Summary
Hip fracture patients often display an acute confusional state (delirium) which is associated with worse outcomes. In this observational study, we found that co-management of hip fracture ...patients by a multidisciplinary team including a geriatrician and an orthopaedic surgeon could reduce the incidence of delirium.
Introduction
Delirium after hip fracture is common and is associated with negative outcomes. We investigated if orthogeriatric co-management reduced the incidence of delirium in hip fracture patients.
Methods
In this single-centre, prospective observational study, we compared the incidence of delirium and subsyndromal delirium (SSD) before (usual care group,
n
= 94) and after (orthogeriatric group,
n
= 103) the introduction of orthogeriatric co-management as an integrated care model. The outcome measure ‘no delirium/SSD/delirium’ was treated as an ordinal variable and analysed using the chi-squared test and multivariable ordinal logistic regression.
Results
The groups had similar baseline characteristics except for a higher proportion of patients with pre-existing cognitive impairment in the usual care group (51% vs. 37%,
p
= 0.045). Fewer patients in the orthogeriatric group developed SSD or delirium (no delirium: 59% vs. 40%/SSD: 6% vs. 13%/delirium: 35% vs. 47%;
p
= 0.021). The number needed to treat (NNT) to avoid one case of SSD or delirium was 5.3 (95% CI: 3.1 to 19.7). In a multivariable analysis adjusted for age, sex, ASA class, pre-existing cognitive impairment, time to surgery, type of surgery, and medical or surgical complications, the odds ratio for the development of SSD/delirium was lower in the orthogeriatric group (OR = 0.46, 95% CI: 0.23–0.89,
p
= 0.023).
Conclusion
Orthogeriatric co-management as an integrated care model reduced the incidence of SSD/delirium in hip fracture patients.
We engineered an automated biomechatronics system, MyoRobot, for robust objective and versatile assessment of muscle or polymer materials (bio-)mechanics. It covers multiple levels of muscle ...biosensor assessment, e.g. membrane voltage or contractile apparatus Ca2+ ion responses (force resolution 1µN, 0–10mN for the given sensor; Ca2+ range ~ 100nM–25µM). It replaces previously tedious manual protocols to obtain exhaustive information on active/passive biomechanical properties across various morphological tissue levels. Deciphering mechanisms of muscle weakness requires sophisticated force protocols, dissecting contributions from altered Ca2+ homeostasis, electro-chemical, chemico-mechanical biosensors or visco-elastic components. From whole organ to single fibre levels, experimental demands and hardware requirements increase, limiting biomechanics research potential, as reflected by only few commercial biomechatronics systems that can address resolution, experimental versatility and mostly, automation of force recordings. Our MyoRobot combines optical force transducer technology with high precision 3D actuation (e.g. voice coil, 1µm encoder resolution; stepper motors, 4µm feed motion), and customized control software, enabling modular experimentation packages and automated data pre-analysis. In small bundles and single muscle fibres, we demonstrate automated recordings of (i) caffeine-induced-, (ii) electrical field stimulation (EFS)-induced force, (iii) pCa-force, (iv) slack-tests and (v) passive length-tension curves. The system easily reproduces results from manual systems (two times larger stiffness in slow over fast muscle) and provides novel insights into unloaded shortening velocities (declining with increasing slack lengths). The MyoRobot enables automated complex biomechanics assessment in muscle research. Applications also extend to material sciences, exemplarily shown here for spider silk and collagen biopolymers.
•An automated, high-precision biomechatronics system, the MyoRobot, was engineered.•It assesses single cell, multi-cellular, whole muscle and biopolymer biomechanics.•Sensitivity of the contractile Ca2+ ion biosensor is automatically assessed in 2min.•Extracellular matrix puts a brake on unloaded speed of shortening in fibre bundles.•Material parameters of spider silk and collagen fibres were assessed.
The Wingate Anaerobic Test (WAnT) is generally used to evaluate anaerobic cycling performance, but knowledge of the metabolic profile of WAnT is limited. Therefore the energetics of WAnT was analysed ...with respect to working efficiency and performance. A group of 11 male subjects mean (SD), age 21.6 (3.8) years, height 178.6 (6.6) cm, body mass 82.2 (12.1) kg performed a maximal incremental exercise test and a WAnT. Lactic and alactic anaerobic energy outputs were calculated from net lactate production and the fast component of the kinetics of post-exercise oxygen uptake. Aerobic metabolism was determined from oxygen uptake during exercise. The WAnT mean power of 683 (96.0) W resulted from a total energy output above the value at rest of 128.1 (23.2) kJ x 30 s(-1) mean metabolic power=4.3 (0.8) kW corresponding to a working efficiency of 16.2 (1.6)%. The WAnT working efficiency was lower (P < 0.01) than the corresponding value of 24.1 (1.7)% at 362 (41) W at the end of an incremental exercise test. During WAnT the fractions of the energy from aerobic, anaerobic alactic and lactic acid metabolism were 18.6 (2.5)%, 31.1 (4.6)%, and 50.3 (5.1)%, respectively. Energy from metabolism of anaerobic lactic acid explained 83% and 81% of the variance of WAnT peak and mean power, respectively. The results indicate firstly that WAnT requires the use of more anaerobically derived energy than previously estimated, secondly that anaerobic metabolism is dominated by glycolysis, thirdly that WAnT mechanical efficiency is lower than that found in aerobic exercise tests, and fourthly that the latter finding partly explains discrepancies between previously published and the present data about the metabolic profile of WAnT.
