Efficacy and Safety Evaluation of Energy Devices in Bench Surgery for Pancreas Transplantation.

INTRODUCTION: Bench surgery for the preparation of deceased donor pancreatic grafts is labor-intensive and time-consuming. We hypothesized that energy devices could be used during bench surgery to decrease the bench surgery time. However, because bench surgery has two unique characteristics, wet conditions and no blood flow in the vessels, it is necessary to verify the safety and efficacy under such conditions. METHODS: In an animal tissue model, we validated both ultrasonic and bipolar energy devices: Harmonic Shears and the LigaSure (LS) vessel-sealing device by evaluating heat spread and pressure resistance under bench surgery conditions. In a clinical evaluation of the LS, we compared the outcomes of 22 patients in two different bench surgery groups: with and without the use of the LS. RESULTS: Clinically, the bench surgery time was significantly shorter in the LS group than that in the conventional group (P < 0.001). In the animal tissue experiments, the highest temperature in bench surgery conditions was 60.4°C after 1 s at a 5-mm distance in the LS group. Pressure resistance of ≥ 750 mmHg was achieved in almost all trials in both veins and arteries, with no difference between Harmonic Shears and LS. There was more surgical smoke visually in bench conditions versus in dry conditions and under half bite versus full bite conditions. CONCLUSIONS: The encouraging results of our exploratory clinical and animal studies of the energy devices suggest that they may be useful in the setting of bench surgery.

Computer Simulations of Responsive Nanogels at Lipid Membrane.

The swelling and collapse of responsive nanogels on a planar lipid bilayer are studied by means of mesoscopic computer simulations. The effects of molecular weight, cross-linking density, and adhesion strength are examined. The conditions for collapse-mediated engulfing by the bilayer are found. In particular, the results show that at low hydrophobicity level the increase in the nanogel softness decreases the engulfing rate. On the contrary, for stronger hydrophobicity level the trend changes to the opposite one. At the same time, when the cross-linking density is too low or the adhesion strength is too high the nanogel deformation at the membrane suppresses the engulfing regardless of the network swelling ratio. Finally, for comparative reasons, the behavior of the nanogels is also studied at the solid surface. These results may be useful in the design of soft particles capable of tuning of their elasticity and porosity for successful intracellular drug delivery.

Cycling and spiral-wave modes in an active cyclic Potts model.

We studied the nonequilibrium dynamics of a cycling three-state Potts model using simulations and theory. This model can be tuned from thermal-equilibrium to far-from-equilibrium conditions. At low cycling energy, the homogeneous dominant state cycles via nucleation and growth, while spiral waves are formed at high energy. For large systems, a discontinuous transition occurs from these cyclic homogeneous phases to spiral waves, while the opposite transition is absent. Conversely, these two modes can coexist for small systems. The waves can be reproduced by a continuum theory, and the transition can be understood from the competition between nucleation and growth.

Safety and feasibility of in-hospital autonomous transportation using a driverless mobility for patients with musculoskeletal disorders: preliminary clinical study to achieve mobility as a service in medical care.

BACKGROUND: Recent advancements in and the proliferation of autonomous mobility technology, such as intelligent wheelchairs, have made it possible to provide mobility services for patients with reduced mobility due to musculoskeletal disorders. In the present study, we conducted a preliminary clinical study to assess the safety and feasibility of in-hospital autonomous transportation using a driverless mobility (wheelchair) for patients with musculoskeletal disorders. METHODS: From January to February 2022, 51 patients with musculoskeletal disorders exhibiting gait disturbance who presented to our institution were included in the present study. Driverless mobility rides were conducted over a straight-line distance of 100 m from the orthopaedic outpatient reception to the payment counter after the outpatient consultation. We assessed the quality of life using an EQ-5D-5 L index and pain using a VAS score before riding the mobility to investigate the patient's condition. After the ride, a questionnaire survey was conducted to assess patient satisfaction on a 5-point scale. In addition, adverse events during the mobility ride were investigated. RESULTS: Overall satisfaction levels showed that 44 out of 51 (86%) patients rated the level as 3 or higher. There were no significant differences in the level of satisfaction based on the cause of disorders or EQ-5D-5 L Index. Among 19 patients who rated the level of satisfaction as 2-3, the ratio of postoperative patients and those with pain tended to be higher (p < 0.05). While 26 of 51 (51%) patients reported moments of feeling unsafe during the mobility ride, no actual adverse events, such as collisions, were observed. CONCLUSIONS: An in-hospital autonomous transportation service using a driverless mobility for patients with musculoskeletal disorders demonstrated high satisfaction levels and was safe with no severe adverse events observed. The expansion of autonomous mobility deployment is expected to achieve mobility as a service in medical care.

