Accessibility of osteochondral lesion at the capitellum during elbow arthroscopy: an anatomical study.

INTRODUCTION: Osteochondrosis dissecans (OCD) at the capitellum is a common pathology in young patients. Although arthroscopic interventions are commonly used, there is a lack of information about the accessibility of the defects during elbow arthroscopy by using standard portals. MATERIALS AND METHODS: An elbow arthroscopy using the standard portals was performed in seven fresh frozen specimens. At the capitellum, the most posterior and anterior cartilage surface reachable was marked with K-wires. Using a newly described measuring method, we constructed a circular sector around the rotational center of the capitellum. The intersection of K-wire "A" and "B" with the circular sector was marked, and the angles between the K-wires and the Rogers line, alpha angle for K-Wire "A" and beta angle for K-wire "B", and the corridor not accessible during arthroscopy was digitally measured. RESULTS: On average, we found an alpha angle of 53° and a beta angle of 104°. Leaving a sector of 51° which was not accessible via the standard portals during elbow arthroscopy. CONCLUSION: Non-accessible capitellar lesions during elbow arthroscopy should be considered preoperatively, and the informed consent discussion should always include the possibility of open procedures or the use of flexible instruments.

Treatment of radial head and neck fractures: in favor of anatomical reconstruction.

Radial head fractures represent the most common elbow fractures. Undisplaced fractures usually occur in isolation and can be treated nonsurgically. Displaced fractures should be treated surgically. Simple two-part fractures can easily be handled by osteosynthesis, but comminuted fractures pose a major problem for reconstruction. As the radial head is an important stabilizer of the elbow joint-especially in the context of concomitant ligamentous injuries-its resection may lead to pain, limited range of motion, and instability. Therefore, radial head resection is not recommended for the acute situation and open reduction internal fixation (ORIF) or prosthetic replacement should be aimed for. Complications such as secondary loss of fixation, radial head necrosis, and nonunion due to insufficient stability of the osteosynthesis have often been described. Therefore, prosthetic replacement is recommended if stable reconstruction is impossible. With the development of new locking plates especially designed for the maintenance of radial head fractures, the indications for osteosynthesis may be extended. As radial head fractures are complicated by a high percentage of ligamentous injuries and concomitant elbow fractures such as the coronoid, capitellum, and proximal ulna, these additional injuries have to be taken into account. The current treatment concepts are discussed within this paper.

TRAIL-transduced multipotent mesenchymal stromal cells (TRAIL-MSC) overcome TRAIL resistance in selected CRC cell lines in vitro and in vivo.

Tumor-integrating multipotent mesenchymal stromal cells (MSC) expressing transgenes with anti-tumor activity may serve as vehicles for tumor therapy. Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) represents such a factor; however, TRAIL-resistant tumor cells exist. Based on our previous work, here we investigated whether MSC with lentiviral TRAIL expression (TRAIL-MSC) inhibit the growth of TRAIL-resistant colorectal carcinoma (CRC) cells. Our data show that TRAIL-MSC induce apoptosis in selected TRAIL-resistant CRC cell lines and effectively inhibit the growth of TRAIL-resistant HCT8 cells. This sensitization to TRAIL-induced apoptosis required the presence of MSC-expressed TRAIL. However, for the first time we show that selected CRC cells are resistant to TRAIL-MSC. In the cell line HT29, this resistance could be overcome by concomitant subapoptotic genotoxic damage in vitro. However, such sensitization was not achieved in vivo as treatment of mixed HT29/TRAIL-MSC xenografts with 5-FU rather resulted in enhanced growth. Taken together, our data prove that TRAIL-MSC overcome TRAIL resistance in selected CRC cells through direct intercellular interaction and may, therefore, represent a clinical tool to overcome TRAIL resistance. However, such potential clinical use requires further preclinical studies as our data also prove that TRAIL-MSC-resistant CRC cells exist. Our data add to the notion that TRAIL resistance of CRC cells is conferred by different mechanisms.

Bevacizumab in combination with sequential high-dose chemotherapy in solid cancer, a feasibility study.

