Prognostic Scoring System for Patients Undergoing Reconstructive Foot and Ankle Surgery for Charcot Neuroarthropathy: The Charcot Reconstruction Preoperative Prognostic Score

Charcot neuroarthropathy is a destructive process that occurs in patients with peripheral neuropathy, often due to poorly controlled diabetes mellitus. Surgical reconstruction can be necessary to provide a plantigrade foot that is wound free. A risk of major amputation exists after a Charcot event and after attempted reconstruction. We retrospectively reviewed the data from 34 patients (36 reconstructions) who had undergone reconstructive surgery for Charcot neuroarthropathy. The mean patient age was 56.44 years. The mean follow-up period was 56 months. We collected patient age, body mass index, presence of wound or osteomyelitis, anatomic location, activity of disease, and hemoglobin A1c. Using these data, each patient was given a score using our novel prognostic scoring system, the Charcot Reconstruction Preoperative Prognostic Score (CRPPS). Our primary outcome measure was no wound and no major amputation at the final follow-up visit. The limb salvage rate was 89% (32 of 36), and 78% (28 of 36) had no wound at the final follow-up examination. For patients without a wound or major amputation at the final follow-up visit, the mean CRPPS was 2.96?±?1.23. The mean CRPPS for those with a wound or major amputation at the final follow-up visit was 4.33?±?1.07 (p?=?.0024). Univariate logistic regression revealed 2 statistically significant predictors of wound and/or amputation: anatomic location (odds ratio [OR] 5.0, 95% confidence interval [CI] 1.051 to 23.789; p?=?.043) and CRPPS (OR 2.724, 95% CI 1.274 to 5.823, p?=?.01). A CRPPS of ≥4 was also predictive of a negative outcome (OR 7.286, 95% CI 1.508 to 35.211; p?=?.013). This scoring system, with a sensitivity of 75%, specificity of 71%, and negative predictive value of 85%, is a potential starting point when educating patients and making treatment decisions in this exceptionally challenging group.     

Enzymic degradation of a beta-lactam antibiotic,ampicillin, in the gut: a novel treatment modality

Antibiotics can cause severe alterations in the gut microflora and promote diarrhoea and overgrowth of pathogenic bacteria. The present study investigated the potency of targeted recombinant beta-lactamase (TRBL) to degrade a beta-lactam antibiotic in the jejunum of fistula-operated beagles. We used different peroral doses of purified beta-lactamase (PenP) of Bacillus licheniformis in enteric-coated pellets together with intravenous ampicillin. Serum and jejunal samples were collected for ampicillin and beta-lactamase analysis. A dose-response effect of TRBL on ampicillin concentrations in the jejunal samples could be observed. The highest doses applied decreased the jejunal ampicillin concentrations to undetectable levels. In the serum samples, the ampicillin concentrations were not affected by the beta-lactamase dose used. Our results indicate that it may be possible to evolve a targeted treatment to degrade beta-lactam antibiotics intestinally and, thus, decrease antibiotic-induced adverse effects on the gut microflora.     

Implementing a Measurement Feedback System: A Tale of Two Sites

A randomized experiment was conducted in two outpatient clinics evaluating a measurement feedback system called contextualized feedback systems. The clinicians of 257 Youth 11–18 received feedback on progress in mental health symptoms and functioning either every 6 months or as soon as the youth’s, clinician’s or caregiver’s data were entered into the system. The ITT analysis showed that only one of the two participating clinics (Clinic R) had an enhanced outcome because of feedback, and only for the clinicians’ ratings of youth symptom severity on the SFSS. A dose–response effect was found only for Clinic R for both the client and clinician ratings. Implementation analyses showed that Clinic R had better implementation of the feedback intervention. Clinicians’ questionnaire completion rate and feedback viewing at Clinic R were 50 % higher than clinicians at Clinic U. The discussion focused on the differences in implementation at each site and how these differences may have contributed to the different outcomes of the experiment.     

Effect of multiple activation stimuli on the generation of Th1-polarizing dendritic cells

It was originally reported that only a small fraction of total matured dendritic cells (DCs) produced interleukin (IL)-12, but it has never been determined whether different combinations of activating signals now shown to maximize secreted IL-12 do so through increasing output by the same IL-12 producers, or by recruiting additional cytokine-secreting cells. We therefore tested all combinations of bacterial lipopolysaccharide (LPS) (TLR4 ligand), R848 (TLR8 ligand), interferon (IFN)-γ, and CD40L for activating human monocyte-derived dendritic cells (DC), and determined by intracellular flow cytometry that enhanced IL-12 secretion was accomplished in large part by markedly increasing the proportion of cells producing IL-12, with the triple and quadruple combinations recruiting the most DC. This optimization requirement for multiple signals was not reflected in differential Toll-like receptor (TLR) expression by the cells. Interestingly, DCs activated with single TLR ligands plus IFN-γ were capable of responding with a second burst of IL-12 upon later CD40L stimulation, whereas DCs activated with R848 plus LPS were not, despite the trend of the latter for superior polarization of naive T cells toward IFN-γ-secreting Th1. These results have implications for the biology of IL-12-secreting DCs and choice of activation regimen for prospective use in DC-based immunotherapy.     

