Transforming a hospital nursing research fellowship into an evidence-based practice fellowship

An established hospital-based nursing research fellowship program was transformed into an evidence-based practice fellowship despite its previous high satisfaction ratings from nursing leaders and nurse fellow participants. The faculty for the fellowship program determined that the long-term outcomes of the research program were insufficient in light of the hospital resources committed to the fellowship program. An evidence-based practice approach was then created in anticipation that greater short-term and more sustained longer-term benefits for the hospital would be realized. The transformation of the fellowship and the short-term outcomes are described.     

Book Review

Performance Breakthroughs for Adolescents With Learning Disabilities or ADD. G. Markel & J. Greenbaum.     

Parafibromin,Galectin-3, PGP9.5, Ki67, and Cyclin D1: Using an Immunohistochemical Panel to Aid in the Diagnosis of Parathyroid Cancer

Background

Parathyroid cancer is rare. Differentiating parathyroid carcinoma from degenerative changes at histopathology can be difficult and studies investigating the value of single immunohistochemical markers have had variable results. In this study we aimed to investigate whether a panel of immunohistochemistry markers could aid the diagnosis of parathyroid cancer.

Methods

All cases of parathyroid cancer at our institution from 1998 to 2012 were identified retrospectively. Cases were classified as definite cancers (those with evidence of metastatic spread) or histological cancers (those with features of carcinoma without evidence of metastasis). Controls with benign parathyroid disease were included for comparison. Immunohistochemistry for parafibromin, galectin-3, PGP9.5, Ki67, and cyclin D1 was analysed by an experienced endocrine pathologist.

Results

There were 24 cases and 14 benign adenomas. Four cases had evidence of metastatic spread and 20 were diagnosed on histological criteria alone. Sixteen of the 24 cases had further surgery with ipsilateral thyroid lobectomy and 15 also had a prophylactic level VI lymph node dissection. Apart from one patient with distant metastases at presentation, none developed recurrence at follow-up (median = 38 months). Immunohistochemistry results associated with parathyroid cancer were seen in 11/24 parafibromin, 13/24 galectin-3, 8/24 PGP9.5, 5/24 Ki67, and 2/24 cyclin D1. None of the controls had immunohistochemical staining suggestive of cancer. Nineteen of the 24 patients had at least one immunohistochemical result associated with parathyroid cancer (sensitivity 79 %, specificity 100 %). Cyclin D1 did not suggest malignancy in any case that did not already have another abnormal marker, and so did not add value to the panel in this study.

Conclusion

A panel of immunohistochemistry (PGP9.5, galectin-3, parafibromin, and Ki67) is better than any single marker and can be used to supplement classical histopathology in diagnosing parathyroid cancer.     

Characterization of Renal Toxicity in Mice Administered the Marine Biotoxin Domoic Acid

