Target fishing reveals PfPYK-1 and PfRab6 as potential targets of an antiplasmodial 4-anilino-2-trichloromethylquinazoline hit compound.

We present investigations about the mechanism of action of a previously reported 4-anilino-2-trichloromethylquinazoline antiplasmodial hit-compound (Hit A), which did not share a common mechanism of action with established commercial antimalarials and presented a stage-specific effect on the erythrocytic cycle of P. falciparum at 8 < t < 16 h. The target of Hit A was searched by immobilising the molecule on a solid support via a linker and performing affinity chromatography on a plasmodial lysate. Several anchoring positions of the linker (6,7 and 3') and PEG-type linkers were assessed, to obtain a linked-hit molecule displaying in vitro antiplasmodial activity similar to that of unmodified Hit A. This allowed us to identify the PfPYK-1 kinase and the PfRab6 GTP-ase as potential targets of Hit A.

MiRNome variations in milk fractions during feed restrictions of different intensities in dairy cows.

BACKGROUND: In dairy cows, diet is one factor that can affect their milk production and composition. However, the effect of feed restriction on milk miRNome has not yet been described. Indeed, milk is the body fluid with the highest RNA concentration, which includes numerous microRNA. Its presence in the four different milk fractions, whole milk, fat globules, mammary epithelial cells and extracellular vesicles, is still poorly documented. This study aimed to describe the effects of different feed restrictions on the miRNome composition of different milk fractions. RESULTS: Two feed restrictions were applied to lactating dairy cows, one of high intensity and one of moderate intensity. 2,896 mature microRNA were identified in the different milk fractions studied, including 1,493 that were already known in the bovine species. Among the 1,096 microRNA that were sufficiently abundant to be informative, the abundance of 1,027 of them varied between fractions: 36 of those were exclusive to one milk fraction. Feed restriction affected the abundance of 155 microRNA, with whole milk and milk extracellular vesicles being the most affected, whereas milk fat globules and exfoliated mammary epithelial cells were little or not affected at all. The high intensity feed restriction led to more microRNA variations in milk than moderate restriction. The target prediction of known microRNA that varied under feed restriction suggested the modification of some key pathways for lactation related to milk fat and protein metabolisms, cell cycle, and stress responses. CONCLUSIONS: This study highlighted that the miRNome of each milk fraction is specific, with mostly the same microRNA composition but with variations in abundance between fractions. These specific miRNomes were affected differently by feed restrictions, the intensity of which appeared to be a major factor modulating milk miRNomes. These findings offer opportunities for future research on the use of milk miRNA as biomarkers of energy status in dairy cows, which is affected by feed restrictions.

Milk yield loss in response to feed restriction is associated with mammary epithelial cell exfoliation in dairy cows.

In dairy cows, feed restriction is known to decrease milk yield by reducing the number of mammary epithelial cells (MEC) in the udder through a shift in the MEC proliferation-apoptosis balance, by reducing the metabolic activity of MEC, or both. The exfoliation of MEC from the mammary epithelium into milk is another process that may participate in regulating the number of MEC during feed restriction. The aim of the present study was to clarify the mechanisms that underlie the milk yield loss induced by feed restriction. Nineteen Holstein dairy cows producing 40.0 ± 0.7 kg/d at 77 ± 5 d in milk were divided into a control group (n = 9) and a feed-restricted group (n = 10). Ad libitum dry matter intake (DMI) was recorded during a pre-experimental period of 2 wk. For 29 d (period 1), cows were fed either 100 (control) or 80% (feed-restricted) of their ad libitum DMI measured during the pre-experimental period. Then, all cows were fed ad libitum for 35 d (period 2). Milk production and DMI were recorded daily. Blood and milk samples were collected once during the pre-experimental period; on d 5, 9, and 27 of period 1; and on d 5, 9, and 30 of period 2. Mammary epithelial cells were purified from milk using an immunomagnetic method to determine the rate of MEC exfoliation. Mammary tissue samples were collected by biopsy at the end of each period to analyze the rates of cell proliferation and apoptosis and the expression of genes involved in synthesizing constituents of milk. Feed restriction decreased milk yield by 3 kg/d but had no effect on rates of proliferation and apoptosis in the mammary tissue or on the expression of genes involved in milk synthesis. The daily MEC exfoliation rate was 65% greater in feed-restricted cows than in control cows. These effects in feed-restricted cows were associated with reduced insulin-like growth factor-1 and cortisol plasma concentrations. When all cows returned to ad libitum feeding, no significant difference on milk yield or MEC exfoliation rate was observed between feed-restricted and control cows, but refeeding increased prolactin release during milking. These results show that the exfoliation process may play a role in regulating the number of MEC in the udders of dairy cows during feed restriction without any carryover effect on their milk production.

