Arteriolar hyalinization at 0-hour biopsy predicts long-term graft function in deceased kidney transplantation.

OBJECTIVES: Regarding the relationship between donor kidney quality and renal graft function after deceased kidney transplantation (KTx) following donation after cardiac death (DCD), the evaluation timing varies depending on the study. Evaluation of histology and changes in long-term renal graft function is limited. METHODS: A retrospective single-center study included 71 recipients who underwent 0-hour biopsy for KTx from DCD. The recipients were divided into two groups to evaluate factors related to renal graft function (study1). The two groups were categorized as stable graft function and poor graft function with the change of estimated glomerular filtration rate (eGFR) after KTx. The recipients were then divided into four groups to assess whether the factors identified in study1 were related to the change in long-term renal graft function (study2). They were categorized as follows: Improved, Stable, Deteriorated, and Primary non-function with the change of eGFR after KTx. RESULTS: In study1, donor age ≥ 50 years (29.5% vs. 65.2%; p = 0.09), banff arteriolar hyalinosis (ah) score (0.66 ± 0.78 vs. 1.2 ± 1.0; p = 0.018), and presence of glomerulosclerosis (43.2% vs. 76.2%; p = 0.017) were significant risk factors for poor long-term graft function. When the recipients were divided into four groups, the severity of ah correlated well with changes in long-term renal function. CONCLUSIONS: We can predict the shift in long-term renal graft function after KTx from DCD according to the severity of ah by 0-hour biopsy.

Does human foot anthropometry relate to plantar flexor fascicle mechanics and metabolic energy cost across various walking speeds?

Foot structures define the leverage in which the ankle muscles push off against the ground during locomotion. While prior studies have indicated that inter-individual variation in anthropometry (e.g. heel and hallux lengths) can directly affect force production of ankle plantar flexor muscles, its effect on the metabolic energy cost of locomotion has been inconclusive. Here, we tested the hypotheses that shorter heels and longer halluces are associated with slower plantar flexor (soleus) shortening velocity and greater ankle plantar flexion moment, indicating enhanced force potential as a result of the force-velocity relationship. We also hypothesized that such anthropometry profiles would reduce the metabolic energy cost of walking at faster walking speeds. Healthy young adults (N=15) walked at three speeds (1.25, 1.75 and 2.00 m s-1), and we collected in vivo muscle mechanics (via ultrasound), activation (via electromyography) and whole-body metabolic energy cost of transport (via indirect calorimetry). Contrary to our hypotheses, shorter heels and longer halluces were not associated with slower soleus shortening velocity or greater plantar flexion moment. Additionally, longer heels were associated with reduced metabolic cost of transport, but only at the fastest speed (2.00 m s-1, R2=0.305, P=0.033). We also found that individuals with longer heels required less increase in plantar flexor (soleus and gastrocnemius) muscle activation to walk at faster speeds, potentially explaining the reduced metabolic cost.

Hyporesponsiveness against donor's ABO antigens of renal grafts after ABO-incompatible kidney transplantation.

BACKGROUND: ABO antigens expressed on the red blood cells (RBCs) are not identical to those expressed on the renal endothelial cells. The isohemagglutinin assay employing the RBCs is the gold standard for evaluating anti-ABO antibody (Ab) levels. However, it remains unclear whether the anti-ABO Abs detected by the isohemagglutinin assay after ABO-incompatible (ABOi) kidney transplantations (KTx) that are not associated with antibody-mediated rejection can bind to renal graft endothelial cells. METHODS: Ninety plasma samples were collected from patients with stable graft function after ABO-compatible (ABOc) or ABOi KTx. Anti-ABO Ab titers were examined by both the isohemagglutinin assay and the CD31-ABO microarray, which was developed as a mimic of the ABO antigens expressed on the renal endothelial cells. RESULTS: The antibody titers detected by the isohemagglutinin assay and the CD31-ABO microarray after the ABOc KTx relatively correlated with each other. However, the CD31-ABO microarray results showed low antibody levels against donor blood group antigens after ABOi KTx and did not correlate with the isohemagglutinin assay. In contrast, the antibody levels against non-donor blood group antigens after ABOi KTx were comparable to those after the ABOc KTx. Fourteen patients received graft biopsies, and no antibody-mediated rejection was observed in ABOi KTx recipients, except for two patients who had anti-donor-HLA Abs. CONCLUSION: The present study suggested that the anti-ABO Abs detected by the isohemagglutinin assay after ABOi KTx with stable graft function were hyporeactive to the ABO antigen of graft renal endothelial cells.

