Perioperative multi-system optimization protocol in elderly hip fracture patients: a randomized-controlled trial.

PURPOSE: Hip fractures in elderly patients are associated with increased postoperative morbidity and mortality. We evaluated whether a perioperative multi-system optimization protocol can reduce postoperative complications in these patients. METHODS: Immediately after diagnosis of hip fracture, patients ≥ 60 yr were randomized to an intervention or control group. Patients in the intervention group were admitted to our postanesthesia care unit where they were treated with goal-directed hemodynamic management, optimized pain therapy, oxygen therapy, and optimized nutrition. Patients in the control group were managed according to our usual standard of care on a regular ward. Postoperative complications during hospital stay included pre-determined cardiovascular, respiratory, neurologic, renal, or surgical events. RESULTS: The incidence of at least one postoperative complication (primary outcome) was seen in 32 of 65 (49%) controls compared with 24 of 62 (39%) in the intervention group (relative risk [RR], 0.79; 95% confidence interval [CI], 0.53 to 1.17; P = 0.23). The secondary unadjusted outcomes showed that patients in the intervention group received more Ringer's acetate compared with controls (median difference, 1.3 L; 95% CI, 0.6 to 2.1 L; P < 0.001), had more frequently a mean arterial pressure > 70 mmHg (57% control vs 75% intervention; median percentage difference, 16%; 95% CI, 7 to 25%; P = 0.001), better pain control (numeric rating scale < 4 at all postoperative measurements; 25% control vs 81% intervention; RR, 0.26; 95% CI, 0.15 to 0.43; P < 0.001), and possibly a lower incidence of acute renal failure (RR, 0.37; 95% CI, 0.14 to 0.98; P = 0.04). CONCLUSIONS: The implementation of a perioperative multi-system optimization protocol algorithm did not significantly reduce the risk of postoperative complications. Nevertheless, we likely over-estimated the potential treatment effect in our study design and thus were under-powered to show an effect. TRIAL REGISTRATION: Clinicaltrials.gov (NCT01673776). Registered 23 August, 2012.

Oligodendrocytes in mouse corpus callosum are coupled via gap junction channels formed by connexin47 and connexin32.

According to previously published ultrastructural studies, oligodendrocytes in white matter exhibit gap junctions with astrocytes, but not among each other, while in vitro oligodendrocytes form functional gap junctions. We have studied functional coupling among oligodendrocytes in acute slices of postnatal mouse corpus callosum. By whole-cell patch clamp we dialyzed oligodendrocytes with biocytin, a gap junction-permeable tracer. On average 61 cells were positive for biocytin detected by labeling with streptavidin-Cy3. About 77% of the coupled cells stained positively for the oligodendrocyte marker protein CNPase, 9% for the astrocyte marker GFAP and 14% were negative for both CNPase and GFAP. In the latter population, the majority expressed Olig2 and some NG2, markers for oligodendrocyte precursors. Oligodendrocytes are known to express Cx47, Cx32 and Cx29, astrocytes Cx43 and Cx30. In Cx47-deficient mice, the number of coupled cells was reduced by 80%. Deletion of Cx32 or Cx29 alone did not significantly reduce the number of coupled cells, but coupling was absent in Cx32/Cx47-double-deficient mice. Cx47-ablation completely abolished coupling of oligodendrocytes to astrocytes. In Cx43-deficient animals, oligodendrocyte-astrocyte coupling was still present, but coupling to oligodendrocyte precursors was not observed. In Cx43/Cx30-double deficient mice, oligodendrocyte-to-astrocyte coupling was almost absent. Uncoupled oligodendrocytes showed a higher input resistance. We conclude that oligodendrocytes in white matter form a functional syncytium predominantly among each other dependent on Cx47 and Cx32 expression, while astrocytic connexins expression can promote the size of this network.

Ticagrelor and Rivaroxaban Elimination With CytoSorb Adsorber Before Urgent Off-Pump Coronary Bypass.

