BACKGROUND AND PURPOSE To develop recommendations for the establishment of comprehensive stroke centers capable of delivering the full spectrum of care to seriously ill patients with stroke and cerebrovascular disease. Recommendations were developed by members of the Brain Attack Coalition (BAC), which is a multidisciplinary group of members from major professional organizations involved with the care of patients with stroke and cerebrovascular disease. SUMMARY OF REVIEW A comprehensive literature search was conducted from 1966 through December 2004 using Medline and Pub Med. Articles with information about clinical trials, meta-analyses, care guidelines, scientific guidelines, and other relevant clinical and research reports were examined and graded using established evidence-based medicine approaches for therapeutic and diagnostic modalities. Evidence was also obtained from a questionnaire survey sent to leaders in cerebrovascular disease. Members of BAC reviewed literature related to their field and graded the scientific evidence on the various diagnostic and treatment modalities for stroke. Input was obtained from the organizations represented by BAC. BAC met on several occasions to review each specific recommendation and reach a consensus about its importance in light of other medical, logistical, and financial factors. CONCLUSIONS There are a number of key areas supported by evidence-based medicine that are important for a comprehensive stroke center and its ability to deliver the wide variety of specialized care needed by patients with serious cerebrovascular disease. These areas include:(1) health care personnel with specific expertise in a number of disciplines, including neurosurgery and vascular neurology;(2) advanced neuroimaging capabilities such as MRI and various types of cerebral angiography;(3) surgical and endovascular techniques, including clipping and coiling of intracranial aneurysms, carotid endarterectomy, and intra-arterial thrombolytic therapy; and (4) other specific infrastructure and programmatic elements such as an intensive care unit and a stroke registry. Integration of these elements into a coordinated hospital-based program or system is likely to improve outcomes of patients with strokes and complex cerebrovascular disease who require the services of a comprehensive stroke center.

AIMS Determine whether certain, natural phenolic compounds enhance activity of commercial antifungal drugs against yeast strains of Candida and Cryptococcus neoformans. METHODS AND RESULTS Twelve natural phenolics were examined for fungicidal activity against nine reference strains of Candida and one of C. neoformans. Six compounds were selected for synergistic enhancement of antifungal drugs, amphotericin B (AMB), fluconazole (FLU) and itraconazole (ITR). Matrix assays of phenolic and drug combinations conducted against one reference strain, each, of Candida albicans and C. neoformans showed cinnamic and benzoic acids, thymol, and 2,3- and 2,5-dihydroxybenzaldehydes (-DBA) had synergistic interactions depending upon drug and yeast strain. 2,5-DBA was synergistic with almost all drug and strain combinations. Thymol was synergistic with all drugs against Ca. albicans and with AMB in C. neoformans. Combinations of benzoic acid or thymol with ITR showed highest synergistic activity. Of 36 combinations of natural product and drug tested, none were antagonistic. CONCLUSIONS Relatively nontoxic natural products can synergistically enhance antifungal drug activity, in vitro. SIGNIFICANCE AND IMPACT OF THE STUDY This is a proof-of-concept, having clinical implications. Natural chemosensitizing agents could lower dosages needed for effective chemotherapy of invasive mycoses. Further studies against clinical yeast strains and use of animal models are warranted.

HASH(0x2b758062e3a0)

Total parenteral nutrition (TPN) remains an important component of the management of short bowl syndrome in pediatric patients. However, prolonged TPN is known to be associated with cholestasis. Recently, the use of omega-3-fatty acid (Omegaven) has been proposed to improve TPN cholestasis. We present the early outcome after administration of Omegaven in four patients with ultra-short bowel syndrome. Based on our experience, it appears that omega-3 fatty acid can reverse and prevent the advent of TPN-related cholestasis, thereby significantly improving the process of intestinal adaptation. We suggest that clinicians consider this treatment option before proceeding to invasive surgery to reverse cholestasis. Prospective randomized trials are necessary to define a standard protocol and elucidate other potential benefits of this novel agent.

