Complications of invasive video-EEG monitoring with subdural grid electrodes.

OBJECTIVE: To evaluate the risk factors, type, and frequency of complications during video-EEG monitoring with subdural grid electrodes. METHODS: The authors retrospectively reviewed the records of all patients who underwent invasive monitoring with subdural grid electrodes (n = 198 monitoring sessions on 187 patients; median age: 24 years; range: 1 to 50 years) at the Cleveland Clinic Foundation from 1980 to 1997. RESULTS: From 1980 to 1997, the complication rate decreased (p = 0.003). In the last 5 years, 19/99 patients (19%) had complications, including two patients (2%) with permanent sequelae. In the last 3 years, the complication rate was 13.5% (n = 5/37) without permanent deficits. Overall, complications occurred during 52 monitoring sessions (26.3%): infection (n = 24; 12.1%), transient neurologic deficit (n = 22; 11.1%), epidural hematoma (n = 5; 2.5%), increased intracranial pressure (n = 5; 2.5%), and infarction (n = 3; 1.5%). One patient (0.5%) died during grid insertion. Complication occurrence was associated with greater number of grids/electrodes (p = 0.021/p = 0.052; especially >60 electrodes), longer duration of monitoring (p = 0.004; especially >10 days), older age of the patient (p = 0.005), left-sided grid insertion (p = 0.01), and burr holes in addition to the craniotomy (p = 0.022). No association with complications was found for number of seizures, IQ, anticonvulsants, or grid localization. CONCLUSIONS: Invasive monitoring with grid electrodes was associated with significant complications. Most of them were transient. Increased complication rates were related to left-sided grid insertion and longer monitoring with a greater number of electrodes (especially more than 60 electrodes). Improvements in grid technology, surgical technique, and postoperative care resulted in significant reductions in the complication rate.     

Long-term follow-up of a 26-year-old male with duplication of 16p: clinical report and review

We report on a 26-year-old male with profound psychomotor retardation and a pattern of dysmorphic features and malformations characteristic for duplication of the short arm of chromosome 16. He has an elongated face, sparse hair, upslanting palpebral fissures, anteverted nostrils, hypoplastic thumbs on both hands, and dislocation of several joints. His chromosome aberration was diagnosed at birth and was due to an unbalanced segregation of a maternal translocation t(2;16)(q36;p11). At 26 years of age he is, to the best of our knowledge, the oldest patient with duplication of 16p reported to date. We present a long-term observation of growth, psychomotor development, dysmorphic features and evolution of his skeletal and joint defects as well as a review of the literature.     

Equivalence and noninferiority testing in regression models and repeated-measures designs

Equivalence and noninferiority designs are useful when the superiority of one intervention over another is neither expected nor required. Equivalence trials test whether a difference between groups falls within a prespecified equivalence region, whereas noninferiority trials test whether a preferred intervention is either better or at least not worse than the comparator, with worse being defined a priori. Special designs and analyses are needed because neither of these conclusions can be reached from a nonsignificant test for superiority. Using the data from a companion article, we demonstrate analyses of basic equivalence and noninferiority designs, along with more complex model-based methods. We first give an overview of methods for design and analysis of data from superiority, equivalence, and noninferiority trials, including how to analyze each type of design using linear regression models. We then show how the analogous hypotheses can be tested in a repeated-measures setting in which there are multiple outcomes per subject. We especially address interactions between the repeated factor, usually time, and treatment. Although we focus on the analysis of continuous outcomes, extensions to other data types as well as sample size consideration are discussed.     

Multidimensional scaling analysis identifies pathological and prognostically relevant profiles of circulating T‐cells in chronic lymphocytic leukemia