CytoSorb hemoadsorption (CytoSorbents Inc, Monmouth Junction, NJ) was performed shortly before an urgent off-pump coronary artery bypass operation in a 58-year-old man at high risk of bleeding as a result of treatment of coronary artery disease with ticagrelor and treatment of atrial fibrillation with rivaroxaban. The patient experienced dissection of the left anterior descending artery during a percutaneous coronary intervention. Preoperatively, CytoSorb hemoadsorption was applied to eliminate the coagulative active medications. His intraoperative and postoperative courses were uneventful, with adequate bleeding control. This case highlights a promising approach for managing antiplatelet drugs and anticoagulant agents such as ticagrelor and rivaroxaban before off-pump coronary artery bypass.

Astrocytes discriminate and selectively respond to the activity of a subpopulation of neurons within the barrel cortex.

Sensory information from single whiskers in rodents projects to defined morphological units in the cortex, the barrels. We found that astrocytes selectively respond with an increase in the cytosolic Ca(2+) concentration to activation of layer 4 neurons, the input cells of the barrel columns. The neuronal Ca(2+) signal also spread across barrel column borders mainly in layer 2/3, but the glutamate-mediated astrocyte response stayed restricted to the barrel column. In contrast, when interfering with inhibitory pathways by blocking either purinergic, adenosine or gamma-aminobutyric acid(A) receptors, the stimulation activated a Ca(2+) response in a much larger astrocyte population no longer restricted to the borders of the barrel column. We also observed spontaneous and evoked Ca(2+) activity in the synaptic target cells of layer 4 neurons, the layer 2/3 pyramidal cells, but again, we never recorded Ca(2+) responses in astrocytes following activity in this neuronal population. Our data show that astrocytes can discriminate and selectively respond to the activity of a subpopulation of excitatory neurons within a given brain region. This selectivity in the astrocyte response describes a new level of complexity and integration in the reaction of astrocytes to neuronal activity.

Store-operated Ca2+ entry in astrocytes: different spatial arrangement of endoplasmic reticulum explains functional diversity in vitro and in situ.

Ca(2+) signaling is the astrocyte form of excitability and the endoplasmic reticulum (ER) plays an important role as an intracellular Ca(2+) store. Since the subcellular distribution of the ER influences Ca(2+) signaling, we compared the arrangement of ER in astrocytes of hippocampus tissue and astrocytes in cell culture by electron microscopy. While the ER was usually located in close apposition to the plasma membrane in astrocytes in situ, the ER in cultured astrocytes was close to the nuclear membrane. Activation of metabotropic receptors linked to release of Ca(2+) from ER stores triggered distinct responses in cultured and in situ astrocytes. In culture, Ca(2+) signals were commonly first recorded close to the nucleus and with a delay at peripheral regions of the cells. Store-operated Ca(2+) entry (SOC) as a route to refill the Ca(2+) stores could be easily identified in cultured astrocytes as the Zn(2+)-sensitive component of the Ca(2+) signal. In contrast, such a Zn(2+)-sensitive component was not recorded in astrocytes from hippocampal slices despite of evidence for SOC. Our data indicate that both, astrocytes in situ and in vitro express SOC necessary to refill stores, but that a SOC-related signal is not recorded in the cytoplasm of astrocytes in situ since the stores are close to the plasma membrane and the refill does not affect cytoplasmic Ca(2+) levels.

Technology for home dementia care: A prototype locating system put to the test.

INTRODUCTION: The user experience of persons with dementia and their primary caregivers with locating systems is not firmly established. METHODS: Eighteen dyads used a prototype locating system during 4 weeks. Primary outcome measures were ratings of usability, and product functions and features. Secondary outcome measures were caregiver burden, perceived self-efficacy, frequency of use, and willingness to purchase the prototype. Changes in scores between baseline (T1) and end of testing period (T2) were compared by performing independent and dependent samples correlations and descriptive statistics. RESULTS: Seventeen dyads made up the final sample. Ratings of usability and product functions and features were fair, but usability ratings were significantly reduced after 4 weeks. Although the prototype was used infrequently by majority of the participants, most caregivers would be willing to purchase the prototype, with men more willing than women. No significant change in technological willingness, caregiver burden, or perceived self-efficacy was found between T1 and T2. Perceived self-efficacy significantly negatively correlated with willingness to purchase the prototype after 4 weeks. DISCUSSION: Results highlight the importance of including end users in the research and development phase of locating systems to improve the user experience in home dementia care. Necessary indications for further research are carrying out randomized controlled trials with larger, more representative samples and developing innovative software and hardware solutions.