The aim of this study was to characterise the intra and extra-oral phenotype associated with agenesis of the permanent maxillary lateral incisor. We compared three groups: (1) subjects with agenesis ...of one or both permanent maxillary lateral incisors (n=80); (2) first and second degree relatives of group 1 with no agenesis of the permanent maxillary lateral incisor and (3) subjects with no agenesis of the maxillary lateral incisor or family history of it (n=49). For each of the 201 subjects detailed clinical information was reviewed and panoramic radiographs were analysed. Considering only the sample with unilateral agenesis, microdontia of the contralateral permanent maxillary lateral incisor was significantly more frequent in group 1 (82.4%) than in group 2 (25%) and the control group (2%). This supports the theory that microdontia is a variable expression of the same developmental disturbance that causes tooth agenesis. The absence of third molars occurred more often in group 1 (36.2%) than in groups 2 and 3 (18.6% and 18.9% respectively), confirming that agenesis of third molars was markedly associated with the agenesis of the permanent maxillary lateral incisor. Agenesis of teeth other than third molars was not significantly different among subjects with agenesis of the permanent maxillary lateral incisor and their relatives. The frequencies of supernumerary teeth, permanent maxillary canine impaction, general health condition and minor anomalies were not significantly different between the three groups.
During mammalian development, a subpopulation of endothelial cells in the cardinal vein (CV) expresses lymphatic‐specific genes and subsequently develops into the first lymphatic structures, ...collectively termed as lymph sacs. Budding, sprouting and ballooning of lymphatic endothelial cells (LECs) have been proposed to underlie the emergence of LECs from the CV, but the exact mechanisms of lymph vessel formation remain poorly understood. Applying selective plane illumination‐based ultramicroscopy to entire wholemount‐immunostained mouse embryos, we visualized the complete developing vascular system with cellular resolution. Here, we report emergence of the earliest detectable LECs as strings of loosely connected cells between the CV and superficial venous plexus. Subsequent aggregation of LECs resulted in formation of two distinct, previously unidentified lymphatic structures, the dorsal peripheral longitudinal lymphatic vessel (PLLV) and the ventral primordial thoracic duct (pTD), which at later stages formed a direct contact with the CV. Providing new insights into their function, we found vascular endothelial growth factor C (VEGF‐C) and the matrix component CCBE1 indispensable for LEC budding and migration. Altogether, we present a significantly more detailed view and novel model of early lymphatic development.
Ultramicroscopy of wholemount mouse embryos uncovers the first, previously unknown lymphatic structures in mammals: the dorsal longitudinal lymphatic vessel and the ventral primordial thoracic duct, which eventually connect with the cardinal vein as previously described.
To compare the functional outcome, health-related quality of life (HRQoL), and satisfaction of patients who underwent primary total hip arthroplasty (THA) and a single debridement, antibiotics and ...implant retention (DAIR) procedure for deep infection, using either the transgluteal or the posterior surgical approach for both procedures.
The study was registered at clinicaltrials.gov (ID: NCT03161990) on 15 May 2017. Patients treated with a single DAIR procedure for deep infection through the same operative approach as their primary THA (either the transgluteal or the posterior approach) were identified in the Norwegian Arthroplasty Register and given a questionnaire. Median follow-up after DAIR by questionnaire was 5.5 years in the transgluteal group (n = 87) and 2.5 years in the posterior approach group (n = 102).
Patients in the posterior approach group were less likely to limp after the DAIR procedure (17% vs 36% limped all the time; p = 0.005), had a higher mean Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) function score (80 vs 71; p = 0.013), and were more likely to achieve a patient acceptable symptom state for the WOMAC function score (76% vs 55%; p = 0.002). In a multivariable analysis, the point estimate for the increase in WOMAC function score using the posterior approach was 10.2 (95% CI 3.1 to 17.2; p = 0.005), which is above the minimal clinically important improvement. The patients in the posterior approach group also reported better mean HRQoL scores and were more likely to be satisfied with their hip arthroplasty (77% vs 55%; p = 0.001).
In patients treated with a single, successful DAIR procedure for deep infection of a primary THA, the use of the posterior approach in both primary surgery and DAIR was associated with less limping, better functional outcome, better HRQoL, and higher patient satisfaction compared with cases where both were performed using the transgluteal approach. The observed differences in functional outcome and patient satisfaction were clinically relevant. Cite this article:
2020;102-B(12):1662-1669.
