Can the ischemic penumbra be identified on noncontrast CT of acute stroke?

<p><b>Background and Purpose:</b> Early ischemic changes on noncontrast CT in acute stroke include both hypoattenuation and brain swelling, which may have different pathophysiological significance.</p> <p><b>Methods:</b> Noncontrast CT and CT perfusion brain scans from patients with suspected acute stroke <6 hours after onset were reviewed. Five raters independently scored noncontrast CTs blind to clinical data using the Alberta Stroke Program Early CT Score (ASPECTS). Each ASPECTS region was scored as hypodense or swollen. A separate reviewer measured time to peak and cerebral blood volume in each ASPECTS region on CT perfusion. Time to peak and cerebral blood volume were compared for each region categorized as normal, hypodense, or isodense and swollen.</p> <p><b>Results:</b> Scans of 32 subjects a median 155 minutes after onset yielded 228 regions with both CT perfusion and noncontrast CT data. Isodense swelling was associated with significantly higher cerebral blood volume (P=0.016) and with penumbral perfusion (posttest:pretest likelihood ratio 1.44 [95% CI: 0.68 to 2.90]), whereas hypodensity was associated with more severe time to peak delay and with core perfusion (likelihood ratio 3.47 [95% CI: 1.87 to 6.34]). Neither isodense swelling nor hypodensity was sensitive for prediction of perfusion pattern, but appearances were highly specific (87.2% and 91.0% for penumbra and core, respectively). Intrarater agreement was good or excellent, but interrater agreement for both hypodensity and swelling was poor.</p> <p><b>Conclusions:</b> Regions exhibiting hypoattenuation are likely to represent the infarct core, whereas regions that are isodense and swollen have increased cerebral blood volume and are more likely to signify penumbral perfusion. Although noncontrast CT is not sensitive for detection of core and penumbra, appearances are specific. Some information on tissue viability can therefore be obtained from noncontrast CT.</p&gt

The F-actin cytoskeleton in syncytia from non-clonal progenitor cells

The actin cytoskeleton of plant syncytia (a multinucleate cell arising through fusion) is poorly known: to date, there have only been reports about F-actin organization in plant syncytia induced by parasitic nematodes. To broaden knowledge regarding this issue, we analyzed F-actin organization in special heterokaryotic Utricularia syncytia, which arise from maternal sporophytic tissues and endosperm haustoria. In contrast to plant syncytia induced by parasitic nematodes, the syncytia of Utricularia have an extensive F-actin network. Abundant F-actin cytoskeleton occurs both in the region where cell walls are digested and the protoplast of nutritive tissue cells fuse with the syncytium and also near a giant amoeboid in the shape nuclei in the central part of the syncytium. An explanation for the presence of an extensive F-actin network and especially F-actin bundles in the syncytia is probably that it is involved in the movement of nuclei and other organelles and also the transport of nutrients in these physiological activity organs which are necessary for the development of embryos in these unique carnivorous plants. We observed that in Utricularia nutritive tissue cells, actin forms a randomly arranged network of F-actin, and later in syncytium, two patterns of F-actin were observed, one characteristic for nutritive cells and second—actin bundles—characteristic for haustoria and suspensors, thus syncytia inherit their F-actin patterns from their progenitors

Lithium side effects and toxicity: prevalence and management strategies

Despite its virtually universal acceptance as the gold standard in treating bipolar disorder, prescription rates for lithium have been decreasing recently. Although this observation is multifactorial, one obvious potential contributor is the side effect and toxicity burden associated with lithium. Additionally, side effect concerns assuredly play some role in lithium nonadherence. This paper summarizes the knowledge base on side effects and toxicity and suggests optimal management of these problems. Thirst and excessive urination, nausea and diarrhea and tremor are rather common side effects that are typically no more than annoying even though they are rather prevalent. A simple set of management strategies that involve the timing of the lithium dose, minimizing lithium levels within the therapeutic range and, in some situations, the prescription of side effect antidotes will minimize the side effect burden for patients. In contrast, weight gain and cognitive impairment from lithium tend to be more distressing to patients, more difficult to manage and more likely to be associated with lithium nonadherence. Lithium has adverse effects on the kidneys, thyroid gland and parathyroid glands, necessitating monitoring of these organ functions through periodic blood tests. In most cases, lithium-associated renal effects are relatively mild. A small but measurable percentage of lithium-treated patients will show progressive renal impairment. Infrequently, lithium will need to be discontinued because of the progressive renal insufficiency. Lithium-induced hypothyroidism is relatively common but easily diagnosed and treated. Hyperparathyroidism from lithium is a relatively more recently recognized phenomenon

Evaluation of appendicitis risk prediction models in adults with suspected appendicitis

