[Fast track strategies in hip arthroplasty]. / Fast-Track-Strategien in der Hüftendoprothetik.

BACKGROUND: Fast track arthroplasty is becoming increasingly accepted in German-speaking countries. By optimizing treatment processes fast track programs promise faster recovery, increased patient satisfaction, quality improvement and reduction in the length of hospital stay. OBJECTIVES: The philosophy and treatment principles of fast track hip arthroplasty during the pre, intra and postoperative phase are described in the light of the current body of evidence. The challenges concerning fast track arthroplasty within the German health system are discussed. MATERIAL AND METHODS: Besides presenting our own data concerning a patient seminar and an opiate saving pain treatment, the most relevant literature related to fast track hip arthroplasty from a pubmed search is discussed. RESULTS: Fast track concepts can only be successfully implemented through close interdisciplinary team work. Preoperatively, a patient seminar can help to prepare patients better for surgery. Postoperatively, early mobilisation and pain treatment play a central role, whereat a clear reduction in opiate application can be achieved. CONCLUSION: Fast track hip arthroplasty makes rethinking with respect to traditional treatment principles necessary and demands a high degree of interdisciplinary team work. Particularly, as result of the specifics of the health system (DRG system and stationary rehabilitation), a nationwide establishment in Germany has not taken place so far.

[Cell-based and future therapeutic strategies for femoral head necrosis]. / Zellbasierte und zukünftige Therapieansätze der Femurkopfnekrose.

BACKGROUND: The application of cell- and growth factor-based techniques in conjunction with conventional surgical approaches has great therapeutic potential for the treatment of avascular necrosis of the femoral head (AVNFH). OBJECTIVES: This review provides an overview of new strategies for the treatment of AVNFH, with emphasis on cell and growth factor-based approaches. MATERIALS AND METHODS: The results of a literature search are summarised, the most relevant publications are presented and discussed by the authors. RESULTS: In the focus of new strategies for treatment of AVNFH are bone marrow-derived cell concentrates and ex vivo-expanded mesenchymal stem cells. Besides local application during core decompression, the systemic administration of cells via blood vessels supplying the femoral head is an interesting approach. The application of osteogenic and angiogenic growth factor-laden scaffold materials has also been clinically tested. Initial results of randomised clinical trials using cell- and growth factor-based approaches underline the potential of these innovative therapeutic strategies. Cell-based therapies are governed by EU law and generally require a manufacturing authorization. CONCLUSION: To date, only few randomized controlled clinical trials are available which additionally display a considerable diversity concerning cell parameters, cell processing, adjuvant surgical techniques and the quality outcome parameters. Therefore, a final statement about the effectiveness of new cell and growth factor-based strategies is currently not possible.

Self-esteem as an important factor in quality of life and depressive symptoms in anosmia: A pilot study.

OBJECTIVES: Previous research has reported a negative impact of olfactory dysfunction on quality of life (QoL) and depressive symptoms. As self-esteem was identified as a contributing factor to depression, this study aimed to investigate QoL, depressive symptoms and self-esteem in patients with smell loss. DESIGN: Prospective controlled study. SETTING: Department of Biomedical Imaging and Image-guided Therapy, Medical University of Vienna, in co-operation with the Department of Ear, Nose and Throat Diseases, Medical University of Vienna, Austria. PARTICIPANTS: Twenty-two anosmic patients (12 females, 10 males) and 25 healthy controls (15 females, 10 males) participated in this study. MAIN OUTCOME MEASURES: Olfactory performance was assessed using the Sniffin' Sticks battery. In addition, psychological questionnaires that covered the topics quality of life (WHOQOL-BREF), depressive symptoms (BDI-II) and self-esteem (MSWS) were conducted. RESULTS: The results of this study revealed a decrease in QoL and reduced body-related self-esteem in anosmic patients. Furthermore, QoL and self-esteem were correlated with depressive symptoms. CONCLUSION: As self-esteem, QoL and depressive symptoms in anosmia interact with each other, we suggest that self-esteem should be considered in the medical history, in order to provide a personalised intervention, adapted to the patient's needs.

