The Acute STroke Registry and Analysis of Lausanne (ASTRAL): design and baseline analysis of an ischemic stroke registry including acute multimodal imaging.

BACKGROUND AND PURPOSE: Stroke registries are valuable tools for obtaining information about stroke epidemiology and management. The Acute STroke Registry and Analysis of Lausanne (ASTRAL) prospectively collects epidemiological, clinical, laboratory and multimodal brain imaging data of acute ischemic stroke patients in the Centre Hospitalier Universitaire Vaudois (CHUV). Here, we provide design and methods used to create ASTRAL and present baseline data of our patients (2003 to 2008). METHODS: All consecutive patients admitted to CHUV between January 1, 2003 and December 31, 2008 with acute ischemic stroke within 24 hours of symptom onset were included in ASTRAL. Patients arriving beyond 24 hours, with transient ischemic attack, intracerebral hemorrhage, subarachnoidal hemorrhage, or cerebral sinus venous thrombosis, were excluded. Recurrent ischemic strokes were registered as new events. RESULTS: Between 2003 and 2008, 1633 patients and 1742 events were registered in ASTRAL. There was a preponderance of males, even in the elderly. Cardioembolic stroke was the most frequent type of stroke. Most strokes were of minor severity (National Institute of Health Stroke Scale [NIHSS] score ≤ 4 in 40.8% of patients). Cardioembolic stroke and dissections presented with the most severe clinical picture. There was a significant number of patients with unknown onset stroke, including wake-up stroke (n=568, 33.1%). Median time from last-well time to hospital arrival was 142 minutes for known onset and 759 minutes for unknown-onset stroke. The rate of intravenous or intraarterial thrombolysis between 2003 and 2008 increased from 10.8% to 20.8% in patients admitted within 24 hours of last-well time. Acute brain imaging was performed in 1695 patients (97.3%) within 24 hours. In 1358 patients (78%) who underwent acute computed tomography angiography, 717 patients (52.8%) had significant abnormalities. Of the 1068 supratentorial stroke patients who underwent acute perfusion computed tomography (61.3%), focal hypoperfusion was demonstrated in 786 patients (73.6%). CONCLUSIONS: This hospital-based prospective registry of consecutive acute ischemic strokes incorporates demographic, clinical, metabolic, acute perfusion, and arterial imaging. It is characterized by a high proportion of minor and unknown-onset strokes, short onset-to-admission time for known-onset patients, rapidly increasing thrombolysis rates, and significant vascular and perfusion imaging abnormalities in the majority of patients.

Hypertension pulmonaire: difficulté diagnostique et intérêt de l'échocardiographie [Pulmonary hypertension: difficult diagnosis and role of echocardiography]

Pulmonary hypertension (PH) is a complex disease leading, in its advance form, to a decreased quality of life and early mortality. In the early stage, non specific signs and symptoms are the rule. The diagnosis is often missed, leaving the patient alone to face the disease and its repercussion on his daily life. This article reviews the main PH causes and predisposing conditions. Signs and symptoms suggesting the diagnosis are reviewed as well as conditions recognised at high risk for the disease. The key role of echocardiography in establishing the diagnosis, assessing PH severity, cardiac repercussions and/or potential aetiologies, is addressed. Finally the importance of a multidisciplinary approach is recommended.

Registries in rheumatological and musculoskeletal conditions. Paediatric Behçet's disease: an international cohort study of 110 patients. One-year follow-up data.

