Dalbavancin reduces biofilms of methicillin-resistant Staphylococcus aureus (MRSA) and methicillin-resistant Staphylococcus epidermidis (MRSE).

Activity of dalbavancin against methicillin-resistant Staphylococcus aureus (MRSA) and methicillin-resistant Staphylococcus epidermidis (MRSE) in biofilm was investigated and the microbicidal biofilm concentrations (MBC) were determined. Biofilms obtained from ten MRSA and ten MRSE bloodstream isolates, collected from patients in the General Hospital of Vienna between 2012 and 2015, were incubated with dalbavancin in trypticase soy broth (TSB) in serial dilution from 0.0625 mg/l to 256 mg/l using a microtiter plate biofilm model. The plates were incubated for 24 h at 37 ° C and 50% humidity. Biofilms were fixed with 2.5% glutaraldehyde and stained with crystal violet. Subsequently the optical density (OD620) was used to measure the MBC, defined as the concentration of dalbavancin leading to a 50% reduction of biofilm. MBC for MRSA was 1 mg/l-4 mg/l (minimal inhibitory concentrations (MIC) 0.0312 mg/l-0.064 mg/l). MBC for MRSE was 2 mg/l-16 mg/l (MIC 0.023 mg/l-0.0625 mg/l). Dalbavancin successfully reduced MRSA and MRSE in biofilms, and therefore provides a promising option for the treatment of biofilm-associated infections.

A refined risk stratification scheme for clinical stage 1 NSGCT based on evaluation of both embryonal predominance and lymphovascular invasion.

BACKGROUND: Active surveillance is an increasingly accepted approach for managing patients with germ-cell tumors (GCTs) after an orchiectomy. Here we investigate a time-to-relapse stratification scheme for clinical stage 1 (CS1) nonseminoma GCT (NSGCT) patients according to factors associated with relapse and identify a group of patients with a lower frequency and longer time-to-relapse who may require an alternative surveillance strategy. PATIENTS AND METHODS: We analyzed 266 CS1 GCT patients from the IRB-approved DFCI GCT database that exclusively underwent surveillance following orchiectomy from 1997 to 2013. We stratified NSGCT patients according to predominance of embryonal carcinoma (EmbP) and lymphovascular invasion (LVI), using a 0, 1, and 2 scoring system. Cox regression and conditional risk analysis were used to compare each NSGCT group to patients in the seminomatous germ-cell tumor (SGCT) category. Median time-to-relapse values were then calculated among those patients who underwent relapse. Relapse-free survival curves were generated using the Kaplan-Meier method. RESULTS: Fifty (37%) NSGCT and 20 (15%) SGCT patients relapsed. The median time-to-relapse was 11.5 versus 6.3 months for the SGCT and NSGCT groups, respectively. For NSGCT patients, relapse rates were higher and median time-to-relapse faster with increasing number of risk factors (RFs). Relapse rates (%) and median time-to-relapse (months) were 25%/8.5 months, 41%/6.8 months and 78%/3.8 months for RF0, RF1 and RF2, respectively. We found a statistically significant difference between SGCT and patients with one or two RFs (P < 0.001) but not between SGCT and NSGCT RF0 (P = 0.108). CONCLUSION: NSGCT patients grouped by a risk score system based on EmbP and LVI yielded three groups with distinct relapse patterns -and patients with neither EmbP nor LVI appear to behave similar to SGCT.

Higher plasma vitamin D is associated with reduced risk of Clostridium difficile infection in patients with inflammatory bowel diseases.