Small hepatocellular carcinomas (HCCs) can be effectively cured by surgery with good clinical outcomes. However, conventional AFP marker is ineffective to detect small tumors. Here we employed proteomic profiling approach to identify candidate marker for HCC (</= 2 cm) in tumor tissues and then evaluate its clinical feasibility in patients' sera. The study was divided into 2 phases -(i) biomarker discovery: we collected 76 frozen liver tissues (40 HCC and 36 controls) for proteomics profiling. Candidate protein markers were identified by MALDI-TOF/TOF and confirmed by immunoblot and qPCR.(ii) Clinical evaluation: Selected biomarker was tested by ELISA for sensitivity and specificity using serum samples from a separate cohort of 152 subjects (88 HCC and 64 controls). Vimentin was found significantly over-expressed in HCC, in particular the small-size subgroup (</= 2cm) with p < 0.01. When tested in the serum samples, vimentin level was significantly higher in small tumors than the non-neoplastic controls (AUC=0.69 and p <0.01). Further analysis suggested that elevated circulating vimentin level could detect small HCC at 40.91% sensitivity and 87.50% specificity. Moreover, vimentin was found to be superior to serum AFP assayed at different cut-offs in detecting small tumors. When combined with AFP, the detection sensitivity and specificity could be further enhanced to 58.77% and 98.15%, respectively. In conclusion, serum vimentin is a potential surrogate marker, either alone or in combination with AFP, for detection of small HCCs.

Glaucoma is a leading cause of permanent blindness. ARGALI, an automated system for glaucoma detection, employs several methods for segmenting the optic cup and disc from retinal images, combined using a fusion network, to determine the cup to disc ratio (CDR), an important clinical indicator of glaucoma. This paper discusses the use of SVM as an alternative fusion strategy in ARGALI, and evaluates its performance against the component methods and neural network (NN) fusion in the CDR calculation. The results show SVM and NN provide similar improvements over the component methods, but with SVM having a greater consistency over the NN, suggesting potential for SVM as a viable option in ARGALI.

BACKGROUND Inguinal hernias are commonly seen in the paediatric population. Controversies still exist regarding the need for contralateral groin exploration when an unilateral inguinal hernia is presented, since the true incidence of contralateral patent processus vaginalis is not known. With the advent of laparoscopic hernioplasty, the status of the contralateral side can be evaluated at the same setting. Here, we describe our experience in this issue after the introduction of laparoscopic hernioplasty in our unit. METHODS A retrospective review was carried out between October 2002 and January 2008. All patients presented with unilateral inguinal hernias were included. The demographics of the patients and the operative findings at laparoscopy were recorded. Statistics were performed using Student t-test or chi(2) test as appropriate and p < 0.05 was taken as statistically significant. RESULTS During the study period, 363 children were included in our study, of which there were 292 males and 71 females. 212 patients presented with right-sided hernias and 151 were left-sided. The mean age of patients at presentation was 48.8 months. The incidence of contralateral PPV overall was 39.7%. There was no decrease in incidence of having a contralateral inguinal hernia in relation to age. CONCLUSION Laparoscopy can accurately diagnose contralateral PPV in children who undergo unilateral inguinal hernia repair and thus holds an advantage over open herniotomy. Furthermore, there should not be an age criteria for contralateral exploration for surgeons who perform open herniotomy.

OBJECTIVE To investigate the demographics and clinical outcomes of intimate partner violence victims presenting to an emergency department. DESIGN Retrospective, observational study. SETTING Emergency department of a regional hospital in Hong Kong. PATIENTS Adults presented with intimate partner violence during years 1999 to 2004. RESULTS We assessed 1695 victims of intimate partner violence with a mean age of 39 (range, 18-84) years, of whom 87% were female. Most of the patients were in the age-group of 31 to 40 years and the overall male-to-female ratio was 1:7. In Tin Shui Wai and Yuen Long districts, such cases appeared to be on the increase. Nearly two thirds (65%) of all the victims presented to the emergency department outside the office hours of medical social workers. Approximately 10% had been abused once before, and 40% more than twice. The head (39%), face (30%), upper limbs (37%), and lower limbs (17%) were commonly the injured parts. The majority (73%) had mild injuries; severe injuries being relatively less common. The latter included lacerations or cuts (6.6%), nasal bone fractures (0.3%), limb fractures (0.8%), and ruptured tympanic membranes (0.9%). In-patient management was undertaken for 8% of the victims, due to physical injury in 68% of these individuals and psychological trauma in the remaining 32%. The hospital admission rate dropped from 12% in 2001 to 4% in 2004. CONCLUSIONS Variations in demographic data had a significant impact on future service planning and management of intimate partner violence. Accident and Emergency Department and Emergency Medicine Ward services together with extended social worker support could provide timely, multidisciplinary care to meet the various needs of victims and subsequently reduce hospital admissions.