Antitumor immunity in chronic lymphocytic leukemia (CLL) is hampered by highly dysfunctional T‐cells. Although certain T‐cell subsets have been reported to be of prognostic significance in this disease, their interplay is complex and it remains incompletely understood which of these subsets significantly drive CLL progression. Here, we determined immunological profiles of 24 circulating T‐cell subsets from 79 untreated individuals by multiparametric flow cytometry. This screening cohort included healthy donors, patients with monoclonal B‐cell lymphocytosis (MBL), Rai 0 CLL and advanced CLL. We applied multidimensional scaling analysis as rigorous and unbiased statistical tool to globally assess the composition of the circulating T‐cell environment and to generate T‐cell scores reflecting its integrity. These scores allowed clear distinction between advanced CLL and healthy controls, whereas both MBL and Rai 0 CLL showed intermediate scores mirroring the biological continuum of CLL and its precursor stages. T‐cell stimulation and suppression assays as well as longitudinal T‐cell profiling showed an increasingly suppressive regulatory function initiating at the MBL stage. Effector function was impaired only after transition to CLL and partially recovered after chemoimmunotherapy. In an independent validation cohort of 52 untreated CLL cases, aberrant T‐cell profiles were significantly associated with shorter time to treatment independently of other prognostic parameters. Random forest modeling predicted regulatory T‐cell, gamma/delta and NKT‐cells, as well as exhaustion of the CD8+ subset as potential drivers of progression. Our data illustrate a pathological T‐cell environment in MBL that evolves toward a more and more suppressive and prognostically relevant profile across the disease stages.     

The neural mechanisms of affect infusion in social economic decision-making: a mediating role of the anterior insula

Though emotions have been shown to have sometimes dramatic effects on decision-making, the neural mechanisms mediating these biases are relatively unexplored. Here, we investigated how incidental affect (i.e. emotional states unrelated to the decision at hand) may influence decisions, and how these biases are implemented in the brain. Nineteen adult participants made decisions which involved accepting or rejecting monetary offers from others in an Ultimatum Game while undergoing functional magnetic resonance imaging (fMRI). Prior to each set of decisions, participants watched a short video clip aimed at inducing either a sad or neutral emotional state. Results demonstrated that, as expected, sad participants rejected more unfair offers than those in the neutral condition. Neuroimaging analyses revealed that receiving unfair offers while in a sad mood elicited activity in brain areas related to aversive emotional states and somatosensory integration (anterior insula) and to cognitive conflict (anterior cingulate cortex). Sad participants also showed a diminished sensitivity in neural regions associated with reward processing (ventral striatum). Importantly, insular activation uniquely mediated the relationship between sadness and decision bias. This study is the first to reveal how subtle mood states can be integrated at the neural level to influence decision-making.     

Variability in the Dynamics of Mortality and Immobility Responses of Freshwater Arthropods Exposed to Chlorpyrifos

The species sensitivity distribution (SSD) concept is an important probabilistic tool for environmental risk assessment (ERA) and accounts for differences in species sensitivity to different chemicals. The SSD model assumes that the sensitivity of the species included is randomly distributed. If this assumption is violated, indicator values, such as the 50% hazardous concentration, can potentially change dramatically. Fundamental research, however, has discovered and described specific mechanisms and factors influencing toxicity and sensitivity for several model species and chemical combinations. Further knowledge on how these mechanisms and factors relate to toxicologic standard end points would be beneficial for ERA. For instance, little is known about how the processes of toxicity relate to the dynamics of standard toxicity end points and how these may vary across species. In this article, we discuss the relevance of immobilization and mortality as end points for effects of the organophosphate insecticide chlorpyrifos on 14 freshwater arthropods in the context of ERA. For this, we compared the differences in response dynamics during 96 h of exposure with the two end points across species using dose response models and SSDs. The investigated freshwater arthropods vary less in their immobility than in their mortality response. However, differences in observed immobility and mortality were surprisingly large for some species even after 96 h of exposure. As expected immobility was consistently the more sensitive end point and less variable across the tested species and may therefore be considered as the relevant end point for population of SSDs and ERA, although an immobile animal may still potentially recover. This is even more relevant because an immobile animal is unlikely to survive for long periods under field conditions. This and other such considerations relevant to the decision-making process for a particular end point are discussed.     

Guideline for preventive child health care: 'Detection and referral criteria in short stature'

The main goal of this guideline for preventive child health care (PCHC) is to improve early detection of disorders that induce short stature. Based on research, evidence-based referral criteria for children aged 0-10 years with a short stature were formulated. These criteria are important for all professionals working with children, such as PCHC, general practitioners and paediatricians. Previous referral criteria dated 1997 and titled 'Diagnostics of short stature in children' had a very low specificity and were therefore considerably revised. They should no longer be applied. The guideline also provides information on the cause of short stature, psychosocial aspects and the use of growth hormone.