Medicine and Health Sciences Commons^™

Utilization Of Intensive Care Interventions In Critically Ill Patients With Candidemia Versus Bacteremia: A Multicenter Retrospective Cohort Study, Mary North Jones, Masayuki Nigo, Stefano Casarin, James Kurian, Aarjav Sanghvi, Enshuo Hsu, Stephen L Jones, Ashton Connor, David B Corry, Cesar A Arias, Max W Adelman

Faculty, Staff and Students Publications

Objectives: Candida species are one of the most common causes of ICU-onset bloodstream infection (BSI). Yet, there is no robust guidance on when to initiate empiric antifungals for ICU patients suspected of BSI. We compared patients with ICU-onset candidemia vs. ICU-onset bacteremia to determine which patients may benefit from empiric antifungals.

Design: We compared characteristics between patients with bacteremia vs. candidemia at time of culture. We determined risk factors for death and constructed a multivariable regression to determine if candidemia is an independent risk factor for death.

Setting/patients: We included ICU patients from a hospital system in Houston, Texas (n …

Markvcid2 Consortium For Clinical Validation Of Biomarkers Of Cerebral Small Vessel Disease: Validation Framework And Baseline Characteristics, Steven M Greenberg, Marylin S Albert, Hongyu An, Konstantinos Arfanakis, Arnold M Evia, Arvind Caprihan, Andria L Ford, Myriam Fornage, Gregory S Day, Jason D Hinman, Gregory A Jicha, Amir H Kashani, Joel H Kramer, Christian Lachner, Jin-Moo Lee, Peiying Liu, Hanzhang Lu, Pauline Maillard, Ronald C Petersen, Bruce M Psaty, John M Ringman, Gary A Rosenberg, Claudia L Satizabal, Sean I Savitz, Julie A Schneider, Sudha Seshadri, Prashanthi Vemuri, Danny J J Wang, Donna M Wilcock, B Gwen Windham, Rong Zhang, Carissa Tuozzo, Herpreet Singh, Sue Moy, Vilma Okey-Ewurum, Courtney B Page, Hillary Mulder, Pia Kivisäkk, Deborah Blacker, Lidiya Mazina, Karl G Helmer, Kristin Schwab, Lisa M Wruck, Roderick A Corriveau

Faculty, Staff and Student Publications

Objective: To establish a framework for validating candidate biomarkers of cerebral small vessel diseases (SVD) associated with cognitive impairment and characterize individuals enrolled by the MarkVCID2 consortium under this framework.

Methods: Participants age 60 to 90 years were enrolled across 17 MarkVCID2 sites. Recruitment was targeted to enrich in cognitive symptoms (mild dementia, mild cognitive impairment, subjective cognitive decline), defined risk factors (diabetes mellitus, advanced hypertension), and Black/African American, White, and Hispanic/Latino subgroups. Enrolled participants underwent baseline visits that included cognitive testing, multimodal magnetic resonance imaging (MRI), and biofluid collection. Provisional risk for SVD-related cognitive decline was estimated primarily by …

Outcomes Of Witnessed Versus Unwitnessed Patients With Stroke After Endovascular Therapy In The Extended Time Window, Liisa Tomppo, Nicolas Martinez-Majander, Muhammad M Qureshi, Thanh N Nguyen, Raul G Nogueira, Simon Nagel, Jelle Demeestere, Volker Puetz, Hilde Henon, Marta Olive-Gadea, João Pedro Marto, Anne Dusart, Peter A Ringleb, Osama O Zaidat, Diogo C Haussen, Mahmoud H Mohammaden, Mohamad Abdalkader, Jean Raymond, Santiago Ortega-Gutierrez, Sunil A Sheth, Hiroshi Yamagami, João Nuno Ramos, Francois Caparros, Daniel P O Kaiser, Marc Ribo, Sergio Salazar-Marioni, Kanta Tanaka, Pekka Virtanen, Ajit S Puri, James E Siegler, Syed F Zaidi, Mouhammad Jumaa, Eugene Lin, Jordi Mayol, Rita Ventura, Simon Winzer, Piers Klein, Flavio Bellante, Jorge Cespedes, Anke Wouters, Hesham E Masoud, Liqi Shu, Alicia C Castonguay, Christian Herweh, Monica Cheng, Wei Hu, Daniel Roy, Shadi Yaghi, Robin Lemmens, Charlotte Cordonnier, Markus A Möhlenbruch, Daniel Strbian

Faculty, Staff and Student Publications

Background: It remains unclear whether outcomes of patients treated with endovascular thrombectomy with large-vessel occlusion and unwitnessed onset of stroke differ from those with witnessed onset in the extended time window.

