Incorporation of resident macrophages in engineered tissues: Multiple cell type response to microenvironment controlled macrophage‐laden gelatine hydrogels

The success of tissue engineering strategy is strongly related to the inflammatory response, mainly through the activity of macrophages that are key cells in initial immune response to implants. For engineered tissues, the presence of resident macrophages can be beneficial for maintenance of homeostasis and healing. Thus, incorporation of macrophages in engineered tissues can facilitate the integration upon implantation. In this study, an in‐vitro model of interaction was developed between encapsulated naive monocytes, macrophages induced with M1/M2 stimulation and incoming cells for immune assisted tissue engineering applications. To mimic the wound healing cascade, naive THP‐1 monocytes, endothelial cells and fibroblasts were seeded on the gels as incoming cells. The interaction was first monitored in the absence of the gels. To mimic resident macrophages, THP‐1 cells were encapsulated in the presence or absence of IL‐4 to control their phenotype and then these hydrogels were seeded with incoming cells. Without encapsulation, activated macrophages induce apoptosis in endothelial cells. Once encapsulated no adverse effects were seen. Macrophage‐laden hydrogels attracted more endothelial cells and fibroblasts compared to monocytes‐laden hydrogels. The induction (M2 stimulation) of encapsulated macrophages did not change the overall number of attracted cells; but significantly affected their morphology. M1 stimulation by a defined media resulted in more secretion of both pro‐ and anti‐inflammatory cytokines compared to M2 stimulation. It was demonstrated that there is a distinct effect of encapsulated macrophages on the behaviour of the incoming cells; this effect can be harnessed to establish a microenvironment more prone to regeneration upon implantation.     

Bioactive nano‐fibrous scaffold for vascularized craniofacial bone regeneration

There has been a growing demand for bone grafts for correction of bone defects in complicated fractures or tumours in the craniofacial region. Soft flexible membrane like material that could be inserted into defect by less invasive approaches; promote osteoconductivity and act as a barrier to soft tissue in growth while promoting bone formation is an attractive option for this region. Electrospinning has recently emerged as one of the most promising techniques for fabrication of extracellular matrix such as nano‐fibrous scaffolds that can serve as a template for bone formation. To overcome the limitation of cell penetration of electrospun scaffolds and improve on its osteoconductive nature, in this study, we fabricated a novel electrospun composite scaffold of polyvinyl alcohol (PVA)‐poly (ε) caprolactone (PCL)‐Hydroxyapatite based bioceramic (HAB), namely, PVA‐PCL‐HAB. The scaffold prepared by dual electrospinning of PVA and PCL with HAB overcomes reduced cell attachment associated with hydrophobic PCL by combination with a hydrophilic PVA and the HAB can contribute to enhance osteoconductivity. We characterized the physicochemical and biocompatibility properties of the new scaffold material. Our results indicate PVA‐PCL‐HAB scaffolds support attachment and growth of stromal stem cells; [human bone marrow skeletal (mesenchymal) stem cells and dental pulp stem cells]. In addition, the scaffold supported in vitro osteogenic differentiation and in vivo vascularized bone formation. Thus, PVA‐PCL‐HAB scaffold is a suitable potential material for therapeutic bone regeneration in dentistry and orthopaedics.     

Slow Infusion of Low‐dose Ketamine Reduces Bothersome Side Effects Compared to Intravenous Push: A Double‐blind,Double‐dummy,Randomized Controlled Trial

Objective

We compared the analgesic efficacy and incidence of side effects when low‐dose (0.3 mg/kg) ketamine (LDK) is administered as a slow infusion (SI) over 15 minutes versus an intravenous push (IVP) over 1 minute.

Methods

This was a prospective, randomized, double‐blind, double‐dummy, placebo‐controlled trial of adult ED patients presenting with moderate to severe pain (numerical rating scale [NRS] score ≥ 5). Patients received 0.3 mg/kg ketamine administered either as a SI or a IVP. Our primary outcome was the proportion of patients experiencing any psychoperceptual side effect over 60 minutes. A secondary outcome was incidence of moderate or greater psychoperceptual side effects. Additional outcomes included reduction in pain NRS scores at 60 minutes and percent maximum summed pain intensity difference (%SPID).

