Efficacy of personalized exercise program on physical function in elderly patients with rheumatoid arthritis at high risk for sarcopenia: study protocol for a randomized controlled trial.

BACKGROUND: Patients with rheumatoid arthritis (RA) are prone to muscle atrophy due to inflammatory cytokines and corticosteroid use and immobility due to joint pain and deformity. Although resistance training is effective and safe in reversing muscle atrophy in RA, some patients are unable to perform a conventional high-load exercise program due to disease-related limitations. This study aims to examine the efficacy of individualized exercise therapy on physical function in elderly patients with RA who are at a high risk for sarcopenia. METHODS: This study is a single-center, parallel-group, two-arm, healthcare provider- and outcome assessor-blinded, superiority randomized controlled trial with a 1:1 allocation ratio. A total of 160 participants with RA between 60 and 85 years of age with a positive screening test for sarcopenia will be included. The intervention group will receive nutritional guidance and a four-month individualized exercise program in addition to the usual treatment. The control group will receive nutritional guidance in addition to the usual care. The primary endpoint will be physical function assessed using the Short Physical Performance Battery (SPPB) at 4 months. The data on outcome measures will be collected at baseline and at the two- and four-month follow-ups. Linear mixed-effects models for repeated measures will be conducted using the modified intention-to-treat analysis population. DISCUSSION: This study will provide evidence on whether a personalized exercise program can improve physical function and quality of life in elderly patients with RA. Some limitations include limited generalizability due to the single-center study and lack of blinding of the patients to the intervention assignment because of the nature of the exercise. Physical therapists may use this knowledge in their daily practice to improve RA treatment. Tailored exercise may enhance the health outcomes of the RA population and contribute to a reduction in healthcare costs. TRIAL REGISTRATION: The study protocol was retrospectively registered at the University hospital Medical Information Network-Clinical Trial Repository (UMIN-CTR) (registration number: UMIN000044930, https://www.umin.ac.jp/ctr/index-j.htm ) on January 4, 2022.

Management of sarcopenia in patients with rheumatoid arthritis.

This review summarizes the evidence for the management of sarcopenia in patients with rheumatoid arthritis (RA) in terms of drugs, exercise, and nutrition. Sarcopenia is a decrease in skeletal muscle mass and muscle strength or physical function. The prevalence of sarcopenia in patients with RA is higher than that in the general population. The treatment and management of sarcopenia in patients with RA are clinically important for long-term prognosis. One of the mechanisms of muscle metabolism is the pro-inflammatory cytokine pathway, which involves tumour necrosis factor α and interleukin-6, and is a common pathway in the pathogenesis of RA. Thus, tumour necrosis factor α and interleukin-6 inhibitors may play a potential role in controlling sarcopenia. In exercise therapy, a combination of moderate resistance and aerobic exercise may be effective in improving muscle strength, muscle mass, and physical function; however, intense exercise may exacerbate the inflammatory response in RA. Regarding nutrition, protein intake is generally considered beneficial, but other nutrients such as vitamin D and carotenoids have also been studied. Overall, there remains a lack of concrete evidence on sarcopenia treatment and management in patients with RA from any perspective; more longitudinal and intervention studies are needed in the future.

Prevalence and factors associated with sarcopenia in patients with rheumatoid arthritis.

Objectives: Sarcopenia is characterized by loss of muscle strength and mass, leading to falls and adverse health outcomes. Our aim was to determine the prevalence of sarcopenia in patients with rheumatoid arthritis (RA) and to identify factors associated with sarcopenia in these patients. Methods: A cross-sectional study of 388 consecutive women with RA was conducted, assessing muscle mass and strength, and walking speed. Falls and bone fractures sustained over the prior year were evaluated. The association between sarcopenia and RA characteristics, falls, and bone fractures was evaluated using logistic regression analyses. Results: The prevalence of sarcopenia was 37.1% (14.7%, severe sarcopenia; 22.4%, sarcopenia), with 49.0% classified as having low muscle mass. The incidence of falls, fractures, and lower bone mineral density was higher in patients with than without sarcopenia. Age, RA duration, Steinbrocker's stage, the high Mini-Nutritional Assessment-Short Form score and the use of biological disease-modifying anti-rheumatic drugs (bDMARDs) were independent factors associated with sarcopenia. Conclusion: We confirmed that sarcopenia develops in a significant proportion of patients with RA. Age, longer disease duration, joint destruction and malnutrition were positively associated with sarcopenia, with the use of bDMARDs being negatively associated.

Comment on "The effect of disease-modifying anti-rheumatic drugs on skeletal muscle mass in rheumatoid arthritis patients: a systematic review with meta-analysis".

