Prevention of Incisional Hernias by Prophylactic Mesh-augmented Reinforcement of Midline Laparotomies for Abdominal Aortic Aneurysm Treatment: Five-year Follow-up of a Randomized Controlled Trial.

INTRODUCTION: The incidence of incisional hernias (IHs) after open repair of an abdominal aortic aneurysm (AAA) is high. Several randomized controlled trials have reported favorable results with the use of prophylactic mesh to prevent IHs, without increasing complications. In this analysis, we report on the results of the 60-month follow-up of the PRIMAAT trial. METHODS: In a prospective, multicenter, open-label, randomized design, patients were randomized between prophylactic retrorectus mesh reinforcement (mesh group), and primary closure of their midline laparotomy after open AAA repair (no-mesh group). This article reports on the results of clinical follow-up after 60 months. If performed, ultrasonography or computed tomography were used for the diagnosis of IHs. RESULTS: Of the 120 randomized patients, 114 were included in the intention-to-treat analysis. Thirty-three patients in the no-mesh group (33/58-56.9%) and 34 patients in the mesh group (34/56-60.7%) were evaluated after 5 years. In each treatment arm, 10 patients died between the 24-month and 60-month follow-up. The cumulative incidence of IHs in the no-mesh group was 32.9% after 24 months and 49.2% after 60 months. No IHs were diagnosed in the mesh group. In the no-mesh group, 21.7% (5/23) underwent reoperation within 5 years due to an IH. CONCLUSIONS: Prophylactic retrorectus mesh reinforcement after midline laparotomy for the treatment of AAAs safely and effectively decreases the rate of IHs. The cumulative incidence of IHs after open AAA repair, when no mesh is used, continues to increase during the first 5 years after surgery, which leads to a substantial rate of hernia repairs.

Outcome after subtalar screw arthroereisis in children with flexible flatfoot depends on time of treatment: Midterm results of 95 cases.

OBJECTIVES: The subtalar screw arthroereisis (SSA) is a treatment option for painful pediatric flexible flatfeet (PFF). Hence, the optimal time point for a SSA is discussed controversially. Therefore the present study evaluates the influence of the patient's age at surgery on the radiological outcome to provide further evidence in this matter. METHODS: From 08/2007 to 12/2015 50 patients with 95 PFF were included. Inclusion criteria were: 1) Patients with PFF under or equal 15 years of age, 2) treatment with SSA and 3) presence of pre-op, post-op and follow up (FU) routine biplane radiographs. A subdivision was made into group A: 5-8 years, group B: 9-12 years and group C: 13-15 years. The radiographs were analyzed for: 1) calcaneal-pitch (CP), 2) lateral talocalcaneal angle (lat. TCA), 3) a.p. talocalcaneal angle (a.p. TCA, kite angle) and 4) navicular-cuboidal-index (NCI) and meary angle. RESULTS: Our study showed the best deformity correction when surgery was conducted between 9 and 12 years of age (group B), with significant improvement in all measured parameters without secondary deterioration during FU. In group A, the SSA show inferior results with poorer long-term success with only an improvement in the a.p. TCA. Group C showed mixed results. While CP and NCI improved, the lat. TCA deteriorated in FU. In conclusion, the ideal age for surgical intervention by SSA is between 9 and 12 years. Surgery before the age of 8 years did not show long-term success and delayed treatment at the age of 13-15 was only partially successful with deterioration during FU period. LEVEL OF EVIDENCE: IV.

Postoperative continuation of antidepressant therapy is associated with reduced short-term weight loss following Roux-en-Y gastric bypass surgery.

