Total ankle arthroplasty incorporating a total talar prosthesis: a comparative study against the standard total ankle arthroplasty.

AIMS: Total ankle arthroplasty (TAA) has become the most reliable surgical solution for patients with end-stage arthritis of the ankle. Aseptic loosening of the talar component is the most common complication. A custom-made artificial talus can be used as the talar component in a combined TAA for patients with poor bone stock of the talus. The purpose of this study was to investigate the functional and clinical outcomes of combined TAA. PATIENTS AND METHODS: Ten patients (two men, eight women; ten ankles) treated using a combined TAA between 2009 and 2013 were matched for age, gender, and length of follow-up with 12 patients (one man, 11 women; 12 ankles) who underwent a standard TAA. All had end-stage arthritis of the ankle. The combined TAA features a tibial component of the TNK ankle (Kyocera, Kyoto, Japan) and an alumina ceramic artificial talus (Kyocera), designed using individualized CT data. The mean age at the time of surgery in the combined TAA and standard TAA groups was 71 years (61 to 82) and 75 years (62 to 82), respectively. The mean follow-up was 58 months (43 to 81) and 64 months (48 to 88), respectively. The outcome was assessed using the Japanese Society for Surgery of the Foot (JSSF) ankle-hindfoot scale, the Ankle Osteoarthritis Scale (AOS), and the Self-Administered Foot Evaluation Questionnaire (SAFE-Q). RESULTS: The mean preoperative JSSF score of the combined TAA and standard TAA groups was 44 (sd 11) and 49 (sd 10), respectively. The mean postoperative JSSF scores were 89 (sd 6.1) and 72 (sd 15), respectively. The mean postoperative JSSF score of the combined TAA group was significantly higher (p = 0.0034). The mean preoperative AOS scores for pain and function in the combined TAA and standard TAA groups were 5.8 (sd 3.3) and 5.5 (sd 3.1), and 8.6 (sd 1.3), and 7.1 (sd 2.9), respectively. The mean postoperative AOS scores of pain and function were 2.5 (sd 2.5) and 2.2 (sd 1.9), and 2.5 (sd 3.3) and 3.4 (sd 2.9), respectively. There were no significant differences between the two groups in terms of postoperative AOS scores. The mean postoperative SAFE-Q scores were: for pain, 76 (sd 23) and 70 (sd 23); for physical function, 66 (sd 25) and 55 (sd 27); for social function, 73 (sd 35) and 62 (sd 34); for shoe-related, 73 (sd 19) and 65 (sd 26); and for general health, 78 (sd 28) and 67 (sd 29), respectively. There were no significant differences between the two groups in terms of postoperative SAFE-Q scores. CONCLUSION: Combined TAA resulted in better clinical results than standard TAA. Cite this article: Bone Joint J 2019;101-B:443-446.

Effects of transgene expression level per cell in mice livers on induction of transgene-specific immune responses after hydrodynamic gene transfer.

We previously showed that high and sustained transgene expression of antigenic proteins induced transgene-specific immune responses. In the present study, a detailed relationship between the level of transgene expression per cell and immune response after hydrodynamic gene transfer was investigated. Cypridina luciferase (cLuc), a secretory antigenic reporter protein, was selected as a model antigen, and pROSA-cLuc, a plasmid expressing cLuc, was constructed. A fixed dose (30 µg) of pROSA-cLuc was delivered to mice by a single hydrodynamic injection or three injections at 24-h intervals because the number of cells transfected with plasmids is dependent on the number of hydrodynamic injections. Serum cLuc activity, an indicator of the total amount of cLuc transgene expression, was almost equal between these two groups. In contrast, the high-dose single injection induced higher levels of cLuc-specific humoral and cellular immune responses than the three low-dose injections. Moreover, the serum cLuc activity of the high-dose single injection group began to decline ~10 days after injection, whereas the activity remained constant in the three low-dose injection group. These results indicate that it is preferable to reduce the level of transgene expression per cell to avoid induction of the transgene-specific immune response after hydrodynamic gene transfer.

An elevated preoperative serum carbohydrate antigen 19-9 level is a significant predictor for peritoneal dissemination and poor survival in colorectal cancer.