DeltaA mRNA and protein distribution in the zebrafish nervous system

Physical interaction between the transmembrane proteins Delta and Notch allows only a subset of neural precursors to become neurons, as well as regulating other aspects of neural development. To examine the localization of Delta protein during neural development, we generated an antibody specific to zebrafish DeltaA (Dla). Here, we describe for the first time the subcellular localization of Dla protein in distinct puncta at cell cortex and/or membrane, supporting the function of Dla in direct cell–cell communication. In situ RNA hybridization and immunohistochemistry revealed dynamic, coordinated expression patterns of dla mRNA and Dla protein in the developing and adult zebrafish nervous system. Dla expression is mostly excluded from differentiated neurons and is maintained in putative precursor cells at least until larval stages. In the adult brain, dla mRNA and Dla protein are expressed in proliferative zones normally associated with stem cells. Developmental Dynamics 238:3226–3336, 2009. © 2009 Wiley‐Liss, Inc.     

Long-term Functional and Quality of Life Outcomes of Patients After Repair of Large Perianal Skin Defects for Paget’s and Bowen’s Disease

Introduction  

The assessment of long- term functional and quality of life outcomes of these patients following repair of large defects after surgical excision has not been reported.     

The Role of Lymph Node Metastasis in the Systemic Dissemination of Breast Cancer

Background  

Lymphatic invasion is necessary for regional lymph node (RLN) metastasis in breast cancer (BC), while systemic metastasis requires blood vessel (BV) invasion. The site of BV invasion could be at the primary BC site or through lymphovascular anastomoses. The vague pathologic term “lymphovascular invasion” (LVI) encourages the belief that peri/intratumoral BV invasion may be common. We investigated the relative contribution of RLN metastasis to systemic metastasis by studying the relationship among LVI and RLN and/or systemic metastasis in a population-based cohort of breast cancer patients.     

Niaspan increases angiogenesis and improves functional recovery after stroke

OBJECTIVE: High-density lipoprotein (HDL) is implicated in the modulation of angiogenesis. In this study, we investigated whether the Niacin-mediated increase of HDL regulates angiogenesis and thereby improves functional outcome after stroke. METHODS: Adult male rats were subjected to middle cerebral artery occlusion and were treated with or without different doses (40 and 80 mg/kg) of Niaspan, starting 24 hours after middle cerebral artery occlusion and daily for 14 days. Neurological functional tests were performed, and serum HDL level was measured. Angiogenesis and angiogenic factor expression were measured by immunohistochemistry, corneal neovascularization and capillary tube formation assay, and Western blot, respectively. RESULTS: Niaspan significantly increased HDL level, promoted angiogenesis in the ischemic brain, and improved functional outcome after stroke. Niaspan also significantly increased corneal neovascularization compared with nontreatment control. Mechanisms underlying the Niaspan-induced vascular remodeling were investigated. Niaspan increased the expression of vascular endothelial growth factor and angiopoietin-1 (Ang1), and phosphorylation of Akt, endothelial nitric oxide synthase (NOS), and Tie2 in the ischemic brain. Niacin upregulated Ang1 expression in cultured brain endothelial cells and increased vascular endothelial growth factor, Ang1, and endothelial NOS expression in cultured astrocytes, and dose-dependently increased capillary tube formation compared with nontreatment control. Inhibition of NOS partially decreased Niacin-induced capillary tube formation. Inhibition of phosphoinositide 3-kinase or knockdown of Tie2 substantially and significantly decreased Niacin-induced capillary tube formation. INTERPRETATION: Niacin increases HDL and promotes angiogenesis, which may contribute to improvement of functional outcome after stroke. The Ang1/Tie2, phosphoinositide 3-kinase/Akt, and endothelial NOS pathways appear to mediate Niacin-induced angiogenesis.     

Rate of cognitive change measured by neuropsychologic test performance in 3 distinct dementia syndromes

Progressive decline in cognition is a hallmark feature of dementia, and the rate and profile of cognitive decline has been well characterized in Alzheimer disease (AD). Less is known about decline in cognition over time in other forms of dementia such as the behavioral variant of frontotemporal dementia (FTD) and primary progressive aphasia (PPA). The present study examined rate of cognitive decline across domains of memory, language, and executive function measured by neuropsychologic tests, in AD (n=84), FTD (n=66), and PPA (n=44). Patients were in the mild stages of dementia, with comparable duration of illness at the baseline evaluation. A best linear unbiased predictor (BLUP) analysis was used in which the slope of the relationship between a cognitive measure and time was estimated for each person. AD subjects demonstrated a floor effect on measures of memory at baseline and a decline on measures of language and executive functioning over time. FTD showed the greatest decline over time on the Mini-Mental State Examination, executive functioning, and naming. PPA patients demonstrated prominent decline on language measures, verbal memory measures, and attention. Results suggest that the profile of rate of change over time has unique features on the basis of the type of dementia syndrome. However, there is overlap in the profiles of decline likely influenced by the overlap in cognitive constructs measured by neuropsychologic tests. The comparison of the rate of decline in FTD and PPA may also reflect the neuroanatomic overlap in these syndromes over time.     

A comparison of veteran and nonveteran motivations and reasons for participating in clinical trials

OBJECTIVE: Knowledge of distinct motivations and reasons toward or against future trial participation is invaluable to any organization conducting trial research. Study delays often occur due to lack of recruitment. This study's primary objective was to compare veteran and nonveteran motivations and reasons. METHODS: People in two outpatient waiting rooms were approached. The questionnaire assessed motivation toward trial involvement through use of five-point Likert-type scales and hypothetical trial scenarios; it also analyzed reasons for participation through subject ranking of reasons. RESULTS: Veterans were more likely to participate in a trial in which all participants received the active treatment (p = 0.025). Veterans had different reasons for participation than nonveterans. Specifically, veterans felt altruism and "paying back" people who treated them were more important (p = 0.024 and p = 0.003) while financial compensation for volunteering was less important (p < 0.001). CONCLUSIONS: Knowledge of the varying reasons for participation could potentially aid recruitment efforts.