Functional outcome and quality of life in surgically treated talar neck and body fractures; how is it affected by complications.

BACKGROUND: Since talus fractures are rare, study populations are frequently small. The aim of this study is to describe how surgical treatment of talar neck and body fractures and postoperative complications affect functional outcome and quality of life measured by validated questionnaires. METHODS: All patients following surgically treated talar neck and/or body fracture between January 2000 and December 2019 at a level 1 trauma center were included in this retrospective cohort study. Primary outcomes were functional outcomes measured by Lower Extremity Functional Score (LEFS), the Foot Function Index (FFI), and the Quality of Life (QOL) measured by the EuroQol 5-dimension questionnaire (EQ-5D). Linear regression was used to assess the relationship between continuous variables and the outcome, and multivariable linear regression was used to identify the predictors of the functional outcome. RESULTS: Ninety patients were included, of which 73 responded to our questionnaires. The median follow-up time was 50.5 (interquartile range (IQR), 18.3-97.3) months. Our study showed the following results: a mean LEFS of 58.4 (range, 17-80), a median FFI of 15.7 (IQR, 3.5-35.2), a median EQ-5D index score of 0.83 (IQR, 0.81-1.00), a median patient satisfaction of 9.0 (IQR, 8.0-10.0), a patient reported health status of 76.8 (range, 20-100), and a mean AOFAS score of 75.7 (range, 28-100). Implant removal and secondary arthrodesis were associated with a reduced AOFAS outcome score (p=0.001, p<0.001), and implant removal was also a predictive factor for a less favorable LEFS outcome score (p=0.001). CONCLUSION: Patients who underwent implant removal and/or secondary arthrodesis had poorer functional outcome compared to patients who did not undergo additional procedures. Careful consideration of re-intervention must be made in combination with patient expectation management. Future studies should focus on how to lower the rate of complications and the effect of secondary intervention with the use of validated questionnaires.

Long-Term Follow-up of Functional and Radiographic Outcome After Revision Surgery for Fibula Malunion.

Background. Ankle fractures are some of the most common injuries seen in the emergency department. Malunited ankle fractures are uncommon. Patients with malunion frequently present with multiple complaints. Radiographs often show abnormalities in anatomical alignment. Aim. To evaluate the anatomical alignment on radiographic imaging in patients with malunited ankle fractures. Secondary aims were to evaluate patient satisfaction after reconstruction and to investigate the relationships between radiological alignment and functional outcome. Methods. All consecutive patients (n = 25) treated for a fibula malunion between January 1, 2002, and September 1, 2017, were included. The primary outcome was anatomical alignment of the ankle mortise. The talocrural angle (TCA), talar tilt (TT), and medial clear space (MCS) were used to investigate to what extent revision surgery had improved alignment. The patient-related outcome measure consisted of the Olerud and Molander Ankle Score (OMAS). To assess quality of life (QoL) the EQ-5D-5L was used. Results. The median TCA was 78.4° before revision and 79.25° after revision; P = .297. The median TT was 2.95° before revision and 0.70° after; P < .001. The MCS before revision was 5.2 mm and 3.17 mm after; P < .000). The OMAS had a median of 67.5 points. Analysis of the QoL questionnaires yielded a score of 0.84 points. Conclusion. Anatomical alignment improves significantly after revision surgery of malunited ankles. Measurements of the TCA appeared less useful in determining the anatomical alignment. In our series, 60% of patients reported good to excellent results. The QoL scores of our patient were comparable to those in the healthy population in the Netherlands.Levels of Evidence: Level IV: Case series.

Functional outcome of routine versus on-demand removal of the syndesmotic screw: a multicentre randomized controlled trial.