AIM: Many studies support the role of carcinoembryonic antigen (CEA) as a strong indicator of the status of colorectal cancer patients, but evidence for carbohydrate antigen 19-9 (CA19-9) is poor. For this reason the study aimed to evaluate the prognostic value of preoperative serum CA19-9 levels in colorectal cancer patients. METHOD: In all, 1190 colorectal cancer patients were included in this study, of whom 955 underwent a potentially curative resection. These were analysed for recurrence and survival. The 255 patients with Stage IV disease were analysed for metastatic status. RESULTS: Patients with an elevated preoperative CEA with Stage II and III disease showed a significantly poorer survival than those with normal levels. In contrast patients with elevated preoperative CA19-9 levels were associated with a significantly poorer survival irrespective of disease stage. Of the 255 patients with Stage IV disease, 92 (39.1%) had peritoneal dissemination at laparotomy observed more frequently in patients with an elevated CA19-9 (47.9%). Of the 955 patients having a curative resection, 18 (1.9%) developed peritoneal dissemination. In multivariate analysis, an elevated preoperative CA19-9 level was a significant risk factor for postoperative peritoneal recurrence. CONCLUSION: After curative surgery for colorectal cancer the preoperative CA19-9 level is a strong prognostic indicator of higher risk of peritoneal dissemination.

Effects of upregulated indoleamine 2, 3-dioxygenase 1 by interferon γ gene transfer on interferon γ-mediated antitumor activity.

Interferon γ (IFN-γ), an anticancer agent, is a strong inducer of indoleamine 2,3-dioxygenase 1 (IDO1), which is a tryptophan-metabolizing enzyme involved in the induction of tumor immune tolerance. In this study, we investigated the IDO1 expression in organs after IFN-γ gene transfer to mice. IFN-γ gene transfer greatly increased the mRNA expression of IDO1 in many tissues with the highest in the liver. This upregulation was associated with reduced L-tryptophan levels and increased L-kynurenine levels in serum, indicating that IFN-γ gene transfer increased the IDO activity. Then, Lewis lung carcinoma (LLC) tumor-bearing wild-type and IDO1-knockout (IDO1 KO) mice were used to investigate the effects of IDO1 on the antitumor activity of IFN-γ. IFN-γ gene transfer significantly retarded the tumor growth in both strains without any significant difference in tumor size between the two groups. By contrast, the IDO1 activity was increased only in the wild-type mice by IFN-γ gene transfer, suggesting that cells other than LLC cells, such as tumor stromal cells, are the major contributors of IDO1 expression in LLC tumor. Taken together, these results imply that IFN-γ gene transfer mediated IDO1 upregulation in cells other than LLC cells has hardly any effect on the antitumor activity of IFN-γ.

Histological and molecular characterization of the femoral attachment of the human ligamentum capitis femoris.

The ligamentum capitis femoris (LCF) has increased in clinical significance through the development of hip arthroscopy. The histological pathologies and molecular composition of the femoral attachment of the LCF and the degeneration caused by LCF disruption were investigated in the human hip joint. Twenty-four LCFs were retrieved at surgery for femoral neck fracture (age range: 63-87 years). In the "intact" (i.e., intact throughout its length, n = 12) group, the attachment consisted of rich fibrocartilage. Fibrocartilage cells were present in the midsubstance. In contrast, the construction of the attachment in the "disrupted" (i.e., ligament no longer attached to the femoral head, n = 12) group had disappeared. The attachment in the disrupted group was not labeled for type II collagen or aggrecan, while that in the intact group was labeled for types I, II and III collagen, chondroitin 4-sulfate, chondroitin 6-sulfate, aggrecan, and versican. The percentage of single-stranded DNA-positive chondrocytes was significantly higher in the disrupted group than in the intact group. We conclude that the femoral attachment of the LCF has a characteristic fibrocartilaginous structure that is likely to adjust to the mechanical load, and suggest that its degeneration is advanced by disruption and should be regarded as a clinical pathology.

Regulation of immunological balance by sustained interferon-γ gene transfer for acute phase of atopic dermatitis in mice.

