Hypophosphatemia after high-dose iron repletion with ferric carboxymaltose and ferric derisomaltose-the randomized controlled HOMe aFers study.

BACKGROUND: In patients with iron deficiency anemia, ferric carboxymaltose (FCM) and ferric derisomaltose (FDI) allow high-dose iron repletion. While FCM is reported to induce hypophosphatemia, the frequency of hypophosphatemia after an equivalent dosage of FDI had not been assessed prospectively. METHODS: In the prospective, single-center, double-blind HOMe aFers study, 26 women with iron deficiency anemia (hemoglobin < 12 g/dL plus either plasma ferritin ≤ 100 ng/mL or a plasma ferritin ≤ 300 ng/mL and transferrin saturation (TSAT) ≤ 30%) were randomized to a single intravenous infusion of 20 mg/kg body weight (up to a maximum of 1000 mg) FCM or FDI. The primary endpoint was the incidence of hypophosphatemia (plasma phosphorus levels < 2.0 mg/dL at day 1, day 7 ± 2, and/or day 35 ± 2 after the infusion). In order to investigate potential skeletal and cardiovascular implications, we assessed changes in other components of mineral and bone metabolism, left ventricular function, and arrhythmias. RESULTS: Hypophosphatemia occurred more frequently in women treated with FCM (9 out of 12 [75%]) than in those treated with FDI (1 out of 13 [8%]; p = 0.001). Within 24 h after iron supplementation, women in the FCM group had significant higher plasma intact FGF23 (p < 0.001) and lower plasma 1.25-dihydroxyvitamin D (p < 0.001). As an indicator of urinary phosphorus losses, urinary fractional phosphorus excretion was higher in the FCM group (p = 0.021 at day 7 ± 2 after iron supplementation). We did not observe differences in skeletal and cardiovascular markers, potentially because of the limited number of participants. CONCLUSIONS: While both FCM and FDI provide efficient iron repletion in participants with iron deficiency anemia, FCM induced hypophosphatemia more often than FDI. TRIAL REGISTRATION: Clinical Trials.gov NCT02905539. Registered on 8 September 2016. 2015-004808-36 (EudraCT Number) U1111-1176-4563 (WHO Universal Trial Number) DRKS00010766 (Deutsches Register Klinischer Studien).

Mechanical characteristic and biological behaviour of implanted and restorative bioglasses used in medicine and dentistry: A systematic review.

OBJECTIVE: Nowadays bioactive glasses are finding increasing applications in medical practice due to their ability to stimulate re-mineralisation. However, they are intrinsically brittle materials and the study of new compositions will open up new scenarios enhancing their mechanical properties and maintaining the high bioactivity for a broader range of applications. This systematic review aims to identify the relationship between the composition of bioactive glasses used in medical applications and their influence on the mechanical and biological properties. METHODS: Various electronic databases (PubMed, Science Direct) were used for collecting articles on this subject. This research includes papers from January 2011 to March 2016. PRISMA guidelines for systematic review and meta-analysis have been used. 109 abstracts were collected and screened, 68 articles were read as relevant articles and a total of 22 papers were finally selected for this study. RESULTS: Most of the studies obtained enhanced mechanical properties and the conservation of bioactivity behaviours; although a lack of homogeneity in the characterization methods makes it difficult to compare data. SIGNIFICANCE: New compositions of bioactive glasses incorporating specific ions and the addition in polymers will be the most important direction for future researches in developing new materials for medical applications and especially for dentistry.

Universal Landau pole.

Our understanding of quantum gravity suggests that at the Planck scale the usual geometry loses its meaning. If so, the quest for grand unification in a large non-Abelian group naturally endowed with the property of asymptotic freedom may also lose its motivation. Instead, we propose a unification of all fundamental interactions at the Planck scale in the form of a universal Landau pole, at which all gauge couplings diverge. The Higgs quartic coupling also diverges while the Yukawa couplings vanish. The unification is achieved with the addition of fermions with vector gauge couplings coming in multiplets and with hypercharges identical to those of the standard model. The presence of these particles also prevents the Higgs quartic coupling from becoming negative, thus avoiding the instability (or metastability) of the standard model vacuum.