AIMS: The aim of this study was to investigate whether on-demand removal (ODR) is noninferior to routine removal (RR) of syndesmotic screws regarding functional outcome. METHODS: Adult patients (aged above 17 years) with traumatic syndesmotic injury, surgically treated within 14 days of trauma using one or two syndesmotic screws, were eligible (n = 490) for inclusion in this randomized controlled noninferiority trial. A total of 197 patients were randomized for either ODR (retaining the syndesmotic screw unless there were complaints warranting removal) or RR (screw removed at eight to 12 weeks after syndesmotic fixation), of whom 152 completed the study. The primary outcome was functional outcome at 12 months after screw placement, measured by the Olerud-Molander Ankle Score (OMAS). RESULTS: There were 152 patients included in final analysis (RR = 73; ODR = 79). Of these, 59.2% were male (n = 90), and the mean age was 46.9 years (SD 14.6). Median OMAS at 12 months after syndesmotic fixation was 85 (interquartile range (IQR) 60 to 95) for RR and 80 (IQR 65 to 100) for ODR. The noninferiority test indicated that the observed effect size was significantly within the equivalent bounds of -10 and 10 scale points (p < 0.001) for both the intention-to-treat and per-protocol, meaning that ODR was not inferior to RR. There were significantly more complications in the RR group (12/73) than in the ODR group (1/79) (p = 0.007). CONCLUSION: ODR of the syndesmotic screw is not inferior to routine removal when it comes to functional outcome. Combined with the high complication rate of screw removal, this offers a strong argument to adopt on demand removal as standard practice of care after syndesmotic screw fixation. Cite this article: Bone Joint J 2021;103-B(11):1709-1716.

Wound infection following implant removal of foot, ankle, lower leg or patella; a protocol for a multicenter randomized controlled trial investigating the (cost-)effectiveness of 2 g of prophylactic cefazolin compared to placebo (WIFI-2 trial).

BACKGROUND: Elective implant removal (IR) after fracture fixation is one of the most common procedures within (orthopedic) trauma surgery. The rate of surgical site infections (SSIs) in this procedure is quite high, especially below the level of the knee. Antibiotic prophylaxis is not routinely prescribed, even though it has proved to lower SSI rates in other (orthopedic) trauma surgical procedures. The primary objective is to study the effectiveness of a single intravenous dose of 2 g of cefazolin on SSIs after IR following fixation of foot, ankle and/or lower leg fractures. METHODS: This is a multicenter, double-blind placebo controlled trial with a superiority design, including adult patients undergoing elective implant removal after fixation of a fracture of foot, ankle, lower leg or patella. Exclusion criteria are: an active infection, current antibiotic treatment, or a medical condition contraindicating prophylaxis with cefazolin including allergy. Patients are randomized to receive a single preoperative intravenous dose of either 2 g of cefazolin or a placebo (NaCl). The primary analysis will be an intention-to-treat comparison of the proportion of patients with a SSI at 90 days after IR in both groups. DISCUSSION: If 2 g of prophylactic cefazolin proves to be both effective and cost-effective in preventing SSI, this would have implications for current guidelines. Combined with the high infection rate of IR which previous studies have shown, it would be sufficiently substantiated for guidelines to suggest protocolled use of prophylactic antibiotics in IR of foot, ankle, lower leg or patella. Trial registration Nederlands Trial Register (NTR): NL8284, registered on 9th of January 2020, https://www.trialregister.nl/trial/8284.

Claims in orthopedic foot/ankle surgery, how can they help to improve quality of care? A retrospective claim analysis.

BACKGROUND: Orthopedic foot/ankle surgery is a high risk specialty when it comes to malpractice claims. This study aims to evaluate the incidence, characteristics and outcome of claims in this area. METHODS: This was a retrospective, 10-year claim analysis, with data from an anonymous database. Baseline claim/claimant characteristics were collected from all orthopedic foot/ankle-related cases. RESULTS: Of 460 claims in total, most were related to delay in/wrong diagnosis or to (complications of) elective surgical procedures. Whether a claim was settled was related to type of injury (fracture) and type of claim (diagnostic mistake). Median amount disbursed in settled claims was €12,549. Claim incidence did not increase over the years. CONCLUSION: Missed fracture diagnosis and "failed"/disappointing results of elective surgical procedures were the most common causes for claims. Sufficient knowledge of missed (foot) fractures and clear communication/expectation management before elective procedures could help to improve quality of healthcare and patient satisfaction.

Determining the Correlation Between Lateral Radiograph Morphology and the Outcome Following Surgically Treated Intra-Articular Calcaneal Fractures.

