Citations

AbstractObjectives/HypothesisTest a new jellyfish collagen biomaterial aimed to increase duration of injection medialization laryngoplasty (IL) against two products in clinical practice.Study DesignAnimal model.MethodsLeft recurrent laryngeal nerve sectioning and IL were performed in New Zealand White rabbits (N = 6/group). Group 1 received micronized cross‐linked jellyfish collagen (MX‐JC) and adipose derived stem cells (ADSCs), Group 2, MX‐JC alone, Group 3, cross‐linked hyaluronic acid (X‐HA), and Group 4, micronized acellular dermis (MACD). Animals were sacrificed at 4 and 12 weeks. Major outcomes were MRI tissue volumes and histopathology.ResultsAfter 100 μL IL MRI volumes (means ± STD) at 4 and 12 weeks were: Group 1: 27.2 ± 15.6 and 13.1 ± 5.2 μL, Group 2: 60.8 ± 18 and 27.8 ± 2.47 μL, Group 3: 27.4 ± 12 and 10.6 ± 8 μL, and Group 4: 37.5 ± 11 and 9.85 ± 1 μL. Group 2 volumes were largest and Group 3 were smallest in all comparisons (P < .05). Histologically, low grade inflammatory responses were observed in Group 1, mild histiocytic infiltration in Group 2, widespread muscle fiber loss in Group 3, and plasmocytic infiltration in Group 4.ConclusionsMX‐JC showed the least resorption at 4 and 12 weeks among all groups. T cell inflammatory responses were observed with MX‐JC but were reduced by 12 weeks while B cell immune responses, indicative of antibody priming, were predominantly noted with MACD. MX‐JC + ADSC showed low grade immunity while the XHA showed greater myocyte loss compared to the other groups.Level of EvidenceNA Laryngoscope, 131:E2452–E2460, 2021

Abstract Current therapies for breast cancer prevention only prevent estrogen receptor positive (ER+) disease and toxicity limits use of these agents. Vitamin D is a potential prevention therapy for both ER+ and ER− disease and is safe with few side effects. This study evaluates the effect of 1-year of vitamin D supplementation on mammographic density (MD), a biomarker of breast cancer risk in a multicenter randomized controlled trial. Premenopausal women with ≥25% MD and no history of cancer were randomly assigned to 2,000 international units (IU) of vitamin D or placebo orally daily for 1 year. Change in percent MD was evaluated using Cumulus software after all participants completed treatment. Three hundred women enrolled between January 2011 and December 2013 with a mean age of 43 and diverse ethnicity [14% Hispanic, 12% African American (AA)]. Supplementation significantly increased vitamin D levels compared with placebo (14.5 ng/mL vs. −1.6 ng/mL; P &lt; 0.0001) with all participants on the vitamin D arm achieving vitamin D sufficiency at 12 months. Vitamin D was safe and well tolerated. After adjustment for baseline MD, the mean between-arm difference (vitamin D vs. placebo) at 1 year was −0.75 (−0.26, 1.76; P = 0.56). A greater effect was seen for women with ≥50% MD and AA women, although neither reached significance. This randomized controlled trial demonstrated significant improvement in vitamin D levels with 2,000 IU for 1 year, with 100% of supplemented women achieving sufficiency. However, a null effect was seen regarding change in MD for premenopausal women (the primary outcome of the study). Prevention Relevance: Current therapies for breast cancer prevention only prevent estrogen receptor positive (ER+) disease and are underutilized due to toxicity and side effects. Vitamin D is a potential prevention therapy for both ER+ and ER− disease and is safe with few side effects.

Gestational diabetes mellitus (GDM) is a frequently observed complication of pregnancy and is associated with an elevated risk of adverse maternal and neonatal outcomes. Many women with GDM will go on to have future pregnancies, and these pregnancies may or may not be affected by GDM. We conducted a literature search, and based on data from key studies retrieved during the search, we describe the epidemiology of GDM recurrence. This includes a summary of the observed clinical risk factors of increasing maternal age, weight, ethnicity, and requirement for insulin in the index pregnancy. We then present our data from Mayo Clinic (January 2013–December 2017) which identifies a GDM recurrence rate of 47.6%, and illustrates the relevance of population-based studies to clinical practice. Lastly, we examine the available evidence on strategies to prevent GDM recurrence, and note that more research is needed to evaluate the effect of interventions before, during and after pregnancy.