[New experimental strategies in cartilage surgery]. / Neue experimentelle Ansätze in der Knorpelchirurgie.

BACKGROUND: Cell and growth factor based strategies bear great potential to support the healing processes in cartilage repair and the therapy of osteoarthritic joints. OBJECTIVES: The following review provides an overview of novel experimental strategies for the therapy of focal cartilage defects and osteoarthritis, with emphasis on cell and growth factor based approaches. MATERIALS AND METHODS: The authors summarize their own data regarding the intraarticular injection of stem cells to treat osteoarthritis of the knee and provide a synopsis of the available literature discussing the most significant publications. RESULTS: The development of novel strategies for the treatment of focal and arthrotic cartilage lesions focuses on the application of growth factors, platelet rich plasma (PRP), bone marrow (BMSAC) or adipose derived (stromal vascular fraction - SVF) cell concentrates, and ex vivo expanded mesenchymal stem cells (MSC). First clinical data on the use of expanded MSCs show the potential of this innovative therapeutic strategy. These approaches, however, are governed by EU law and often require approval by regulatory bodies. CONCLUSION: Currently, only a limited number of published, randomized, controlled trials available. Therefore, it is not possible to finally assess the efficacy of these strategies at this point in time.

[Patellar tendon injuries after total knee arthroplasty : Classification and management]. / Rupturen der Patellarsehne nach Kniegelenkersatz : Klassifikation und Management.

BACKGROUND: Ruptures of the patellar tendon after total knee arthroplasty represent a rare but severe complication, which in general requires surgical therapy. OBJECTIVES: To implement a classification and correspondent therapy algorithm in consideration of the current literature for the treatment of patellar tendon ruptures after TKA. MATERIAL AND METHODS: A review of the recent literature and the author's experience are summarized in a classification and correspondent therapy algorithm for the treatment of patellar tendon ruptures after TKA. RESULTS: Ruptures of the patella tendon can be classified as avulsions (Type I), acute (Type II) and chronic ruptures (Type III). Avulsions are often of iatrogenic nature and can be sufficiently treated by transosseous refixation prior to implantation of the revision TKA. Acute ruptures of the patellar tendon can originate from trauma or intraoperative injury. The rupture can be restored by primary suture in combination with a wire cerclage in the case of good tendon quality and the absence of patient comorbidities (Type IIA). In the case of poor tendon quality or existing comorbidities (Type IIB) additional augmentation of the ruptured tendon, utilizing the autologous semitendinosus/gracilis tendon, is recommended. Chronic ruptures revealing a good patellar bone stock (Type IIIA) can be treated by a combination of a semitendinosus augmentation and a turndown quadriceps tendon flap. In the case of a poor patellar bone stock (Type IIIB) transpatellar fixation of the semitendinosus tendon is virtually impossible, so that an allograft augmentation or the use of a soft tissue muscle flap (i. e. the gastrocnemius flap) has to be considered. A failed complex reconstruction with or without infection (Type IIIC) is an invidious surgical task and needs to be addressed by the utilization of a muscle flap, an allograft or a patellectomy with or without arthrodesis.

In vivo effect of immobilisation of bone morphogenic protein 2 on titanium implants through nano-anchored oligonucleotides.

The aim of the present study was to test the hypothesis that immobilisation of bone morphogenic proteins on the surface of titanium implants through nano-anchored oligonucleotides can enhance peri-implant bone formation. Non-coding 60-mer DNA oligonucleotides (ODN) were anchored to the surface of custom made sandblasted acid etched (SAE) titanium screw implants through anodic polarisation, gamma-sterilised with a standard dose of 25 kGy, and were hybridised with complementary 30-mer strands of DNA oligonucleotides conjugated to rhBMP2. Blank SAE implants, SAE implants with nano-anchored ODN and SAE implants with nano-anchored ODN and non-conjugated rhBMP2 served as controls. The implants were inserted into the tibiae of 36 Sprague Dawley rats. Perforations at the head and the tip of the implants allowed for bone ingrowth. Bone ingrowth into perforations and bone implant contact (BIC) as well as bone density (BD) at a distance of 200 µm from the implant surface were assessed after 1 , 4 and 13 weeks. Implants with nano-anchored ODN strands hybridised with conjugated rhBMP2 exhibited enhanced bone ingrowth into the perforations and increased BIC after 1 week as well as increased BIC after 4 weeks compared to controls. No difference was seen after 13 weeks. Bone density around the outer implant surface did not differ significantly at any of the intervals. It is concluded that rhBMP2 immobilised on the surface of titanium implants through nano-anchored oligonucleotide strands can enhance bone implant contact. The conditions of sterilisation tested allowed for handling under clinically relevant conditions.