Methods: We enrolled patients with anterior circulation large-vessel occlusion (internal carotid artery, M1, or M2 segment of the middle cerebral artery) undergoing endovascular thrombectomy within 6 to 24 hours from the time last seen well, from 2014 to 2022, at 66 sites in Europe, North America, and Asia. Patients with a prestroke modified Rankin Scale score of >3 or age < 18 were excluded. We categorized patients by onset mode as witnessed or unwitnessed. The primary outcome was the modified Rankin Scale shift at 90 days. Secondary outcomes were functional independence, a composite of functional independence or return of Rankin to prestroke level, symptomatic intracranial hemorrhage, mortality, and a composite of severe disability or mortality at 90 days. We applied inverse probability of treatment weighting to compare outcomes between the groups.

Results: Of 5098 patients assessed for eligibility, we included …

Circulating Fatty Acid Binding Protein 4 (Fabp-4) Concentrations And Mortality In Individuals With Colorectal Cancer In The European Prospective Investigation Into Cancer And Nutrition Study, Thu Thi Pham, Katharina Nimptsch, Krasimira Aleksandrova, Mazda Jenab, Veronika Fedirko, Anja Olsen, Anne Tjønneland, Claire Cadeau, Gianluca Severi, Matthias B Schulze, Renée Turzanski Fortner, Verena Katzke, Claudia Agnoli, Carlotta Sacerdote, Rosario Tumino, Simona Signoriello, Camino Trobajo-Sanmartín, Jesús-Humberto Gómez, María-Dolores Chirlaque, Maria-Jose Sánchez, Marta Crous-Bou, Anne May, Alicia Heath, Dagfinn Aune, Elisabete Weiderpass, Tobias Pischon

Faculty, Staff and Student Publications

Human fatty acid binding protein‐4 (FABP‐4), a protein elevated in obesity that promotes colon cancer cell invasiveness and metastasis, may be associated with higher mortality in individuals with colorectal cancer (CRC) and may serve as a mediator of the obesity–mortality association in these individuals. We used a causal diagram to inform covariate selection and applied Cox proportional hazards models to estimate hazard ratios (HRs) for CRC‐specific, non‐CRC‐specific, and all‐cause mortality by FABP‐4 levels measured in baseline blood samples from 1371 incident CRC cases from the European Prospective Investigation into Cancer and Nutrition cohort. Competing risk analyses were adapted for CRC …

Hypoglossal Neuropathy In The Pathogenesis Of Fibrosis-Related Late-Radiation Associated Dysphagia: A Correlative Analysis Utilizing Electromyography To Explore The Frequency Of Clinical And Subclinical Neuropathy In A Pilot Dysphagia Trial, Holly Mcmillan, Christine Okoro, Sheila Buoy, Karin Woodman, Nicolaas Anderson, Clifton Fuller, Stephen Y Lai, Katherine Hutcheson

Faculty, Staff and Student Publications

Background: Late radiation-associated dysphagia (late-RAD) commonly presents in patients with signs of hypoglossal neuropathy, with hallmark clinical features including lingual atrophy, deviation, and fasciculation. Gold-standard electromyography (EMG) has not been used to explore the frequency of hypoglossal neuropathy in patients with late-RAD.

Methods: Exploratory post hoc secondary analysis of MANTLE trial (NCT03612531) was completed. The presence of cranial nerve XII (CN XII) neuropathy was classified by (1) features of clinical assessment as well as (2) intramuscular genioglossus EMG pre-MANTLE intervention in disease-free HNC survivors ≥ 2 years post-radiotherapy (RT) with grade ≥ 2 fibrosis and dysphagia.

Results: All …

Impact Of Treatment Interruption On Outcomes In Head And Neck Cancer: Nrg/Rtog Secondary Analysis, Laila A Gharzai, Emily Morris, Matthew J Schipper, Kelley M Kidwell, Phuc Felix Nguyen-Tân, David I Rosenthal, Maura L Gillison, Richard C Jordan, Adam S Garden, Shlomo A Koyfman, Jimmy J Caudell, Dukagjin M Blakaj, Neal E Dunlap, Greg A Krempl, John M Longo, Christopher U Jones, Michael F Gensheimer, Thomas J Galloway, Lyudmila Demora, Quynh-Thu Le, Jennifer L Shah, Krithika Suresh, Michelle Mierzwa

Faculty, Staff and Student Publications

Importance: Historical evidence demonstrated that delays or interruptions in radiotherapy (RT) are associated with poorer oncologic outcomes in head and neck squamous cell carcinoma (HNSCC). Substantial concerns arose during the COVID-19 pandemic, when treatment schedules were frequently disrupted.