PURPOSE: Bariatric surgery candidates are frequently treated with antidepressants. Several of these drugs have been associated with weight gain and could potentially interfere with weight loss after bariatric surgery. This cohort study aimed to investigate the short-term effects of antidepressants on weight loss during the first 24 months after a Roux-en-Y gastric bypass. METHODS: Patients with a fully documented antidepressant treatment status for at least 12 months were retrospectively included. Weight loss was expressed as the percentage excess BMI loss (%EBMIL) or percentage total weight loss (%TWL). A mixed linear effects model was used to determine the impact of continued and discontinued treatment with antidepressants on weight loss. RESULTS: A total of 751 patients were included in this study. At 24 months, patients had lost 77.38 ± 30.10 %EBMIL (30.63 ± 13.12 %TWL). In patients treated with antidepressants (n = 125), the %EBMIL and %TWL was reduced with - 2.81% (p = 0.025) and - 1.36% (p = 0.002) respectively, and with - 5.52 %EBMIL (p < 0.001; - 1.05 %TWL, p = 0.012) after multivariate adjustment. Serotonin-norepinephrine reuptake inhibitors (- 12.47 %EBMIL, p < 0.001) and tricyclic antidepressants (- 11.01 %EBMIL, p = 0.042) were predominantly responsible for worse outcomes. Beyond 24 months, at 36 months (- 4.83%, p < 0.001) and 48 months (- 3.54%, p = 0.006), the %EBMIL was still reduced. No significant effects of antidepressants on metabolic outcomes after surgery were observed. CONCLUSIONS: Treatment with antidepressants was associated with reduced weight loss after gastric bypass surgery, but only if treatment was continued for at least 1 year postoperatively. Mainly tricyclic antidepressants and serotonin-norepinephrine reuptake inhibitors were responsible for this reduction in weight loss.

Cronkhite-Canada syndrome causing pouch outlet obstruction 5 years after roux-en-y gastric bypass.

OBJECTIVE: We present the case of a 57-year-old man with a history of Roux-en-Y gastric bypass (RYGB) and colonic polyps who presented with an upper gastrointestinal obstruction based on massive stomach polyposis in the pouch. METHODS: Two months prior to this acute admission, he had undergone resection of the gastric remnant due to massive refractory intraluminal bleeding from a polypoid mass. Ten years earlier, right colectomy was performed due to hypertrophic polyposis unsuitable for endoscopic polypectomy. Upper gastrointestinal endoscopy showed a polypoid mass in the pouch causing obstruction. Benign biopsies were obtained. A resection of the stomach pouch with esophagojejunostomy was performed. Macroscopic evaluation of the pouch lumen showed massive polyposis with a sharp demarcation near the Z-line and at the gastrojejunostomy. On clinical examination, the presence of atrophic nail changes, alopecia, and palmar hyperpigmentation was noticed. RESULTS: Postoperative course was uneventful and feeding was restarted successfully. Histological analysis revealed hyperplastic polypoid tissue, which resembled the polyps in the stomach remnant and colon. Together with the ectodermal changes, the diagnose of Cronkhite-Canada syndrome was established. CONCLUSION: Diffuse polyposis in Cronkhite-Canada syndrome is a rare cause for pouch obstruction after RYGB. Clinical examination should focus on dermatologic findings.

5-Year survival after splenectomy in a patient with recurrent cutaneous melanoma: a case report.

OBJECTIVE: Splenic metastases of melanoma are uncommon and generally part of a disseminated disease with a poor prognosis. In case of solitary visceral metastasis, surgical resection often remains an effective treatment. This case describes a long-term survival after splenectomy for a recurrent melanoma. METHODS: We present a 55-year-old female with a solitary splenic metastasis. Her medical history revealed a melanoma of the foot in 2007 and an in-transit metastasis in 2011. A PET-CT revealed in 2012 the presence of a small aspecific lesion in the spleen. Close follow-up was chosen. Since PET-CT and MRI showed a progressive lesion, a laparoscopic splenectomy was performed. RESULTS: Histological report confirmed the diagnosis of a metastatic lesion. Sixty months after the first radiographic evidence of the splenic metastasis, follow-up revealed no signs of residual disease. CONCLUSIONS: Although current systemic approaches demonstrate to provide clinically important benefit, patients with oligometastatic disease should be evaluated for surgical metastasectomy. A laparoscopic approach for splenic metastasis is shown to be a safe treatment. This disease-free survival of 60 months in a patient with a history of an in-transit metastasis has not been published before. A splenectomy for a solitary metastasis could prolong the survival, even in a recurrent melanoma.