Angiogenic functionalisation of titanium surfaces using nano-anchored VEGF - an in vitro study.

The aim of the present study was to test the hypothesis that sandblasted and acid etched titanium surfaces can be functionalised with vascular endothelial growth factor (VEGF) using oligonucleotides for anchorage and slow release. rhVEGF165 molecules were conjugated to strands of 30-mer non-coding DNA oligonucleotides (ODN) and hybridised to complementary ODN anchor strands which had been immobilised to the surface of sandblasted/acid etched (SAE) Ti specimens. Specimens with non-conjugated VEGF adsorbed to ODN anchor strands and to blank SAE surfaces served as controls. Specific binding of conjugated VEGF exhibited the highest percentage of immobilised VEGF (71.0 %), whereas non-conjugated VEGF only achieved 53.2 and 30.7 %, respectively. Cumulative release reached 54.0 % of the immobilised growth factor in the group of specifically bound VEGF after 4 weeks, whereas non-conjugated VEGF adsorbed to ODN strands released 78.9% and VEGF adsorbed to SAE Ti surfaces released 97.4 %. Proliferation of human umbilical vein endothelial cells (HUVECs) was significantly increased on the surfaces with specifically bound VEGF compared to the control surfaces and SAE Ti surfaces without VEGF. Moreover, the released conjugated VEGF exhibited biological activity by induction of von Willebrand Factor (vWF) in mesenchymal stem cells. It is concluded that the angiogenic functionalisation of SAE titanium surfaces can be achieved by conjugation of VEGF to ODN strands and hybridisation to complementary ODN strands that are anchored to the titanium surface. The angiogenic effect is exerted both through the immobilised and the released portion of the growth factor.

[Reconstruction of osteochondral defects with a collagen I hydrogel. Results of a prospective multicenter study]. / Rekonstruktion von Gelenkknorpeldefekten mit einem Kollagen-I-Hydrogel. Ergebnisse einer prospektiven Multicenterstudie.

STUDY GOALS: The aim of the study was to evaluate the therapeutic benefit of CaReS®, a type I collagen hydrogel-based autologous chondrocyte implantation technique, for the treatment of osteochondral defects of the knee (Outerbridge grades III and IV) within a prospective multicenter study. MATERIAL AND METHODS: A total of 116 patients in 9 clinical centers were treated with CaReS between 2003 and 2008. The Cartilage Injury Evaluation Package 2000 of the International Cartilage Repair Society (ICRS) was employed for data acquisition and included the subjective International Knee Documentation Committee score (IKDC score), the pain level (visual analog scale, VAS), the physical and mental SF-36 score, the overall treatment satisfaction and the functional IKDC status of the indexed knee. Follow-up evaluation was performed 3, 6 and 12 months after surgery and annually thereafter. RESULTS: The mean defect size treated was 5.4 ± 2.7 cm(2) with 30% of the cartilage defects being ≤4 cm(2) and 70% ≥4 cm(2). The mean follow-up period was 30.2 ± 17.4 months (minimum 12 months and maximum 60 months). The mean IKDC score significantly improved from 42.4 ± 13.8 preoperatively to 70.5 ± 18.7 (p < 0.01) in the mean follow-up period. Global pain level significantly decreased (p < 0.001) from 6.7 ± 2.2 preoperatively to 3.2 ± 3.1 at the latest follow-up. Both the physical and mental components of the SF-36 score significantly increased. At the latest follow-up 80% of the patients rated the overall treatment satisfaction as either good or very good. The functional IKDC knee status clearly improved from preoperative to the latest follow-up when 23.4% of the patients reported having no restriction of knee function (I), 56.3% had mild restriction (II), 17,2% had moderate restriction (III) and 3.1% revealed severe restriction (IV). CONCLUSIONS: The CaReS technique is a clinically effective and safe method for the reconstruction of isolated osteochondral defects of the knee joint and reveals promising clinical outcome up to 5 years after surgery. A longer follow-up period and larger patient cohorts are needed to evaluate the sustainability of CaReS treatment.