Identification of Respiratory Pauses during Swallowing by Unconstrained Measuring Using Millimeter Wave Radar.

Breathing temporarily pauses during swallowing, and the occurrence of inspiration before and after these pauses may increase the likelihood of aspiration, a serious health problem in older adults. Therefore, the automatic detection of these pauses without constraints is important. We propose methods for measuring respiratory movements during swallowing using millimeter wave radar to detect these pauses. The experiment involved 20 healthy adult participants. The results showed a correlation of 0.71 with the measurement data obtained from a band-type sensor used as a reference, demonstrating the potential to measure chest movements associated with respiration using a non-contact method. Additionally, temporary respiratory pauses caused by swallowing were confirmed by the measured data. Furthermore, using machine learning, the presence of respiring alone was detected with an accuracy of 88.5%, which is higher than that reported in previous studies. Respiring and temporary respiratory pauses caused by swallowing were also detected, with a macro-averaged F1 score of 66.4%. Although there is room for improvement in temporary pause detection, this study demonstrates the potential for measuring respiratory movements during swallowing using millimeter wave radar and a machine learning method.

Single Person Identification and Activity Estimation in a Room from Waist-Level Contours Captured by 2D Light Detection and Ranging.

To develop socially assistive robots for monitoring older adults at home, a sensor is required to identify residents and capture activities within the room without violating privacy. We focused on 2D Light Detection and Ranging (2D-LIDAR) capable of robustly measuring human contours in a room. While horizontal 2D contour data can provide human location, identifying humans and activities from these contours is challenging. To address this issue, we developed novel methods using deep learning techniques. This paper proposes methods for person identification and activity estimation in a room using contour point clouds captured by a single 2D-LIDAR at hip height. In this approach, human contours were extracted from 2D-LIDAR data using density-based spatial clustering of applications with noise. Subsequently, the person and activity within a 10-s interval were estimated employing deep learning techniques. Two deep learning models, namely Long Short-Term Memory (LSTM) and image classification (VGG16), were compared. In the experiment, a total of 120 min of walking data and 100 min of additional activities (door opening, sitting, and standing) were collected from four participants. The LSTM-based and VGG16-based methods achieved accuracies of 65.3% and 89.7%, respectively, for person identification among the four individuals. Furthermore, these methods demonstrated accuracies of 94.2% and 97.9%, respectively, for the estimation of the four activities. Despite the 2D-LIDAR point clouds at hip height containing small features related to gait, the results indicate that the VGG16-based method has the capability to identify individuals and accurately estimate their activities.

Do Stainless-Steel Pins Coated with Fibroblast Growth Factor-Calcium Phosphatase Composite Layers Have Anti-Infective Effects?