OBJECTIVE: To set-up an international cohort of patients suspected with Behçet's disease (BD). The cohort is aimed at defining an algorithm for definition of the disease in children. METHODS: International experts have defined the inclusion criteria as follows: recurrent oral aphthosis (ROA) plus one of following-genital ulceration, erythema nodosum, folliculitis, pustulous/acneiform lesions, positive pathergy test, uveitis, venous/arterial thrombosis and family history of BD. Onset of disease is <16 years, disease duration is ≤3 years, future follow-up duration is ≥4 years and informed consent is obtained. The expert committee has classified the included patients into: definite paediatric BD (PED-BD), probable PED-BD and no PED-BD. Statistical analysis is performed to compare the three groups of patients. Centres document their patients into a single database. RESULTS: At January 2010, 110 patients (56 males/54 females) have been included. Mean age at first symptom: 8.1 years (median 8.2 years). At inclusion, 38% had only one symptom associated with ROA, 31% had two and 31% had three or more symptoms. A total of 106 first evaluations have been done. Seventeen patients underwent the first-year evaluation, and 36 had no new symptoms, 12 had one and 9 had two. Experts have examined 48 files and classified 30 as definite and 18 as probable. Twenty-six patients classified as definite fulfilled the International Study Group criteria. Seventeen patients classified as probable did not meet the international criteria. CONCLUSION: The expert committee has classified the majority of patients in the BD group although they presented with few symptoms independently of BD classification criteria.

Cognitive efficacy of quetiapine in early-onset first-episode psychosis: a 12-week open label trial.

Twenty-three adolescents with psychotic disorders, aged from 13 to 18 years, participated in a 12-week open label trial (17 adolescents completed the study) in order to examine the impact of quetiapine on clinical status and cognitive functions (encompassing processing speed, attention, short-term memory, long-term memory and executive function). An improvement in Clinical Global Impression and Positive and Negative Symptom Scale (P's ≤ 0.001) was observed. In addition, after controlling for amelioration of symptoms, a significant improvement was observed on one executive function (P = 0.044; Trail Making Part B). The remaining cognitive abilities showed stability. In addition, we observed an interaction between quetiapine doses (>300 mg/day or <300 mg/day) and time, where lower doses showed more improvement in verbal short-term memory (P = 0.048), inhibition abilities (P = 0.038) and positive symptoms (P = 0.020). The neuropsychological functioning of adolescents with psychotic disorders remained mainly stable after 12 weeks of treatment with quetiapine. However, lower doses seemed to have a better impact on two components of cognition (inhibition abilities and verbal short-term memory) and on positive symptoms.

Effects of an interleukin-15 antagonist on systemic and skeletal alterations in mice with DSS-induced colitis.

Inflammatory bowel diseases are commonly complicated by weight and bone loss. We hypothesized that IL-15, a pro-inflammatory cytokine expressed in colitis and an osteoclastogenic factor, could play a central role in systemic and skeletal complications of inflammatory bowel diseases. We evaluated the effects of an IL-15 antagonist, CRB-15, in mice with chronic colitis induced by oral 2% dextran sulfate sodium for 1 week, followed by another 1% for 2 weeks. During the last 2 weeks, mice were treated daily with CRB-15 or an IgG2a control antibody. Intestinal inflammation, disease severity, and bone parameters were evaluated at days 14 and 21. CRB-15 improved survival, early weight loss, and colitis clinical score, although colon damage and inflammation were prevented in only half the survivors. CRB-15 also delayed loss of femur bone mineral density and trabecular microarchitecture. Bone loss was characterized by decreased bone formation, but increased bone marrow osteoclast progenitors and osteoclast numbers on bone surfaces. CRB-15 prevented the suppression of osteoblastic markers of bone formation, and reduced osteoclast progenitors at day 14, but not later. However, by day 21, CRB-15 decreased tumor necrosis factor α and increased IL-10 expression in bone, paralleling a reduction of osteoclasts. These results delineate the role of IL-15 on the systemic and skeletal manifestations of chronic colitis and provide a proof-of-concept for future therapeutic developments.

Efficiency and safety of bilateral contemporaneous pallidal stimulation (deep brain stimulation) in levodopa-responsive patients with Parkinson's disease with severe motor fluctuations: a 2-year follow-up review.

