CT-gestützte Osteodensitometriezur Beurteilung der femoralen und periacetabulärenknöchernen Reaktion nach zementfreier Hüftendoprothetikmit schenkelhalserhaltendem Design

Aims Short stemed cementless femoral components in total hip arthroplasty have been designed to preserve proximal femoral bone stock by load transfer to the femoral metaphysis. We present an in-vivo method of computertomography-(CT-)assisted osteodensitometry after total hip arthroplasty that differentiates between cortical and cancellous bone density changes around uncemented femoral components. In a prospective study the cancellous and cortical periprosthetic femoral and acetabular bone reaction one and three years after cementless implanation of C.F.P.-stem and T.O.P.-press-fit cup in 31 patients (average age 59 years) were analysed using computed tomography assisted osteodensitometry. Aim of the study was to evaluate the fixation pattern of the cup and stem implant and to examine if the implant design leads to a more natural load transfer as posted by the manufacturer. Material and Methods Cortical and cancellous bone density were evaluated semiautomatically in the periacetabular region and automatically in the femoral region using CAPPA-Software tool (CAS-Innovations AG, Erlangen). An interobserver assessment was performed to validate the semiautomatic periacetabular analysis. The accuracy of measurement in the acetabular region is already proven [34]. Results The interobserver study could demonstrate a high reproducibility of cortical measurements in all areas and of cancellous measurements in the proximal region. In the diaphysial femoral region the accuracy of measurement was inacceptable concerning the cancellous bone. The femoral neck showed severe and progressive cortikal (-13% 1 year, -22% 3 years post-OP) and cancellous (-17% 1 year, -55% 3 years post-OP) bone density loss. Cortikal (-14% 1 year, -18% 3 years post-OP ) and cancellous (-30% 1 year, -32% 3 years post-OP) bone density loss was also found in the metaphysis of the femur but was non-proressive in this region. The whole diaphysial region showed no significant cortical bone density changes at all. Periacetabular bone density losses were mostly seen in the ventral (cancellous -35% 1 year, -39% 3 years post-OP; cortikal -8% 1 year, - 19% 3 years post-OP) and dorsal (cancellous – 34% 1 year, -40% 3 years post-OP; cortical – 8% 1 year, -16% 3 years post-OP) ROI; the changes proved to be progressive after three years. Only a moderate cancellous bone density loss was found in the cranial ROI (-18% 1 year, -22% 3 years post-OP), while cortical bone density remained stable. Clinical examination provided predominantly excellent (73%) and good (17%) results. No peri- or postoperative complcations had appeared. No revision surgery had been necessary. Conclusion The examined C.F.P.-Prothesis transfers the maximum load to the proximal diaphysial region of the femur in contrast to straigt stem protheses, whose distal-diaphysial fixation leads to atrophy in the proximal diaphysial portion of the femur. After implantation of the C.F.P. stem bone density remains stable in the whole of the diaphysis. However metaphysis and femoral neck do not receive an adequate mechanic stimulus, which results in marked bone density losses in these regions. Thus the implant design only leads to a more proximal, but not as aimed for, to metaphysial fixation. Aditionaly, the curved shape of the stem and the neckplate do not produce sufficient load transfer to the femoral neck to prevent it from atrophy. After implantation of the T.O.P. cup strains are mostly transmitted to the acetabular region cranial to the cup while ventral and dorsal regions experience a high degree of stress shielding. The focussing on cancellous bone as suggested by the name of the protheses (trabeculae oriented pattern) can not be affirmed. The periacetabular remodelling processes showed to be progressive during the first three postoperative years. Longterm studies will have to prove if further progression of cortical and cancellous bone density loss will take place and if this developement is of any clinical relevance at all.Hintergründe und Ziele Das Ziel der Implantation kurzschaftiger Hüftendoprothesen ist eine metaphysäre Kraftübertragung und somit der Erhalt des proximalen femoralen Knochens. Mittels Computertomographie-(CT)-gestützter Osteodensitometrie kann die periprothetische kortikale und spongiöse Knochendichte (KD) nach Implantation zementfreier Hüftendoprothesen in-vivo bestimmt werden. Im Rahmen einer prospektiven Studie wurden bei 31 Patienten (Durchschnittsalter 59 Jahre) mittels CT-gestützter Osteodensitometrie sowohl die spongiöse als auch die kortikale periprothetische Knochenreaktion femoral und acetabulär ein und drei Jahre nach zementfreier Implantation des Collum Femoris Preserving-(C.F.P.