A Prospective, Single Arm, Multi-site, Clinical Evaluation of a Nonradioactive Surgical Guidance Technology for the Location of Nonpalpable Breast Lesions during Excision.

OBJECTIVES: This study was a multicenter evaluation of the SAVI SCOUT(®) breast localization and surgical guidance system using micro-impulse radar technology for the removal of nonpalpable breast lesions. The study was designed to validate the results of a recent 50-patient pilot study in a larger multi-institution trial. The primary endpoints were the rates of successful reflector placement, localization, and removal. METHODS: This multicenter, prospective trial enrolled patients scheduled to have excisional biopsy or breast-conserving surgery of a nonpalpable breast lesion. From March to November 2015, 154 patients were consented and evaluated by 20 radiologists and 16 surgeons at 11 participating centers. Patients had SCOUT(®) reflectors placed up to 7 days before surgery, and placement was confirmed by mammography or ultrasonography. Implanted reflectors were detected by the SCOUT(®) handpiece and console. Presence of the reflector in the excised surgical specimen was confirmed radiographically, and specimens were sent for routine pathology. RESULTS: SCOUT(®) reflectors were successfully placed in 153 of 154 patients. In one case, the reflector was placed at a distance from the target that required a wire to be placed. All 154 lesions and reflectors were successfully removed during surgery. For 101 patients with a preoperative diagnosis of cancer, 86 (85.1 %) had clear margins, and 17 (16.8 %) patients required margin reexcision. CONCLUSIONS: SCOUT(®) provides a reliable and effective alternative method for the localization and surgical excision of nonpalpable breast lesions using no wires or radioactive materials, with excellent patient, radiologist, and surgeon acceptance.

Training to Transition: Using Simulation-Based Training to Improve Resident Physician Confidence in Hospital Discharges.

Introduction: Hospital discharge is a highly critical and complex process that is prone to medical errors, poor communication, and ineffective synchronization of transitional teams. Improving safety during postacute care transitions has become a national focus. Simulation-based training is an underutilized method of instruction for medical resident transitions of care education. Methods: As an integral part of a transitions curriculum, 36 PGY 1 residents from internal medicine and transitional year residency programs underwent a discharge simulation utilizing a trained simulated participant (SP) and a lay caregiver. The objective of the training was to implement a simulation-based education intervention to improve transition practices and discharge communication in graduate medical education. A faculty observer used a case-specific discharge rubric to standardize feedback to the resident and observed the resident navigate the electronic medical record (EMR) for discharge orders. Pretest and posttest surveys assessing resident attitudes and confidence regarding specific areas of the discharge process were distributed to all participating residents for completion. Results: Thirty-six internal medicine and transitional year residents (100%) completed an observed discharge simulation with an SP and a separate encounter with the EMR discharge navigator. All 36 residents (100%) completed the pretest survey, and 23 (63%) completed the postsurvey evaluation. Postsurvey results showed residents agreed (92%, p < .05) that the simulation increased their confidence in safely discharging a patient. Discussion: Simulation encounters are an effective adjunct to postacute care transition education.

Immunohistochemical demonstration of the mineralocorticoid receptor, 11beta-hydroxysteroid dehydrogenase-1 and -2, and hexose-6-phosphate dehydrogenase in rat ovary.

An IHC survey using several monoclonal antibodies against different portions of the rat mineralocorticoid receptor (MR) molecule demonstrated significant specific MR immunoreactivity in the ovary, prompting further study of the localization of MR and of determinants of extrinsic MR ligand specificity, 11beta-hydroxysteroid dehydrogenase (11beta-HSD) types 1 and 2, and hexose-6-phosphate dehydrogenase (H6PDH). MR expression (real-time RT-PCR and Western blot) did not differ significantly in whole rat ovaries at early diestrus, late diestrus, estrus, and a few hours after ovulation. MR immunostaining was most intense in corporal lutea cells, light to moderate in oocytes and granulosa cells, and least intense in theca cells. Light immunoreactivity for 11beta-HSD2 occurred in most cells, with some mural granulosa cells of mature follicles staining more strongly. The distribution of immunoreactivity for 11beta-HSD1 and H6PDH required to generate NADPH, the cofactor required for reductase activity of 11beta-HSD1, was similar, with the most-intense staining in the cytoplasm of corporal lutea and theca cells and light or no staining in the granulosa and oocytes. MR function in the ovary is as yet unclear, but distinct patterns of distribution of 11beta-HSD1 and -2 and H6PDH suggest that the ligand for MR activation in different cells of the ovary may be differentially regulated.

Story of an Unfortunate Fall: Cardiac Contusion Presenting with an Atrioventricular Block.