Interferon (IFN)-γ, a potent T helper 1 (Th1) cell cytokine, is suggested to suppress Th2 cell responses. Here, we aimed to investigate whether pCpG-Muγ, a plasmid continuously expressing murine IFN-γ, is an effective treatment of atopic dermatitis, a Th2-dominant skin disease. Nishiki-nezumi Cinnamon/Nagoya (NC/Nga) atopic mice with early dermatitis were transfected with pCpG-Muγ by a hydrodynamic tail vein injection at a dose of 0.05 or 0.2 pmol per mouse. The skin lesions improved only in mice receiving the high dose of pCpG-Muγ. IFN-γ gene transfer resulted in a high mRNA expression of IFN-γ and interleukin (IL)-12 and regulatory T cell (Treg) related cytokines, such as IL-10 and transforming growth factor-ß, in the spleen, whereas it reduced the IL-4 mRNA expression, and serum levels of immunoglobulin (Ig) G1 and IgE. In addition, the gene transfer markedly inhibited the epidermal thickening, infiltration of inflammatory cells into the skin, the occurrence of dry skin and pruritus. No exacerbating effect on the Th1-mediated contact dermatitis was observed after IFN-γ gene transfer. Taken together, these results indicate that sustained IFN-γ gene transfer induced polarized Th1 immunity under Th2-dominant conditions in NC/Nga mice, leading to an improvement in the symptoms of acute atopic dermatitis without adverse side effects.

The use of a ceramic talar body prosthesis in patients with aseptic necrosis of the talus.

The purpose of this study was to evaluate the clinical results of a newly designed prosthesis to replace the body of the talus in patients with aseptic necrosis. Between 1999 and 2006, 22 tali in 22 patients were replaced with a ceramic prosthesis. A total of eight patients were treated with the first-generation prosthesis, incorporating a peg to fix into the retained neck and head of the talus, and the remaining 14 were treated with the second-generation prosthesis, which does not have the peg. The clinical results were assessed by the American Orthopaedic Foot and Ankle Society ankle/hindfoot scale. The mean follow-up was 98 months (18 to 174). The clinical results of the first-generation prostheses were excellent in three patients, good in one, fair in three and poor in one. There were, however, radiological signs of loosening, prompting a change in design. The clinical results of the second-generation prostheses were excellent in three patients, good in five, fair in four and poor in two, with more favourable radiological appearances. Revision was required using a total talar implant in four patients, two in each group. Although the second-generation prosthesis produced better results, we cannot recommend the use of a talar body prosthesis. We now recommend the use of a total talar implant in these patients.

Single-incision laparoscopic colectomy using the Gelport system for early colon cancer.

BACKGROUND: Laparoscopic surgery has spread quickly during the past twenty years, and has become one of the important treatments in the field of colorectal surgery. Recently, natural orifice transluminal endoscopic surgery (NOTES) has been studied as the next generation of minimally-invasive surgery, but the feasibility and safety of the NOTES method have not been evaluated. In such a situation, single-incision laparoscopic surgery has attracted interest from surgeons worldwide. However, single-incision laparoscopic colorectal surgery has not yet been standardized. METHODS: From February 2010, single-incision laparoscopic colectomy was performed for 7 patients presenting with early colon cancer. All procedures were performed by two experts with the License of Endoscopic Surgical Skill Qualification System (ESSQS) of Japan Society for Endoscopic Surgery (JSES) in the field of colorectal Surgery. RESULTS: We used the Gelport system (Applied Medical, Rancho Santa Margarita, CA, USA) as the access port and 3 trocars of different sizes (Ethicon, Inc., Cincinnati, OH, USA). Using this technique, we did not experience any difficulties or use any articulated instruments. All of the present 7 patients underwent the single-incision laparoscopic colectomy successfully and had no complications. CONCLUSION: Single-incision laparoscopic surgery using the Gelport was performed safely in the present cases. The use of the Gelport as an access port can address the technical difficulty associated with this new technique.

Inhibition of nuclear delivery of plasmid DNA and transcription by interferon γ: hurdles to be overcome for sustained gene therapy.

Sustained expression of murine interferon (IFN)-γ (Muγ) was found to be effective in preventing tumor metastasis and atopic dermatitis in mouse models. However, our preliminary experiments suggested that the time-dependent decrease in the Muγ expression was not compensated for by repeated injections of Muγ-expressing plasmid. To identify the mechanism underlying this observation, a reporter plasmid was hydrodynamically injected into mice and the levels of the plasmid, mRNA and reporter protein were measured in mice receiving a pre- or co-administration of Muγ-expressing plasmid. Co-injection of Muγ-expressing plasmid had no significant effects on transgene expression from the reporter plasmid. In contrast, pre-injection of Muγ-expressing plasmid greatly inhibited the expression of the reporter protein. Moreover, pre-injection of Muγ-expressing plasmid also reduced the amount of the reporter plasmid in the nuclear fraction of mouse liver to < 10%, and that of reporter mRNA to < 1%. The degree of reduction in the expression of reporter protein was comparable with the reduction in mRNA. These results indicate that the difficulty in regaining the expression level of IFN-γ is due to the impaired delivery of plasmid to the nucleus and to the suppression of transcription from the plasmid.