Oxytocin Induces Mammary Epithelium Disruption and Could Stimulate Epithelial Cell Exfoliation.

Mammary epithelial cells (MEC) are exfoliated from the epithelium into milk, influencing the number of MEC present in the udder. This process is associated with epithelium integrity. The release of oxytocin (OT) induced by milking causes myoepithelial cell contraction, which, in turn, may stimulate MEC exfoliation through mechanical forces. To investigate the role of OT in MEC exfoliation, we inhibited or induced myoepithelial cell contraction by injecting the OT receptor antagonist atosiban (Ato) or a supraphysiological dose of OT, respectively. Eight cows were assigned to 2 treatments during 2 milkings according to a crossover experimental design: Control+OT (cows were first milked to collect standard milk and then received 5 IU of OT to collect residual milk through a second milking) and Ato + OT (cows were injected with Ato (50 µg/kg of body weight) and milked to collect cisternal milk, then received 5 IU of OT to collect alveolar milk through a second milking). Milk MEC were purified to determine their concentration and number in milk. Mammary epithelium integrity was assessed by measuring the kinetics of plasma lactose concentration. Inhibiting myoepithelial cell contraction by Ato injection decreased the number of exfoliated MEC in milk. In contrast, OT injection increased the concentration of MEC in the residual milk and the number of MEC in the alveolar milk. Ato injection reduced plasma lactose concentration, whereas, in both treatments, OT injections increased it. Our results suggested that myoepithelial cell contraction caused by OT could stimulate MEC exfoliation into milk and was associated with epithelium disruption.

Imaging of dense cell cultures by multiwavelength lens-free video microscopy.

They present results for lens-free microscopy for the imaging of dense cell culture. With this aim, they use a multiwavelength LED illumination with well separated wavelengths, together with the implementation of an appropriate holographic reconstruction algorithm. This allows for a fast and efficient reconstruction of the phase image of densely packed cells (up to 700 cells/mm2 ) over a large field of view of 29.4 mm2 . Combined with the compactness of the system which fits altogether inside an incubator, lens-free microscopy becomes a unique tool to monitor cell cultures over several days. The high contrast phase shift images provide robust cell segmentation and tracking, and enable high throughput monitoring of individual cell dimensions, dry mass, and motility. They tested the multiwavelength lens-free video-microscope over a broad range of cell lines, including mesenchymal, endothelial, and epithelial cells. © 2017 International Society for Advancement of Cytometry.

Mammary epithelium disruption and mammary epithelial cell exfoliation during milking in dairy cows.

The presence of mammary epithelial cells (MEC) in the milk of ruminants indicates that some MEC are shed from the mammary epithelium; however, the mechanisms that regulate the MEC exfoliation process are not known. Through the release of oxytocin, prolactin, and cortisol and through oxytocin-induced mechanical forces on the mammary epithelium, milking could participate in regulating the MEC exfoliation process. The aims of the present study were to determine the rate of MEC exfoliation throughout milking and to investigate its relationship to mammary epithelium integrity and milking-induced hormone release. Milk samples from 9 Holstein dairy cows producing 40.6 ± 1.36 kg of milk/d were collected at the beginning (after 1 and 2 min), in the middle, and at the end of milking. Milk MEC were purified using an immunomagnetic method. Blood samples were collected before, during, and after milking, and the oxytocin, prolactin, and cortisol concentrations in the samples were measured. Tight junction opening was assessed by plasma lactose concentration and the Na+:K+ ratio in milk. The somatic cell count in milk varied during the course of milking; it decreased at the beginning of milking and then increased, reaching the highest values at the end of milking. Exfoliated MEC were present in all milk samples collected. The presence of MEC in the milk sample collected during min 1 of milking, likely corresponding to the cisternal milk fraction, suggests that MEC were exfoliated between milkings. The observed increase in the Na+:K+ ratio in milk and in the plasma concentration of lactose indicated that disruption of mammary epithelium integrity occurred during milking. The MEC exfoliation rate at milking was not correlated with the variables describing milking-induced prolactin release but was negatively correlated with cortisol release, suggesting that cortisol may play a role in limiting exfoliation. In conclusion, milking induced a disruption of the mammary epithelial barrier. Mammary epithelial cells may be continuously exfoliated between milkings or exfoliated during milking as a consequence of the oxytocin-induced mechanical forces and the disruption of mammary epithelium integrity.

