Intraocular pressure (IOP) is believed to influence the mechanical properties of ocular tissues including cornea and sclera. The elastic properties of the crystalline lens have been mainly investigated with regard to presbyopia, the age-related loss of accommodation power of the eye. However, the relationship between the elastic properties of the lens and IOP remains to be established. The objective of this study is to measure the elastic wave velocity, which represents the mechanical properties of tissue, in the crystalline lens ex vivo in response to changes in IOP. The elastic wave velocities in the cornea and lens from seven enucleated bovine globe samples were estimated using ultrasound shear wave elasticity imaging. To generate and then image the elastic wave propagation, an ultrasound imaging system was used to transmit a 600 µs pushing pulse at 4.5 MHz center frequency and to acquire ultrasound tracking frames at 6 kHz frame rate. The pushing beams were separately applied to the cornea and lens. IOP in the eyeballs was varied from 5 to 50 mmHg. The results indicate that while the elastic wave velocity in the cornea increased from 0.96 ± 0.30 m s−1to 6.27 ± 0.75 m s−1as IOP was elevated from 5 to 50 mmHg, there were insignificant changes in the elastic wave velocity in the crystalline lens with the minimum and the maximum speeds of 1.44 ± 0.27 m s−1and 2.03 ± 0.46 m s−1, respectively. This study shows that ultrasound shear wave elasticity imaging can be used to assess the biomechanical properties of the crystalline lens noninvasively. Also, it was observed that the dependency of the crystalline lens stiffness on the IOP was significantly lower in comparison with that of cornea.
Purpose: To develop and validate the Pediatric Risk Estimation Score for Children Using Extracorporeal Respiratory Support (Ped-RESCUERS). Ped-RESCUERS is designed to estimate the in-hospital mortality risk for children prior to receiving respiratory extracorporeal membrane oxygenation (ECMO) support. Methods: This study used data from an international registry of patients aged 29 days to less than 18 years who received ECMO support from 2009 to 2014. We divided the registry into development and validation datasets by calendar date. Candidate variables were selected for model inclusion if the variable independently changed the mortality risk by at least 2 % in a Bayesian logistic regression model with in-hospital mortality as the outcome. We characterized the model’s ability to discriminate mortality with the area under curve (AUC) of the receiver operating characteristic. Results: From 2009 to 2014, 2458 non-neonatal children received ECMO for respiratory support, with a mortality rate of 39.8 %. The development dataset contained 1611 children receiving ECMO support from 2009 to 2012. The model included the following variables: pre-ECMO pH, pre-ECMO arterial partial pressure of carbon dioxide, hours of intubation prior to ECMO support, hours of admission at ECMO center prior to ECMO support, ventilator type, mean airway pressure, pre-ECMO use of milrinone, and a diagnosis of pertussis, asthma, bronchiolitis, or malignancy. The validation dataset included 438 children receiving ECMO support from 2013 to 2014. The Ped-RESCUERS model from the development dataset had an AUC of 0.690, and the validation dataset had an AUC of 0.634. Conclusions: Ped-RESCUERS provides a novel measure of pre-ECMO mortality risk. Future studies should seek external validation and improved discrimination of this mortality prediction tool.
by
Rine Nakanishi;
Heidi Gransar;
Piotr Slomka;
Reza Arsanjani;
Aryeh Shalev;
Yuka Otaki;
John D. Friedman;
Sean W. Hayes;
Louise E. B. Thomson;
Mathews Fish;
Guido Germano;
Aiden Abidov;
Leslee J Shaw;
Alan Rozanski;
Daniel S. Berman
Background: While uncommon, normal stress SPECT myocardial perfusion imaging (MPI) can be seen in patients with high-risk coronary artery disease (CAD) by invasive coronary angiography (ICA).The predictors of high-risk CAD in patients with normal SPECT-MPI have not been described. Methods: We studied 580 patients (age 64 ± 12 years, 49% men) without known CAD who underwent stress-gated SPECT-MPI [exercise (41%) or vasodilator (59%)] <2 months before ICA and had summed stress score (SSS) <4. High-risk CAD was defined as 3 vessels with ≥70% stenosis, 2 vessels with ≥70% stenosis including proximal left anterior descending, or left main with ≥50% stenosis. Obstructive non-high-risk CAD was defined by the presence of a ≥70% stenosis but without having other high-risk criteria. Tenfold cross-validated receiver operating characteristic (ROC) estimates were obtained to assess the predictors of high-risk CAD. Results: Forty-two subjects (7.2%) had high-risk CAD and 168 (29.0%) had obstructive non-high-risk CAD. Variables associated with high-risk CAD were pretest probability of CAD ≥66% (Odds ratio [OR] 3.63, 95% CI 1.6-8.3, P = .002), SSS > 0 (OR 7.46, 95% CI 2.6-21.1, P < 0.001), and abnormal TID (OR 2.16, 95% CI 1.0-4.5, P = 0.044). When substituted for TID, EF change was also predictive of high-risk CAD (OR 0.93, 95% CI 0.9-1.0, P = 0.023). The prevalence of high-risk CAD increased as the number of these predictors increased. In a sub-analysis of patients in whom quantitative total perfusion deficit (TPD) was available, TPD > 0 was also a predictor of high-risk CAD (OR 6.01, 95% CI 1.5-22.2, P = 0.011). Conclusion: Several clinical, stress, and SPECT-MPI findings are associated high-risk CAD among patients with normal SPECT-MPI. Consideration of these factors may improve the overall assessment of the likelihood of high-risk CAD in patients undergoing stress SPECT-MPI.
