Evidence-Based Medicine for Nonsurgical Facial Rejuvenation.

Options for nonsurgical facial rejuvenation treatment have increased significantly in both availability and popularity over the past two decades. However, there remains a paucity of clinical practice guidelines and evidence-based recommendations for these procedures. The purpose of this article is to assess the presence of current high-level research for various methods of nonsurgical facial rejuvenation using the Oxford Centre for Evidence-Based Medicine. Botulinum toxin injections remain the best-studied method, with several randomized controlled trials guiding recommendations for safety and efficacy. Several studies on injectable fillers document complications and recommendations to avoid these, but sample sizes are small and many are noncomparative. Deoxycholic acid has been well examined and Food and Drug Administration approved to address submental fat but has not been studied in other areas of the face. Although chemical peels, laser skin resurfacing, energy-based facial rejuvenation, microneedling, and platelet-rich plasma have a variety of facial rejuvenation applications with minimal side effect profiles, there is significant variability with treatment protocols, outcomes measures, and randomized controlled trials with extended follow-up to develop clinical practice guidelines.

Evaluation of (89)Zr-pertuzumab in Breast cancer xenografts.

Pertuzumab is a monoclonal antibody that binds to HER2 and is used in combination with another HER2-specific monoclonal antibody, trastuzumab, for the treatment of HER2+ metastatic breast cancer. Pertuzumab binds to an HER2 binding site distinct from that of trastuzumab, and its affinity is enhanced when trastuzumab is present. We aim to exploit this enhanced affinity of pertuzumab for its HER2 binding epitope and adapt this antibody as a PET imaging agent by radiolabeling with (89)Zr to increase the sensitivity of HER2 detection in vivo. Here, we investigate the biodistribution of (89)Zr-pertuzumab in HER2-expressing BT-474 and HER2-nonexpressing MDA-MB-231 xenografts to quantitatively assess HER2 expression in vivo. In vitro cell binding studies were performed resulting in retained immunoreactivity and specificity for HER2-expressing cells. In vivo evaluation of (89)Zr-pertuzumab was conducted in severely combined immunodeficient mice, subcutaneously inoculated with BT-474 and MDA-MB-231 cells. (89)Zr-pertuzumab was systemically administered and imaged at 7 days postinjection (p.i.) followed by terminal biodistribution studies. Higher tumor uptake was observed in BT-474 compared to MDA-MB-231 xenografts with 47.5 ± 32.9 and 9.5 ± 1.7% ID/g, respectively at 7 days p.i (P = 0.0009) and blocking studies with excess unlabeled pertuzumab showed a 5-fold decrease in BT-474 tumor uptake (P = 0.0006), confirming the in vivo specificity of this radiotracer. Importantly, we observed that the tumor accumulation of (89)Zr-pertuzumab was increased in the presence of unlabeled trastuzumab, at 173 ± 74.5% ID/g (P = 0.01). Biodistribution studies correlate with PET imaging quantification using max SUV (r = 0.98, P = 0.01). Collectively, these results illustrate that (89)Zr-pertuzumab as a PET imaging agent may be beneficial for the quantitative and noninvasive assessment of HER2 expression in vivo especially for patients undergoing trastuzumab therapy.

United States emergency department visits for children with cerebrospinal fluid shunts.

OBJECTIVE: CSF shunt placement is the primary therapy for hydrocephalus; however, shunt malfunctions remain common and lead to neurological deficits if missed. There is a lack of literature characterizing the epidemiology of children with possible shunt malfunctions presenting to United States emergency departments (EDs). METHODS: A retrospective study was conducted of the 2006-2017 National Emergency Department Sample. The data were queried using an exhaustive list of Current Procedural Terminology and International Classification of Diseases, Ninth Revision and International Classification of Diseases, Tenth Revision codes representing children with hydrocephalus diagnoses, diagnostic imaging for shunt malfunctions, and shunt-related surgical revision procedures. RESULTS: In 2017, there were an estimated 16,376 ED visits for suspected shunt malfunction. Children were more commonly male (57.9%), ages 0-4 years (42.2%), and publicly insured (55.8%). Many did not undergo diagnostic imaging (37.2%), and of those who did, most underwent head CT scans (43.7%). Between 2006 and 2017, pediatric ED visits for suspected shunt malfunction increased 18% (95% CI 12.1-23.8). The use of MRI increased substantially (178.0%, 95% CI 176.9-179.2). Visits resulting in discharge home from the ED increased by 76.3% (95% CI 73.1-79.4), and those involving no surgical intervention increased by 32.9% (95% CI 29.2-36.6). CONCLUSIONS: Between 2006 and 2017, ED visits for children to rule out shunt malfunction increased, yet there was a decline in surgical intervention and an increase in discharges home from the ED. Possible contributing factors include improved clinical criteria for shunt evaluation, alternative CSF diversion techniques, changing indications for shunt placement, and increased use of advanced imaging in the ED. ABBREVIATIONS: CPT = Current Procedural Terminology; ED = emergency department; ETV = endoscopic third ventriculostomy; ICD-9 = International Classification of Diseases, Ninth Revision; ICD-10 = International Classification of Diseases, Tenth Revision; NEDS = National Emergency Department Sample.