OBJECT: The aim of this study was to evaluate the long-term safety and efficacy of bilateral contemporaneous deep brain stimulation (DBS) in patients who have levodopa-responsive parkinsonism with untreatable motor fluctuations. Bilateral pallidotomy carries a high risk of corticobulbar and cognitive dysfunction. Deep brain stimulation offers new alternatives with major advantages such as reversibility of effects, minimal permanent lesions, and adaptability to individual needs, changes in medication, side effects, and evolution of the disease. METHODS: Patients in whom levodopa-responsive parkinsonism with untreatable severe motor fluctuations has been clinically diagnosed underwent bilateral pallidal magnetic resonance image-guided electrode implantation while receiving a local anesthetic. Pre- and postoperative evaluations at 3-month intervals included Unified Parkinson's Disease Rating Scale (UPDRS) scoring, Hoehn and Yahr staging, 24-hour self-assessments, and neuropsychological examinations. Six patients with a mean age of 55 years (mean 42-67 years), a mean duration of disease of 15.5 years (range 12-21 years), a mean "on/off' Hoehn and Yahr stage score of 3/4.2 (range 3-5), and a mean "off' time of 40% (range 20-50%) underwent bilateral contemporaneous pallidal DBS, with a minimum follow-up period lasting 24 months (range 24-30 months). The mean dose of levodopa in these patients could not be changed significantly after the procedure and pergolide was added after 12 months in five patients because of recurring fluctuations despite adjustments in stimulation parameters. All but two patients had no fluctuations until 9 months. Two of the patients reported barely perceptible fluctuations at 12 months and two at 15 months; however, two patients remain without fluctuations at 2 years. The mean improvements in the UPDRS motor score in the off time and the activities of daily living (ADL) score were more than 50%; the mean off time decreased from 40 to 10%, and the mean dyskinesia and complication of treatment scores were reduced to one-third until pergolide was introduced at 12 months. No significant improvement in "on" scores was observed. A slight worsening after 1 year was observed and three patients developed levodopa- and stimulation-resistant gait ignition failure and minimal fluctuations at 1 year. Side effects, which were controlled by modulation of stimulation, included dysarthria, dystonia, and confusion. CONCLUSIONS: Bilateral pallidal DBS is safe and efficient in patients who have levodopa-responsive parkinsonism with severe fluctuations. Major improvements in motor score, ADL score, and off time persisted beyond 2 years after the operation, but signs of decreased efficacy started to be seen after 12 months.

Quality of care and survival of haemodialysed patients in western Switzerland.

BACKGROUND: Many factors affect survival in haemodialysis (HD) patients. Our aim was to study whether quality of clinical care may affect survival in this population, when adjusted for demographic characteristics and co-morbidities. METHODS: We studied survival in 553 patients treated by chronic HD during March 2001 in 21 dialysis facilities in western Switzerland. Indicators of quality of care were established for anaemia control, calcium and phosphate product, serum albumin, pre-dialysis blood pressure (BP), type of vascular access and dialysis adequacy (spKt/V) and their baseline values were related to 3-year survival. The modified Charlson co-morbidity index (including age) and transplantation status were also considered as a predictor of survival. RESULTS: Three-year survival was obtained for 96% of the patients; 39% (211/541) of these patients had died. The 3-year survival was 50, 62 and 69%, respectively, in patients who had 0-2, 3 and >or=4 fulfilled indicators of quality of care (test for linear trend, P < 0.001). In a Cox multivariate analysis model, the absence of transplantation, a higher modified Charlson's score, decreased fulfilment of indicators of good clinical care and low pre-dialysis systolic BP were independent predictors of death. CONCLUSION: Good clinical care improves survival in HD patients, even after adjustment for availability of transplantation and co-morbidities.

Circadian variations of ischemic burden among patients with myocardial infarction undergoing primary percutaneous coronary intervention.

BACKGROUND: Several parameters of cardiovascular physiology and pathophysiology exhibit circadian rhythms. Recently, a relation between infarct size and the time of day at which it occurs has been suggested in experimental models of myocardial infarction. The aim of this study is to investigate whether circadian rhythms could cause differences in ischemic burden in patients with ST-elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PPCI).¦METHODS: In 353 consecutive patients with STEMI treated by PPCI, time of symptom onset, peak creatine kinase (CK), and follow-up at 30 days were obtained. We divided 24 hours into 4 time groups based on time of symptom onset (00:00-05:59, 06:00-11:59, 12:00-17:59, and 18:00-23:59).¦RESULTS: There was no difference between the groups regarding baseline patients and management's characteristics. At multivariable analysis, there was a statistically significant difference between peak CK levels among patients with symptom onset between 00:00 and 05:59 when compared with peak CK levels of patients with symptom onset in any other time group (mean increase 38.4%, P < .05). Thirty-day mortality for STEMI patients with symptom onset occurring between 00:00 and 05:59 was significantly higher than any other time group (P < .05).¦CONCLUSION: This study demonstrates an independent correlation between the infarct size of STEMI patients treated by PPCI and the time of the day at which symptoms occurred. These results suggest that time of the day should be a critical issue to look at when assessing prognosis of patients with myocardial infarction.