Safety levels for exposure of cornea and lens to very high-frequency ultrasound.

OBJECTIVE: Very high-frequency (50-MHz) ultrasound is widely used for imaging the anterior segment of the eye. Our aim was to determine whether exposures to ultrasound at and above those used in diagnostic imaging systems might cause bioeffects in ocular tissues. METHODS: We characterized the output parameters of a polyvinylidene difluoride transducer using a needle hydrophone. We exposed sites on the cornea or lens of rabbits for up to 30 minutes at a 10-kHz pulse repetition frequency. Tissue obtained immediately or 24 hours after exposure was examined by light microscopy. A numeric model was implemented to calculate expected temperature elevations in the cornea and lens under experimental conditions. RESULTS: No tissue changes were observed directly or by slit lamp. Light microscopy showed no abnormalities attributable to ultrasound exposure. Simulations showed that even long-term exposures should produce temperature elevations of less than 1 degree C in both the cornea and lens. CONCLUSION: With the use of exposure parameters 4 to 5 orders of magnitude greater than encountered in a clinical situation, no tissue changes were observed. This is consistent with the small (0.2 degrees C) temperature rises computed in simulations. The lack of biological effects is attributable to the small dimensions of the focal zone, allowing rapid dissipation of heat, and the low total acoustic power produced by the transducer.

High-resolution ultrasonic imaging and characterization of the ciliary body.

PURPOSE: To develop a means for noninvasive in vivo visualization of the ciliary processes using very-high-frequency (50 MHz) ultrasound and to develop quantitative morphologic descriptors that may relate to physiologic function. METHODS: The region of the ciliary body was scanned with very-high-frequency ultrasound, both in rabbits and in normal human subjects. Data were acquired in a series of planes so that the spacing between them was less than the beam width of the transducer in its focal plane. Three-dimensional perspective images were constructed, representing the anatomy of the angle region, including the ciliary processes. The automatically detected boundaries of the ciliary processes were analyzed to compute their periphery, area, shape factor, and fractal dimension. These measures were compared between the human and the rabbit eye and analyzed for periodicities related to the spacing of successive processes. RESULTS: Three-dimensional images allowed visualization of the radial arrangement of the processes. All biometric descriptors were significantly different between the rabbit and human eye and showed periodicities consistent with spacing between processes. CONCLUSIONS: The methods described in this report are sensitive descriptors of the state of the ciliary processes. These techniques may be of value in measurement of changes in the ciliary body associated with disease, medical therapy, and aging.

Study of ultrasonic contrast agents using a dual-frequency band technique.

We have developed a dual-frequency band technique to study frequency-dependent phenomena associated with ultrasonic contrast agents. Our technique uses a superimposed high-frequency (10 MHz) broad-band ultrasound (US) pulse to investigate contrast agent interaction with a low-frequency (e.g., 0.5 MHz) ultrasonic field. Our digitally controlled system has the ability to produce two colinear, confocal US pulses at different center frequencies, to adjust the relative phasing and pulse repetition frequency of each pulse, and to acquire digital backscatter data. A series of experimental studies demonstrated that the high-frequency backscatter signal responded to several phenomena induced in contrast agent particles by the low-frequency beam. These phenomena included radial pulsations, nonlinear oscillations and depletion. Initial results also demonstrated a relative phase shift between the high- and low-frequency signals; this shift is due to a difference in sound velocity at these frequencies, and it may convey information about the contrast agent concentration.

A comparison of ultrasonic beams for thermal treatment of ocular tumors.