Regulation of cell number in the mammary gland by controlling the exfoliation process in milk in ruminants.

Milk yield is partly influenced by the number of mammary epithelial cells (MEC) in the mammary gland. It is well known that variations in MEC number are due to cell proliferation and apoptosis. The exfoliation of MEC from the mammary epithelium into milk is another process that might influence MEC number in the mammary tissue. The rate of MEC exfoliation can be assessed by measuring the milk MEC content through light microscopy, flow cytometry analysis, or an immuno-magnetic method for MEC purification. Various experimental models have been used to affect milk yield and study the rate of MEC exfoliation. Reducing milking frequency from twice to once daily did not seem to have any effect on MEC loss in goat and cow milk after 7 d, but increased MEC loss per day in goats when applied for a longer period. An increase in MEC exfoliation was also observed during short days as compared with long days, or in response to an endotoxin-induced mastitis in cows. Other animal models were designed to investigate the endocrine control of the exfoliation process and its link with milk production. Suppression of ovarian steroids by ovariectomy resulted in a greater persistency of lactation and a decrease in MEC exfoliation. Administering prolactin inhibitors during lactation or at dry-off enhanced MEC exfoliation, whereas exogenous prolactin during lactation tended to prevent the negative effect of prolactin inhibitors. These findings suggest that prolactin could regulate MEC exfoliation. In most of these studies, variations of MEC exfoliation were associated with variations in milk yield and changes in mammary epithelium integrity. Exfoliation of MEC could thus influence milk yield by regulating MEC number in mammary tissue.

Prospective Clinical Utility Study of the Use of the 21-Gene Assay in Adjuvant Clinical Decision Making in Women With Estrogen Receptor-Positive Early Invasive Breast Cancer: Results From the SWITCH Study.

BACKGROUND: The 21-gene Oncotype DX Recurrence Score assay is a validated assay to help decide the appropriate treatment for estrogen receptor-positive (ER+), early-stage breast cancer (EBC) in the adjuvant setting. The choice of adjuvant treatments might vary considerably in different countries according to various treatment guidelines. This prospective multicenter study is the first to assess the impact of the Oncotype DX assay in the French clinical setting. METHODS: A total of 100 patients with ER+, human epidermal growth factor receptor 2-negative EBC, and node-negative (pN0) disease or micrometastases in up to 3 lymph nodes (pN1mi) were enrolled. Treatment recommendations, physicians' confidence before and after knowing the Recurrence Score value, and physicians' perception of the assay were recorded. RESULTS: Of the 100 patients, 95 were evaluable (83 pN0, 12 pN1mi). Treatment recommendations changed in 37% of patients, predominantly from chemoendocrine to endocrine treatment alone. The proportion of patients recommended chemotherapy decreased from 52% pretest to 25% post-test. Of patients originally recommended chemotherapy, 61% were recommended endocrine treatment alone after receiving the Recurrence Score result. For both pN0 and pN1mi patients, post-test recommendations appeared to follow the Recurrence Score result for low and high values. Physicians' confidence improved significantly. CONCLUSION: These are the first prospective data on the impact of the Oncotype DX assay on adjuvant treatment decisions in France. Using the assay was associated with a significant change in treatment decisions and an overall reduction in chemotherapy use. These data are consistent with those presented from European and non-European studies.