Prevention of Incisional Hernias by Prophylactic Mesh-augmented Reinforcement of Midline Laparotomies for Abdominal Aortic Aneurysm Treatment: A Randomized Controlled Trial.

BACKGROUND: The incidence of incisional hernias after abdominal aortic aneurysm repair is high. Prophylactic mesh-augmented reinforcement during laparotomy closure has been proposed in patients at high risk of incisional hernia. METHODS: A multicenter randomized trial was conducted on patients undergoing elective abdominal aortic aneurysm repair through a midline laparotomy (Clinical.Trials.gov: NCT00757133). In the study group, retromuscular mesh-augmented reinforcement was performed with a large-pore polypropylene mesh (Ultrapro, width 7.5 cm). The primary endpoint was the incidence of incisional hernias at 2-year follow-up. RESULTS: Between February 2009 and January 2013, 120 patients were recruited at 8 Belgian centers. Patients' characteristics at baseline were similar between groups. Operative and postoperative characteristics showed no difference in morbidity or mortality. The cumulative incidence of incisional hernias at 2-year follow-up after conventional closure was 28% (95% confidence interval [CI], 17%-41%) versus 0% (95% CI, 0%-6%) after mesh-augmented reinforcement (P < 0.0001; Fisher exact test). The estimated "freedom of incisional hernia" curves (Kaplan-Meier estimate) were significantly different across study arms (χ = 19.5, P < 0.0001; Mantel-Cox test). No adverse effect related to mesh-augmented reinforcement was observed, apart from an increased mean time to close the abdominal wall for mesh-augmented reinforcement compared with the control group: 46 minutes (SD, 18.6) versus 30 minutes (SD, 18.5), respectively (P < 0.001; Mann-Whitney U test). CONCLUSIONS: Prophylactic retromuscular mesh-augmented reinforcement of a midline laparotomy in patients with abdominal aortic aneurysm is safe and effectively prevents the development of incisional hernia during 2 years, with an additional mean operative time of 16 minutes.

Ligand structures of synthetic deoxa-pyranosylamines with raucaffricine and strictosidine glucosidases provide structural insights into their binding and inhibitory behaviours.

Insight into the structure and inhibition mechanism of O-ß-d-glucosidases by deoxa-pyranosylamine type inhibitors is provided by X-ray analysis of complexes between raucaffricine and strictosidine glucosidases and N-(cyclohexylmethyl)-, N-(cyclohexyl)- and N-(bromobenzyl)-ß-d-gluco-1,5-deoxa-pyranosylamine. All inhibitors anchored exclusively in the catalytic active site by competition with appropriate enzyme substrates. Thus facilitated prospective elucidation of the binding networks with residues located at <3.9 Å distance will enable the development of potent inhibitors suitable for the production of valuable alkaloid glucosides, raucaffricine and strictosidine, by means of synthesis in Rauvolfia serpentina cell suspension cultures.

Erythrocytapheresis in Children and Young Adults with Hemoglobinopathies and Iron Overload in Need of Iron Chelation Therapy.

Limited data regarding erythrocytapheresis in children, adolescents, and young adults have been published. The aim of this study was to evaluate erythrocytapheresis, either as a standalone therapy or in combination with iron chelation therapy, in children and young adults with hemoglobinopathies in whom current iron chelation therapy is not sufficient in decreasing the iron overload during management. We retrospectively analysed erythrocytapheresis in 19 patients with hemoglobinopathies in need of iron chelation therapy diagnosed with sickle cell disease (SCD) or ß-thalassemia major. Patients were divided into (1) a case cohort who received erythrocytapheresis alone or in combination with iron chelation therapy and (2) a control cohort who received oral iron chelation therapy alone. Serum ferritin and haemoglobin levels were compared at five different time points over a one-year period. In the erythrocytapheresis cohort, there was a significant decrease in serum ferritin (p < 0.001). In the iron chelation therapy alone cohort, there was no significant decrease in serum ferritin over time (p = 0.156). Comparing the evolution of median serum ferritin between therapy with erythrocytapheresis and iron chelation therapy showed a statistically significant difference (p = 0.008). Patients with ß-thalassemia major receiving erythrocytapheresis showed a greater reduction in serum ferritin compared to patients without (p = 0.036). A difference could not be shown between the erythrocytapheresis and iron chelation single therapies (p = 0.100). This study showed an overall significant reduction in serum ferritin in patients with hemoglobinopathies treated with erythrocytapheresis in addition to iron chelation. A clinical, although not statistical, trend of higher haemoglobin levels was maintained. Erythrocytapheresis in paediatric patients with ß-thalassemia major was as effective in decreasing ferritin levels as in previously reported studies with SCD. Erythrocytapheresis is a promising therapy for treating and preventing transfusion-related iron overload.

