Efficacy of cetuximab in metastatic castration-resistant prostate cancer might depend on EGFR and PTEN expression: results from a phase II trial (SAKK 08/07).

PURPOSE: The EGF receptor (EGFR) is overexpressed in the majority of metastatic castration-resistant prostate cancers (mCRPC) and might represent a valid therapeutic target. The combination of docetaxel and cetuximab, the monoclonal antibody against EGFR, has not been tested in patients with prostate cancer. EXPERIMENTAL DESIGN: Patients with mCRPC progressing during or within 90 days after at least 12 weeks of docetaxel were included in this phase II trial. Treatment consisted of docetaxel (75 mg/m(2) every 3 weeks or 35 mg/m(2) on days 1, 8, 15 every 4 weeks) in combination with cetuximab (400 mg/m(2) on day 1 and then 250 mg/m(2) weekly). The primary endpoint was progression-free survival (PFS) at 12 weeks defined as the absence of prostate-specific antigen (PSA), radiographic, or clinical progression. Evaluation of known biomarkers of response and resistance to cetuximab (EGFR, PTEN, amphiregulin, epiregulin) was conducted. RESULTS: Thirty-eight patients were enrolled at 15 Swiss centers. Median age was 68 years and median PSA was 212 ng/mL. PFS at 12 weeks was 34% [95% confidence interval (CI), 19%-52%], PFS at 24 weeks was 20%, and median overall survival (OS) was 13.3 months (95% CI, 7.3-15.4). Seven patients (20%) had a confirmed ≥ 50% and 11 patients (31%) a confirmed ≥ 30% PSA decline. About 47% of enrolled patients experienced grade 3 and 8% grade 4 toxicities. A significantly improved PFS was found in patients with overexpression of EGFR and persistent activity of PTEN. CONCLUSIONS: EGFR inhibition with cetuximab might improve the outcome of patients with mCRPC. A potential correlation between EGFR overexpression, persistent expression of PTEN, and EGFR inhibition should be investigated further.

The long and painful path towards arthroplasty: A qualitative study

Hip or knee arthroplasty is proposed after osteoarthritis or an accident. It is decided after a long path of pain and decrease in the quality of life. This research explores the period of illness until surgery. Twenty-four semi-structured interviews were conducted one month before surgery and a thematic discourse analysis performed. The diversity and complexity of the patient experience, in a commonly performed surgical intervention underlines important topics, requiring attention in order to improve patient preparations and information prior to arthroplasty: information adapted to individual concerns, needs and representations. Psychological and physical acceptance is necessary for integration of the prosthesis.

An image quality comparison of standard and dual-side read CR systems for pediatric radiology.

An objective analysis of image quality parameters was performed for a computed radiography (CR) system using both standard single-side and prototype dual-side read plates. The pre-sampled modulation transfer function (MTF), noise power spectrum (NPS), and detective quantum efficiency (DQE) for the systems were determined at three different beam qualities representative of pediatric chest radiography, at an entrance detector air kerma of 5 microGy. The NPS and DQE measurements were realized under clinically relevant x-ray spectra for pediatric radiology, including x-ray scatter radiations. Compared to the standard single-side read system, the MTF for the dual-side read system is reduced, but this is offset by a significant decrease in image noise, resulting in a marked increase in DQE (+40%) in the low spatial frequency range. Thus, for the same image quality, the new technology permits the CR system to be used at a reduced dose level.

Variability of ascending aorta diameter measurements as assessed with electrocardiography-gated multidetector computerized tomography and computer assisted diagnosis software.

Recently, morphometric measurements of the ascending aorta have been done with ECG-gated multidector computerized tomography (MDCT) to help the development of future novel transcatheter therapies (TCT); nevertheless, the variability of such measurements remains unknown. Thirty patients referred for ECG-gated CT thoracic angiography were evaluated. Continuous reformations of the ascending aorta, perpendicular to the centerline, were obtained automatically with a commercially available computer aided diagnosis (CAD). Then measurements of the maximal diameter were done with the CAD and manually by two observers (separately). Measurements were repeated one month later. The Bland-Altman method, Spearman coefficients, and a Wilcoxon signed-rank test were used to evaluate the variability, the correlation, and the differences between observers. The interobserver variability for maximal diameter between the two observers was up to 1.2 mm with limits of agreement [-1.5, +0.9] mm; whereas the intraobserver limits were [-1.2, +1.0] mm for the first observer and [-0.8, +0.8] mm for the second observer. The intraobserver CAD variability was 0.8 mm. The correlation was good between observers and the CAD (0.980-0.986); however, significant differences do exist (P<0.001). The maximum variability observed was 1.2 mm and should be considered in reports of measurements of the ascending aorta. The CAD is as reproducible as an experienced reader.