Background: The most problematic complication of external fixation is infection at the pin insertion site. Technology that improves the adhesion of the external fixation pin to the skin, subcutaneous tissue, and bone may prevent infection at the pin site. The purpose of this study is to formulate a calcium phosphate-fibroblast growth factor (Cp-FGF) coating on a stainless-steel external fixation pin and to verify its effectiveness in reducing infection at the pin site and its possible influence on bone fixation in animal experiments. Methods: We compared stainless-steel screws without coating (SS group; n = 32), those with a calcium phosphate coating (Cp group; n = 30), those with a Cp-FGF coating (FGF group; n = 32), and those with a Cp-FGF coating having enhanced biological activity (FGF+ group; n = 32) in male Japanese white domesticated rabbits. Screws were inserted percutaneously into the bilateral proximal tibial diaphysis of the rabbits and implanted for 4 weeks. Screws and periscrew tissue were observed postoperatively for qualitatively assessing infection. Results: Infection assessment by gross findings after 4 weeks (at screw removal) showed no significant differences between the groups. Histopathological evaluation of soft tissue infection and bone tissue infection showed no significant differences between the groups for either soft tissue or bone tissue. Since neither the FGF+ group nor the FGF group showed anti-infective effects, the biological activity of FGF is not the only determining factor. We compared SEM, XRD, coating detaching test, sustained release test, and bioassay to examine physicochemical properties among the coatings but found no sufficient differences. Conclusions: It is suggested that improving the tissue adhesion to and/or biocompatibility of pins is also important to improve the in vivo performance of Cp-FGF-coated external fixation pins.

A lesson from polybutylene succinate plastisphere to the discovery of novel plastic degrading enzyme genes in marine vibrios.

Polybutylene succinate (PBS) is an eco-friendly green plastic. However, PBS was shown as being non-biodegradable in marine environments, and up until now, only a limited number of PBS-degrading marine microbes have been discovered. We first set up in vitro PBS- and PBSA (polybutylene succinate adipate)-plastispheres to characterize novel PBS-degrading marine microbes. Microbial growth and oxygen consumption were observed in both PBS- and PBSA-plastispheres enriched with natural seawater collected from Usujiri, Hokkaido, Japan, and Vibrionaceae and Pseudoalteromonadaceae were significantly enriched on these films. Further gene identification indicated that vibrios belonging to the Gazogenes clade possess genes related to a PBS degrading enzyme (PBSase). The PBS degradation assay for six Gazogenes clade vibrios identified Vibrio ruber, Vibrio rhizosphaerae, and Vibrio spartinae as being capable of degrading PBS. We further identified the gene responsible for PBSase from the type strain of V. ruber, and the purified recombinant vibrio PBSase was found to have low-temperature adaptation and was active under high NaCl concentrations. We also provided docking models between the vibrio PBSase and PBS and PBSA units to show how vibrio PBSase interacts with each substrate compared to the Acidovorax PBSase. These results could contribute to a more sustainable society through further utilization of PBS in marine environments and plastic recycling.

Phase-Separated Giant Liposomes for Stable Elevation of α-Hemolysin Concentration in Lipid Membranes.

Staphylococcus aureus α-hemolysin (αHL) is one of the most popular proteins in nanopore experiments within lipid membranes. Higher concentrations of αHL within the lipid membrane are desirable to enhance the mass transport capacity through nanopores. However, the reconstitution of αHL at high concentrations is associated with the problem of membrane lytic disruption. In this study, we present a method that effectively increases αHL concentration while maintaining membrane stability. This method is achieved by using phase-separated giant liposomes, where coexisting liquid-disordered (Ld) and liquid-ordered phases (Lo) are enriched in unsaturated lipids and saturated lipids with cholesterol (Chol), respectively. Fluorescence observation of αHL in liposomes revealed that the presence of Chol facilitates αHL insertion into the membrane. Despite the preferential localization of αHL in the Ld phase rather than the Lo phase, the coexistence of both Lo and Ld phases prevents membrane disruption in the presence of concentrated αHL. We have explained this stabilization mechanism considering the lower membrane tension exhibited by phase-separated liposomes compared to homogeneous liposomes. Under hypertonic conditions, we have successfully increased the local concentration of αHL by invagination of the lipid-only region in the Ld phase, leaving αHL behind. This method exhibits potential for the reconstitution of various nanochannels and membrane proteins that prefer the Ld phase over the Lo phase, thus enabling the production of giant liposomes at high concentrations and the replication of the membrane-crowding condition observed in cells.

Membrane domain formation induced by binding/unbinding of curvature-inducing molecules on both membrane surfaces.