Purpose. It is currently still common practice to obtain conventional radiographs in the follow-up of surgically treated displaced intra-articular calcaneal fractures at regular intervals. There is, however, insufficient evidence that these radiographs can be used to predict functional outcome. The aim of the current study was to evaluate the correlation between the most commonly used angles on lateral radiographs and disease-specific patient-reported outcome measures (PROMs). Methods. Two available databases, containing a total of 233 patients, were used in this study. Eleven angles on the lateral images of the preoperative and at 1-year follow-up radiographs were measured. The 6 most commonly used angles were also measured immediately postoperatively. These 6 most commonly used angles were correlated with PROMs (American Orthopaedic Foot and Ankle Society hindfoot score, Foot Function Index) by a Spearman's rho analysis. After a Bonferroni correction was applied, a P value of <.0042 was considered to be statistically significant. Results. After exclusion of bilateral fractures, primary arthrodesis, open fractures, wound infections, other wound complications, nonavailable radiographs, and nonresponders, 86 patients remained. No significant correlations were found between the measured angles on the preoperative and at 1-year follow-up radiographs and the PROMs. Conclusion. No apparent correlation between lateral radiograph morphology and outcome was detected. Therefore, long-term follow-up radiographs after confirmed healing may be restricted to patients with persistent complaints on indication.Levels of Evidence: Prognostic, Level IV: Retrospective.

Surgical Site Infections After Routine Syndesmotic Screw Removal: A Systematic Review.

OBJECTIVES: To investigate the incidence of surgical site infections (SSIs) after routine removal of syndesmotic screws (SSs) placed to stabilize syndesmotic injuries. DATA SOURCES: A systematic literature search was performed in the PubMed, Cochrane, and EMBASE databases for studies published online before February 2020, using the key words and synonyms of "syndesmotic screw" ("ankle fractures" or "syndesmotic injury") and "implant removal." STUDY SELECTION: Studies were eligible for inclusion when they described >10 adult patients undergoing elective/scheduled removal of the SS. DATA EXTRACTION: The 15 included articles were assessed for quality and risk of bias using the Newcastle-Ottawa Scale. Baseline characteristics of the studies, the study population, the intervention, the potential confounders, and the primary outcome (% of SSIs) were extracted using a customized extraction sheet. DATA SYNTHESIS: The primary outcome was presented as a proportion of included patients and as a weighted mean, using inverse variance, calculated in RStudio. Furthermore, potential confounders were identified. CONCLUSIONS: The percentage of SSIs ranged from 0% to 9.2%, with a weighted mean of 4%. The largest proportion of these infections were superficial (3%, 95% confidence interval: 2-5), compared with 2% deep infections (95% confidence interval: 1-4). These rates were comparable to those of other foot/ankle procedures indicating that the individual indication for SS removal (SSR) should be carefully considered. Future studies should focus on valid indications for SSR, the influence of prophylactic antibiotics on an SSI after SSR, and complications of retaining the SS to enable a fair benefits/risks comparison of routine versus on-demand removal of the SS. LEVEL OF EVIDENCE: Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence.

How Does Mechanism of Injury Relate to Similar Fracture Patterns in Bilateral Displaced Intra-articular Calcaneal Fractures?

Several biomechanical/cadaver studies have established a correlation between mechanism of injury and fracture classification in calcaneal fractures. However, this has never been backed up by clinical studies. In this study, the hypothesis is tested whether the alleged similar mechanism of injury for both feet in bilateral calcaneal fractures leads to similar fracture types. In this retrospective cross-sectional cohort study, patients with unilateral and bilateral calcaneal fractures treated between 2000 and 2017 were classified according to Essex-Lopresti and Sanders. Positive predictive values were computed, signifying the chance that the fracture type in the left foot corresponded to that in the right foot. These were compared to the a priori chance of a fracture type (percentage of fracture type in unilateral fractures) by constructing 95% confidence intervals of the positive predictive value of each fracture type. Of the 451 patients, 413 (91.6%) had unilateral and 38 (8.4%) bilateral calcaneal fractures. Mechanisms of injury were similar for uni- and bilateral fractures. Using the Essex-Lopresti fracture classification, 34 cases (90%) had the same classification in both feet, compared with 24 (63%) in the Sanders classification. The chance of a fracture type in the left, with the right foot as reference, was significantly larger than expected from a priori chance in the unilateral population. This leads to a new hypothesis, that, more than mechanism of injury, the magnitude of the impact and the position of the foot are important in predicting fracture classification in the calcaneus.

Comparison of 2g vs 1 g of Prophylactic Cefazolin in Surgical Site Infections in Trauma Surgery Below the Knee.