-) Schaftes und der Trabeculae Oriented Pattern- (T.O.P.-)Pfanne analysiert. Ziel der vorliegenden Arbeit war es hierbei, aus den gewonnenen Daten das Verankerungsmuster des Pfannen- und Schaftimplantates abzuleiten und zu untersuchen, ob die vom Hersteller durch das Implantatdesign angestrebte physiologischere Krafteinleitung tatsächlich erreicht wird. Methodik Die so gewonnenen Daten wurden mittels des CAPPA-Softwaretool (CAS-Innovations AG, Erlangen) im Bereich des Schaftes semiautomatisch und im Bereich der Pfanne manuell ausgewertet. Zur Beurteilung der Messpräzision der semiautomatischen Schaftauswertung wurde eine Interobserver-Pilotstudie durchgeführt. Daten zur Beurteilung der Messgenauigkeit im Bereich der Pfanne liegen bereits vor [34]. Ergebnisse Mittels der Pilotstudie konnte eine hohe Reproduzierbarkeit der Messungen der kortikalen Knochendichte in allen Bereichen sowie der spongiösen Knochendichte im proximalen Schaftbereich nachgewiesen werden. Lediglich im diaphysären Schaftbereich (Schicht 10-50 mm) war die Messgenauigkeit für den spongiösen Knochen nicht akzeptabel. Im Bereich des Schenkelhalses kam es zu deutlichen, im zeitlichen Verlauf progredienten kortikalen (-13% 1 Jahr, -22% 3 Jahre post-OP) und spongiösen (-17% 1 Jahr, -55% 3 Jahre post-OP) Knochendichteabnahmen. Auch im metaphysären Schaftbereich waren kortikale (-14% 1 Jahr, -18% 3 Jahre post-OP) und spongiöse (-30% 1 Jahr, -32% 3 Jahre post-OP) Dichteverluste nachzuweisen, die jedoch kaum Progredienz aufwiesen. Im Verlauf der gesamten Diaphyse hingegen blieb die kortikale Knochendichte ein und drei Jahre postoperativ im Vergleich zum Ausgangswert im Wesentlichen konstant. Der periacetabuläre Knochen wies vorwiegend in der ventralen und dorsalen Region of Interest (ROI) ausgeprägte spongiöse (-35%, bzw. -34% 1 Jahr, -39%, bzw. -40% 3 Jahre post-OP) und mäßige kortikale (je -8% 1 Jahr, -9%, bzw. -16% 3 Jahre post-OP) Dichteverluste auf, die nach drei Jahren ebenfalls zugenommen hatten. In der kranialen ROI war hingegen lediglich ein spongiöser (-18% 1 Jahr, -22% 3 Jahre post-OP) Dichterückgang zu verzeichnen, während kortikal kaum Veränderungen zu beobachten waren. Die klinische Untersuchung der Patienten ein und drei-Jahre postoperativ erbrachte überwiegend sehr gute (73%) und gute Ergebnisse (17%). Es waren weder peri- noch postoperative Komplikationen aufgetreten. In keinem Fall war eine Prothesenrevision nötig geworden. Schlussfolgerungen Der analysierte Hüftendoprothesenschaft verankert sich proximal-diaphysär. Er unterscheidet sich somit von geradschaftigen Prothesentypen, bei denen die distal-diaphysäre Krafteinleitung Atrophierungsvorgänge im proximalen diaphysären Schaftbereich nach sich zieht. Nach Implantation des C.F.P.-Schaftes bleibt die Knochendichte im gesamten diaphysären Bereich konstant. Metaphyse und Schenkelhals hingegen erfahren keine adäquate Belanspruchung, was hier zu deutlichen Knochendichteverlusten führt. Durch das Prothesendesign wird demnach lediglich eine proximalere, jedoch nicht wie angestrebt eine metaphysäre Verankerung erreicht. Auch kann durch die gebogene Schaftform und die Kragenplatte keine adäquate Beanspruchung des Schenkelhalses erreicht werden, die einer Knochendichteabnahme effizient entgegenwirken könnte. Nach Implantation der T.O.P.-Pfanne erfolgte die Kraftübertragung auf die acetabuläre Region kranial der Pfanne, während die Bereiche ventral und dorsal der Pfanne in hohem Maße von stress-shielding betroffen sind. Die durch den Namen der Prothese suggerierte Ausrichtung auf den spongiösen Knochen (Trabeculae Oriented Pattern) kann demnach nicht bestätigt werden. Die periacetabulären Knochenabbauvorgänge zeigen sich innerhalb der ersten drei postoperativen Jahre progredient. Inwieweit die kortikalen und spongiösen Knochendichteabnahmen weiterhin progredient sein werden und insbesondere ob dies überhaupt von klinischer Relevanz ist, werden Langzeitbeobachtungen zeigen müssen