Results

Fifty‐nine participants completed the study. A total of 86.2% of the IVP arm and 70.0% of the SI arm experienced any side effect (difference = 16.2%, 95% confidence interval [CI] = –5.4 to 37.8). We found a large reduction in moderate or greater psychoperceptual side effects with SI administration—75.9% reported moderate or greater side effects versus 43.4% in the SI arm (difference = 32.5%, 95% CI = 7.9 to 57.1). Additionally, the IVP arm experienced more hallucinations (n = 8, 27.6%) than the SI arm (SI n = 2, 6.7%, difference = 20.9%, 95% CI = 1.8 to 43.4). We found no significant differences in analgesic efficacy. At 60 minutes, the mean %SPID values in the IVP and SI arms were 39.9 and 33.5%, respectively, with a difference of 6.5% (95% CI = –5.8 to 18.7).

Conclusion

Most patients who are administered LDK experience a psychoperceptual side effect regardless of administration via SI or IVP. However, patients receiving LDK as a SI reported significantly fewer moderate or greater psychoperceptual side effects and hallucinations with equivalent analgesia.

     

Prehospital Echocardiography During Resuscitation Impacts Treatment in a Physician-Staffed Helicopter Emergency Medical Service: an Observational Study

Background: Patients in cardiac arrest must receive algorithm-based management such as basic life support and advanced (cardiac) life support. International guidelines dictate diagnosing and treating any factor that may have caused the arrest or may be complicating the resuscitation. Ultrasound may be of potential value in this process and can be used in a prehospital setting. The objective is to evaluate the use of prehospital ultrasound during traumatic and non-traumatic CPR and determine its impact on prehospital treatment decisions in a Dutch helicopter emergency medical service (HEMS). Methods: We conducted an observational study in cardiac arrest patients, of any cause, in whom the Nijmegen HEMS performed CPR with concurrent echocardiography. The participating physicians had to adhere to Advanced Life Support protocols as per standard operating procedure. Simultaneous with the interruptions of chest compressions to allow for heart rhythm analysis, ultrasound-trained HEMS physicians performed echocardiography according to study protocol. The HEMS nurse and physician recorded patient data and data on impacted (supported or altered) patient treatment decisions. Results: From February 2014 through November 2016, we included 56 patients who underwent 102 ultrasound examinations. Sixty-two (61%) ultrasound examinations impacted 78 treatment decisions in 49 patients (88%). The impacted treatment was related to termination of CPR in 32 (57%), fluid management (14%), drugs selection and doses (14%), and choice of destination hospital (5%). Causes of cardiac arrest included trauma (48%), cardiac (21%), medical (14%), asphyxia (9%), and other (7%). Conclusion: Prehospital echocardiography has an impact on patient treatment and may be a useful tool to support decision-making during CPR in a Dutch HEMS.     

Bioengineered AAV Capsids with Combined High Human Liver Transduction In Vivo and Unique Humoral Seroreactivity

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Ear measurement of temperature is only useful for screening for fever in an adult emergency department

Background

A new generation of ear thermometers with preheated tips and several measurements points should allow a more precise temperature measurement. The aim of the study was to evaluate if the ear temperature measured by this ear thermometer can be used to screen for fever and whether the thermometer is in agreement with the rectal temperature and if age, use of hearing devices or time after admission influences the temperature measurements.

Methods

Open cross-sectional clinical single site study patients, >?18?years old, who were acutely admitted to the short stay unit at the ED. A sample size of 99 patient per subgroup was recruited as random convenience series. As ear thermometer Braun Thermoscan Pro 4000® and as rectal thermometer Omron Flex Temp Smart ® was used. For different cut off of temperature the AUC was calculated and Bland-Altman analysis for calculation of 95% limits of agreement with rectal temperature, with subgroup analysis concerning age, time span from admission time and use of hearing aid.

Results

Among 599 patients the sensitivity to detect fever with an ear thermometer varied between 68 and 70% with AUC from 0.88–0.97. If the ear temperature was ≥37.5 oC, the sensitivity to detect patients with ≥38.0 oC rectally was 95% which raised to 100% for a rectal temperature of ≥38.3 oC. For the ear thermometer’s ability to determine the exact temperature the 95% limits of agreement were +/??0.8 oC. with no influence from age, duration of hospital stay or hearing aids.

Conclusion

The examined ear thermometer is able to detect fever, defined as ≥38 oC rectally in an adult ED population by using an ear cut-point of 37.5 oC, but not to measure the exact temperature. Used in this way around a fifth of the patients will still be in need of a rectal temperature measurement, but less than 5% with fever ≥38.0 oC will remain undetected and none with fever ≥38.3 oC. Age, admission time and use of hearing aid did not influence the temperature measurements.

Trial registration

Clinical Trials: ID NCT02977481, date 11/18/2016.