We read with great interest the article by Hein et al., which described the meta-analysis study on the impact of disease-modifying anti-rheumatic drugs (DMARDs) therapy on skeletal muscle mass in rheumatoid arthritis (RA) patients. While the data presented are impressive, we add some remarks about methodological issues that should be considered. First, this meta-analysis does not include several necessary studies that have provided data on the relationship between anti-tumor necrosis factor (anti-TNF) therapy and body composition. To make the meta-analysis more comprehensive, it could be necessary to incorporate these studies into this analysis. Second, this study did not employ a representative measure of skeletal muscle mass that was adjusted for body size, such as skeletal muscle mass index (SMI). It is well recognized that skeletal muscle mass varies with body size, particularly height and body mass index. Given the heterogeneity background of body size in the studies included in this meta-analysis, it may be worthwhile to conduct an additional analysis regarding the associations between DMARDs and the adjusted measure of skeletal muscle mass such as SMI, which is recommended in several guidelines when determining and contrasting the quantity of skeletal muscle mass. Third, when determining body composition, several reports show variances between bioelectrical impedance analysis (BIA) and dual-energy X-ray absorptiometry (DEXA) in RA as well as in general. In this regard, it may not be appropriate to simultaneously perform a meta-analysis of skeletal muscle mass determined by DEXA and BIA. With the issues described above, we conclude by recommending additional investigations to strengthen the arguments presented by this valuable meta-analysis.

Perceptions and behaviours related to COVID-19 in patients with rheumatoid arthritis: a cross-sectional study.

OBJECTIVES: To study the perceptions and behavioural changes related to the coronavirus disease 2019 (COVID-19) in patients with rheumatoid arthritis (RA) and determine their associations with patient characteristics, such as health literacy. METHODS: This cross-sectional study was conducted from September to November of 2020 and included 400 outpatients with RA aged 18 and above. We measured self-reported perceptions as outcomes, such as awareness, knowledge and behaviours related to COVID-19. Health literacy and other characteristics as exposures were investigated using self-report questionnaires and electronic health records. To analyse the association between patient factors and the outcomes, multivariable linear and logistic regression models were performed. RESULTS: In total, 365 patients completed the survey. More than half (51%) of patients reported that they were 'very worried' about possible infection with COVID-19, whereas over 80% believed the possibility of getting COVID-19 was low. In the multivariable analyses, patients with low health literacy had limited knowledge about COVID-19 and did not change daily routines and perform preventive measures. CONCLUSIONS: In this pandemic, healthcare providers may need to be aware of more vulnerable individuals and share COVID-19 related information promptly and effectively with their patients. Key Points • This cross-sectional study aimed to investigate the perceptions and behavioural changes related to COVID-19 in patients with RA. • All patients were aware of COVID-19 and most of them worried about getting infected. • Health literacy, age, sex, disease activity and rheumatic drugs were associated with perceptions and behaviours related to COVID-19.

UV irradiation of immunized mice induces type 1 regulatory T cells that suppress tumor antigen specific cytotoxic T lymphocyte responses.

We previously showed that exposure to UV radiation after immunization suppresses Th1 and Th2 immune responses, leading to impaired Ab and allo-immune responses, but the impact of UV radiation after immunization on anti-tumor immune responses mediated by tumor-specific CD8(+) T cell responses remains less clear. Furthermore, the exact phenotypic and functional characteristics of regulatory T cell population responsible for the UV-induced immunosuppression still remain elusive. Using the MBL-2 lymphoma cell line engineered to express OVA as a surrogate tumor Ag, here we demonstrate that UV irradiation after tumor Ag-immunization suppresses the anti-tumor immune response in a manner dependent on the immunizing Ag. This suppression was mediated by interleukin (IL)-10 released from CD4(+) CD25(+) T cells, by which impaired the induction of cytotoxic T lymphocytes (CTL) able to kill Ag-expressing tumor cells. In addition, we generated a panel of T cell clones from UV-irradiated and non-irradiated mice, and all of the clones derived from UV-irradiated mice had a Tr1-type regulatory T cell phenotype with expression of IL-10 and c-Maf, but not Foxp3. These Tr1-type regulatory T cell clones suppressed tumor rejection in vivo as well as Th cell activation in vitro in an IL-10 dependent manner. Given that suppression of Ag-specific CTL responses can be induced in Ag-sensitized mice by UV irradiation, our results may imply that exposure to UV radiation during premalignant stage induces tumor-Ag specific Tr1 cells that mediate tumor-Ag specific immune suppression resulting in the promotion of tumor progression.

Thioredoxin suppresses airway inflammation independently of systemic Th1/Th2 immune modulation.

