National perspective on hospital readmissions following adrenalectomy.

Background: Examining risk factors of readmission in adrenalectomy patients and estimated the cost burden of unplanned readmission on the United States' healthcare system. Methods: According to the Nationwide Readmission Database, 20,494 patients underwent adrenalectomy between 2010-2014. Demographics, comorbidities, clinical data, length of stay (LOS), annual case volume, and discharge disposition of 30- and 90-day readmission cohorts were compared to the non-readmitted cohort. Results: A total of 1,463 (7.9%) and 1,959 (12.7%) adrenalectomy patients were readmitted at 30 and 90 days after discharge, respectively. Prolonged initial hospital stays [odds ratio (OR) =1.93; 95% confidence interval (CI): 1.63-2.27] and postoperative complications (OR =4.91; 95% CI: 1.98-12.16) were associated with a higher risk of readmission. Complications were significantly more frequent in patients with a primary or secondary malignancy (OR =1.42; 95% CI: 1.23-1.64) and in patients undergoing a procedure at a low adrenalectomy volume hospital [hazard ratio (HR) =0.75; 95% CI: 0.62-0.91; P=0.003]. Readmission extended overall LOS by an average of 2.06 days, costing an additional $18,529.49 per admission. Conclusions: Readmission adds significantly to the burden of disease after adrenalectomy. Understanding contributing factors may identify strategies to reduce readmissions and improve healthcare for patients.

IL-10 promotes endothelial progenitor cell infiltration and wound healing via STAT3.

Endothelial progenitor cells (EPCs) contribute to de novo angiogenesis, tissue regeneration, and remodeling. Interleukin 10 (IL-10), an anti-inflammatory cytokine that primarily signals via STAT3, has been shown to drive EPC recruitment to injured tissues. Our previous work demonstrated that overexpression of IL-10 in dermal wounds promotes regenerative tissue repair via STAT3-dependent regulation of fibroblast-specific hyaluronan synthesis. However, IL-10's role and specific mode of action on EPC recruitment, particularly in dermal wound healing and neovascularization in both normal and diabetic wounds, remain to be defined. Therefore, inducible skin-specific STAT3 knockdown mice were studied to determine IL-10's impact on EPCs, dermal wound neovascularization and healing, and whether it is STAT3-dependent. We show that IL-10 overexpression significantly elevated EPC counts in the granulating wound bed, which was associated with robust capillary lumen density and enhanced re-epithelialization of both control and diabetic (db/db) wounds at day 7. We noted increased VEGF and high C-X-C motif chemokine 12 (CXCL12) levels in wounds and a favorable CXCL12 gradient at day 3 that may support EPC mobilization and infiltration from bone marrow to wounds, an effect that was abrogated in STAT3 knockdown wounds. These findings were supported in vitro. IL-10 promoted VEGF and CXCL12 synthesis in primary murine dermal fibroblasts, with blunted VEGF expression upon blocking CXCL12 in the media by antibody binding. IL-10-conditioned fibroblast media also significantly promoted endothelial sprouting and network formation. In conclusion, these studies demonstrate that overexpression of IL-10 in dermal wounds recruits EPCs and leads to increased vascular structures and faster re-epithelialization.

Clinical annotations for prostate cancer research: Defining data elements, creating a reproducible analytical pipeline, and assessing data quality.

BACKGROUND: Routine clinical data from clinical charts are indispensable for retrospective and prospective observational studies and clinical trials. Their reproducibility is often not assessed. We developed a prostate cancer-specific database for clinical annotations and evaluated data reproducibility. METHODS: For men with prostate cancer who had clinical-grade paired tumor-normal sequencing at a comprehensive cancer center, we performed team-based retrospective data collection from the electronic medical record using a defined source hierarchy. We developed an open-source R package for data processing. With blinded repeat annotation by a reference medical oncologist, we assessed data completeness, reproducibility of team-based annotations, and impact of measurement error on bias in survival analyses. RESULTS: Data elements on demographics, diagnosis and staging, disease state at the time of procuring a genomically characterized sample, and clinical outcomes were piloted and then abstracted for 2261 patients (with 2631 samples). Completeness of data elements was generally high. Comparing to the repeat annotation by a medical oncologist blinded to the database (100 patients/samples), reproducibility of annotations was high; T stage, metastasis date, and presence and date of castration resistance had lower reproducibility. Impact of measurement error on estimates for strong prognostic factors was modest. CONCLUSIONS: With a prostate cancer-specific data dictionary and quality control measures, manual clinical annotations by a multidisciplinary team can be scalable and reproducible. The data dictionary and the R package for reproducible data processing are freely available to increase data quality and efficiency in clinical prostate cancer research.

The birth of quantum mechanics from the spirit of radiation theory.

This paper starts from the observation that the major hallmarks in the history of quantum mechanics centrally involved light and radiation. Consequently, we ask how precisely did concepts and ideas from radiation theory define the creation of quantum mechanics? And why was it a quantum theory of mechanics and not a quantum theory of electrodynamics that was crafted in the years 1925/26? Following these questions, this paper provides a reading of the history of the old quantum theory from the perspective of radiation. We argue that both wave and matrix mechanics, while emerging from widely different trajectories, emerged as spin-offs from nascent, ultimately unsuccessful quantum theories of radiation. We discuss the epistemological implications of this development for the historical and philosophical analysis of quantum mechanics and quantum field theory.

Skin-specific knockdown of hyaluronan in mice by an optimized topical 4-methylumbelliferone formulation.

Hyaluronan (HA) is abundant in the skin; while HA can be synthesized by the synthases (HAS1-3), HAS2 is the leading contributor. Dysregulation and accumulation of HA is implicated in the pathogenesis of diseases such as keloid scarring, lymphedema and metastatic melanoma. To understand how HA synthesis contributes to skin physiology, and pathologic and fibrotic disorders, we propose the development of skin-specific HA inhibition model, which tests an optimal delivery system of topical 4-methylumbelliferone (4-MU). A design-of-experiments (DOE) approach was employed to develop an optimal 4-MU skin-delivery formulation comprising propylene glycol, ethanol, and water, topically applied to dorsal skin in male and female C57BL/6J wildtype mice to determine the effect on HAS gene expression and HA inhibition. Serum and skin samples were analyzed for HA content along with analysis of expression of HAS1-3, hyaluronidases (HYAL 1-2), and KIAA1199. Using results from DOE and response surface methodology with genetic algorithm optimization, we developed an optimal topical 4-MU formulation to result in ∼70% reduction of HA in dorsal skin, with validation demonstrating ∼50% reduction in HA in dorsal skin. 4-MU topical application resulted in significant decrease in skin HAS2 expression in female mice only. Histology showed thicker dermis in male mice, whereas female mice had thinner dermal layer with more adiposity; and staining for HA-binding protein showed that topical 4-MU resulted in breakdown in HA. Our data suggest a topical 4-MU formulation-based dermal HA inhibition model that would enable elucidating the skin-specific effects of HA in normal and pathologic states.