Functional adaptation after femoral intertrochanteric valgus osteotomy in Legg-Calvé-Perthes disease.

Legg-Calvé-Perthes disease (LCPD) requires individualized treatment in order to regain a functional hip joint. In severe cases, in which a congruent joint cannot be achieved, other options are necessary in order to improve functionality and prevent early osteoarthritis. Therefore, we analysed the clinical and radiologic outcome of 28 patients after valgus osteotomy of the proximal femur (VOF). We examined the range of hip motion, functionality and health-related quality of life (HRQoL) via modified Harris Hip Score (mHHS) and Kidscreen-10. Radiographic analysis contained quantitative and qualitative measurements of hip morphology. In particular, we correlated the results with the change of the pelvic-femoral angle (PFA). PFA was defined as the angle between the anatomical diaphyseal line of the femur and a vertical line through the pelvis. The mean follow-up was 5.5 years. Patients showed high mHHS and good HRQoL postoperatively. An increase in ROM with an improvement of 30.5° abduction and 10.3° internal rotation was evident. PFA correlated with adduction contracture and improved significantly after surgery. In consideration of careful patient selection, VOF showed a positive effect on ROM, pain, HRQoL, radiographic congruence and outcome. We identified the age at surgery and an increasing adduction contracture-objectified by a decreased PFA-as a prognostic factor.

Nonunion of the radial neck in children: a rare but severe complication after fractures of the radial neck.

PURPOSE: Nonunion of the radial neck poses an enormous challenge for treating surgeons. It is a very rare complication of the radial neck with limited experiences. In this current major study, the authors report of their own experiences concerning this problem. METHODS: 11 patients with severe displaced radial neck fracture Metaizeau type IV with elbow dislocation and 2 ongoing fractures. 9 fractures had to be treated with open reduction, six with intramedullary nailing, two with K-wires and one with periosteal suture fixation. In two children, aged 4 and 5, the fracture was not diagnosed initially. The patients showed a successful reduction intraoperatively. RESULTS: All patients developed nonunion of the radial neck. 9 out of 11 children presented with pain and 5 out of 11 with valgus deformity. All children underwent surgical management of the complications. 3 children received a debridement of the elbow joint with resection of the fragmented radial head. 7 cases needed a following reduction, spongiosa-plasty and periosteal flap reconstruction and plate osteosynthesis. One patient received radial intramedullary pinning. All nonunions showed reunion. All patients with obtained radial head showed significant improvement concerning complaints and range of motion. Only one child showed a slight deterioration in range of motion. Children with resected radial head showed good range of motion but complaints and instability in loaded joint needing further surgical treatment. CONCLUSION: Treatment of radial neck nonunion in children should not be delayed until pain, deformity and limited function occurs because this goes along with severe transition of the radial head right up to bone atrophy.

Results of hybrid procedures for treatment of aortoiliac Trans-Atlantic Inter-Society Consensus II D lesions with self-expanding covered heparin-bonded stent grafts.

BACKGROUND: According to the guidelines aortoiliac TASC D lesions should be treated by bypass. The purpose of this study was to examine the results of hybrid procedures with the use of a self-expanding covered heparin-bonded stent graft (Viabahn) in patients with extensive aorto-iliac lesions who were not considered to be suitable for open aorto-iliac surgery. METHODS: All patients who received a hybrid procedure in combination with a Viabahn stent in our clinic to treat aortoiliac lesions between October 2011 and April 2017 were included in this retrospective analysis. Study endpoints were primary patency, amputation-free survival (AFS) and major adverse limb event (MALE) free survival after 2 years. RESULTS: We included 23 hybrid procedures (endarterectomy of the common femoral artery or cross over bypass and aortoiliac stent) in 20 patients (median age 59 years). Indication was critical limb ischemia in 70.0%. The reasons why patients were on high risk for alternative open aortoiliac revascularization were hostile abdomen in 35.0%, cardiopulmonary contraindications in 35%, cancer in 10.0%, age >80 years in 10.0% and alcoholic cirrhosis in 10.0%. The 30-day mortality was 15.0%, the major amputation rate was 4.3%. We had no early graft occlusion. After 2 years primary patency was 100%, AFS 58.2% and MALE free survival 95.7%. CONCLUSIONS: A hybrid procedure with the use of a Viabahn stent in severe aortoiliac pathologies showed good patency results in this selected patient group. Therefore, it should be considered a feasible alternative to aortoiliac bypass surgery in surgical high-risk patients.

Unlocked and locked elastic stable intramedullary nailing in an ovine tibia fracture model: a biomechanical study.

In the present study, four different systems of elastic stable intramedullary nails (unlocked, Ender stainless steel nails locked with 3-mm screws, titanium nails locked with end caps, titanium nails locked with plugs and 3-mm screws) were implanted in cadaveric ovine tibiae. Fractures were simulated by a transverse diaphyseal osteotomy. The specimens were subjected to simultaneous axial and torsional fatigue loading of 5000 and 1000 cycles, respectively. The unlocked systems failed at an axial load of 200 N peak amplitude. End caps systems withstood axial loads up to 800 N for 1000 cycles, and ender nails and plugs lasted up to 1000 N for 1000 cycles. All systems showed a decrease of axial stiffness with higher loads and endured cycles. Ender nails and nails locked with plugs failed by penetration of the distal epiphysis rather than by loosening of the interlocking system. Overall, the titanium nails locked with plugs and 3-mm screws exhibited superior test results.