Long gamma nail in the treatment of subtrochanteric fractures.

INTRODUCTION: The purpose of our study was to retrospectively evaluate the clinical and radiological results of subtrochanteric fractures treated with a long gamma nail (LGN). The LGN has been the implant of choice at our level-1 trauma center since 1992. MATERIALS AND METHODS: Over a period of 7 years, we have treated 90 consecutive patients with subtrochanteric fractures. In order to evaluate the clinical and radiological outcomes, we reviewed the clinical and radiographic charts of these patients followed for a mean time of 2 years (range 13-36 months). RESULTS: We found no intra- or perioperative complications nor early or late infection. Clinical and radiological union was achieved at a mean of 4.3 months in all of the patients (range 3-9 months); in 24 cases (30%) the distal locking bolts were retrieved in order to enhance callus formation and remodeling as a planned secondary surgery. Three patients (3.3%) needed unplanned secondary surgery for problems related to the nailing technique. Two mechanical failures with breakage of the nail were encountered due to proximal varus malalignment, of which one was treated with exchange nailing and grafting and the other one by removal of the broken hardware, blade-plating, and bone grafting. One fracture below a short LGN was treated by exchange nailing. CONCLUSIONS: The minimally invasive technique and simple application of the LGN lead to a low percentage of complications in these difficult fractures after a relatively short learning curve. The biomechanical properties of this implant allow early mobilization and partial weight-bearing even in patients with advanced osteoporosis.

Differences in osteogenic and apoptotic genes between osteoporotic and osteoarthritic patients.

BACKGROUND Osteoporosis is a metabolic disorder characterized by a reduction in bone mass and deterioration in the microarchitectural structure of the bone, leading to a higher risk for spontaneous and fragility fractures.The main aim was to study the differences between human bone from osteoporotic and osteoarthritic patients about gene expression (osteogenesis and apoptosis), bone mineral density, microstructural and biomechanic parameters. METHODS We analyzed data from 12 subjects: 6 with osteoporotic hip fracture (OP) and 6 with hip osteoarthritis (OA), as the control group. All subjects underwent medical history, analytical determinations, densitometry, histomorphometric and biochemical study. The expression of 86 genes of osteogenesis and 86 genes of apoptosis was studied in pool of bone samples from patients with OP and OA by PCR array. RESULTS We observed that most of the genes of apoptosis and osteogenesis show a decrease in gene expression in the osteoporotic group in comparison with the osteoarthritic group. The histomorphometric study shows a lower bone quality in the group of patients with hip fractures compared to the osteoarthritic group. CONCLUSIONS The bone tissue of osteoporotic fracture patients is more fragile than the bone of OA patients. Our results showed an osteoporotic bone with a lower capacities for differentiation and osteoblastic activity as well as a lower rate of apoptosis than osteoarthritic bone. These results are related with structural and biochemical parameters.

Angiographic demonstration of neoangiogenesis after intra-arterial infusion of autologous bone marrow mononuclear cells in diabetic patients with critical limb ischemia.

Critical limb ischemia in diabetic patients is associated with high rates of morbidity and mortality. Suboptimal responses to the available medical and surgical treatments are common in these patients, who also demonstrate limited vascular homeostasis. Neovasculogenesis induced by stem cell therapy could be a useful approach for these patients. Neovasculogenesis and clinical improvement were compared at baseline and at 3 and 12 months after autologous bone marrow-derived mononuclear cell (BMMNC) transplantation in diabetic patients with peripheral artery disease. We conducted a prospective study to evaluate the safety and efficacy of intra-arterial administration of autologous BMMNCs (100-400 × 10(6) cells) in 20 diabetic patients with severe below-the-knee arterial ischemia. Although the time course of clinical effects differed among patients, after 12 months of follow-up all patients presented a notable improvement in the Rutherford-Becker classification, the University of Texas diabetic wound scales, and the Ankle-Brachial Index in the target limb. The clinical outcome was consistent with neovasculogenesis, which was assessed at 3 months by digital subtraction angiography and quantified by MetaMorph software. Unfortunately, local cell therapy in the target limb had no beneficial effect on the high mortality rate in these patients. In diabetic patients with critical limb ischemia, intra-arterial perfusion of BMMNCs is a safe procedure that generates a significant increase in the vascular network in ischemic areas and promotes remarkable clinical improvement.