Human hippocampal theta power indicates movement onset and distance travelled

Theta frequency oscillations in the 6- to 10-Hz range dominate the rodent hippocampal local field potential during translational movement, suggesting that theta encodes self-motion. Increases in theta power have also been identified in the human hippocampus during both real and virtual movement but appear as transient bursts in distinct high- and low-frequency bands, and it is not yet clear how these bursts relate to the sustained oscillation observed in rodents. Here, we examine depth electrode recordings from the temporal lobe of 13 presurgical epilepsy patients performing a selfpaced spatial memory task in a virtual environment. In contrast to previous studies, we focus on movement-onset periods that incorporate both initial acceleration and an immediately preceding stationary interval associated with prominent theta oscillations in the rodent hippocampal formation. We demonstrate that movementonset periods are associated with a significant increase in both low (2–5 Hz)- and high (6–9 Hz)-frequency theta power in the human hippocampus. Similar increases in low- and high-frequency theta power are seen across lateral temporal lobe recording sites and persist throughout the remainder of movement in both regions. In addition, we show that movement-related theta power is greater both before and during longer paths, directly implicating human hippocampal theta in the encoding of translational movement. These findings strengthen the connection between studies of theta-band activity in rodents and humans and offer additional insight into the neural mechanisms of spatial navigation

Spectral fingerprints or spectral tilt? Evidence for distinct oscillatory signatures of memory formation

Decreases in low-frequency power (2–30 Hz) alongside high-frequency power increases (>40 Hz) have been demonstrated to predict successful memory formation. Parsimoniously, this change in the frequency spectrum can be explained by one factor, a change in the tilt of the power spectrum (from steep to flat) indicating engaged brain regions. A competing view is that the change in the power spectrum contains several distinct brain oscillatory fingerprints, each serving different computations. Here, we contrast these two theories in a parallel magnetoencephalography (MEG)–intracranial electroencephalography (iEEG) study in which healthy participants and epilepsy patients, respectively, studied either familiar verbal material or unfamiliar faces. We investigated whether modulations in specific frequency bands can be dissociated in time and space and by experimental manipulation. Both MEG and iEEG data show that decreases in alpha/beta power specifically predicted the encoding of words but not faces, whereas increases in gamma power and decreases in theta power predicted memory formation irrespective of material. Critically, these different oscillatory signatures of memory encoding were evident in different brain regions. Moreover, high-frequency gamma power increases occurred significantly earlier compared to low-frequency theta power decreases. These results show that simple “spectral tilt” cannot explain common oscillatory changes and demonstrate that brain oscillations in different frequency bands serve different functions for memory encoding

Ovarian cancer symptom awareness and anticipated delayed presentation in a population sample

