[Balloonsacroplasty: C-arm or CT controlled application? : Experience with 46 patients]. / Ballonsakroplastie: C-Bogen-kontrolliert oder CT-gesteuert? : Erfahrungen bei 46 Patienten.

INTRODUCTION: Sacral insufficiency fractures are often overlooked and lead to severe therapy-resistant pain. These fractures can be most sensitively detected with magnetic resonance imaging (MRI). Similar to balloon kyphoplasty, sacroplasty provides fixation of these fractures with cement. OBJECTIVES: This study was carried out to investigate whether pain is reduced using this method and whether computed tomography (CT)-guided cement application results in less cement extravasation and fewer complications than C-arm controlled application. MATERIAL AND METHODS: In a retrospective multicenter study, 46 patients (41 female, 5 male) with an average age of 75 years were treated by sacroplasty. The procedure was performed with CT-guidance for 25 patients and with C-arm control for 21 patients. Pain was evaluated using a visual analog scale. Patients were followed up for 6 months. RESULTS: The average operation time was 35 min and postinterventional hospital stay averaged 4 days. In the CT group pain decreased from an average score of 8.8 ± 0.7 preoperatively to 2.6 ± 0.6 postoperatively (p < 0.001) and in the C-arm group pain decreased from 8.2 ±1.0 to 2.2± 1.4 (p < 0.001). There were no cases of cement extravasation in the CT group (0 out of 25 = 0 %) and 8 asymptomatic cases in the C-arm group (8 out of 21 = 38 %). In addition, there were two injuries to the superior gluteal artery with hematoma in the area of puncture, one requiring operative treatment. There were two mortalities in the CT group from lung disease and stroke during the study but this was unrelated to the operation. CONCLUSION: Balloon sacroplasty results in a reliable and significant reduction in pain for sacral insufficiency fractures. The C-arm controlled cement application resulted in more frequent extravasation and complications than CT-guided application.

[Geriatric complex treatment of proximal femoral fractures? Who profits the most?]. / Geriatrische Komplexbehandlung bei proximalen Femurfrakturen. Wer profitiert am meisten?

BACKGROUND: Geriatric complex treatment (GCT) is a new type of early rehabilitative care. The main goal is to maintain personal autonomy. GCT includes 21 treatments by physio-, occupational and speech therapists, accompanied by specialized nurses. The aim of this study was to investigate how elderly patients benefit from the GCT after hip fractures (HF). PATIENTS AND METHODS: In all, 124 patients [≥70 years; 50 patients underwent GCT, 74 underwent standard traumatologic care (STC)] after operative treatment for HF were included. Cognitive impairment was diagnosed in 46% of GCT patients and 70% were classified as ASA III. In the STC group, 23% were cognitively impaired and 50% were classified ASA III. RESULTS: Significantly more patients of the GCT group were both cognitively impaired and classified as ASA III. Among the cognitively impaired, the STC group reached a median of 20 points on the Barthel index, while the GCT group reached 60 points. CONCLUSION: The GCT patients in our study were more likely to be dependent on care and have cognitive deficits. Only cognitively impaired patients were shown to benefit from GCT. In the remaining patients no difference was found, thus, only cognitively impaired patients currently undergo GCT at our clinic.

Constitutional mismatch repair-deficiency and whole-exome sequencing as the means of the rapid detection of the causative MSH6 defect.

BACKGROUND: Cases of children with more than one type of cancer either diagnosed simultaneously or successively, rarely occur in pediatric oncology. A second malignant neoplasm may be caused by mutagenic effects of the treatment of the primary malignancy and/or may point towards an underlying genetic cancer susceptibility syndrome. One example of such a syndrome is constitutional mismatch repair-deficiency, (CMMR-D) which carries an increased risk of various tumors including childhood hematologic malignancies and Lynch syndrome associated tumors. Timely diagnosis of CMMR-D is crucial, since this diagnosis has implications for the entire family. PATIENT: We report the case of a 15-year-old girl who was born to consanguineous parents. At the age of 20 months she was diagnosed with a T-cell non-Hodgkin lymphoma. Treatment was given according to NHL-BFM 95. 12 years later, an invasive adenocarcinoma of the colon was surgically removed which relapsed shortly afterwards. METHODS: Whole-exome sequencing of germline DNA was employed to rapidly detect the underlying mutation in this suspected CMMR-D patient. RESULTS: After a short turnaround time of less than 3 weeks, the diagnosis of CMMR-D could be confirmed by the identification of a homozygous 29-bp deletion in MSH6 (exon 6), which was confirmed by independent methods. CONCLUSIONS: We demonstrate that "bed-side" whole-exome sequencing is both feasible and cost-effective and may be the method of choice to rapidly uncover the genetical basis of (inherited) diseases.

