Factors associated with biopsy site identification, postponement of surgery, and patient confidence in a dermatologic surgery practice.

BACKGROUND: Biopsy site identification is critical to avoid wrong-site surgery and may impact patient-centered outcomes. OBJECTIVE: We sought to evaluate risk factors for biopsy site misidentification, postponement of surgery, and patient confidence in surgical site selection and to assess the near-miss rate for wrong-site surgeries. METHODS: This was a prospective observational cohort study. RESULTS: Near-miss wrong-site surgeries were detected and averted in 1.3% (3 of 239) of patients with biopsy site photographs. Risk factors for biopsy site misidentification by patients were 6 weeks or longer between biopsy and surgery (odds ratio [OR] 2.19, 95% confidence interval [CI] 1.12-4.27; P = .028) and patient inability to see biopsy site (OR 3.95, 95% CI 1.50-10.37; P = .002). Risk factors for physician misidentification were 6 or more weeks between biopsy and surgery (OR 3.68, 95% CI 1.40-9.66; P = .007) and biopsy specimens from multiple sites (OR 4.39, 95% CI 1.67-11.54; P = .003). Postponement of surgery was associated with absence of a biopsy site photograph (OR 12.5, 95% CI 2.79-62.21; P < .001). Patient confidence in surgical site identification was associated with the presence of a biopsy site photograph (OR 5.48, 95% CI 1.96-15.30; P = .001). LIMITATIONS: This was a single-site observational study. CONCLUSION: Biopsy site photography is associated with reduced rates of postponed surgeries and improved rates of patient confidence in surgical site selection. Risk factors for biopsy site misidentification should be considered before definitive treatment.

The Impact of an Infectious Diseases Transition Service on the Care of Outpatients on Parenteral Antimicrobial Therapy.

BACKGROUND: Many hospitalized patients with complicated infections are discharged on outpatient parenteral antimicrobial therapy (OPAT). However, little is known about how to improve the postdischarge care of OPAT patients. OBJECTIVE: The impact of an infectious diseases transitions service (IDTS) on OPAT patient readmissions, as well as on processes of care, was evaluated. METHODS: We performed a controlled, quasi-experimental evaluation over 15 months in an academic medical center. Intervention-arm patients, before and after the introduction of an IDTS, were seen by the general infectious diseases consult teams, while control-arm patients (discharged on OPAT after hospitalization with bacteremia) were not. The IDTS prospectively tracked all OPAT patients and coordinated follow-up. The impact of the IDTS was calculated using a differences-in-differences approach where the interaction between time (before vs after the IDTS intervention) and study arm (intervention vs control arm) was the variable of interest. The control arm was used only in primary outcome analyses (readmissions and emergency department visits). Secondary outcomes included process of care measures and non-readmission clinical outcomes. RESULTS: Of 488 consecutive patients requiring OPAT, 362 were in the intervention arm (215 pre-intervention and 147 post-intervention) and 126 in the control arm (70 pre-intervention and 56 post-intervention). Compared to the control arm, the IDTS was not associated with changes in 60-day readmissions and/or emergency department visits (adjusted odds ratio [OR] = 0.48; 95% confidence interval [CI] = 0.13-1.79). In the intervention arm, implementation of the IDTS was associated with fewer antimicrobial therapy errors (OR = 0.062; 95% CI = 0.015-0.262), increased laboratory test receipt (OR = 27.85; 95% CI = 12.93-59.99), and improved outpatient follow-up (OR = 2.44; 95% CI = 1.50-3.97). CONCLUSIONS: In a controlled evaluation, the IDTS did not affect readmissions despite improving process of care measures for targeted patients. Care coordination services may improve OPAT quality of care, but their relationship to readmissions is unclear.

Observation of alumina nanoparticles generated from aqueous solutions of a "flat" aluminum-13 cluster.

Amorphous alumina nanoparticles were synthesized via dynamic processes during the dissolution of aluminum hydroxide by nitric acid, a method commonly used to produce aqueous solutions of aluminum oxide molecular clusters. These particles were characterized by DLS measurements, and corroborated by other solution and solid state analyses. The methods used represent a highly tuneable, facile synthetic pathway that allows for size targeting and scalability for industrial purposes, and provides insight into pH- and temperature-dependent alumina speciation and aggregation.

