Test of four colon cancer risk-scores in formalin fixed paraffin embedded microarray gene expression data.

BACKGROUND: Prognosis prediction for resected primary colon cancer is based on the T-stage Node Metastasis (TNM) staging system. We investigated if four well-documented gene expression risk scores can improve patient stratification. METHODS: Microarray-based versions of risk-scores were applied to a large independent cohort of 688 stage II/III tumors from the PETACC-3 trial. Prognostic value for relapse-free survival (RFS), survival after relapse (SAR), and overall survival (OS) was assessed by regression analysis. To assess improvement over a reference, prognostic model was assessed with the area under curve (AUC) of receiver operating characteristic (ROC) curves. All statistical tests were two-sided, except the AUC increase. RESULTS: All four risk scores (RSs) showed a statistically significant association (single-test, P < .0167) with OS or RFS in univariate models, but with HRs below 1.38 per interquartile range. Three scores were predictors of shorter RFS, one of shorter SAR. Each RS could only marginally improve an RFS or OS model with the known factors T-stage, N-stage, and microsatellite instability (MSI) status (AUC gains < 0.025 units). The pairwise interscore discordance was never high (maximal Spearman correlation = 0.563) A combined score showed a trend to higher prognostic value and higher AUC increase for OS (HR = 1.74, 95% confidence interval [CI] = 1.44 to 2.10, P < .001, AUC from 0.6918 to 0.7321) and RFS (HR = 1.56, 95% CI = 1.33 to 1.84, P < .001, AUC from 0.6723 to 0.6945) than any single score. CONCLUSIONS: The four tested gene expression-based risk scores provide prognostic information but contribute only marginally to improving models based on established risk factors. A combination of the risk scores might provide more robust information. Predictors of RFS and SAR might need to be different.

Efficacy of daptomycin in implant-associated infection due to methicillin-resistant Staphylococcus aureus: importance of combination with rifampin.

Limited treatment options are available for implant-associated infections caused by methicillin (meticillin)-resistant Staphylococcus aureus (MRSA). We compared the activity of daptomycin (alone and with rifampin [rifampicin]) with the activities of other antimicrobial regimens against MRSA ATCC 43300 in the guinea pig foreign-body infection model. The daptomycin MIC and the minimum bactericidal concentration in logarithmic phase and stationary growth phase of MRSA were 0.625, 0.625, and 20 microg/ml, respectively. In time-kill studies, daptomycin showed rapid and concentration-dependent killing of MRSA in stationary growth phase. At concentrations above 20 microg/ml, daptomycin reduced the counts by >3 log(10) CFU/ml in 2 to 4 h. In sterile cage fluid, daptomycin peak concentrations of 23.1, 46.3, and 53.7 microg/ml were reached 4 to 6 h after the administration of single intraperitoneal doses of 20, 30, and 40 mg/kg of body weight, respectively. In treatment studies, daptomycin alone reduced the planktonic MRSA counts by 0.3 log(10) CFU/ml, whereas in combination with rifampin, a reduction in the counts of >6 log(10) CFU/ml was observed. Vancomycin and daptomycin (at both doses) were unable to cure any cage-associated infection when they were given as monotherapy, whereas rifampin alone cured the infections in 33% of the cages. In combination with rifampin, daptomycin showed cure rates of 25% (at 20 mg/kg) and 67% (at 30 mg/kg), vancomycin showed a cure rate of 8%, linezolid showed a cure rate of 0%, and levofloxacin showed a cure rate of 58%. In addition, daptomycin at a high dose (30 mg/kg) completely prevented the emergence of rifampin resistance in planktonic and adherent MRSA cells. Daptomycin at a high dose, corresponding to 6 mg/kg in humans, in combination with rifampin showed the highest activity against planktonic and adherent MRSA. Daptomycin plus rifampin is a promising treatment option for implant-associated MRSA infections.

La prothèse de St Jude medical chez les patients âges de plus de 65 ans [St Jude's Medical prosthesis in patients over 65].

