[Spondylolisthesis in the growing spine]. / Spondylolisthese im Wachstumsalter.

BACKGROUND: Spondylolisthesis (Greek for sliding vertebra) in children is usually the result of a defect (=lysis) or an elongation of the interarticular portion. The cause can be a congenital dysplasia of the dorsal stabilizing structures or pressure of the facet on the interarticular portion. This is a consequence of lumbar lordosis which is necessary for an upright posture. TREATMENT: The treatment depends on the symptoms and the risk of progression. This is related to the sliding distance, the degree of secondary dysplasia of the vertebral bodies and the sagittal profile, which is considered in the Mac-Thiong classification. For low-grade olistheses, conservative therapy is an option; for a symptomatic lysis without disc degeneration, pars repair should be considered. In higher-grade olistheses, repositioning and spondylodesis are usually recommended. Repositioning improves the fusion rate and sagittal profile, but increases the risk of nerve root damage, so complete repositioning should not be forced.

Interfacial electrostatics of poly(vinylamine hydrochloride), poly(diallyldimethylammonium chloride), poly-l-lysine, and poly-l-arginine interacting with lipid bilayers.

Charge densities of cationic polymers adsorbed to lipid bilayers are estimated from second harmonic generation (SHG) spectroscopy and quartz crystal microbalance with dissipation monitoring (QCM-D) measurements. The systems surveyed included poly(vinylamine hydrochloride) (PVAm), poly(diallyldimethylammonium chloride) (PDADMAC), poly-l-lysine (PLL), and poly-l-arginine (PLR), as well as polyalcohol controls. Upon accounting for the number of positive charges associated with each polyelectrolyte, the binding constants and apparent free energies of adsorption as estimated from SHG data are comparable despite differences in molecular masses and molecular structure, with ΔGads values of -61 ± 2, -58 ± 2, -57 ± 1, -52 ± 2, -52 ± 1 kJ mol-1 for PDADMAC400, PDADMAC100, PVAm, PLL, and PLR, respectively. Moreover, we find charge densities for polymer adlayers of approximately 0.3 C m-2 for poly(diallyldimethylammonium chloride) while those of poly(vinylamine) hydrochloride, poly-l-lysine, and poly-l-arginine are approximately 0.2 C m-2. Time-dependent studies indicate that polycation adsorption to supported lipid bilayers is only partially reversible for most of the polymers explored. Poly(diallyldimethylammonium chloride) does not demonstrate reversible binding even over long timescales (>8 hours).

[Hyaluronic acid gels for pressure regulation in glaucoma treatment]. / Hyaluronsäuregele zur Druckregulierung in der Glaukomtherapie.

BACKGROUND: The increasing numbers of glaucoma patients and complications occuring during treatment, such as restenosis and hypotony, require new treatment options to prevent blindness in patients. Therefore, the abovementioned problems should be solved to prolong the lifetime of implants and to prevent repeated surgery. OBJECTIVE: Can a novel stent with hyaluronic acid hydrogels (HA gel) as a functional unit be used to regulate pressure in glaucoma therapy in the long term? MATERIAL AND METHODS: Model stents were filled with HA gels and it was investigated if these could regulate the pressure and what the underlying mechanism is. RESULTS: The results of the investigations showed that the HA gel inside the stent functions as a pressure valve. Under certain equilibrium pressures the HA gel closes the stent and therefore retains the fluid. At a certain overpressure the HA gel enables the fluid to be released and leads to a self-regulated adjustment of the equilibrium pressure. DISCUSSION: The next step will involve miniaturization of the stents. Experiments will then show if the valve function will also work in the dimensions necessary for an eye implant and if the current problem of hypotension in glaucoma therapy can be solved.

The AP-1 transcription factor FOSL1 causes melanocyte reprogramming and transformation.

