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Bone regeneration and the osteoinductive capacity of implants are challenging issues in clinical medicine. Currently, recombinant growth factors and nonviral gene transfer are the most frequently investigated methods for bone growth enhancement, although the more favorable method remains unclear. There is a lack of knowledge in literature about the in vivo comparison of these methods for bone regeneration. BMP‐2, which is the most commonly used growth factor for osteogenesis, was applied at its most efficient dose as a recombinant growth factor (rhBMP‐2) and as a growth‐factor‐encoding copolymer protected gene vector (pBMP‐2) in a critical size bone defect (CSD) model to determine the most suitable method for bone regeneration. CSDs were induced bilaterally in 32 Sprague–Dawley rats. RhBMP‐2 (62.5 μg) or pBMP‐2 (2.5 μg) was embedded in poly(d,l‐)lactide‐coated titanium discs. Survival times were set at 14, 28, 56, and 112 days. After euthanasia, samples were analyzed via micro‐computed tomography, polychrome sequential fluorescent labeling, and immunohistochemistry. Whereas defects in both groups were bridged with new bone after 56 days, rhBMP‐2 initially induced ectopic new bone formation that was later remodeled in an unorganized hypodense manner. In contrast, pBMP‐2 led to slower but steady bone regeneration with physiological tissue morphology, as confirmed by high osteoblast activity shown by osteocalcin staining. CD68 and TRAP staining verified high osteoclast activity for the rhBMP‐2 group. pBMP‐2 successfully induced locally controlled physiological bone regeneration, whereas rhBMP‐2 triggered rapid and ectopic but insufficient bone formation. Thus, nonviral gene transfer appears to be more favorable for clinical applications. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 107A: 163–173, 2019. [ABSTRACT FROM AUTHOR]

Transvascular kidney biopsy in adolescent patients - safe alternative to open procedures. [Extracted from the article]

OBJECTIVES. Hypertonic-hyperoncotic solutions are used for the improvement of micro- and macrocirculation in various types of shock. In pediatric intensive care medicine, controlled, randomized studies with hypertonichyperoncotic solutions are lacking. Hypertonic-hyperoncotic solutions may improve cardiac function in children. The primary objective of this controlled, randomized, blinded study was to evaluate the hemodynamic effects and safety of hypertonic-hyperoncotic solution infusions in children shortly after open-heart surgery for congenital cardiac disease. The secondary objective was to determine whether the administration of hypertonic-hyperoncotic solutions could be a potential and effective therapeutic option for preventing a probable capillary leakage syndrome that frequently occurs in children after open-heart surgery. METHODS. The children were randomly assigned to 2 groups of 25. The hypertonic-hyperoncotic solution group received Poly-(O-2)-hydroxyethyl-starch 60.0 g, with molecular weight of 200 kDa, [Na.sup.+] 1232 mmol/L and osmolality of 2464 mOsmol/L (7.2% sodium chloride with 6% hydroxyethyl-starch 200 kDa). The isotonic saline solution group received isotonic saline solution (0.9% sodium chloride). Atrial and ventricular septal defects were corrected using a homograft patch. Monitoring consisted of an arterial, a central venous, and a thermodilution catheter (PULSIOCATH). Cardiac index, extravascular lung water index, stroke volume index, mean arterial blood pressure, and systemic vascular resistance index were measured (Pulse Contour Cardiac Output technique). Immediately after surgery, patients were loaded either with hypertonic-hyperoncotic solution or with isotonic saline solution (4 mL/kg). Blood samples (sodium concentration, osmolality, thrombocyte count, fibrinogen, and arterial blood gases) were drawn directly before; immediately after; 15 minutes after; and, 1, 4, 12, and 24 hours after the end of volume loading. Hemodynamic parameters were registered at the same time. The total amount of dobutamine required was documented, as well as the 24- and 48-hour fluid balances. RESULTS. In the hypertonic-hyperoncotic solution group, cardiac index was 3.6 [+ or -] 0.26 L/min per [m.sup.2] before volume administration and increased to 5.96 [+ or -] 0.27 after the administration of the study solution (64%). Fifteen and 60 minutes after administration, the cardiac index remained significantly elevated (5.55 [+ or -] 0.29 L/min per [m.sup.2] and 4.65 [+ or -] 0.18 L/min per [m.sup.2], respectively) and returned to preadministration values after 4 hours. In the isotonic saline solution group, the cardiac index did not change during the entire observation period (3.39 [+ or -] 0.21 before and 3.65 [+ or -] 0.23 L/min per [m.sup.2] after isotonic saline solution). The systemic vascular resistance index decreased in the hypertonic-hyperoncotic solution group after administration from 1396 [+ or -] 112 to 868 [+ or -] 63 dyn/sec per [cm.sup.-5]/[m.sup.2]. The decrease of systemic vascular resistance index in the hypertonic-hyperoncotic solution group was transiently significant within 60 minutes after administration but stayed lower than before volume load (999 [+ or -] 70 dyn/sec per [cm.sup.-5]/[m.sup.2]). In the isotonic saline solution group, we found no statistically relevant change in systemic vascular resistance index. Stroke volume index significantly increased after hypertonic-hyperoncotic solution infusion (53.9 [+ or -] 3.0 mL/[m.sup.2] directly after, 48.8 [+ or -] 2.46 mL/[m.sup.2] 15 minutes after, and 41.4 [+ or -] 2.2 mL/[m.sup.2] 60 minutes after) when compared with stroke volume index before administration (32.4 [+ or -] 2.6 mL/[m.sup.2]). In the hypertonic-hyperoncotic solution group, an increase in mean arterial blood pressure remained transiently significant within 60 minutes after administration when compared with the isotonic saline solution group, in which the mean arterial blood pressure remained unchanged. Both central venous pressure and heart rate were unchanged during the whole time of observation in both groups. In the hypertonic-hyperoncotic solution group, extravascular lung water index decreased from 10.6 [+ or -] 1.2 to 5.6 [+ or -] 1.2 mL/kg and remained significantly decreased 15 minutes after (6.5 [+ or -] 1.2 mL/kg) when compared with before volume administration. In the isotonic saline solution group, extravascular lung water index increased from 12.3 [+ or -] 1.1 mL/kg to 18.1 [+ or -] 1.7 mL/kg directly after administration and remained elevated for 60 minutes after volume loading (15.6 [+ or -] 1.5 mL/kg). In all patients, no hypoxia (Pa[o.sub.2] 60 mm Hg) was observed. Arterial blood gas analysis showed pH and base excess within physiologic range, and this did not change throughout the whole period of observation. After infusion of hypertonic-hyperoncotic solution, sodium concentration increased from 139.2 [+ or -] 0.7 to 147.5 [+ or -] 0.7 mmol/L. The maximum sodium concentration was 153 mmol/L, measured immediately after hypertonic-hyperoncotic solution in 1 patient. The total amount of fluid infused was similar in both groups. The postoperative need for infused dobutamine in the patients in the hypertonic-hyperoncotic solution group was decreased compared with the isotonic saline solution group (46.9 [+ or -] 8.8 [micro]g/kg vs 308.2 [+ or -] 46.6 [micro]g/kg). No patient presented with severe bleeding. Short- and long-term cardiac and neurologic outcome was not reduced and all patients left the hospital in a clinically sufficient state. DISCUSSION. This study demonstrates a profound increase of cardiac i KEYWORDS. hypertonic-hyperoncotic solutions, pediatrics, capillary leakage, low-output failure, cardiopulmonary bypass. PEDIATRICS 2006;118:e76-e84. URL: www.pediatrics.org/cgi/doi/10.1542/peds.2005-2795