The purpose was to examine in free-living individuals from a high-density city (1) the objectively determined physical activity levels across quartiles derived from pedometer step counts,(2) the pedometer steps day(-1) required to meet health-enhancing guidelines of accruing 30 min day(-1) of moderate physical activity and (3) the agreement between three objective criteria for the pedometer guidelines. Over 7 days 49 Hong Kong Chinese aged 15-55 years (n = 30 males) wore a polar heart rate monitor (HRM), an MTI and Tritrac accelerometer, plus a Yamax pedometer for >or=600 min day(-1). Participants averaged 9,839 +/- 3,088 steps day(-1), whilst accumulating 44.5 +/- 22.6, 43.1 +/- 21.7, and 24.7 +/- 19.3 min day(-1) of moderate physical activity by the Tritrac, MTI and HRM, respectively. Significant differences between quartiles of pedometer-determined activity were predominantly seen in the accelerometry data, especially during moderate and moderate-to-vigorous intensity activity (effect sizes >1.5 between upper and lower quartiles), but not seen in the HRM data. Using both criterion accelerometer datasets, a threshold of 8,000 steps day(-1) accurately categorized approximately 90% of those achieving, and approximately 80% of those not achieving, 30 min day(-1) of appropriate activity. They also produced a screening sensitivity of approximately 95% and a specificity of approximately 70%, which were considerably higher than those from the HRM data. Overall, the agreement between the three criterion measures suggests 8,000 steps day(-1) might be a valid screening tool as a proxy for classifying those meeting public health physical activity recommendations of 30 min day(-1) of moderate activity.

BACKGROUND AND PURPOSE Not only clinical factors, including the CHADS(2) score, but also echocardiographic findings have been reported to be useful for predicting the risk of ischemic stroke in patients with nonvalvular atrial fibrillation (NVAF). However, it remains to be determined which of these factors might be more relevant for evaluation of the risk of stroke in each patient. METHODS In 490 patients with NVAF who underwent transesophageal echocardiography (TEE), we examined the long-term incidence of ischemic stroke events (mean follow-up time, 5.7±3.3 years). For each patient, the predictive values of gender, the CHADS(2) risk factors (congestive heart failure, hypertension, age ≥75 years, diabetes mellitus, history of cerebral ischemia), the CHADS(2) score, and the findings on echocardiography, including TEE risk markers, were assessed. RESULTS The ischemic stroke rate was significantly correlated with the CHADS(2) score (p<0.05). According to the results of univariate analyses, age ≥75 years, history of cerebral ischemia, CHADS(2) score ≥2, and presence of TEE risk were significantly correlated with the incidence of ischemic stroke. Cox proportional hazards regression analyses identified age ≥75 years and presence of TEE risk as significant predictors of subsequent ischemic stroke events in patients with NVAF. As compared with that in persons below 75 years of age without TEE risk, the ischemic stroke rate was significantly higher in persons who were ≥75 years of age with TEE risk (4.3 vs. 0.56%/year, adjusted hazard ratio=8.94, p<0.001). CONCLUSIONS TEE findings might be more relevant predictors of ischemic stroke than the CHADS(2) score in patients with NVAF. The stroke risk was more than 8-fold higher in patients aged ≥75 years with TEE risk.