A passive exoskeleton can assist split-belt adaptation.

An exoskeletal device can assist walking in those with gait deficits. A passive exoskeleton can be a favorable choice for local or home rehabilitation settings because it is affordable, light weight, and less complex to utilize. While there is research that investigates the effects of exoskeleton on gait research examining the effects of such devices on gait adaptation, is rare. This is important because in diseases like stroke, the ability to flexibly adapt is affected, such that functional recovery becomes difficult. The purpose of this study was to characterize gait adaptation patterns that result from exoskeleton usage during a split-belt adaptation task. Healthy young participants were randomly assigned to a unilateral exoskeleton or a no-exoskeleton group. Each participant performed the specific split-belt adaptation tasks on the treadmill, where the speed of each belt could be controlled independently. Symmetry indices of spatiotemporal variables were calculated to quantify gait adaptation. To analyze the adaptation, trials were divided into early and late adaptation. We also analyzed degree of adaptation, and transfer effects. We also measured the symmetry of the positive power generated by the individual legs during the split-belt task to determine if using exoskeleton assistance reduced power in the exoskeleton group versus the no-exoskeleton group. Use of a passive exoskeleton device altered gait adaptation during a split-belt treadmill task in comparison to the control group. Such adaptation was found to be largely restricted to the temporal domain. Changes in the gait coordination patterns consisted of both early and late adaptive changes, especially in intra-limb patterns like stance time rather than inter-limb patterns like step time. Although the symmetry of the positive power generated during the split-belt task was found to be reduced for the exoskeleton-assistance group, it was shown that this was primarily the result of increased positive power generated by the side not receiving exoskeletal assistance. An unpowered assistive device can provide a unique solution for coordinating the lower limbs during different gait tasks. Such a solution could reduce the neural burden of adaptation consequently resulting in a reduction of the mechanical burden of walking during the bilateral gait coordination task. This may be useful for accelerating gait rehabilitation in different patient populations. However, balance control is important to consider during unilateral exoskeletal assistance.

A Novel Method of CD31-Combined ABO Carbohydrate Antigen Microarray Predicts Acute Antibody-Mediated Rejection in ABO-Incompatible Kidney Transplantation.

Isohemagglutinin assays employing red blood cells (RBCs) are the most common assays used to measure antibody titer in ABO-incompatible kidney transplantation (ABOi KTx). However, ABO antigens expressed on RBCs are not identical to those of kidney and antibody titers do not always correlate with clinical outcome. We previously reported that CD31 was the main protein linked to ABO antigens on kidney endothelial cells (KECs), which was different from those on RBCs. We developed a new method to measure antibody titer using a microarray of recombinant CD31 (rCD31) linked to ABO antigens (CD31-ABO microarray). Mass spectrometry analysis suggested that rCD31 and native CD31 purified from human kidney had similar ABO glycan. To confirm clinical use of CD31-ABO microarray, a total of 252 plasma samples including volunteers, hemodialysis patients, and transplant recipients were examined. In transplant recipients, any initial IgG or IgM antibody intensity >30,000 against the donor blood type in the CD31-ABO microarray showed higher sensitivity, specificity, positive predictive value, and negative predictive value of AABMR, compared to isohemagglutinin assays. Use of a CD31-ABO microarray to determine antibody titer specifically against ABO antigens expressed on KECs will contribute to precisely predicting AABMR or preventing over immunosuppression following ABOi KTx.

Novel Bi-Specific Immuno-Modulatory Tribodies Potentiate T Cell Activation and Increase Anti-Tumor Efficacy.

Cancer immunotherapy has already shown significant improvements by combining different antibodies specific for distinct immune checkpoints, such as Ipilimumab and Nivolumab. Here, we tested combinatorial treatments of immunomodulatory antibodies, previously generated in our laboratory, for their effects on hPBMC activation, either upon stimulation with SEB or in co-cultures with tumor cells by cytokine secretion assays. We found that some of them showed additive or synergistic effects, and on the basis of these observations, we constructed, for the first time, four novel bispecific tribodies (TR), made up of a Fab derived from one anti-IC mAb and two scFvs derived from another mAb targeting a different IC. All four TRs cotargeting either programmed cell death protein 1 (PD-1) and Lymphocyte Activating 3 (LAG-3) or programmed death-ligand 1 (PD-L1) and LAG-3 retained binding affinity for their targets and the antagonistic effects of their parental mAbs, but some of them also showed an increased ability to induce lymphocyte activation and increased in vitro cytotoxicity against tumor cells compared to parental antibodies used either alone or in combinatorial treatments. Furthermore, none of the tribodies showed significant increased cytotoxicity on human cardiomyocytes. Considering that the tribody format reduces production costs (as only one construct provides the inhibitory effects of two antibodies), has an intermediate molecular size (100 kDa) which is well suited for both tumor penetration and an acceptable half-life, we think that these novel immunomodulatory TRBs have the potential to become precious tools for therapeutic applications, particularly in monotherapy-resistant cancer patients.