BACKGROUND: The rate of surgical site infections (SSIs) after foot or ankle surgery remains high, despite the implementation of antibiotic prophylaxis. Recently, guidelines suggest a single dose of 2 g instead of 1 g of cefazolin for implant surgery; this decision is largely based on pharmacokinetic studies. However, the clinical effect of this higher dose has never been investigated in foot and ankle surgery. This retrospective cohort study investigated the effect of 2 g compared with 1 g of prophylactic cefazolin on the incidence of SSIs in foot and ankle surgery. METHODS: All patients undergoing trauma-related surgery of the foot, ankle, or lower leg between September 2015 and March 2019 were included. The primary outcome was the incidence of an SSI. SSIs were compared between patients receiving 1 g and 2 g of cefazolin as surgical prophylaxis, using a propensity score to correct for possible confounders. RESULTS: A total of 293 patients received 1 g and 126 patients received 2 g of cefazolin. The overall number of SSIs was 19 (6.5%) in the 1-g group and 6 (4.8%) in the 2-g group. Corrected for possible confounders, this was not statistically significant (OR, 0.770; P = .608). CONCLUSION: Even though the decrease in SSI rate from 6.5% to 4.8% was found not to be statistically significant, it might be clinically relevant considering the reduction in morbidity, mortality, and healthcare costs. Research linking pharmacokinetic and clinical results of prophylactic cefazolin is needed to establish whether or not the current recommendations and guidelines are sufficient for preventing SSIs in foot and ankle surgery. LEVEL OF EVIDENCE: Level III, retrospective comparative series.

High versus low dose Stereotactic Body Radiation Therapy for hepatic metastases.

INTRODUCTION: Stereotactic Body Radiation Therapy (SBRT) is a treatment option for patients with liver metastases. This study evaluated the impact of high versus low dose image-guided SBRT of hepatic metastases. METHODS AND MATERIALS: This is a single-center retrospective study of patients with liver metastases treated with SBRT. For analyses, patients were divided into two groups: ≤100 Gy and >100 Gy near-minimum Biological Effective Doses (BED98%). The main outcomes were local control (LC), toxicity and overall survival (OS). Cox regression analyses were performed to determine prognostic variables on LC and OS. RESULTS: Ninety patients with 97 liver metastases (77% colorectal) were included. Median follow-up was 28.6 months. The two-year LC rates in the ≤100 Gy and >100 Gy BED98% group were 60% (CI: 41-80%) and 90% (CI: 80-100%), respectively (p = 0.004). Grade 3 toxicity occurred in 7% vs 2% in the ≤100 Gy and >100 Gy group (p = 0.23). Two-year OS rates in the ≤100 Gy and >100 Gy group were 48% (CI: 32-65%) and 85% (CI: 73-97%), respectively (p = 0.007). In multivariable Cox regression analyses, group dose and tumor volume were significantly correlated with LC (HR: 3.61; p = 0.017 and HR: 1.01; p = 0.005) and OS (HR: 2.38; p = 0.005 and HR: 1.01; p = <0.0001). CONCLUSION: High dose SBRT provides significantly better local control and overall survival than low dose SBRT without increasing toxicity. When surgical resection is not feasible, high dose SBRT provides an effective and safe treatment for liver metastases.

What is the added value of pedobarography for assessing functional outcome of displaced intra-articular calcaneal fractures? A systematic review of existing literature.

BACKGROUND: Displaced intra-articular calcaneal fractures often result in permanent disability, reduced quality of life and high socio-economic costs. Since they often result in a change in geometry of the foot, pedobarography may be useful in predicting outcome at an early stage. The aim of this study was to examine whether a correlation exists between pedobarography and functional outcomes in patients with a displaced intra-articular fracture. METHODS: In this systematic review, studies were included when they investigated the correlation between pedobarography and functional outcome in displaced intra-articular calcaneal fractures. Excluded were studies on <10 patients or on animals/cadavers. Collected were baseline patient/treatment characteristics, pedobarographic data (peak pressures, maximum force and centre of pressure) and functional outcome scores. FINDINGS: Out of 153 abstracts, 40 remained for full text screening and 9 were included. Pedobarographic measurements (pressure plate or insoles) showed a lateralization of centre of pressure, decreased pressures underneath the hindfoot, first and second toe and increased pressure underneath the midfoot and forefoot. Correlations with functional outcome were found in some combined pedobarographic results (entire foot/multiple measurements), but hardly in pressures underneath specific foot areas. INTERPRETATION: Even though increased or decreased pressures in specific areas of the foot may not be directly related to functional outcome, combined scores often did. For pedobarography to serve as a prediction tool, it should be more standardised. However, assessing centre of pressure and altered peak pressures underneath the foot, may be useful in developing customized aids such as insoles, aiming for a more individualized improvement.