[Bone tissue engineering. Reconstruction of critical sized segmental bone defects in the ovine tibia]. / Knochen-Tissue-Engineering. Rekonstruktion segmentaler Knochendefekte kritischer Größe in der Schafstibia.

Well-established therapies for bone defects are restricted to bone grafts which face significant disadvantages (limited availability, donor site morbidity, insufficient integration). Therefore, the objective was to develop an alternative approach investigating the regenerative potential of medical grade polycaprolactone-tricalcium phosphate (mPCL-TCP) and silk-hydroxyapatite (silk-HA) scaffolds.Critical sized ovine tibial defects were created and stabilized. Defects were left untreated, reconstructed with autologous bone grafts (ABG) and mPCL-TCP or silk-HA scaffolds. Animals were observed for 12 weeks. X-ray analysis, torsion testing and quantitative computed tomography (CT) analyses were performed. Radiological analysis confirmed the critical nature of the defects. Full defect bridging occurred in the autograft and partial bridging in the mPCL-TCP group. Only little bone formation was observed with silk-HA scaffolds. Biomechanical testing revealed a higher torsional moment/stiffness (p < 0.05) and CT analysis a significantly higher amount of bone formation for the ABG group when compared to the silk-HA group. No significant difference was determined between the ABG and mPCL-TCP groups. The results of this study suggest that mPCL-TCP scaffolds combined can serve as an alternative to autologous bone grafting in long bone defect regeneration. The combination of mPCL-TCP with osteogenic cells or growth factors represents an attractive means to further enhance bone formation.

High-density SNP association study and copy number variation analysis of the AUTS1 and AUTS5 loci implicate the IMMP2L-DOCK4 gene region in autism susceptibility.

Autism spectrum disorders are a group of highly heritable neurodevelopmental disorders with a complex genetic etiology. The International Molecular Genetic Study of Autism Consortium previously identified linkage loci on chromosomes 7 and 2, termed AUTS1 and AUTS5, respectively. In this study, we performed a high-density association analysis in AUTS1 and AUTS5, testing more than 3000 single nucleotide polymorphisms (SNPs) in all known genes in each region, as well as SNPs in non-genic highly conserved sequences. SNP genotype data were also used to investigate copy number variation within these regions. The study sample consisted of 127 and 126 families, showing linkage to the AUTS1 and AUTS5 regions, respectively, and 188 gender-matched controls. Further investigation of the strongest association results was conducted in an independent European family sample containing 390 affected individuals. Association and copy number variant analysis highlighted several genes that warrant further investigation, including IMMP2L and DOCK4 on chromosome 7. Evidence for the involvement of DOCK4 in autism susceptibility was supported by independent replication of association at rs2217262 and the finding of a deletion segregating in a sib-pair family.

[Paraganglioma--a rare cause of mediastinal lesions]. / Das Paragangliom--seltene Ursache einer mediastinalen Raumforderung.

A 73-year-old female patient was admitted to our clinic for further clarification of a suspicious mediastinal lesion. Endosonographically, we performed a fine-needle aspiration biopsy. Clinical and radiological findings as well as cytology hardened the suspicion of a paraganglioma as being the cause of the mediastinal lesion. Finally, this diagnosis was confirmed histologically after complete surgical resection of the lesion. This case report on a mediastinal paraganglioma includes a concise summary of diagnostic procedures and therapeutic options for this rare disease.