Magnetic anisotropy, magnetization reversal and switching in Ni4Nb2O9single crystals.

Ni4Nb2O9is an insulating compensated ferrimagnet withTN= 77 K andTcomp= 33 K. We report here the study of the magnetic anisotropy using millimeter-size crystals grown in an image furnace. The magnetization measurements, vs temperature, performed withHaligned along the three main crystallographic axes, show similar Curie-Weiss temperatures (Θp≈ 190 K) and rather similar effective paramagnetic moments (from 3.5µBto 3.6µB). This suggests that the strongest magnetic interaction is the antiferromagnetic one, coupling the ferromagnetic distorted honeycomb layers and zigzag ribbons via face sharing NiO6octahedra. This strong antiferromagnetic coupling is supported by DFT calculations that do not evidence any inter site ferromagnetic interaction, leading to total compensation between magnetic moments of both Ni2+sites. Measurements vs magnetic field belowTNreveal an anisotropic behaviour, with square magnetization loops forHin theabplane, whereas linearM(H) curves without hysteresis are observed forH‖c. This anisotropy betweenabplane andcaxis occurs also in the magnetization reversal (MR), which is observed in theabplane only. Starting fromM(H) virgin curves collected just belowTcomp= 33 K withH‖aorH‖b, the memory-like effect was tested through magnetization switching induced byHorTalternating changes. BelowTcomp, smallerHis needed to switchMsymmetrically forHalongbthan alonga, and, forTswitching (2 K interval, constantH), a largerMchange is obtained alongathan alongb. The comparison with ferrimagnetic oxides which exhibit MR, like spinels or rare earth orthoferrites, shows that Ni4Nb2O9is unique since only one magnetic cation over two sites in octahedral coordination is at play, thus providing a unique platform to studyMswitching but also a challenge for theoretical interpretation.

Incidental findings on brain MRI in the general population.

BACKGROUND: Magnetic resonance imaging (MRI) of the brain is increasingly used both in research and in clinical medicine, and scanner hardware and MRI sequences are continually being improved. These advances are likely to result in the detection of unexpected, asymptomatic brain abnormalities, such as brain tumors, aneurysms, and subclinical vascular pathologic changes. We conducted a study to determine the prevalence of such incidental brain findings in the general population. METHODS: The subjects were 2000 persons (mean age, 63.3 years; range, 45.7 to 96.7) from the population-based Rotterdam Study in whom high-resolution, structural brain MRI (1.5 T) was performed according to a standardized protocol. Two trained reviewers recorded all brain abnormalities, including asymptomatic brain infarcts. The volume of white-matter lesions was quantified in milliliters with the use of automated postprocessing techniques. Two experienced neuroradiologists reviewed all incidental findings. All diagnoses were based on MRI findings, and additional histologic confirmation was not obtained. RESULTS: Asymptomatic brain infarcts were present in 145 persons (7.2%). Among findings other than infarcts, cerebral aneurysms (1.8%) and benign primary tumors (1.6%), mainly meningiomas, were the most frequent. The prevalence of asymptomatic brain infarcts and meningiomas increased with age, as did the volume of white-matter lesions, whereas aneurysms showed no age-related increase in prevalence. CONCLUSIONS: Incidental brain findings on MRI, including subclinical vascular pathologic changes, are common in the general population. The most frequent are brain infarcts, followed by cerebral aneurysms and benign primary tumors. Information on the natural course of these lesions is needed to inform clinical management.

Minor head injury: CT-based strategies for management--a cost-effectiveness analysis.