Comparing cortical signatures of atrophy between late-onset and autosomal dominant Alzheimer disease.

Defining a signature of cortical regions of interest preferentially affected by Alzheimer disease (AD) pathology may offer improved sensitivity to early AD compared to hippocampal volume or mesial temporal lobe alone. Since late-onset Alzheimer disease (LOAD) participants tend to have age-related comorbidities, the younger-onset age in autosomal dominant AD (ADAD) may provide a more idealized model of cortical thinning in AD. To test this, the goals of this study were to compare the degree of overlap between the ADAD and LOAD cortical thinning maps and to evaluate the ability of the ADAD cortical signature regions to predict early pathological changes in cognitively normal individuals. We defined and analyzed the LOAD cortical maps of cortical thickness in 588 participants from the Knight Alzheimer Disease Research Center (Knight ADRC) and the ADAD cortical maps in 269 participants from the Dominantly Inherited Alzheimer Network (DIAN) observational study. Both cohorts were divided into three groups: cognitively normal controls (nADRC = 381; nDIAN = 145), preclinical (nADRC = 153; nDIAN = 76), and cognitively impaired (nADRC = 54; nDIAN = 48). Both cohorts underwent clinical assessments, 3T MRI, and amyloid PET imaging with either 11C-Pittsburgh compound B or 18F-florbetapir. To generate cortical signature maps of cortical thickness, we performed a vertex-wise analysis between the cognitively normal controls and impaired groups within each cohort using six increasingly conservative statistical thresholds to determine significance. The optimal cortical map among the six statistical thresholds was determined from a receiver operating characteristic analysis testing the performance of each map in discriminating between the cognitively normal controls and preclinical groups. We then performed within-cohort and cross-cohort (e.g. ADAD maps evaluated in the Knight ADRC cohort) analyses to examine the sensitivity of the optimal cortical signature maps to the amyloid levels using only the cognitively normal individuals (cognitively normal controls and preclinical groups) in comparison to hippocampal volume. We found the optimal cortical signature maps were sensitive to early increases in amyloid for the asymptomatic individuals within their respective cohorts and were significant beyond the inclusion of hippocampus volume, but the cortical signature maps performed poorly when analyzing across cohorts. These results suggest the cortical signature maps are a useful MRI biomarker of early AD-related neurodegeneration in preclinical individuals and the pattern of decline differs between LOAD and ADAD.

Spatial patterns of neuroimaging biomarker change in individuals from families with autosomal dominant Alzheimer's disease: a longitudinal study.

BACKGROUND: Models of Alzheimer's disease propose a sequence of amyloid ß (Aß) accumulation, hypometabolism, and structural decline that precedes the onset of clinical dementia. These pathological features evolve both temporally and spatially in the brain. In this study, we aimed to characterise where in the brain and when in the course of the disease neuroimaging biomarkers become abnormal. METHODS: Between Jan 1, 2009, and Dec 31, 2015, we analysed data from mutation non-carriers, asymptomatic carriers, and symptomatic carriers from families carrying gene mutations in presenilin 1 (PSEN1), presenilin 2 (PSEN2), or amyloid precursor protein (APP) enrolled in the Dominantly Inherited Alzheimer's Network. We analysed 11C-Pittsburgh Compound B (11C-PiB) PET, 18F-Fluorodeoxyglucose (18F-FDG) PET, and structural MRI data using regions of interest to assess change throughout the brain. We estimated rates of biomarker change as a function of estimated years to symptom onset at baseline using linear mixed-effects models and determined the earliest point at which biomarker trajectories differed between mutation carriers and non-carriers. This study is registered at ClinicalTrials.gov (number NCT00869817) FINDINGS: 11C-PiB PET was available for 346 individuals (162 with longitudinal imaging), 18F-FDG PET was available for 352 individuals (175 with longitudinal imaging), and MRI data were available for 377 individuals (201 with longitudinal imaging). We found a sequence to pathological changes, with rates of Aß deposition in mutation carriers being significantly different from those in non-carriers first (across regions that showed a significant difference, at a mean of 18·9 years [SD 3·3] before expected onset), followed by hypometabolism (14·1 years [5·1] before expected onset), and lastly structural decline (4·7 years [4·2] before expected onset). This biomarker ordering was preserved in most, but not all, regions. The temporal emergence within a biomarker varied across the brain, with the precuneus being the first cortical region for each method to show divergence between groups (22·2 years before expected onset for Aß accumulation, 18·8 years before expected onset for hypometabolism, and 13·0 years before expected onset for cortical thinning). INTERPRETATION: Mutation carriers had elevations in Aß deposition, reduced glucose metabolism, and cortical thinning compared with non-carriers which preceded the expected onset of dementia. Accrual of these pathologies varied throughout the brain, suggesting differential regional and temporal vulnerabilities to Aß, metabolic decline, and structural atrophy, which should be taken into account when using biomarkers in a clinical setting as well as designing and evaluating clinical trials. FUNDING: US National Institutes of Health, the German Center for Neurodegenerative Diseases, and the Medical Research Council Dementias Platform UK.