Purpose 18 F-Fluciclovine (anti-1-amino-3-[ 18 F]fluorocyclobutane-1-carboxylic acid) is a novel positron emission tomography (PET)/computed tomography (CT) radiotracer that has demonstrated utility for detection of prostate cancer. Our goal is to report the initial results from a randomized controlled trial of the integration of 18 F-fluciclovine PET-CT into treatment planning for defining prostate bed and lymph node target volumes. Methods and Materials We report our initial findings from a cohort of 41 patients, of the first enrolled on a randomized controlled trial, who were randomized to the 18 F-fluciclovine arm. All patients underwent 18 F-fluciclovine PET-CT for the detection of metabolic abnormalities and high-resolution CT for treatment planning. The 2 datasets were registered first by use of a rigid registration. If soft tissue displacement was observable, the rigid registration was improved with a deformable registration. Each 18 F-fluciclovine abnormality was segmented as a percentage of the maximum standard uptake value (SUV) within a small region of interest around the lesion. The percentage best describing the SUV falloff was integrated in planning by expanding standard target volumes with the PET abnormality. Results In 21 of 55 abnormalities, a deformable registration was needed to map the 18 F-fluciclovine activity into the simulation CT. The most selected percentage was 50% of maximum SUV, although values ranging from 15% to 70% were used for specific patients, illustrating the need for a per-patient selection of a threshold SUV value. The inclusion of 18 F-fluciclovine changed the planning volumes for 46 abnormalities (83%) of the total 55, with 28 (51%) located in the lymph nodes, 11 (20%) in the prostate bed, 10 (18%) in the prostate, and 6 (11%) in the seminal vesicles. Only 9 PET abnormalities were fully contained in the standard target volumes based on the CT-based segmentations and did not necessitate expansion. Conclusions The use of 18 F-fluciclovine in postprostatectomy radiation therapy planning was feasible and led to augmentation of the target volumes in the majority (30 of 41) of the patients studied.
Objective We examined Vaccine Information Statements (VIS) dissemination practices and parental use and perceptions. Methods We conducted a national online panel survey of 2603 US parents of children aged <7. Primary outcomes included reported VIS receipt, delivery timing, reading experiences, and perceived utility. Results Most parents received a VIS (77.2%; [95% CI: 74.5–79.7%]), 59.7% [56.6–62.7%] before vaccination but 14.5% [12.5–16.8%] reported receiving it after their child's immunization; 15.1% [13.0–17.6%] were unsure of receipt status or timing; another 10.7% [9.0–12.6%] reported non-receipt of a VIS. Less than half who received a VIS before vaccination completed it before vaccination (46.2% [42.4, 50.0%]), but most who read at least some found the information useful (95.7% [93.8–97.0%]). Parents who delayed or refused at least one recommended non-influenza vaccine reported fewer opportunities to ask providers VIS questions. Conclusions Most parents report receiving VIS before vaccination as per federal guidelines. Continued effort is needed to enhance VIS distribution practice and parent-provider VIS content communication.
Objective Understanding the current status of parents’ vaccine decision making is crucial to inform public policy. We sought to assess changes in vaccine decisions among parents of young children. Methods We conducted a web-based national poll of parents of children <7 years in 2012 and 2014. Participants reported vaccine decisions for their youngest child. We calculated survey-weighted population estimates of overall immunizations decisions, and delay/refusal rates for specific vaccines. Results In 2012, 89.2% (95% CI, 87.3–90.8%) reported accepting or planning to accept all recommended non-influenza childhood vaccines, 5.5% (4.5–6.6%) reported intentionally delaying one or more, and 5.4% (4.1–6.9%) reported refusing one or more vaccines. In 2014, the acceptance, delay, and refusal rates were 90.8% (89.3–92.1%), 5.6% (4.6–6.9%), and 3.6% (2.8–4.5%), respectively. Between 2012 and 2014, intentional vaccine refusal decreased slightly among parents of older children (2–6 years) but not younger children (0–1 years). The proportion of parents working to catch up on all vaccines increased while those refusing some but not all vaccines decreased. The South experienced a significant increase in estimated acceptance (90.1–94.1%) and a significant decrease in intentional ongoing refusal (5.0–2.1%). Vaccine delay increased in the Northeast (3.2–8.8%). Conclusions Nationally, acceptance and ongoing intentional delay of recommended non-influenza childhood vaccines were stable. These findings suggest that more effort is warranted to counter persistent vaccine hesitancy, particularly at the local level. Longitudinal monitoring of immunization attitudes is also warranted to evaluate temporal shifts over time and geographically.
