The pathophysiology after polytrauma represents a complex network of interactions. While it was thought for a long time that the direct and indirect effects of hypoperfusion are most relevant due to ...the endothelial permeability changes, it was discovered that the innate immune response to trauma is equally important in modifying the organ response. Recent multi center studies provided a “genetic storm” theory, according to which certain neutrophil changes are activated at the time of injury. However, a second hit phenomenon can be induced by activation of certain molecules by direct organ injury, or pathogens (damage associated molecular patterns, DAMPS - pathogen associated molecular patterns, PAMPS). The interactions between the four pathogenetic cycles (of shock, coagulopathy, temperature loss and soft tissue injuries) and cross-talk between coagulation and inflammation have also been identified as important modifiers of the clinical status. In a similar fashion, overzealous surgeries and their associated soft tissue injury and blood loss can induce secondary worsening of the patient condition. Therefore, staged surgeries in certain indications represent an important alternative, to allow for performing a “safe definitive surgery” strategy for major fractures. The current review summarizes all these situations in a detailed fashion
Summary
A Patient Blood Management programme was established at the University Hospital of Zurich, along with a monitoring and feedback programme, at the beginning of 2014 with a first analysis ...reported in 2015. Our study aimed to investigate the further impact of this Patient Blood Management monitoring and feedback programme on transfusion requirements and related costs. We included adult patients discharged between 2012 and 2017. A total of 213,882 patients underwent analysis: 66,659 patients in the baseline period (2012–2013); 35,309 patients in the year after the introduction of the Patient Blood Management monitoring and feedback programme (2014) and 111,914 patients in the continued sustainability period (2015–2017). The introduction of the Patient Blood Management monitoring and feedback programme reduced allogeneic blood product transfusions by 35%, from 825 units per 1000 hospital discharges in 2012 to 536 units in 2017. The most sustained effect was an approximately 40% reduction in red blood cell transfusions, from 535 per 1000 discharges to 319 units. Fewer patients were transfused in the periods after the introduction of the Patient Blood Management monitoring and feedback programme (6251 (9.4%) vs. 2932 (8.3%) vs. 8196 (7.3%); p < 0.001). Compared with 2012, the yearly OR for being exposed to any blood transfusion declined steadily after the introduction of the Patient Blood Management monitoring and feedback programme to 0.64 (95%CI 0.61–0.68; p < 0.001) in 2017. For patients requiring extracorporeal membrane oxygenation, transfusion requirements were also sustainably reduced. This reduction in allogeneic blood transfusions led to savings of 12,713,754 Swiss francs (£ 9,497,000 sterling; EUR 11,100,000; US$ 12,440,000) in blood product acquisition costs over 4 years. In‐hospital mortality was not affected by the programme. The Patient Blood Management monitoring and feedback programme sustainably reduced transfusion requirements and related costs, without affecting in‐hospital mortality.
Sleep, in particular REM sleep, has been shown to improve the consolidation of emotional memories. Here, we investigated the role of sleep and sleep deprivation on the consolidation of fear memories ...and underlying neuronal mechanisms. We employed a Pavlovian fear conditioning paradigm either followed by a night of polysomnographically monitored sleep, or wakefulness in forty healthy participants. Recall of learned fear was better after sleep, as indicated by stronger explicitly perceived anxiety and autonomous nervous responses. These effects were positively correlated with the preceding time spent in REM sleep and paralleled by activation of the basolateral amygdala. These findings suggest REM sleep-associated consolidation of fear memory in the human amygdala. In view of the critical participation of fear learning mechanisms in the etiology of anxiety and post-traumatic stress disorder, deprivation of REM sleep after exposure to distressing events is an interesting target for further investigation.
•Sleeping the first night after learning facilitates the consolidation of fear memories.•Improved recall is paralleled by enhanced activation of the basolateral amygdala.•Autonomous nervous responses correlate with REM sleep duration.•Sleep deprivation might curtail the formation of fear memories after stressful events.
Brain µ-opioid receptors (MOR) mediate reward and help coping with pain, social rejection, anxiety and depression. The dorsal midline thalamus (dMT) integrates visceral/emotional signals and biases ...behavior towards aversive or defensive states through projections to the amygdala. While a dense MOR expression in the dMT has been described, the exact cellular and synaptic mechanisms of µ-opioidergic modulation in the dMT-amygdala circuitry remain unresolved. Here, we hypothesized that MORs are important negative modulators of dMT-amygdala excitatory networks. Using retrograde tracers and targeted channelrhodopsin expression in combination with patch-clamp electrophysiology, we found that projections of dMT neurons onto both basal amygdala principal neurons (BA PN) and central amygdala (CeL) neurons are attenuated by stimulation of somatic or synaptic MORs. Importantly, dMT efferents to the amygdala drive feedforward excitation of centromedial amygdala neurons (CeM), which is dampened by MOR activation. This downregulation of excitatory activity in dMT-amygdala networks puts the µ-opioid system in a position to ameliorate aversive or defensive behavioral states associated with stress, withdrawal, physical pain or social rejection.
Summary
This matched case-control study compared the computed tomography (CT)-based regional bone density of patients with fragility fractures of the sacrum to a control without fracture. Patients ...with a sacral fracture demonstrated a significantly lower regional bone density of the sacrum, the sacral bone density not being correlated with the BMD by DXA of the spine.