OBJECTIVE: This study examined the relative merits of different ultrasonic beams and exposure modalities for treating ocular melanomas. METHODS: Simulations were conducted to evaluate temperature patterns and lesion shapes induced by intense-ultrasound treatment of ocular tumors. In-vitro insonification experiments were conducted in bovine lenses. RESULTS: Simulated hyperthermia exposures did not effectively treat tumor margins because of thermal conduction into nearby fluid-like media. Standard high-intensity focused beams produced narrow lesions during 2-s exposures. A high-intensity, multi-lobed beam, produced by a transducer with strip electrodes, generated asymmetric lesions with a single large dimension; this lesion shape could expedite the production of lesion matrices within large tumors. In-vitro cataract shapes were consistent with simulation results for focused high-intensity beams. CONCLUSIONS: Thermal conduction and perfusion can cause underheating of tumor margins during hyperthermia unless special beam designs are used. The strip-electrode transducer configuration promises to expedite treatment of extended tumor volumes.

Correlation of high-frequency ultrasound backscatter with tumor microstructure in iris melanoma.

OBJECTIVE: This study aimed to correlate histologic characteristics with high-frequency ultrasound backscatter spectra in malignant melanomas of the iris. DESIGN: The study design was a cohort (case series) study of patients diagnosed with iris melanoma in the authors' clinic. PARTICIPANTS: Sixteen patients with iris melanoma participated. INTERVENTION: The patients were scanned with a 50-MHz ultrasound unit equipped for digitization of raw echo data. Spectral parameter images representing the spatial distribution of size and concentration of tissue inhomogeneities were produced. MAIN OUTCOME MEASURES: The variation of spectral properties within and between tumors was determined. In the two tumors in this series for which histologic material was available, the authors compared scatterer concentration and size with histology and mathematically modeled the effect of melanocyte distribution on spectra. RESULTS: Ultrasound scattering characteristics differed considerably among tumors. Where histology was available, acoustic parameters correlated with the size and number of melanocytes present. CONCLUSIONS: Iris melanomas exhibited a wide range in acoustic backscatter properties. Whereas characteristics such as vascularity and necrosis might contribute to this, in the two cases examined here, backscatter characteristics could be largely accounted for by melanocyte distribution. A better understanding of the relationship of histology to noninvasive ultrasound data will enhance the diagnostic utility of this technique.

Imaging and spectrum analysis of contrast agents in the in vivo rabbit eye using very-high-frequency ultrasound.

We have conducted initial studies that demonstrated the feasibility of employing ultrasonic contrast agents with very-high-frequency ultrasound (VHFU), using wideband transducers with center frequencies near 40 MHz. These studies were undertaken with an ultimate objective of quantifying perfusion in vessels in the eye and other organs. We expanded the model developed by Lizzi et al. (1983) to incorporate the scattering characteristics from encapsulated bubbles, such as contrast agents. Our analysis shows how the spectral slopes and intercepts measured from contrast agents are related to factors that include the radii and concentration of contrast-agent particles. We conducted in vitro experiments to validate the theoretical predictions and obtained excellent agreement. We obtained in vivo VHFU data from the eyes of anesthetized rabbits before and after injection of Albunex and Aerosomes. Digitally computed B-mode images demonstrated echo enhancement within the ciliary body and its processes. The magnitudes of these enhancements were quantified using calibrated spectrum-analysis techniques.

Correlation of ultrasound parameter imaging with microcirculatory patterns in uveal melanomas.

Previous studies demonstrated a correlation between acoustic backscatter parameters and survival in ocular melanoma. The histologic presence of microvascular networks in ocular melanoma is also associated with death from metastases. This study tests the hypothesis that melanomas grouped on the basis of these microvascular patterns are separable by ultrasound spectrum analysis. We scanned 40 melanomas using a 10-MHz ultrasound unit equipped for digitization of radio frequency data. After enucleation, tumors were sectioned in planes corresponding to the ultrasonographic examination and stained to demonstrate microcirculation. Acoustic spectral parameters were compared between 14 melanomas with a nevuslike microcirculation and 26 with foci of high-risk microvascular structures. Smaller scatterer size, lower acoustic concentration and greater spatial variability were found to correlate with high-risk microvascular patterns and areas of cystic degeneration. We suggest that nonvascular extracellular matrix components associated with microvessels may be responsible for the correlation of acoustic parameters with microvascular pattern and distribution.