Objective: To determine the association of RT interruptions with locoregional failure (LRF) and overall survival (OS).

Design, setting, and participants: This retrospective review and secondary analysis of 3 randomized clinical trials (NRG/RTOG 0129, 0522, and 1016) included patients enrolled in the trials who were treated with RT. Patients with HNSCC were grouped as (1) p16-positive oropharynx (p16+ OPSCC) and (2) p16-negative oropharynx …

Circulating Metabolites, Genetics And Lifestyle Factors In Relation To Future Risk Of Type 2 Diabetes, Jun Li, Jie Hu, Huan Yun, Zhendong Mei, Xingyan Wang, Kai Luo, Marta Guasch-Ferré, Xikun Han, Buu Truong, Jordi Merino, Chengyong Jia, Miguel Ruiz-Canela, Casey M Rebholz, Eun Hye Moon, Taryn Alkis, Guning Liu, Jie Yao, Xiyuan Zhang, Bianca C Porneala, Jordi Salas-Salvadó, Thomas J Wang, Josée Dupuis, Elizabeth Selvin, Xiuqing Guo, Shilpa N Bhupathiraju, Jennifer A Brody, Yongmei Liu, Alexis C Wood, Kari E North, Su Yon Jung, Ching-Ti Liu, Nona Sotoodehnia, Simin Liu, Lesley F Tinker, A Heather Eliassen, Joann E Manson, Jose C Florez, Robert E Gerszten, Clary B Clish, Liming Liang, Rozenn N Lemaitre, Katherine L Tucker, Stephen S Rich, Jerome I Rotter, Miguel Angel Martínez-González, Kathryn M Rexrode, James B Meigs, Eric Boerwinkle, Robert C Kaplan, Frank B Hu, Bing Yu, Qibin Qi

Faculty, Staff and Student Publications

The human metabolome reflects complex metabolic states affected by genetic and environmental factors. However, metabolites associated with type 2 diabetes (T2D) risk and their determinants remain insufficiently characterized. Here we integrated blood metabolomic, genomic and lifestyle data from up to 23,634 initially T2D-free participants from ten cohorts. Of 469 metabolites examined, 235 were associated with incident T2D during up to 26 years of follow-up, including 67 associations not previously reported across bile acid, lipid, carnitine, urea cycle and arginine/proline, glycine and histidine pathways. Further genetic analyses linked these metabolites to signaling pathways and clinical traits central to T2D pathophysiology, including …

Acta2 Pathogenic Variants Activating Heat Shock Factor 1 And Increasing Cholesterol Biosynthesis In Smooth Muscle Cells Predispose To Early Onset Atherosclerosis, Maura L Boerio, Abhijnan Chattopadhyay, Xue-Yan Duan, Aamuktha Karla, Ernesto Calderon Martinez, Amelie Pinard, Andrew K Morse, Darshan Reddy, Sree Dharma, Walter Velasco-Torrez, Julien Marcadier, Siddharth K Prakash, Sherene Shalhub, Julie De Backer, Richmond Jeremy, Shaine A Morris, Anji T Yetman, Alan C Braverman, Dianna M Milewicz

Faculty, Staff and Student Publications

Background: ACTA2 pathogenic variants predispose to thoracic aortic disease, and a subset of variants lead to early onset atherosclerotic cardiovascular disease (ASCVD). The molecular pathway linking misfolded SMA (α-smooth muscle actin) monomers to augmented atherosclerosis-associated smooth muscle cell phenotypic modulation can be modeled in vitro by stably expressing the ACTA2 p.R149C variant in Acta2-/- smooth muscle cells.