The domain formation of curvature-inducing molecules, such as peripheral or transmembrane proteins and conical surfactants, is studied in thermal equilibrium and nonequilibrium steady states using meshless membrane simulations. These molecules can bind to both surfaces of a bilayer membrane and also move to the opposite leaflet by a flip-flop. Under symmetric conditions for the two leaflets, the membrane domains form checkerboard patterns in addition to striped and spot patterns. The unbound membrane stabilizes the vertices of the checkerboard. Under asymmetric conditions, the domains form kagome-lattice and thread-like patterns. In the nonequilibrium steady states, a flow of the binding molecules between the upper and lower solutions can occur via flip-flop.

Estimation of anisotropic bending rigidities and spontaneous curvatures of crescent curvature-inducing proteins from tethered-vesicle experimental data.

The Bin/amphiphysin/Rvs (BAR) superfamily proteins have a crescent binding domain and bend biomembranes along the domain axis. However, their anisotropic bending rigidities and spontaneous curvatures have not been experimentally determined. Here, we estimated these values from the bound protein densities on tethered vesicles using a mean-field theory of anisotropic bending energy and orientation-dependent excluded volume. The dependence curves of the protein density on the membrane curvature are fitted to the experimental data for the I-BAR and N-BAR domains reported by C. Prévost et al. Nat. Commun., 2015, 6, 8529 and F.-C. Tsai et al. Soft Matter, 2021, 17, 4254-4265, respectively. For the I-BAR domain, all three density curves of different chemical potentials exhibit excellent fits with a single parameter set of anisotropic bending energy. When the classical isotropic bending energy is used instead, one of the curves can be fitted well, but the others exhibit large deviations. In contrast, for the N-BAR domain, two curves are not well fitted simultaneously the anisotropic model, although it is significantly improved compared to the isotropic model. This deviation likely suggests a cluster formation of the N-BAR domains.

Size-mismatched transplantation from large donors to small recipients is associated with pancreas graft thrombosis: A retrospective national observational study.

INTRODUCTION: Donor-recipient (D/R) size mismatch has been evaluated for a number of organs but not for pancreas transplantation. METHODS: We retrospectively evaluated 438 patients who had undergone pancreas transplantation. The D/R body surface area (BSA) ratio was calculated, and the relationship between the ratio and graft prognosis was evaluated. We divided the patients into two groups and evaluated graft survival. The incidence of pancreas graft thrombosis resulting in graft failure within 14 days and 1-year graft survival were compared using Kaplan-Meier curves, and the prognostic factors associated with graft thrombosis were identified by univariate and multivariate analyses. RESULTS: The mean/median donor and recipient BSAs were 1.63 m2 /1.65 m2 , and 1.57 m2 /1.55 m2 , respectively; the mean and median D/R BSAs were both 1.05. The receiver operating characteristic curve cutoff for the D/R BSA ratio was 1.09, and significant differences were identified between patients with ratios of ≥1.09 (high group) versus <1.09 (low group). The incidence of graft thrombosis resulting in pancreas graft failure within 14 days was significantly higher in the high group than in the low group (p < .01). One-year overall and death-censored pancreas graft survival were significantly higher in the low group than in the high group (p < .01). Multivariate analysis identified recipient height, donor BSA, and donor hemoglobin A1c as significant independent factors for graft thrombosis. Cubic spline curve analysis indicated an increased risk of graft thrombosis with increasing D/R BSA ratio. CONCLUSION: D/R size mismatch is associated with graft thrombosis after pancreas transplantation.

Utilization of the Pancreas From Donors With an Extremely High Pancreas Donor Risk Index: Report of the National Registry of Pancreas Transplantation.