BACKGROUND: Patients with inflammatory bowel diseases (IBD) have an increased risk of clostridium difficile infection (CDI). Cathelicidins are anti-microbial peptides that attenuate colitis and inhibit the effect of clostridial toxins. Plasma calcifediol [25(OH)D] stimulates production of cathelicidins. AIM: To examine the association between plasma 25(OH)D and CDI in patients with IBD. METHODS: From a multi-institutional IBD cohort, we identified patients with at least one measured plasma 25(OH)D. Our primary outcome was development of CDI. Multivariate logistic regression models adjusting for potential confounders were used to identify independent effect of plasma 25(OH)D on risk of CDI. RESULTS: We studied 3188 IBD patients of whom 35 patients developed CDI. Patients with CDI-IBD were older and had greater co-morbidity. The mean plasma 25(OH)D level was significantly lower in patients who developed CDI (20.4 ng/mL) compared to non-CDI-IBD patients (27.1 ng/mL) (P = 0.002). On multivariate analysis, each 1 ng/mL increase in plasma 25(OH)D was associated with a 4% reduction in risk of CDI (OR 0.96, 95% CI 0.93-0.99, P = 0.046). Compared to individuals with vitamin D >20 ng/mL, patients with levels <20 ng/mL were more likely to develop CDI (OR 2.27, 95% CI 1.16-4.44). The mean plasma 25(OH)D in patients with CDI who subsequently died was significantly lower (12.8 ± 8.1 ng/mL) compared to those who were alive at the end of follow-up (24.3 ± 13.2 ng/mL) (P = 0.01). CONCLUSIONS: Higher plasma calcifediol [25(OH)D] is associated with reduced risk of C. difficile infection in patients with IBD. Further studies of therapeutic supplementation of vitamin D in patients with inflammatory bowel disease and C. difficile infection may be warranted.

The effectiveness of kinesio taping for athletes with medial elbow epicondylar tendinopathy.

Kinesio taping has also been used for athletes with Medial Elbow Epicondylar Tendinopathy (MET) as an additional treatment method. The purpose of this study was to determine the clinical effectiveness of Kinesio tape on maximal grip strength and absolute and related force sense in athletes with MET when applied to the medial forearm. 27 male athletes who voluntarily participated in this study were divided into a healthy group (n=17) and a MET group (n=10). All subjects were assessed for the maximal grip strength and grip force sense (absolute and related force sense) under 3 taping conditions: 1) without taping; 2) with placebo Kinesio taping; and 3) with Kinesio taping. No significant interaction was found between groups and taping condition in maximal grip force and related force sense error, except for absolute force sense error (p=0.04). Both groups with absolute force sense measurements had significantly decreased errors in the placebo Kinesio taping and Kinesio taping conditions. Both taping may enhance discrimination of magnitude of grip force control (absolute force sense) in both groups when applied to the forearm. However, Kinesio taping did not change maximal grip strength in either group. The effects of Kinesio taping on other muscle functions remain to be studied.

Psychiatric co-morbidity is associated with increased risk of surgery in Crohn's disease.

BACKGROUND: Psychiatric co-morbidity, in particular major depression and anxiety, is common in patients with Crohn's disease (CD) and ulcerative colitis (UC). Prior studies examining this may be confounded by the co-existence of functional bowel symptoms. Limited data exist examining an association between depression or anxiety and disease-specific endpoints such as bowel surgery. AIMS: To examine the frequency of depression and anxiety (prior to surgery or hospitalisation) in a large multi-institution electronic medical record (EMR)-based cohort of CD and UC patients; to define the independent effect of psychiatric co-morbidity on risk of subsequent surgery or hospitalisation in CD and UC, and to identify the effects of depression and anxiety on healthcare utilisation in our cohort. METHODS: Using a multi-institution cohort of patients with CD and UC, we identified those who also had co-existing psychiatric co-morbidity (major depressive disorder or generalised anxiety). After excluding those diagnosed with such co-morbidity for the first time following surgery, we used multivariate logistic regression to examine the independent effect of psychiatric co-morbidity on IBD-related surgery and hospitalisation. To account for confounding by disease severity, we adjusted for a propensity score estimating likelihood of psychiatric co-morbidity influenced by severity of disease in our models. RESULTS: A total of 5405 CD and 5429 UC patients were included in this study; one-fifth had either major depressive disorder or generalised anxiety. In multivariate analysis, adjusting for potential confounders and the propensity score, presence of mood or anxiety co-morbidity was associated with a 28% increase in risk of surgery in CD (OR: 1.28, 95% CI: 1.03-1.57), but not UC (OR: 1.01, 95% CI: 0.80-1.28). Psychiatric co-morbidity was associated with increased healthcare utilisation. CONCLUSIONS: Depressive disorder or generalised anxiety is associated with a modestly increased risk of surgery in patients with Crohn's disease. Interventions addressing this may improve patient outcomes.

Hyaluronic acid instillation following arthroscopic anterior cruciate ligament reconstruction: a double-blinded, randomised controlled study.