Domoic acid (DA), an excitatory amino acid produced by diatoms belonging to the genus Pseudo-nitzschia, is a glutamate analog responsible for the neurologic condition referred to as amnesic shellfish poisoning. To date, the renal effects of DA have been underappreciated, although renal filtration is the primary route of systemic elimination and the kidney expresses ionotropic glutamate receptors. To characterize the renal effects of DA, we administered either a neurotoxic dose of DA or doses below the recognized limit of toxicity to adult Sv128/Black Swiss mice. DA preferentially accumulated in the kidney and elicited marked renal vascular and tubular damage consistent with acute tubular necrosis, apoptosis, and renal tubular cell desquamation, with toxic vacuolization and mitochondrial swelling as hallmarks of the cellular damage. Doses≥0.1 mg/kg DA elevated the renal injury biomarkers kidney injury molecule-1 and neutrophil gelatinase-associated lipocalin, and doses≥0.005 mg/kg induced the early response genes c-fos and junb. Coadministration of DA with the broad spectrum excitatory amino acid antagonist kynurenic acid inhibited induction of c-fos, junb, and neutrophil gelatinase-associated lipocalin. These findings suggest that the kidney may be susceptible to excitotoxic agonists, and renal effects should be considered when examining glutamate receptor activation. Additionally, these results indicate that DA is a potent nephrotoxicant, and potential renal toxicity may require consideration when determining safe levels for human exposure.Domoic acid (DA), a water-soluble, heat-stable tricarboxylic acid produced by diatoms belonging to the genus Pseudo-nitzschia, is responsible for a condition known as amnesic shellfish poisoning in humans.^1–4 Shellfish, such as clams and mussels, and fish that accumulate DA serve as vectors of exposure to various species of birds and aquatic mammals in addition to humans.^5,6 Initially recognized as a human toxicant when more than 100 people became ill after eating contaminated mussels in eastern Canada in 1987, DA poisoning was defined by the occurrence of gastrointestinal or neurologic symptoms ranging from abdominal cramps and headache to more severe cases of memory loss, seizures, coma, and even death.^2,4 Increased awareness and governmental regulation, which set a limit of 20 μg DA/g in shellfish tissue, has reduced the incidence of DA toxicity in humans since the 1987 outbreak. However, there is concern that exposure will increase because of the growing presence of toxic diatom-producing algal blooms, which are often attributed to human factors, such as pollution, shipping, and global warming, leading to greater nutrient availability, greater distribution of algal species, and longer growth periods.^7–14 Although the overt gastrointestinal and neurologic manifestations have defined the disease, emerging evidence from animal and human studies support previously unrecognized threats and novel toxicologic syndromes caused by subclinical toxicity from acute and chronic DA exposures, which may ultimately challenge the adequacy of the current acceptable limit.^15–18DA is a potent activator of kainate receptors (KRs) as well as a subpopulation of α-amino-3-hydroxy-5-methyl-4-isoxazoleproprionic acid receptors (AMPARs).¹⁹ The toxic response produced by DA is a coordinated effort, which involves initial activation of KR and AMPAR by DA and secondary activation of N-methyl-D-aspartate receptors (NMDARs) by glutamate, and it is associated with an influx of Ca²⁺ across the plasma membrane, inflammation, neuronal cell injury and death, and neurobehavioral alterations.^19–22 Although they are extensively characterized in the central nervous system, glutamate receptors are also expressed at peripheral sites and have been shown to exhibit toxicity in multiple tissues, including the kidney, where NMDARs contribute to organ damage in models of ischemia-reperfusion injury and gentamicin nephrotoxicity.^23–26 There is limited information about the effects of DA on the kidney; however, oral dosing in coho salmon has shown that the kidney is a primary site of DA accumulation in this species, and studies in rodents have shown that renal excretion is the exclusive route of systemic DA elimination.^27,28 Examination of sea lions after DA poisoning has also revealed some evidence of interstitial nephritis, renal edema, and elevated BUN, although the exact cause of these findings cannot be definitively attributed to DA toxicity.^29,30 Furthermore, sea lions with acute DA toxicosis seem to have an elevated hematocrit,³¹ suggesting that water reabsorption or red blood cell production could be affected, both of which are functions of the kidney. Despite this circumstantial evidence, a detailed examination of the renal response to DA administration has not been fully explored. The purpose of the current study was to characterize the acute renal effects of DA at doses that produce neurotoxicity and neurobehavioral changes (1.0–2.5 mg/kg) as well as several lower doses (0.0005–0.5 mg/kg), which are considered below the limit of toxicity.     

Prophylactic central neck disection in papillary thyroid cancer: a consensus report of the European Society of Endocrine Surgeons (ESES)

Background

There remains still no clear answer as to whether or not prophylactic central compartment neck dissection (pCCND) is indicated for the treatment of patients with papillary thyroid cancer.

Methods

The published studies, including single cohort, comparative studies and meta-analysis, were critically appraised. Aspects beyond postoperative complications and loco-regional recurrence rates in the analysis, as the impact of pre- and post-ablation thyroglobuline levels, multifocality, bilaterality and additional risk factors for recurrence, were also considered.

Results

Thirty studies and five meta-analyses were assessed. The lack of randomized clinical trials on the subject and the heterogeneity of study populations are the main limiting factors to draw clear conclusions, and a comprehensive list of bias sources has been identified. Recent comparative studies and systematic reviews all associate the pCCND with higher proportions of temporary postoperative hypocalcemia but not with significantly higher permanent hypoparathyroidism, recurrent laryngeal nerve injury or permanent vocal cord paralysis. The risk of recurrence appears to be reduced after pCCND, and the number of patients needed to treat to avoid a recurrence is between 20 and 31.

