Characterization and prognostic impact of ACTBL2-positive tumor-infiltrating leukocytes in epithelial ovarian cancer.

Actin beta-like 2 (ACTBL2) was recently identified as a new mediator of migration in ovarian cancer cells. Yet, its impact on tumor-infiltrating and thus migrating leukocytes (TILs) remains to date unknown. This study characterizes the subset of ACTBL2-expressing TILs in epithelial ovarian cancer (EOC) and elucidates their prognostic influence on the overall survival of EOC patients with special regard to different histological subtypes. Comprehensive immunohistochemical analyses of Tissue-Microarrays of 156 ovarian cancer patients revealed, that a tumor infiltration by ACTBL2-positive leukocytes was significantly associated with an improved overall survival (OS) (61.2 vs. 34.4 months; p = 0.006) and was identified as an independent prognostic factor (HR = 0.556; p = 0.038). This significant survival benefit was particularly evident in patients with low-grade serous carcinoma (OS: median not reached vs. 15.6 months, p < 0.001; HR = 0.058, p = 0.018). In the present cohort, ACTBL2-positive TILs were mainly composed of CD44-positive cytotoxic T-cells (CD8+) and macrophages (CD68+), as depicted by double-immunofluorescence and various immunohistochemical serial staining. Our results provide significant evidence of the prognostic impact and cellular composition of ACTBL2-expressing TILs in EOC. Complementary studies are required to analyze the underlying molecular mechanisms of ACTBL2 as a marker for activated migrating leukocytes and to further characterize its immunological impact on ovarian carcinogenesis.

Peritonitis in a neonate due to Cyberlindnera fabianii, an ascomycetic yeast.

The ascomycetous yeast Cyberlindera fabianii is not only present in the environment, but is also occasionally pathogenic. Especially, neonates seem to be prone to infection. Here, we describe a case of peritoneal infection of a neonate after congenital heart surgery. The correct identification of this peculiar species is made by MALDI-TOF and especially by molecular biology methods, whereas the standard biochemical identification methods fail.The neonate with a hypoplastic left heart syndrome had a Norwood palliation followed by transient ECMO therapy for 3 days. The patient developed a renal insufficiency, so that peritoneal dialysis was initiated. After a few days, a peritoneal infection due to C. fabianii emerged. The proper source of this rare and particular yeast remains obscure. In spite of a reasonable antimycotic therapy, the patient developed a capillary leak syndrome and died finally in septic shock with multiorgan failure. One reason is probably that the yeast population, which was highly susceptible to all common antimycotic drugs at the beginning of therapy with fluconazole (and for a short period with caspofungin and liposomal amphotericin B), became rapidly resistant.

Segmentation of dynamic PET images with kinetic spectral clustering.

Segmentation is often required for the analysis of dynamic positron emission tomography (PET) images. However, noise and low spatial resolution make it a difficult task and several supervised and unsupervised methods have been proposed in the literature to perform the segmentation based on semi-automatic clustering of the time activity curves of voxels. In this paper we propose a new method based on spectral clustering that does not require any prior information on the shape of clusters in the space in which they are identified. In our approach, the p-dimensional data, where p is the number of time frames, is first mapped into a high dimensional space and then clustering is performed in a low-dimensional space of the Laplacian matrix. An estimation of the bounds for the scale parameter involved in the spectral clustering is derived. The method is assessed using dynamic brain PET images simulated with GATE and results on real images are presented. We demonstrate the usefulness of the method and its superior performance over three other clustering methods from the literature. The proposed approach appears as a promising pre-processing tool before parametric map calculation or ROI-based quantification tasks.

Using PET with 18F-AV-45 (florbetapir) to quantify brain amyloid load in a clinical environment.