Efficacy and safety of colorectal endoscopic submucosal dissection in patients with sarcopenia.

BACKGROUND: Endoscopic submucosal dissection (ESD) for early-stage colorectal cancer (CRC) has become a common and useful treatment. Although sarcopenia has been identified as an independent risk factor for complications after surgery for CRC, whether sarcopenia is also an independent risk factor for complications after colorectal ESD remains to be clarified. The aim of this study was to compare the outcomes of colorectal ESD in patients with and those without sarcopenia. METHODS: This is a retrospective cohort study. A total of 334 patients underwent colorectal ESD for 361 neoplasms at Hiratsuka City Hospital from March 2012 to October 2018. The neoplasms were divided into two groups depending on the presence or absence of sarcopenia in the patients. RESULTS: Overall, 334 patients underwent colorectal ESD for 361 neoplasms during the study period. We excluded 90 patients (90 neoplasms), and 244 patients (277 neoplasms) were included in the final analysis (134 from the sarcopenia group, 137 from the non-sarcopenia group). The en-bloc resection rate was high and was not significantly different between the sarcopenia group [126/134 (94.1%)] and the non-sarcopenia group [133/137 (97.1%)], P = 0.1778). The rate of perforation and the rate of delayed bleeding were not significantly different between the sarcopenia group and the non-sarcopenia group [6/134 (4.5%) vs. 9/137 (6.6%), P = 0.314, 4/134 (3%) vs. 6/137 (4.4%), P = 0.3885, respectively]. CONCLUSIONS: The presence of sarcopenia did not influence the rate of complications after ESD. Colorectal ESD is safe and effective even in patients with sarcopenia. Prospective multicenter studies are necessary to confirm our results.

Reducing stiffness of shock-absorbing pylon amplifies prosthesis energy loss and redistributes joint mechanical work during walking.

BACKGROUND: A shock-absorbing pylon (SAP) is a modular prosthetic component designed to attenuate impact forces, which unlike traditional pylons that are rigid, can compress to absorb, return, or dissipate energy. Previous studies found that walking with a SAP improved lower-limb prosthesis users' comfort and residual limb pain. While longitudinal stiffness of a SAP has been shown to affect gait kinematics, kinetics, and work done by the entire lower limb, the energetic contributions from the prosthesis and the intact joints have not been examined. The purpose of this study was to determine the effects of SAP stiffness and walking speed on the mechanical work contributions of the prosthesis (i.e., all components distal to socket), knee, and hip in individuals with a transtibial amputation. METHODS: Twelve participants with unilateral transtibial amputation walked overground at their customary (1.22 ± 0.18 ms-1) and fast speeds (1.53 ± 0.29 ms-1) under four different levels of SAP stiffness. Power and mechanical work profiles of the leg joints and components distal to the socket were quantified. The effects of SAP stiffness and walking speed on positive and negative work were analyzed using two-factor (stiffness and speed) repeated-measure ANOVAs (α = 0.05). RESULTS: Faster walking significantly increased mechanical work from the SAP-integrated prosthesis (p < 0.001). Reducing SAP stiffness increased the magnitude of prosthesis negative work (energy absorption) during early stance (p = 0.045) by as much as 0.027 Jkg-1, without affecting the positive work (energy return) during late stance (p = 0.159), suggesting a damping effect. This energy loss was partially offset by an increase in residual hip positive work (as much as 0.012 Jkg-1) during late stance (p = 0.045). Reducing SAP stiffness also reduced the magnitude of negative work on the contralateral sound limb during early stance by 11-17% (p = 0.001). CONCLUSIONS: Reducing SAP stiffness and faster walking amplified the prostheses damping effect, which redistributed the mechanical work, both in magnitude and timing, within the residual joints and sound limb. With its capacity to absorb and dissipate energy, future studies are warranted to determine whether SAPs can provide additional user benefit for locomotor tasks that require greater attenuation of impact forces (e.g., load carriage) or energy dissipation (e.g., downhill walking).