Blunt cardiac injury (BCI), also referred to in the literature as a cardiac contusion, is a known cause of myocardial injury. It is often challenging to diagnose this condition in the absence of clear diagnostic criteria. Furthermore, its clinical presentation is highly variable depending on the severity, type, and duration of the trauma, as well as the timing from the initial insult. The clinical manifestation of BCI ranges from none to fatal arrhythmias to cardiac wall rupture seen on post-mortem examination. Cardiac biomarkers and electrocardiograms (EKG) are usually helpful in identifying cardiac trauma but are not necessarily abnormal in all cases. Falls by slipping on ice are common in the winter, but rarely do people present with a myocardial injury with these mechanical events. We describe the case of a cardiac contusion with an unusual presentation and an unusual cause, whereby both the initial EKG and troponin level were normal, and the patient presented with an atrioventricular (AV) block two weeks after "slipping on ice".

Hexose-6-phosphate dehydrogenase and 11beta-hydroxysteroid dehydrogenase-1 tissue distribution in the rat.

Intracellular concentrations of the glucocorticoids cortisol and corticosterone are modulated by the enzymes 11beta-hydroxysteroid dehydrogenase (11beta-HSD) 1 and 2. 11beta-HSD1 is a reduced nicotinamide adenine dinucleotide phosphate (NADPH)-dependent microsomal reductase that converts the inactive glucocorticoids cortisone and 11-dehydrocorticosterone to their active forms, cortisol and corticosterone. Hexose-6-phosphate dehydrogenase (H6PDH) is an enzyme that generates NADPH from oxidized NADP (NADP(+)) within the endoplasmic reticulum. In the absence of NADPH or H6PDH to regenerate NADPH, 11beta-HSD1 acts as a dehydrogenase and inactivates glucocorticoids, as does 11beta-HSD2. A monoclonal antibody against H6PDH was produced to study the possibility that 11beta-HSD1 in the absence of H6PDH may be responsible for hydroxysteroid dehydrogenase activity in tissues that do not express significant amounts of 11beta-HSD2. H6PDH and 11beta-HSD1 expression was surveyed in a variety of rat tissues by real-time RT-PCR, Western blot analysis, and immunohistochemistry. H6PDH was found in a wide variety of tissues, with the greatest concentrations in the liver, kidney, and Leydig cells. Although the brain as a whole did not express significant amounts of H6PDH, some neurons were clearly immunoreactive by immunohistochemistry. H6PDH was amply expressed in most tissues examined in which 11beta-HSD1 was also expressed, with the notable exception of the renal interstitial cells, in which dehydrogenase activity by 11beta-HSD1 probably moderates activation of the glucocorticoid receptor because rat renal interstitial cells do not have significant amounts of mineralocorticoid receptors. This antibody against the H6PDH should prove useful for further studies of enzyme activity requiring NADPH generation within the endoplasmic reticulum.

Molecular targeted therapies for renal cell carcinoma.

New advances in technology to directly target specific molecular events in the proliferation of cancer have led to promising results in renal cell carcinoma. Response rates in excess of 70% and complete responses in advanced (metastatic) renal cell carcinoma have caused a change in the paradigm of treatment from immunotherapy. Toxicities are significant, but manageable and pushing the toxicity to tolerability may increase the response rate.

Quality Improvement Intervention for Reduction of Redundant Testing.

Laboratory data are critical to analyzing and improving clinical quality. In the setting of residual use of creatine kinase M and B isoenzyme testing for myocardial infarction, we assessed disease outcomes of discordant creatine kinase M and B isoenzyme +/troponin I (-) test pairs in order to address anticipated clinician concerns about potential loss of case-finding sensitivity following proposed discontinuation of routine creatine kinase and creatine kinase M and B isoenzyme testing. Time-sequenced interventions were introduced. The main outcome was the percentage of cardiac marker studies performed within guidelines. Nonguideline orders dominated at baseline. Creatine kinase M and B isoenzyme testing in 7496 order sets failed to detect additional myocardial infarctions but was associated with 42 potentially preventable admissions/quarter. Interruptive computerized soft stops improved guideline compliance from 32.3% to 58% (P < .001) in services not receiving peer leader intervention and to >80% (P < .001) with peer leadership that featured dashboard feedback about test order performance. This successful experience was recapitulated in interrupted time series within 2 additional services within facility 1 and then in 2 external hospitals (including a critical access facility). Improvements have been sustained postintervention. Laboratory cost savings at the academic facility were estimated to be ≥US$635 000 per year. National collaborative data indicated that facility 1 improved its order patterns from fourth to first quartile compared to peer norms and imply that nonguideline orders persist elsewhere. This example illustrates how pathologists can provide leadership in assisting clinicians in changing laboratory ordering practices. We found that clinicians respond to local laboratory data about their own test performance and that evidence suggesting harm is more compelling to clinicians than evidence of cost savings. Our experience indicates that interventions done at an academic facility can be readily instituted by private practitioners at external facilities. The intervention data also supplement existing literature that electronic order interruptions are more successful when combined with modalities that rely on peer education combined with dashboard feedback about laboratory order performance. The findings may have implications for the role of the pathology laboratory in the ongoing pivot from quantity-based to value-based health care.