Ultrasonically induced hyperthermia for adjunctive treatment of intraocular malignant melanoma.

PURPOSE: This report describes results of a prospective pilot trial to evaluate the safety and efficacy of hyperthermia as an adjunct to enucleation or brachytherapy in the treatment of patients with intraocular malignant melanoma. METHODS: Twenty-five patients with intraocular malignant melanomas were treated with ultrasonically induced hyperthermia. In 14 patients, hyperthermia was administered before enucleation (median follow-up period, 44 months), and in 11 patients, hyperthermia was used as an adjunct to brachytherapy (median follow-up period, 79 months). RESULTS: Patient survival in each group was compared with that of a control group treated with enucleation or brachytherapy alone, using Kaplan-Meier and Cox analysis. Taking into account the simultaneous effects of tumor size and location, the relative risk ratios and 95% confidence bounds associated with adjunctive hyperthermia were 1.68 (range, 0.60-4.72) and 0.68 (range, 0.16-2.89) for the enucleation and brachytherapy groups, respectively. CONCLUSIONS: Patients receiving adjunctive hyperthermia with brachytherapy showed increased survival, whereas those receiving hyperthermia before enucleation showed decreased survival. Neither trend was statistically significant in this small series. The synergism of hyperthermia with radiation may offer the possibility of improved tumor management.

Statistical framework for ultrasonic spectral parameter imaging.

This study examines the statistics of ultrasonic spectral parameter images that are being used to evaluate tissue microstructure in several organs. The parameters are derived from sliding-window spectrum analysis of radiofrequency echo signals. Calibrated spectra are expressed in dB and analyzed with linear regression procedures to compute spectral slope, intercept and midband fit, which is directly related to integrated backscatter. Local values of each parameter are quantitatively depicted in gray-scale cross-sectional images to determine tissue type, response to therapy and physical scatterer properties. In this report, we treat the statistics of each type of parameter image for statistically homogeneous scatterers. Probability density functions are derived for each parameter, and theoretical results are compared with corresponding histograms clinically measured in homogeneous tissue segments in the liver and prostate. Excellent agreement was found between theoretical density functions and data histograms for homogeneous tissue segments. Departures from theory are observed in heterogeneous tissue segments. The results demonstrate how the statistics of each spectral parameter and integrated backscatter are related to system and analysis parameters. These results are now being used to guide the design of system and analysis parameters, to improve assays of tissue heterogeneity and to evaluate the precision of estimating features associated with effective scatterer sizes and concentrations.

Three-dimensional high-frequency ultrasonic parameter imaging of anterior segment pathology.

PURPOSE: High-frequency ultrasound allows high-resolution imaging of anterior segment anatomy and pathology. Acoustic echo data, however, contain information relating to the microanatomic structure of the interrogated tissue which is not evident in B-mode images. The aim of this study is to develop imaging techniques to demonstrate and quantify the distribution of acoustic scattering properties in ocular tissues in three dimensions. METHODS: A tumor of the iris and a hyphema were scanned using a 50-MHz ultrasound probe mounted on a computer-controlled two-axis positioning system. Scan data from sequential parallel planes were used to make three-dimensional reconstructions. Digital signal processing and a mathematical model of acoustic backscatter then were used to represent the effective size and acoustic concentration of scattering elements using a false color representation superimposed on B-mode images. RESULTS: Three-dimensional reconstructions improved appreciation of the size and extent of pathology and allowed computation of tissue volumes. Parameter images demonstrated distinctive differences between diffuse and organized blood and allowed quantification of tumor scattering properties. CONCLUSIONS: Three-dimensional imaging of the anterior segment with high-frequency ultrasound allows construction of perspective images, which adds to the already significant clinical use of individual high-resolution B-mode images. Acoustic backscatter properties determined by tissue microstructure can be computed from echo data and represented in false color in three-dimensional reconstructions.