Methods: The Montalcino Aortic Consortium patient registry was used to identify cases with ACTA2 pathogenic/likely pathogenic missense variants. These patients were surveyed, and medical records were reviewed, to identify cases with early onset ASCVD. The variants for these cases, as well as …

Retrospective Analysis Of Cutaneous Immune-Related Adverse Events Following Checkpoint Inhibitor Therapy In Melanoma Patients Reveals Increased Risk Associated With The Hla-B*51:01 Allele, Mckenzie Dileo, Samantha Oglesby, Cheuk Hong Leung, Kristen E Pauken, Sahira Farooq, Lauren E Haydu, Shelby L Kubicki, Rebeca Martinez, Macartney Welborn, Sana Zahiruddin, Jun Zou, Kai Cao, Anisha B Patel

Faculty, Staff and Student Publications

Background: While immune checkpoint inhibitors (ICIs) have shown significant efficacy, a common side effect is cutaneous immune-related adverse events (irAEs). This study focuses on exploring the association between specific human leukocyte antigen (HLA) alleles and the development of cutaneous irAEs in melanoma patients undergoing ICI monotherapy and combination therapy. As certain HLA types are indicative of susceptibility to autoimmune diseases, it was hypothesized that HLA typing could serve as a potential screening tool for identifying patients at increased risk for developing irAEs.

Methods: A retrospective chart review was performed of 515 patients with melanoma who underwent ICI therapy, either as …

Stimulated Cytokine Production, Attachment, And Emotional Well-Being In Dementia Spousal Caregivers, Daniel L Argueta, Sarah Roberts, Kelly N Brice, E Lydia Wu-Chung, Vincent D Lai, Jensine Paoletti-Hatcher, Bryan T Denny, Charles Green, Samantha Henry, Luis D Medina, Paul E Schulz, Jennifer Stinson, Cobi Heijnen, Christopher P Fagundes

Faculty, Staff and Student Publications

Background: Proinflammatory cytokine production may be related to poor emotional adjustment in dementia spousal caregivers. People who display attachment insecurity may be at increased risk for adverse caregiving experiences and poor psychosocial outcomes.

Objective: This study aimed to understand whether proinflammatory cytokine production was associated with anticipatory grief, caregiver burden, and depressive symptoms and whether those relationships were stronger for caregivers higher on attachment anxiety or avoidance.

Method: A sample of 103 dementia spousal caregivers provided self-report data on demographics, health information, and psychosocial outcomes. We also determined lipopolysaccharide-induced whole-blood interleukin-6, interleukin-1β, tumor necrosis factor-α, and interleukin-10 production and combined …

Role Of Childhood Trauma In Interoception And Alexithymia In Schizophrenia, Samantha Narvaez, Krista Wisner, Alina Siatka, L Elliot Hong, Joshua Chiappelli

Faculty, Staff and Student Publications

Childhood trauma (CT) is a notable risk factor for schizophrenia. Separately, CT has been associated with alexithymia, referring to difficulties in identifying and describing one's own feelings, as well as disturbed interoception, referring to difficulties sensing and responding to signals that originate from within the body. Both self-perception impairments have been observed in schizophrenia; however, the role of CT in these observations in schizophrenia is unclear. To address this gap, interoception was assessed using the Multidimensional Assessment of Interoceptive Awareness (MAIA), alexithymia was assessed using the Toronto Alexithymia Scale (TAS-20), and CT was measured using the Childhood Trauma Questionnaire (CTQ) …

Cardiometabolic Parameter Change By Weight Regain On Tirzepatide Withdrawal In Adults With Obesity: A Post Hoc Analysis Of The Surmount-4 Trial, Deborah B Horn, Bruno Linetzky, Melanie J Davies, Luke J Laffin, Hui Wang, Madhumita A Murphy, Sarah Zimner-Rapuch, Eva Lau, Avigdor D Arad, Clare J Lee

Faculty, Staff and Student Publications

Importance: In the SURMOUNT-4 trial, most adults with obesity who had tirzepatide withdrawn following a 36-week treatment regained weight. The association between the degree of weight regain and cardiometabolic parameters after tirzepatide withdrawal is unknown.

Objective: To assess changes in cardiometabolic parameters by degree of weight regain after withdrawal of tirzepatide.

Design, setting, and participants: This post hoc analysis of the SURMOUNT-4 trial included tirzepatide-treated participants with 10% or greater weight reduction at week 36 initially randomized to placebo. Data were collected from March 2021 to May 2023, and data were analyzed from February 2024 to March 2025.