Oxidative stress plays an important role in the pathogenesis of asthma via the upregulation of local inflammatory mediators and/or promoting Th2-skewing during Ag sensitization. Thioredoxin (TRX), a 12 kDa redox-active protein with antioxidative property, has been recently shown to play a protective role in various inflammatory diseases. Using a mouse model of asthma, we show here that IL-13 and eotaxin production are decreased in TRX-Tg mice leading to reduced eosinophils recruitment and mucus metaplasia. The reduction in airway inflammation occurs without the attenuation of systemic Th2 immunity in that comparable levels of Th2-type cytokines and Ig were detected in LN and serum, respectively, from TRX-Tg and WT mice. Likewise, CD4(+) T cells from both strains of mice developed similar Th1 and Th2 responses in vitro. Asthmatic lungs of TRX-Tg and WT mice contained similar amounts of GATA-3(+) and Foxp3(+) T cells. Finally, production of MIF, an upstream modulator of airway inflammation, was significantly reduced in the lungs of TRX-Tg mice. Our data suggest that TRX suppresses airway inflammation by inhibiting MIF production thereby limiting the downstream recruitment of eosinophils to the lung independently of modulating systemic Th1/Th2 immunity.

Serum vitamin D status inversely associates with a prevalence of severe sarcopenia among female patients with rheumatoid arthritis.

Sarcopenia is an age-related disease with an increased risk of mortality. It is emerging that low serum 25-hydroxyvitamin D [25(OH)D] affects the sarcopenic state in general, but in rheumatoid arthritis (RA), these associations are not understood although the prevalence of vitamin D insufficiency is high in RA. We conducted a cross-sectional study of older female outpatients from our cohort (KURAMA) database. We measured skeletal muscle mass, handgrip strength, and gait-speed to diagnose severe sarcopenia. The serum 25(OH)D concentration was measured using electrochemiluminescence immunoassay. A total of 156 female patients with RA (sarcopenia:44.9%, severe sarcopenia: 29.5%, and without sarcopenia: 25.6%) were enrolled. Classification of vitamin D status at a cutoff point of median 25(OH)D concentration revealed that low 25(OH)D status was associated with a high prevalence of severe sarcopenia and with low measured values of muscle mass, handgrip, and gait speed. Furthermore, multivariable logistic regression analysis identified that low 25(OH)D status was associated with a high prevalence of severe sarcopenia (OR 6.00; 95% CI 1.99-18.08).The same association was observed when the cut-off value was set at 20 ng/ml. In components of sarcopenia, both low physical performance and muscle mass were associated with low 25(OH)D status. In conclusion, vitamin D status was inversely associated with severe sarcopenia, low physical performance, and low skeletal muscle mass. Modification of vitamin D status including vitamin D supplementation should be investigated as a therapeutic strategy for sarcopenic patients with RA.

Factors associated with anxiety and depression in rheumatoid arthritis patients: a cross-sectional study.

BACKGROUND: The management of anxiety and depression symptoms in rheumatoid arthritis (RA) patients is vital. Previous study findings on this topic are conflicting, and the topic remains to be thoroughly investigated. This study aimed to clarify the association of RA disease activity with anxiety and depression symptoms after controlling for physical disability, pain, and medication. METHODS: We conducted a cross-sectional study of RA patients from the XXX Rheumatoid Arthritis Management Alliance cohort. We assessed patients using the Disease Activity Score (DAS28), Health Assessment Questionnaire Disability Index (HAQ-DI), and Hospital Anxiety and Depression Scale (HADS). Anxiety and depression symptoms were defined by a HADS score ≥ 8. We analyzed the data using multivariable logistic regression analyses. RESULTS: Of 517 participants, 17.6% had anxiety symptoms and 27.7% had depression symptoms. The multivariable logistic regression analysis demonstrated that DAS28 was not independently associated with anxiety symptoms (odds ratio [OR] [95% confidence interval; CI] 0.93 [0.48-1.78]; p = 0.82) and depression symptoms (OR [95% CI] 1.45 [0.81-2.61]; p = 0.22). However, DAS28 patient global assessment (PtGA) severity was associated with anxiety symptoms (OR [95% CI] 1.15 [1.02-1.29]; p = 0.03) and depression symptoms (OR [95% CI] 1.21 [1.09-1.35]; p < 0.01). Additionally, HAQ-DI scores ≤ 0.5 were associated with anxiety symptoms (OR [95% CI] 3.51 [1.85-6.64]; p < 0.01) and depression symptoms (OR [95% CI] 2.65 [1.56-4.50]; p < 0.01). Patients using steroids were more likely to have depression than those not using steroids (OR [95% CI] 1.66 [1.03-2.67]; p = 0.04). CONCLUSIONS: No association was found between RA disease activity and anxiety and depression symptoms in the multivariable logistic regression analysis. Patients with high PtGA scores or HAQ-DI scores ≤ 0.5 were more likely to experience anxiety and depression symptoms, irrespective of disease activity remission status. Rather than focusing solely on controlling disease activity, treatment should focus on improving or preserving physical function and the patient's overall sense of well-being.