Correlation of florbetaben PET imaging and the amyloid peptide Aß42 in cerebrospinal fluid.

Today, the use of biomarkers such as amyloid-specific positron emission tomography (PET) tracers and information derived from cerebrospinal fluid (CSF) can support the diagnosis of Alzheimer's disease (AD) as an indicator for the presence of amyloid pathology. We here show that the PET signal of the 18F-labelled tracer florbetaben (NeuraCeq™), that binds to amyloid-beta plaques, inversely correlates with CSF levels of Aß42, another biomarker for AD. Results from the two biomarkers were concordant in 35 out of 38 subjects. In 7 AD subjects (20%) at least one biomarker was inconsistent with the clinical diagnosis. This confirms known limitations of the clinical AD diagnosis and highlights the potential of biomarker-assisted diagnosis to improve accuracy.

Astrocyte function is modified by Alzheimer's disease-like pathology in aged mice.

Alzheimer's disease (AD) may affect all cell types in the central nervous system. Astrocytes have rarely been investigated in the aged brain and the role of astrocytes in AD is poorly understood. In this study, we used acute brain slices from an amyloid-beta overexpressing double transgenic mouse line where astrocytes express the enhanced green fluorescent protein under the control of the glial fibrillary acidic protein promoter. Using the patch-clamp technique, we analyzed cell coupling and glutamate reactivity, two main features of astrocytes, in the living tissue of aged mice in an AD mouse model. We found large astrocytic networks in the aged (20 to 27 months) transgenic animals in the neocortex, but not in the hippocampus. In contrast, coupling was low in all brain regions of aged control mice. We furthermore noticed significant changes in the responses of astrocytes to glutamate. The expression of functional glutamate transporters and AMPA/kainate-type glutamate receptors increases in the amyloid-beta protein precursor overexpressing mice. Thus, exposure to amyloid-beta leads to altered astrocyte properties and this change might be beneficial to maintain synaptic function.

Activity-dependent ATP-waves in the mouse neocortex are independent from astrocytic calcium waves.

In the corpus callosum, astrocytic calcium waves propagate via a mechanism involving ATP-release but not gap junctional coupling. In the present study, we report for the neocortex that calcium wave propagation depends on functional astrocytic gap junctions but is still accompanied by ATP-release. In acute slices obtained from the neocortex of mice deficient for astrocytic expression of connexin43, the calcium wave did not propagate. In contrast, in the corpus callosum and hippocampus of these mice, the wave propagated as in control animals. In addition to calcium wave propagation in astrocytes, ATP-release was recorded as a calcium signal from 'sniffer cells', a cell line expressing high-affinity purinergic receptors placed on the surface of the slice. The astrocyte calcium wave in the neocortex was accompanied by calcium signals in the 'sniffer cell' population. In the connexin43-deficient mice we recorded calcium signals from sniffer cells also in the absence of an astrocytic calcium wave. Our findings indicate that astrocytes propagate calcium signals by two separate mechanisms depending on the brain region and that ATP release can propagate within the neocortex independent from calcium waves.

Effects of subtotal fasting on plasmatic coagulation, fibrinolytic status and platelet activation: a controlled pilot study in healthy subjects.

BACKGROUND AND AIM: There is considerable controversy as to whether fasting can be recommended to patients with cardiovascular disease. The objective of this study was to determine whether a well-known method of 1-week subtotal fasting affects hemostasis in healthy subjects. METHODS AND RESULTS: Analyses were carried out before, four times during and 3 days after fasting in 12 fasting subjects (< 300 kcal/day, only from carbohydrates) (group 1), and 8 control subjects (group 2). Plasmatic coagulation (prothrombin time, partial thromboplastin time, p < or = 0.001) and fibrinolysis (plasminogen, plasmin-antiplasmin-complex, p < 0.05) increased during fasting but remained within the normal limits. While the platelet count was similar in both groups, platelet sensitivity to stimulators was reduced in group 1 (P-selectin and activated GP IIb/IIIa on ADP-stimulated platelets, p < or = 0.01). Furthermore, soluble P-selectin (p < or = 0.01) and C-reactive protein were decreased in comparison to group 2 (p < or = 0.05). CONCLUSIONS: Hemostasis and inflammation parameters during 1-week subtotal fasting do not imply an increase in cardiovascular risk.