PURPOSE: To assess the effect of hyaluronic acid instillation after arthroscopic anterior cruciate ligament (ACL) reconstruction for improving pain, range of movement, and function of the knee. METHODS: 28 men and 4 women underwent arthroscopic ACL reconstruction for isolated ACL rupture (partial or complete) and instability after recreational sports injury 2 to 120 months earlier. They were randomised to undergo arthroscopic ACL reconstruction followed by intra-articular viscoseal instillation (13 men and 3 women) or arthroscopic ACL reconstruction alone (15 men and 1 woman). The knee injury osteoarthritis outcome score (for pain, symptoms, activities of daily living, sport and recreation function, and quality of life), range of movement, knee circumference, and analgesic use were assessed on days -1, 1, and 2, and weeks 2, 6 and 12. RESULTS: Patient demographics were similar at baseline. At postoperative days 1 and 2, all subscales of the knee injury osteoarthritis outcome score (except for quality of life) were significantly higher in the viscoseal group. At weeks 2, 6, and 12, improvement in both groups equalised. Knee swelling (change in knee circumference) was significantly less in the viscoseal group at days 1 and 2 (p=0.009 and p=0.038, respectively, Mann-Whitney U test). Only one patient in the viscoseal group had a limited range of movement. No patient developed any adverse reaction. CONCLUSION: Intra-articular viscoseal instillation improved pain control and swelling 2 days after arthroscopic ACL reconstruction.

Human immunogenic T cell epitopes in nucleoprotein of human influenza A (H5N1) virus.

1. Two novel HLA-A2.1 specific H5N1 nucleoprotein epitopes(NP373-381 AMDSNTLEL and NP458-466 FQGRGVFEL) capable of activating cytotoxic T-cells in vitro were identified. 2. When the H5N1 nucleoprotein epitopes (NP373-381AMDSNTLEL and NP458-466FQGRGVFEL) were used with the single chain trimer system, they elicited effective cytotoxic T-cell responses against the corresponding nucleoprotein peptide-loaded cells in an HHD transgenic mouse model.

Assessment of post-radiotherapy salivary glands.

Salivary glands are usually irradiated during radiotherapy for head and neck cancers, which can lead to radiation-induced damage. Radiation-induced xerostomia (oral dryness) is the most common post-radiotherapy complication for head and neck cancer patients and can reduce the patient's quality of life. Accurate and efficient salivary gland assessment methods provide a better understanding of the cause and degree of xerostomia, and may help in patient management. At present, there are different methods for the assessment of salivary gland hypofunction; however, none of them are considered to be standard procedure. This article reviews the value of common methods in the assessment of post-radiotherapy salivary glands.

Delay correction for the assessment of blood-brain barrier permeability using first-pass dynamic perfusion CT.

SUMMARY: Hemorrhagic transformation is a serious potential complication of ischemic stroke with damage to the BBB as one of the contributing mechanisms. BBB permeability measurements extracted from PCT by using the Patlak model can provide a valuable assessment of the extent of BBB damage. Unfortunately, Patlak assumptions require extended PCT acquisition, increasing the risk of motion artifacts. A necessary correction is presented for obtaining accurate BBB permeability measurements from first-pass PCT.

Blood-brain barrier permeability assessed by perfusion CT predicts symptomatic hemorrhagic transformation and malignant edema in acute ischemic stroke.