The MAPK pathway is activated in the majority of melanomas and is the target of therapeutic approaches. Under normal conditions, it initiates the so-called immediate early response, which encompasses the transient transcription of several genes belonging to the AP-1 transcription factor family. Under pathological conditions, such as continuous MAPK pathway overactivation due to oncogenic alterations occurring in melanoma, these genes are constitutively expressed. The consequences of a permanent expression of these genes are largely unknown. Here, we show that FOSL1 is the main immediate early AP-1 member induced by melanoma oncogenes. We first examined its role in established melanoma cells. We found that FOSL1 is involved in melanoma cell migration as well as cell proliferation and anoikis-independent growth, which is mediated by the gene product of its target gene HMGA1, encoding a multipotent chromatin modifier. As FOSL1 expression is increased in patient melanoma samples compared to nevi, we investigated the effect of enhanced FOSL1 expression on melanocytes. Intriguingly, we found that FOSL1 acts oncogenic and transforms melanocytes, enabling subcutaneous tumor growth in vivo. During the process of transformation, FOSL1 reprogrammed the melanocytes and downregulated MITF in a HMGA1-dependent manner. At the same time, AXL was upregulated, leading to a shift in the MITF/AXL balance. Furthermore, FOSL1 re-enforced pro-tumorigenic transcription factors MYC, E2F3 and AP-1. Together, this led to the enhancement of several growth-promoting processes, such as ribosome biogenesis, cellular detachment and pyrimidine metabolism. Overall, we demonstrate that FOSL1 is a novel reprogramming factor for melanocytes with potent tumor transformation potential.

[Management of postoperative wound infections following spine surgery : First results of a multicenter study]. / Management postoperativer Wundinfektionen nach Wirbelsäuleneingriffen : Erste Ergebnisse einer multizentrischen Studie.

INTRODUCTION: The number of spinal surgeries has increased significantly in the last decade, which has led to a correlating increase in the number of problems related to wound healing infection. Current literature has reported a spinal wound infection rate of 0.4 to 20 %. The gold standard for surgical restoration of the infection is to use supportive antibiotics, but this concept of wound management in infections is often not sufficiently standardized and shows a large variance between individual clinics. The present study is to first collect data on the number of wound infections, the clinic's internal standards, the use of methods and tools and the management of revisions in Germany. MATERIAL AND METHODS: A questionnaire has been designed for detecting the number of postoperative wound infections, which need to be treated surgically, and the various treatment regimens used. The questionnaire was sent to all members of the DWG (n = 1275). An example of the questionnaire was to determine clinical internal standards and the procedure for the initial treatment of wound infection, the procedure for second look surgery and the number of revisions requested to infection healing. RESULTS: The study has accepted 67 answer sheets covering a period from June 2013-November 2013. On average, the participating hospitals perform 582 spinal operations and an average of 8 revision surgeries due to infection annually. The average rate of infection was 1.7 %. 55 % reported having no fixed standard of care. 97 % reported wound irrigation and debridement during the first revision. Indication for second look revisions was based on the local examination of the wound conditions. On average 2.2 revisions had been performed to reach effective wound healing. 81 % of the colleagues showed readiness to participate in a multicenter trial. CONCLUSION: The results show that there is a need for uniform standards in the treatment of postoperative infections. Surgical debridement and lavage have a major role in the treatment of infection. The overall rate of postoperative infections, of the clinics surveyed, was approximately 1.7 % per year. The infections were healed with approximately 2 revisions utilizing variety of different treatment strategies.

Surface or full cementation of the tibial component in total knee arthroplasty: a matched-pair analysis of mid- to long-term results.

INTRODUCTION: Despite the clinical success of cemented TKA, aseptic loosening of the tibial component remains a potential long-term complication. Considering the constantly growing revision burden, there is a need for clarification regarding controversial views on primary fixation techniques. In this retrospective analysis, surface (SC) or full cementation (FC) of tibial components was compared in a matched-pair and long-term setting. METHODS: Matching pairs were identified in a patient series from 1989 to 1994. Hence, 25 primary TKA (SC) were compared to 42 TKA (FC). The study population included 34 patients with rheumatoid arthritis. Patients were matched in a 1:1.7 fashion according to age, gender and initial diagnosis. Outcome was assessed by multiple clinical parameters, detailed radiographic evaluation and survivorship analysis. RESULTS: Clinical follow-up (FU) was at 10.3 years (range 1.5-15.6) for the SC and 12 years (range 0.2-16.2) for the FC group. Survivorship at 10 years was 100 % for the surface cemented trays and 93.3 % (95 % CI 80.5-100) for the fully cemented implants considering aseptic loosening as endpoint (p = 0.3918). Improvement of the AKS Score was greater in the SC group (p = 0.044) and patients in this group were more satisfied (p = 0.013). For any other clinical parameter, no difference could be observed (p > 0.05). CONCLUSION: Results of this study showed no statistically significant difference regarding long-term survivorship for the two cementing techniques. This finding questions the claimed advantage of full cementation for tibial components. The presented data do not support the concern that surface cementation results in insufficient fixation in patients with rheumatoid arthritis.