Conventional anatomical imaging with CT and MRI has limitations in the evaluation of prostate cancer. PET is a powerful imaging technique, which can be directed toward molecular targets as diverse as glucose metabolism, density of prostate-specific membrane antigen receptors, and skeletal osteoblastic activity. Although 2-deoxy-2- 18 F-FDG-PET is the mainstay of molecular imaging, FDG has limitations in typically indolent prostate cancer. Yet, there are many useful and emerging PET tracers beyond FDG, which provide added value. These include radiotracers interrogating prostate cancer via molecular mechanisms related to the biology of choline, acetate, amino acids, bombesin, and dihydrotestosterone, among others. Choline is used for cell membrane synthesis and its metabolism is upregulated in prostate cancer. 11 C-choline and 18 F-choline are in wide clinical use outside the United States, and they have proven most beneficial for detection of recurrent prostate cancer. 11 C-acetate is an indirect biomarker of fatty acid synthesis, which is also upregulated in prostate cancer. Imaging of prostate cancer with 11 C-acetate is overall similar to the choline radiotracers yet is not as widely used. Upregulation of amino acid transport in prostate cancer provides the biologic basis for amino acid–based radiotracers. Most recent progress has been made with the nonnatural alicyclic amino acid analogue radiotracer anti-1-amino-3- 18 F-fluorocyclobutane-1-carboxylic acid (FACBC or fluciclovine) also proven most useful for the detection of recurrent prostate cancer. Other emerging PET radiotracers for prostate cancer include the bombesin group directed to the gastrin-releasing peptide receptor, 16β- 18 F-fluoro-5α-dihydrotestosterone (FDHT) that binds to the androgen receptor, and those targeting the vasoactive intestinal polypeptide receptor 1 (VPAC-1) and urokinase plasminogen activator receptor (uPAR), which are also overexpressed in prostate cancer.
AIM: This study evaluates the effect of dapagliflozin, a SGLT2 inhibitor, on fluid or electrolyte balance and its effect on urea transporter-A1 (UT-A1), aquaporin-2 (AQP2) and Na-K-2Cl cotransporter (NKCC2) protein abundance in diabetic rats. METHODS: Diabetes mellitus (DM) was induced by injection of streptozotocin into the tail vein. Serum Na+, K+, Cl- concentration, urine Na+, K+, Cl- excretion, blood glucose, urine glucose excretion, urine volume, urine osmolality and urine urea excretion were analyzed after the administration of dapagliflozin. UT-A1, AQP2 and NKCC2 proteins were detected by western blot. RESULTS: Dapagliflozin treatment decreased blood glucose concentration by 38% at day 7 and by 47% at day 14 and increased the urinary glucose excretion rate compared with the untreated diabetic animals. Increased 24-hour urine volume, decreased urine osmolality and hyponatremia, hypokalemia and hypochloremia observed in diabetic rats were attenuated by dapagliflozin treatment. Western blot analysis showed that UT-A1, AQP2 and NKCC2 proteins are upregulated in DM rats over control rats; dapagliflozin treatment results in a further increase in inner medulla tip UT-A1 protein abundance by 42% at day 7 and by 46% at day 14, but it did not affect the DM-induced upregulation of AQP2 and NKCC2 proteins. CONCLUSION: Dapagliflozin treatment augmented the compensatory changes in medullary transport proteins in DM. These changes would tend to conserve solute and water even with persistent glycosuria. Therefore, diabetic rats treated with dapagliflozin have a mild osmotic diuresis compared to nondiabetic animals, but this does not result in an electrolyte disorder or significant volume depletion.
Th17 cells represent a distinct subset of CD4 + effector T cells with potent pathogenic qualities, capable of directly mediating tumor cell destruction. IL-2 has frequently been shown to have a negative effect on Th17 differentiation while supporting regulatory T-cell (FoxP3 + CD4 + , T REG ) growth and development in both in vitro models and in vivo animal models. We investigated the effect of in vivo IL-2 on both the Th17 and FoxP3 + CD4 + T-cell compartments in a human model of cancer. High-dose IL-2 (HDIL-2) was administered at a dose of 720,000 IU/kg to patients with melanoma (n=7) and peripheral blood was collected at baseline and at 24, 48, 72, and 96 hours posttreatment. Peripheral blood mononuclear cells (PBMCs) were isolated and subjected to intracellular cytokine and extracellular receptor staining for flow cytometry. We report that HDIL-2 increased both frequencies and absolute numbers of Th17 cells on day 4 of treatment. The administration of HDIL-2 to patients with melanoma increased IL- 6 production by peripheral immune cells, a cytokine vital in the downregulation of FoxP3 expression and expansion of the Th17- cell population. Furthermore, we demonstrated that FoxP3 + CD4 + T cells express IL-17 in patients with melanoma undergoing HDIL-2 therapy. Taken together, our findings indicate that HDIL- 2 combined with the conditions of malignancy create an immune environment supportive of Th17 differentiation and that expansion of this compartment may occur through the transdifferentiation of IL-17-secreting FoxP3 + CD4 + T cells.