[Dislocated femoral neck fractures in geriatric patients. One-year follow-up]. / Die dislozierte Schenkelhalsfraktur des geriatrischen Patienten. Einjahresergebnisse.

BACKGROUND: In geriatric patients with Pauwels II and III type femoral neck fractures, endoprosthesis is the treatment of choice. PURPOSE: What are the long-term results after surgery? MATERIALS AND METHODS: In 2007 and 2008, 104 public health insurance (AOK) patients with displaced femoral neck fractures were treated surgically at our hospital. This number of included patients places us in the 97th percentile of all hospitals in Germany. Because the patients were publicly insured, all health information was available, including completely retrospective posthospital discharge, inpatient course, and 1-year mortality. RESULTS: A total of 77 women and 27 men (average age of 83.5 years) were included in the study. In addition to the femoral neck injury, 19% of the patients had an accompanying PCCL of 3, and 44% had a PCCL of 4. In addition, 16% suffered from heart failure, 23% from diabetes, and 19% from renal insufficiency. Time to surgery averaged 1-day postinjury. A dual head prosthesis (hemiprosthesis) was implanted in 81.4 % of cases, and a total joint prosthesis in 18.6%. Average operative time skin to skin was 53 min. Average inpatient stay was 14 days in 2007 and 12 days in 2008. On discharge, 71% of patients could ambulate independently. Of the remaining patients, two-thirds were already not ambulating independently prior to the fracture. Hospital mortality averaged 6% (national average 8.1%), and 30-day and 90-day mortality rates were 6% (n = 7) and 16.3% (n = 17). Within 1 year, 22.2% of patients (n = 23) died (national average 26.8%), with a natural mortality probability of 7.1% for an age of 83.5 years. Five patients were re-admitted, for contralateral prosthetic implantation (n = 4) or revision after periprosthetic fracture (n = 1), and 54.6% of patients were admitted to hospital during the year for other diseases (national average 53.8%). CONCLUSION: Endoprosthesis placement for displaced femoral neck fractures is a common, safe procedure. However, the patients are old and have comorbidities. Despite recent decreases in hospital mortality, the risk of death remains more than twice as high within 1 year than that for uninjured patients of the same age.

[Pericardial perforation 2.5 years after kyphoplasty. A rare complication after cement extravasation]. / Herzperforation 2,5 Jahre nach Kyphoplastie. Eine seltene Komplikation nach Zementaustritt.

Kyphoplasty is an established method in the treatment of osteoporotic spine fractures. In 10-15% of cases cement extravasation and leakage into veins occur. We report about the rare course of an extravasation. In 2008 an osteoporotic compression fracture of L(4) and L(5) in a 62-year-old female patient was treated by kyphoplasty. In the treated vertebra filling of an outgoing vein towards the proximal right side occurred. Postoperatively the patient was free of complaints (VAS preoperative 9/10, postoperative 1/10). In the chest X-ray a small asymptomatic filling of a lung vessel on the left side was present. The patient arrived as an emergency case 2.5 years later with decompensated heart failure. In the chest CT and angiography cement emboli in the lung were seen as well as a perforation of the pericardium with beginning tamponade. A thoracotomy was performed. Intraoperatively two 4 cm long sharp cement pieces were removed from the heart, which had perforated the right ventricle. Leakages were closed by suture. The patient survived the operation and was dismissed after 2 weeks of intensive care for rehabilitation and from there dismissed home. Six months later she had no more problems. When filling vertebra in several levels one must pay attention to introducing cement with a thick consistency, otherwise venous emboli and lung emboli may occur. These are as a rule asymptomatic, but may result in exceptional life-threatening complications.