Pancreas transplants from expanded criteria donors are performed widely in Japan because there is a shortage of brain-dead donors. However, the effectiveness of this strategy is unknown. We retrospectively studied 371 pancreas transplants to evaluate the possibility of pancreas transplantation from expanded criteria donors by the Pancreas Donor Risk Index (PDRI). Patients were divided into five groups according to quintiles of PDRI values (Q1-Q5). The 1-year pancreas graft survival rates were 94.5% for Q1, 91.9% for Q2, 90.5% for Q3, 89.3% for Q4, and 79.6% for Q5, and were significantly lower with a lower PDRI (p = 0.04). A multivariate analysis showed that the PDRI, donor hemoglobin A1c values, and pancreas transplantation alone significantly predicted 1-year pancreas graft survival (all p < 0.05). Spline curve analysis showed that the PDRI was incrementally associated with an increased risk of 1-year graft failure. In the group with a PDRI ≥ 2.87, 8/56 patients had graft failures within 1 month, and all were due to graft thrombosis. The PDRI is a prognostic factor related to the 1-year graft survival rate. However, pancreas transplantation from high-PDRI donors shows acceptable results and could be an alternative when the donor pool is insufficient.

Trends in cervical laminoplasty and 30-day postoperative complications: 10-year results from a retrospective, multi-institutional study of 1095 patients.

PURPOSE: This study aimed to investigate the recent 10-year trends in cervical laminoplasty and 30-day postoperative complications. METHODS: This retrospective multi-institutional cohort study enrolled patients who underwent laminoplasty for cervical spondylotic myelopathy (CSM) or ossification of the posterior longitudinal ligament. The primary outcome was the occurrence of all-cause 30-day complications. Trends were investigated and compared in the early (2008-2012) and late (2013-2017) periods. RESULTS: Among 1095 patients (mean age, 66 years; 762 [70%] male), 542 and 553 patients were treated in the early and late periods, respectively. In the late period, patients were older at surgery (65 years vs. 68 years), there were more males (66% vs. 73%), and open-door laminoplasty (50% vs. 69%) was the preferred procedure, while %CSM (77% vs. 78%) and the perioperative JOA scores were similar to the early period. During the study period, the rate of preservation of the posterior muscle-ligament complex attached to the C2/C7-spinous process (C2, 89% vs. 93%; C7, 62% vs. 85%) increased and the number of laminoplasty levels (3.7 vs. 3.1) decreased. While the 30-day complication rate remained stable (3.9% vs. 3.4%), C5 palsy tended to decrease (2.4% vs. 0.9%, P = 0.059); superficial SSI increased significantly (0% vs. 1.3%, P = 0.015), while the decreased incidence of deep SSI did not reach statistical significance (0.6% vs. 0.2%). CONCLUSIONS: From 2008 to 2017, there were trends toward increasing age at surgery and surgeons' preference for refined open-door laminoplasty. The 30-day complication rate remained stable, but the C5 palsy rate halved.

Effect of platelet-rich plasma on the acceleration of graft bone catabolism in lateral lumbar interbody fusion in a short-term assessment.

This study aimed to demonstrate whether impregnating the graft bone with platelet-rich plasma (PRP) accelerates graft bone catabolism in lateral lumbar interbody fusion (LLIF). Consecutive patients who underwent LLIF were assessed. Of the two spaces for bone grafts in the intervertebral cage, one space was filled with graft bone impregnated with PRP, and the other was filled with graft bone without PRP, which divided the graft bones into PRP and non-PRP groups. The mean Hounsfield units (HU) of the graft bone at the center of the cage space in the coronal and axial slices were measured using computed tomography (CT) images 1 week and 6 months after surgery. The delta value of HU from 1 week to 6 months after surgery was calculated for the PRP and non-PRP groups. We compared the delta values of the HU between the two groups. The PRP and non-PRP groups comprised 16 bone grafts. In the coronal slices, the HU value in the PRP group (delta value: 526.1 ± 352.2) tended to have a greater decrease at 6 months after surgery compared with that in the non-PRP group (delta value: 217.6 ± 240.4) (p = 0.065). In the axial slices, the HU value in the PRP group (delta value: 501.3 ± 319.6) was significantly decreased at 6 months after surgery compared with that in the non-PRP group (delta value: 159.2 ± 215.3) (p = 0.028). Impregnating the graft-bone with PRP accelerated graft bone catabolism in LLIF within 6 months after surgery.