Prise en charge initiate du sepsis sévère et du choc septique [Management of severe sepsis and septic shock].

Severe sepsis and septic shock are systemic manifestations of the host response to infection. Mortality remains high despite advances in pathophysiological knowledge. Hemodynamic and respiratory management is largely supportive, while early antibiotics administration and source of infection's control are crucial for patient outcome. We review the principles guiding the initial management of these patients in emergency situation.

The fibrinogen- and fibronectin-binding domains of Staphylococcus aureus fibronectin-binding protein A synergistically promote endothelial invasion and experimental endocarditis.

Staphylococcus aureus experimental endocarditis relies on sequential fibrinogen binding (for valve colonization) and fibronectin binding (for endothelial invasion) conferred by peptidoglycan-attached adhesins. Fibronectin-binding protein A (FnBPA) reconciles these two properties--as well as elastin binding--and promotes experimental endocarditis by itself. Here we attempted to delineate the minimal subdomain of FnBPA responsible for fibrinogen and fibronectin binding, cell invasion, and in vivo endocarditis. A large library of truncated constructs of FnBPA was expressed in Lactococcus lactis and tested in vitro and in animals. A 127-amino-acid subdomain spanning the hinge of the FnBPA fibrinogen-binding and fibronectin-binding regions appeared necessary and sufficient to confer the sum of these properties. Competition with synthetic peptides could not delineate specific fibrinogen- and fibronectin-binding sites, suggesting that dual binding arose from protein folding, irrespective of clearly defined binding domains. Moreover, coexpressing the 127-amino-acid subdomain with remote domains of FnBPA further increased fibrinogen binding by &gt; or =10 times, confirming the importance of domain interactions for binding efficacy. In animals, fibrinogen binding (but not fibronectin binding) was significantly associated with endocarditis induction, whereas both fibrinogen binding and fibronectin binding were associated with disease severity. Moreover, fibrinogen binding also combined with fibronectin binding to synergize the invasion of cultured cell lines significantly, a feature correlating with endocarditis severity. Thus, while fibrinogen binding and fibronectin binding were believed to act sequentially in colonization and invasion, they appeared unexpectedly intertwined in terms of both functional anatomy and pathogenicity (in endocarditis). This unforeseen FnBPA subtlety might bear importance for the development of antiadhesin strategies.

Therapy of mild to moderate luminal Crohn's disease.

The management of luminal Crohn's disease, the most common form of initial presentation of the disease, depends on the location and the severity of the lesions. Mild to moderate disease represents a relatively large proportion of patients with a first flare of luminal disease, which may also be associated with perianal disease. As quality of life of these patients correlates with disease activity, adequate therapy is a central goal of the overall patient management. Treatment options include mainly sulfasalazine, budesonide and systemic steroids, while the role of mesalazine and antibiotics remains controversial. The role of biological therapies in mild to moderate disease has not been thoroughly evaluated and will not be discussed here.

The scarf osteotomy for the treatment of hallux valgus deformity: a review of 84 cases.