Introduction: Antibiotic time-outs (ATO) are a recommended antimicrobial stewardship action, but data assessing their impact are lacking. This study investigated the impact of a systematic, pharmacist initiated ATO intervention. Methods: This pre-post study included inpatients on hospitalist and intensivist services receiving empiric antibiotics for ≥48 hours. The ATO was initiated by pharmacists after 48 hours of empiric therapy and the outcome was documented including antibiotic indication, plan, and duration. An electronic medical record (EMR) alert facilitated ATO completion and pharmacists and prescribers received education prior to implementation. The primary outcome was EMR documentation of an antibiotic plan by 72 hours. Secondary outcomes included antibiotic utilization and antibiotic therapy modifications by 2 hours. Results: 399 patients were included, 199 pre- and 200 post-intervention. The most common indications were pneumonia (32%), intra-abdominal infection (20%) and urinary tract infection (19%), with no between-group differences. EMR documentation of an antibiotic plan significantly improved in the post-intervention group (19% vs. 79%, p<0.0001) as did modifications to antibiotic therapy. The median duration of in-hospital antibiotic therapy was similar between groups (4.0 vs. 4.0 days, p = 0.2499). Approximately 45% of patients in each group received discharge antibiotics and median duration of discharge antibiotic therapy prescribed was reduced (7 vs. 5 days in the pre- and post-intervention groups, respectively; p = 0.0140). Discussion: Implementation of pharmacist initiated ATO was associated with improvements in supporting EMR documentation and antibiotic therapy modifications. These findings highlight an important role in which pharmacists can serve as part of a collaborative antibiotic stewardship team.

PolyQ ATXN3 is a pharmacodynamic marker for SCA3, and a SNP associated with the expanded allele may serve to specifically target mutant ATXN3 .

Although the ε2 allele of apolipoprotein E ( APOE2 ) benefits longevity, its mechanism is not understood. The protective effects of the APOE 2 on Alzheimer’s disease (AD) risk, particularly through their effects on amyloid or tau accumulation, may confound APOE2 effects on longevity. Herein, we showed that the association between APOE2 and longer lifespan persisted irrespective of AD status, including its neuropathology, by analyzing clinical datasets as well as animal models. Notably, APOE2 was associated with preserved activity during aging, which also associated with lifespan. In animal models, distinct apoE isoform levels, where APOE2 has the highest, were correlated with activity levels, while some forms of cholesterol and triglycerides were associated with apoE and activity levels. These results indicate that APOE2 can contribute to longevity independent of AD. Preserved activity would be an early-observable feature of APOE2 -mediated longevity, where higher levels of apoE2 and its-associated lipid metabolism might be involved.

Abstract Introduction The cytoprotective PTEN‐induced kinase 1 (PINK1)‐parkin RBR E3 ubiquitin protein ligase (PRKN) pathway selectively labels damaged mitochondria with phosphorylated ubiquitin (pS65‐Ub) for their autophagic removal (mitophagy). Because dysfunctions of mitochondria and degradation pathways are early features of Alzheimer's disease (AD), mitophagy impairments may contribute to the pathogenesis. Methods Morphology, levels, and distribution of the mitophagy tag pS65‐Ub were evaluated by biochemical analyses combined with tissue and single cell imaging in AD autopsy brain and in transgenic mouse models. Results Analyses revealed significant increases of pS65‐Ub levels in AD brain, which strongly correlated with granulovacuolar degeneration (GVD) and early phospho‐tau deposits, but were independent of amyloid beta pathology. Single cell analyses revealed predominant co‐localization of pS65‐Ub with mitochondria, GVD bodies, and/or lysosomes depending on the brain region analyzed. Discussion Our study highlights mitophagy alterations in AD that are associated with early tau pathology, and suggests that distinct mitochondrial, autophagic, and/or lysosomal failure may contribute to the selective vulnerability in disease.

Abstract Background Black race is associated with worse outcomes in early breast cancer. We evaluated clinicopathologic characteristics, the 21-gene recurrence score (RS), treatment delivered, and clinical outcomes by race and ethnicity among women who participated in the Trial Assigning Individualized Options for Treatment. Methods The association between clinical outcomes and race (White, Black, Asian, other or unknown) and ethnicity (Hispanic vs non-Hispanic) was examined using proportional hazards models. All P values are 2-sided. Results Of 9719 eligible women with hormone receptor–positive, HER2-negative, node-negative breast cancer, there were 8189 (84.3%) Whites, 693 (7.1%) Blacks, 405 (4.2%) Asians, and 432 (4.4%) with other or unknown race. Regarding ethnicity, 889 (9.1%) were Hispanic. There were no substantial differences in RS or ESR1, PGR, or HER2 RNA expression by race or ethnicity. After adjustment for other covariates, compared with White race, Black race was associated with higher distant recurrence rates (hazard ratio [HR] = 1.60, 95% confidence intervals [CI] = 1.07 to 2.41) and worse overall survival in the RS 11-25 cohort (HR = 1.51, 95% CI = 1.06 to 2.15) and entire population (HR = 1.41, 95% CI = 1.05 to 1.90). Hispanic ethnicity and Asian race were associated with better outcomes. There was no evidence of chemotherapy benefit for any racial or ethnic group in those with a RS of 11-25. Conclusions Black women had worse clinical outcomes despite similar 21-gene assay RS results and comparable systemic therapy in the Trial Assigning Individualized Options for Treatment. Similar to Whites, Black women did not benefit from adjuvant chemotherapy if the 21-gene RS was 11-25. Further research is required to elucidate the basis for this racial disparity in prognosis.