Between September 1979 and December 1982, 56 St Jude Medical valvular prostheses were implanted in 54 patients over 65 years of age. Surgery consisted in simple aortic valve replacement (35 cases), simple mitral valve replacement (12 cases), double aortic and mitral valve replacement (2 cases), valve replacement and coronary artery bypass surgery (3 cases), aortic valve replacement and replacement of the ascending aorta (1 case) and mitral valve replacement and tricuspid annuloplasty (1 case). The operative mortality (within 30 days of surgery) was 3.5% (2 cases). Patients were assessed by clinical examination, ECG, chest X-ray, echocardiogram and laboratory investigations on average 19 months after surgery. There were 3 late deaths (1 endocarditis, 1 cardiac failure and 1 subdural haematoma). No cases of significant haemolysis were observed. There were no cases of thrombosis of the valve or any deaths directly related to the valve. Four patients had cerebral embolism (4.9% per patient/year). None were fatal and only 1 patient had sequellae. Clinical improvement was very significant; 96% of the patients are now in the NYHA Classes I and II whilst 80% were in Class III or IV before surgery. The cardiothoracic ratio decreased significantly from 0.56 to 0.51 (p less than 0.01). The authors conclude that elderly patients may derive great benefits from valvular cardiac surgery and that age in itself is not a contraindication to this type of surgery. The St Jude Medical prosthesis is an excellent prosthesis but thromboembolism remains a major problem as with other mechanical prostheses. Anticoagulation for life is essential.

Patients avec syndrome de Brugada et défibrillateur implanté : suivi clinique

Introduction :¦Le syndrome de Brugada (SB) se définit par une élévation du segment ST dans les dérivations précordiales droites (V1-V3) associée à une incidence élevée de mort subite par arythmies chez des patients sans cardiopathie structurelle. La prévention de la mort subite repose sur la pose d'un défibrillateur automatique implantable (DAI).¦Matériel et méthode :¦Cette étude est une analyse rétrospective de tous les patients avec SB implantés d'un DAI au CHUV entre 1998 et 2010. Le profil des patients, les complications, ainsi que les thérapies appropriées et inappropriées délivrées par le défibrillateur ont été évaluées. Une thérapie appropriée est définie par l'action appropriée du DAI (choc ou stimulation anti-tachycardie = ATP) en réponse à une TV ou une FV correctement détectée. La thérapie inappropriée est définie comme une thérapie délivrée par l'appareil en l'absence d'une arythmie ventriculaire.¦Résultats :¦Durant la période étudiée (01.01.1998 - 31.12.2010) nous avons collecté au total 23 patients soit 19 hommes (83%) et 4 femmes (17%) âgés de 12 à 60 ans (41 13 ans). Le rapport hommes/femmes est de 4.75. Le suivi quant à lui porte sur 21 patients: un patient, après échec de primo-implantation au CHUV, a été implanté d'un défibrillateur dans un autre canton et un second patient a été perdu de vue entre l'implantation et le premier contrôle prévu. Le suivi moyen des 21 patients restants est de 8432 mois (37-149 mois, médiane : 78 mois). Il y a eu au total 45 thérapies délivrées : 12 appropriées (8 chocs; 4 ATP) et 33 inappropriées. 18% des patients ont eu ≥ 1 thérapie appropriée alors que 43% ont eu ≥ 1 choc inapproprié. 14 des 23 patients (61%) ont eu ≥ 1 complication (9 avec chocs inappropriés, 7 avec complications opératoires après primo-implantations ou ré-interventions, 6 avec dysfonction de sonde ventriculaire et 1 avec explantation).¦Conclusion :¦Le profil de ce petit collectif de patients avec SB implantés d'un DAI au CHUV est comparable à celui décrit dans la littérature. Durant un suivi moyen de 7 ans après la primo-implantation, l'incidence d'arythmies ventriculaires malignes est faible, avec un taux annuel de 2.6%. Le taux de complication est quant à lui élevé (8.7%/an). Près des trois-quarts des thérapies délivrées par le DAI sont inappropriées et les patients avec thérapies inappropriées sont 2.4x plus fréquents que les patients avec thérapies appropriées.

Determination of sea surface salinity and wind speed by L-band microwave radiometry from a fixed platform

The European Space Agency Soil Moisture andOcean Salinity (SMOS) mission aims at obtaining global maps ofsoil moisture and sea surface salinity from space for large-scale andclimatic studies. It uses an L-band (1400–1427 MHz) MicrowaveInterferometric Radiometer by Aperture Synthesis to measurebrightness temperature of the earth’s surface at horizontal andvertical polarizations ( h and v). These two parameters will beused together to retrieve the geophysical parameters. The retrievalof salinity is a complex process that requires the knowledge ofother environmental information and an accurate processing ofthe radiometer measurements. Here, we present recent resultsobtained from several studies and field experiments that were partof the SMOS mission, and highlight the issues still to be solved.

Symptom-triggered vs fixed-schedule doses of benzodiazepine for alcohol withdrawal: a randomized treatment trial.