Angiogenesis is a prerequisite for solid tumor growth and metastasis. Elucidation of the signaling pathways that control tumor angiogenesis constitutes the basis for a rational antiangiogenic tumor ...therapy. Here we show that the production of vascular endothelial growth factor (VEGF) in HeLa and HL-60 cells is directed by the constitutive photomorphogenesis 9 signalosome (CSN). The CSN is a kinase complex that cooperates with the ubiquitin/26S proteasome system in regulating the stability of proteins involved in signal transduction. VEGF expression is controlled by the transcription factors activator protein (AP)-1, AP-2, SP-1, and hypoxia-inducible factor 1. Inhibition of CSN kinase activity by 50 microM curcumin for 2 h decreases the cellular c-Jun concentration, resulting in a reduction of the VEGF production by approximately 75%. The removal of the inhibitor from the cells led to a time-dependent recovery of endogenous c-Jun that is paralleled by increasing VEGF production. Elevated cellular CSN activity induced by CSN subunit 2 overexpression causes increased VEGF production in HeLa cells. A competitor of CSN-dependent c-Jun phosphorylation, the NH(2)-terminal c-Jun fragment Deltac-Jun(1-226), inhibits VEGF production in HeLa cells. The transcription factors AP-2 and SP-1 act independently of the CSN. They contribute less than a quarter to basal VEGF production. Under our experimental conditions, hypoxia-inducible factor 1alpha protein was not detected. Overexpression of the tumor suppressor p53 reduces VEGF production in HeLa cells. p53 competes with c-Jun for CSN-specific phosphorylation with the consequence of c-Jun destabilization. We conclude that CSN-directed c-Jun signaling mediates high VEGF production in HeLa and HL-60 cells. The data provide an explanation for the known antiangiogenic and antitumorigenic activities of curcumin. Because the CSN regulates the major part of VEGF production in the tested tumor cells, it constitutes a potentially important target for tumor therapy.
In higher eukaryotic cells, the p53 protein is degraded by the ubiquitin–26S proteasome system mediated by Mdm2 or the human papilloma virus E6 protein. Here we show that COP9 signalosome ...(CSN)‐specific phosphorylation targets human p53 to ubiquitin–26S proteasome‐dependent degradation. As visualized by electron microscopy, p53 binds with high affinity to the native CSN complex. p53 interacts via its N‐terminus with CSN subunit 5/Jab1 as shown by far‐western and pull‐down assays. The CSN‐specific phosphorylation sites were mapped to the core domain of p53 including Thr155. A phosphorylated peptide, Δp53(145–164), specifically inhibits CSN‐mediated phosphorylation and p53 degradation. Curcumin, a CSN kinase inhibitor, blocks E6‐dependent p53 degradation in reticulocyte lysates. Mutation of Thr155 to valine is sufficient to stabilize p53 against E6‐dependent degradation in reticulocyte lysates and to reduce binding to Mdm2. The p53T155V mutant accumulates in both HeLa and HL 60 cells and exhibits a mutant (PAb 240+) conformation. It induces the cyclin‐dependent inhibitor p21. In HeLa and MCF‐7 cells, inhibition of CSN kinase by curcumin or Δp53(145–164) results in accumulation of endogenous p53.
The effects of thalidomide after intraperitoneal instillation on the healing of colonic anastomoses are not known. A series of 40 New Zealand White rabbits underwent an end‐to‐end colonic ...anastomosis. The animals were randomized into four groups. Groups 1 (n = 10) and 2 (n = 10) were treated with dissolved thalidomide 200 mg/kg intraperitoneally, whereas groups 3 (n = 10) and 4 (n = 10) were treated only with the dissolver. Animals were sacrificed at day 3 (groups 1, 3) and day 7 (groups 2, 4). Anastomotic healing was tested by measuring the bursting pressure in vitro. Immunohistochemical staining of the anastomotic site was performed with polyclonal antibodies against CD31 and Mib‐1, to determine a possible antiangiogenic or antiproliferative effect. Statistical analysis was performed using Spearman’s log rank correlation and paired t‐test. On postoperative day 3 (p > 0.19) and postoperative day 7 (p > 0.73), there was no difference in bursting pressure in the treatment and the control groups. Angiogenesis scores were reduced at day 3 in the thalidomide group (p < 0.05), but did not differ between the groups at day 7. White blood cell counts were decreased in the treatment groups at day 3 (p < 0.01) and day 7, compared to control groups (p < 0.01). There was no difference in the expression of Mib‐1 in either group at day 3 or day 7. The intraperitoneal administration of thalidomide does not interfere with the healing of colonic anastomosis. Although the angiogenesis score is diminished at day 3, this did not lead to a reduced bursting pressure at day 3 or day 7.
PDF