Comparison of platelet-rich plasma and VEGF-transfected mesenchymal stem cells on vascularization and bone formation in a critical-size bone defect.

Both platelet-rich plasma (PRP) and vascular endothelial growth factor (VEGF) can promote regeneration. The aim of this study was to compare the effects of these two elements on bone formation and vascularization in combination with bone marrow stromal cells (BMSC) in a critical-size bone defect in rabbits. The critical-size defects of the radius were filled with: (1) a calcium-deficient hydroxyapatite (CDHA) scaffold + phVEGF(165)-transfected BMSC (VEGF group), (2) CDHA and PRP, or (3) CDHA, autogenous BMSC, and PRP. As controls served: (4) the CDHA scaffold alone and (5) the CDHA scaffold and autogenous BMSC. The volume of new bone was measured by means of micro-CT scans, and vascularization was assessed in histology after 16 weeks. Bone formation was higher in the PRP + CDHA, BMSC + CDHA, and PRP + BMSC + CDHA groups than in the VEGF group (p < 0.05). VEGF transfection significantly promoted vascularization of the scaffolds in contrast to BMSC and PRP (p < 0.05), but was similar to the result of the CDHA + PRP + BMSC group. The results show that VEGF-transfected BMSC as well as the combination of PRP and BMSC improve vascularization, but bone healing was better with the combination of BMSC and PRP than with VEGF-transfected BMSC. Expression of VEGF in BMSC as a single growth factor does not seem to be as effective for bone formation as expanded BMSC alone or PRP which contains a mixture of growth factors.

[Sintering prophylaxis of a vertebral body replacement: anterior cement augmentation of vertebral end plates]. / Sinterungsprophylaxe eines Wirbelkörperersatzes : Anteriore Zementaugmentation von Wirbelkörperendplatten.

Due to the increasing number of elderly patients with osteoporosis, the incidence of more complex operations demanding a vertebral body replacement is increasing in this population. Cement augmentation of pedicle screws helps to prevent screw pullout. Similarly it is possible to augment the end plates in anterior spine surgery in order to prevent cage subsidence. The technique is simple, quick and safe, as needles can be placed under visual control. In a series of 20 patients neither surgery-related complications nor aseptic loosening were found.

[Dynamic instrumentation techniques in early-onset scoliosis]. / Dynamische Verfahren bei der juvenilen Skoliose.

Similar to the situation in idiopathic scoliosis, the decision for operative or conservative treatment is based on the progression of the curve. Apart from age and Cobb angle, the rib-vertebral angle difference and rotation of the vertebrae are decisive for the prognosis. Surgery is indicated if, despite consistent brace treatment, a progression of >10 degrees or a Cobb angle of more than 45 degrees is found. Two different dorsal dynamic systems are presently used. With the growing rod technique, one or two rods are fixed to the spine cranially and caudally and are repeatedly"lengthened." Surgery is mandatory at least every 6 months. The Orthobiom system follows a new approach in which a rigid fixation is done in the middle of the curve, while the ends of the rods are linked to flexible connectors that can slide while the child grows. No long-time results are presently available for either system, so no general recommendations can be given.

Follow-up of 11-16 years after modular fixed-bearing TKA.

To present representative data of long-term survivorship and clinical outcome for the PFC total knee arthroplasty (PFC-TKA). A consecutive series of 141 TKA was followed for a mean of 13 years (range, 11-16 years). Sixty-five knees were evaluated, 30 of these clinically and radiographically. Twenty-eight knees could only be assessed with the use of a questionnaire. Six patients were living in nursing homes. Fifty-four patients (65 knees) had died. Eleven had undergone a revision. One patient was considered lost to follow-up. With re-operation for any reason as the endpoint, the 10-year survival rate was 92% (n = 91 patients at risk), and the 14-year survival rate was 91% (n = 12). With aseptic loosening of the implant as the endpoint, the 10- and 14-year survival rates were 97%. The mean Knee Society and function scores were 76 and 48 points, respectively. In this multi-surgeon series modular fixed-bearing TKA had good clinical and radiographic results with excellent long-term survivorship.

[Pain therapy after spinal surgery]. / Schmerztherapie nach wirbelsäulenchirurgischen Eingriffen.