MIRD Pamphlet No. 27: MIRDcell V3, a Revised Software Tool for Multicellular Dosimetry and Bioeffect Modeling.

Radiopharmaceutical therapy is growing rapidly. However, yet to be addressed is the implementation of methods to plan treatments for circulating tumor cells, disseminated tumor cells, and micrometastases. Given the capacity of radiopharmaceuticals to specifically target and kill single cells and multicellular clusters, a quality not available in chemotherapy and external-beam radiation therapy, it is important to develop dosimetry and bioeffect modeling tools that can inform radiopharmaceutical design and predict their effect on microscopic disease. This pamphlet describes a new version of MIRDcell, a software tool that was initially released by the MIRD committee several years ago. Methods: Version 3 (V3) of MIRDcell uses a combination of analytic and Monte Carlo methods to conduct dosimetry and bioeffect modeling for radiolabeled cells within planar colonies and multicellular clusters. A worked example is provided to assist users to learn old and new features of MIRDcell and test its capacity to recapitulate published responses of tumor cell spheroids to radiopharmaceutical treatments. Prominent capabilities of the new version include radially dependent activity distributions, user-imported activity distributions, cold regions within the cluster, complex bioeffect modeling that accounts for radiation type and subcellular distribution, and a rich table of output data for subsequent analysis. Results: MIRDcell V3 effectively reproduces experimental responses of multicellular spheroids to uniform and nonuniform distributions of therapeutic radiopharmaceuticals. Conclusion: MIRDcell is a versatile software tool that can be used for educational purposes and design of radiopharmaceutical therapies.

A scalable, eco-friendly ultralow-temperature approach to forming Al2O3 water-repellent cotton coatings via UV photo-annealing.

Hydrophobic coatings on cotton fabrics were successfully prepared via solution deposition of a "flat" nanoscale aluminum hydroxo cluster and a photo-assisted anneal using ultraviolet light. The coatings have a low surface roughness and high uniformity confirmed by SEM imaging and elemental analysis. The method represents a robust, scalable, and environmentally benign procedure suitable for industrial processes.

Design and testing of a microcontroller that enables alpha particle irradiators to deliver complex dose rate patterns.

There is increasing interest in using alpha particle emitting radionuclides for cancer therapy because of their unique cytotoxic properties which are advantageous for eradicating tumor cells. The high linear energy transfer (LET) of alpha particles produces a correspondingly high density of ionizations along their track. Alpha particle emitting radiopharmaceuticals deposit this energy in tissues over prolonged periods with complex dose rate patterns that depend on the physical half-life of the radionuclide, and the biological uptake and clearance half-times in tumor and normal tissues. We have previously shown that the dose rate increase half-time that arises as a consequence of these biokinetics can have a profound effect on the radiotoxicity of low-LET radiation. The microcontroller hardware and software described here offer a unique way to deliver these complex dose rate patterns with a broad-beam alpha particle irradiator, thereby enabling experiments to study the radiobiology of complex dose rate patterns of alpha particles. Complex dose rate patterns were created by precise manipulation of the timing of opening and closing of the electromechanical shutters of an α-particle irradiator. An Arduino Uno and custom circuitry was implemented to control the shutters. The software that controls the circuits and shutters has a user-friendly Graphic User Interface (GUI). Alpha particle detectors were used to validate the programmed dose rate profiles. Circuit diagrams and downloadable software are provided to facilitate adoption of this technology by other radiobiology laboratories.

Landscape of business models in teledermatology.

Effective business models for teledermatology must be implemented to make the practice a feasible option for dermatologists to deliver care. This study sought to detect and report types of teledermatology business models in practice. We interviewed 19 private and academic dermatologists who have been reimbursed for teledermatology services. Most respondents described teledermatology business models fitting 4 categories-standard fee-for-service reimbursement from insurance, capitated service contracts, per-case service contracts, and direct to consumer-which are described in this article. We also anticipate new teledermatology business models will be needed as technology and insurance reimbursements evolve.

Mono-(2-Ethylhexyl) Phthalate Promotes Pro-Labor Gene Expression in the Human Placenta.