PURPOSE: Positron emission tomography (PET) imaging of brain amyloid load has been suggested as a core biomarker for Alzheimer's disease (AD). The aim of this study was to test the feasibility of using PET imaging with (18)F-AV-45 (florbetapir) in a routine clinical environment to differentiate between patients with mild to moderate AD and mild cognitive impairment (MCI) from normal healthy controls (HC). METHODS: In this study, 46 subjects (20 men and 26 women, mean age of 69.0 ± 7.6 years), including 13 with AD, 12 with MCI and 21 HC subjects, were enrolled from three academic memory clinics. PET images were acquired over a 10-min period 50 min after injection of florbetapir (mean ± SD of radioactivity injected, 259 ± 57 MBq). PET images were assessed visually by two individuals blinded to any clinical information and quantitatively via the standard uptake value ratio (SUVr) in the specific regions of interest, which were defined in relation to the cerebellum as the reference region. RESULTS: The mean values of SUVr were higher in AD patients (median 1.20, Q1-Q3 1.16-1.30) than in HC subjects (median 1.05, Q1-Q3 1.04-1.08; p = 0.0001) in the overall cortex and all cortical regions (precuneus, anterior and posterior cingulate, and frontal median, temporal, parietal and occipital cortex). The MCI subjects also showed a higher uptake of florbetapir in the posterior cingulate cortex (median 1.06, Q1-Q3 0.97-1.28) compared with HC subjects (median 0.95, Q1-Q3 0.82-1.02; p = 0.03). Qualitative visual assessment of the PET scans showed a sensitivity of 84.6% (95% CI 0.55-0.98) and a specificity of 38.1% (95% CI 0.18-0.62) for discriminating AD patients from HC subjects; however, the quantitative assessment of the global cortex SUVr showed a sensitivity of 92.3% and specificity of 90.5% with a cut-off value of 1.122 (area under the curve 0.894). CONCLUSION: These preliminary results suggest that PET with florbetapir is a safe and suitable biomarker for AD that can be used routinely in a clinical environment. However, the low specificity of the visual PET scan assessment could be improved by the use of specific training and automatic or semiautomatic quantification tools.

Spatio-temporal diffusion of dynamic PET images.

Positron emission tomography (PET) images are corrupted by noise. This is especially true in dynamic PET imaging where short frames are required to capture the peak of activity concentration after the radiotracer injection. High noise results in a possible bias in quantification, as the compartmental models used to estimate the kinetic parameters are sensitive to noise. This paper describes a new post-reconstruction filter to increase the signal-to-noise ratio in dynamic PET imaging. It consists in a spatio-temporal robust diffusion of the 4D image based on the time activity curve (TAC) in each voxel. It reduces the noise in homogeneous areas while preserving the distinct kinetics in regions of interest corresponding to different underlying physiological processes. Neither anatomical priors nor the kinetic model are required. We propose an automatic selection of the scale parameter involved in the diffusion process based on a robust statistical analysis of the distances between TACs. The method is evaluated using Monte Carlo simulations of brain activity distributions. We demonstrate the usefulness of the method and its superior performance over two other post-reconstruction spatial and temporal filters. Our simulations suggest that the proposed method can be used to significantly increase the signal-to-noise ratio in dynamic PET imaging.

Acquisition and interactive 3D exploration of the internal structure of a dissected specimen.

We present a system to keep track of a destructive process such as a medical specimen dissection, from data acquisition to interactive and immersive visualization, in order to build ground truth models. Acquisition is a two-step process, first involving a 3D laser scanner to get a 3D surface, and then a high resolution camera for capturing the texture. This acquisition process is repeated at each step of the dissection, depending on the expected accuracy and the specific objects to be studied. Thanks to fiducial markers, surfaces are registered on each others. Experts can then explore data using interaction hardware in an immersive 3D visualization. An interactive labeling tool is provided to the anatomist, in order to identify regions of interest on each acquired surface. 3D objects can then be reconstructed according to the selected surfaces. We aim to produce ground truths which for instance can be used to validate data acquired with MRI. The system is applied to the specific case of white fibers reconstruction in the human brain.

Total hip arthroplasty revision using the press-fit CLS Spotorno cementless stem. Twenty-four hips followed between 1987 and 1998.

A retrospective study of uncemented femoral revision for loosening after total hip arthroplasty was conducted for the period 1987-1998. The study included 24 hips in 22 patients (7 men, 15 women). The revision procedure consisted of the replacement of the loose hip prosthesis using the CLS (Protek) press-fit stem. Patients were followed for a mean duration of 4.5 years. The mean interval between the primary operation and the revision was 10 years (range 2-16 years). Using the Merle D'Aubigné hip score and radiographic findings, a favorable outcome was noted in 20 hips. We suggest that the femoral revision procedure using the uncemented Spotorno stem is a very useful method of correction of loosening after total hip replacement.

The use of fibrin tissue adhesive to reduce blood loss and the need for blood transfusion after total knee arthroplasty. A prospective, randomized, multicenter study.