A dorsal approach during spinal surgery offers the possibility to distribute drugs directly to the nerve root or epidurally. This can be done via a single intraoperative dose or by placing an epidural catheter. A safe and effective analgesia can thereby be achieved. As placement is done under visual control, no major complications are to be expected. In nerve root compressions, additional local application of steroids and preoperative gabapentin seems sensible. No advantage of preemptive administration of other analgesics can be determined. Another problem, especially of ventral fusions, is the commonly needed autologous pelvic bone grafts. Here the local application of local anesthetics or opioids makes sense. In transthoracic approaches epidural analgesia is recommended by thoracic surgeons, but this is difficult to perform especially in children with deformities. Furthermore it is generally important not to compromise neuralgic controls by analgesic measures.

[Can failed back surgery be prevented? Psychological risk factors for postoperative pain after back surgery]. / Lässt sich eine "failed back surgery" verhindern? Psychologische Risikofaktoren für postoperative Schmerzen nach Wirbelsäulenoperationen.

Aside from the surgical technique used, the development of peri- and postoperative pain and impairments in patients following intervertebral disk surgery is also determined to a crucial extent by psychological factors. Based on a systematic literature review, we checked whether evidence-based recommendations could be deduced on how to take into account psychological risk factors in back surgery in order to avoid postoperative complications, such as failed back surgery syndrome. The current state of research suggests three groups of risk factors: (1) negative psychological factors, (2) preexisting pain chronification, and (3) psychological disorders. In the case of elective intervertebral disk surgery, these factors should therefore be determined and identified preoperatively and taken into account in the indication for surgery. Multimodal treatments could conceivably prove to be more effective, or else psychological pain management therapy might be considered prior to surgery so as to avoid postoperative complications. If surgery is medically unavoidable despite existing risk factors, postoperative treatment should incorporate psychological pain management therapy at an early stage in the context of a multidisciplinary approach.

[Pain and its treatment reflected in time]. / Der Schmerz und seine Therapie im Spiegel der Zeit.

This article describes the history of pain therapy and anesthesiology with respect to the field of surgery. The history of this part of medicine is dependent upon the development of the appropriate medication groups, which were of great importance in the field of pain therapy and anesthesiology. Specifically the development of nitrous oxide, ether, morphine and the first local anesthesiologic substances will be described and discussed. The above mentioned developments combined with the knowledge of physiology of pain and new results from psychological studies led to the modern pain therapy in recent perioperative treatment concepts. Modern pain therapy is a multimodal therapy concept with a variety of specialties working as a team to optimize an individualized therapy plan which respects the needs of every single patient under different circumstances (acute, perioperative and chronic pain).

VEGF producing bone marrow stromal cells (BMSC) enhance vascularization and resorption of a natural coral bone substitute.

Bone graft substitutes often exhibit poor bone regeneration in large defects because of inadequate vascularization. Studies have shown that if blood supply is compromised, application of osteogenic factors alone could not induce successful healing. This study was to evaluate the effects of vascular endothelial growth factor, which combined with a coralline scaffold, on vascularization, scaffold resorption and osteogenesis in a rabbit radius critical size defect model. The scaffold was either coated with a control-plasmid DNA (group 1), coated with VEGF-plasmid DNA (group 2), loaded with mesenchymal stem cells (BMSC) transfected with control plasmid (group 3) or with both stem cells and the VEGF plasmid (group 4). X-rays were taken every 4 weeks up to week 16, when animals were euthanized. The volume of new bone was measured by mu-CT scans and blood vessels were counted after anti-CD31 staining of endothelial cells. The results from the solitary VEGF- and VEGF-transfected cells (groups 2 and 4) demonstrated significantly enhanced vascularization, osteogenesis and resorption of the carrier when compared to the control group. The highest degree of osteogenesis was found when the carrier was loaded with BMSC (group 3), whereas VEGF-transfected cells led to the highest vascularization and fastest resorption of the bone substitute. Additionally, VEGF-transfected BMSC led to a more homogenous vascularization of the defect. The results indicate that VEGF can be a helpful factor to improve healing in large bone defects, in which bone substitutes will otherwise not be vascularized and replaced by fresh bone.

Compliance with continuous passive movement is low after surgical treatment of idiopathic club foot in infants: a prospective, double-blinded clinical study.