The Role of Leaky Gut in Nonalcoholic Fatty Liver Disease: A Novel Therapeutic Target.

The liver directly accepts blood from the gut and is, therefore, exposed to intestinal bacteria. Recent studies have demonstrated a relationship between gut bacteria and nonalcoholic fatty liver disease (NAFLD). Approximately 10-20% of NAFLD patients develop nonalcoholic steatohepatitis (NASH), and endotoxins produced by Gram-negative bacilli may be involved in NAFLD pathogenesis. NAFLD hyperendotoxicemia has intestinal and hepatic factors. The intestinal factors include impaired intestinal barrier function (leaky gut syndrome) and dysbiosis due to increased abundance of ethanol-producing bacteria, which can change endogenous alcohol concentrations. The hepatic factors include hyperleptinemia, which is associated with an excessive response to endotoxins, leading to intrahepatic inflammation and fibrosis. Clinically, the relationship between gut bacteria and NAFLD has been targeted in some randomized controlled trials of probiotics and other agents, but the results have been inconsistent. A recent randomized, placebo-controlled study explored the utility of lubiprostone, a treatment for constipation, in restoring intestinal barrier function and improving the outcomes of NAFLD patients, marking a new phase in the development of novel therapies targeting the intestinal barrier. This review summarizes recent data from studies in animal models and randomized clinical trials on the role of the gut-liver axis in NAFLD pathogenesis and progression.

Walking with added mass magnifies salient features of human foot energetics.

The human foot serves numerous functional roles during walking, including shock absorption and energy return. Here, we investigated walking with added mass to determine how the foot would alter its mechanical work production in response to a greater force demand. Twenty-one healthy young adults walked with varying levels of added body mass: 0%, +15% and +30% (relative to their body mass). We quantified mechanical work performed by the foot using a unified deformable segment analysis and a multi-segment foot model. We found that walking with added mass tended to magnify certain features of the foot's functions. Magnitudes of both positive and negative mechanical work, during stance in the foot, increased when walking with added mass. Yet, the foot preserved similar amounts of net negative work, indicating that the foot dissipates energy overall. Furthermore, walking with added mass increased the foot's negative work during early stance phase, highlighting the foot's role as a shock-absorber. During mid to late stance, the foot produced greater positive work when walking with added mass, which coincided with greater work from the structures spanning the midtarsal joint (i.e. arch). While this study captured the overall behavior of the foot when walking with varying force demands, future studies are needed to further determine the relative contribution of active muscles and elastic tissues to the foot's overall energy.

Therapeutic potential of ciclesonide inahalation for COVID-19 pneumonia: Report of three cases.

No specific and effective anti-viral treatment has been approved for COVID-19 so far. Systemic corticosteroid has been sometimes administered to severe infectious diseases combined with the specific treatment. However, as lack of the specific anti-SARS-CoV-2 drug, systemic steroid treatment has not been recommended for COVID-19. We report here three cases of the COVID-19 pneumonia successfully treated with ciclesonide inhalation. Rationale of the treatment is to mitigate the local inflammation with inhaled steroid that stays in the lung and to inhibit proliferation of the virus by antiviral activity. Larger and further studies are warranted to confirm the result of these cases.

Locomotor patterns change over time during walking on an uneven surface.

During walking, uneven surfaces impose new demands for controlling balance and forward progression at each step. It is unknown to what extent walking may be refined given an amount of stride-to-stride unpredictability at the distal level. Here, we explored the effects of an uneven terrain surface on whole-body locomotor dynamics immediately following exposure and after a familiarization period. Eleven young, unimpaired adults walked for 12 min on flat and uneven terrain treadmills. The whole-body center of mass excursion range (COMexc) and peak velocity (COMvel), step length and width were estimated. On first exposure to uneven terrain, we saw significant increases in medial-lateral COMexc and lateral COMvel, and in the variability of COMexc, COMvel and foot placement in both anterior-posterior and medial-lateral directions. Increases in step width and decreases in step length supported the immediate adoption of a cautious, restrictive solution on uneven terrain. After familiarization, step length increased and the variability of anterior-posterior COMvel and step length reduced, while step width and lateral COMvel reduced, alluding to a refinement of movement and a reduction of conservative strategies over time. However, the variability of medial-lateral COMexc and lateral COMvel increased, consistent with the release of previously constrained degrees of freedom. Despite this increase in variability, a strong relationship between step width and medial-lateral center of mass movement was maintained. Our results indicate that movement strategies of unimpaired adults when walking on uneven terrain can evolve over time with longer exposure to the surface.