Coupling of biotin-(poly(ethylene glycol))amine to poly(D,L-lactide-co-glycolide) nanoparticles for versatile surface modification.

Generally, polymeric nanoparticles (NP) for drug targeting are designed to entrap the drug moiety in the core and to present the targeting moiety on the surface. However, in most cases, common preparation techniques of polymeric NP need to be specifically arranged for each compound to be entrapped or attached. In the present work, we introduce a method for versatile conjugation of targeting moieties to the surface of preformed, polymeric NP. Moreover, due to taking advantage of biotin-avidin interactions, our regime opens the additional possibility of a rapid fluorescence labeling of NP. Poly(D,L-lactide-co-glycolide) (PLGA) NP in the size of 210 nm were prepared by the classic oil-in-water method. Such NP were functionalized with biotin-(poly(ethylene glycol))amine (BPEG) by means of cyanuric chloride chemistry. The amount of surface-associated biotin was 850 pmol per milligram of polymer, corresponding to roughly 2650 molecules of biotin per NP. When drawn to scale, such surface coating appeared to be well-suited for subsequent binding of avidin or avidin-linked ligands. By resonant mirror measurements, we could prove specific binding of biotinylated NP to a NeutrAvidin (NAv)-coated surface. Furthermore, after coupling of NAv-linked fluorescence dyes to BPEG-functionalized NP, differences in binding and uptake could be demonstrated using two epithelial cell lines (Caco-2, A549).

Nanoparticles--an efficient carrier for drug delivery into the hair follicles.

The penetration and storage behavior of dye-containing nanoparticles (diameter 320 nm) into the hair follicles was investigated. The results were compared to the findings obtained with the same amount of dye in the non-particle form. In the first part of the experiments, the penetration of the dye into the hair follicles was investigated in vitro on porcine skin, which is an appropriate model for human tissue. It was found that the nanoparticles penetrate much deeper into the hair follicles than the dye in the non-particle form, if a massage had been applied. Without massage, similar results were obtained for both formulations. Subsequently, the storage behavior of both formulations in the hair follicles was analyzed in vivo on human skin by differential stripping. Using the same application protocol, the nanoparticles were stored in the hair follicles up to 10 days, while the non-particle form could be detected only up to 4 days. Taking into consideration the surface structure of the hair follicles, it was assumed that the movement of the hairs may act as a pumping mechanism pushing the nanoparticles deep into the hair follicles.

Nanoparticles made of fluorescence-labelled Poly(L-lactide-co-glycolide): preparation, stability, and biocompatibility.

Nanoparticles have recently been demonstrated in a rat model to be a promising tool for targeting inflamed areas of the intestinal mucosa in inflammatory bowel diseases whilst concentrating anti-inflammatory drugs at their site of action. Still, however, this novel concept has to be proven in vivo in humans. As a first step biodegradable and biocompatible fluorescent nanoparticles were prepared and characterized to serve as markers for successful inflammation targeting in future clinical trials. To achieve stable fluorescence labelling, fluoresceinamine was covalently bound to poly(L-lactide-co-glycolide) (PLGA) as described by Horisawa et al. The modification rate of carboxyl-end groups of the PLGA chains determined by 1H NMR was 65%. From this modified polymer, nanoparticles (FA-PLGA nanoparticles) of approximately 270 nm size were prepared via nanoprecipitation. Apart from an initial burst effect, most of the label (> 88%) appeared to be strongly bound and was leaked only slowly from the particles. In contrast, we found an immediate leakage of encapsulated sodium fluorescein with nanoparticles prepared by a double emulsion method. In degradation experiments we studied and visualized the changes in morphology and elastic properties of the FA-PLGA nanoparticles within 15 weeks using atomic force microscopy. When FA-PLGA nanoparticles were applied on an in vitro model of the intestinal mucosa (Caco-2 cell culture), only minor amounts of their fluorescent degradation products (approximately 0.02% after 6 h) were transported. In a cytotoxicity study with Caco-2 cells, FA-PLGA nanoparticles yielded an IC50 value as for plain PLGA nanoparticles. In conclusion, the polymer modification method allows to prepare fluorescently labelled nanoparticles from a well-known biodegradable pharmaceutical polymer with sufficient stability to be monitored over a period of several days. Some initial leakage of fluorescence label appears to be unavoidable but negligible with respect to potential absorption and cytotoxicity when applied in vivo.

Multiphoton microscopy for the investigation of dermal penetration of nanoparticle-borne drugs.

Multiphoton microscopy (MPM) of a dually fluorescence-labeled model system in excised human skin is employed for high-resolution three-dimensional (3D) visualization in order to study the release, accumulation, and penetration properties of drugs released from nanoscale carrier particles in dermal administration. Polymer particles were covalently labeled with fluorescein, whereas Texas Red as a drug-model was dissolved in the particles to be released to the formulation matrix. Single nanoparticles on skin could easily be localized and imaged with diffraction-limited resolution. The temporal evolution of the fluorescent drug-model concentration in various skin compartments over more than 5 hours was investigated by multiphoton spectral imaging of the same area of the specimen. The 3D penetration profile of the drug model in correlation with skin morphology and particle localization information is obtained by multiple laser line excitation experiments. MPM combined with spectral imaging was found to allow noninvasive long-term studies of particle-borne drug-model penetration into skin with subcellular resolution. By dual color labeling, a clear discrimination between particle-bound and released drug model was possible. The introduced technique was shown to be a powerful tool in revealing the dermal penetration properties and pathways of drugs and nanoscale drug vehicles on microscopic level.