Management of bone disease in cystinosis: Statement from an international conference.

Cystinosis is an autosomal recessive storage disease due to impaired transport of cystine out of lysosomes. Since the accumulation of intracellular cystine affects all organs and tissues, the management of cystinosis requires a specialized multidisciplinary team consisting of pediatricians, nephrologists, nutritionists, ophthalmologists, endocrinologists, neurologists' geneticists, and orthopedic surgeons. Treatment with cysteamine can delay or prevent most clinical manifestations of cystinosis, except the renal Fanconi syndrome. Virtually all individuals with classical, nephropathic cystinosis suffer from cystinosis metabolic bone disease (CMBD), related to the renal Fanconi syndrome in infancy and progressive chronic kidney disease (CKD) later in life. Manifestations of CMBD include hypophosphatemic rickets in infancy, and renal osteodystrophy associated with CKD resulting in bone deformities, osteomalacia, osteoporosis, fractures, and short stature. Assessment of CMBD involves monitoring growth, leg deformities, blood levels of phosphate, electrolytes, bicarbonate, calcium, and alkaline phosphatase, periodically obtaining bone radiographs, determining levels of critical hormones and vitamins, such as thyroid hormone, parathyroid hormone, 25(OH) vitamin D, and testosterone in males, and surveillance for nonrenal complications of cystinosis such as myopathy. Treatment includes replacement of urinary losses, cystine depletion with oral cysteamine, vitamin D, hormone replacement, physical therapy, and corrective orthopedic surgery. The recommendations in this article came from an expert meeting on CMBD that took place in Salzburg, Austria, in December 2016.

Flow velocities after carotid artery stenting: impact of stent design. A fluid dynamics study in a carotid artery model with laser Doppler anemometry.

PURPOSE: To study the influence of a newly developed membrane stent design on flow patterns in a physiologic carotid artery model. METHODS: Three different stents were positioned in silicone models of the carotid artery: a stainless steel stent (Wall-stent), a nitinol stent (SelfX), and a nitinol stent with a semipermeable membrane (MembraX). To increase the contact area of the membrane with the vessel wall, another MembranX model was modified at the outflow tract. The membrane consists of a biocompatible silicone-polyurethane copolymer (Elast-Eon) with a pore size of 100 mum. All stents were deployed across the bifurcation and the external carotid artery origin. Flow velocity measurements were performed with laser Doppler anemometry (LDA), using pulsatile flow conditions (Re = 220; flow 0.39 l/min; flow rate ratio ICA:ECA = 70:30) in hemodynamically relevant cross-sections. The hemodynamic changes were analyzed by comparing velocity fluctuations of corresponding flow profiles. RESULTS: The flow rate ratio ICA:ECA shifted significantly from 70/30 to 73.9/26.1 in the MembraX and remained nearly unchanged in the SelfX and Wallstent. There were no changes in the flow patterns at the inflow proximal to the stents. In the stent no relevant changes were found in the SelfX. In the Wallstent the separation zone shifted from the orifice of the ICA to the distal end of the stent. Four millimeters distal to the SelfX and the Wallstent the flow profile returned to normal. In the MembraX an increase in the central slipstreams was found with creation of a flow separation distal to the stent. With a modification of the membrane this flow separation vanished. In the ECA flow disturbances were seen at the inner wall distal to the stent struts in the SelfX and the Wallstent. With the MembraX a calming of flow could be observed in the ECA with a slight loss of flow volume. CONCLUSIONS: Stent placement across the carotid artery bifurcation induces alterations of the physiologic flow behavior. Depending on the stent design the flow alterations are located in different regions. All the stents tested were suitable for the carotid bifurcation. The MembraX prototype has shown promising hemodynamic properties ex vivo.

Microembolic signals detected by transcranial Doppler sonography during carotid endarterectomy and correlation with serial diffusion-weighted imaging.

BACKGROUND AND PURPOSE: Embolic events are a major cause for procedure-related strokes after carotid endarterectomy (CEA). Transcranial Doppler sonography can reveal embolic events as microembolic signals (MES) during CEA. MES during declamping and shunting are frequently detected. MES during shunting are rare and known to be correlated with the neurological outcome of the patient. In the present study, we analyzed the occurrence of MES within different stages of CEA and whether MES within those stages were correlated with cerebral ischemia, as detected by diffusion-weighted imaging (DWI), and brain infarction, as detected by contrast-enhanced MRI. METHODS: Thirty-three patients were monitored intraoperatively for MES using transcranial Doppler sonography. DWI was performed within 24 hours before and after surgery. Positive postoperative DWI led to reexamination with contrast-enhanced T1-MRI 7 to 10 days after CEA for detection of cerebral infarction. RESULTS: MES were detected in 32 of 33 patients. The highest number of MES was found during shunting and declamping. A significant correlation was found between MES and DWI-lesions during dissection. A significant correlation was found between MES during dissection and shunting, and nonsignificant correlation was found between MES and the occurrence of cerebral infarction. CONCLUSIONS: MES could be regularly detected during CEA. Dissection and shunting seem to be the most vulnerable stages of the procedure.

Changes in carotid artery flow velocities after stent implantation: a fluid dynamics study with laser Doppler anemometry.

PURPOSE: To study the influence of stent size and location on flow patterns in a physiological carotid model. METHODS: Wallstents were positioned in silicon models of the carotid artery at various locations: 2 stents appropriately sized to the anatomy were placed in (1) the internal carotid artery (ICA) and (2) the ICA extending completely into the common carotid artery so as to cover the external carotid artery (ECA) orifice. Another 2 stents were placed in the ICA extending (1) partially and (2) completely into the bulb to simulate stent displacement and disproportion between stent size and the original vessel geometry. Measurements were performed with laser Doppler anemometry (LDA) using pulsatile flow conditions (Reynolds number=250; flow 0.431 L/min; ICA:ECA flow rate ratio 70:30) in hemodynamically relevant cross sections. The hemodynamic changes were analyzed with 1-dimensional flow profiles. RESULTS: With the stent in the ICA, no changes of the normal flow profile were seen. For stents positioned in the ICA and extending partially or completely into the carotid bulb, the flow behavior was affected by the resistance of the stent to flow in the ECA. Hemodynamically relevant disturbances were seen in the ICA and ECA, especially in the separation zones (regions along the walls just after a bifurcation, bend, or curve). The ICA:ECA flow rate ratios shifted from 70:30 to 71.3:28.7 and from 70:30 to 75.1:24.9, respectively, in the 2 malpositioned stent models. With the stent placed in the ICA extending completely into the CCA, the ICA:ECA flow rate ratio shifted from 70:30 to 72.4:27.6. In this configuration, there were no notable flow changes in the ICA, but a clear diminishing of the separation zones in the ECA separation zones. CONCLUSIONS: Anatomically correct positioning of appropriately sized stents does not lead to relevant flow disturbances in the ICA. In the ECA, depending on the position, size, and interstices of the stent, the physiological flow was considerably disturbed when any part of the stent covered the inflow of the vessel. Disturbances were seen when the stent was positioned into the bulb. For clinical application, stent location and size must be carefully determined so that the stent covers the bifurcation completely or is in the ICA only.