Interventions: After …

Cardiometabolic Indicators Of Cognitive Impairment In The Cameron County Hispanic Cohort, Fadi I Musfee, Seema Agarwal, Vahed Maroufy, Chelsea Liu, Joseph B Mccormick, Susan Fisher-Hoch, Sean I Savitz

Faculty, Staff and Student Publications

Background

Objective

Methods

Striatum Volume And Affective Symptomatology Are Associated With Sleep In Schizophrenia, Alia R Warner, Xiaoming Du, Yizhou Ma, Kyle R Noll, Si Gao, Bhim Adhikari, Bruno Kluwe-Schiavon, Alina Siatka, Anya Savransky, Peter Kochunov, L Elliot Hong

Faculty, Staff and Student Publications

Sleep dysfunction is common among individuals with schizophrenia spectrum disorders (SSD). Sleep duration and other sleep quality metrics are associated with worse patient clinical and social outcomes. We examined if accumulative stress, gray matter structural volume measured with high-resolution structural brain MRI, diffusion tensor imaging measures of white matter microstructure, and psychopathology (for the schizophrenia group) may act as predictors of sleep quality and compared individuals with SSD (N = 101) and healthy controls (N = 86). We created an adjusted Pittsburgh Sleep Quality Index (PSQI-A) score to measure sleep quality and account for abnormally long sleep duration as dysfunctional. …

Participant Retention In A Prospective Multicenter Cohort Of Participants With Pancreatitis And Factors Associated With Attrition, Radmila Choate, Jun Xu, Jeffrey J Easler, Samuel Han, Anna E Phillips, Melena D Bellin, William E Fisher, Evan L Fogel, Chris Forsmark, Phil A Hart, Stephen J Pandol, Walter G Park, Jose Serrano, Stephen K Van Den Eeden, Santhi Swaroop Vege, Liang Li, Darwin L Conwell, Dhiraj Yadav

Faculty, Staff and Students Publications

Objectives: Participant retention is essential in prospective studies to minimize bias and maintain validity. This study aimed to estimate retention rates and identify factors influencing attrition in a multicenter cohort (PROCEED) of US adults with acute/recurrent acute pancreatitis (AP/RAP) and chronic pancreatitis (CP).

Methods: Participants from the PROCEED study with AP/RAP or CP eligible for follow-up within the designated visit window were included. Retention was defined as completing at least one follow-up visit during the observation period. Retention was analyzed by follow-up mode (in-person and/or medical record review) and disease type (AP/RAP and CP). Retention factors were assessed using univariate …

Intersecting Challenges: Substance Use And Mental Health Disparities Across Self-Reported Disability Status, Jessica Williams, Xiao Li, Hannah S Szlyk, Erin Kasson, Nathaniel A Dell, Alex Ramsey, Patricia A Cavazos-Rehg

2020-Current year OA Pubs

PURPOSE: Substance use and substance use disorders (SUD) disproportionately affect people with disabilities (PWD), yet PWD remain under-represented in addiction treatment literature. While recent work has begun to address SUD prevalence and recovery service gaps, little is known about how disability status shapes substance use outcomes. The present study is the first to our knowledge to investigate how recovery, mental health comorbidities, and barriers to care differ across disability status using structured survey data from people who use substances.

METHODS: 333 participants who use substances and provided information about their disability status in the baseline survey for a digital intervention …

Evaluating The Effectiveness Of Escalating To Weekly Adalimumab Dosing For The Treatment Of Noninfectious Uveitis: A Multicenter Study, Shani Pillar, Akshay Thomas, Lynn M Hassman, Howard Chen, Sapna Gangaputra, Laura J Kopplin, Kelly Boyd, Kareem Moussa, Derek C Pham, Keren Chen, Nicholas J Jackson, Edmund Tsui

2020-Current year OA Pubs

PURPOSE: To evaluate the effectiveness of adalimumab dosage escalation in patients with noninfectious uveitis that is controlled inadequately with standard dosing.

DESIGN: Multicenter retrospective interventional case series.

PARTICIPANTS: Patients with noninfectious uveitis receiving active standard biweekly adalimumab dosing who underwent treatment escalation to weekly adalimumab dosing at 6 tertiary referral centers.

METHODS: Demographic data and clinical findings were assessed at the time of adalimumab dosage escalation and 6 months later. Mixed-model analysis was performed to analyze clinical outcomes and to assess predictive factors of success.

MAIN OUTCOME MEASURES: Treatment success composite criteria included: (1) disease quiescence (≤ 0.5+ anterior chamber …

Phase 1 Study Of Inbrx-105, A Tnfrsf9 (4-1bb) And Pd-L1 Bispecific Antibody, In Patients With Select Solid Tumors, Jong Chul Park, Doug R Adkins, Et Al.

2020-Current year OA Pubs

PURPOSE: INBRX-105, a tetravalent, PD-L1-targeted TNFRSF9 (4-1BB) agonist, demonstrated preclinical antitumor activity. This first-in-human study evaluated INBRX-105 in solid tumors.