Background Appendicitis is the most common general surgical emergency worldwide, but its diagnosis remains challenging. The aim of this study was to determine whether existing risk prediction models can reliably identify patients presenting to hospital in the UK with acute right iliac fossa (RIF) pain who are at low risk of appendicitis. Methods A systematic search was completed to identify all existing appendicitis risk prediction models. Models were validated using UK data from an international prospective cohort study that captured consecutive patients aged 16–45 years presenting to hospital with acute RIF in March to June 2017. The main outcome was best achievable model specificity (proportion of patients who did not have appendicitis correctly classified as low risk) whilst maintaining a failure rate below 5 per cent (proportion of patients identified as low risk who actually had appendicitis). Results Some 5345 patients across 154 UK hospitals were identified, of which two‐thirds (3613 of 5345, 67·6 per cent) were women. Women were more than twice as likely to undergo surgery with removal of a histologically normal appendix (272 of 964, 28·2 per cent) than men (120 of 993, 12·1 per cent) (relative risk 2·33, 95 per cent c.i. 1·92 to 2·84; P < 0·001). Of 15 validated risk prediction models, the Adult Appendicitis Score performed best (cut‐off score 8 or less, specificity 63·1 per cent, failure rate 3·7 per cent). The Appendicitis Inflammatory Response Score performed best for men (cut‐off score 2 or less, specificity 24·7 per cent, failure rate 2·4 per cent). Conclusion Women in the UK had a disproportionate risk of admission without surgical intervention and had high rates of normal appendicectomy. Risk prediction models to support shared decision‐making by identifying adults in the UK at low risk of appendicitis were identified

Intensive glycemic control has no impact on the risk of heart failure in type 2 diabetic patients: Evidence from a 37,229 patient meta-analysis

Background More intensive glycemic control reduces the risk of microvascular disease in patients with diabetes mellitus but has not been proven to reduce the risk of macrovascular events such as myocardial infarction and stroke. Poorer glycemic control, as indicated by glycated hemoglobin level concentration, is associated with an increased risk of heart failure (HF), but it is not known whether improved glycemic control reduces this risk. We conducted a meta-analysis of randomized controlled trials comparing strategies of more versus less intensive glucose-lowering that reported HF events. Methods Two investigators independently searched PubMed, the Cochrane CENTRAL register of controlled trials, metaRegister, pre-MEDLINE, and CINAHL from January 1970 to October 2010 for prospective controlled randomized trials comparing a more intensive glucose-lowering regimen to a standard regimen. The outcome of interest was HF-related events (both fatal and nonfatal). Odds ratios (ORs) were calculated from published data from relevant trials and pooled with a random-effects meta-analysis. Results A total of 37,229 patients from 8 randomized trials were included in the analysis. Follow-up ranged from 2.3 to 10.1 years, and the overall number of HF-related events was 1469 (55% in the intensive treatment arm). The mean difference in glycated hemoglobin level between patients given standard treatment and those allocated to a more intensive regimen was 0.9%. Overall, the risk of HF-related events did not differ significantly between intensive glycemic control and standard treatment (OR 1.20, 95% CI 0.96-1.48), but the effect estimate was highly heterogeneous (I(2) = 69%). At subgroup analysis, intensive glycemic control achieved with high thiazolidinediones use significantly increased HF risk (OR 1.33, 95% CI 1.02-1.72). Conclusions More intensive glycemic control in patients with type 2 diabetes mellitus did not reduce the occurrence of HF events. Furthermore, intensive glycemic control with thiazolidinediones increased the risk of HF. These findings question a direct mechanistic link between hyperglycemia and HF. (Am Heart J 2011;162:938-948.e2.

Objective perimetry and progression of multiple sclerosis

Introduction: We re-examined the per-region response amplitudes and delays obtained from multifocal pupillographic objective perimetry (mfPOP) after 10 years in 44 persons living with multiple sclerosis (PwMS), both to examine which parts of the visual field had progressed in terms of response properties and to examine if the baseline data could predict the overall progression of disease. Methods: Expanded Disability Status Scale (EDSS) scores were assessed in 2009 and 2019. Both eyes of each participant were concurrently tested at 44 locations/eye on both occasions. Several measures of clinical progression were examined, using logistic regression to determine the odds of progression. Results: At the second examination the 44 PwMS (31 females) were aged 61.0 ± 12.2 y. Mean EDSS had not changed significantly (3.69 ± 1.23 in 2009, 3.81 ± 2.00 in 2019). mfPOP delay increased progressively from inferior to superior regions of the visual fields while amplitudes demonstrated a temporal to nasal gradient. The mean of the 3 most delayed visual field regions was correlated with progression of MS by 2019 (p = 0.023). Logistic regression indicated a significant association between delay and odds of progression (p = 0.045): an individual with 3 regions at least 1 SD (40 ms) slower than the mean in 2009 had 2.05× (±SE: 1.43× to 2.95×) the odds of progression by 2019. A 1 SD shorter delay was associated with 2.05× lower odds of progression. Amplitude changes were not predictive of progression. Significance: mfPOP may provide a rapid, convenient method of monitoring and predicting MS progression