The effects of ankle stiffness on mechanics and energetics of walking with added loads: a prosthetic emulator study.

BACKGROUND: The human ankle joint has an influential role in the regulation of the mechanics and energetics of gait. The human ankle can modulate its joint 'quasi-stiffness' (ratio of plantarflexion moment to dorsiflexion displacement) in response to various locomotor tasks (e.g., load carriage). However, the direct effect of ankle stiffness on metabolic energy cost during various tasks is not fully understood. The purpose of this study was to determine how net metabolic energy cost was affected by ankle stiffness while walking under different force demands (i.e., with and without additional load). METHODS: Individuals simulated an amputation by using an immobilizer boot with a robotic ankle-foot prosthesis emulator. The prosthetic emulator was controlled to follow five ankle stiffness conditions, based on literature values of human ankle quasi-stiffness. Individuals walked with these five ankle stiffness settings, with and without carrying additional load of approximately 30% of body mass (i.e., ten total trials). RESULTS: Within the range of stiffness we tested, the highest stiffness minimized metabolic cost for both load conditions, including a ~ 3% decrease in metabolic cost for an increase in stiffness of about 0.0480 Nm/deg/kg during normal (no load) walking. Furthermore, the highest stiffness produced the least amount of prosthetic ankle-foot positive work, with a difference of ~ 0.04 J/kg from the highest to lowest stiffness condition. Ipsilateral hip positive work did not significantly change across the no load condition but was minimized at the highest stiffness for the additional load conditions. For the additional load conditions, the hip work followed a similar trend as the metabolic cost, suggesting that reducing positive hip work can lower metabolic cost. CONCLUSION: While ankle stiffness affected the metabolic cost for both load conditions, we found no significant interaction effect between stiffness and load. This may suggest that the importance of the human ankle's ability to change stiffness during different load carrying tasks may not be driven to minimize metabolic cost. A prosthetic design that can modulate ankle stiffness when transitioning from one locomotor task to another could be valuable, but its importance likely involves factors beyond optimizing metabolic cost.

Uneven terrain exacerbates the deficits of a passive prosthesis in the regulation of whole body angular momentum in individuals with a unilateral transtibial amputation.

BACKGROUND: Uneven ground is a frequently encountered, yet little-studied challenge for individuals with amputation. The absence of control at the prosthetic ankle to facilitate correction for surface inconsistencies, and diminished sensory input from the extremity, add unpredictability to an already complex control problem, and leave limited means to produce appropriate corrective responses in a timely manner. Whole body angular momentum, L, and its variability across several strides may provide insight into the extent to which an individual can regulate their movement in such a context. The aim of this study was to explore L in individuals with a transtibial amputation, when challenged by an uneven surface. We hypothesized that, similar to previous studies, sagittal plane L would be asymmetrical on uneven terrain, and further, that uneven terrain would evoke a greater variability in L from stride to stride in individuals with amputation in comparison to unimpaired individuals, due to a limited ability to discern and correct for changing contours beneath the prosthetic foot. METHODS: We examined sagittal plane L in ten individuals with a unilateral transtibial amputation and age- and gender- matched control participants walking on flat (FT) and uneven (UT) treadmills. The average range of L in the first 50% of the gait cycle (LR), the average L at foot contact (LC) and their standard deviations (vLR, vLC) were computed over 60 strides on each treadmill. RESULTS: On both surfaces we observed a higher LR on the prosthetic side and a reduced LC on the sound side (p < 0.001) in the amputee cohort, consistent with previous findings. UT invoked an increase in LC (p = 0.006), but not LR (p = 0.491). vLR, and vLC were higher in individuals with amputation (p < 0.001, p = 0.002), and increased in both groups on UT (p < 0.001). CONCLUSIONS: These findings support previous assertions that individuals with amputation regulate L less effectively, and suggest that the deficits of the prosthesis are exacerbated on uneven terrain, potentially to the detriment of balance. Further, the results indicate that a greater demand may be placed on the unaffected side to control movement.