Influence of the ankle arthropathies on the 3D kinematics of the lower limbs during gait: analysis with an ambulatory system.

Introduction: Ankle arthropathy is associated with a decreased motion of the ankle-hindfoot during ambulation. Ankle arthrodesis was shown to result in degeneration of the neighbour joints of the foot. Inversely, total ankle arthroplasty conceptually preserves the adjacent joints because of the residual mobility of the ankle but this has not been demonstrated yet in vivo. It has also been reported that degenerative ankle diseases, and even arthrodesis, do not result in alteration of the knee and hip joints. We present the preliminary results of a new approach of this problem based on ambulatory gait analysis. Patients and Methods: Motion analysis of the lower limbs was performed using a Physilog® (BioAGM, CH) system consisting of three-dimensional (3D) accelerometer and gyroscope, coupled to a magnetic system (Liberty©, Polhemus, USA). Both systems have been validated. Three groups of two patients were included into this pilot study and compared to healthy subjects (controls) during level walking: patients with ankle osteoarthritis (group 1), patients treated by ankle arthrodesis (group 2), patients treated by total ankle prosthesis (group 3). Results: Motion patterns of all analyzed joints over more than 20 gait cycles in each subject were highly repeatable. Motion amplitude of the ankle-hindfoot in control patients was similar to recently reported results. Ankle arthrodesis limited the motion of the ankle-hindfoot in the sagittal and horizontal planes. The prosthetic ankle allowed a more physiologic movement in the sagittal plane only. Ankle arthritis and its treatments did not influence the range of motion of the knee and hip joint during stance phase, excepted for a slight decrease of the hip flexion in groups 1 and 2. Conclusion: The reliability of the system was shown by the repeatability of the consecutive measurements. The results of this preliminary study were similar to those obtained through laboratory gait analysis. However, our system has the advantage to allow ambulatory analysis of 3D kinematics of the lower limbs outside of a gait laboratory and in real life conditions. To our knowledge this is a new concept in the analysis of ankle arthropathy and its treatments. Therefore, there is a potential to address specific questions like the difficult comparison of the benefits of ankle arthroplasty versus arthrodesis. The encouraging results of this pilot study offer the perspective to analyze the consequences of ankle arthropathy and its treatments on the biomechanics of the lower limbs ambulatory, in vivo and in daily life conditions.

Grade I and II acromioclavicular dislocations: results of conservative treatment.

The purpose of this study was to assess the results of acute grade I and II acromioclavicular (AC) joint sprains treated by conservative measures. Between 1993 and 1997, 37 consecutive patients were treated conservatively for AC joint sprains, grade I and II in the Tossy classification. Of these patients, 4 were excluded (three lost to follow-up and one sustained a further AC injury), leaving a series of 33 patients. Among them, in 9 (27%), chronic AC joint pathology that required subsequent surgery developed at a mean of 26 months after injury. The remaining 24 were reviewed clinically and radiologically at a mean of 6.3 years (range, 4-8 years) after injury. At the latest follow-up, 17 of the 33 patients (52%) remained asymptomatic. Of the 24 patients reviewed, 7 complained of activity-related pain. Eight patients presented with residual anteroposterior instability. Tenderness at the AC joint as well as a positive cross-body test was observed in 12 patients. The mean Constant score at follow-up was 82 points. The x-ray films showed degenerative changes in 13 patients, ossification of the coracoclavicular ligaments in 2, an association of degenerative changes with ossification of the coracoclavicular ligaments in 3, and distal clavicular osteolysis in 3. Only 4 cases had no radiographic changes after this kind of AC injury. On the basis of these results, we conclude that the severity of the consequences after grade I and II AC sprains is underestimated.

Acetylcholinesterase inhibitors and healing of hip fracture in Alzheimer's disease patients: a retrospective cohort study.

OBJECTIVES This study was designed to assess effects of cholinergic stimulation using acetylcholinesterase inhibitors (AChEIs), a group of drugs that stimulate cholinergic receptors and are used to treat Alzheimer's disease (AD), on healing of hip fractures. METHODS A retrospective cohort study was performed using 46-female AD patients, aged above 75 years, who sustained hip fractures. Study analyses included the first 6-months after hip fracture fixation procedure. Presence of AChEIs was used as predictor variable. Other variables that could affect study outcomes: age, body mass index (BMI), mental state or type of hip fracture, were also included. Radiographic union at fracture site (Hammer index), bone quality (Singh index) and fracture healing complications were recorded as study outcomes. The collected data was analyzed by student's-t, Mann-Whitney-U and chi-square tests. RESULTS No significant differences in age, BMI, mental state or type of hip fracture were observed between AChEIs-users and nonusers. However, AChEIs-users had better radiographic union at the fracture site (relative risk (RR),2.7; 95%confidence interval (CI),0.9-7.8), better bone quality (RR,2.0; 95%CI,1.2-3.3) and fewer healing complications (RR,0.8; 95%CI,0.7-1.0) than nonusers. CONCLUSION In elderly female patients with AD, the use of AChEIs might be associated with an enhanced fracture healing and minimized complications.