PATIENTS AND METHODS: This open-label, 4-part, phase 1 study evaluated INBRX-105 alone or with pembrolizumab in adults with locally advanced/metastatic, unresectable solid tumors (NCT03809624). INBRX-105 was administered intravenously once every 2 weeks or 4 weeks in parts 1 (single-agent dose escalation; 0.001-3 mg/kg) and 2 (single-agent expansion) or once every 3 weeks in parts 3 (combination dose escalation; INBRX-105 0.03-1.0 mg/kg) and 4 (combination expansion). Part 2 enrolled patients with checkpoint inhibitor-relapsed/refractory (CPI-R/R) tumors. Part 4 enrolled patients with CPI-R/R …

Divergent Humoral Immune Signatures In Response To Klebsiella Pneumoniae Bacteremia, Paeton L Wantuch, Nadia Wattad, David A Rosen

2020-Current year OA Pubs

OBJECTIVES: Klebsiella pneumoniae is an increasingly threatening global pathogen with high rates of antibiotic resistance and no licensed vaccines available. Despite its worldwide importance, little is known about the human adaptive immune response to K. pneumoniae infection.

METHODS: Herein we observed the longitudinal antibody responses of three immunocompetent patients hospitalized with K. pneumoniae bacteremia. We analyzed the human serum for antibody titers and in vitro functionality. Further, serum function was evaluated via an in vivo mouse model.

RESULTS: We found that in each case, anti-K. pneumoniae antibodies against the infecting strain were still detectable a year after the initial infection. …

Patient-Reported Outcomes In The Serena-6 Trial Of Camizestrant Plus Cdk4/6 Inhibitor In Patients With Advanced Breast Cancer And Emergent Esr1 Mutations During First-Line Endocrine-Based Therapy, E L Mayer, C Ma, Et Al.

2020-Current year OA Pubs

BACKGROUND: In SERENA-6, switching from aromatase inhibitor (AI) to camizestrant with continuation of CDK4/6 inhibitor (CDK4/6i) guided by emergence of ESR1 mutations (ESR1-mut) during first-line AI-CDK4/6i in patients with hormone receptor (HR)-positive advanced breast cancer (ABC) resulted in statistically significant and clinically meaningful improvement in progression-free survival compared with AI-CDK4/6i and reduction in the risk of deterioration in global health status (GHS)/quality of life (QoL) (hazard ratio 0.54). Here we report additional data from patient-reported outcomes (PROs).

PATIENTS AND METHODS: Patients completed PRO questionnaires at pre-specified timepoints, including the European Organisation for Research and Treatment of Cancer (EORTC) oncology-specific EORTC …

Palbociclib With Adjuvant Endocrine Therapy In Early Breast Cancer: 5-Year Follow-Up Analysis Of The Global Multicenter, Open-Label, Randomized Phase Iii Pallas Trial (Abcsg-42/Aft-05/Pre0109/Big-14-13), E L Mayer, K Clifton, Et Al.

2020-Current year OA Pubs

BACKGROUND: In the phase III PALLAS trial, the addition of 2 years of palbociclib to adjuvant endocrine therapy (ET) did not improve short-term invasive disease-free survival (iDFS) compared with ET alone in high-risk early-stage hormone receptor (HR)-positive/human epidermal growth factor receptor 2 (HER2)-negative breast cancer. In this article, we report 5-year efficacy outcomes, including updated iDFS and overall survival (OS).

PATIENTS AND METHODS: PALLAS is an international, open-label, randomized phase III trial evaluating the addition of 2 years of palbociclib to adjuvant ET in patients with stage II-III HR-positive/HER2-negative breast cancer. The primary endpoint was iDFS.

RESULTS: The trial enrolled …

"Another One Bite The Dust-It Happens So Much In Black Neighborhoods": Structural Barriers And Grassroots Resources Among Black Men Who Use Drugs Facing Fentanyl-Era Overdose And Treatment Disparities, Devin E Banks, Kaytryn D Campbell, Maria E Paschke, Rashmi Ghonasgi, Bridget Coffey, Jameala Jones, Brittany Blanchard, Ryan W Carpenter, Daje Bradshaw, Rachel P Winograd

2020-Current year OA Pubs

INTRODUCTION: Black men in the United States have been disproportionately impacted by fatal drug overdose since the proliferation of synthetic opioids like fentanyl. This community based participatory research study examined determinants of overdose risk and substance use treatment disparities among Black men based on their lived experience.