Anterior inferior tibiofibular ligament avulsion fractures in operatively treated ankle fractures: a retrospective analysis.

BACKGROUND: There is no consensus about the optimal treatment of anterior inferior ligament avulsion fractures of the ankle. The aim of this study is to provide insights regarding the incidence of anterior inferior ligament avulsion fractures, the association with fracture type, and correlation with treatment. METHODS: This study is a retrospective analysis in a level-1 trauma center of adult patients with an ankle fracture operated between the dates 01-01-2009 and 01-09-2017 who had a pre- and postoperative CT-scan. Within the study population, the incidence of AITFL avulsion fracture was defined. Primary outcome was the type of avulsion fracture and related treatment. Secondary outcome was additional surgery in relation to the initial treatment. RESULTS: In total, 65 of 252 (25.8%) patients were diagnosed with an anterior inferior ligament avulsion fracture. Zero patients had a Wagstaffe type 1 fracture, 28 (43.1%) had a type 2, 32 (49.2%) had a type 3, and 5 (7.7%) had a type 4. There was a correlation between Wagstaffe type 2 and Weber B fractures, p < 0.0001, and Wagstaffe type 3 avulsions were correlated with a Weber C fracture, p < 0.0001. Thirty-five of the avulsed fragments (53.8%) were smaller than 5 mm. In 13 (20%) of patients with anterior inferior ligament avulsion fracture, the avulsed fragments were directly fixated during initial surgery. Size and direct fixation of the fragment were significantly correlated (p < 0.0001). Within the anterior inferior ligament avulsion fracture group, only a total of four patients (6.2%) underwent a revision. CONCLUSION: In the current study, an incidence of 25.8% of anterior inferior ligament avulsion fracture in surgically treated ankle fractures is reported. A correlation between the type of Wagstaffe injury and Weber classification was showed. Most fragments smaller than 5 mm were not fixated; however, not all injuries needed syndesmotic screws due to syndesmotic instability. LEVEL OF EVIDENCE: Level IV.

Target site antibiotic concentrations in orthopedic/trauma extremity surgery: is prophylactic cefazolin adequately dosed? A systematic review and meta-analysis.

Background and purpose - The incidence of surgical site infections (SSIs) in trauma/orthopedic surgery varies between different body parts. Antibiotic prophylaxis (e.g., with cefazolin) lowers infection rates in closed fracture surgery and in primary arthroplasty. For prophylactic antibiotics to prevent infections, sufficient concentrations at the target site (location of surgery) are required. However, dosage recommendations and the corresponding efficacy are unclear. This review assesses target site cefazolin concentrations and the effect of variation in dose and location of target site during orthopedic extremity surgery. Methods - For this meta-analysis and systematic review, the literature was searched using the following keywords: "cephalosporins," "orthopedic," "extremity," "surgical procedures," and "pharmacokinetics". Trials measuring target site antibiotic concentrations (bone, soft tissue, synovia) during orthopedic surgery after a single dose of cefazolin were included. Results - The search identified 14 studies reporting on concentrations in the shoulder (n = 1), hip (n = 8), knee (n = 8), or foot (n = 1). A large variation was seen between studies, but the pooled results of 4 studies showed higher concentrations in hip than in knee (mean difference: 4 ug/g, 95% CI 0.8-7). Articles comparing different doses of cefazolin reported higher bone concentrations after 2 g than before, but pooling results did not lead to a statistically significant difference. Interpretation - Although not all results could be pooled, this study shows that cefazolin concentrations are higher in the hip than in the knee. These findings suggest that the dose of prophylactic cefazolin might not be sufficient in distal parts of the extremity. Further research should investigate whether a higher dose of cefazolin can lead to higher concentrations and fewer SSIs.