Treatment by continuous passive movement at home is an alternative to immobilisation in a cast after surgery for club foot. Compliance with the recommended treatment, of at least four hours daily, is unknown. The duration of treatment was measured in 24 of 27 consecutive children with a mean age of 24 months (5 to 75) following posteromedial release for idiopathic club foot. Only 21% (5) of the children used the continuous passive movement machine as recommended. The mean duration of treatment at home each day was 126 minutes (11 to 496). The mean range of movement for plantar flexion improved from 15.2 degrees (10.0 degrees to 20.6 degrees ) to 18.7 degrees (10.0 degrees to 33.0 degrees ) and for dorsiflexion from 12.3 degrees (7.4 degrees to 19.4 degrees ) to 18.9 degrees (10.0 degrees to 24.1 degrees ) (both, p = 0.0001) when the first third of therapy was compared with the last third. A low level of patient compliance must be considered when the outcome after treatment at home is interpreted.

Surgical management of paralytic scoliosis in myelomeningocele.

A retrospective analysis of 54 patients with paralytic scoliosis due to myelomeningocele, who underwent surgical treatment, was performed. The aim of this study was to compare different surgical techniques and to identify clinical parameters influencing primary and midterm results. Three surgical techniques were used: 1) group I, posterior fusion/instrumentation; 2) group II, anterior fusion/no instrumentation combined with posterior fusion/instrumentation; and 3) group III, anterior and posterior fusion/instrumentation. Average age at surgery was 13.1 years. A preoperative scoliosis angle of 90 degrees [interquartile range (25th-75th percentile) (IQR), 76-106 degrees] was primarily reduced to 38 degrees (IQR, 30-50 degrees). At final follow-up (mean, 3.3 years), correction deteriorated to 44 degrees (IQR, 38-65 degrees). The group III procedure resulted in a better midterm correction of scoliosis compared with group I (P = 0.02). The extension of anterior fusion correlated with primary and midterm correction of scoliosis (P < 0.03). Patients with a thoracic level of paralysis had a higher relative loss of correction compared with patients with a lumbar level (P < 0.06). This finding can be attributed mostly to group I patients (P = 0.011). Hardware complications occurred in 16 patients (30%). Relative loss of correction among these patients was high (P < 0.01) and relative midterm correction low (P = 0.001). We recommend anterior and posterior fusion, each with instrumentation for the treatment of paralytic scoliosis in myelomeningocele. In patients with a thoracic level of paralysis, the two-stage procedure is mandatory to reduce the risk of hardware complications and subsequent major loss of correction.

Complications of scoliosis surgery in children with myelomeningocele.

The purpose of the present study was to evaluate whether the high incidence of complications in scoliosis surgery in myelomeningocele (MMC) could be attributed to the surgical technique and whether improvements were possible. Between 1984 and 1996, 77 patients with MMC and scoliosis were treated surgically. The clinical and radiological follow-up ranged from 1 to 10 years with a mean follow-up of 3.6 years. The mean age at time of surgery was 12 years 8 months. The average preoperative scoliosis measured 90.20 degrees and was corrected by 47%. The first four patients were stabilized with Harrington rods after anterior correction with a Zielke device (group 1). Twenty-five patients were operated only from posterior, using Cotrel-Dubousset (CD) instrumentation (group 2). In 13 patients an anterior release and discectomy was performed prior to CD posterior instrumentation (group 3). In 26 patients (group 4) this was combined with an anterior instrumentation. The 9 patients of group 5 had congenital vertebral malformations which made a special treatment necessary. Complications could be divided into hardware problems, such as implant failure, dislocation or pseudarthrosis, infections, anesthetic, and neurologic complications. Hardware problems were seen in 29% of all patients. More hardware problems were seen with the Harrington rod (75%) and after solitary posterior instrumentation (30%). The occurrence of pseudarthrosis was dependent on the surgical technique, the extent of posterior spondylodesis, and lumbosacral fusion. Patients with hardware problems had a mean loss of correction of 49% compared to 13% in the other patients. Depending on the different surgical techniques a loss of more than 30% was seen in 12-75% of the cases. Early postoperative shunt failure occurred in four cases; delayed failure - after more than 1 year - in three cases. One patient died within 1 day due to an acute hydrocephalus, another died after 2 1/2 years because of chronic shunt insufficiency with herniation. Wound problems were not dependent on the surgical technique, but on the extent of posterior spondylodesis and the lumbosacral fusion. Based on this analysis we believe our current practice of instrumented anterior and posterior fusion is justified. Further, we are very careful to check shunt function prior to acute correction of spinal deformity.