METHODS: Between February and December 2023, we enrolled 35 Black men reporting past-30-day opioid use to complete semi-structured qualitative interviews. Interviews were analyzed by a team of academic and community-based coders with lived experience using an inductive-deductive approach to thematic analysis.

RESULTS: Six key themes were identified. Four themes described racism-related inequities posing …

Prediabetes Associates With Musculoskeletal Alterations Independent Of Total Body Adiposity, Alan Fappi, Clifton J Holmes, Chao Cao, Vasavi Shabrish, Aman P Aher, Karen Shen, Paul K Commean, Dwight A Towler, Dominic N Reeds, Gretchen A Meyer, Bettina Mittendorfer

2020-Current year OA Pubs

BACKGROUND: Excess adiposity is a major risk factor for insulin resistance, prediabetes, and Type 2 diabetes and increases the risk for sarcopenia and osteosarcopenia later in life. It has been proposed that altered metabolic function and musculoskeletal status in people with obesity are directly linked, presumably because they share common pathophysiological mechanisms. However, the effect of metabolic dysfunction, independent of adiposity, on musculoskeletal status is unknown.

METHODS: We performed a comprehensive assessment of musculoskeletal status in people with overweight/obesity and prediabetes (n = 12; 72% women; age: 67 ± 6 years; weight: 81 ± 11 kg; mean ± SD) and …

Association Of Sleep Disturbance With Survival After Colorectal Cancer Diagnosis: Results From The Colocare Study, Anita R Peoples, Adetunji T Toriola, Et Al.

2020-Current year OA Pubs

INTRODUCTION: Sleep problems are common among cancer patients. The relationship between sleep disruption and clinical outcomes after colorectal cancer (CRC) diagnosis remains poorly understood. We investigated associations of sleep disruption with survival and recurrence in patients with CRC.

METHODS: CRC patients with stages I-IV (N = 895) were included in this study. Self-reported sleep disturbance was assessed presurgery using the sleep item from the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core-30 and classified into "no/mild" or "moderate/severe" sleep disturbance. Cox-proportional hazard models were computed (HRs and 95% confidence intervals) to investigate associations of sleep disturbance …

Seeg-Guided Responsive Neurostimulation To Treat Neocortical Epilepsy: A Multicenter Retrospective Study Of The Efficacy And Safety Of Depth Electrode-Mediated Neuromodulation, Sina Sadeghzadeh, Jon T Willie, Et Al.

2020-Current year OA Pubs

OBJECTIVES: Pivotal trials have established the effectiveness of the Responsive Neurostimulation System (RNS® System) in treating focal epilepsy. In clinical trials, depth leads were primarily used to treat mesial temporal seizure onsets while cortical strip leads were used to treat neocortical seizure onsets. Here, we systematically analyze the safety and efficacy of stereoelectroencephalography (sEEG)-guided depth leads to provide responsive stimulation to neocortical gray matter.

METHODS: Patients were stratified as strong responders (>median cohort seizure reduction %), weak responders (>0% and ≤median cohort seizure reduction %), and anti-responders (≤0%) based on percent seizure reduction at 1 year post-implant (1-Y). …

Blood Dna Methylation-Predicted Plasma Protein Levels And Colorectal Cancer Survival, Alicia R Richards, Maria F Gomez, Bianca I Dowling, Esther Jean-Baptiste, Biljana Gigic, Jane C Figueiredo, Christopher I Li, David Shibata, Adetunji T Toriola, Doratha A Byrd, Cornelia M Ulrich, Paul A Stewart, Erin M Siegel, Jacob K Kresovich

2020-Current year OA Pubs

BACKGROUND: Protein EpiScores are a novel class of DNA methylation (DNAm)-based metrics proposed to measure peripheral immune system characteristics. Although Protein EpiScores have been associated with chronic disease risk, their relationship with colorectal cancer (CRC) survival has not been investigated.

