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BACKGROUND: Compared to an endotracheal tube, laryngeal mask airways are known to cause less hemodynamic alteration during the extubation phase of routine perioperative airway management. This study aims to examine the hypothesis that the LMA-ProSeal (PLMA, The Laryngeal Mask Company Limited, St. Helier, Jersey, Channel Islands) is an adequate tool for elective postoperative care in the intensive care unit (ICU) and potentially associated with less hemodynamic alteration during extubation in the ICU environment compared to an endotracheal tube. METHODS: Forty-eight patients were enrolled for this prospective randomized, controlled trial and were allocated to either control (ICU-T) or study group (ICU-P). In the ICU-P group, the endotracheal tube was replaced by a PLMA at the end of surgery. RESULTS: Forty-patients completed the study. Cardiovascular parameters increased significantly less in the ICU-P group: systolic blood pressure increased by 18.10 +/- 5.57 mmHg versus 34.65 +/- 5.63 mmHg (P < 0.05), mean arterial blood pressure increased by 11.23 +/- 3.25 mmHg versus 22.65 +/- 3.36 mmHg (P < 0.05), and heart rate increased by 9.3 +/- 2.9 versus 12.9 +/- 2.2 min (P < 0.05). Ventilation via the PLMA during transfer from the operation room to the ICU as well as during ICU stay was successful and without any adverse events. CONCLUSIONS: Removal of the PLMA after recovery from anesthesia was associated with less cardiovascular change compared to the endotracheal tube. Ventilation was possible without reported adverse events during the entire trial. Elective endotracheal tube replacement by the PLMA may be a useful procedure in selected patients. [ABSTRACT FROM AUTHOR]

Background: ANCA-associated vasculitis is an organ and life-threatening disease with the highest incidence in elderly patients. However, few studies have focussed on characteristics and treatment outcomes in a direct comparison of elderly and younger patients., Methods: In a retrospective, single-centre, renal biopsy-cohort, patients were dichotomized by age ≥ 65 years to analyse baseline clinical, histological, laboratory and immunological characteristics and outcome differences in elderly and younger patients as regard to mortality, renal recovery from dialysis and eGFR after two years., Results: In the biopsy registry, n = 774 patients were identified, of whom 268 were ≥ 65 years old. Among them, ANCA-associated vasculitis was the most prevalent kidney disease (n = 54 ≈ 20%). After a follow-up of 2 years, overall mortality was 13.4%, with 19% and 4% in patients ≥ and < 65 years of age, respectively. While 41% of elderly and 25% of younger patients were dialysis-dependent at the time of biopsy, renal recovery was achieved in 41% and 57% of patients, respectively. The accuracy of prediction differed significantly between the whole cohort and elderly patients as regard to mortality (sensitivity 46% vs. 90%, respectively) and between younger and elderly patients as regard to eGFR (r 2  = 0.7 vs. 0.46, respectively). Age-group-wise analysis revealed patients above 80 years of age to have particularly dismal renal outcome and survival., Conclusion: In our cohort, ANCA-associated vasculitis is the single most frequent histopathological diagnosis among the elderly patients in our cohort. Elderly and younger patients have comparable chances of recovering from dialysis-dependent renal failure, with comparable residual independent kidney function after two years. This study suggests (1) relevant predictors differ between age groups and hence (2) models involving all patients with ANCA-associated vasculitis neglect important features of vulnerable subgroups, i.e., patients above 80 years old., (© 2023. The Author(s).)

Introduction: Acute antibody-mediated rejection (ABMR) is an important threat to renal allograft survival in the early transplant period and the major single cause of graft loss in the first postoperative year. Semi-selective immunoadsorption (IA) remains one of the commonly applied treatments in ABMR, reducing allo-reactive antibody load. Adding double filtration plasmapheresis (DFPP) to IA might enhance therapeutic efficacy by also addressing innate humoral effectors like complement factors., Methods: Four patients with ABMR were treated with DFPP + IA. Clinical, histological, and immunological data and adverse events were retrospectively collected., Results: Here we present four high-risk treatment-refractory ABMR cases with C1q-binding donor-specific antibodies and histology of humoral rejection under treatment with DFPP + IA. While the earlier cases (within the first year after transplantation) showed marked reduction in ABMR severity and improvement of kidney function, the later cases did not respond accordingly. Late ABMR patient 1 stabilized, whereas late ABMR patient 2 did not respond to treatment., Conclusions: Our data support the consideration of DFPP + IA as a rescue treatment option in early, severe, high-risk ABMR cases in which other treatments failed., (© 2023 The Author(s). Published by S. Karger AG, Basel.)