This study reviewed the subjective, clinical and radiological outcome of 71 patients (84 feet) treated by scarf osteotomy for hallux valgus deformity at our institution from 1995 to 1998 with an average follow-up time of 22 months (range, 17 to 48 months). At the time of follow-up, 39% of the patients were very satisfied, 50% were satisfied and 11% were not satisfied. The mean AOFAS score raised significantly from 43 points (14-68) preoperatively to 82 points (39 to 100) at follow-up (p &lt; 0.001). The radiological angles including M1-M2, M1-P1, M1-M5 and DMAA improved significantly (p &lt; 0.001). Among the 16 complications recorded, seven (8%) were minor and nine (11%) required an additional procedure. The scarf osteotomy of the first metatarsal coupled with a lateral soft-tissue release and, in three-quarters of our cases, with a basal closing wedge varisation osteotomy of the first phalanx, resulted in overall high satisfaction rate as well as significant clinical and radiological improvements in our series. Nevertheless, the range of motion of the first MP joint remained low: 30 degrees to 74 degrees in 52 patients (62%) and &lt;30 degrees in four patients (5%). Furthermore, the mobility of the first ray as well as the consequences of the procedure in the sagittal plane need to be assessed more accurately, and this may be achieved by incorporating measurement of the plantar pressures in the forefoot area into the global rating system.

Ruling out coronary artery disease in primary care: development and validation of a simple prediction rule.

BACKGROUND: Chest pain can be caused by various conditions, with life-threatening cardiac disease being of greatest concern. Prediction scores to rule out coronary artery disease have been developed for use in emergency settings. We developed and validated a simple prediction rule for use in primary care. METHODS: We conducted a cross-sectional diagnostic study in 74 primary care practices in Germany. Primary care physicians recruited all consecutive patients who presented with chest pain (n = 1249) and recorded symptoms and findings for each patient (derivation cohort). An independent expert panel reviewed follow-up data obtained at six weeks and six months on symptoms, investigations, hospital admissions and medications to determine the presence or absence of coronary artery disease. Adjusted odds ratios of relevant variables were used to develop a prediction rule. We calculated measures of diagnostic accuracy for different cut-off values for the prediction scores using data derived from another prospective primary care study (validation cohort). RESULTS: The prediction rule contained five determinants (age/sex, known vascular disease, patient assumes pain is of cardiac origin, pain is worse during exercise, and pain is not reproducible by palpation), with the score ranging from 0 to 5 points. The area under the curve (receiver operating characteristic curve) was 0.87 (95% confidence interval [CI] 0.83-0.91) for the derivation cohort and 0.90 (95% CI 0.87-0.93) for the validation cohort. The best overall discrimination was with a cut-off value of 3 (positive result 3-5 points; negative result <or= 2 points), which had a sensitivity of 87.1% (95% CI 79.9%-94.2%) and a specificity of 80.8% (77.6%-83.9%). INTERPRETATION: The prediction rule for coronary artery disease in primary care proved to be robust in the validation cohort. It can help to rule out coronary artery disease in patients presenting with chest pain in primary care.

Intratympanic application of an antiviral agent for the treatment of Ménière's disease.

It has been suggested that Ménière's disease is part of a polyganglionitis in which symptoms result from the reactivation of neurotropic virus within the internal auditory canal, and that intratympanic applications of an antiviral agent might be an efficient therapy. In 2002, we performed a pilot study ending with encouraging results. Control of vertigo was achieved in 80% of the 17 patients included. We present here a prospective, double-blind study, with a 2-year follow-up, in 29 patients referred by ENT practitioners for a surgical treatment after failure of a medical therapy. The participation in the study was offered to patients prior to surgery. A solution of ganciclovir 50 mg/ml or of NaCl 9% was delivered for 10 consecutive days via a microwick inserted into the tympanic membrane in the direction of the round window or through a ventilation tube. One patient was withdrawn from the study immediately after the end of the injections. He could not complete the follow-up period, because of persisting vertigo. As he had received the placebo, he was then treated with the solution of ganciclovir. Symptoms persisted and he underwent a vestibular neurectomy. Among the remaining 28 patients, surgery could be postponed in 22 (81%). Surgery remained necessary to control vertigo in 3 patients from the group that received the antiviral agent, and in 3 from the control group. Using an analogical scale, patients of both groups indicated a similar improvement of their health immediately after the intratympanic injections. The scores obtained with a 36-item short-form health survey quality of life questionnaire and the Dizziness Handicap Inventory were also similar for both groups. In conclusion, most patients were improved after the intratympanic injections, but there was no obvious difference between the treated and control groups. The benefit might be due to the middle ear ventilation or reflect an improvement in the patients' emotional state.