Modeling the acute mucosal toxicity to fractionated radiotherapy combined with the ATM inhibitor WSD0628.

ATM inhibitors are being developed as radiosensitizers to improve the antitumor effects of radiotherapy, but ATM inhibition can also radiosensitize normal tissues. Therefore, understanding the elevated risk for normal tissue toxicities is critical for radiosensitizer development. This study focused on modeling the relationship between acute mucosal toxicity, radiation dose, fractionation schedule, and radiosensitizer exposure.

DNA-PK inhibition shows differential radiosensitization in orthotopic GBM PDX models based on DDR pathway deficits.

Glioblastoma (GBM) remains one of the most therapy-resistant malignancies with frequent local failures despite aggressive surgery, chemotherapy, and ionizing radiation (IR). Small molecule inhibitors of DNA-dependent protein kinase (DNA-PKi's) are potent radiosensitizers currently in clinical trials. Determining which patients may benefit from radiosensitization with DNA-PKi's is critical to avoid unnecessary increased risk of normal tissue toxicity.

"Bubbly lung", a honeycombing variant with more favorable outcome.

Background: Although radiologic honeycombing is generally associated with progressive fibrosis and a dismal prognosis, some patients display an unexpectedly indolent clinical course. We aimed to assess for variants of honeycombing associated with a more favorable prognosis.

Methods: A computer-assisted search was conducted to identify patients encountered at Mayo Clinic from 1998 to 2022 who had undergone chest CT that manifested exuberant honeycombing.

Relationship of Rurality and Confidence in Video Skills With Persistent Nonuse of Video Appointments for Health Care.

Introduction: Limited research has examined how technology and digital literacy may affect patients' use of video visits. This study explored the relationship of demographic factors and patient-reported confidence in digital literacy skills to access to video visits among patients who never used them during the COVID-19 pandemic.

Methods: Using existing survey data, the current study examined data from respondents who did not engage in video appointments but instead attended face-to-face appointments between April and December 2020 for nonemergent health concerns.

The clinical impact of estimating low-density lipoprotein cholesterol (LDL-C) using different equations in the general population.

Background: Low-density lipoprotein cholesterol (LDL-C) is associated with atherosclerotic cardiovascular disease (ASCVD). Friedewald, Sampson, and Martin-Hopkins equations are used to calculate LDL-C. This study compares the impact of switching between these equations in a large geographically defined population.

Efficacy and safety of targeted therapies in VEXAS syndrome: retrospective study from the FRENVEX.

Objectives: Vacuoles, E1 enzyme, X-linked, autoinflammatory and somatic (VEXAS) syndrome is an adult-onset autoinflammatory disease associated with somatic ubiquitin-like modifier-activating enzyme 1 (UBA1) mutations. We aimed to evaluate the efficacy and safety of targeted therapies.

Methods: Multicentre retrospective study including patients with genetically proven VEXAS syndrome who had received at least one targeted therapy.

Adapting a Financial Incentives Intervention for Smoking Cessation With Alaska Native Families: Phase 1 Qualitative Research to Inform the Aniqsaaq (To Breathe) Study.

Introduction: Alaska Native and American Indian (ANAI) peoples in Alaska currently experience a disproportionate burden of morbidity and mortality from tobacco cigarette use. Financial incentives for smoking cessation are evidence-based, but a family-level incentive structure has not been evaluated. We used a community-based participatory research and qualitative approach to culturally adapt a smoking cessation intervention with ANAI families.

Discordance Between Very Low-Density Lipoprotein Cholesterol and Low-Density Lipoprotein Cholesterol Increases Cardiovascular Disease Risk in a Geographically Defined Cohort.

Background: Clinical risk scores are used to identify those at high risk of atherosclerotic cardiovascular disease (ASCVD). Despite preventative efforts, residual risk remains for many individuals. Very low-density lipoprotein cholesterol (VLDL-C) and lipid discordance could be contributors to the residual risk of ASCVD.

Aberrant ATM signaling and homology-directed DNA repair as a vulnerability of p53-mutant GBM to AZD1390-mediated radiosensitization.

ATM is a key mediator of radiation response, and pharmacological inhibition of ATM is a rational strategy to radiosensitize tumors. AZD1390 is a brain-penetrant ATM inhibitor and a potent radiosensitizer. This study evaluated the spectrum of radiosensitizing effects and the impact of mutation status in a panel of wild-type (WT) glioblastoma (GBM) patient-derived xenografts (PDXs).

Demographics and Social Factors Associated With Persistent Nonuse of Video Appointments at a Multisite Health Care Institution: Cross-Sectional Study.

Background: During the COVID-19 outbreak, video appointments became a popular method for health care delivery, particularly in the early stages of the pandemic. Although Mayo Clinic aimed to reduce face-to-face (F2F) appointments to prevent the spread of the virus, some patients continued seeing their health care providers in person. In the later stages of the pandemic, many patients became comfortable with video appointments, even if they were initially hesitant.