Correlation of microcirculation architecture with ultrasound backscatter parameters of uveal melanoma.

Ultrasound tissue characterization parameters of size and acoustic concentration can be used to sub-classify uveal melanoma and estimate the patient's risk of death. Histologically determined microcirculation patterns have also been found to sub-classify uveal melanoma and predict patient's risk of death. This study examines the spatial relationship between tumor features detected by the two techniques. Three dimensional ultrasound images that depict the size and relative concentration of scattering elements in uveal melanoma within a range of approximately 50-120 microns were compared with PAS (without hematoxylin) stained histological sections graded and localized according to tumor microvascular patterns. Both ultrasound parameter imaging and histopathology were accomplished by workers masked to the other procedure. In three of five patients vascular networks were identified histopathologically. The predominant ultrasound feature seen in the regions of the histologically identified networks were clusters of scatterers in the range of approximately 50-80 microns. In the two cases without a network vascular pattern, lower range scatterers dominated the tumor volume. All the cases could be distinguished by the size and distribution of contiguous spatial clusters of acoustic scatterers. Scatterer size features detected in three dimensional ultrasound parameter images can identify tumor regions containing a specific microvascular pattern. Ultrasound tissue characterization features used to sub-classify uveal melanoma may have a biophysical basis related to patterns of tumor microcirculation.

The effect of transducer bandwidth on ultrasonic image characteristics.

PURPOSE: This study was conducted to determine the effect of transducer bandwidth on the characteristics of ophthalmic ultrasound images. METHODS: B-scan images produced using two transducers, one with a narrow bandwidth and the other with a broad bandwidth, both having nominal center frequencies of 10 MHz, were evaluated. Comparative scans were made of a tissue-mimicking phantom, an intraocular tumor, and a vitreous hemorrhage. RESULTS: Results showed that broadband transducers gave improved resolution and finer speckle texture, but had lower sensitivity. Broadband transducers were most suitable for situations in which resolution was more important than sensitivity, such as imaging of tumors. The greater sensitivity of the narrowband probe made it most useful for evaluation of vitreous complications, such as hemorrhage and membranes. CONCLUSION: In addition to transducer frequency, bandwidth should be taken into account when choosing a transducer for a specific ophthalmic imaging application. Both broad- and narrowband transducers have relative advantages in particular applications.

Diagnostic ultrasound in dermatology: current uses and future potential.

Although ultrasound has been used for many years for a variety of medical diagnostic purposes, only recently have systems been designed that allow for its application to skin. High-resolution ultrasound systems now permit accurate, quantitative, noninvasive assessment of skin and cutaneous diseases. This technique will assist in the management of both inflammatory and neoplastic processes. Scans of skin obtained with a prototype high-resolution ultrasound system are presented. The computer-assisted creation of three-dimensional images from sequential B-mode scans is described.

Three-dimensional imaging for diagnostic ultrasound in dermatology.

BACKGROUND: Visual examination and cutaneous biopsies, two major tools in dermatologic diagnosis, do not provide structural information regarding the entire tissue volume. OBJECTIVE: Our purpose was to develop a high-resolution ultrasound system that quickly, with minimal operator interaction, displays structural data on the entire tissue volume. METHODS: A prototype ultrasound B-scan system was developed and operated at nominal center frequencies between 35 and 50 MHz, with computer processing of data to produce three-dimensional images. These images displayed as three-dimensional "blocks" can be sectioned to provide multiple images of internal structure (i.e., "acoustic biopsies"). RESULTS: B-scans and associated three-dimensional images were obtained from assorted skin sites in selected patients. CONCLUSION: This technique provides a valuable diagnostic tool that is now being further evaluated.