18F-Sodium Fluoride Positron Emission Tomography/Computed Tomography in Ex Vivo Human Coronary Arteries With Histological Correlation.

OBJECTIVE: 18F-sodium fluoride (NaF) position emission tomography (PET) activity correlates with high-risk plaque. We examined the correlation between 18F-NaF PET activity and extent of calcification (microcalcification and macrocalcification) in coronary arteries. Approach and Results: Eighteen ex vivo human coronary arteries were imaged with 18F-NaF PET/CT, and target to background ratios were analyzed from 101 plaques. Histopathologic analysis evaluated for microcalcification and macrocalcification, plaque morphology, and inflammation. Plaques with microcalcification demonstrated higher 18F-NaF PET activity (n=84; mean target to background ratio±SD, 9.0±9.7,) than plaques without microcalcification (n=17, 2.9±3.8; P<0.0001). Higher 18F-NaF PET activity was associated with advanced plaques characterized by fibroatheroma (n=54, 10.7±10.3) compared with plaques with intimal thickening (n=22, 3.5±3.9) or pathological intimal thickening (n=25, 6.1±8.4; P=0.004). No significant association was found between 18F-NaF PET activity and inflammation (P=0.08). CONCLUSIONS: In ex vivo human coronary arteries, higher 18F-NaF PET activity was associated with microcalcification and advanced plaque morphology. Since microcalcification and fibroatheromas are high-risk plaque features, 18F-NaF PET/CT may improve risk-stratification.

Complex implementation factors demonstrated when evaluating cost-effectiveness and monitoring racial disparities associated with [18F]DCFPyL PET/CT in prostate cancer men.

Prostate cancer (PC) staging with conventional imaging often includes multiparametric magnetic resonance (MR) of the prostate, computed tomography (CT) of the chest, abdomen, and pelvis, and whole-body bone scintigraphy. The recent development of highly sensitive and specific prostate specific membrane antigen (PSMA) positron emission tomography (PET) has suggested that prior imaging techniques may be insufficiently sensitive or specific, particularly when evaluating small pathologic lesions. As PSMA PET/CT is considered to be superior for multiple clinical indications, it is being deployed as the new multidisciplinary standard-of-care. Given this, we performed a cost-effectiveness analysis of [18F]DCFPyL PSMA PET/CT imaging in the evaluation of PC relative to conventional imaging and anti-3-[18F]FACBC (18F-Fluciclovine) PET/CT. We also conducted a single institution review of PSMA PET/CT scans performed primarily for research indications from January 2018 to October 2021. Our snapshot of this period of time in our catchment demonstrated that PSMA PET/CT imaging was disproportionately accessed by men of European ancestry (EA) and those residing in zip codes associated with a higher median household income. The cost-effectiveness analysis demonstrated that [18F]DCFPyL PET/CT should be considered as an alternative to anti-3-[18F]FACBC PET/CT and standard of care imaging for prostate cancer staging. [18F]DCFPyL PET/CT is a new imaging modality to evaluate PC patients with higher sensitivity and specificity in detecting disease than other prostate specific imaging studies. Despite this, access may be inequitable. This discrepancy will need to be addressed proactively as the distribution network of the radiotracer includes both academic and non-academic sites nationwide.

Access to cardiac PET/CT by sarcoidosis patients and cost-effectiveness analysis of cardiac PET/MR compared to the standard of care.