Background: While ovarian cancer is recognised as having identifiable early symptoms, understanding of the key determinants of symptom awareness and early presentation is limited. A population-based survey of ovarian cancer awareness and anticipated delayed presentation with symptoms was conducted as part of the International Cancer Benchmarking Partnership (ICBP). Methods: Women aged over 50 years were recruited using random probability sampling (n = 1043). Computer-assisted telephone interviews were used to administer measures including ovarian cancer symptom recognition, anticipated time to presentation with ovarian symptoms, health beliefs (perceived risk, perceived benefits/barriers to early presentation, confidence in symptom detection, ovarian cancer worry), and demographic variables. Logistic regression analysis was used to identify the contribution of independent variables to anticipated presentation (categorised as < 3 weeks or ≥ 3 weeks). Results: The most well-recognised symptoms of ovarian cancer were post-menopausal bleeding (87.4%), and persistent pelvic (79.0%) and abdominal (85.0%) pain. Symptoms associated with eating difficulties and changes in bladder/bowel habits were recognised by less than half the sample. Lower symptom awareness was significantly associated with older age (p ≤ 0.001), being single (p ≤ 0.001), lower education (p ≤ 0.01), and lack of personal experience of ovarian cancer (p ≤ 0.01). The odds of anticipating a delay in time to presentation of ≥ 3 weeks were significantly increased in women educated to degree level (OR = 2.64, 95% CI 1.61 – 4.33, p ≤ 0.001), women who reported more practical barriers (OR = 1.60, 95% CI 1.34 – 1.91, p ≤ 0.001) and more emotional barriers (OR = 1.21, 95% CI 1.06 – 1.40, p ≤ 0.01), and those less confident in symptom detection (OR = 0.56, 95% CI 0.42 – 0.73, p ≤ 0.001), but not in those who reported lower symptom awareness (OR = 0.99, 95% CI 0.91 – 1.07, p = 0.74). Conclusions: Many symptoms of ovarian cancer are not well-recognised by women in the general population. Evidence-based interventions are needed not only to improve public awareness but also to overcome the barriers to recognising and acting on ovarian symptoms, if delays in presentation are to be minimised

Trends in the neurological emergency room, focusing on persons with seizures

Background and purpose Previous studies in neurological emergency rooms (nERs) have reported many non‐acute, self‐presenting patients, patients with delayed presentation of stroke, and frequent visits of persons with seizures (PWS). The aim of this study was to evaluate trends during the last decade, with special focus on PWS. Methods We retrospectively analyzed patients who presented to our specialized nER during the course of 5 months in 2017 and 2019, and included information on admission/referral, hospitalization, discharge diagnosis, and diagnostic tests/treatment in the nER. Results A total of 2791 patients (46.6% male, mean age 57 ± 21 years) were included. The most common diagnoses were cerebrovascular events (26.3%), headache (14.1%), and seizures (10.5%). Most patients presented with symptoms lasting &gt;48 h (41.3%). The PWS group included the largest proportion of patients presenting within 4.5 h of symptom onset (171/293, 58.4%), whereas only 37.1% of stroke patients presented within this time frame (273/735). Self‐presentation was the most common admission pathway (31.1%), followed by emergency service referral (30.4%, including the majority of PWS: 197/293, 67.2%). Despite known diagnosis of epilepsy in 49.2%, PWS more often underwent accessory diagnostic testing including cerebral imaging, compared to the overall cohort (accessory diagnostics 93.9% vs. 85.4%; cerebral imaging 70.1% vs. 64.1%). Electroencephalography in the nER was only performed in 20/111 patients (18.0%) with a first seizure. Nearly half of the patients (46.7%) were discharged home after nER work‐up, including most self‐presenters (632/869, 72.7%) and headache patients (377/393, 88.3%), as well as 37.2% (109/293) of PWS. Conclusion After 10 years, nER overuse remains a problem. Stroke patients still do not present early enough, whereas PWS, even those with known epilepsy, often seek acute and extensive assessment, indicating gaps in pre‐hospital management and possible over‐assessment. </sec

Data-driven re-referencing of intracranial EEG based on independent component analysis (ICA)

