Excellent Clinical Outcomes From a National Donation‐After‐Determination‐of‐Cardiac‐Death Lung Transplant Collaborative

Donation‐after‐Determination‐of‐Cardiac‐Death (DDCD) donor lungs can potentially increase the pool of lungs available for Lung Transplantation (LTx). This paper presents the 5‐year results for Maastricht category III DDCD LTx undertaken by the multicenter Australian National DDCD LTx Collaborative. The Collaborative was developed to facilitate interaction with the Australian Organ Donation Authority, standardization of definitions, guidelines, education and audit processes. Between 2006 and 2011 there were 174 actual DDCD category III donors (with an additional 37 potentially suitable donors who did not arrest in the mandated 90 min postwithdrawal window), of whom 71 donated lungs for 70 bilateral LTx and two single LTx. In 2010 this equated to an “extra” 28% of donors utilized for LTx. Withdrawal to pulmonary arterial flush was a mean of 35.2 ± 4.0 min (range 18–89). At 24 h, the incidence of grade 3 primary graft dysfunction was 8.5%[median PaO₂/FiO₂ ratio 315 (range 50–507)]. Overall the incidence of grade 3 chronic rejections was 5%. One‐ and 5‐year actuarial survival was 97% and 90%, versus 90% and 61%, respectively, for 503 contemporaneous brain‐dead donor lung transplants. Category III DDCD LTx therefore provides a significant, practical, additional quality source of transplantable lungs.     

Evaluation of Hyphecan (1‐4,2‐acetamide‐deoxy‐B‐D‐glucan polymer) on wound healing in a rodent model

Objective: To evaluate the effect of an artificial skin Hyphecan (1‐4,2‐acetamide‐deoxy‐B ‐D ‐glucan polymer) on wound healing in a rodent model. Materials and Method: The prospective study was conducted at a basic science laboratory at a tertiary teaching hospital. Two 4 cm × 4 cm full‐thickness wounds were created on the dorsal surface of 10 Spraque–Dawley rats and covered with Hyphecan and Kaltostat, respectively. Wounds were examined and measured on days 4, 10, 21 and 28, and would continue after day 28 until healed up completely. Punch biopsies (3 mm) were taken on days 4, 10 and 28 for histological examination of the response of healing and repair. Results: Despite the fact that the wound healing rate was similar for both groups on days 4, 10, 21 and 28, the average healing time for the Hyphecan group (29.1 ± 1.7 days) was significantly shorter statistically (P = 0.03) than the Kaltostat group (30.7 ± 2.8 days). Conversely, the marked healing response elicited by Hyphecan on day 4 persisted on days 10 and 28 in contrast to Kaltostat, which had only a mild degree of healing response on days 10 and 28. The study suggests that wounds treated by Hyphecan heal faster than Kaltostat. Conclusion: The findings provide basic scientific evidence supporting the clinical use of Hyphecan in different wounds and might also reduce the cost of wound management as Hyphecan is cheaper than Kaltostat and requires a shorter treatment time.      

Investigation of High‐Speed Erythrocyte Flow and Erythrocyte‐Wall Impact in a Lab‐on‐a‐Chip

To better understand erythrocyte high‐speed motion, collision characteristics, and collision‐induced hemolysis probability in rotary blood pumps, a visual experimental investigation of high‐speed erythrocyte flow and erythrocyte‐wall collision in a lab‐on‐a‐chip was performed. The erythrocyte suspension was driven by a microsyringe pump connected to the microchip, and the erythrocyte flow and erythrocyte‐wall impact process were observed and imaged by an optical microscope and a high‐speed camera. Two types of microchips with different impact surfaces (flat and curved) were employed. The motion and deformation features before and after collision were studied in detail. The results show that erythrocytes not only move along the flow direction in the flow plane but also rotate and roll in three‐dimensional space. Erythrocytes keep discoid shape during the movement in the straight channel, but their deformations during collision are mainly classified into two types: erythrocyte structure is still stable and the erythrocyte performance can be ensured to a certain extent in the TypeA deformation, while the TypeB deformation makes the membrane more likely to fracture on the stretched side, increasing the probability of hemolysis. Furthermore, the movements and deformations of the erythrocytes after collision are analyzed and classified into two types: bouncing and slipping. Moreover, a simulation method for the flow in microchip was performed and validated through a comparison of the streamlines and experimental erythrocytes tracks, which can be further employed to predict the high‐speed blood flow, associated with collision process in mechanical blood pump.     