A humanised tissue-engineered bone model allows species-specific breast cancer-related bone metastasis in vivo.

Bone metastases frequently occur in the advanced stages of breast cancer. At this stage, the disease is deemed incurable. To date, the mechanisms of breast cancer-related metastasis to bone are poorly understood. This may be attributed to the lack of appropriate animal models to investigate the complex cancer cell-bone interactions. In this study, two established tissue-engineered bone constructs (TEBCs) were applied to a breast cancer-related metastasis model. A cylindrical medical-grade polycaprolactone-tricalcium phosphate scaffold produced by fused deposition modelling (scaffold 1) was compared with a tubular calcium phosphate-coated polycaprolactone scaffold fabricated by solution electrospinning (scaffold 2) for their potential to generate ectopic humanised bone in NOD/SCID mice. While scaffold 1 was found not suitable to generate a sufficient amount of ectopic bone tissue due to poor ectopic integration, scaffold 2 showed excellent integration into the host tissue, leading to bone formation. To mimic breast cancer cell colonisation to the bone, MDA-MB-231, SUM1315, and MDA-MB-231BO breast cancer cells were cultured in polyethylene glycol-based hydrogels and implanted adjacent to the TEBCs. Histological analysis indicated that the breast cancer cells induced an osteoclastic reaction in the TEBCs, demonstrating analogies to breast cancer-related bone metastasis seen in patients.

[Hospital admisions and consultations in a dialysis population]. / Consultas e ingresos hospitalarios de una población de un centro de diálisis.

UNLABELLED: The hemodialysis (HD) population continues growing and aging, reason why they are required to adapt the human, economic and materials resources to be taken care of. OBJECTIVE: To analyze the distribution of the consultations and the times of admissions in the different Hospital services of which an peripheral arranged HD Center depends. METHOD: We analyzed all the consultations to the Hospital Urgencies Departments and Hospitable admissions of all the patients who received HD in the arranged Center Ponfedial, (sanitary area Ponferrada of 150,000 inhabitants) in period 01/12/02 to the 31/05/05. RESULTS: We prospectively examined a population of 87 HD patients (71.0+/-12.5 years, 77.9 % male, 31.4% diabetics) time in HD 21.0+/-22.7 months. They were a total of 286 (9.5/month) consultations in the Service of Urgencies (2.31 consult/patient/year), 37.4% of them did not motivate admissions. The most frequent consultation (28,9%) was the complications of vascular access (70,9% of them required positioning a transitory catheter; 1.1 complication of catheter/months, 1 permanent catheter is placed/1.2 months and 1 fistulography/1.2 months), cardiac causes 10.3%, acute pulmonar edema: 9.3%, infectious: 8.4% and traumatologic: 8.4%. There were 179 admissions (5.9/month; 1.44 hospitalizations/patient/year; 4.0+/-14.2 days of admissions): cardiovascular cause: 37.4%, by vascular access: 18.4%, infectious disease: 17.0%, digestive: 6.7%, traumatologic: 3.9% and by other causes: 11.0%. The cardiovascular group takes 46.5% (60.8% of them by vascular peripheral disease) of the total of days of hospitalizations, infectious 16.7%, neoplasic 8.4% and vascular access 7.6%. The neoplasic causes were the greater average with 36.0+/-21.6 days of hospitalization, by amputations 23.0+/-38.1 days, by stroke 14.5+/-10.6 days, infected ulcers of lower extremities members 10.0+/-19.0, other vascular treatments 10.0+/-4.7, ischemic heart disease 8.5+/-20.3 and heart failure 7.5+/-5.2 days. Our prevalent population of 49.5 patients needed 3 to 7 hospitable beds, 0.33 temporal catheter, 1 tunneled permanent catheter and 1 fistulography per month. CONCLUSIONS: The cardiovascular causes, the accesses and the infectious ones are the main causes of consultations, hospital admissions and time of hospitalizations.

Functional brain networks during picture encoding and recognition in different odor contexts.