PURPOSE: To compare the cost-effectiveness of using selective computed tomographic (CT) strategies with that of performing CT in all patients with minor head injury (MHI). MATERIALS AND METHODS: The internal review board approved the study; written informed consent was obtained from all interviewed patients. Five strategies were evaluated, with CT performed in all patients with MHI; selectively according to the New Orleans criteria (NOC), Canadian CT head rule (CCHR), or CT in head injury patients (CHIP) rule; or in no patients. A decision tree was used to analyze short-term costs and effectiveness, and a Markov model was used to analyze long-term costs and effectiveness. n-Way and probabilistic sensitivity analyses and value-of-information (VOI) analysis were performed. Data from the multicenter CHIP Study involving 3181 patients with MHI were used. Outcome measures were first-year and lifetime costs, quality-adjusted life-years, and incremental cost-effectiveness ratios. RESULTS: Study results showed that performing CT selectively according to the CCHR or the CHIP rule could lead to substantial U.S. cost savings ($120 million and $71 million, respectively), and the CCHR was the most cost-effective at reference-case analysis. When the prediction rule had lower than 97% sensitivity for the identification of patients who required neurosurgery, performing CT in all patients was cost-effective. The CHIP rule was most likely to be cost-effective. At VOI analysis, the expected value of perfect information was $7 billion, mainly because of uncertainty about long-term functional outcomes. CONCLUSION: Selecting patients with MHI for CT renders cost savings and may be cost-effective, provided the sensitivity for the identification of patients who require neurosurgery is extremely high. Uncertainty regarding long-term functional outcomes after MHI justifies the routine use of CT in all patients with these injuries.

Evolution of milk composition, milk fat globule size, and free fatty acids during milking of dairy cows.

The objective of this study was to measure milk composition (fat, protein, and calcium contents; fatty acid profile), milk fat globule size, and free fatty acid content throughout milking. Composition was measured from milk samples collected every 1 min during morning milking in 2 previously published experiments. Experiments 1 and 2 used 9 and 6 dairy cows, respectively. From the beginning to end of milking in experiments 1 and 2, lactose content decreased (-0.45 percentage units), as did protein content (-0.28 and -0.17 percentage units, respectively). In contrast, fat content increased (+5.66 and +5.57 percentage units, respectively). Milk fat globule size increased (+1.51 and +0.43 µm, respectively), whereas free fatty acid content (measured after 24 h of storage at 4°C) decreased quickly during the first minutes (-0.45 mEq/100 g of fat from time point 1 to time point 4 in experiment 1, and -0.85 mEq/100 g of fat from time point 1 to time point 5 in experiment 2), and then largely stabilized, with a slight tendency to increase toward the end of milking period in experiment 2 (+0.32 mEq/100 g of fat). The evolution of milk fatty acid composition depended on the experiment. From the beginning to the end of milking, the concentration of C16:0 consistently increased (+3.4 wt/wt % in experiment 1 and +3.3 wt/wt % from time point 2 to time point 7 in experiment 2), whereas the C18:1/C16:0 ratio increased during the first minutes of milking and then slightly decreased (-0.050 in experiment 1 and -0.031 from time point 2 to time point 7 in experiment 2). Calcium content decreased in experiment 2 (-58 mg/kg). In conclusion, milk composition changed greatly during milking, suggesting that different mechanisms are involved in synthesis and excretion, depending on the type of milk component.

Alternation of inverse problem approach and deep learning for lens-free microscopy image reconstruction.

A lens-free microscope is a simple imaging device performing in-line holographic measurements. In the absence of focusing optics, a reconstruction algorithm is used to retrieve the sample image by solving the inverse problem. This is usually performed by optimization algorithms relying on gradient computation. However the presence of local minima leads to unsatisfactory convergence when phase wrapping errors occur. This is particularly the case in large optical thickness samples, for example cells in suspension and cells undergoing mitosis. To date, the occurrence of phase wrapping errors in the holographic reconstruction limits the application of lens-free microscopy in live cell imaging. To overcome this issue, we propose a novel approach in which the reconstruction alternates between two approaches, an inverse problem optimization and deep learning. The computation starts with a first reconstruction guess of the cell sample image. The result is then fed into a neural network, which is trained to correct phase wrapping errors. The neural network prediction is next used as the initialization of a second and last reconstruction step, which corrects to a certain extent the neural network prediction errors. We demonstrate the applicability of this approach in solving the phase wrapping problem occurring with cells in suspension at large densities. This is a challenging sample that typically cannot be reconstructed without phase wrapping errors, when using inverse problem optimization alone.

Quantitative phase imaging of adherent mammalian cells: a comparative study.