BACKGROUND: Total knee arthroplasty is associated with major postoperative blood loss of approximately 800 to 1200 milliliters, and blood transfusion is frequently required. With the increased concern about the risks of blood transfusion, various methods of blood conservation in orthopaedic surgery have been studied. The most appropriate solution, however, is to reduce the loss of blood during and after an operation. The present prospective, controlled, randomized study was designed to evaluate the hemostatic efficacy of the use of fibrin tissue adhesive in patients managed with total knee arthroplasty. METHODS: Fifty-eight patients who were scheduled to have a total knee arthroplasty were randomly divided into two groups: a control group, in which the standard means of hemostasis were applied, and a treatment group, in which the standard means to control local bleeding were applied and a fibrin tissue adhesive was sprayed on the internal aspects of the operative field before skin closure. All operations were performed in a bloodless field with use of a pneumatic tourniquet. All patients received low-molecular-weight heparin as thromboprophylaxis twelve hours before the operation and every twelve hours postoperatively. Blood loss during the operation was evaluated by measuring the volume in the suction apparatus and by estimating the amount of lost blood in the swabs at the end of the operation. The apparent postoperative lost blood was determined by measuring the volume in the suction-drain bottles. All blood transfusions were recorded. RESULTS: The mean apparent postoperative blood loss (and standard deviation) in the fibrin-tissue-adhesive group was 360+/-287.7 milliliters compared with 878+/-403.0 milliliters in the control group, with a mean difference of 518 milliliters (p<0.001). The decrease in the level of hemoglobin was 25+/-10 grams per liter in the treatment group compared with 37+/-12 grams per liter in the control group (p<0.001). Sixteen patients (55 percent) in the control group required a blood transfusion and eight (28 percent) required two units of blood, whereas only five (17 percent) of the patients in the fibrin-tissue-adhesive group required a blood transfusion and only one (3 percent) required two units (p = 0.004). The number of adverse events was comparable between the two groups. None of the adverse events were considered to be related to the use of fibrin tissue adhesive. One death, which was due to massive pulmonary embolism, was reported in the control group. No seroconversion was reported at three and six months after the operation. CONCLUSION: The use of fibrin tissue adhesive in total knee arthroplasty seems to be an effective and safe means with which to reduce blood loss and blood-transfusion requirements. Furthermore, the importance of these findings was enhanced by a significant reduction in blood loss, in the postoperative decrease in the level of hemoglobin, and in blood-transfusion requirements despite preoperative thromboprophylaxis with low-molecular-weight heparin.

Acetabular supporting ring in total hip replacement.

A series of 14 total hip arthroplasties with a Müller acetabular supporting ring including 3 primary and 11 revision arthroplasties is reviewed. This device was used in cases of acetabular bone deficiency, and bone graft was added in 11 cases. The mean length of follow-up was 39.9 months. Twelve patients had good or satisfactory results, while two operations failed. These results indicate that the acetabular supporting ring is a useful implant in cases with acetabular bone stock deficiency.

Gaucher disease--the orthopaedic aspect. Report of seven cases.

Seven patients with Gaucher type 1 disease are presented: five female and two male. The orthopaedic problems encountered were: avascular necrosis of both femoral heads in two girls, bilateral bone infarctions of the femurs in all three girls, complicated by staphylococcal osteomyelitis of the right femur in one girl and by pathological fractures of both femurs in another girl, osteonecrosis of both humeral heads in one male adult patient, osteonecrosis of the femoral heads in two further adults (male and female), and a pathological fracture of the fourth lumbar vertebra in another adult woman with concomitant humeral head involvement. The patient with osteonecrosis of the humeral head was treated with a total shoulder arthroplasty, and the two patients with osteonecrosis of the femoral heads were treated with total hip arthroplasties, with satisfactory intermediate and long-term results.

Blood levels of vitamin D metabolites in gonarthrosis.

The blood levels of the active metabolites of vitamin D3 25-hydroxycholecalciferol [25(OH)D3]. 1,25-dihydroxycholecalciferol [1,25(OH)2D3], and 24,25-dihydroxycholecalciferol [24,25(OH)2D3] were determined in 27 patients suffering from arthrosis of the knee, including 4 patients with non-insulin-dependent diabetes mellitus. The blood level of 24,25-dihydroxycholecalciferol was found to be significantly lower in patients with gonarthrosis than in patients with coxarthrosis. With the exclusion of the diabetic patients, the mean value for this metabolite was lower than in the coxarthrosis group, but the difference was not significant statistically.

Blood levels of active metabolites of vitamin D3 in fracture repair in humans. A preliminary report.

Blood levels of the active metabolites of vitamin D3, 25-hydroxycholecalciferol [25(OH)D3], 1,25-dihydroxycholecalciferol [1,25(OH)2D3] and 24,25-dihydroxycholecalciferol [24,25(OH)2D3] were determined in seven patients. Two subjects suffered from delayed union of tibial fractures; one showed a delayed union after a proximal tibial osteotomy; one patient suffered from bilateral femoral neck fractures, of which one failed to unite and the other united late; two patients had multiple fractures that united normally; and one patient exhibited staged bilateral femoral neck fractures whose occurrence was separated by a short interval and which united without undue delay. The blood levels of 25(OH)D3 were within the normal range. A relative decrease in 24,25(OH)2D3 values was noted in all patients, whereas in three subjects the decrease was absolute, to non-detectable levels. A decrease in 1,25(OH)2D3 levels was noted in only two patients. We postulate that these changes reflect the consumption of these metabolites during healing at the fracture site.