Background: Attentional deficits in patients with chronic pain are common and well studied. Yet, few studies have examined the effects of chronic pain on more complex cognitive abilities that rely on well-functioning attentional systems. With the current study, we aimed to investigate whether the impact of chronic pain on attention affects creative ideation as measured with an adaptation of the alternate uses task (AUT)., Methods: Performance in the AUT was compared between 33 patients suffering from chronic pain and 33 healthy matched controls. While solving the task, EEG was recorded to measure the degree of internally directed attention assessed by means of task-related power (TRP) changes., Results: The results revealed that patients with chronic pain generated less creative ideas than healthy controls. This lack of performance was accompanied by lower event-related synchronization (ERS), especially in right parietal sites. Furthermore, these ERS differences explained one-third of the inter-group variance in AUT performance., Conclusions: These results suggest that performance decrements in creative ideation in patients with chronic pain may be at least partly attributable to attentional impairments associated with chronic pain., Significance: Chronic pain negatively affects attention and more complex cognitive abilities. However, the underlying psychophysiological mechanisms and the role of attention as a source of these impairments in more complex abilities are poorly understood. By analyzing task-related power changes in the EEG, the role of internal attention in creative ideation could be determined, revealing the functional relationship between chronic pain, attention, and a more complex cognitive ability., (© 2022 The Authors. European Journal of Pain published by John Wiley & Sons Ltd on behalf of European Pain Federation - EFIC ®.)

Although the interrupting effect of chronic pain on voluntary-directed attention is well-documented, research on the impact of chronic pain on involuntary-directed attention remains incomplete. This study aimed to investigate the influence of chronic pain on involuntary as well as voluntary allocation of attention as, respectively, indexed by the P3a and P3b components in the event-related potential derived from the electroencephalogram. Both involuntary and voluntary captures of attention were compared between 33 patients with chronic pain and 33 healthy controls using an auditory three-stimulus oddball task (with standard, target, and unexpected distractor tones). The results revealed a reduced P3a amplitude as well as a reduced P3b amplitude in patients with chronic pain compared to healthy controls, indicating a detrimental effect of chronic pain on involuntary and voluntary attention, respectively. This study extends the picture of the impairing effects of chronic pain on attentional allocation to a current task and attentional allocation to information outside the focus of attention. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Cryo-electron tomography (cryo-ET) is a groundbreaking technology for 3D visualisation and analysis of biomolecules in the context of cellular structures. It allows structural investigations of single proteins as well as their spatial arrangements within the cell. Cryo-tomograms provide a snapshot of the complex, heterogeneous and transient subcellular environment. Due to the excellent structure preservation in amorphous ice, it is possible to study interactions and spatial relationships of proteins in their native state without interference caused by chemical fixatives or contrasting agents. With the introduction of focused ion beam (FIB) technology, the preparation of cellular samples for electron tomography has become much easier and faster. The latest generation of integrated FIB and scanning electron microscopy (SEM) instruments (dual beam microscopes), specifically designed for cryo-applications, provides advances in automation, imaging and the preparation of high-pressure frozen bulk samples using cryo-lift-out technology. In addition, correlative cryo-fluorescence microscopy provides cellular targeting information through integrated software and hardware interfaces. The rapid advances, based on the combination of correlative cryo-microscopy, cryo-FIB and cryo-ET, have already led to a wealth of new insights into cellular processes and provided new 3D image data of the cell. Here we introduce our recent developments within the cryo-tomography workflow, and we discuss the challenges that lie ahead. LAY DESCRIPTION: This article describes our recent developments for the cryo-electron tomography (cryo-ET) workflow. Cryo-ET offers superior structural preservation and provides 3D snapshots of the interior of vitrified cells at molecular resolution. Before a cellular sample can be imaged by cryo-ET, it must be made accessible for transmission electron microscopy. This is achieved by preparing a 200-300 nm thin cryo-lamella from the cellular sample using a cryo-focused ion beam (cryo-FIB) microscope. Cryo-correlative light and electron microscopy (cryo-CLEM) is used within the workflow to guide the cryo-lamella preparation to the cellular areas of interest. We cover a basic introduction of the cryo-ET workflow and show new developments for cryo-CLEM, which facilitate the connection between the cryo-light microscope and the cryo-FIB. Next, we present our progress in cryo-FIB software automation to streamline cryo-lamella preparation. In the final section we demonstrate how the cryo-FIB can be used for 3D imaging and how bulk-frozen cellular samples (obtained by high-pressure freezing) can be processed using the newly developed cryo-lift-out technology., (© 2020 The Authors. Journal of Microscopy published by John Wiley & Sons Ltd on behalf of Royal Microscopical Society.)