Analysis of the prevalence of systemic de novo thrombotic microangiopathy after ABO-incompatible kidney transplantation and the associated risk factors.

OBJECTIVES: To analyze the prevalence of systemic de novo thrombotic microangiopathy in ABO-incompatible kidney transplantation and risk factors associated with this condition. METHODS: A total of 201 patients who received living-donor kidney transplantation (114 patients with ABO-identical kidney transplantation and 87 patients with ABO-incompatible kidney transplantation) were retrospectively analyzed. Systemic de novo thrombotic microangiopathy was diagnosed clinically according to the presence of thrombocytopenia with microangiopathic hemolytic anemia and pathological findings of thrombotic microangiopathy. Anti-A and anti-B antibodies were purified from human plasma, and these antibodies' bindings to human kidney were investigated in vitro. RESULTS: ABO-incompatible kidney transplantation was a significant risk factor of systemic de novo thrombotic microangiopathy (odds ratio 55.9, 95% CI 1.8-8.9, P < 0.001) after transplantation. Multivariate logistic regression analysis showed that non-use of mycophenolate mofetil, pretreatment immunoglobulin G antibody titer ≥64-fold and pretransplant immunoglobulin M antibody titer ≥16-fold were significant risk factors for systemic de novo thrombotic microangiopathy in ABO-incompatible kidney transplantation. Microvascular inflammation of 1-h post-transplant biopsy could be observed more frequently in thrombotic microangiopathy patients than in non-thrombotic microangiopathy patients. Anti-A and anti-B antibodies purified from human plasma showed a strong in vitro reaction against human kidney when the antibody titer was ≥16-fold. CONCLUSIONS: Antibody titer should be decreased to ≤16-fold until the day of ABO-incompatible kidney transplantation by desensitization therapy including mycophenolate mofetil. The 1-h biopsy results might help to diagnose systemic de novo thrombotic microangiopathy.

[Practical Utilization of Home Care Support System and Influence of Home Care on the Regional Core Hospital].

The home care support system, newly established in 2014, is a system that always secures the hospitalization of pre-registered home care patients who need to be hospitalized. Ashigarakami Hospital has operated this system since April 2014. As of May 2018, a total of 215 people registered, and 156 people have died. Among the deceased patients, 77(49.4%)died at home, which was higher than the proportion of home deaths(13.0%)in the Japanese population dynamics survey in 2016. In patients who had malignant diseases, they could spend more than half of the period from their introduction to the system up to death being treated at home. Even in the case of death at a hospital, the duration of the last hospitalization was 18 days on average(median of 12 days). In most cases, patients were treated at home until shortly before death.

Interaction between step-to-step variability and metabolic cost of transport during human walking.

Minimizing the metabolic cost of transport can affect selection of the preferred walking speed. While many factors can affect metabolic cost of transport during human walking, its interaction with step-to-step variability is unclear. Here, we aimed to determine the interaction between metabolic cost of transport and step length variability during human walking at different speeds. In particular, two aspects of step length variability were analyzed: the amount of variations ('variations') and the organization of the step-to-step fluctuations ('fluctuations'). Ten healthy, young participants walked on a treadmill at five speeds, ranging from 0.75 to 1.75 m s-1 Metabolic cost of transport, step length variations (coefficient of variation) and step length fluctuations (quantified via detrended fluctuation analysis) were calculated. A mixed-model ANOVA revealed that variations and walking speed were strong predictors of metabolic cost of transport (R2=0.917, P<0.001), whereas fluctuations were not. Preferred walking speed (1.05±0.20 m s-1) was not significantly different from the speed at which metabolic cost of transport was minimized (1.04±0.05 m s-1; P=0.792), nor from the speed at which fluctuations were most persistent (1.00±0.41 m s-1; P=0.698). The minimization of variations occurred at a faster speed (1.56±0.17 m s-1) than the preferred walking speed (P<0.001). Step length variations likely affect metabolic cost of transport because greater variations are indicative of suboptimal, mechanically inefficient steps. Fluctuations have little or no effect on metabolic cost of transport, but still may relate to preferred walking speed.

Prosthetic energy return during walking increases after 3 weeks of adaptation to a new device.