Active metabolites of vitamin D in patients with coxarthrosis and with aseptic loosening of total hip endoprostheses.

The blood levels of the active metabolites of vitamin D--25-hydroxycholecalciferol (25(OH)D), 1,25 dihydroxycholecalciferol (1,25(OH)2D), and 24,25 dihydroxycholecalciferol (24,25(OH)2D)--were determined in 15 patients suffering from arthrosis of the hip and in 13 patients with aseptic loosening of total hip endoprostheses. Normal values were found in all but one patient with aseptic loosening, in whom 24,25(OH)2D was not detectable. The difference between the two groups of patients was not statistically significant.

Disruption of the symphysis pubis and fatigue fractures of the pelvis in a patient with rheumatoid arthritis. A case report.

A 40-year-old woman, who suffered from severe rheumatoid arthritis causing avascular necrosis of the femoral head and protrusio acetabuli of the right hip, developed a severe spontaneous disruption of the symphysis pubis concomitant with a stress fracture of the left ilium adjacent to the left sacroiliac joint. After successful total hip arthroplasty, the symphysiolysis improved, but a new stress fracture of the left superior pubic ramus developed. Fourteen months after operation both stress fractures are healed. Altered hip and pelvic girdle mechanics acting on osteoporotic bone may account for this sequence of events.

Computerized tomography in the diagnosis and treatment of osteoid osteoma.

Thirteen cases of osteoid osteoma demonstrated with computerized tomography are reported. Twelve patients underwent definitive surgery and were relieved of their symptoms. The histological examination confirmed the preoperative diagnosis in 11 cases. Six lesions were located in the proximal femur, three in the neck of the talus, two in the proximal tibia, and one each in the proximal humerus and the calcaneus. Radionuclide technetium 99m MDP scans were performed in 11 cases and showed an increased uptake in the vicinity of the lesions. Computerized tomography showed the precise location of the nidus, thus helping in the preoperative planning of the surgical approach and enabling us to perform a precise and economic resection.

Lateral patellar release and bone grafting of the tibial plateau in total condylar knee arthroplasties. A technical note.

In a review of 50 primary total condylar knee arthroplasties in 25 female and in 14 male patients the factors affecting the necessity of lateral patellar release and bone grafting of the medial tibial plateau were established. Lateral patellar release was performed in 18 of 33 arthroplasties in female patients, in only two of 17 operations in male patients, and on all but one of the knees with preoperative valgus deformity. Bone grafting of the medial tibial plateau was necessary mainly in small knees, i.e., for six of 18 small prostheses in contrast to one of 15 standard-sized implants in female patients and in none of the operated knees in males.

Female pelvic anatomy: MR assessment of variations during the menstrual cycle and with use of oral contraceptives.

Magnetic resonance (MR) imaging was performed on 21 women in different phases of the menstrual cycle, nine who used oral contraceptives and 12 who did not. Sagittal images in a dual spin-echo sequence were obtained to assess conspicuity and dimensions of the corpus uteri, cervix, vagina, and their component tissues. The endometrium, junctional zone, myometrium, cervical canal, fibrous stroma, and vaginal canal were seen in all cases and the vesicovaginal septum, rectovaginal septum, and levator ani in 90%, 86%, and 100%, respectively. The uterus was retrodisplaced in 19% of the women. In the nonpill group, endometrial width was significantly larger (P less than .025) in the secretory phase (mean, 5 mm) than in the follicular phase (3.1 mm). In the pill-using group, endometrial width was 1.1 mm in both phases, significantly smaller than in the nonpill group (P less than .025, follicular; P less than .0005, secretory). Junctional zone width was significantly smaller in the pill-using group (P less than .005). Qualitatively, the myometrium was relatively brighter on second echo images in the pill-using group, compatible with known edema that occurs with use of oral contraceptives. MR can reliably demonstrate gynecologic structure and anatomic changes that occur during the menstrual cycle and with use of oral contraceptives.

Spinal configuration during lifting.

The change in spinal configuration of the cervical, thoracic, and lumbar regions in relation to an amount of weight lifted was determined using videophotogrammetry. Fifteen healthy male subjects, 20-38 years of age, with no previous history of back pain participated in the study. The subjects lifted a crate containing 0, 10, and 20 kg weights using the straight-legs, bent-over-back method of lifting. The results showed that cervical and thoracic spinal segment configurations were not significantly influenced by the amount of weight lifted and that the mobility of the lumbar spinal segment was significantly decreased with increasing load (p = .03).