IMPORTANCE: Cardiac sarcoidosis is associated with a high mortality rate. Given multiple barriers to obtaining cardiac PET imaging, we suspect individuals with access to this imaging modality are not representative of the Sarcoid patient population, which in the United States are predominantly Black females. OBJECTIVE: To evaluate the demographics of patients with cardiac PET access and the cost-effectiveness of cardiac PET/MR imaging relative to standard of care. DESIGN: This is a retrospective, observational study. The demographic information of patients with suspected cardiac sarcoidosis and cardiac PET/CT imaging within a national registry of sarcoidosis were reviewed (n = 4561). An individual-level, continuous, time-state transition model was used for the evaluation of long-term cost-effectiveness for the combined cardiac PET/MR compared to standard of care cardiac MR followed by cardiac PET/CT. RESULTS: Patients who underwent cardiac PET in the national registry had 88.35% higher odds of being male (p < 0.001) and 43.82% higher odds of being White (p = 0.003) than their counterparts who did not have cardiac PET imaging. Combined cardiac PET/MR had overall lower total lifetime costs ($8761 vs $10,777) and overall improved expected quality of life-years compared to the standard of care (0.77 vs 0.69). CONCLUSION AND RELEVANCE: The findings suggest that patients with access to cardiac PET/CT are not representative of the patient population most likely to have cardiac sarcoidosis in this limited study evaluation. Universal insurance coverage should be considered for Cardiac PET imaging as same day cardiac PET and MR imaging has potential long-term cost and quality of life benefit.

Serotonin-induced regulation of the actin network for learning-related synaptic growth requires Cdc42, N-WASP, and PAK in Aplysia sensory neurons.

Application of Clostridium difficile toxin B, an inhibitor of the Rho family of GTPases, at the Aplysia sensory to motor neuron synapse blocks long-term facilitation and the associated growth of new sensory neuron varicosities induced by repeated pulses of serotonin (5-HT). We have isolated cDNAs encoding Aplysia Rho, Rac, and Cdc42 and found that Rho and Rac had no effect but that overexpression in sensory neurons of a dominant-negative mutant of ApCdc42 or the CRIB domains of its downstream effectors PAK and N-WASP selectively reduces the long-term changes in synaptic strength and structure. FRET analysis indicates that 5-HT activates ApCdc42 in a subset of varicosities contacting the postsynaptic motor neuron and that this activation is dependent on the PI3K and PLC signaling pathways. The 5-HT-induced activation of ApCdc42 initiates reorganization of the presynaptic actin network leading to the outgrowth of filopodia, some of which are morphological precursors for the learning-related formation of new sensory neuron varicosities.

Metabolic Characterization of Inflammatory Breast Cancer With Baseline FDG-PET/CT: Relationship With Pathologic Response After Neoadjuvant Chemotherapy, Receptor Status, and Tumor Grade.

BACKGROUND: The aim of this study was to determine if, in inflammatory breast cancer (IBC), baseline metabolic activity (maximum standardized uptake value [SUVmax]) of primary tumor and involved regional lymph nodes (IRLN) are prognostic markers of response after neoadjuvant systemic therapy (NAS). PATIENTS AND METHODS: Baseline 2-deoxy-2-[18F]fluoro-D-glucose (FDG) positron emission tomography/computed tomography scans were retrospectively reviewed among 61 women with IBC who received NAS, had mastectomy, and had available pathology reports. Primary tumor and IRLN SUVmax were compared between patients with a pathologic complete response (pCR) versus those with residual disease after NAS. A multivariate Cox model was fit to evaluate the effects of SUVmax on overall survival, adjusting for pCR and stratified by receptor status and disease stage. RESULTS: SUVmax in primary IBC tumors tended to increase with tumor grade (trend test P = .06) and was lower for stage III, non-triple-negative (TN) versus stage III, TN and stage IV, non-TN disease (P = .04). Neither primary tumor nor IRLN SUVmax was significantly different comparing pCR versus residual disease after NAS. Adjusting for pathology response in the overall survival model stratified by stage and receptor status, baseline SUVmax in primary IBC tumor was associated with an estimated hazard ratio of 1.10 (95% confidence interval, 0.97-1.25; P = .15) for patients with stage III, TN and stage IV, non-TN disease. This hazard ratio corresponded to a 1.74-fold risk of death with 1 standard deviation (SD = 5.9) increase in baseline SUVmax in primary IBC tumor. CONCLUSION: 2-deoxy-2-[18F]fluoro-D-glucose positron emission tomography/computed tomography provides prognostic information for newly diagnosed IBC. Larger studies are needed to confirm these findings and assess how such early information could affect treatment choices for IBC in the neoadjuvant setting.