Background: Calciphylaxis is a life threatening complication in renal patients. Of great importance is the identification of concomitant factors for calciphylaxis. Due to the variability of clinical presentation the evaluation of such factors may be obscured when calciphylaxis diagnosis is based just on clinical features. We aimed to characterize associated factors only in patients with calciphylaxis proven by histomorphological parameters in addition to clinical presentation., Methods: In a single center retrospective study we analyzed 15 patients in an 8 year period from 2008 to 2016. Only patients with clinical features and histomorphological proof of calciphylaxis were included. Criteria for histological diagnosis of calciphylaxis were intimal hyperplasia, micro thrombi or von Kossa stain positive media calcification., Results: The mean age of patients was 64.8 years. Nine patients (60%) were female; 12 (80%) were obese with a Body-Mass-Index (BMI) > 30 kg/m 2 ; 3 (20%) had no renal disease; 12 (80%) had CKD 4 or 5 and 10 (66.7%) had end-stage renal disease (ESRD). One-year mortality in the entire cohort was 73.3%. With respect to medication history, the majority of patients (n = 13 (86.7%)) received vitamin K antagonists (VKA); 10 (66.7%) were treated with vitamin D; 6 (40%) had oral calcium supplementation; 5 (33.3%) had been treated with corticosteroids; 12 (80%) were on proton pump inhibitors (PPI); 13 (86.7%) patients had a clinical proven hyperparathyroidism. Ten (66.7%) patients presented with hypoalbuminemia at diagnosis., Conclusions: The evaluation of biopsy proven calciphylaxis demonstrates that especially treatment with vitamin K antagonists and liver dysfunction are most important concomitant factors in development of calciphylaxis. As progression and development of calciphylaxis are chronic rather than acute processes, early use of DOACs instead of VKA might be beneficial and reduce the incidence of calciphylaxis.