BACKGROUND: In alcohol withdrawal, fixed doses of benzodiazepine are generally recommended as a first-line pharmacologic approach. This study determines the benefits of an individualized treatment regimen on the quantity of benzodiazepine administered and the duration of its use during alcohol withdrawal treatment. METHODS: We conducted a prospective, randomized, double-blind, controlled trial including 117 consecutive patients with alcohol dependence, according to the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, entering an alcohol treatment program at both the Lausanne and Geneva university hospitals, Switzerland. Patients were randomized into 2 groups: (1) 56 were treated with oxazepam in response to the development of signs of alcohol withdrawal (symptom-triggered); and (2) 61 were treated with oxazepam every 6 hours with additional doses as needed (fixed-schedule). The administration of oxazepam in group 1 and additional oxazepam in group 2 was determined using a standardized measure of alcohol withdrawal. The main outcome measures were the total amount and duration of treatment with oxazepam, the incidence of complications, and the comfort level. RESULTS: A total of 22 patients (39%) in the symptom-triggered group were treated with oxazepam vs 100% in the fixed-schedule group (P<.001). The mean oxazepam dose administered in the symptom-triggered group was 37.5 mg compared with 231.4 mg in the fixed-schedule group (P<.001). The mean duration of oxazepam treatment was 20.0 hours in the symptom-triggered group vs 62.7 hours in the fixed-schedule group (P<.001). Withdrawal complications were limited to a single episode of seizures in the symptom-triggered group. There were no differences in the measures of comfort between the 2 groups. CONCLUSIONS: Symptom-triggered benzodiazepine treatment for alcohol withdrawal is safe, comfortable, and associated with a decrease in the quantity of medication and duration of treatment.

Aqueous dynamic and histological findings after deep sclerectomy with collagen implant in an animal model.

AIM: The use of an animal model to study the aqueous dynamic and the histological findings after deep sclerectomy with (DSCI) and without collagen implant. METHODS: Deep sclerectomy was performed on rabbits' eyes. Eyes were randomly assigned to receive collagen implants. Measurements of intraocular pressure (IOP) and aqueous outflow facility using the constant pressure method through cannulation of the anterior chamber were performed. The system was filled with BSS and cationised ferritin. Histological assessment of the operative site was performed. Sections were stained with haematoxylin and eosin and with Prussian blue. Aqueous drainage vessels were identified by the reaction between ferritin and Prussian blue. All eyes were coded so that the investigator was blind to the type of surgery until the evaluation was completed. RESULTS: A significant decrease in IOP (p<0.05) was observed during the first 6 weeks after DSCI (mean IOP was 13.07 (2.95) mm Hg preoperatively and 9.08 (2.25) mm Hg at 6 weeks); DS without collagen implant revealed a significant decrease in IOP at weeks 4 and 8 after surgery (mean IOP 12.57 (3.52) mm Hg preoperatively, 9.45 (3.38) mm Hg at 4 weeks, and 9.22 (3.39) mm Hg at 8 weeks). Outflow facility was significantly increased throughout the 9 months of follow up in both DSCI and DS groups (p<0.05). The preoperative outflow facility (OF) was 0.15 (0.02) micro l/min/mm Hg. At 9 months, OF was 0.52 (0.28) microl/min/mm Hg and 0.46 (0.07) micro l/min/mm Hg for DSCI and DS respectively. Light microscopy studies showed the appearance of new aqueous drainage vessels in the sclera adjacent to the dissection site in DSCI and DS and the apparition of spindle cells lining the collagen implant in DSCI after 2 months. CONCLUSION: A significant IOP decrease was observed during the first weeks after DSCI and DS. DS with or without collagen implant provided a significant increase in outflow facility throughout the 9 months of follow up. This might be partly explained by new drainage vessels in the sclera surrounding the operated site. Microscopic studies revealed the appearance of spindle cells lining the collagen implant in DSCI after 2 months.

Fixed bearing for TKR provides better results for individuals aged 70 and above

55 patients, scheduled to undergo total knee replacement, were randomized to receive either fixed or mobile-bearings. The results from a 5 year follow-up indicated that elderly patients (>70 years of age) with fixed bearings had better improvements in gait parameters in comparison to those with mobile bearings. These results was in fact reversed for patients less than 70 years of age, as they performed best with mobile bearings.

Comparison of radial deformability of stent posts of different aortic bioprostheses.