BACKGROUND: There is no clear consensus about antithrombotic treatment in atrial fibrillation (AF) patients at low-intermediate thromboembolic risk. Transesophageal echocardiography (TEE) is useful for prediction of thromboembolic events in AF. METHODS AND RESULTS: Of 498 patients with nonvalvular AF, incidence of stroke, cardiac events, and mortality was investigated in 280 patients with CHADS(2) score 0 or 1 (mean age 64 years, mean follow-up 6.4±3.1 years). Left atrial abnormality (low left atrial appendage flow, spontaneous echo contrast, or thrombi), complex aortic plaque (mobile, ulcerated, pedunculate, or thickness≥4mm), or both were defined as TEE risk. The incidences of ischemic stroke, cardiovascular events, and death were higher in patients with TEE risk than in those without the risk (2.0%/year vs. 0.5%/year, p<0.05; 4.7%/year vs. 1.9%/year, p<0.01; and 4.7%/year vs. 2.0%/year, p<0.01, respectively). This was also true for patients with CHADS(2) score of 0 (1.7%/year vs. 0.3%/year, p<0.05; 4.1%/year vs. 1.6%/year, p<0.05; and 3.9%/year vs. 1.4%/year, p<0.01; respectively). On multivariate analysis, TEE risk predicted ischemic stroke, cardiovascular events, and mortality independently of clinical variables or CHADS(2) score. CONCLUSIONS: TEE could be useful for further stratification of patients with nonvalvular AF stratified at low-intermediate risk (CHADS(2) score 0 or 1) and could indicate who should receive anticoagulation treatment.

AIM Atrial septal aneurysm (ASA) is a risk factor for arterial embolism. Despite prior reports concerning paradoxical embolism through a patent foramen ovale, atrial dysfunction and atrial arrhythmias might represent an additional mechanism for arterial embolism.The aim of this study was to evaluate right and left atrial appendage contractilty in patients with ASA. METHODS AND RESULTS A total of 30 patients with ASA (10 males/20 females, mean age 50.2 +/- 15.3 years) and 30 controls (12 males/ 18 females, mean age 47.7 +/- 10 years) were included. Conventional transthoracic and multiplane transoesophageal echocardiography were performed in patient and control groups. Flow and myocardial velocity were measured in both atrial appendages. Baseline characteristics of both groups were comparable. Flow velocity and myocardial contraction velocity in both atrial appendages were significantly lower in ASA patients. Compared to the control group, patients with ASA had a larger length, base and area of both appendages. CONCLUSION In ASA patients right and left atrial appendage function are impaired. Biatrial dysfunction may cause arrhythmia and thromboembolism.

BACKGROUND/AIM Obliterating the left atrial appendage from systemic circulation in patients with atrial fibrillation has been proposed to reduce thromboembolic events. The goal of this study was to assess the effectiveness of a circular method of epicardial surgical ligation in obliterating the left atrial appendage and maintaining sustained exclusion. METHODS Patients with permanent atrial fibrillation and an indication for elective cardiac surgery were enrolled. All patients underwent preoperative cardiac gated computerized tomography (CT) and transesophageal echocardiography (TEE). During the cardiac procedure circular ligation of the appendage was performed. RESULTS Twelve patients, mean (SD) age 65 (12) years completed the study. Intraoperative TEE demonstrated all patients (12/12) had complete postligation occlusion of the left atrial appendage. At three-month follow-up, cardiac gated CT demonstrated that 75%(9/12) of the patients had communication of contrast dye from the left atrial appendage to body of left atrium. Left atrial appendage orifice area and volume were reduced from mean (SD)(5.5 cm(2)[1.8] to 0.5 cm(2)[0.4] p = 0.002) and (14.0 cm(3)[8.3] to 2.7 cm(3)[1.3] p =.005) postligation, respectively. No clinically significant thromboembolic events were reported. CONCLUSIONS Epicardial suture ligation of the left atrial appendage resulted in successful intra-operative exclusion on TEE; however, a significant portion of patient's demonstrated communication of contrast on CT. This is suggestive of incomplete long-term exclusion. The clinical significance of reduction in left atrial appendage orifice area and volume with a persistent communication requires further study.