[Evaluation of cardiac MRI in the follow up assessment of patients with pulmonary arterial hypertension]. / Évaluation de l'IRM cardiaque dans le suivi des patients ayant une hypertension artérielle pulmonaire (EVITA). IRM cardiaque dans le suivi de l'hypertension artérielle pulmonaire.

Haemodynamic follow up in pulmonary arterial hypertension (PAH) is currently based on right heart catheterisation (RHC). The primary objective of the EVITA study is to compare the use of cardiac magnetic resonance imaging (cMRI) with RHC in the identification of an unfavourable hemodynamic status. The secondary objectives are to determine the role of cMRI in the follow up process. Patients will undergo at diagnosis and at follow up visits both RHC and cMRI. Patients will be followed and treated according to the current guidelines. The primary endpoint will be an unfavourable haemodynamic status defined by cardiac index<2.5L/min/m2 or a right atrial pressure≥8mm Hg measured with RHC compared with a cardiac index<2.5L/min/m2 or right ventricle ejection fraction<35% or an absolute decrease of 10% from the previous measurement with cMRI. Exact values of sensitivity, specificity and 95% confidence intervals will be computed. A population of 180 subjects will have a power of 90% with an α risk of 5%. Univariate and multivariate Cox analysis will allow answering to the secondary objectives. We expect to demonstrate that cMRI could be partly used instead of RHC in the follow up of patients with PAH.

Natural history of benign multiple sclerosis: Clinical and HLA correlates in a Western Australian cohort.

BACKGROUND: Benign multiple sclerosis (BMS) is a controversial term that has been used for MS patients with minimal disability decades after disease onset. Herein, we evaluated disease status after 20 years in a Western Australian cohort defined as BMS based on an Expanded Disability Status Scale (EDSS) score ≤ 3.0 at 10 years from onset. METHODS: MS patients with an EDSS score ≤ 3.0 at 10 years from onset and minimum of 20 years follow up were included in the study. The 20-year EDSS score was considered the primary outcome. Associations with demographic and clinical characteristics and HLA-DRB1 genotype were investigated. RESULTS: Among 120 patients with a benign course at 10 years, 78 (65%) remained benign at the 20-year follow up, but patients with an EDSS ≥ 2.5 were more likely to go on to develop more severe disability in the next decade. When considering factors associated with an increase in EDSS score ≤ 1 from 10 to 20 years, indicating limited progression, apart from the EDSS score at 10 years, poly-symptomatic presentation (p = 0.004) and cerebellar/brainstem mono-symptomatic presentation (p = 0.016) were independently associated with more rapid progression compared with other mono-symptomatic presentations. Carriage of the high risk HLA-DRB1*1501 allele was marginally associated with slower progression. CONCLUSIONS: In this geographically isolated MS cohort of predominantly Anglo-Celtic origin clinical progression in the benign MS group was similar to that in other published series from Western countries. These results are in keeping with the view that patients labeled as benign MS are part of a heterogeneous continuum of disease progression and do not possess unique clinical characteristics. Possible genetic determinants of a benign course warrant further investigation.

Combined baseline and one-month changes in big endothelin-1 and brain natriuretic peptide plasma concentrations predict clinical outcomes in patients with left ventricular dysfunction after acute myocardial infarction: Insights from the Eplerenone Post-Acute Myocardial Infarction Heart Failure Efficacy and Survival Study (EPHESUS) study.

OBJECTIVE: Increased levels of neuro-hormonal biomarkers predict poor prognosis in patients with acute myocardial infarction (AMI) complicated by left ventricular systolic dysfunction (LVSD). The predictive value of repeated (one-month interval) brain natriuretic peptides (BNP) and big-endothelin 1 (BigET-1) measurements were investigated in patients with LVSD after AMI. METHODS: In a sub-study of the Eplerenone Post-Acute Myocardial Infarction Heart Failure Efficacy and Survival Study (EPHESUS trial), BNP and BigET-1 were measured at baseline and at 1month in 476 patients. RESULTS: When included in the same Cox regression model, baseline BNP (p=0.0003) and BigET-1 (p=0.026) as well as the relative changes (after 1month) from baseline in BNP (p=0.049) and BigET-1 (p=0.045) were predictive of the composite of cardiovascular death or hospitalization for worsening heart failure. Adding baseline and changes in BigET-1 to baseline and changes in BNP led to a significant increase in prognostic reclassification as assessed by integrated discrimination improvement index (5.0%, p=0.01 for the primary endpoint). CONCLUSIONS: Both increased baseline and changes after one month in BigET-1 concentrations were shown to be associated with adverse clinical outcomes, independently from BNP baseline levels and one month changes, in patients after recent AMI complicated with LVSD. This novel result may be of clinical interest since such combined biomarker assessment could improve risk stratification and open new avenues for biomarker-guided targeted therapies. KEY MESSAGES: In the present study, we report for the first time in a population of patients with reduced LVEF after AMI and signs or symptoms of congestive HF, that increased baseline values of BNP and BigET-1 as well as a further rise of these markers over the first month after AMI, were independently predictive of future cardiovascular events. This approach may therefore be of clinical interest with the potential of improving risk stratification after AMI with reduced LVEF while further opening new avenues for biomarker-guided targeted therapies.