Development of a panel of monoclonal antibodies against the mineralocorticoid receptor.

Mineralocorticoid receptors (MR) bind both mineralocorticoids and glucocorticoids. They are expressed in multiple tissues and mediate diverse functions. Less is known about MR regulation and function compared with other major steroid receptors, although its importance has become increasingly apparent. A significant obstacle to such studies has been the dearth of specific high-affinity MR antibodies. We have produced monoclonal antibodies against 10 different peptide conjugates, six from the N terminus (A/B domain) and four from the C terminus (steroid binding domain), with the anticipation that their individual affinities for the MR would differ depending upon its conformation, which in turn, is dependent upon the location of the receptor within the cell and the proteins associated with it. Hybridoma clones with high titers to the cognate peptide ELISA were analyzed by Western blots using protein from Chinese hamster ovary cells transfected with enhanced green fluorescent protein-rat MR cDNA and from hippocampal cytosol from adrenalectomized rats. Immunohistochemistry was done on kidney, heart, colon, and brain. Antibodies that proved to be most useful for Western blot analysis and immunohistochemistry include those raised against peptides comprising amino acids 1-18, 64-82, 79-97, and 365-381. The intensity of immunoreactivity in the cytosol compared with nucleus in the same cells differed between antibodies, suggesting that certain receptor epitopes were more or less exposed depending on the location of the receptor within the cell. In summary, several antibodies are described that recognize different parts of the MR that should facilitate the study of this important mediator of two classes of steroid hormone action.

Diverse immunostaining patterns of mineralocorticoid receptor monoclonal antibodies.

The mineralocorticoid receptor (MR) is a widely distributed ligand activated nuclear transcription factor that is bound by various chaperone proteins that alter its conformation depending upon its location in the cell and whether it is ligand-bound. We describe the development and characterization of new monoclonal antibodies produced against a rat recombinant protein corresponding to aminoacids 5-550 of the MR to produce antibodies that recognize the receptor in specific conformations. Most of the resulting monoclonal antibodies studied were similar to those we produced by immunization with peptide isotopes, however two detected a single band at the appropriate molecular mass as the MR and had distinct immunostaining characteristics in neurons. One labeled cytosolic MR, the other labeled membranes and cytosol, including axons. These antibodies will permit study of the subcellular localization of the MR under various physiological and pathological conditions. We have also confirmed that the MR is highly unstable and requires special handling.

Osteoporosis screening: factors associated with bone mineral density testing of older women.

BACKGROUND: Osteoporosis is a major public health problem. Guidelines recommend osteoporosis screening, primarily with bone mineral density (BMD) testing, of all women aged > or =65 and younger women at increased risk. However, BMD testing is underused, and osteoporosis screening practices are not in compliance with guidelines. METHODS: This was a retrospective cohort study of 809 women patients > or =65 years. The proportion of patients having evidence of BMD testing and factors associated with BMD testing were evaluated. RESULTS: The overall proportion of patients having evidence of BMD testing was 42.9%. A higher proportion of patients from the gynecology practice (72%) had evidence of BMD testing compared with family medicine (42%), general internal medicine (36%), and the Veterans Administration practice (30%) (p < 0.0001). The proportion of patients with evidence of BMD testing was higher in patients seen by faculty (48%) than in patients seen by midlevel providers (35%) or residents (21%) (p < 0.0001) and was higher in patients of female providers (54%) than in patients of male providers (31%) (p < 0.0001). Negative associations with BMD testing were seen with increasing age and numbers of medications (p < 0.0001 and p < 0.05, respectively). The numbers of visits and numbers of total and unique ICD-9 codes were each negatively associated with BMD testing (p < 0.05, p < 0.005, and p < 0.05, respectively). In patients with commercial insurance, 48% had evidence of BMD testing vs. 25% in the rest of the subjects (p < 0.0001). The proportion of patients with evidence of BMD testing also varied by body mass index (BMI). CONCLUSIONS: Consideration of factors associated with BMD testing may be useful in developing interventions to increase osteoporosis screening rates.