The Quantitative phase imaging methods have several advantages when it comes to monitoring cultures of adherent mammalian cells. Because of low photo-toxicity and no need for staining, we can follow cells in a minimally invasive way over a long period of time. The ability to measure the optical path difference in a quantitative manner allows the measurement of the cell dry mass, an important metric for studying the growth kinetics of mammalian cells. Here we present and compare cell measurements obtained with three different techniques: digital holographic microscopy, lens-free microscopy and quadriwave lateral sheering interferometry. We report a linear relationship between optical volume density values measured with these different techniques and estimate the precisions of this measurement for the different individual instruments.

Review: the cellular mechanisms underlying mammary tissue plasticity during lactation in ruminants.

The mammary tissue is characterized by its capacity to adapt in response to a wide variety of changing conditions. This adaptation capacity is referred to as the plasticity of mammary tissue. In dairy ruminants, lactation is challenged by modifications that can either be induced on purpose, such as by modifying management practices, or occur involuntarily, when adverse environmental constraints arise. These modifications can elicit both immediate changes in milk yield and composition and carryover effects that persist after the end of the challenge. This review focuses on the current knowledge concerning the cellular mechanisms underlying mammary tissue plasticity. The main mechanisms contributing to this phenomenon are changes in the activity and number of mammary epithelial cells (MECs). Changes in the number of these cells result from variations in the rates of cell proliferation and death as well as changes in the rate MEC exfoliation. The number of MECs also depends on the number of resident adult mammary stem cells and their progenitors, which can regenerate the pools of the various mammary cells. Several challenges, including changes in milking frequency, changes in level of feed supply and hormonal manipulations, have been shown to modulate milk yield together with changes in mammary cell activity, turnover and exfoliation. Epigenetic changes may be an additional mechanism of adaptation. Indeed, changes in DNA methylation and reductions in milk yield have been observed during once-daily milking and during mastitis in dairy cows and may affect cell activity persistently. In contrast to what has been assumed for a long time, no carryover effect on milk yield were observed after feed supply challenges in dairy cows and modification of milking frequency in dairy goats, even though the number of mammary cells was affected. In addition, mammary tissue plasticity has been shown to be influenced by the stage of lactation, health status and genetic factors. In conclusion, the cellular mechanisms underlying mammary tissue plasticity are diverse, and the mammary tissue either does or does not show elastic properties (with no permanent deformation), in response to environmental changes.

Biotechnological approaches for cocoa waste management: A review.

Cocoa beans provide raw materials for global food industries valued in excess of $47 billion in world exportations. Through on-farm processing, about 80% of cocoa fruit is discarded as residual biomass, including cocoa pod husks, cocoa bean shells and cocoa sweatings. Farmers routinely discard these residues/by-products during the initial cocoa bean processing steps, occupying vast areas and raising social and environmental concerns. Alternatively, this residual biomass is used as cocoa tree fertilizer. However, its disposal is performed without proper treatment, resulting in putrid odors and plant diseases. Recently, some studies have reported the use of cocoa by-products in the production of high-value-adding molecules with potential applications in the food, pharmaceutical and cosmetic industries. In this aspect, biotechnological approaches have been shown to be a viable alternative for the transformation of this residual biomass into fine products. This article reviews the biotechnological approaches implemented for the management and exploitation of cocoa by-product. Related topics on cocoa production and residual biomass generation, sustainability and valorization of cocoa chain are addressed and discussed.

Is a fetal origin of the posterior cerebral artery a risk factor for TIA or ischemic stroke? A study with 16-multidetector-row CT angiography.

