, 58% female), poor vision, but not hearing, was associated with lower global cognition (β = -0.03, p < .05). Poor vision (OR = 1.57, 95% CI = 1.30-1.91) and hearing (OR = 1.35, 95% CI = 1.14-1.61) were associated with higher odds of being lonely after adjusting for demographics and comorbidities, but not when adjusting for limitations in daily activities and depressive symptoms.

Discussion: Poor vision is a potentially modifiable risk factor for lower cognition and loneliness among Mexican adults. …

Understanding Utilization And Prevention Measures Associated With A Caries Risk Assessment In Oral Health Transformation, Melody Mcgee, Ryan Brandon, Muhammad Walji, Joel White, Kristen Moses, Eric P Tranby, Lisa J Heaton, Kristen Simmons

Faculty, Staff and Student Publications

Objectives: Dental decay is endemic in the United States, underscoring the need to measure the utilization of caries risk management tools to elucidate the effect of prevention interventions in reducing the dental decay rates of individuals. An academic institution partnered with a third-party institute to call attention to the utilization and prevention measures associated with caries risk assessment (CRA) used with children 0-18 years. This environmental scan examined claims across the United States to evaluate the proportion of dental examinations, CRAs, and caries prevention procedures within a calendar year.

Methods: A 12-month deidentified participant list categorized by age, race, sex, …

Neighborhood Socioeconomic Disadvantage Is Not Associated With Adverse Outcomes Following Elective Spine Surgery In Older Veterans, Andrea L Strayer, Yubo Gao, Michael A Jacobs, Heather Davila, Carly A Jacobs, Susanne Schmidt, Leslie R M Hausmann, Paula K Shireman, George Wehby, Daniel E Hall, Mary Vaughan Sarrazin, Katherine E Hadlandsmyth

Faculty, Staff and Student Publications

Background: In the US, over half of all cervical and lumbar arthrodesis spine surgeries are for people ≥60 years of age. The extent to which adverse outcomes vary by social (eg, disadvantaged neighborhoods) and demographic factors have been scarcely investigated in spine surgery. We investigated the association of social, demographic, and clinical factors with complications, 30-day readmission, and 30-day mortality in older Veterans undergoing elective spine surgery.

Methods: Veterans (N=5,277) aged ≥65 years who underwent inpatient elective spine surgery for degenerative disease in the Veterans Affairs Surgical Quality Improvement Program (VASQIP) comprised our retrospective cohort. VASQIP (2013-2019) data were merged …

Implementation Of An Opt-Out And Rapid Point-Of-Care Syphilis Testing Program For Pregnant Patients Presenting To The Emergency Department, Irene Stafford, Carrie Bakunas, Joe Haydamous, Ana Mosqueda, Jeffrey D Klausner, Leandro Mena, Sean C Blackwell

Faculty, Staff and Student Publications

Background: Adult and congenital syphilis rates are rising in the United States. The aim of this pre- and post-implementation study was to determine whether implementation of an opt-out laboratory-based and rapid syphilis point-of-care testing program in the emergency department (ED) improves the detection and treatment of syphilis during pregnancy in a high-prevalence region.

Methods: This pre- and post-implementation study was conducted at the University of Texas Health Science Center, Houston, TX. During the pre-implementation phase (November 1, 2023-February 29, 2024), pregnant patients presenting to the ED underwent laboratory-based syphilis testing using the reverse algorithm only when clinically indicated. In the …

The Promising Use Of An Emergency Department Observation Unit To Manage Patients With Opioid Use Disorder, Thai Tran, Nicholas Imperato, Akiva Dym, Anthony Rosania, Lewis Nelson, Christine Ramdin, Cynthia Santos

Faculty, Staff and Student Publications

Introduction: The opioid epidemic continues to grow, placing a significant strain on Emergency Departments (EDs), resulting in patients presenting daily with opioid-related concerns including intoxication, withdrawal, infections, injury, and death. Consequently, in recent years many EDs, including our own, have utilized Emergency Department Observation Units (EDOU) to not only manage withdrawal and overdose, but also initiate long-term treatment. This study aims to evaluate the outcomes of patients with opioid use disorder (OUD) who were managed in our EDOU.

Methods: This was a retrospective study of patients placed in an EDOU who had the primary diagnosis of OUD in a single …

Is There An Association Between Inflammatory Biomarkers And Organ Space Surgical Site Infection After Emergency Laparotomy In Massively Transfused Trauma Patients?, Stephanie Martinez Ugarte, Mokunfayo O Fajemisin, Chelsea J Guy-Frank, James M Klugh, Xu Zhang, Erin E Fox, Charles E Wade, Kimberly A Mankiewicz, Lillian S Kao

Faculty, Staff and Student Publications

Background: The relationship between inflammatory biomarkers (IB) and organ space surgical site infections (OS-SSIs) after emergency laparotomy (EL) is poorly understood.

