Medicine and Health Sciences Commons^™

Identifying Personalized Metabolic Signatures In Breast Cancer., Priyanka Baloni, Wikum Dinalankara, John C Earls, Theo A Knijnenburg, Donald Geman, Luigi Marchionni, Nathan D Price

Articles, Abstracts, and Reports

Cancer cells are adept at reprogramming energy metabolism, and the precise manifestation of this metabolic reprogramming exhibits heterogeneity across individuals (and from cell to cell). In this study, we analyzed the metabolic differences between interpersonal heterogeneous cancer phenotypes. We used divergence analysis on gene expression data of 1156 breast normal and tumor samples from The Cancer Genome Atlas (TCGA) and integrated this information with a genome-scale reconstruction of human metabolism to generate personalized, context-specific metabolic networks. Using this approach, we classified the samples into four distinct groups based on their metabolic profiles. Enrichment analysis of the subsystems indicated that amino …

Upper And Lower Limb Movement Kinematics In Aging, Zheng Wang, Callie Lane, Matthew Terza, Pravin Khemani, Su Lui, Walker S Mckinney, Matthew W Mosconi

Articles, Abstracts, and Reports

Fragile X-associated tremor/ataxia syndrome (FXTAS) is a neurodegenerative disorder associated with a premutation cytosine-guanine-guanine (CGG) trinucleotide repeat expansion of the FMR1 gene. FXTAS is estimated to be the most common single-gene form of ataxia in the aging population. Gait ataxia and intention tremor are the primary behavioral symptoms of FXTAS, though clinical evaluation of these symptoms often is subjective, contributing to difficulties in reliably differentiating individuals with FXTAS and asymptomatic premutation carriers. This study aimed to clarify the extent to which quantitative measures of gait and upper limb kinematics may serve as biobehavioral markers of FXTAS degeneration. Nineteen premutation carriers …

Modulation Of Immune Checkpoints By Chemotherapy In Human Colorectal Liver Metastases., Neda Jabbari, Heidi L Kenerson, Christopher Lausted, Xiaowei Yan, Changting Meng, Kevin M Sullivan, Priyanka Baloni, Dani E Bergey, Venu G Pillarisetty, Leroy Hood, Raymond S Yeung, Qiang Tian

Articles, Abstracts, and Reports

Metastatic colorectal cancer (CRC) is a major cause of cancer-related death, and incidence is rising in younger populations (younger than 50 years). Current chemotherapies can achieve response rates above 50%, but immunotherapies have limited value for patients with microsatellite-stable (MSS) cancers. The present study investigates the impact of chemotherapy on the tumor immune microenvironment. We treat human liver metastases slices with 5-fluorouracil (5-FU) plus either irinotecan or oxaliplatin, then perform single-cell transcriptome analyses. Results from eight cases reveal two cellular subtypes with divergent responses to chemotherapy. Susceptible tumors are characterized by a stemness signature, an activated interferon pathway, and suppression …

Conversion From Knee Arthrodesis Back To Arthroplasty: A Particular Challenge In Combination With Fungal Periprosthetic Joint Infection., Sven Frieler, Emre Yilmaz, Ryan Goodmanson, Yannik Hanusrichter, Thomas A Schildhauer, Hinnerk Baecker

Articles, Abstracts, and Reports

A 58-year-old female treated at an outside facility with knee arthrodesis due to persistent periprosthetic joint infection fulfilled all prerequisites for a conversion back to arthroplasty, as part of a 2-stage revision. Owing to the detection of Candida parapsilosis, the treatment concept was converted to a three-stage procedure. A scheduled spacer exchange with additional amphotericin B-loaded polymethylmethacrylate was conducted as an intermediate revision before reimplantation. Conversion in the setting of fungal periprosthetic joint infection presents a challenge, and successful treatment hinges on the use of proper antifungal and antimicrobial protocols, advanced surgical techniques, and a multidisciplinary team approach. At …

Effect Of Pembrolizumab Plus Neoadjuvant Chemotherapy On Pathologic Complete Response In Women With Early-Stage Breast Cancer: An Analysis Of The Ongoing Phase 2 Adaptively Randomized I-Spy2 Trial., Rita Nanda, Minetta C Liu, Christina Yau, Rebecca Shatsky, Lajos Pusztai, Anne Wallace, A Jo Chien, Andres Forero-Torres, Erin D Ellis, Heather Han, Amy Clark, Kathy Albain, Judy C Boughey, Nora T Jaskowiak, Anthony Elias, Claudine Isaacs, Kathleen Kemmer, Teresa Helsten, Melanie Majure, Erica Stringer-Reasor, Catherine Parker, Marie C Lee, Tufia Haddad, Ronald N Cohen, Smita Asare, Amy Wilson, Gillian L Hirst, Ruby Singhrao, Katherine Steeg, Adam Asare, Jeffrey B Matthews, Scott Berry, Ashish Sanil, Richard Schwab, W Fraser Symmans, Laura Van 'T Veer, Douglas Yee, Angela Demichele, Nola M Hylton, Michelle Melisko, Jane Perlmutter, Hope S Rugo, Donald A Berry, Laura J Esserman

Articles, Abstracts, and Reports

Importance: Approximately 25% of patients with early-stage breast cancer who receive (neo)adjuvant chemotherapy experience a recurrence within 5 years. Improvements in therapy are greatly needed.

Objective: To determine if pembrolizumab plus neoadjuvant chemotherapy (NACT) in early-stage breast cancer is likely to be successful in a 300-patient, confirmatory randomized phase 3 neoadjuvant clinical trial.

Design, Setting, and Participants: The I-SPY2 study is an ongoing open-label, multicenter, adaptively randomized phase 2 platform trial for high-risk, stage II/III breast cancer, evaluating multiple investigational arms in parallel. Standard NACT serves as the common control arm; investigational agent(s) are added to this backbone. Patients with …

Progressive Shifts In The Gut Microbiome Reflect Prediabetes And Diabetes Development In A Treatment-Naive Mexican Cohort., Christian Diener, María De Lourdes Reyes-Escogido, Lilia M Jimenez-Ceja, Mariana Matus, Claudia M Gomez-Navarro, Nathaniel D Chu, Vivian Zhong, M Elizabeth Tejero, Eric Alm, Osbaldo Resendis-Antonio, Rodolfo Guardado-Mendoza

Articles, Abstracts, and Reports

Type 2 diabetes (T2D) is a global epidemic that affects more than 8% of the world's population and is a leading cause of death in Mexico. Diet and lifestyle are known to contribute to the onset of T2D. However, the role of the gut microbiome in T2D progression remains uncertain. Associations between microbiome composition and diabetes are confounded by medication use, diet, and obesity. Here we present data on a treatment-naive cohort of 405 Mexican individuals across varying stages of T2D severity. Associations between gut bacteria and more than 200 clinical variables revealed a defined set of bacterial genera that …