Serum ion levels after ceramic‐on‐ceramic and metal‐on‐metal total hip arthroplasty: 8‐year minimum follow‐up

Alternative bearing surfaces for total hip arthroplasty, such as metal‐on‐metal and ceramic‐on‐ceramic, offer the potential to reduce mechanical wear and osteolysis. In the short and medium term, the second generation of metal‐on‐metal bearings demonstrated high systemic metal ion levels, whereas ceramic‐on‐ceramic bearings showed the lowest ones. We aimed to verify whether the long‐term ion release in metal‐on‐metal subjects was still relevant at a median 10‐year follow‐up, and whether a fretting process at the modular junctions occurred in ceramic‐on‐ceramic patients and induced an ion dissemination. Serum levels were measured in 32 patients with alumina‐on‐alumina implants (group A), in 16 subjects with metal‐on‐metal implants (group B), and in 47 healthy subjects (group C). Group B results were compared with medium‐term findings. Cobalt and chromium levels were significantly higher in metal‐on‐metal implants than in ceramic‐on‐ceramic ones and controls. Nevertheless, ion levels showed a tendency to decrease in comparison with medium‐term content. In ceramic‐on‐ceramic implants, ion values were not significantly different from controls. Both in groups A and B, aluminum and titanium release were not significantly different from controls. In conclusion, negligible serum metal ion content was revealed in ceramic‐on‐ceramic patients. On the contrary, due to the higher ion release, metal‐on‐metal coupling must be prudently considered, especially in young patients, in order to obtain definitive conclusions. © 2008 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res     

Enhanced healing of goat femur‐defect using BMP7 gene‐modified BMSCs and load‐bearing tissue‐engineered bone

Segmental defect regeneration is still a clinical challenge. In this study, we investigated the feasibility of bone marrow stromal cells (BMSCs) infected with adenoviral vector containing the bone morphogenetic protein 7 gene (AdBMP7) and load‐bearing to enhance bone regeneration in a critically sized femoral defect in the goat model. The defects were implanted with AdBMP7‐infected BMSCs/coral (BMP7 group) or noninfected BMSCs/coral (control group), respectively, stabilized with an internal fixation rod and interlocking nails. Bridging of the segmental defects was evaluated by radiographs monthly, and confirmed by biomechanical tests. Much callus was found in the BMP7 group, and nails were taken off after 3 months of implantation, indicating that regenerated bone in the defect can be remodeled by load‐bearing, whereas after 6 months in control group. After load‐bearing, it is about 5 months; the mechanical property of newly formed bone in the BMP7 group was restored, but 8 months in control group. Our data suggested that the BMP7 gene‐modified BMSCs and load‐bearing can promote bone regeneration in segmental defects. © 2009 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 28:412–418, 2010     

Low‐order multi‐rate linear time‐invariant decentralized trackers using the new observer‐based sub‐optimal method for unknown sampled‐data nonlinear time‐delay system with closed‐loop decoupling

This paper presents the low‐order multi‐rate linear time‐invariant decentralized trackers using the new observer‐based sub‐optimal method for a class of unknown sampled‐data nonlinear time‐delay system with closed‐loop decoupling. For the unknown sampled‐data nonlinear time‐delay system, we assume that the inner time delay is clearly known. Under this prerequisite, the appropriate (low‐) order decentralized linear observer for the unknown sampled‐data nonlinear system is determined by the off‐line observer/Kalman filter identification (OKID) method with artificial delay input and actual delay output. Then, the above observer has been further improved based on the proposed new observer‐based sub‐optimal approach. Sequentially, the decentralized tracker with the high gain property is proposed, so that the closed‐loop system has the decoupling property. The proposed approach constructs complete mathematics method including the concept of optimal control theory and state‐matching digital redesign technique and is quite useful for the complicated interconnected large‐scale sampled‐data nonlinear time‐delay system with unknown system equation. Copyright © 2010 John Wiley & Sons, Ltd.     