Preventive and chronic mineralocorticoid receptor antagonism is highly beneficial in obese SHHF rats.

BACKGROUND AND PURPOSE: Mineralocorticoid receptor (MR) activation contributes to heart failure (HF) progression. Its overactivity in obesity is thought to accelerate cardiac remodelling and HF development. Given that MR antagonists (MRA) are beneficial in chronic HF patients, we hypothesized that early MRA treatment may target obesity-related disorders and consequently delay the development of HF. EXPERIMENTAL APPROACH: Twenty spontaneously hypertensive HF dyslipidaemic obese SHHF(cp/cp) rats and 18 non-dyslipidaemic lean SHHF(+/+) controls underwent regular monitoring for their metabolic and cardiovascular phenotypes with or without MRA treatment [eplerenone (eple), 100 mg∙kg(-1) ∙day(-1) ] from 1.5 to 12.5 months of age. KEY RESULTS: Eleven months of eple treatment in obese rats (SHHF(cp/cp) eple) reduced the obesity-related metabolic disorders observed in untreated SHHF(cp/cp) rats by reducing weight gain, triglycerides and total cholesterol levels and by preserving adiponectinaemia. The MRA treatment predominantly preserved diastolic and systolic functions in obese rats by alleviating the eccentric cardiac hypertrophy observed in untreated SHHF(cp/cp) animals and preserving ejection fraction (70 ± 1 vs. 59 ± 1%). The MRA also improved survival independently of these pressure effects. CONCLUSION AND IMPLICATIONS: Early chronic eple treatment resulted in a delay in cardiac remodelling and HF onset in both SHHF(+/+) and SHHF(cp/cp) rats, whereas SHHF(cp/cp) rats further benefited from the MRA treatment through a reduction in their obesity and dyslipidaemia. These findings suggest that preventive MRA therapy may provide greater benefits in obese patients with additional risk factors of developing cardiovascular complications.

Local recurrence after ductal carcinoma in situ breast conserving treatment. Analysis of 195 cases.

PURPOSE: Ductal carcinoma in situ overall prognosis is excellent, but after breast conserving surgery, with or without radiotherapy, local recurrences can lead to locoregional or distant evolution and death. However, there are few data on optimal local recurrences treatment and long-term impact on survival. PATIENTS AND METHODS: This study included 195 women treated from 1985 to 1996 by conservative surgery (CS) or conservative surgery followed by radiotherapy (CS+RT), presenting local recurrences, with a 156-month median follow-up. RESULTS: Eighty-two out of 195 (42%) local recurrences were non-invasive (in situ) and 113 (58%) invasive. In situ local recurrence was discovered by mammography in 80.5% of the cases versus 47.5% for invasive local recurrence (P=0.0001). Salvage mastectomy was used in 53% of the cases after conservative surgery and 75% after conservative surgery followed by radiotherapy. The axillary nodal involvement rates were 11.8% and 25.8% among 17 and 62 patients with in situ and invasive local recurrences. Among 113 patients with invasive local recurrences and 82 with in situ local recurrences, 19 (16.8%) and three (3.6%) developed metastases, respectively. Among invasive local recurrences, comedocarcinoma subtype was highly predictive of subsequent metastases (32% versus 4.4%, P<0.0007). CONCLUSION: Invasive local recurrence after ductal carcinoma in situ treatment could be a dramatic event, fully changing long-term prognosis. Early mammographic local recurrence diagnosis (if possible still at non-invasive stage) seems essential to avoid or minimize metastatic risk. Mastectomy remains the safest option but, in some cases, a new conservative approach could be discussed.