BACKGROUND: Evidence of a link between small rises in cardiac troponin I (cTnI) and an increased risk of thromboembolic events (TE) in atrial fibrillation (AF) is currently scarce. OBJECTIVES: We aimed to assess the relation between cTnI and findings of an increased thromboembolic risk in patients with non-valvular AF using transesophageal echocardiography. METHODS: We have included 245 patients performing transthoracic and transesophageal echocardiogram, alongside with laboratory assessment (including cTnI) in a cross-sectional survey. Changes associated to TE were sought on transesophageal echocardiogram: left atrial or left atrial appendage thrombus, dense spontaneous echocardiographic contrast, low flow velocities in the left atrial appendage and protuberant aortic plaques. Comparisons were performed according to the baseline concentration of cTnI, regarding the prevalence of these changes. We have added cTnI to CHADS(2) and CHA(2)DS(2)-VASc scores in order to assess its capability to refine risk stratification using transesophageal markers as surrogate endpoints and assessed it by means of ROC-curve analysis and Net Reclassification Improvement (NRI). RESULTS: A direct relation between rising concentrations of cTnI and a higher prevalence of transesophageal echocardiogram changes was found. Furthermore, the addition of cTnI to CHADS(2) and CHA(2)DS(2)-VASc scores improved their ability to predict changes associated to TE on transesophageal echocardiography both through ROC-curve analysis and NRI. CONCLUSION: cTnI seems to be associated to thromboembolic risk in patients with AF. The possible role of cTnI in the refinement of risk stratification schemes needs to be tested in further prospective studies using clinical endpoints.

OBJECTIVE The goals of this study were to determine: 1) if the CHADS(2) score correlates with left atrial (LA) or left atrial appendage (LAA) thrombus on pre-cardioversion transesophageal echocardiography (TEE) in nonvalvular atrial fibrillation (NVAF); and 2) what, if any, components of the CHADS(2) score are most important in predicting LA/LAA thrombus. BACKGROUND It is unknown if CHADS(2) score, a marker of thromboembolic risk in NVAF, accurately predicts LA/LAA thrombus on pre-cardioversion TEE. METHODS We retrospectively studied patients undergoing precardioversion TEE for NVAF at a tertiary hospital. TEE reports were reviewed for presence of LA/LAA thrombus. Using medical records and an ICD-9 coding database, a CHADS(2) score was derived, and the association between CHADS(2) and thrombus was evaluated with Mantel-Haenszel Chi-Square. The relation between the singular components of CHADS(2) and thrombus were analyzed using Pearson's Chi-Square. RESULTS In 643 consecutive patients undergoing pre-cardioversion TEE, LA/LAA thrombus was identified in 46 (7.2 %). A strong association was present between CHADS(2)score and LA/LAA thrombus (p = 0.0005). No thrombi were identified in patients with CHADS(2)= 0. Among 46 patients with thrombus, all (100%) had CHF. Of the singular components, CHF was the only factor independently associated with thrombus (p < 0.0001). CONCLUSIONS In non-valvular atrial fibrillation, CHADS(2) is strongly associated with LA thrombus on TEE. Our findings suggest pre-cardioversion TEE may be unnecessary if the CHADS(2) score = 0. Of the components of the CHADS(2) score, CHF was the only independently associated risk factor which correlated with LA/LAA thrombus.

Atrial fibrillation (AF) is a common arrhythmia associated with substantial morbidity and mortality, particularly due to thromboembolic strokes, the prevalence of which is expected to rise over the next few decades. This article reviews the complex mechanisms behind thromboembolism, compares the newer risk stratification models for identifying those at risk for stroke or bleeding, and highlights the potential advantages and disadvantages of available therapies. Newer oral anticoagulants like Dabigatran, Rivoroxaban, and Apixiban are discussed. There is also discussion on non pharmacological therapies such as left atrial appendage ligation and occlusion devices. This article is intended to help clinicians gain a better understanding of available risk stratification tools and therapies available for prevention of stroke in patients with atrial fibrillation.