We evaluated the feasibility and toxicity of bevacizumab in combination with sequential high-dose (HD) ifosfamide, carboplatin and etoposide refractory to standard chemotherapy in patients with sarcoma and germ cell cancer (GCC). Sixteen patients (13 sarcomas, 3 GCC) received SD-ICE followed by 4 cycles of HD-ICE, qd22 with stem cell support in combination with bevacizumab. All 16 patients were evaluable for toxicity and efficacy, and received 51 cycles (median 3.3). There was no increase in toxicity except of a relatively high incidence of ifosfamide encephalopathy in 17 cycles when compared with previous HD-ICE protocols. One almost complete response in the patient with GCC, previously progressive with three preceding protocols, was observed. Six patients had a partial response (sarcoma 4/13 patients; GCC 2/3 patients), and five patients stable disease (sarcoma 5/13 patients). The median PFS/OS for sarcoma was 5 months (confidence interval (CI): 3.1-6.9) and 13 months (CI: 3.6-24.4), respectively. To our knowledge, this is the first report of the addition of bevacizumab to HD-ICE. This combination did not show new unexpected toxicities except for a relatively high rate of ifosfamide encephalopathy. The efficacy in these heavily pretreated patients including possible reversal of chemotherapy resistance by the addition of bevacizumab indicates a possible potential of bevacizumab in this combination.

Analysis of OCT4 expression in an extended panel of human tumor cell lines from multiple entities and in human mesenchymal stem cells.

OCT4 is considered a main regulator of embryonic stem cell pluripotency and self renewal capacity. It was shown that relevant OCT4 expression only occurs in cells of embryonic pluripotent nature. However, several recent publications claimed to have demonstrated OCT4 expression in human somatic tumor cells, human adult stem or progenitor cells and differentiated cells.We analysed 42 human tumor cell lines from 13 entities and human bone marrow-derived mesenchymal stem cells (MSC). To validate OCT4 expression we used germ cell tumor (GCT) cell lines, derived xenografts and GCT samples. Analysis by RT-PCR, western blotting, immunocytochemistry and immunohistochemistry was performed. With exception of typical embryonal carcinoma cells, we did not observe reliable OCT4 expression in somatic tumor cell lines and MSC. We suggest that a high level of expression of the OCT4 protein together with its nuclear localization still remains a reliable and definitive feature of cells with embryonic pluripotent nature.

Dynamic biomechanical analysis of different olecranon fracture fixation devices--tension band wiring versus two intramedullary nail systems: an in-vitro cadaveric study.

BACKGROUND: The aim of this study was to develop a test-setup with continuous angle alteration to imitate joint motion for the evaluation of 3 different olecranon fracture fixation devices. METHODS: Twenty-one fresh cadaver upper extremities underwent olecranon fracture by the means of transverse osteotomy and received 3 different fixation systems. Group 1: Tension band wiring according to Weber. Group 2: XS-nail with 9 holes, all locked with 2mm threaded K-wires. Group 3: Olecranon Nailing System with 90 mm length, locked with 2.7 mm screws, a variable angle locking hole for the proximal fragment and a proximal locking end cap. The servo-pneumatical test stand worked with a rotational angle-adjusted and a linear force-adjusted engine. The fracture model was dynamically tested under cyclic loading imitating elbow motion. There was a continuous angle alteration between 0 degrees and 100 degrees of flexion with continuous changing pull force between 25 N and 150 N. Two steel pins were placed in the proximal, two in the distal olecranon fragment for video analysis of the motion between the two pairs of pins. Displacement in the fracture gap was determined after 4 and 300 cycles. FINDINGS: After 300 cycles the displacement in the fracture fixation model was significantly higher in the tension-band-wiring-group than in the XS-nail group and the olecranon-nailing-system-group. INTERPRETATION: Other studies evaluating biomechanical properties of olecranon-osteosynthesis with joint-involvement did not change the force-direction dynamically. We introduce a test-setup with continuous angle alteration to imitate joint motion. This is an important step for accurate biomechanical evaluation of the treatment of different fixation methods in olecranon fractures. The tested nailing systems showed a higher stability in comparison to tension band wiring.

The phenomenon and efficiency of ligamentotaxis after dorsal stabilization of thoracolumbar burst fractures.