Fluorescence-Guided Thoracic Duct Dissection in Robotic en Bloc Esophagectomy.

En bloc resection of the thoracic duct compartment enhances adequate lymph node removal and may improve oncologic outcomes in esophagectomy for malignant esophageal diseases. However, it also increases the risk of postoperative chylothorax, with a reported incidence of 5% to 20%. This report describes a technique that facilitates intraoperative identification of the thoracic duct, as well as proximal and distal ligation, during robot-assisted esophagectomy by lymphangiography-guided injection of indocyanine green in the right groin in a patient in the left lateral position. This approach can be swiftly applied at any time during any thoracoscopic procedure using the lateral position when visualization of the thoracic duct anatomy is needed.

Influence of a Calcium Phosphate Coating (BONIT®) on the Proliferation and Differentiation Potential of Human Mesenchymal Stroma Cells in the Early Phase of Bone Healing.

When implanting osteosynthetic materials or orthopedic implants, the surface condition plays a decisive role for mid- to long-term osseointegration. BONIT®, an electrochemically produced calcium phosphate (CaP) coating, has been used in the surface refinement of implants since 1995. More than 3.5 million coated implants have been successfully placed so far. BONIT® has thus been able to demonstrate clinical success. However, due to its surface properties and solubility, and the resulting difficulty in culturing cells, there are no in vitro studies investigating its influence at the molecular level, particularly on bone metabolism. In a first step, the cells from a total of ten donors were seeded separately on four different surfaces: 1. a pure corundum-blasted titanium surface (CELLTex®, CT), 2. CT with additional BONIT® coating (CT + B), 3. a hydroxyapatite-blasted titanium surface (DUOTex®, DT), 4. DT with additional BONIT® coating (DT + B). In a second step, the cells were grown for 48 h. The proliferation behavior and differentiation potential of hMSCs were investigated at three consecutive time points (12 h, 24 h and 48 h) by quantifying the mRNA expression of ten important differentiation markers using quantitative real-time polymerase chain reaction (qRT-PCR). We were able to show that BONIT® has an influence on the early proliferation and differentiation behavior of hMSCs in patients of all age groups. The additional BONIT® coating on CELLTex® or DUOTex® led to a defined mRNA expression pattern for the investigated factors: a tendency towards a higher expression rate with coating present could be found for bone morphogenetic protein 2 (BMP2), osteopontin (OPN), osteocalcin (OC), receptor activator of NF-κB ligand (RANKL) and osteoprotegerin (OPG). A similar or lower expression rate was detected for runt-related transcription factor 2 (RUNX2), alpha-1 type I collagen (COL1A1), alkaline phosphatase (AP), osteonectin (ON) and insulin-like growth factor I (IGF1). We have developed a new method that allows the cultivation of human mesenchymal stromal cells (hMSCs) on the soluble coating BONIT® for gene expression analysis. BONIT® has a significant influence on the proliferation and differentiation behavior of human mesenchymal stroma cells. This study describes a defined gene expression pattern of bone metabolism that may help to understand the influence of this CaP coating on the early phase of implant osseointegration.

Review, Performance Comparison, and Validation of Models Predicting Type 2 Diabetes Remission After Bariatric Surgery in a Western European Population.