Short disease-free interval is a significant risk factor for intrapulmonary recurrence after resection of pulmonary metastases in colorectal cancer.

OBJECTIVE: Surgical resection has been the first choice of treatment for resectable pulmonary metastases from colorectal cancer. However, early intrapulmonary recurrence is often observed and appropriate assessment of prognostic factors is controversial. The aim of this study was to define the factors affecting survival and intrapulmonary recurrence after surgical treatment of metastatic pulmonary tumours from colorectal cancer. METHOD: A retrospective analysis was performed of 56 consecutive patients who underwent pulmonary resection for colorectal metastases with a focus on prognostic factors and risk factors for intrapulmonary recurrence. RESULTS: The overall 5-year survival rate was 48.2%. In a univariate analysis, a short disease-free interval (DFI), multiple pulmonary metastases and abnormal prethoracotomy carcinoembryonic antigen (CEA) levels were poor prognostic factors. In a multivariate analysis, a short DFI and abnormal prethoracotomy CEA levels were independent prognostic factors. Twenty-two (39.3%) of the 56 patients had recurrences in the remnant lung after resection for pulmonary metastases, and 8 (36.4%) of these 22 patients underwent repeated pulmonary resections. The median DFI between first and second lung metastasis was 13 months. Univariate analyses revealed that multiple and bilateral lung metastases were risk factors for intrapulmonary recurrence. There was also a strong correlation between the DFI for intrapulmonary recurrence after the first pulmonary resection and the DFI for first pulmonary metastases. CONCLUSIONS: A short DFI was a risk factor for early tumour recurrence after resection for pulmonary metastases. The DFI might reflect oncological characteristics such as the tumour doubling time in colorectal cancer.

Spectrocolorimetric evaluation of human articular cartilage.

OBJECTIVE: The aim of this study was to investigate whether human articular cartilage can be quantitatively evaluated using a spectrocolorimeter. MATERIALS AND METHODS: Human articular cartilage specimens were analyzed using a spectrocolorimeter after macroscopic evaluation using the Outerbridge classification. The cartilage characteristics were examined, the L*, a*, b* colorimetric system, the spectral reflectance distribution and the yellow/red spectral reflectance percentage (Y/R SRP). Moreover, the results of the spectrocolorimetric evaluation were compared with the histological score described by Mankin et al. RESULTS: There were significant differences among the macroscopic four grades in the L*, a* and Y/R SRP values. The spectral reflectance distribution of grade 1 cartilage exhibited a gradual increase in the spectral reflectance ratio as the wavelength increased. The spectral reflectance curves of grades 2 to 4 cartilage had dips at a wavelength of around 580 nm. Across all the measured wavelengths, there were lower reflectance ratios with the progression of cartilage degeneration. Moreover, correlations were observed between the spectrocolorimetric values and Mankin score. A strong relationship existed between Mankin score and he Y/R SRP values. CONCLUSIONS: The present study is the first to clearly demonstrate the relationship between spectrocolorimetric evaluation and the degeneration of human articular cartilage. The spectrocolorimeter may be a new quantitative evaluation tool for articular cartilage with clinical potential.

Inhibition of tumor cell growth in the liver by RNA interference-mediated suppression of HIF-1alpha expression in tumor cells and hepatocytes.

Hypoxia-inducible factor-1 (HIF-1) is a ubiquitously expressed oxygen-regulated transcription factor composed of alpha and beta subunits. HIF-1 activates transcription of various genes including those involved in metastatic tumor growth. In the present study, HIF-1alpha expression in tumor-bearing mouse liver was examined after inoculation of tumor cells into portal vein. We found that tumor-bearing liver showed greatly increased HIF-1alpha expression. Plasmid DNA (pDNA) expressing short hairpin RNA targeting HIF-1alpha (pshHIF-1alpha) was effective in suppressing protein expression of HIF-1alpha in vitro. Intravenous injection of pshHIF-1alpha by hydrodynamics-based procedure reduced the HIF-1alpha protein expression in both normal and tumor cells and tumor cell number in the liver. Pre-injection of pshHIF-1alpha to mice, by which pDNA was delivered only to liver cells, not to tumor cells, was also effective in reducing the number of tumor cells inoculated 3 days after pDNA injection. These findings indicate that HIF-1alpha expression is increased in normal liver cells as well as tumor cells, and HIF-1alpha expression plays an important role in tumor progression. Use of the RNA interference (RNAi) of HIF-1 is an effective strategy for inhibiting tumor cell growth, and both tumor and normal cells can be the target for RNAi-based anticancer treatment.Gene Therapy (2008) 15, 572-582; doi:10.1038/sj.gt.3303103; published online 14 February 2008.