BACKGROUND AND PURPOSE: SHT and ME are feared complications in patients with acute ischemic stroke. They occur >10 times more frequently in tPA-treated versus placebo-treated patients. Our goal was to evaluate the sensitivity and specificity of admission BBBP measurements derived from PCT in predicting the development of SHT and ME in patients with acute ischemic stroke. MATERIALS AND METHODS: We retrospectively analyzed a dataset consisting of 32 consecutive patients with acute ischemic stroke with appropriate admission and follow-up imaging. We calculated admission BBBP by using delayed-acquisition PCT data and the Patlak model. Collateral flow was assessed on the admission CTA, while recanalization and reperfusion were assessed on the follow-up CTA and PCT, respectively. SHT and ME were defined according to ECASS III criteria. Clinical data were obtained from chart review. In our univariate and forward selection-based multivariate analysis for predictors of SHT and ME, we incorporated both clinical and imaging variables, including age, admission NIHSS score, admission blood glucose level, admission blood pressure, time from symptom onset to scanning, treatment type, admission PCT-defined infarct volume, admission BBBP, collateral flow, recanalization, and reperfusion. Optimal sensitivity and specificity for SHT and ME prediction were calculated by using ROC analysis. RESULTS: In our sample of 32 patients, 3 developed SHT and 3 developed ME. Of the 3 patients with SHT, 2 received IV tPA, while 1 received IA tPA and treatment with the Merci device; of the 3 patients with ME, 2 received IV tPA, while 1 received IA tPA and treatment with the Merci device. Admission BBBP measurements above the threshold were 100% sensitive and 79% specific in predicting SHT and ME. Furthermore, all patients with SHT and ME--and only those with SHT and ME--had admission BBBP measurements above the threshold, were older than 65 years of age, and received tPA. Admission BBBP, age, and tPA were the independent predictors of SHT and ME in our forward selection-based multivariate analysis. Of these 3 variables, only BBBP measurements and age were known before making the decision of administering tPA and thus are clinically meaningful. CONCLUSIONS: Admission BBBP, a pretreatment measurement, was 100% sensitive and 79% specific in predicting SHT and ME.

Dynamic perfusion-CT assessment of early changes in blood brain barrier permeability of acute ischaemic stroke patients.

BACKGROUND AND PURPOSE: Damage to the blood brain barrier (BBB) may lead to haemorrhagic transformation after ischaemic stroke. The purpose of this study was to evaluate the effect of patient characteristics and stroke severity on admission BBB permeability (BBBP) values measured with perfusion-CT (PCT) in acute ischaemic stroke patients. METHODS: We retrospectively identified 65 patients with proven ischaemic stroke admitted within 12 hours after symptom onset. Patients' charts were reviewed for demographic variables and vascular risk factors. The Patlak's model was applied to calculate BBBP values from the PCT data in the infarct core, penumbra and non-ischaemic tissue in the contralateral hemisphere. Mean BBBP values and their 95% confidence intervals (CI) were calculated in the different tissue types. Effects of demographic variables and risk factors on BBBP were analyzed using a multivariate, generalized estimating equations (GEE) model. RESULTS: BBBP values in the infarct core (mean [95%CI]: 2.48 [2.16-2.85]) and penumbra (2.48 [2.21-2.79]) were significantly higher than in non-ischaemic tissue (2.12 [1.88-2.39]). Multivariate analysis demonstrated that collateral filling has effect on BBBP. Less elevated BBBP values were associated with more than 50% collateral filling. CONCLUSIONS: BBBP values are increased in ischaemic brain tissue on the admission PCT scan of acute ischaemic stroke patients. Less abnormally elevated BBBP values were observed in patients with more than 50% collateral filling, possibly explaining why there is a relationship between more collateral filling and a lower incidence of haemorrhagic transformation.

The triple rule-out for acute ischemic stroke: imaging the brain, carotid arteries, aorta, and heart.

BACKGROUND AND PURPOSE: Ischemic stroke is commonly embolic, either from carotid atherosclerosis or from cardiac origin. These potential sources of emboli need to be investigated to accurately prescribe secondary stroke prevention. Moreover, the mortality in ischemic stroke patients due to ischemic heart disease is greater than that of age-matched controls, thus making evaluation for coronary artery disease important in this patient population. The purpose of this study was to evaluate the image quality of a comprehensive CTA protocol in patients with acute stroke that expands the standard CTA coverage to include all 4 chambers of the heart and the coronary arteries. MATERIALS AND METHODS: One hundred twenty patients consecutively admitted to the emergency department with suspected cerebrovascular ischemia undergoing standard-of-care CTA were prospectively enrolled in our study. We used an original tailored acquisition protocol using a 64-section CT scanner, consisting of a dual-phase intravenous injection of iodinated contrast and saline flush, in conjunction with a dual-phase CT acquisition, ascending from the top of the aortic arch to the vertex of the head, then descending from the top of the aortic arch to the diaphragm. No beta blockers were administered. The image quality, attenuation, and CNRs of the carotid, aortic, vertebral, and coronary arteries were assessed. RESULTS: Carotid, aorta, and vertebral artery image quality was 100% diagnostic (rated good or excellent) in all patients. Coronary artery image quality was diagnostic in 58% of RCA segments, 73% of LAD segments, and 63% of LCX segments. When we considered proximal segments only, the diagnostic quality rose to 71% in the RCA, 83% in the LAD, and 74% in the LCX. CONCLUSIONS: Our stroke protocol achieved excellent opacification of the left heart chambers, the cervical arteries, and each coronary artery, in addition to adequate carotid and coronary artery image quality.