Methods: Retrospective, single-center analysis of patients in the Pragmatic, Randomized Optimal Platelet and Plasma Ratios (PROPPR) trial who underwent EL and survived 48 h after admission was performed. IB levels of IL-6, IL-8, G-CSF, MCP-1, neutrophil to lymphocyte ratio, and platelet to lymphocyte ratio were analyzed. IB and OS-SSIs association was evaluated using the Wilcoxon rank sum test.

Results: Of 74 eligible patients, 80 % were male, 69 % sustained blunt trauma, the injury severity score was 31 (24-41), …

Predicting Discharge Destination And Length Of Stay After Open Reduction Internal Fixation Of Distal Femur Fractures, Akash A Shah, Brian K Zukotynski, Chohee Kim, Brendan Y Shi, Changhee Lee, Sai K Devana, Alexander Upfill-Brown, Erik N Mayer, Nelson F Soohoo, Christopher Lee

Faculty, Staff and Student Publications

Introduction: Prediction of nonhome discharge after open reduction internal fixation (ORIF) of distal femur fractures may facilitate earlier discharge planning, potentially decreasing costs and improving outcomes. We aim to develop algorithms predicting nonhome discharge and time to discharge after distal femur ORIF and identify features important for model performance.

Methods: This is a retrospective cohort study of adults in the American College of Surgeons National Surgical Quality Improvement Program database who underwent distal femur ORIF between 2010 and 2019. The primary outcome was nonhome discharge, and the secondary outcome was time to nonhome discharge. We developed logistic regression and machine …

The Macrophage Sterol Transport Protein Orp2 Promotes Cholesterol Efflux And Prevents Foam Cell Formation And Atherosclerosis, Xiaowei Wang, Kenan Peng, Yudi Zhao, Liwen Qiu, Chenxi Liang, Yaqian Dou, Qianqian Dong, Xiaoting Ma, Jinye Tang, Yidan Ma, Lin Liu, Mingqi Zheng, Hongyuan Yang, Mingming Gao

Faculty, Staff and Student Publications

Cholesterol-loaded macrophage foam cells are a key feature of atherosclerotic plaques. Oxysterol-binding protein-related protein 2 (ORP2) facilitates the transport of cholesterol from lysosomes to the plasma membrane in cultured cell lines. However, the role of ORP2 in macrophages and its involvement in atherosclerosis remain unclear. In this study, we found ORP2 expression was reduced in atherosclerotic vessels and in macrophages exposed to oxidized LDL (ox-LDL). Myeloid-specific human ORP2 overexpression (hORP2MOE) mice were generated and crossed with atherosclerotic-prone ApoE−/− mice and then fed a high-fat diet (HFD) to induce atherosclerosis. Our results showed that myeloid-specific hORP2 overexpression significantly reduced the atherosclerotic …

Time To Weight Plateau With Tirzepatide Treatment In The Surmount-1 And Surmount-4 Clinical Trials, Deborah B Horn, Scott Kahan, Rachel L Batterham, Dachuang Cao, Clare J Lee, Madhumita Murphy, Sylvia Gonsahn-Bollie, Farai Chigutsa, Adam Stefanski, Julia P Dunn

Faculty, Staff and Student Publications

The rate of weight reduction during obesity treatment declines over time and eventually reaches a weight plateau. We investigated factors associated with time to weight plateau (TTWP) in tirzepatide-treated participants with obesity or overweight in a post-hoc analysis of SURMOUNT-1 and SURMOUNT-4 trials. Participants adherent to tirzepatide treatment and achieving ≥5% weight loss by primary endpoint (week 72 SURMOUNT-1; week 88 SURMOUNT-4) were included. Weight plateau was defined as a weight change < 5% over a 12-week interval and all subsequent 12-week intervals. TTWP was time from randomization to the start of the first 12-week interval. Association between baseline characteristics and TTWP was assessed. Overall, 1438 participants in SURMOUNT-1 and 259 in SURMOUNT-4 were included. Across BMI categories (overweight, class I, II, and III), median TTWP in SURMOUNT-1 was 24.3, 26.0, 36.1, and 36.1 weeks, respectively (p < .05, class II and III vs. overweight). By week 72, 90.2%, 88.9%, 87.6%, and 87.8% of participants in SURMOUNT-1 had reached a weight plateau across respective BMI categories [Correction added on 22 January 2025, after first online publication: The "72%" has been changed to "72" in this version.]. Higher doses of tirzepatide (10/15 mg), younger age, and female sex were more likely to reach a weight plateau later. Results in SURMOUNT-4 were similar. In this post-hoc analysis, most participants reached a weight plateau by week 72. Higher doses of tirzepatide, younger age, and female sex were associated with a longer TTWP. Further research into modifiers of weight reduction phases with tirzepatide may inform treatment decisions for its use in chronic weight management. Clinical Trial Registration: ClinicalTrials.gov, identifiers NCT04184622 (SURMOUNT-1) and NCT04660643 (SURMOUNT-4), available at http://www.clinicaltrials.gov/.