Contextual odors can serve as retrieval cues when applied during encoding and recall/recognition of information. To investigate the neuronal basis of these observations, we collected functional MRI data while participants (n=51) performed an encoding and recognition memory task during which odors (congruent: CO or incongruent: IO) were presented as contextual cues. Recognition performance was not influenced by odor, but there was increased activation in the piriform cortex during successful encoding in the CO group, possibly indicating enhanced retrieval of information previously integrated with an olfactory percept. Moreover, group-independent component analysis revealed a stronger task-modulation of subcortical networks for IO versus CO during the recognition task, pointing to differences in olfactory processing. These observations provide a deeper understanding of the involvement of functional neuronal networks in memory tasks and a basis for further evaluation of the impact of odor contexts.

Scaffold-cell bone engineering in a validated preclinical animal model: precursors vs differentiated cell source.

The properties of osteoblasts (OBs) isolated from the axial skeleton (tOBs) differ from OBs of the orofacial skeleton (mOBs) due to the different embryological origins of the bones. The aim of the study was to assess and compare the regenerative potential of allogenic bone marrow-derived mesenchymal progenitor cells with allogenic tOBs and allogenic mOBs in combination with a mPCL-TCP scaffold in critical-sized segmental bone defects in sheep tibiae. After 6 months, the tibiae were explanted and underwent biomechanical testing, micro-computed tomography (microCT) and histological and immunohistochemical analyses. Allogenic MPCs demonstrated a trend towards a better outcome in biomechanical testing and the mean values of newly formed bone. Biomechanical, microCT and histological analysis showed no significant differences in the bone regeneration potential of tOBs and mOBs in our in vitro study, as well as in the bone regeneration potential of different cell types in vivo. Copyright © 2015 John Wiley & Sons, Ltd.

Needlestick injuries during medical training.

Medical students are at risk of acquiring infections caused by needlestick injuries, although it is unknown when needlestick injuries are most likely to occur during medical training. The aim of this study was to define high-risk periods over the course of medical training. A cross-sectional study was conducted among medical students in the first, third, fourth and fifth years of training at two medical schools in Munich. Overall, 1317 (85%) students returned a questionnaire on demographic data, vaccination status against hepatitis B, lifetime prevalence of needlestick injuries, level of knowledge about measures after such accidents, and transmission risks. Lifetime prevalence of needlestick injuries was 23%, ranging from 12% in first year students to 41% in fourth year students. These accidents happened most commonly during medical internships, especially during blood-taking practices; an activity that usually starts during the third year of training. The frequency of respondents not vaccinated against hepatitis B also varied between first (21%) and fourth (6.6%) year students. Needlestick injuries occur frequently and early on in medical training. In order to decrease the risk of preventable infections, complete coverage of vaccination against hepatitis B should be achieved early in medical training.

[Acute effects on the health of children after accidental exposure to epichlorohydrine]. / Akute gesundheitliche Effekte bei Kindern nach einer akzidentellen Freisetzung von Epichlorhydrin.

PURPOSE: In September 2002, two freight trains collided at Bad Muender, Germany. The inhabitants were potentially exposed to combustion products and to the human carcinogen epichlorohydrine (ECH). We aimed to describe the geographical distribution of and potential risk factors for acute symptoms among children residing in Bad Muender. METHODS: The parents of a random sample of children were invited to answer a mail-in questionnaire (response rate 63%). The main outcome measures were self-reported acute symptoms potentially associated with combustion products (e. g., irritation of the eyes, nose, or throat) and stress-related unspecific symptoms (e. g., gastrointestinal complaints, sleep problems, headaches). The main location during the first 26 hours after the train accident served as exposure proxy measure. In addition, potential predictors for the symptoms under study were assessed. RESULTS: The prevalence of symptoms associated with combustion products was 5.9%. Unspecific symptoms were reported for 6.3% of the children. Main location and prevalence of symptoms were not significantly associated. Physician-diagnosed asthma and nasal allergies were the main predictors of symptoms. CONCLUSION: The prevalence of acute symptoms was relatively high in a random sample of children living close to the incident. However, associations between exposure to the accident and symptoms could not be established conclusively.