BACKGROUND: There are many studies that have investigated biomechanical differences among prosthetic feet, but not changes due to adaptation over time. There is a need for objective measures to quantify the process of adaptation for individuals with a transtibial amputation. Mechanical power and work profiles are a primary focus for modern energy-storage-and-return type prostheses, which strive to increase energy return from the prosthesis. The amount of energy a prosthesis stores and returns (i.e., negative and positive work) during stance is directly influenced by the user's loading strategy, which may be sensitive to alterations during the course of an adaptation period. The purpose of this study was to examine changes in lower limb mechanical work profiles during walking following a three-week adaptation to a new prosthesis. METHODS: A retrospective analysis was performed on 22 individuals with a unilateral transtibial amputation. Individuals were given a new prosthesis at their current mobility level (K3 or above) and wore it for three weeks. Kinematic and kinetic measures were recorded from overground walking at 0, 1.5, and 3 weeks into the adaptation period at a self-selected pace. Positive and negative work done by the prosthesis and sound ankle-foot were calculated using a unified deformable segment model and a six-degrees-of-freedom model for the knee and hip. RESULTS: Positive work from the prosthesis ankle-foot increased by 6.1% and sound ankle-foot by 5.7% after 3 weeks (p = 0.041, 0.036). No significant changes were seen in negative work from prosthesis or sound ankle-foot (p = 0.115, 0.192). There was also a 4.1% increase in self-selected walking speed after 3 weeks (p = 0.038). Our data exhibited large inter-subject variations, in which some individuals followed group trends in work profiles while others had opposite trends in outcome variables. CONCLUSIONS: After a 3-week adaptation, 14 out of 22 individuals with a transtibial amputation increased energy return from the prosthesis. Such findings could indicate that individuals may better utilize the spring-like function of the prosthesis after an adaptation period.

Gait training using a stationary, one-leg gait exercise assist robot for chronic stroke hemiplegia: a case report.

[Purpose] The Gait Exercise Assist Robot (GEAR) is a stationary, one-leg robot for gait training. The purpose of this case study was to evaluate the efficacy of rehabilitation using GEAR training for chronic stroke hemiplegia. [Participant and Methods] The participant was a 66-year-old male stroke survivor with left hemiparesis due to a right putaminal hemorrhage. He could walk slowly under supervision, although his gait had a constant forward trunk lean, with flexed knee, and a lack of hip extension movement on the affected side. Gait training using GEAR and physical therapy were performed for 14 days. Under both training conditions, the physical therapist made the participant conscious of extension movement of the hip joint in the affected-side stance phase. The robotic assistance was adjusted to maximize voluntary movement while observing gait. Physical function and gait ability parameters were evaluated before and after training. [Results] After training, extension motion of the hip joint increased in the affected-side stance phase, and body weight was transferred smoothly onto the affected-side limb, leading to an improvement in gait speed. [Conclusion] Gait training using GEAR and physical therapy may improve gait pattern and speed in patients with chronic stroke hemiplegia.

Results of a multicenter prospective clinical study in Japan for evaluating efficacy and safety of desensitization protocol based on rituximab in ABO-incompatible kidney transplantation.

BACKGROUND: Deceased organ donations are rare in Japan, with most kidney transplants performed from a limited number of living donors. Researchers have thus developed highly successful ABO-incompatible transplantation procedures, emphasizing preoperative desensitization and postoperative immunosuppression. A recent open-label, single-arm, multicenter clinical study prospectively examined the efficacy and safety of rituximab/mycophenolate mofetil desensitization in ABO-incompatible kidney transplantation without splenectomy. METHODS: Mycophenolate mofetil and low dose steroid were started 28 days pretransplant, followed by two doses of rituximab 375 mg/m2 at day -14 and day -1, and postoperative immunosuppression with tacrolimus or ciclosporin and basiliximab. The primary endpoint was the non-occurrence rate of acute antibody-mediated rejection. Patient survival and graft survival were monitored for 1 year posttransplant. RESULTS: Eighteen patients received rituximab and underwent ABO-incompatible kidney transplantation. CD19-positive peripheral B cell count decreased rapidly after the first rituximab infusion and recovered gradually after week 36. The desensitization protocol was tolerable, and most rituximab-related infusion reactions were mild. No anti-A/B antibody-mediated rejection occurred with this series. One patient developed anti-HLA antibody-mediated rejection (Banff 07 type II) on day 2, which was successfully managed. Patient and graft survival were both 100 % after 1 year. CONCLUSION: Our desensitization protocol was confirmed to be clinically effective and with acceptable toxicities for ABO-I-KTx (University Hospital Medical Information Network Registration Number: UMIN000006635).