Lipophilic prodrugs of a triazole-containing colchicine analogue in liposomes: biological effects on human tumor cells.

Colchicine site binders--blockers of tubulin polymerization--are potential antimitotic agents for anticancer therapy. To reduce their systemic toxicity and improve biodistribution, encapsulation in nanosized liposomes may be employed. Liposomes present a convenient means for preparation of injectable formulations of hydrophobic compounds, however colchicine as such is known to leak through the lipid bilayer. In this study, newly synthesized triazole-containing analogues of colchicine and allocolchicine, and their palmitic and oleic esters (lipophilic prodrugs) were tested for anti-proliferative activity and apoptosis-inducing potential. In contrast to colchicine conjugates, whose activities ranged with those of colchicine, allocolchicine derivatives exhibited drastically lower effects and were discarded. Liposomes of about 100 nm in diameter composed of egg phosphatidylcholine--yeast phosphatidylinositol--palmitic or oleic prodrug, 8 : 1: 1, by mol, were prepared by standard extrusion technique and tested in a panel of four human tumor cell lines. Liposome formulations preserved the biological activities of the parent colchicinoid the most towards human epithelial tumor cells. Moreover, liposomal form of the oleoyl bearing colchicinoid inhibited cell proliferation more efficiently than free lipophilic prodrug. Due to substantial loading capacity of the liposomes, the dispersions contain sufficient concentration of the active agent to test wide dose range in experiments on systemic administration to animals.

[Kyphoplasty in the treatment of osteoporotic spine fractures. Experience in over 500 patients]. / Kyphoplastie zur Behandlung osteoporotischer Wirbelfrakturen. Eigene Erfahrungen mit über 500 Behandlungen.

For over 10 years, kyphoplasty has been established for the treatment of painful osteoporotic vertebral compression fractures. Its effectiveness has been substantiated in multiple clinical studies. Not only is prompt pain reduction achieved, but according to a new, large, long-term study, long-term survival is also increased. Balloon kyphoplasty was performed for 564 patients from 1 January 2008 until 31 July 2011. In all cases, pain was rated more than 6/10 points, and recent fracture was evident on cross-sectional imaging (CT or MRT) performed to supplement spine x-rays. Average patient age was 75.3 years; 71.3% of patients were female. Treated fracture levels ranged from Th3 to L5. A single level was treated in 372 cases, with two levels treated simultaneously in 128 cases, three levels in 48 cases, and four levels in 22 cases. Average operative time for all patients was 36 min. Eight different surgeons performed the procedures. Average convalescence time was 8 days which decreased progressively over the years. Pain was reduced from 8 preoperative to 2.4 points postoperative in the visual analogue scale. Six major complications (1.06%) occurred. Kyphoplasty is a good procedure to treat painful osteoporotic fractures from the lumbar to thoracic spine. Major complications occur seldom after kyphoplasty; however, they must be considered and clarified.

Kidney Transplantation in Abernethy Malformation: A Case Report.

Abernethy malformation is a rare disorder defined by congenital portosystemic shunt. Advances in clinical imaging have led to increased identification of this anomaly, which has proven to be more common and more clinically diverse than previously assumed. Late presentations are not uncommon. We present a 35-year-old patient with type Ia Abernethy malformation and biopsy-confirmed mesangiocapillary glomerulonephritis who was referred for deceased donor kidney transplantation. After the diagnosis was confirmed, the patient remained stable and asymptomatic on a supervised low-protein, high-carbohydrate diet. The patient received the kidney transplant from a brain-dead donor with standard characteristics. The procedure was uneventful; no vascular or vesical abnormalities could be identified at the surgical site. Recovery was uneventful with excellent graft function. Unique issues with immunosuppression were identified. Pharmacologic adjustments accounting for congenital complete portosystemic shunting affecting liver first pass effect as well as multiple drug interactions were necessary and sufficient. Abernethy malformation may follow indolent course into adulthood and may be an unrelated finding in a patient with chronic kidney disease. Kidney transplantation proved to be feasible and safe in this young male with apparently efficient compensatory mechanisms.

[Kyphoplasty update : What are the limits - what is possible?]. / Kyphoplastie Update : Wo liegen die Grenzen - was geht?