Differential Distribution of the DNA-PKcs Inhibitor Peposertib Selectively Radiosensitizes Patient-derived Melanoma Brain Metastasis Xenografts.

Radioresistance of melanoma brain metastases limits the clinical utility of conventionally fractionated brain radiation in this disease, and strategies to improve radiation response could have significant clinical impact. The catalytic subunit of DNA-dependent protein kinase (DNA-PKcs) is critical for repair of radiation-induced DNA damage, and inhibitors of this kinase can have potent effects on radiation sensitivity. In this study, the radiosensitizing effects of the DNA-PKcs inhibitor peposertib were evaluated in patient-derived xenografts of melanoma brain metastases (M12, M15, M27).

Defining the natural history of tumefactive demyelination: A retrospective cohort of 257 patients.

Objective: To describe demographic, clinical, and radiographic features of tumefactive demyelination (TD) and identify factors associated with severe attacks and poor outcomes.

Methods: Retrospective review of TD cases seen at Mayo Clinic, 1990-2021.

Results: Of 257 patients with TD, 183/257 (71%) fulfilled the 2017 multiple sclerosis (MS) McDonald criteria at the last follow-up, 12/257 (5%) had myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD), 0 had aquaporin-4-IgG seropositive neuromyelitis optic spectrum disorders (AQP4+ NMOSD), and 62/257 (24%) were cryptogenic.

Association Between Fluctuations in Blood Lipid Levels Over Time With Incident Alzheimer Disease and Alzheimer Disease-Related Dementias.

Background And Objectives: Prevention strategies for Alzheimer disease and Alzheimer disease-related dementias (AD/ADRDs) are urgently needed. Lipid variability, or fluctuations in blood lipid levels at different points in time, has not been examined extensively and may contribute to the risk of AD/ADRD. Lipid panels are a part of routine screening in clinical practice and routinely available in electronic health records (EHR).

Rural and urban residents' attitudes and preferences toward COVID-19 prevention behaviors in a midwestern community.

Rural populations are more vulnerable to the impacts of COVID-19 compared to their urban counterparts as they are more likely to be older, uninsured, to have more underlying medical conditions, and live further from medical care facilities. We engaged the Southeastern MN (SEMN) community (N = 7,781, 51% rural) to conduct a survey of motivators and barriers to masking to prevent COVID-19. We also assessed preferences for types of and modalities to receive education/intervention, exploring both individual and environmental factors primarily consistent with Social Cognitive Theory.

WSD-0922, a novel brain-penetrant inhibitor of epidermal growth factor receptor, promotes survival in glioblastoma mouse models.

Background: Although the epidermal growth factor receptor (EGFR) is a frequent oncogenic driver in glioblastoma (GBM), efforts to therapeutically target this protein have been largely unsuccessful. The present preclinical study evaluated the novel EGFR inhibitor WSD-0922.

Methods: We employed flank and orthotopic patient-derived xenograft models to characterize WSD-0922 and compare its efficacy to erlotinib, a potent EGFR inhibitor that failed to provide benefit for GBM patients.

Aniqsaaq (To Breathe): Study protocol to develop and evaluate an Alaska Native family-based financial incentive intervention for smoking cessation.

Background: Alaska Native and American Indian (ANAI) communities in Alaska are disproportionately affected by commercial tobacco use. Financial incentive interventions promote cigarette smoking cessation, but family-level incentives have not been evaluated. We describe the study protocol to adapt and evaluate the effectiveness and implementation of a remotely delivered, family-based financial incentive intervention for cigarette smoking among Alaskan ANAI people.

Spinal cord and brain corticospinal tract lesions are associated with motor progression in tumefactive multiple sclerosis.

Background: Spinal cord lesions have been associated with progressive disease in individuals with typical relapsing remitting MS (RRMS).

Objective: In the current study, we aimed to determine if progressive disease is associated with spinal cord lesions in those with tumefactive multiple sclerosis (MS).

Methods: Retrospective chart review of individuals presenting to Mayo Clinic with tumefactive MS with spinal cord MRIs available (n=159).

Cerebrospinal fluid 2-hydroxyglutarate (2-HG) as a monitoring biomarker for IDH-mutant gliomas.

D-2-hydroxyglutarate (D-2-HG) is a well-established oncometabolite of isocitrate dehydrogenase (IDH) mutant gliomas. While prior studies have demonstrated that D-2-HG is elevated in the cerebrospinal fluid (CSF) of patients with IDH-mutant gliomas , no study has determined if CSF D-2-HG can provide a plausible method to evaluate therapeutic response. We are obtaining CSF samples from consenting patients during their disease course via intra-operative collection and Ommaya reservoirs.