OBJECTIVES Little is known about the stent deformability required for optimal stented heart valve bioprosthesis design. Therefore, two bioprosthetic valves with known good long-term clinical results were tested. The strain in the radial direction of the stent posts of these valves was compared with contemporary bioprosthetic valves and a native porcine aortic root. METHODS Medtronic Intact and Carpentier-Edwards Standard (CES), and four contemporary bioprostheses, including one self-expanding prosthesis, were tested with three sonomicrometry probes per valve fixed at commissure attachment points. The mean values from 2400 data points from three measurements of the interprobe distances were used to calculate the radius of the circle circumscribed around the three probes. Changes in the radius of the aortic root at pressures 70-90 and 120-140 mmHg (pressure during diastole and systole) and that of the stent posts at 70-90 and 0-10 mmHg (transvalvular pressure gradient during diastole and systole) were compared. RESULTS An increase in radius by 7.3 ± 2.6, 8.7 ± 0.0 and 3.9 ± 0.0% for the porcine aortic root, CES and Intact valves, respectively, was observed during transition from diastolic to systolic pressure and less for contemporary bioprostheses-mean 2.5 ± 0.9%, lowest 1.2 ± 0.0. CONCLUSIONS The results indicate that the radial deformability of bioprosthetic valve stent posts can be as low as 1.2% for xenoaortic and 3.0% for xenopericardial prostheses with no compromise of valve durability. Although these results suggest that valve stent post-deformability might not be of critical importance, a concrete answer to the question of the significance of stent deformability for valve durability can be obtained only by acquiring long-term follow-up results for valve prostheses with rigid stents.

Evaluation of an intravitreal fluocinolone acetonide implant versus standard systemic therapy in noninfectious posterior uveitis.

PURPOSE: To evaluate the safety and efficacy of an intravitreal fluocinolone acetonide (FA) implant compared with standard therapy in subjects with noninfectious posterior uveitis (NIPU). DESIGN: Randomized, controlled, phase 2b/3, open-label, multicenter superiority trial. PARTICIPANTS: Subjects with unilateral or bilateral NIPU. METHODS: One hundred forty subjects received either a 0.59-mg FA intravitreal implant (n = 66) or standard of care (SOC; n = 74) with either systemic prednisolone or equivalent corticosteroid as monotherapy (> or =0.2 mg/kg daily) or, if judged necessary by the investigator, combination therapy with an immunosuppressive agent plus a lower dose of prednisolone or equivalent corticosteroid (> or =0.1 mg/kg daily). MAIN OUTCOME MEASURES: Time to first recurrence of uveitis. RESULTS: Eyes that received the FA intravitreal implant experienced delayed onset of observed recurrence of uveitis (P<0.01) and a lower rate of recurrence of uveitis (18.2% vs. 63.5%; P< or =0.01) compared with SOC study eyes. Adverse events frequently observed in implanted eyes included elevated intraocular pressure (IOP) requiring IOP-lowering surgery (occurring in 21.2% of implanted eyes) and cataracts requiring extraction (occurring in 87.8% of phakic implanted eyes). No treatment-related nonocular adverse events were observed in the implant group, whereas such events occurred in 25.7% of subjects in the SOC group. CONCLUSIONS: The FA intravitreal implant provided better control of inflammation in patients with uveitis compared with systemic therapy. Intraocular pressure and lens clarity of implanted eyes need close monitoring in patients receiving the FA intravitreal implant.

Objective evaluation of shoulder function using body-fixed sensors: a new way to detect early treatment failures?

Background: Variable definitions of outcome (Constant score, Simple Shoulder Test [SST]) have been used to assess outcome after shoulder treatment, although none has been accepted as the universal standard. Physicians lack an objective method to reliably assess the activity of their patients in dynamic conditions. Our purpose was to clinically validate the shoulder kinematic scores given by a portable movement analysis device, using the activities of daily living described in the SST as a reference. The secondary objective was to determine whether this device could be used to document the effectiveness of shoulder treatments (for glenohumeral osteoarthritis and rotator cuff disease) and detect early failures.Methods: A clinical trial including 34 patients and a control group of 31 subjects over an observation period of 1 year was set up. Evaluations were made at baseline and 3, 6, and 12 months after surgery by 2 independent observers. Miniature sensors (3-dimensional gyroscopes and accelerometers) allowed kinematic scores to be computed. They were compared with the regular outcome scores: SST; Disabilities of the Arm, Shoulder and Hand; American Shoulder and Elbow Surgeons; and Constant.Results: Good to excellent correlations (0.61-0.80) were found between kinematics and clinical scores. Significant differences were found at each follow-up in comparison with the baseline status for all the kinematic scores (P < .015). The kinematic scores were able to point out abnormal patient outcomes at the first postoperative follow-up.Conclusion: Kinematic scores add information to the regular outcome tools. They offer an effective way to measure the functional performance of patients with shoulder pathology and have the potential to detect early treatment failures.Level of evidence: Level II, Development of Diagnostic Criteria, Diagnostic Study. (C) 2011 Journal of Shoulder and Elbow Surgery Board of Trustees.