Background: Intracranial recordings from patients implanted with depth electrodes are a valuable source of information in neuroscience. They allow for the unique opportunity to record brain activity with high spatial and temporal resolution. A common pre-processing choice in stereotactic EEG (S-EEG) is to re-reference the data with a bipolar montage. In this, each channel is subtracted from its neighbor, to reduce commonalities between channels and isolate activity that is spatially confined. New Method: We challenge the assumption that bipolar reference effectively performs this task. To extract local activity, the distribution of the signal source of interest, interfering distant signals, and noise need to be considered. Referencing schemes with fixed coefficients can decrease the signal to noise ratio (SNR) of the data, they can lead to mislocalization of activity and consequently to misinterpretation of results. We propose to use Independent Component Analysis (ICA), to derive filter coefficients that reflect the statistical dependencies of the data at hand. Results: We describe and demonstrate this on human S-EEG recordings. In a simulation with real data, we quantitatively show that ICA outperforms the bipolar referencing operation in sensitivity and importantly in specificity when revealing local time series from the superposition of neighboring channels. Comparison with Existing Method: We argue that ICA already performs the same task that bipolar referencing pursues, namely undoing the linear superposition of activity and will identify activity that is local. Conclusions: When investigating local sources in human S-EEG, ICA should be preferred over re-referencing the data with a bipolar montage

Quantitative EEG may predict weaning failure in ventilated patients on the neurological intensive care unit

Neurocritical patients suffer from a substantial risk of extubation failure. The aim of this prospective study was to analyze if quantitative EEG (qEEG) monitoring is able to predict successful extubation in these patients. We analyzed EEG-monitoring for at least six hours before extubation in patients receiving mechanical ventilation (MV) on our neurological intensive care unit (NICU) between November 2017 and May 2019. Patients were divided in 2 groups: patients with successful extubation (SE) versus patients with complications after MV withdrawal (failed extubation; FE), including reintubation, need for non-invasive ventilation (NIV) or death. Bipolar six channel EEG was applied. Unselected raw EEG signal underwent automated artefact rejection and Short Time Fast Fourier Transformation. The following relative proportions of global EEG spectrum were analyzed: relative beta (RB), alpha (RA), theta (RT), delta (RD) as well as the alpha delta ratio (ADR). Coefficient of variation (CV) was calculated as a measure of fluctuations in the different power bands. Mann–Whitney U test and logistic regression were applied to analyze group differences. 52 patients were included (26 male, mean age 65 ± 17 years, diagnosis: 40% seizures/status epilepticus, 37% ischemia, 13% intracranial hemorrhage, 10% others). Successful extubation was possible in 40 patients (77%), reintubation was necessary in 6 patients (12%), 5 patients (10%) required NIV, one patient died. In contrast to FE patients, SE patients showed more stable EEG power values (lower CV) considering all EEG channels (RB: p < 0.0005; RA: p = 0.045; RT: p = 0.045) with RB as an independent predictor of weaning success in logistic regression (p = 0.004). The proportion of the EEG frequency bands (RB, RA RT, RD) of the entire EEG power spectrum was not significantly different between SE and FE patients. Higher fluctuations in qEEG frequency bands, reflecting greater fluctuation in alertness, during the hours before cessation of MV were associated with a higher rate of complications after extubation in this cohort. The stability of qEEG power values may represent a non-invasive, examiner-independent parameter to facilitate weaning assessment in neurocritical patients

Hippocampal neurons code individual episodic memories in humans

The hippocampus is an essential hub for episodic memory processing. However, how human hippocampal single neurons code multi-element associations remains unknown. In particular, it is debated whether each hippocampal neuron represents an invariant element within an episode or whether single neurons bind together all the elements of a discrete episodic memory. Here we provide evidence for the latter hypothesis. Using single-neuron recordings from a total of 30 participants, we show that individual neurons, which we term episode-specific neurons, code discrete episodic memories using either a rate code or a temporal firing code. These neurons were observed exclusively in the hippocampus. Importantly, these episode-specific neurons do not reflect the coding of a particular element in the episode (that is, concept or time). Instead, they code for the conjunction of the different elements that make up the episode

A scoping study of interventions to increase the uptake of physical activity (PA) amongst individuals with mild-to-moderate depression (MMD)