BACKGROUND AND PURPOSE: Fetal origin of the posterior cerebral artery (PCA) is not uncommon. Whether patients with this anomaly have a higher risk of ischemic stroke in the territory of the PCA is not known. The clinical benefit of screening for a fetal origin in patients with TIA or stroke in the territory of the PCA and an ipsilateral atherosclerotic carotid stenosis is not clear. This study assessed the frequency of a fetal origin of the PCA in patients with a TIA or infarct in the territory of the PCA with 16-multidetector-row CT angiography (CTA). METHODS: 82 patients (52 male; mean age = 64; range 19 to 90 years) with isolated homonymous hemianopia and/or a PCA infarct underwent CTA of the carotid artery and circle of Willis. RESULTS: A fetal origin of the PCA at the symptomatic side was present in 14 patients (17 %) and at the asymptomatic side in 18 patients (22%) (OR: 0.7; 95 % CI: 0.3 to 1.7). Severity of stenosis (NASCET criteria) of the ICA at the symptomatic side was < 30%, 30-49% and > or = 50% in 72, 2 and 8 patients, respectively. Number and frequency of a fetal origin in these groups were 12 (17 %), 0 (0%) and 2 (25 %), respectively. There was no association between a severe carotid stenosis and a fetal origin of the PCA at the symptomatic side. CONCLUSION: This study does not provide arguments for an increased risk of ischemic stroke in the territory of the PCA in patients with a fetal origin of the PCA. A few patients with a TIA or infarct in the territory of the PCA have a fetal origin of the PCA in combination with a high-grade stenosis of the ipsilateral ICA, but not more often than one would expect from chance. Nevertheless, these patients may benefit from carotid endarterectomy.

Assessment of feasibility of endovascular treatment of ruptured intracranial aneurysms with 16-detector row CT angiography.

BACKGROUND: It is unclear whether 16-detector row CT angiography (CTA) can replace digital subtraction angiography (DSA) to assess the feasibility of endovascular treatment (EVT) in the acute phase after aneurysmal subarachnoid hemorrhage. METHODS: We studied 80 consecutive patients with aneurysmal subarachnoid hemorrhage, who underwent both CTA and DSA. Two interventional neuroradiologists independently scored CTA and, immediately thereafter, DSA with respect to feasibility of EVT. We determined whether CTA without DSA was sufficient for a definite judgment. We also assessed interobserver agreement. RESULTS: The 2 readers judged EVT to be feasible in 24 and 37 patients with CTA alone and not feasible in 34 and 20 patients. In these patients, DSA yielded additional information in 6 (reader 1) and 5 patients (reader 2), which did not affect treatment decision. In 19 and 7 patients, DSA was considered inferior to CTA. In the remaining patients (n = 22 and 23, respectively), feasibility of EVT could not be judged with CTA alone, and DSA results were required in addition for a treatment decision. Interobserver agreement on feasibility of EVT was just fair (kappa <0.40). CONCLUSIONS: In our series of patients, 16-detector row CTA was a reliable investigation to assess feasibility of EVT of ruptured intracranial aneurysms in most patients. Further, we found that interobserver disagreement on feasibility of EVT was considerable.

Predicting intracranial traumatic findings on computed tomography in patients with minor head injury: the CHIP prediction rule.

BACKGROUND: Prediction rules for patients with minor head injury suggest that the use of computed tomography (CT) may be limited to certain patients at risk for intracranial complications. These rules apply only to patients with a history of loss of consciousness, which is frequently absent. OBJECTIVE: To develop a prediction rule for the use of CT in patients with minor head injury, regardless of the presence or absence of a history of loss of consciousness. DESIGN: Prospective, observational study. SETTING: 4 university hospitals in the Netherlands that participated in the CT in Head Injury Patients (CHIP) study. PATIENTS: Consecutive adult patients with minor head injury (> or =16 years of age) with a Glasgow Coma Scale (GCS) score of 13 to 14 or with a GCS score of 15 and at least 1 risk factor. MEASUREMENTS: Outcomes were any intracranial traumatic CT finding and neurosurgical intervention. The authors performed logistic regression analysis by using variables from existing prediction rules and guidelines, with internal validation by using bootstrapping. RESULTS: 3181 patients were included (February 2002 to August 2004): 243 (7.6%) had intracranial traumatic CT findings and 17 (0.5%) underwent neurosurgical intervention. A detailed prediction rule was developed from which a simple rule was derived. Sensitivity of both rules was 100% for neurosurgical interventions, with an associated specificity of 23% to 30%. For intracranial traumatic CT findings, sensitivity and specificity were 94% to 96% and 25% to 32%, respectively. Potential CT reduction by implementing the prediction rule was 23% to 30%. Internal validation showed slight optimism for the model's performance. LIMITATION: External validation of the prediction model will be required. CONCLUSION: The authors propose the highly sensitive CHIP prediction rule for the selective use of CT in patients with minor head injury with or without loss of consciousness.