Optimal carotid artery coverage for carotid plaque CT-imaging in predicting ischemic stroke.

OBJECTIVE: To determine the optimal spatial coverage for CT-imaging of carotid atherosclerosis, allowing the most accurate prediction of the associated risk of ischemic stroke. METHODS: In a cross-sectional study, we retrospectively identified 136 consecutive patients admitted to our emergency department with suspected stroke who underwent a CT-angiogram (CTA) of the cervical and intracranial carotid arteries. CTA studies of the carotid arteries were processed using a custom, CT-based automated computer classifier algorithm that quantitatively assesses a battery of carotid CT features. We used this algorithm to individually analyze different lengths of the common and internal carotid arteries for carotid wall features previously shown to be significantly associated with the risk of stroke. Acute stroke patients were categorized into "acute carotid stroke patients" and "non-acute carotid stroke patients" independently of carotid wall CT features. Univariate and multivariate analyses were used to compare the different spatial coverages in terms of their ability to distinguish between the carotid stroke patients and the noncarotid stroke patients using a receiver-operating characteristic curve (ROC) approach. RESULTS: The carotid wall volume was excellent at distinguishing between carotid stroke patients and noncarotid stroke patients, especially for coverages 20mm or less. The number and location of lipid clusters had a good discrimination power, mainly for coverages 15mm or greater. Measurement of minimal fibrous cap thickness was most associated with carotid stroke when assessed using intermediate coverages. Typically, a 20mm coverage on each side of the carotid bifurcation offered the optimal compromise between the individual carotid features. CONCLUSION: We recommend assessment of 20mm of each side of the carotid bifurcation to best characterize carotid atherosclerotic disease and the associated risk of ischemic stroke.

Stonefish envenomation with acute carpal tunnel syndrome.

Stonefish envenomation is a common marine sting. Although stonefish injuries are commonly sustained during maritime activities, this local delicacy can also be considered a regional occupational hazard for chefs. The availability and consumption of stonefish in local restaurants has increased the risk of acute carpal tunnel syndrome after a stonefish injury. This case report describes acute carpal tunnel syndrome following stonefish envenomation. An excellent recovery was achieved after surgical decompression of the carpal tunnel syndrome. Standard management of stonefish injuries should therefore take into account the possibility that this orthopaedic emergency may complicate the injury.

Comparison of total knee arthroplasty using computer-assisted navigation versus conventional guiding systems: a prospective study.

PURPOSE: To compare knee alignments in total knee arthroplasty (TKA) using computer-assisted navigation versus conventional guiding systems. METHODS: Five men and 49 women aged 49 to 79 years underwent TKA for primary osteoarthritis of the knee with varus deformity. All valgus knees were associated with inflammatory arthritis and thus excluded. Computer-assisted navigation was used for the first 35 TKAs, whereas conventional extramedullary tibial and intramedullary femoral guiding systems were used for the next 35 TKAs. The mechanical axis, coronal tibial and femoral angles, sagittal tibial and femoral angles in the 2 groups were compared. RESULTS: Sagittal tibial and femoral angles aligned more optimally in TKAs using computer-assisted navigation. In the respective computer-assisted navigation and conventional guiding systems, 33 (94%) and 26 (74%) of the TKAs attained a postoperative mechanical axis of <3 degrees varus/valgus. CONCLUSION: Computer-assisted navigation gives a more consistent alignment correction and reduces outliers during implant positioning.

Optimal duration of acquisition for dynamic perfusion CT assessment of blood-brain barrier permeability using the Patlak model.