Conclusions

It is suggested that routine level 6 prophylactic dissections should be risk-stratified. Larger tumours (T3, T4), patients aged 45 years and older or 15 years and younger, male patients, patients with bilateral or multifocal tumours, and patients with known involved lateral lymph nodes could all be candidates for routine unilateral level 6 dissection. The operation should be limited to surgeons who have the available expertise and experience     

Obstructive jaundice and acute pancreatitis due to an obstruction of the afferent loop after billroth-II-resection

An obstruction of the afferent loop after Billroth-II-resection is an extremely rare late complication of this procedure. We report on a 76-year-old female patient with a history of Billroth-II-resection 11 years ago who was admitted due to acute pancreatitis and obstructive jaundice. Abdominal sonography lead to the suspicion of a dilated afferent loop, which could be proven by means of magnetic resonance imaging. A tumorous lesion as cause of the obstructive jaundice was not detectable. Intraoperatively a volvulus of the small intestine and strangling adhesions near the Braun's anastomosis were seen, causing the obstruction of the afferent loop. Following reposition of the small intestine and adhesiolysis the patient gained a quick relief of symptoms and the jaundice disappeared completely.     

Native associations of early hematopoietic stem cells and stromal cells isolated in bone marrow cell aggregates

In suspensions of murine bone marrow, many stromal cells are tightly entwined with hematopoietic cells. These cellular aggregations appear to exist normally within the marrow. Previous studies showed that lymphocytes and stem cells adhered to stromal cells via vascular cell adhesion molecule 1 (VCAM1). Injection of anti-VCAM1 antibody into mice disrupts the aggregates, showing the importance of VCAM1 in the adhesion between stromal cells and hematopoietic cells in vivo. Early hematopoietic stem cells were shown to be enriched in aggregates by using a limiting-dilution culture assay. Myeloid progenitors responsive to WEHI-3CM in combination with stem cell factor (c-kit ligand) and B220- B-cell progenitors responsive to insulin-like growth factor-1 in combination with interleukin-7 are not enriched. We propose a scheme of stromal cell-hematopoietic cell interactions based on the cell types selectively retained within the aggregates. The existence of these aggregates as native elements of bone marrow organization presents a novel means to study in vivo stem cell-stromal cell interaction.     

Neonatal imprinting predetermines the sexually dimorphic, estrogen-dependent expression of galanin in luteinizing hormone-releasing hormone neurons.

The incidence of colocalization of galanin (GAL) in luteinizing hormone-releasing hormone (LHRH) neurons is 4- to 5-fold higher in female than male rats. This fact and the finding that the degree of colocalization parallels estradiol levels during the estrous cycle suggest that GAL is an estrogen-inducible product in a subset of LHRH neurons. To analyze further this paradigm we evaluated the effects of gonadectomy and steroid replacement therapy in male and female rats. Ovariectomy resulted in a significant decrease in the number of cells colocalizing LHRH and GAL, whereas estradiol replacement to such animals restored the incidence of colocalization to that observed in controls. In males, however, estradiol treatment failed to enhance the incidence of colocalization of GAL and LHRH, indicating, therefore, that the colocalization of these peptides is gender-determined. This possibility--i.e., gender-specific determination of LHRH neurons coexpressing GAL--was evaluated by neonatal manipulation of hypothalamic steroid imprinting. As mentioned above, male rats did not respond to estrogen or testosterone by increasing GAL/LHRH colocalization as females did. Neonatally orchidectomized rats, whose hypothalami have not been exposed to testosterone during the critical period, when treated with estrogen in adulthood showed an increase in colocalization of GAL and LHRH similar to that seen in female animals. These observations indicate that the colocalization of LHRH/GAL is neonatally determined by an epigenetic mechanism that involves the testis. In summary, this sex difference in the incidence of colocalization of GAL and LHRH represents a unique aspect of sexual differentiation in that only certain phenotypic characteristics of a certain cellular lineage are dimorphic. The subpopulation of LHRH neurons that also produces GAL represents a portion of the LHRH neuronal system that is sexually differentiated and programed to integrate, under steroidal control, a network of LHRH neurons that could synchronize their activity to control the estrous cycle in rats.