Background - Depression is the largest contributor to disease burden globally. The evidence favouring physical activity as a treatment for mild-to-moderate depression is extensive and relatively uncontested. It is unclear, however, how to increase an uptake of physical activity amongst individuals experiencing mild-to-moderate depression. This leaves professionals with no guidance on how to help people experiencing mild-to-moderate depression to take up physical activity. The purpose of this study was to scope the evidence on interventions to increase the uptake of physical activity amongst individuals experiencing mild-to-moderate depression, and to develop a model of the mechanisms by which they are hypothesised to work. Methods - A scoping study was designed to include a review of primary studies, grey literature and six consultation exercises; two with individuals with experience of depression, two pre-project consultations with physical activity, mental health and literature review experts, one with public health experts, and one with community engagement experts. Results - Ten papers met the inclusion criteria and were included in the review. Consultation exercises provided insights into the mechanisms of an uptake of physical activity amongst individuals experiencing mild-to-moderate depression; evidence concerning those mechanisms is (a) fragmented in terms of design and purpose; (b) of varied quality; (c) rarely explicit about the mechanisms through which the interventions are thought to work. Physical, environmental and social factors that may represent mediating variables in the uptake of physical activity amongst people experiencing mild-to-moderate depression are largely absent from studies. Conclusions - An explanatory model was developed. This represents mild-to-moderate depression as interfering with (a) the motivation to take part in physical activity and (b) the volition that it is required to take part in physical activity. Therefore, both motivational and volitional elements are important in any intervention to increase physical activity in people with mild-to-moderate depression. Furthermore, mild-to-moderate depression-specific factors need to be tackled in any physical activity initiative, via psychological treatments such as Cognitive Behavioural Therapy. We argu

Tracking cell turnover in human brain using 15N-thymidine imaging mass spectrometry

Microcephaly is often caused by an impairment of the generation of neurons in the brain, a process referred to as neurogenesis. While most neurogenesis in mammals occurs during brain development, it thought to continue to take place through adulthood in selected regions of the mammalian brain, notably the hippocampus. However, the generality of neurogenesis in the adult brain has been controversial. While studies in mice and rats have provided compelling evidence for neurogenesis occurring in the adult rodent hippocampus, the lack of applicability in humans of key methods to demonstrate neurogenesis has led to an intense debate about the existence and, in particular, the magnitude of neurogenesis in the adult human brain. Here, we demonstrate the applicability of a powerful method to address this debate, that is, the in vivo labeling of adult human patients with 15N-thymidine, a non-hazardous form of thymidine, an approach without any clinical harm or ethical concerns. 15N-thymidine incorporation into newly synthesized DNA of specific cells was quantified at the single-cell level with subcellular resolution by Multiple-isotype imaging mass spectrometry (MIMS) of brain tissue resected for medical reasons. Two adult human patients, a glioblastoma patient and a patient with drug-refractory right temporal lobe epilepsy, were infused for 24 h with 15N-thymidine. Detection of 15N-positive leukocyte nuclei in blood samples from these patients confirmed previous findings by others and demonstrated the appropriateness of this approach to search for the generation of new cells in the adult human brain. 15N-positive neural cells were easily identified in the glioblastoma tissue sample, and the range of the 15N signal suggested that cells that underwent S-phase fully or partially during the 24 h in vivo labeling period, as well as cells generated therefrom, were detected. In contrast, within the hippocampus tissue resected from the epilepsy patient, none of the 2,000 dentate gyrus neurons analyzed was positive for 15N-thymidine uptake, consistent with the notion that the rate of neurogenesis in the adult human hippocampus is rather low. Of note, the likelihood of detecting neurogenesis was reduced because of (i) the low number of cells analyzed, (ii) the fact that hippocampal tissue was explored that may have had reduced neurogenesis due to epilepsy, and (iii) the labeling period of 24 h which may have been too short to capture quiescent neural stem cells. Yet, overall, our approach to enrich NeuN-labeled neuronal nuclei by FACS prior to MIMS analysis provides a promising strategy to quantify even low rates of neurogenesis in the adult human hippocampus after in vivo15N-thymidine infusion. From a general point of view and regarding future perspectives, the in vivo labeling of humans with 15N-thymidine followed by MIMS analysis of brain tissue constitutes a novel approach to study mitotically active cells and their progeny in the brain, and thus allows a broad spectrum of studies of brain physiology and pathology, including microcephaly