Kyphoplasty is an established procedure for the treatment of osteoporotic vertebral compression fractures. Developments in instrumentation and techniques have facilitated its use also for other localizations. In the hands of experienced practitioners smaller working cannulas and balloons have made successful treatment of high thoracic and cervical fractures and metastases possible. Balloon kyphoplasty performed for sacral insufficiency fractures in older patients plagued by chronic pain leads to marked pain reduction as well as faster weight-bearing. There are also early research results regarding the repair of tibial head defects and reinforcement with resorbable cement. These new procedures, which are currently applied by only a few surgeons, will be introduced and described in a case-specific manner.

[Cost-benefit calculation of kyphoplasty in osteoporotic spine fractures]. / Prozesskostenanalyse von Kyphoplastien bei osteoporotischen Sinterungsfrakturen.

BACKGROUND: Kyphoplasty is an established procedure for the treatment of vertebral fractures secondary to osteoporosis. It leads to correction of kyphosis as well as significant pain reduction. However, the material costs of 53% are very expensive. Is kyphoplasty cost effective? METHOD: We performed a cost analysis from patient presentation until discharge. Personnel costs as well as time expenditure were measured exactly, and total costs per case were calculated. RESULTS: In 2009, 118 patients underwent single level kyphoplasty. The average hospital stay was 6 days. The total reimbursement per patient was 6189.77 EUR. Material expenses were 3134.99 EUR (53%) and personnel 1552.86 EUR (26%). Personnel costs were allotted according to physician (8 h 52 min = 551.93 EUR), nursing (20 h 9 min = 629.69 EUR), and medical technician (11 h 15 min = 371.24 EUR) costs. The total cost per patient was 5868.23 EUR. DRG reimbursement was 6189.77 €, yielding an average revenue of 321.54 EUR.

[Kyphoplasty in osteoporotic spinal fractures]. / Kyphoplastie bei osteoporotischen Wirbelfrakturen.

Kyphoplasty has been the standard procedure for osteoporotic fractures for more than 5 years but the material costs are still very high. The aim of this study was to clarify whether pain reduction could be achieved without increasing the rate of new fractures and also in what areas costs could possibly be reduced. From 15.01.2007 until 15.01.2008, a total of 100 patients with 126 recent osteoporotic spinal fractures were treated by kyphoplasty with an average operation time of 38 min and follow-up times up to 12 months. During this follow-up period 15 lateral and 2 dorsal cement leakages remained asymptomatic and 1 dorsal leakage caused an incomplete paraparesis, which was finally cured completely. All patients were very content and pain measured on the visual analogous scale could be lowered from 8.0 before the operation to 2.7 points after the operation. With material costs of 3,056 Euro, there were additional operation costs of 247 Euro per case. The average effective weight was 2.84. On average 7,810 Euro returns could be achieved, deducting material and operation costs left 4,507 Euro per case. More than 40% of gains were reinvested in operation and material costs. Within 12 months 6 new fractures occurred despite medicinal prophylactic treatment which could also be successfully treated by kyphoplasty. The average visual analogous scale after 12 months was 2.1 points.Kyphoplasty still causes financial deficits due to high material costs, however, patients benefit from a reduction of pain.

[How to become a trauma surgeon: analysis of the current situation and concepts for career development in the new common field of orthopaedics and trauma surgery--part I]. / Der Weg zum Unfallchirurgen : Situationsanalyse und Konzepte zur Nachwuchsförderung in der Unfallchirurgie im Umfeld des neuen gemeinsamen Fachs Orthopädie/Unfallchirurgie - Teil I.