Unidirectional porous beta-tricalcium phosphate as a potential bone regeneration material for infectious bony cavity without debridement in pyogenic spondylitis.

An 81-year-old man was initially diagnosed with T11 osteoporotic vertebral fracture. The fractured vertebral body was filled with unidirectional porous beta-tricalcium phosphate (ß-TCP) granules, and posterior spinal fixation was conducted using percutaneous pedicle screws. However, the pain did not improve, the inflammatory response increased, and bone destructive changes extended to T10. The correct diagnosis was pyogenic spondylitis with concomitant T11 fragility vertebral fracture. Revision surgery was conducted 2 weeks after the initial surgery, the T10 and T11 pedicle screws were removed, and refixation was conducted. After the revision surgery, the pain improved and mobilization proceeded. The infection was suppressed by the administration of sensitive antibiotics. One month after surgery, a lateral bone bridge appeared at the T10/11 intervertebral level. This increased in size over time, and synostosis was achieved at 6 months. Resorption of the unidirectional porous ß-TCP granules was observed over time and partial replacement with autologous bone was evident from 6 months after the revision surgery. Two years and 6 months after the revision surgery, although there were some residual ß-TCP and bony defect in the center of the vertebral body, the bilateral walls have well regenerated. This suggested that given an environment of sensitive antibiotic administration and restricted local instability, unidirectional porous ß-TCP implanted into an infected vertebral body may function as a resorbable bone regeneration scaffold without impeding infection control even without debridement of the infected bony cavity.

The relationship between spinal alignment and activity of paravertebral muscle during gait in patients with adult spinal deformity: a retrospective study.

BACKGROUND: Spinal alignment in patients with adult spinal deformity (ASD) changes between rest and during gait. However, it remains unclear at which point the compensated walking posture breaks down and how muscles respond. This study used time-synchronized electromyography (EMG) to investigate the relationship between dynamic spinal alignment and muscle activity during maximum walking duration to reveal compensation mechanisms. METHODS: This study collected preoperative three-dimensional gait analysis data from patients who were candidates for corrective surgery for ASD from April 2015 to May 2019. We preoperatively obtained dynamic spinal alignment parameters from initiation to cessation of gait using a motion capture system with time-synchronized surface integrated EMG (iEMG). We compared chronological changes in dynamic spinal alignment parameters and iEMG values 1) immediately after gait initiation (first trial), 2) half of the distance walked (half trial), and 3) immediately before cessation (last trial). RESULTS: This study included 26 patients (22 women, four men) with ASD. Spinal sagittal vertical axis distance during gait (SpSVA) increased over time (first vs. half vs. last, 172.4 ± 74.8 mm vs. 179.9 ± 76.8 mm vs. 201.6 ± 83.1 mm; P < 0.001). Cervical paravertebral muscle (PVM) and gluteus maximus activity significantly increased (P < 0.01), but thoracic and lumbar PVM activity did not change. Dynamic spinal alignment showed significant correlation with all muscle activity (cervical PVM, r = 0.41-0.54; thoracic PVM, r = 0.49-0.66; gluteus maximus, r = 0.54-0.69; quadriceps, r = 0.46-0.55) except lumbar PVM activity. CONCLUSION: Spinal balance exacerbation occurred continuously in patients with ASD over maximum walking distance and not at specific points. To maintain horizontal gaze, cervical PVM and gluteus maximus were activated to compensate for a dynamic spinal alignment change. All muscle activities, except lumbar PVM, increased to compensate for the spinal malalignment over time.

Binding of anisotropic curvature-inducing proteins onto membrane tubes.