Enhancing Seizure Control In Ultra-Refractory Postencephalitic Epilepsies Using Multinodal Network Neuromodulation, Subhiksha Srinivasan, Surya Suresh, Ganne Chaitanya, Manoj Saranathan, Nitin Tandon, Sandipan Pati

Faculty, Staff and Student Publications

This case series reports the formidable challenge posed by postencephalitic epilepsies, characterized by frequent drug-resistant seizures and neuropsychiatric and cognitive comorbidities. Polypharmacy is frequently required, and surgical resection may not be feasible due to multifocality. Neuromodulation therapies, including Deep Brain Stimulation (DBS) and Responsive Neurostimulation (RNS), offer a potential lifeline. In this case series, we shed light on the intricate landscape of seizure management and neuropsychiatric comorbidities in five individuals with frequent seizures (often weekly) and ultra-refractory epilepsy (defined as resistance to more than six different antiseizure medications, including failed epilepsy surgery) following catastrophic encephalitis. Four out of five patients …

The Great Mimicker: Forgotten But Not Gone, Blayne E Fenner, Kevin M Burningham, Jamael L Thomas, Brent C Kelly, Auris O Huen, Stephen K Tyring

Faculty, Staff and Student Publications

Once subdued after the advent of penicillin, syphilis has re-emerged in recent years, with incidence rates rising in many countries, including the United States. Its reputation as "the great imitator" is well earned due to its widely variable presentation, particularly in its second stage. This contributes to a high rate of delayed diagnosis and misdiagnosis, adding significant burden to patients and the health care system generally. Herein, we present 2 cases in which syphilis was misdiagnosed, leading to unnecessary therapies and delay of symptom clearance until treponemal tests were performed. In the context of recent epidemiologic trends and its notorious …

Ao Spine Clinical Practice Recommendations For Diagnosis And Management Of Degenerative Cervical Myelopathy: Evidence Based Decision Making - A Review Of Cutting Edge Recent Literature Related To Degenerative Cervical Myelopathy, Michael G Fehlings, Nathan Evaniew, Paula Valerie Ter Wengel, Aditya Vedantam, Daipayan Guha, Konstantinos Margetis, Aria Nouri, Aminul I Ahmed, Chris J Neal, Benjamin M Davies, Mario Ganau, Jefferson R Wilson, Allan R Martin, Lukas Grassner, Lindsay Tetreault, Vafa Rahimi-Movaghar, Rex Marco, James Harrop, James Guest, Mohammed Ali Alvi, Karlo M Pedro, Brian K Kwon, Charles G Fisher, Shekar N Kurpad

Faculty, Staff and Student Publications

Study Design

Literature review of key topics related to degenerative cervical myelopathy (DCM) with critical appraisal and clinical recommendations.

Objective

This article summarizes several key current topics related to the management of DCM.

Methods

Recent literature related to the management of DCM was reviewed. Four articles were selected and critically appraised. Recommendations were graded as Strong or Conditional.

Results

Article 1: The Relationship Between pre-operative MRI Signal Intensity and outcomes. Conditional recommendation to use diffusion-weighted imaging MR signal changes in the cervical cord to evaluate prognosis following surgical intervention for DCM. Article 2: Efficacy and Safety of Surgery for Mild …

New Frontiers: The Intern Experience In A Newly Established Integrated Plastic Surgery Program, Hendrik Lintel, Imran Rizvi, Michael Haydon, Erik S Marques, Matthew R Greives, Mohin A Bhadkamkar

Faculty, Staff and Student Publications

The plastic surgery residency pathway has undergone many changes since its inception. The advent of integrated training has largely taken over as the predominant residency model with the addition of a few new programs every year. There is currently a paucity of literature describing the experiences of first-year interns in a new integrated residency program transitioning from the independent model. In this article, we seek to elucidate some of the advantages and difficulties encountered by the initial residents of a newly established integrated program and the steps taken to pave the way for future matched integrated trainees.

Assessment Of Contextualized Reinforcement Pathology In A Community Sample Of Young Adult Substance Users, Ángel García-Pérez, Alba González-Roz, Roberto Secades-Villa, Gema Aonso-Diego, Sara Weidberg, Jin H Yoon

Faculty, Staff and Student Publications

Background: Alcohol, tobacco, and cannabis are the most commonly used substances among young populations, often leading to polysubstance use, which correlates with problematic consumption and adverse health outcomes. The contextualized reinforcer pathology (CRP) model explains addictive behaviors through several constructs, including the following: drug demand, delay discounting (DD), and substance-free and substance-related reinforcement. Most previous studies have focused on a single CRP construct and the couse of only two substances. This study aimed to characterize three subgroups of young adults reporting past month use of alcohol only, alcohol + tobacco or cannabis, and alcohol + tobacco + cannabis, in terms …