Oligodendrocytes make myelin and support axons metabolically with lactate. However, it is unknown how glucose utilization and glycolysis are adapted to the different axonal energy demands. Spiking axons release glutamate and oligodendrocytes express NMDA receptors of unknown function. Here we show that the stimulation of oligodendroglial NMDA receptors mobilizes glucose transporter GLUT1, leading to its incorporation into the myelin compartment in vivo. When myelinated optic nerves from conditional NMDA receptor mutants are challenged with transient oxygen-glucose deprivation, they show a reduced functional recovery when returned to oxygen-glucose but are indistinguishable from wild-type when provided with oxygen-lactate. Moreover, the functional integrity of isolated optic nerves, which are electrically silent, is extended by preincubation with NMDA, mimicking axonal activity, and shortened by NMDA receptor blockers. This reveals a novel aspect of neuronal energy metabolism in which activity-dependent glutamate release enhances oligodendroglial glucose uptake and glycolytic support of fast spiking axons., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Objective: Cryopyrin-associated periodic syndrome (CAPS) is a heterogeneous group of diseases characterized by excessive IL-1β release resulting in severe systemic and organ inflammation. Canakinumab targets IL-1β and is approved at standard dose for children and adults with all CAPS phenotypes. Limited data are available for the real-life effectiveness of canakinumab in patients living with CAPS. Therefore the aim of the study was to evaluate the real-life dosing and effectiveness of canakinumab in CAPS., Methods: A multi-centre study of consecutive children and adults with CAPS treated with canakinumab was performed. Demographics, CAPS phenotype and disease activity, inflammatory markers and canakinumab treatment strategy were recorded. Treatment response was assessed using CAPS disease activity scores, CRP and/or serum amyloid A levels. Comparisons between age groups, CAPS phenotypes and centres were conducted., Results: A total of 68 CAPS patients at nine centres were included. All CAPS phenotypes were represented. Thirty-seven (54%) patients were females, the median age was 25 years and 27 (40%) were children, and the median follow-up was 28 months. Overall, complete response (CR) was seen in 72% of CAPS patients, significantly less often in severe (14%) than in mild CAPS phenotypes (79%). Only 53% attained CR on standard dose canakinumab. Dose increase was more commonly required in children (56%) than in adults (22%). Centres with a treat-to-target approach had significantly higher CR rates (94 vs 50%)., Conclusion: Real-life effectiveness of canakinumab in CAPS was significantly lower than in controlled trials. Treat-to-target strategies may improve the outcome of children and adults living with CAPS., (© The Author 2015. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Neuronal plasticity is essential to enable rehabilitation when the brain suffers from injury, such as following a stroke. One of the most established models to study cortical plasticity is ocular dominance (OD) plasticity in the primary visual cortex (V1) of the mammalian brain induced by monocular deprivation (MD). We have previously shown that OD-plasticity in adult mouse V1 is absent after a photothrombotic (PT) stroke lesion in the adjacent primary somatosensory cortex (S1). Exposing lesioned mice to conditions which reduce the inhibitory tone in V1, such as raising animals in an enriched environment or short-term dark exposure, preserved OD-plasticity after an S1-lesion. Here we tested whether modification of excitatory circuits can also be beneficial for preserving V1-plasticity after stroke. Mice lacking postsynaptic density protein-95 (PSD-95), a signaling scaffold present at mature excitatory synapses, have lifelong juvenile-like OD-plasticity caused by an increased number of AMPA (α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid) -silent synapses in V1 but unaltered inhibitory tone. In fact, using intrinsic signal optical imaging, we show here that OD-plasticity was preserved in V1 of adult PSD-95 KO mice after an S1-lesion but not in PSD-95 wildtype (WT)-mice. In addition, experience-enabled enhancement of the optomotor reflex of the open eye after MD was compromised in both lesioned PSD-95 KO and PSD-95 WT mice. Basic V1-activation and retinotopic map quality were, however, not different between lesioned PSD-95 KO mice and their WT littermates. The preserved OD-plasticity in the PSD-95 KO mice indicates that V1-plasticity after a distant stroke can be promoted by either changes in excitatory circuitry or by lowering the inhibitory tone in V1 as previously shown. Furthermore, the present data indicate that an increased number of AMPA-silent synapses preserves OD-plasticity not only in the healthy brain, but also in another experimental paradigm of cortical plasticity, namely the long-range influence on V1-plasticity after an S1-lesion.

A hallmark of neocortical circuits is the segregation of processing streams into six distinct layers. The importance of this layered organization for cortical processing and plasticity is little understood. We investigated the structure, function and plasticity of primary visual cortex (V1) of adult mice deficient for the glycoprotein reelin and their wild-type littermates. In V1 of rl-/- mice, cells with different laminar fates are present at all cortical depths. Surprisingly, the (vertically) disorganized cortex maintains a precise retinotopic (horizontal) organization. Rl-/- mice have normal basic visual capabilities, but are compromised in more challenging perceptual tasks, such as orientation discrimination. Additionally, rl-/- animals learn and memorize a visual task as well as their wild-type littermates. Interestingly, reelin deficiency enhances visual cortical plasticity: juvenile-like ocular dominance plasticity is preserved into late adulthood. The present data offer an important insight into the capabilities of a disorganized cortical system to maintain basic functional properties.