Prótesis unicompartimental como opción quirúrgica en la gonartrosis medial en el adulto joven

OBJECTIVE: Assess the degree of satisfaction in a series of patients between 50 and 60 years of age who underwent surgery in our unicompartmental prosthesis unit (UPU) for monocompartmental gonarthrosis. Likewise, the definition based on current literature is assessed, as well as our experience in the indications, inconveniences and results of the internal knee unicompartmental arthroplasty discussed with supra-tuberosity tibial osteotomy, which was the common surgical option in these cases.MATERIAL AND METHOD: This study included 19 patients between 50 and 60 years of age (average age 56.7 years) (Interval of 51-60 years) intervened between 7/2007 and 11/2011 by the same surgeon (GDFB). Functional assessment used the Oxford Knee Score (OKS) questionnaire. A bibliographic search was performed in the MEDLINE, COCHRANE and EMBASE databases from 1988 to 2012. RESULTS: With an average follow-up of 29.4 months, 16 of 19 patients stated that they were satisfied with the results obtained and would repeat the intervention. One patient sufered a prosthetic infection and was reviewed for total knee replacement with good results. CONCLUSIONS: the medial, unicompartmental arthroplasty of the knee is a valid surgical option and reproducible in the medium term treatment of monocompartmental gonarthrosis in patients between 50 and 60 years of age.

Tibio-talar arthrodesis with long anterograde nail after complex open fracture-dislocation of the ankle : P17

Introduction: Posttraumatic painful osteoarthritis of the ankle joint after fracture-dislocation often has to be treated with arthrodesis. In the presence of major soft tissue lesions and important bone loss the technique to achieve arthrodesis has to be well chosen in order to prevent hardware failure, infection of bulky implants or non-union. Methods: We present the case of a 53 year-old biker suffering of a fracture-dislocation of the ankle associated with a mayor degloving injury of the heel. After initial immobilization of the lesion by external fixation in Spain the patient was transferred to our hospital for further treatment. The degloving injury of the heel with MRSA infection was initially treated by repeated débridement, changing of the configuration of the Ex Fix and antibiotic therapy with favourable outcome. Because of the bony lesions reconstruction of the ankle-joint was juged not to be an option and arthrodesis was planned. Due to bad soft-tissue situation standard open fixtion with plate and/or screws was not wanted but an option for intramedullary nailing was taken. However the use of a standard retrograde arthrodesis nail comes with two problems: 1) Risk of infection of the heel-part of the calaneus/nail in an unstable soft tissue situation with protruding nail. And 2) talo-calcaneal arthrodesis of an initially healthy subtalar joint. Given the situation of an unstable plantar/heel flap it was decided to perform anklearthrodesis by means of an anterograde nail with static fixation in the talus and in the proximal tibia. Results:This operation was performed with minimal opening at the ankle-site in order to remove the remaining cartilage and improve direct bone to bone contact. Arthrodesis was achieved by means of an anterograde T2 Stryker tibial nail.One year after the anterograde nailing the patient walks without pain for up to 4 hours with a heel of good quality and arthrodesis is achieved. Conclusion: Tibiotalar arthrodesis in the presence of mayor soft tissue lesions and bone loss can be successfully achieved with antegrade nailing.

Tratamiento domiciliario de gonartrosis con parches de microcorrientes

Objective: To outline the treatment by patches of microcurrent at home of patients with disabling knee osteoarthritis to perform their activities of daily life and work. Material and methods: We selected 80 patients in the surgical waiting list for total knee arthroplasty. 40 of whom received active patch and 40 inactive. All were given exercise protocol knee. The variables analyzed were: pain (VAS), joint balance, muscular balance and quality of life (SF-12). Patients were reviewed after two months of treatment. Variables were analyzed with SPSS 17.0 statistical program. Results: Statistically significant results were obtained (p <0.05) for decrease in mean pain according to VAS scale. No significant differences for other variables were found. Conclusions: Microcurrent therapy could be an alternative in the treatment of knee osteoarthritis pain, with no differences with the traditional treatment.