PURPOSE: The majority of patients with type 2 diabetes (T2DM) achieve remission after bariatric surgery. Several models are available to preoperatively predict T2DM remission. This study compares the performance of these models in a Western population one year after surgery and explores their predictive value in comparison to a model specifically designed for our study population. MATERIALS AND METHODS: Prediction models were retrieved using a literature search. Patients were retrospectively selected from a database of the Antwerp University Hospital. Performance of the models was assessed by determining the area under the receiver operating characteristic curve (AUROC), the accuracy, and the goodness of fit, and by comparing them to a custom-made logistic model. RESULTS: The probability of T2DM remission was calculated using 11 predictive scoring models and 8 regression models in a cohort of 250 patients. Complete T2DM remission occurred in 64.0% of patients. The IMS score (AUROC = 0.912; accuracy = 83.6%), DiaBetter score (0.907; 82.0%), and Ad-DiaRem score (0.903; 82.8%) best predicted T2DM remission and closely approached the performance of the custom-constructed model (0.917; 84.0%). The model by Ioffe et al. (0.630; 69.2%), Umemura et al. (0.692; 71.4%), and the ABCD score (0.757; 72.8%) were the least accurate. CONCLUSION: Most T2DM remission models reliably predicted one-year T2DM remission, with limited inter-model differences. The accuracy of most models approached that of the custom-constructed model, indicating a high predictive capability and performance in our patient cohort. To date, most models are only validated to estimate T2DM remission one year after surgery and they do not predict long-term remission.

Enzymatic and chemo-enzymatic approaches towards natural and non-natural alkaloids: indoles, isoquinolines, and others.

The multi-step enzyme catalysed biosyntheses of monoterpenoid indole and isoquinoline alkaloids are described. Special emphasis is placed on those pathways leading to alkaloids of pharmacological and medicinal significance which have been fully elucidated at the enzyme level. The successful identification and cloning of cDNAs of single enzymes and their application provides great opportunities to develop novel strategies for both in vitro and in vivo alkaloid production in whole plants or tissue cultures, as well as in microbial systems such as Escherichia coli and yeast. Enzyme crystallisation, 3D analyses and site-directed mutation allowed rational engineering of enzyme substrate acceptance, which in turn can be used for reprogramming in vivo alkaloid biosynthesis and for the design of biomimetic alkaloid syntheses. These strategies broaden structural diversity and allow the creation of large libraries of unnatural alkaloid with expected optimised or novel biological activities. The chemo-enzymatic syntheses of the above-mentioned alkaloid groups and their precursors (in addition to selected examples of other alkaloid families) provides an overview of how enzyme reactions are integrated into the development of total chemical syntheses.

Improved expression of His(6)-tagged strictosidine synthase cDNA for chemo-enzymatic alkaloid diversification.

Strictosidine synthase (STR1) catalyzes the stereoselective formation of 3alpha(S)-strictosidine from tryptamine and secologanin. Strictosidine is the key intermediate in the biosynthesis of 2,000 plant monoterpenoid indole alkaloids, and it is a key precursor of enzyme-mediated synthesis of alkaloids. An improved expression system is described which leads to optimized His(6)-STR1 synthesis in Escherichia coli. Optimal production of STR1 was achieved by determining the impact of co-expression of chaperones pG-Tf2 and pG-LJE8. The amount and activity of STR1 was doubled in the presence of chaperone pG-Tf2 alone. His(6)-STR1 immobilized on Ni-NTA can be used for enzymatic synthesis of strictosidines on a preparative scale. With the newly co-expressed His(6)-STR1, novel 3alpha(S)-12-azastrictosidine was obtained by enzymatic catalysis of 7-azatryptamine and secologanin. The results obtained are of significant importance for application to chemo-enzymatic approaches leading to diversification of alkaloids with novel improved structures.

Structure-based engineering of strictosidine synthase: auxiliary for alkaloid libraries.