Presynaptic activation of silent synapses and growth of new synapses contribute to intermediate and long-term facilitation in Aplysia.

The time course and functional significance of the structural changes associated with long-term facilitation of Aplysia sensory to motor neuron synaptic connections in culture were examined by time-lapse confocal imaging of individual sensory neuron varicosities labeled with three different fluorescent markers: the whole-cell marker Alexa-594 and two presynaptic marker proteins-synaptophysin-eGFP to monitor changes in synaptic vesicle distribution and synapto-PHluorin to monitor active transmitter release sites. Repeated pulses of serotonin induce two temporally, morphologically, and molecularly distinct presynaptic changes: (1) a rapid activation of silent presynaptic terminals by filling of preexisting empty varicosities with synaptic vesicles, which parallels intermediate-term facilitation, is completed within 3-6 hr and requires translation but not transcription and (2) a slower generation of new functional varicosities which occurs between 12-18 hr and requires transcription and translation. Enrichment of empty varicosities with synaptophysin accounts for 32% of the newly activated synapses at 24 hr, whereas newly formed varicosities account for 68%.

Clinical spectrum of gross hematuria in pediatric patients.

Although isolated gross hematuria is a disturbing symptom, there have been few studies of this finding in pediatric patients. Therefore, this study was performed to examine the associated symptoms and causes of gross hematuria in children and adolescents who presented with this problem as their major clinical manifestation. It also determined the long-term outcome of patients in whom no etiology was found. A retrospective review was performed on the medical records of 100 consecutive patients referred for evaluation of gross hematuria between 1992 and 1999. The etiology was determined based on standard urinalysis methods, clinical laboratory tests, and imaging studies. Patients with gross hematuria in whom an etiology was not found were followed up through 2001. Of the 100 patient records reviewed, 18 were excluded because the clinical evaluation was incomplete. The remaining 82 patients (59 M: 23 F) had a mean age of 9.2 +/- 5.0 years. Glomerular gross hematuria was found in 24 patients. A cause was found in all of these patients, most commonly immunoglobulin A (IgA) nephropathy (n=13) and Alport syndrome (n=6). Nonglomerular gross hematuria was found in 56 patients, and the most common etiologies were hypercalciuria (n=9), urethrorrhagia (n=8), and hemorrhagic cystitis (n=7). No etiology was found in 26 patients with nonglomerular gross hematuria. No diagnosis was made in the case of 2 patients whose hematuria could not be defined as glomerular or nonglomerular. Telephone follow-up was performed in 18 of these children 4.0 +/- 3.2 years (range: 1-9 years) after the initial evaluation and showed that only 3 of these patients had had recurrences of gross hematuria. They and all of the other patients remained otherwise well. The urinalysis, including microscopic examination, was the most important diagnostic test in a patient with isolated gross hematuria. Nonglomerular problems were more than twice as common as glomerular diseases as a cause of isolated gross hematuria in pediatric patients The distribution of the etiologies of gross hematuria was consistent with previous studies. Although nearly half of the patients with nonglomerular gross hematuria could not be given a diagnosis, their long-term prognosis appeared to be good.

The more food young adults are served, the more they overeat.

Young and Nestle suggested that the increase in the portion size of food products evident in the United States during the past 20 years may be responsible for the epidemic of overweight and obesity. They based their conclusion on statistical correlations. The purpose of the present study was to provide experimental evidence to support their proposal. Cornell undergraduate students were given access to a buffet lunch on Monday, Wednesday, and Friday and were told this was a test of flavor enhancers. They were instructed to eat as much or as little as they wanted. On the same days of the following week, the subjects were divided into 3 groups. Each group was served either 100%, 125%, or 150% of the amount of food they had consumed the previous week. When larger amounts were served, significantly greater amounts of food were consumed. Each of the 4 foods that comprised the meal (soup, pasta, breadsticks, ice cream) increased significantly in proportion to the portion size. The data clearly support the hypothesis proposed by Young and Nestle and support the powerful role that environment plays in determining energy intake and potential increases in body weight.