METHODS: We generated new genome-wide DNAm data on pre-treatment whole blood samples from a case-control sample of 136 newly diagnosed CRC patients nested in the ColoCare Study and calculated 107 Protein EpiScores using the developer's algorithm. Over a median follow-up of 7.3 years (range: 0.3-13.8 years), 35 (26%) patients experienced disease recurrence, and 47 (35%) died. Protein EpiScore associations with …

Partial Versus Full Revision In Cementless Single-Stage Exchange For Hip Periprosthetic Joint Infection: A Multicenter Comparative Study With 10-Year Survivorship Analysis, Wenbo Mu, Atthakorn Jarusriwanna, Boyong Xu, Scot A. Brown, Xiaogang Zhang, Alexander Dawes, Javad Parvizi Md, Li Cao

Rothman Institute Papers

BACKGROUND: Periprosthetic joint infection (PJI) is one of the most challenging complications following total hip arthroplasty (THA). Traditional management typically involves full revision to ensure comprehensive infection eradication. However, for patients with well-fixed implants, partial revision in a single-stage cementless approach may provide a viable alternative, potentially preserving bone stock and reducing operative time. The relative efficacy of this approach compared with full revision remains to be fully explored. This multicenter study aims to determine whether partial revision in cementless single-stage exchange surgery offers comparable infection control outcomes to full revision for select patients with well-fixed implants.

METHODS: We conducted …

Olutasidenib In Recurrent/Relapsed Locally Advanced Or Metastatic Idh1-Mutated Chondrosarcoma: Phase 1b/2 Trial, Robin L Jones, Roman Groisberg, Jean-Yves Blay, Howard Colman, Macarena De La Fuente, Patricia Roxburgh, Mwe Mwe Chao, Hua Tian, Florence Duffaud, Rastislav Bahleda, Brian A Van Tine

2020-Current year OA Pubs

Chondrosarcomas are rare cartilaginous neoplasms with limited treatment options. Isocitrate dehydrogenase 1/2 (mIDH1/2) mutations occur in 65% of chondrosarcomas. Here we report safety and efficacy of olutasidenib, an mIDH1 inhibitor, evaluated in patients with locally advanced or metastatic mIDH1 chondrosarcoma (Clinicaltrials.gov identifier: NCT03684811). The primary endpoint was objective response rate by tumor evaluation; secondary endpoints included adverse events, progression-free and overall survival. Patients received olutasidenib 150 mg twice daily. Twenty-three patients were enrolled; 16 were diagnosed with conventional chondrosarcoma (cCS). Median age was 57 (range, 30-71) years. In 21 response-evaluable patients, 11 (52%) had stable disease, 8 (38%) had progressive …

Establishing T1 And Ecv Mapping Based Nomogram Differentiate Acute Ischemic And Nonischemic Myocardial Injury: A Proof-Of-Concept Study, Yanping Su, Kan Liu, Et Al.

2020-Current year OA Pubs

OBJECTIVES: To develop and validate a nomogram based on T1 and extracellular volume fraction (ECV) mapping derived from cardiovascular magnetic resonance (CMR) for differentiating ischemic from nonischemic cardiomyopathies during the acute phase.

METHODS: This retrospective study included patients who underwent CMR at the Fifth Affiliated Hospital of Wenzhou Medical University (internal dataset) and the Fifth Affiliated Hospital of Sun Yat-sen University (external dataset). Patients were assigned to a training set (n = 73), a test set (n = 30), an internal validation set (n = 28), and an external validation set (n = 16). Six multivariable logistic regression models were …

Biomarkers Of Response To Neoadjuvant Palbociclib Plus Anastrozole In Endocrine-Resistant Estrogen Receptor-Positive/Her2-Negative Breast Cancer: A Phase 2 Trial, Tim Kong, Alex Mabry, Maureen Highkin, Jeremy Hoog, Zhanfang Guo, Adrian Gonzales-Gonzales, Shana Thomas, Yingduo Song, Feng Gao, Mateusz Opyrchal, Lindsay Peterson, Foluso Ademuyiwa, Julie Margenthaler, Rebecca Aft, Katherine Glover-Collins, Leslie Nehring, Yu Tao, Souzan Sanati, Ian S Hagemann, Fouad Boulos, Li Ding, Stephen T Oh, Ron Bose, Jason D Weber, Jingqin Luo, Cynthia X Ma, Et Al.

2020-Current year OA Pubs

CDK4/6 inhibitors (CDK4/6i) improve outcomes for estrogen receptor (ER) positive/HER2-negative breast cancers (BCs), yet intrinsic and acquired resistance exist. Here, we evaluated anastrozole in combination with palbociclib (ANA/PAL) in the NeoPalAna Endocrine-Resistant cohort (NCT01723774). Thirty-four patients with clinical stage II/III ER + /HER2- BCs resistant to standard neoadjuvant endocrine therapy (on-treatment Ki67 > 10%) received neoadjuvant ANA/PAL, with serial biopsies analyzed. The primary endpoint, complete cell cycle arrest (CCCA; Ki67