The highly substrate-specific strictosidine synthase (EC 4.3.3.2) catalyzes the biological Pictet-Spengler condensation between tryptamine and secologanin, leading to the synthesis of about 2000 monoterpenoid indole alkaloids in higher plants. The crystal structure of Rauvolfia serpentina strictosidine synthase (STR1) in complex with strictosidine has been elucidated here, allowing the rational site-directed mutation of the active center of STR1 and resulting in modulation of its substrate acceptance. Here, we report on the rational redesign of STR1 by generation of a Val208Ala mutant, further describing the influence on substrate acceptance and the enzyme-catalyzed synthesis of 10-methyl- and 10-methoxystrictosidines. Based on the addition of strictosidine to a crude strictosidine glucosidase preparation from Catharanthus cells, a combined chemoenzymatic approach to generating large alkaloid libraries for future pharmacological screenings is presented.

Roux-en-Y gastric bypass as a re-do procedure for failed restricive gastric surgery.

BACKGROUND: Gastric restrictive procedures such as laparoscopic gastric banding or vertical banded gastroplasty show, at longer follow up, more and more failures and complications. This study focuses on the results of Roux-en-Y gastric bypass procedure (RYGBP) done as a re-do procedure, both after a technically failed restrictive procedure or when the restrictive procedure failed to obtain substantial weight loss. METHODS: We reviewed data concerning the postoperative complications and weight loss of 36 patients undergoing re-do surgery for failed restrictive procedures. RESULTS: Over a period of two years, 36 patients with a mean age of 40.9 years were converted to a RYGBP. Median time to conversion was 4.9 years, median follow up after conversion was 6.6 months. Early postoperative complications (less than 30 days postoperatively) were noted in 11 patients (30%). A greater number of early complications were noticed in group A (technical complications) compared to group B (insufficient weight loss) (39% vs. 22%). Late postoperative complications were seen in six patients (16%). In this relatively short follow up period we noticed a drop in body mass index (BMI) from a mean of 38.8kg/m(2) to 30.9 kg/m(2) with a mean excess body weight loss (EBWL) of 33.1% after the re-do procedure. Body mass index decreased from a mean preoperative value of 37.6kg/m(2) to 28.9 kg/m(2) in group A patients with an EBWL 36%, while group B patients had a change in BMI from 40.1kg/m(2) to 32.9 kg/m(2) with a mean EBWL of 30%. CONCLUSION: Based on the literature, we can presume that restrictive surgery for morbidly obese patients will require many reoperations in the future. The standard operation of choice is RYGBP. In our study this procedure showed a higher, but not significantly early morbidity rate when the indication for re-do surgery was a technical complication of the initial procedure.

Lengthening of newly formed humerus after autologous fibula graft transplantation following intercalary tumor resection.

Secondary limb lengthening after intercalary bone resection in pediatric patients is still challenging. After the resection, a free fibula autograft can be used to reconstruct the osseous gap. However, in particular in young pediatric patients, insufficient growth of the epiphyseal plate after transplantation may lead to a significant limb-length discrepancy (LLD). In this case, the autograft was used for limb lengthening. We report on the lengthening of a humerus regenerate after fibula autograft transplantation into a humeral defect in a pediatric/young adolescent patient. Because of LLD, she underwent callus distraction of the humerus regenerate after transplantation of a fibula autograft using a unilateral external fixator device. An 18-year-old female patient with status postintercalary proliferating chondroma resection (at the age of 7 years) required treatment for correction of a 13 cm humerus shortening. She reported no pain, had no functional limitations, and had a full range of motion of the shoulder and elbow joint. She complained about her short humerus and overall body scheme. A unilateral external fixator device for callus distraction was applied to the transplanted humerus regenerate after free fibula autograft transplantation. Bone lengthening was performed by distraction (2×0.5 mm/day). After 62 days and a lengthening of 6 cm in total, bone distraction was stopped mainly to avoid any complication. At this time, there was no limitation in the range of motion. No nerve palsy or other problems occurred at any time of the distraction. In pediatric patients, the transplantation of a fibula autograft is a well-established option to bridge an osseous gap after intercalary bone resection. This case report shows that even the humerus regenerate after fibula autograft transplantation has excellent potential for callotasis and bone remodeling and therefore bone lengthening in patients with LLD is an option even after transplantation of an autograft. This method provides a new therapeutic option for patients with LLD after fibula transplantation.