Women exposed to phthalates during pregnancy are at increased risk for delivering preterm, but the mechanism behind this relationship is unknown. Placental corticotropin-releasing hormone (CRH) and cyclooxygenase-2 (COX-2) are key mediators of parturition and are regulated by the non-canonical NF-kB (RelB/p52) signaling pathway. In this study, we demonstrate that one of the major phthalate metabolites, mono-(2-ethylhexyl)-phthalate (MEHP), increased CRH and COX-2 mRNA and protein abundance in a dose-dependent manner in primary cultures of cytotrophoblast. This was coupled with an increase in nuclear import of RelB/p52 and its association with the CRH and COX-2 promoters. Silencing of NF-kB inducing kinase, a central signaling component of the non-canonical NF-kB pathway, blocked MEHP-induced upregulation of CRH and COX-2. These results suggest a potential mechanism mediated by RelB/p52 by which phthalates could prematurely induce pro-labor gene activity and lead to preterm birth.

Sox2 is an androgen receptor-repressed gene that promotes castration-resistant prostate cancer.

Despite advances in detection and therapy, castration-resistant prostate cancer continues to be a major clinical problem. The aberrant activity of stem cell pathways, and their regulation by the Androgen Receptor (AR), has the potential to provide insight into novel mechanisms and pathways to prevent and treat advanced, castrate-resistant prostate cancers. To this end, we investigated the role of the embryonic stem cell regulator Sox2 [SRY (sex determining region Y)-box 2] in normal and malignant prostate epithelial cells. In the normal prostate, Sox2 is expressed in a portion of basal epithelial cells. Prostate tumors were either Sox2-positive or Sox2-negative, with the percentage of Sox2-positive tumors increasing with Gleason Score and metastases. In the castration-resistant prostate cancer cell line CWR-R1, endogenous expression of Sox2 was repressed by AR signaling, and AR chromatin-IP shows that AR binds the enhancer element within the Sox2 promoter. Likewise, in normal prostate epithelial cells and human embryonic stem cells, increased AR signaling also decreases Sox2 expression. Resistance to the anti-androgen MDV3100 results in a marked increase in Sox2 expression within three prostate cancer cell lines, and in the castration-sensitive LAPC-4 prostate cancer cell line ectopic expression of Sox2 was sufficient to promote castration-resistant tumor formation. Loss of Sox2 expression in the castration-resistant CWR-R1 prostate cancer cell line inhibited cell growth. Up-regulation of Sox2 was not associated with increased CD133 expression but was associated with increased FGF5 (Fibroblast Growth Factor 5) expression. These data propose a model of elevated Sox2 expression due to loss of AR-mediated repression during castration, and consequent castration-resistance via mechanisms not involving induction of canonical embryonic stem cell pathways.

Deregulation of a Hox protein regulatory network spanning prostate cancer initiation and progression.

PURPOSE: The aberrant activity of developmental pathways in prostate cancer may provide significant insight into predicting tumor initiation and progression, as well as identifying novel therapeutic targets. To this end, despite shared androgen-dependence and functional similarities to the prostate gland, seminal vesicle cancer is exceptionally rare. EXPERIMENTAL DESIGN: We conducted genomic pathway analyses comparing patient-matched normal prostate and seminal vesicle epithelial cells to identify novel pathways for tumor initiation and progression. Derived gene expression profiles were grouped into cancer biomodules using a protein-protein network algorithm to analyze their relationship to known oncogenes. Each resultant biomodule was assayed for its prognostic ability against publically available prostate cancer patient gene array datasets. RESULTS: Analyses show that the embryonic developmental biomodule containing four homeobox gene family members (Meis1, Meis2, Pbx1, and HoxA9) detects a survival difference in a set of watchful-waiting patients (n = 172, P = 0.05), identify men who are more likely to recur biochemically postprostatectomy (n = 78, P = 0.02), correlate with Gleason score (r = 0.98, P = 0.02), and distinguish between normal prostate, primary tumor, and metastatic disease. In contrast to other cancer types, Meis1, Meis2, and Pbx1 expression is decreased in poor-prognosis tumors, implying that they function as tumor suppressor genes for prostate cancer. Immunohistochemical staining documents nuclear basal-epithelial and stromal Meis2 staining, with loss of Meis2 expression in prostate tumors. CONCLUSION: These data implicate deregulation of the Hox protein cofactors Meis1, Meis2, and Pbx1 as serving a critical function to suppress prostate cancer initiation and progression.