Hypertension is the most common cardiovascular disorder and atrial fibrillation is the most common clinically significant arrhythmia. Both these conditions frequently coexist and their prevalence increases rapidly with aging. There are different risk factors and clinical conditions predisposing to the development of atrial fibrillation, but due its high prevalence, hypertension is still the main risk factor for the development of atrial fibrillation. Several pathophysiologic mechanisms (such as structural changes, neurohormonal activation, fibrosis, atherosclerosis, etc.) have been advocated to explain the onset of atrial fibrillation. The presence of atrial fibrillation per se increases the risk of stroke but its coexistence with high blood pressure leads to an abrupt increase of cardiovascular complications. Different risk models are available for the risk stratification and the prevention of thromboembolism in patients with atrial fibrillation. In all of them hypertension is present and is an important risk factor. Antihypertensive treatment may contribute to reduce this risk, and it seems some classes are superior to others in the prevention of new-onset atrial fibrillation and prevention of stroke. Antithrombotic treatment with warfarin is effective in the prevention of thromboembolic events, although quite recently, new classes of anticoagulants that do not require international normalized ratio monitoring have been introduced with promising results.

UNLABELLED Hyperthyroidism is a questionable risk factor for thromboembolism among patients with atrial fibrillation. OBJECTIVE   To correlate clinical risk factors for thromboembolism from a group of patients with atrial fibrillation related to hyperthyroidism with transoesophageal echocardiography (TOE) markers of a thrombogenic milieu. DESIGN   Clinical risk factors for thromboembolism, thyroid hormonal status, time since diagnosis of hyperthyroidism and TOE markers of a thrombogenic milieu were assessed in consecutive patients with atrial fibrillation related to hyperthyroidism. The following TOE parameters were assessed to define the presence of thrombogenic milieu: dense spontaneous echo contrast, thrombi or left atrial appendage blood flow velocities <0·20 m/s. Clinical risk factors for thromboembolism were based on CHADS(2)(Cardiac failure, Hypertension, Age, Diabetes and Stroke) classification. PATIENTS   This study included 31 consecutive patients aged between 18 and 65 years with atrial fibrillation related to hyperthyroidism scheduled for TOE. RESULTS   Thrombogenic milieu was present in 14 of 31 (45·2%) patients. The thyroid status could not predict the presence of a thrombogenic milieu. Despite low CHADS(2) score of 0/1, 6 of 13 (46·1%) patients had a thrombogenic milieu, whereas 10 of 18 (55·6%) patients with score ≥2 had none. The probability of having a thrombogenic milieu did not correlate with the number of clinical risk factors. CONCLUSION   Among patients younger than 65 years of age with atrial fibrillation related to hyperthyroidism, there is no association between clinical risk factors with TOE markers of a thrombogenic milieu. TOE adds useful information that may affect antithrombotic therapy guided by clinical risk classification.

BACKGROUND: To determine whether C-reactive protein (CRP) in combination with a stroke risk stratification scheme can help in identifying transesophageal echocardiographic (TEE) markers of thromboembolism such as left atrial (LA)/left atrial appendage (LAA) thrombus, severe LA/LAA spontaneous echocardiographic contrast (SEC), and aortic plaque≥4mm. METHODS: Transthoracic echocardiography, TEE, and CRP measurement were performed at admission in 178 patients with non-valvular atrial fibrillation not receiving oral anticoagulant therapy. Patients were classified as at low, moderate, or high risk of thromboembolism based on seven clinical risk stratification schemes (SPAF, CHADS(2), Framingham, Birmingham/NICE, ACC/AHA/ESC 2006 guidelines, ACCP 2008, CHA(2)DS(2)VASc). RESULTS: Severe LA/LAA SEC, LA/LAA thrombus, and aortic plaque≥4mm were present in 6.2%, 6.7%, and 10.1% of patients, respectively. The combination of CRP with a cut-off value of 3.4mg/L with the Birmingham/Nice or ACC/AHA/ESC 2006 risk score, led to a negative predictive value of 100% in low-risk patients and 91% in moderate-risk patients. For the detection of severe LA/LAA SEC or thrombus, a good discrimination (area under curve≥0.70) using only clinical risk markers was observed for all classifications except for the Framingham and CHADS(2) risk scores. The addition of CRP did not improve the detection of LA/LAA SEC or thrombus, or of severe LA/LAA SEC, thrombus, or aortic plaque. CONCLUSION: The combination of clinical risk markers and CRP can help to exclude the presence of the TEE markers LA/LAA SEC or LA/LAA thrombus, particularly in patients classified at low or moderate risk of stroke.