Heterologous expression, purification, crystallization and preliminary X-ray analysis of raucaffricine glucosidase, a plant enzyme specifically involved in Rauvolfia alkaloid biosynthesis.

Raucaffricine glucosidase (RG) is an enzyme that is specifically involved in the biosynthesis of indole alkaloids from the plant Rauvolfia serpentina. After heterologous expression in Escherichia coli cells, crystals of RG were obtained by the hanging-drop vapour-diffusion technique at 293 K with 0.3 M ammonium sulfate, 0.1 M sodium acetate pH 4.6 buffer and 11% PEG 4000 as precipitant. Crystals belong to space group I222 and diffract to 2.30 A, with unit-cell parameters a = 102.8, b = 127.3, c = 215.8 A.

Expression, purification, crystallization and preliminary X-ray analysis of perakine reductase, a new member of the aldo-keto reductase enzyme superfamily from higher plants.

Perakine reductase (PR) is a novel member of the aldo-keto reductase enzyme superfamily from higher plants. PR from the plant Rauvolfia serpentina is involved in the biosynthesis of monoterpenoid indole alkaloids by performing NADPH-dependent reduction of perakine, yielding raucaffrinoline. However, PR can also reduce cinnamic aldehyde and some of its derivatives. After heterologous expression of a triple mutant of PR in Escherichia coli, crystals of the purified and methylated enzyme were obtained by the hanging-drop vapour-diffusion technique at 293 K with 100 mM sodium citrate pH 5.6 and 27% PEG 4000 as precipitant. Crystals belong to space group C222(1) and diffract to 2.0 A, with unit-cell parameters a = 58.9, b = 93.0, c = 143.4 A.

Bone Marrow Aspirate Concentrate in Combination With Intravenous Iloprost Increases Bone Healing in Patients With Avascular Necrosis of the Femoral Head: A Matched Pair Analysis.

With disease progression, avascular necrosis (AVN) of the femoral head may lead to a collapse of the articular surface. The exact pathophysiology of AVN remains unclear, although several conditions are known that can result in spontaneous cell death, leading to a reduction of trabecular bone and the development of AVN. Hip AVN treatment is stage-dependent in which two main stages of the disease can be distinguished: pre-collapse (ARCO 0-II) and post-collapse stage (ARCO III-IV, crescent sign). In the pre-collapse phase, core decompression (CD), with or without the addition of bone marrow (e.g. bone marrow aspirate concentrate, BMAC) or bone graft, is a common treatment alternative. In the post-collapse phase, THA (total hip arthroplasty) must be performed in most of the patients. In addition to surgical treatment, the intravenous application of Iloprost has been shown to have a curative potential and analgesic effect. From October 2009 to October 2014, 49 patients with AVN (stages I-III) were treated with core decompression at our institution. All patients were divided into group A (CD + BMAC) and group B (CD alone). Of these patients, 20 were included in a matched pair analysis. The patients were matched to age, gender, ARCO-stage, Kerboul combined necrotic angle, the cause of AVN, and whether Iloprost-therapy was performed. The Merle d'Aubigné Score and the Kerboul combined necrotic angle in a-p and lateral radiographs were evaluated pre- and postoperatively. The primary endpoint was a total hip arthroplasty. In group A, two patients needed THA while in group B four patients were treated with THA. In group A, the Merle d'Aubigné Score improved from 13.5 (pre-operatively) to 15.3 (postoperatively). In group B there was no difference between the pre- (14.3) and postoperative (14.1) assessment. The mean of the Kerboul angle showed no difference in both groups compared pre- to postoperatively (group A: pre-op 212°, postop 220°, group B: pre-op 213, postop 222°). Regarding radiographic evaluation, the interobserver variability revealed a moderate agreement between two raters regarding the pre-(ICC 0.594) and postoperative analysis (ICC 0.604).This study demonstrates that CD in combination with the application of autologous bone marrow aspirate concentrate into the femoral head seems to be a safe and efficient treatment alternative in the early stages of AVN of the femoral head when compared to CD alone.