The lack of clinical residents especially in the surgical domains, including orthopaedics and trauma surgery, is not only omnipresent but also a topic of lively discussions. This lack originates from sociopolitical and healthcare policy issues as well as from a loss of attractiveness of all surgical disciplines. The loss is caused by the high workload and disadvantageous working hours especially in those disciplines with a high rate of emergencies, e.g. trauma surgery. Moreover, it is caused by the poorly structured and unpredictable period of residency. In order to anticipate the bottleneck in supply due to the lack of trainees, a number of structural and contextual measures have to be taken to improve both undergraduate und postgraduate surgical training. Due to the numerous facets of the topic the first part of this analysis refers to the period until the trainee decides on the field of training.A basic insight into the field of orthopaedics and trauma surgery can already be offered far before the period of medical studies itself. During undergraduate medical education the existing structures should be modified, the characteristics of the discipline should be emphasized and the charm of combining theory and practical skills should be highlighted in order to enhance student's perception of the discipline. This might begin during preclinical training and should be continued throughout clinical training and elective courses (basic wound care, TEAM approach, AO course for students and seminars for M.D. candidates). Contextual and structural improvements of the practical year are indispensable to arouse students' interest in our discipline. These options conjoined with the actual offers for students provided by our scientific society, such as guided tours during the annual congress, travelling grants and the recently inaugurated summer school, might provide the basis for clearly structured information and offer a distinct stimulus to apply for residency in our field.

[How to become a trauma surgeon: analysis of the current situation and concepts for career development in the new common field of orthopaedics and trauma surgery--part II]. / Der Weg zum Unfallchirurgen: Situationsanalyse und Konzepte zur Nachwuchsförderung in der Unfallchirurgie im Umfeld des neuen gemeinsamen Faches Orthopädie/Unfallchirurgie--Teil II.

An increasing lack of young fellowship trainees in operative medicine, particularly in orthopaedics and traumatology and the various options to counteract this problem during the phases until the individual decision for residency and the fellowship program is made, were the focus of part I. The present part concentrates on residency and the fellowship phase including the individual perspectives after successful training. With respect to an attractive and highly qualified training in orthopaedics and traumatology, three essential points are to be made: a timely general framework, the establishment of a clinic-specific management of training and a general evaluation of training in the sense of a benchmarking system. A flexible work schedule including structural entities, such as an in-hospital day care facility for children, a structured and reliable curriculum of training according to a model curriculum to be adapted to the corresponding training unit including options of rotation to other facilities of training and the integration of nationwide education and mentoring programs represent further elements of an attractive training program. Thus the quality of training will become a decisive criterion of selection. The fellowship program for specialized traumatology inevitably leads to limitations of the whole spectrum of the field with an increasing specialization. In the future the contents of fellowship training will need a well-considered adaptation to the clinical needs and realities in the light of the emerging national trauma network program. A wide field of activity will open up to specialists in orthopaedics and traumatology with a focus on special traumatology considering the rapid changing field of hospital and outpatient care. Thus a systematic and creative reorganization of the residency and fellowship phases will overcome any problem of attractiveness.

Designing pharmacogenetic projects in industry: practical design perspectives from the Industry Pharmacogenomics Working Group.

Pharmacogenetic association studies have the potential to identify variations in DNA sequence which impact drug response. Identifying these DNA variants can help to explain interindividual variability in drug response; this is the first step in personalizing dosing and treatment regimes to a patient's needs. There are many intricacies in the design and analysis of pharmacogenetic association studies, including having adequate power, selecting proper endpoints, detecting and correcting the effects of population stratification, modeling genetic and nongenetic covariates accurately, and validating the results. At this point there are no formal guidelines on the design and analysis of pharmacogenetic studies. The Industry Pharmacogenomics Working Group has initiated discussions regarding potential guidelines for pharmacogenetic study design and analyses (http://i-pwg.org) and the results from these discussions are presented in this paper.

The kakapo mutation affects terminal arborization and central dendritic sprouting of Drosophila motorneurons.

The lethal mutation l(2)CA4 causes specific defects in local growth of neuronal processes. We uncovered four alleles of l(2)CA4 and mapped it to bands 50A-C on the polytene chromosomes and found it to be allelic to kakapo (. Genetics. 146:275- 285). In embryos carrying our kakapo mutant alleles, motorneurons form correct nerve branches, showing that long distance growth of neuronal processes is unaffected. However, neuromuscular junctions (NMJs) fail to form normal local arbors on their target muscles and are significantly reduced in size. In agreement with this finding, antibodies against kakapo (Gregory and Brown. 1998. J. Cell Biol. 143:1271-1282) detect a specific epitope at all or most Drosophila NMJs. Within the central nervous system of kakapo mutant embryos, neuronal dendrites of the RP3 motorneuron form at correct positions, but are significantly reduced in size. At the subcellular level we demonstrate two phenotypes potentially responsible for the defects in neuronal branching: first, transmembrane proteins, which can play important roles in neuronal growth regulation, are incorrectly localized along neuronal processes. Second, microtubules play an important role in neuronal growth, and kakapo appears to be required for their organization in certain ectodermal cells: On the one hand, kakapo mutant embryos exhibit impaired microtubule organization within epidermal cells leading to detachment of muscles from the cuticle. On the other, a specific type of sensory neuron (scolopidial neurons) shows defects in microtubule organization and detaches from its support cells.