Laboratory effect on platelet activity within 24 h of the first 300-mg oral dose of aspirin given in hospital during the acute phase of ischemic cerebral events.

BACKGROUND AND PURPOSE: Aspirin is the most commonly used antiplatelet treatment during the acute phase of cerebral ischemic events. It inhibits the production of thromboxane (TX) A(2), a powerful platelet activator. Despite this protection, early ischemic recurrences are frequent and considered clinical failures of this therapy. Only a few trials have focused on the use of antiplatelet therapy during this phase, and none has described the laboratory effect of the first dose of aspirin given after an ischemic cerebral event. However, this study may help clinicians to understand the mechanisms of early recurrences, and to design new therapeutic strategies, in particular for patients already treated with a daily dose of aspirin. METHOD: We studied laboratory parameters of the first 300-mg oral dose of aspirin given within 48 h after an ischemic cerebral event. Two blood samples were taken from all of the patients: the first during the third hour following aspirin intake (T1) and the second during the twenty-fourth hour (T2). For patients already treated with a daily dose of aspirin, a supplementary sample was taken before aspirin intake (T0). Platelet reactivity was studied on the basis of serum TXB(2) levels, a metabolite of TXA(2), and light transmission aggregometry after stimulation of platelet-rich plasma by arachidonic acid and by two concentrations of collagen, i.e. 2 µg/ml (Col2), dependent on the TXA(2) pathway, and 20 µg/ml (Col20), independent of the TXA(2) pathway. Results with Col2 were related to results with Col20 (Col2/20 ratio) to limit the impact of variations induced by the effects of preanalytical conditions. RESULTS: Fifty patients were included. TXB(2) values (p < 0.001) and relative values of the Col2/20 ratio (p = 0.037) were significantly higher at T2 compared to T1. For patients already treated with aspirin, TXB(2) levels (p < 0.001) were significantly lower at T1 compared to T0, and the Col2/20 ratio tended to decrease (p = 0.096). CONCLUSION: Platelet reactivity recovers within 24 h following the first 300-mg oral dose of aspirin during the acute phase of a cerebral ischemic event as demonstrated by an increase in TXB(2) levels, and the Col2/20 ratio, at T2 compared to T1. This would favor early ischemic recurrences. However, for patients already treated with aspirin, this dose is able to decrease TXB(2) levels and to complete the inhibition of the TXA(2) pathway, which shows the utility of this prescription in this case.

[Management of paediatric fever: is parents' skill appropriate?]. / Prise en charge de la fièvre de l'enfant: les connaissances et pratiques des parents sont-elles satisfaisantes?

UNLABELLED: Paediatric fever is a frequent reason of consulting a paediatrician or a general practitioner (30% of paediatric consultations). AIM OF THE STUDY: This investigation aimed at reporting the knowledge level concerning child's and infant's fever in a urban population and the resulting practices. Two thousand and six hundred questionnaires were distributed in June 2004 in the 29 scholar institutions of Metz agglomeration (France) classified in 3 categories according to socio-economical conditions of parents: 3 institutions of city centre (high socioeconomical conditions), 18 sub-urban institutions (intermediary conditions) and 8 institutions located in priority education zones (ZEP) (defavorable conditions). RESULTS: One thousand and thirty-eight questionnaires could be analyzed (40%): 176 in city centre, 634 in sub-urban zones and 228 in ZEP. Fever threshold at 38 degrees C is well-known and fever measuring methods used are mostly in accordance with the recommendations. The best room temperature was known and the use of antipyretic physical means underlined only a few cases of obvious mistakes. All parents were informed about worrying signs related with fever even if doctor's resort was excessive. Acetaminophen was the reference molecule before ibuprofen whereas the use of aspirin was decreasing. Antipyretic treatments methods used by parents were often unsuitable, leading to therapeutical inefficacy, overdosage or noxious drug interactions, mainly because of a lack of knowledge about drug components. CONCLUSION: This investigation underlines insufficient knowledge and noxious management practices among parents with unfavourable socio-economical conditions which lead us to recommend targeted information preferentially in areas gathering together most unfavourable socio-economical condition populations.