Thirty-six consecutive patients with burst fractures of the thoracolumbar spine and with a fractured posterior vertebral surface dislocated into the spinal canal without neurological symptoms were treated with the AO internal fixator. Computed tomography-aided planimetry of the spinal canal was undertaken preoperatively and within 1 week postoperatively to elucidate the effect of kyphosis correction and distraction on spinal canal widening (ligamentotaxis). The stenosis of the spinal canal area (SCA) was reduced from 29% preoperatively to 19% postoperatively (+10%) of the estimated original area, and the stenosis of the mid-sagittal diameter (MSD) reduced from 31 to 23% (+8%). The widening of the SCA was greater at the level of L1/L2 (+13%) than at L3/L4 (+6%). High preoperative canal compromise was associated with greater absolute spinal canal widening. Large trapezoid-shaped fragments resisted reduction by ligamentotaxis. Even though the effect of ligamentotaxis after operative treatment with the internal fixator was proven, a certain stenosis of the spinal canal remains in most cases. Especially for patients with fracture-related neurological symptoms, ligamentotaxis alone does not seem sufficient for the requested spinal decompression. Even an exact analysis of preoperative CT scans under consideration of the fracture level will not always allow an exact prognosis of the expected effect of ligamentotaxis.

Increased frequency of homozygosity for HLA class II loci in female patients with chronic lymphocytic leukemia.

The etiology of chronic lymphocytic leukemia (CLL) appears to be influenced by genetic factors which may contribute to its differential, gender- and age-specific incidence. The presented study is the first, which investigated the frequencies of DNA-typed alleles of all relevant human leukocyte antigens (HLA) loci in CLL patients with regard to gender and age at disease onset. The most remarkable result was the higher frequency of homozygosity for MHC class II loci in female patients. Particularly, an increased frequency of overall homozygosity for the DRB3/4/5 loci was observed in female patients compared to gender matched controls (RR = 2.8) and male patients. The previously demonstrated association of DQB1 homozygosity with CLL in general was found to be specific for female patients (RR = 4.4). Considering the lack of an a priori hypothesis which made it virtually impossible to obtain statistical significance it was not unexpected that none of the observed differences remained significant after correction for multiple comparisons. However, these results suggest a recessive, gender-specific susceptibility factor for CLL within or in vicinity of the human MHC class II region and should serve as an a priori hypothesis for future studies focusing on these gene loci. Furthermore, an increased frequency for HLA-Cw*06 was seen in patients with an early onset age (RR = 2.7) but lost significance after correction for multiple comparisons. The previously reported association of HLA-DRB4*0103 with CLL in general was observed in all groups irrespective of gender and age. Conclusively, our study supports the concept, that CLL represents a disease with a complex etiology and genetic susceptibility which appears to be influenced by the human MHC.

Endotoxin-adapted septic shock leukocytes selectively alter production of sIL-1RA and IL-1beta.

During septic shock, circulating levels of anti-inflammatory mediators are increased relative to those of pro-inflammatory. The reduced capacity of septic shock blood leukocytes in expressing pro-inflammatory genes in response to bacterial lipopolysaccharide endotoxin (LPS) may contribute to reductions in these mediators, but the reasons for persistent increases in circulating anti-inflammatory mediators are unknown. We determined whether septic shock leukocytes that have adapted to LPS induction of the IL-1beta gene could continue to express sIL-1RA in response to LPS. Septic shock whole-blood leukocytes and neutrophils (PMNs) selectively maintained production of sIL-1RA after treatment with LPS while limiting that of IL-1beta. Repressed transcription of IL-1beta and rapid decay of IL-1beta mRNA in septic shock neutrophils correlated with reductions in levels of IL-1beta after stimulation with LPS. Transcription of sIL-1RA mRNA was also suppressed, but the ability of LPS to stimulate events that lead to efficient translation of a stable sIL-1RA mRNA appeared responsible for maintaining sIL-1RA production. We conclude that LPS adaptation of septic shock leukocytes selectively influences signaling pathways that regulate transcription, mRNA processing, and translation, leading to changes in the balance of production of pro- and anti-inflammatory mediators.