[Minimally invasive percutaneous instrumentation for spine fractures]. / Minimal-invasive perkutane Instrumentation bei Wirbelsäulenfrakturen.

When operating unstable spine fractures by an open dorsal approach, detachment of paravertebral muscles results in bleeding and later functional disturbances. Long incisions over spinous processes cause pain and later cosmetic issues. With the sextant of Medtronic a system is at our disposal which permits a percutaneous approach with pedicle screws and longitudinal supports by a target device via six small incisions. From 15 November 2007 until 15 May 2008, 36 unstable spine fractures were treated by a minimally invasive technique; 14 men and 22 women were treated. The average age was 61 years (22-88 years). According to the Magerl classification there were mostly A3.3 fractures. The average incision-closure time was 42 min (14-96 min) with an average X-ray exposure time of 3.35 min (1.5-7 min). Blood loss was 10-20 ml and average hospital stay was 11 days. Pain judged according to a visual analog scale decreased from 6.1 to 1.4 points. Incorrect screw positions without clinical relevance were seen in 2% without necessity for revision. From 1 February 2007 until 15 November 2007, 40 patients (24 men, 16 women, average age 53 years) with unstable spine fractures were treated by the same surgeons by open dorsal instrumentation. The average operation time in this control group was 91 min and the average time at hospital 15.5 days. Percutaneous instrumentation with cannulation of pedicles with a guide wire under X-ray control permits a safe application while preserving soft tissues without relevant blood loss. Operating times can be drastically reduced compared with the open technique. The implants are more expensive but pay for themselves by shorter stays in the OR and hospital.

[Operative treatment of instable osteoporotic spine fractures. A good guide in coding of diagnosis]. / Operative Versorgung instabiler osteoporotischer Wirbelsäulenfrakturen. Eine wichtige Kodierhilfe.

The combination of kyphoplasty and fixateur interne is an essential therapy with osteoporotic unstable fractures. Material costs of 5500 Euro are not sufficiently covered by returns through DRG I09. Thus operations are often performed in 2 stages, an initial one and a second 30 days later. This means more strain for the patient and partly also loss of correction. Therefore in 2008 we requested the InEK that codes for one-and two-segmental implantation of material in a vertebrae with preceding restoration of vertebral height (5-839.a0 and 5-839.a1) combined with a percutaneous dorsal operation with a screw-rod system in the future would be represented by I19B in G-DRG system with returns of 11,110,40 Euro. Prerequirement is coding of kyphoplastiy as main procedure and percutaneous implantation of a fixateur with procedure 5-835.5. Some procedures in orthopedic surgery implying technical improvements and rising implant costs are not sufficiently rewarded. Thus is make sense to inform InEK by corresponding proposals.

Presynaptic development at the Drosophila neuromuscular junction: assembly and localization of presynaptic active zones.

We describe the extent to which presynaptic structures at the embryonic neuromuscular junction of Drosophila can form in mutants where development of postsynaptic somatic muscles is affected. Although twist mutant embryos lack mesoderm, motor axons still grow out of the CNS and form morphologically normal presynaptic active zones, independent of their target cells. In myoblast city mutant embryos, myoblasts do not fuse but form fully differentiated mononucleate muscles, which make functional neuromuscular synapses with correctly localized presynaptic active zones. Myoblasts also fail to fuse but still attract appropriate innervation in mef2 mutant embryos. However, these myoblasts fail to differentiate into muscles and presynaptic active zones fail to localize at neuromuscular contacts. Thus, the process of synapse formation can be genetically separated from the process of target recognition, revealing that localization of presynaptic active zones requires mef2-dependent muscle differentiation.