Low tibial osteotomy for varus-type osteoarthritis of the ankle.

In this retrospective study we have assessed the results of low tibial valgus osteotomy for varus-type osteoarthritis of the ankle and its indications. We performed an opening wedge osteotomy in 25 women (26 ankles). The mean follow-up was for eight years and three months (2 years 3 months to 17 years 11 months). Of the 26 ankles, 19 showed excellent or good clinical results. Their mean scores for pain, walking, and activities of daily living were significantly improved but there was no change in the range of movement. In the ankles which were classified radiologically as stage 2 according to our own grading system, with narrowing of the medial joint space, and in 11 as stage 3a, with obliteration of the joint space at the medial malleolus only, the joint space recovered. In contrast, such recovery was seen in only two of 12 ankles classified as stage 3b, with obliteration of the joint space advancing to the upper surface of the dome of the talus. Low tibial osteotomy is indicated for varus-type osteoarthritis of stage 2 or stage 3a.

[The TNK ankle: short- and mid-term results]. / Die TNK-sprunggelenkprothese: kurz- und mittelfristige ergebnisse.

Total ankle replacement has been introduced in the last 30 years. The TNK ankle is build from ceramics, and it was continuously improved. This prosthesis has the longest fellow-up times. Seventy ankle prostheses of the newest generation has been implanted between 1991 and 2001. Of these, 67 prostheses were assessed clinically and radiographically after 62 months (range, 24 to 132 months). Three ankles have been revised. The clinical score improved for the patients with primary or posttraumatic arthritis from 34 to 86, and for the patients with rheumatoid arthritis from 45 to 74. Loosening was found in 4 ankles with non-rheumatoid arthritis, and in 17 ankles with rheumatoid ankles. Total ankle replacement has emerged to a valuable alternative to ankle arthrodesis, and satisfactory results have been achieved with the current implants. The bone-implant interphase might play a most important factor for success. There is evidence that the biologic advantages of ceramics may help to improve long-lasting success in total ankle replacement.

Flow in a tube with an aneurysmal sac: effect of aneurysm and stent.

SUMMARY: Ruptured saccular aneurysms were severe condition for intracerebral Condition. And the cause for their rupture is not yet clear. In this study (I), since the configurations of aneurysms are considered to be a factor for the rupture of aneurysms, several shapes has been modeled using Aspect ratio AR and inclination angle of saccular aneurysms. In vitro the parametric study has been conducted on the range of Reynolds Number in human blood flow for aneurismal models of AR=2.1 and 1.3 and q=90 degrees and 70 degrees , As results, it was con firme d that there are characteristic flow patterns with Reynolds Number, And that the aneurismal configuration has effects on the shear stress and pressure losses. II) The object of this paper is to study the effects of STENTS.We made the model of aneurysm and performed in vitro study in range of Reynolds number of human blood flows using three kinds of STENTS. As results, it was confirmed that flow pattern and pressure loss changes with the kinds of STENTS. This study aims the accumulation of data to predict the hazard of aneurysmal rupture by their shapes and STENTS.

Anatomical consideration of vascularized bone graft transfer from the medial calcaneus to the talus.

To investigate the possibility of use of the calcaneal branches of the posterior tibial artery as the pedicle for the vascularized bone graft to the talus, a detailed anatomical study was carried out on 30 fresh cadaver feet. Although there are several branches from the posterior tibial artery to the calcaneus, the largest posterior branch was defined as the main calcaneal branch. We recognized frequently a large branch nourishing the superior part of the calcaneus and named it the superior calcaneal branch. Twenty feet had the superior calcaneal branches. Pedicled bone grafts using the superior calcaneal branch to the postero-medial portion of the talar body were possible in 18 of 20 feet. Pedicled bone grafts using the main calcaneal branches were possible in 9 of 12 feet in which the superior calcaneal branches were not available. Finally, vascularized bone grafts were judged to be feasible in 27 feet (90%).

Waveguide sidewall roughness measurement on full wafers by SEM-based stereoscopy.

We present a technique aiming at sidewall roughness measurement on integrated optical silica waveguides using a scanning electron microscope. The technique uses the principles of stereoscopy to retrieve sidewall topography. Practical implementation details and first results are provided.