Manipulator‐driven selection of semi‐active MR‐visible markers

Background

A method for the identification of semi‐active fiducial magnetic resonance (MR) markers is presented based on selectively optically tuning and detuning them.

Methods

Four inductively coupled solenoid coils with photoresistors were connected to light sources. A microcontroller timed the optical tuning/detuning of coils and image collection. The markers were tested on an MR manipulator linking the microcontroller to the manipulator control to visibly select the marker subset according to the actuated joint.

Results

In closed‐loop control, the average and maximum were 0.76° ± 0.41° and 1.18° errors for a rotational joint, and 0.87 mm ± 0.26 mm and 1.13 mm for the prismatic joint.

Conclusions

This technique is suitable for MR‐compatible actuated devices that use semi‐active MR‐compatible markers.     

Linear multi‐model time‐optimization

A linear optimization problem with unknown parameters from a given finite set is tackled. The problem is to find the robust time‐optimal control transferring a given initial point to a convex terminal compact set M for all unknown parameters in a shortest time. The robust maximum principle for this minimax problem is formulated. It gives a necessary and sufficient condition of robust optimality. Under natural conditions, the existence and uniqueness of robust optimal controls are proven when the resource set is a convex polytope. Several illustrating examples, including a bang–bang robust optimal control, are considered in detail. Copyright © 2002 John Wiley & Sons, Ltd.     

Role of Toll‐like receptor 4 signaling in cutaneous chronic graft‐versus‐host disease

Cutaneous damage is one of the characterized manifestations in chronic graft‐versus‐host disease (cGVHD). When local effective immunity in the skin is altered to a dysimmune reaction, cutaneous injuries occur. Toll‐like receptor 4 signaling is regarded as a central mediator of inflammation and organ injury. In this study, we found that TLR4 mRNA in peripheral blood from patients with cutaneous cGVHD was markedly increased compared with that from non‐GVHD patients and healthy controls. In addition, NF‐κB expression, TLR4 downstream signaling, and TLR4‐mediated cytokines, including IL‐6 and ICAM‐1, were upregulated. Moreover, ICAM‐1 was widely distributed in skin biopsies from patients with cutaneous cGVHD. We also found that LPS induced TLR4‐mediated NF‐κB activation and IL‐6 and ICAM‐1 secretion in human fibroblasts in vitro. Thus, TLR4, NF‐κB, IL‐6, and ICAM‐1 contribute to the inflammatory response that occurs in cutaneous cGVHD, indicating the TLR4 pathway may be a novel target for cutaneous cGVHD therapy.     

Dynamical analysis of dislocation‐associated factors in total hip replacements by hardware‐in‐the‐loop simulation

Since dislocation of total hip replacements (THR) remains a clinical problem, its mechanisms are still in the focus of research. Previous studies ignored the impact of soft tissue structures and dynamic processes or relied on simplified joint contact mechanics, thus, hindered a thorough understanding. Therefore, the purpose of the present study was to use hardware‐in‐the‐loop (HiL) simulation to analyze systematically the impact of varying implant positions and designs as well as gluteal and posterior muscle function on THR instability under physiological‐like loading conditions during dynamic movements. A musculoskeletal multibody model emulated the in situ environment of the lower extremity during deep sit‐to‐stand with femoral adduction maneuver while a six‐axis robot moved and loaded a THR accordingly to feed physical measurements back to the multibody model. Commercial THRs with hard‐soft bearings were used in the simulation with three different head diameters (28, 36, 44 mm) and two offsets (M, XL). Cup inclination of 45°, cup anteversion of 20°, and stem anteversion of 10° revealed to be outstandingly robust against any instability‐related parameter variation. For the flexion motion, higher combined anteversion angles of cup and stem seemed generally favorable. Total hip instability was either deferred or even avoided even in the presence of higher cup inclination. Larger head diameters (>36 mm) and femoral head offsets (8 mm) deferred occurrence of prosthetic and bone impingement associated with increasing resisting torques. In summary, implant positioning had a much higher impact on total hip stability than gluteal insufficiency and impaired muscle function. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 35:2557–2566, 2017.