Characteristics and outcome of 27 elbow periprosthetic joint infections: results from a 14-year cohort study of 358 elbow prostheses.

Elbow arthroplasty is increasingly performed in patients with rheumatic and post-traumatic arthritis. Data on elbow periprosthetic joint infection (PJI) are limited. We investigated the characteristics and outcome of elbow PJI in a 14-year cohort of total elbow arthroplasties in a single centre. Elbow prosthesis, which were implanted between 1994 and 2007 at Schulthess Clinic in Zurich, were retrospectively screened for infection. PJI was defined as periprosthetic purulence, the presence of sinus tract or microbial growth. A Kaplan-Meier survival method and Cox proportional hazard analysis were performed. Of 358 elbow prostheses, PJI was identified in 27 (7.5%). The median patient age (range) was 61 (39-82) years; 63% were females. Seventeen patients (63%) had a rheumatic disorder and ten (37%) had osteoarthritis. Debridement and implant retention was performed in 78%, followed by exchange or removal of the prosthesis (15%) or no surgery (7%).The relapse-free survival (95% CI) was 79% (63-95%) after 1 year and 65% (45-85%) after 2 years. The outcome after 2 years was significantly better when patients were treated according to the algorithm compared to patients who were not (100% vs. 33%, p &lt;0.05). In 21 patients treated with debridement and retention, the cure rate was also higher when the algorithm was followed (100% vs. 11%, p &lt;0.05). The findings of the present study suggest that the treatment algorithm developed for hip and knee PJI can be applied to elbow PJI. With proper patient selection and antimicrobial therapy, debridement and retention of the elbow prosthesis is associated with good treatment outcome.

Ten years follow-up after deep sclerectomy with collagen implant.

PURPOSE: To evaluate the long-term success rate and complications of nonpenetrating deep sclerectomy with collagen implant in open-angle glaucoma. PATIENTS AND METHODS: Clinical, prospective, monocentric, nonrandomized, unmasked study on 105 patients with medically uncontrolled glaucoma. A standard procedure deep sclerectomy with collagen implant was performed. Complete examinations were performed before surgery and postoperatively at 1 and 7 days; 1, 2, 3, 6, 9, and 12 months and then every 6 months during the 10 following years. RESULTS: The mean follow-up was 101.5+/-43.1 (3 to 144) months [mean+/-SD, (range)]. The preoperative intraocular pressure (IOP) was 26.8+/-7.7 (14 to 52) mm Hg and the best-corrected visual acuity 0.71+/-0.33 (0.02 to 1.5). Ten years after surgery IOP was 12.2+/-4.7 (6 to 20) mm Hg and best-corrected visual acuity 0.63+/-0.34 (0.01 to 1.2) (number of remaining patients=52). The mean number of medications per patient went from 2.3+/-0.7 (1 to 4) down to 1.3+/-1.1 (0 to 3). An IOP <or=21 mm Hg without medication was achieved in 47.7% patients and in 89% with or without treatment. One major complication was reported. Goniopuncture was performed in 61 eyes (59.8%), 5-fluorouracil treatment given to 25 patients postoperatively and included needling (n=5). CONCLUSIONS: On the basis of a 10-year follow-up deep sclerectomy with collagen implant demonstrated its efficacy in controlling IOP with few postoperative complications.

Fixed-angle elastic hadron scattering

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Biocompatibility of an x-shaped zirconium implant in deep sclerectomy in rabbits

ABSTRACT : Background : The aim of this study was to evaluate the midterm biocompatibility of a new x-shaped implant made of zirconium in an animal model of glaucoma surgery. Methods : Preoperatively, ultrasound biomicroscopy (UBM), intraocular pressure (IOP) and outflow facility (OF) data were acquired. Upon surgery, one eye was chosen randomly to receive an implant, while the other received none. Ten rabbits went through a 1-, 2-, 3-, 4- and 6-month follow-up. [OP was measured regularly, UBM performed at 1, 3 and 6 months after surgery. At the end of the follow-up, OF was again measured. Histology sections were analyzed. Results : For both groups IOP control was satisfactory, while OF initially increased at month 1 to resume preoperative values thereafter. Eyes with implants had larger filtration blebs which decreased faster than in eyes without the implant. Drainage vessel density, inflammatory cell number and fibrosis were higher in tissues near the implant. Conclusions : The zirconium implant initially promoted the positive effects of the surgery (IOP control, OF increase). Nevertheless, after several months, foreign body reactions and fibrosis had occurred on some implants that restrained the early benefit of such a procedure. Modifications of the zirconium implant geometry could enhance the overall success rate.