BACKGROUND AND PURPOSE: A previous study demonstrated the need to use delayed acquisition rather than first-pass data for accurate blood-brain barrier permeability surface product (BBBP) calculation from perfusion CT (PCT) according to the Patlak model, but the optimal duration of the delayed acquisition has not been established. Our goal was to determine the optimal duration of the delayed PCT acquisition to obtain accurate BBBP measurements while minimizing potential motion artifacts and radiation dose. MATERIALS AND METHODS: We retrospectively identified 23 consecutive patients with acute ischemic anterior circulation stroke who underwent a PCT study with delayed acquisition. The Patlak model was applied for the full delayed acquisition (90-240 seconds) and also for truncated analysis windows (90-210, 90-180, 90-150, 90-120 seconds). Linear regression of Patlak plots was performed separately for the full and truncated analysis windows, and the slope of these regression lines was used to indicate BBBP. The full and truncated analysis windows were compared in terms of the resulting BBBP values and the quality of the Patlak fitting. RESULTS: BBBP values in the infarct and penumbra were similar for the full 90- to 240-second acquisition (95% confidence intervals for the infarct and penumbra: 1.62-2.47 and 1.75-2.41 mL x100 g(-1) x min(-1), respectively) and the 90- to 210-second analysis window (1.82-2.76 and 2.01-2.74 mL x 100 g(-1) x min(-1), respectively). BBBP values increased significantly with shorter acquisitions. The quality of the Patlak fit was excellent for the full 90- to 240-second and 90- to 210-second acquisitions, but it degraded with shorter acquisitions. CONCLUSIONS: The duration for the delayed PCT acquisition should be at least 210 seconds, because acquisitions shorter than 210 seconds lead to significantly overestimated BBBP values.

Insulin resistance induced by glucosamine in fructose-fed rats.

Glucosamine has been widely used to treat osteoporosis in clinic and it shows an effect on hexosamine biosynthetic pathway in glucose-induced insulin resistance. However, glucosamine and chronic hyperglycemia is not correlative. Thus, we used C (2)C (12) cell line to carry out the uptake assay of 2-[14C]-deoxy-d-glucose and [3H]-glucosamine. Glucosamine inhibited the in vitro glucose uptake in a concentration-dependent manner. The glucose transporter GLUT4 prepared for [3H]-glucosamine uptake showed a concentration-dependent competition between glucose and glucosamine uptake. The effects of glucosamine on glucose tolerance and homeostasis model assessment (HOMA) were also determined in normal Wistar and fructose-fed rats. Both plasma glucose levels and/or HOMA index were not changed in normal rats treated with glucosamine as compared with the saline-treated control. However, we found that glucosamine exhibited an effect on the expression of farnesoid X receptor in liver to exacerbate the values of HOMA and accelerate the development of insulin resistance in fructose-fed rats. Thus, glucosamine should be applied with caution in type-2 diabetic patients.

Age- and anatomy-related values of blood-brain barrier permeability measured by perfusion-CT in non-stroke patients.

BACKGROUND AND PURPOSE: The goal of this study was to determine blood-brain barrier permeability (BBBP) values extracted from perfusion-CT (PCT) using the Patlak model and possible variations related to age, gender, race, vascular risk factors and their treatment and anatomy in non-stroke patients. MATERIALS AND METHODS: We retrospectively identified 96 non-stroke patients who underwent a PCT study using a prolonged acquisition time up to 3 minutes. Patients' charts were reviewed for demographic data, vascular risk factors and their treatment. The Patlak model was applied to calculate BBBP values in regions of interest drawn within the basal ganglia and the gray and white matter of the different cerebral lobes. Differences in BBBP values were analyzed using a multivariate analysis considering clinical variables and anatomy. RESULTS: Mean absolute BBBP values were 1.2 ml 100 g(-1) min(-1) and relative BBBP/CBF values were 3.5%. Statistical differences between gray and white matter were not clinically relevant. BBBP values were influenced by age, history of diabetes and/or hypertension and aspirin intake. CONCLUSION: This study reports ranges of BBBP values in non-stroke patients calculated from delayed phase PCT data using the Patlak model. These ranges will be useful to detect abnormal BBBP values when assessing patients with cerebral infarction for the risk of hemorrhagic transformation.

Mouse studies of SARS coronavirus-specific immune responses to recombinant replication-defective adenovirus expressing SARS coronavirus N protein.

1. A recombinant adenovirus encoding SARS coronavirus(SARS-CoV) nucleocapsid protein (rAd-N) was constructed. 2. The ability of the rAd-N to induce anti-SARS-CoV N antibody production and cellular immune responses was evaluated in an HLA-A2.1/Kb transgenic mouse model.