Introduction
The aim of this study is to compare the computed tomography-based regional bone density measured by Hounsfield units (HUs) in patients with and without fragility fractures of the sacrum.
Methods
Patients aged ≥ 50 years with a fragility fracture of the sacrum were compared to patients of similar age and gender who had a fall from standing height without fracture (
n
= 46). A matched case-control analysis was conducted by retrospective chart review and assessment of areal bone mineral density by lumbar DXA and by volumetric regional HU measurements in uncalibrated CT scans of the sacrum.
Results
Patients with a sacral fracture (age 74 ± 11 years) showed a lower bone density in the body of S1 (HU 85 ± 22) when compared to the matched control group without fracture (age 73 ± 10 years, HU 125 ± 37,
p
< 0.001). The CT-based bone density of S1 did not correlate with the DXA values of the lumbar spine (
r
= 0.223,
p
= 0.136), and lumbar spine T-scores did not differ between the groups (− 2.0 ± 1.3 vs. − 1.9 ± 1.2,
p
= 0.786). All measurements are based on uncalibrated scans, and absolute HU values are restricted to scans made on Siemens SOMATOM Force or SOMATOM Edge scanners.
Conclusions
Patients with fragility fractures of the sacrum demonstrated a lower regional volumetric bone density of the sacrum when compared to a cohort without a fracture. Local sacral volumetric bone density as measured by CT seems to be independent from the areal BMD as measured by DXA of the lumbar spine.
Level of evidence: level III.
Abstract Critical sized bone defects have to be filled with material to allow bone healing. The golden standard for this treatment is autogenous bone grafting. Because of donor size morbidity, ...equivalent synthetic bone scaffolds should be developed. Different materials, especially ceramics and polymers are in the focus of research. Calcium phosphate ceramics show similar properties to bone and are degradable. Different modifications can improve the bioactive features. This article gives an overview about the current materials and their evidence of clinical use.
Purpose
To test the effects of vitamin D intervention and a simple home exercise program (HE) on health-related quality of life (HRQL) in the first 12 months after hip fracture.
Methods
HRQL was ...reported in 173 acute hip fracture patients (mean age 84 years, 79% females, 77% community dwelling) who were enrolled in the 12-month 2 × 2 factorial Zurich Hip Fracture Trial. Pre-fracture HRQL was assessed at baseline (4.2 ± 2.2 days post-surgery) and then again at 6 and 12 months after hip fracture surgery by the EuroQol EQ-5D-3L index value (EQ-5D-3L questionnaire). The effects of vitamin D intervention (2000 vs. 800 IU vitamin D
3
) and exercise (HE vs. no HE) or of the combined interventions on HRQL were assessed using multivariable-adjusted repeated-measures linear mixed-effects regression models.
Results
The EQ-5D-3L index value significantly worsened from 0.71 pre-fracture to 0.57 over 12 months, but the degree of worsening did not differ between individual or combined interventions. However, regarding only the late recovery between 6 and 12 months, the group receiving neither intervention (800 IU/day and no HE) experienced a significant further decline in the EQ-5D-3L index value (adjusted mean change = 0.08 95% CI 0.009, 0.15,
p
= 0.03) while all other groups remained stable.
Conclusion
Hip fractures have a long-lasting negative effect on HRQL up to 12 months after hip fracture. However, HE and/or 2000 IU vitamin D per day may help prevent a further decline in HRQL after the first 6 months following the acute hip fracture event.
Bundling of single polymer chains is a crucial process in the formation of biopolymer network gels that make up the extracellular matrix and the cytoskeleton. This bundled architecture leads to gels ...with distinctive properties, including a large-pore-size gel formation at very low concentrations and mechanical responsiveness through nonlinear mechanics, properties that are rarely observed in synthetic hydrogels. Using small-angle X-ray scattering (SAXS), we study the bundle formation and hydrogelation process of polyisocyanide gels, a synthetic material that uniquely mimics the structure and mechanics of biogels. We show how the structure of the material changes at the (thermally induced) gelation point and how factors such as concentration and polymer length determine the architecture, and with that, the mechanical properties. The correlation of the gel mechanics and the structural parameters obtained from SAXS experiments is essential in the design of future (synthetic) mimics of biopolymer networks.
Minimally invasive intervention strategies after myocardial infarction use state‐of‐the‐art catheter systems that are able to combine mapping of the infarcted area with precise, local injection of ...drugs. To this end, catheter delivery of drugs that are not immediately pumped out of the heart is still challenging, and requires a carrier matrix that in the solution state can be injected through a long catheter, and instantaneously gelates at the site of injection. To address this unmet need, a pH‐switchable supramolecular hydrogel is developed. The supramolecular hydrogel is switched into a liquid at pH > 8.5, with a viscosity low enough to enable passage through a 1‐m long catheter while rapidly forming a hydrogel in contact with tissue. The hydrogel has self‐healing properties taking care of adjustment to the injection site. Growth factors are delivered from the hydrogel thereby clearly showing a reduction of infarct scar in a pig myocardial infarction model.
A supramolecular hydrogel system is reported that can be quickly switched into a liquid at pH > 8.5, with a viscosity low enough to enable passage through a 1‐m long catheter while rapidly forming a hydrogel in contact with myocardial tissue. The hydrogel has self‐healing properties taking care of adjustment to the injection site. Hydrogel delivery of growth factors shows a clear reduction of infarct scar collagen in a pig myocardial infarction model.
PDF