Bin/Amphiphysin/Rvs superfamily proteins and other curvature-inducing proteins have anisotropic shapes and anisotropically bend biomembranes. Here, we report how the anisotropic proteins bind the membrane tube and are orientationally ordered using mean-field theory including an orientation-dependent excluded volume. The proteins exhibit a second-order or first-order nematic transition with increasing protein density depending on the radius of the membrane tube. The tube curvatures for the maximum protein binding and orientational order are different and varied by the protein density and rigidity. As the external force along the tube axis increases, a first-order transition from a large tube radius with low protein density to a small radius with high density occurs once, and subsequently, the protein orientation tilts to the tube-axis direction. When an isotropic bending energy is used for the proteins with an elliptic shape, the force-dependence curves become symmetric and the first-order transition occurs twice. This theory quantitatively reproduces the results of meshless membrane simulation for short proteins, whereas deviations are seen for long proteins owing to the formation of protein clusters.

Risk factors affecting vertebral collapse and kyphotic progression in postmenopausal osteoporotic vertebral fractures.

INTRODUCTION: We aimed to investigate the risk factors that affect vertebral deformity 6 months after osteoporotic vertebral fractures (OVFs) at the time of injury. MATERIALS AND METHODS: From May 2017 to May 2020, 70 postmenopausal women with OVFs were evaluated for age; body mass index; number of previous OVFs; total 25-hydroxy vitamin D [25(OH)D] levels; posterior wall injury on computed tomography; cross-sectional area (CSA) of the psoas major, erector spinae, and multifidus; fat infiltration; vertebral instability (VI) upon admission; collapse rate (CR); and kyphotic angle (KA) at 6 months after injury. A multiple regression analysis was conducted to identify the risk factors for the CR and KA. RESULTS: The CR was correlated with posterior wall injury (r = 0.295, p = 0.022), 25(OH)D levels (r = - 0.367, p = 0.002), and VI (r = 0.307, p = 0.010). In the multiple regression analysis, the 25(OH)D levels (p = 0.032) and VI (p = 0.035) were significant risk factors for the CR at the 6-month follow-up. The KA was correlated with the 25(OH)D levels (r = - 0.262, p = 0.031) and VI (r = 0.298, p = 0.012). In the multiple regression analysis, the CSA of the psoas major (p = 0.011) and VI (p < 0.001) were significant risk factors for the KA at the 6-month follow-up. CONCLUSION: In cases with large VI at the time of injury, the CR and KA were significantly higher at 6 months after injury. Moreover, the CR was affected by the 25(OH)D level, while the KA was affected by the CSA of the psoas major upon admission.

Development and Validation of A Liquid Chromatography-Tandem Mass Spectrometry Method to Simultaneously Measure Tacrolimus and Everolimus Concentrations in Kidney Allograft Biopsies After Kidney Transplantation.

BACKGROUND: Therapeutic drug monitoring is necessary for immunosuppressive therapy with tacrolimus and everolimus after kidney transplantation. Several studies have suggested that the concentrations of immunosuppressive agents in allografts may better reflect clinical outcomes than whole blood concentrations. This study aimed to develop a method for the simultaneous quantification of tacrolimus and everolimus concentrations in clinical biopsy samples and investigate their correlation with histopathological findings in kidney transplant recipients. METHODS: Fourteen biopsy samples were obtained from kidney transplant recipients at 3 months after transplantation. Kidney allograft concentrations (Ctissue) of tacrolimus and everolimus were measured by liquid chromatography-tandem mass spectrometry, and the corresponding whole blood trough concentrations (C0) were obtained from clinical records. RESULTS: The developed method was validated over a concentration range of 0.02-2.0 ng/mL for tacrolimus and 0.04-4.0 ng/mL for everolimus in kidney tissue homogenate. The Ctissue of tacrolimus and everolimus in kidney biopsies ranged from 21.0 to 86.7 pg/mg tissue and 33.5-105.0 pg/mg tissue, respectively. Dose-adjusted Ctissue of tacrolimus and everolimus was significantly correlated with the dose-adjusted C0 (P < 0.0001 and P = 0.0479, respectively). No significant association was observed between the Ctissue of tacrolimus and everolimus and the histopathologic outcomes at 3 months after transplantation. CONCLUSIONS: This method could support further investigation of the clinical relevance of tacrolimus and everolimus allograft concentrations after kidney transplantation.