Habitual fish intake negatively correlates with prevalence of frailty among patients with rheumatoid arthritis.

Frailty is a geriatric syndrome characterized by anabolic-catabolic imbalance and multisystem dysregulation resulting in increased adverse health outcomes, and is closely related with dietary habits in the general population. Although chronic inflammatory diseases are thought to accelerate development of frailty, correlations between rheumatoid arthritis (RA), frailty and dietary habits have not been examined. We performed a cross-sectional study using our cohort database (KURAMA cohort), and classified 306 participants into three groups (robust, prefrail and frail) according to the Study of Osteoporotic Fracture (SOF) criteria. Multivariate logistic analysis revealed that the presence of frailty/prefrailty was significantly correlated with the disease activity score (DAS28-ESR) (OR 1.70 (1.30-2.22), p < 0.0001). Additional analyses of frailty and food intake showed that 5 foods (fish, meat, milk, vegetables and fruits) of 20 groups on the questionnaire were inversely associated with the prevalence of frail/prefrail categories. In multivariate analysis with the five nutrients, fish intake (> two times a week) was an independent covariate negatively correlated with frailty/prefrailty (OR 0.35 (0.19-0.63), p = 0.00060). In conclusion, habitual fish intake may play a key role in nutritional intervention to prevent progression of frailty and RA.

Influence of dietary habits on depression among patients with rheumatoid arthritis: A cross-sectional study using KURAMA cohort database.

OBJECTIVE: Although mental disorder is one of the most common comorbidities of rheumatoid arthritis (RA) and is known as a critical influence on RA remission rates, there is little knowledge regarding a possible therapeutic strategy for depression or anxiety in a RA population. Most recently, clinical evidence of dietary improvement for depression has emerged in a general population, but the relationship between dietary habits and mental disorder has not been investigated in RA. The purpose of this study is to elucidate clinical associations between mental disorder (depression/anxiety), dietary habits and disease activity/physical function in patients with RA. METHODS: A cross-sectional study was performed with 267 female outpatients from the KURAMA database. Using the Hospital Anxiety and Depression Scale (HADS), we classified the participants into three groups by depression state, and their characteristics were compared. Using the 20-items on the self-reported food frequency questionnaire, we investigated the relationship between dietary habits and depression or anxiety, adopting a trend test and a multivariate standardized linear regression analysis for the HADS score of depression or that of anxiety as a dependent variable. RESULTS: According to the classified stage of depression, current disease activity (DAS28-CRP: 28-Joint RA Disease Activity Score-C-reactive protein) and the health assessment questionnaire disability Index (HAQ-DI) were significantly increased. Trend analyses revealed that the depression score was inversely associated with the consumption of three food (fish, vegetables and fruit) out of twenty as was the anxiety score with only fish intake. Furthermore, multiple linear regression analysis revealed that the depression score was negatively associated with frequent fish intake (≥ 3 times per week) (Estimate -0.53, p = 0.033), HAQ-DI score within normal range (Estimate -0.88, p ≤ 0.001) and MTX use (Estimate -0.60, p ≤ 0.023). For the anxiety score, multivariate analysis showed similar but not significant associations with variables except for HAQ-DI score. CONCLUSIONS: In a RA population, both depression and anxiety had a significant and negative association with HAQ-DI score, and depression rather than anxiety had negative association with frequent fish intake. Modification of dietary habits such as increased fish consumption may have a beneficial effect on the depression state in RA patients.

Differential regulatory function of resting and preactivated allergen-specific CD4+ CD25+ regulatory T cells in Th2-type airway inflammation.

Although CD4(+)CD25(+) regulatory T (Treg) cells are known to suppress Th1 cell-mediated immune responses, their effect on Th2-type immune responses remains unclear. In this study we examined the role of Treg cells in Th2-type airway inflammation in mice. Depletion and reconstitution experiments demonstrated that the Treg cells of naive mice effectively suppressed the initiation and development of Th2-driven airway inflammation. Despite effective suppression of Th2-type airway inflammation in naive mice, adoptively transferred, allergen-specific Treg cells were unable to suppress airway inflammation in allergen-presensitized mice. Preactivated allergen-specific Treg cells, however, could suppress airway inflammation even in allergen-presensitized mice by accumulating in the lung, where they reduced the accumulation and proliferation of Th2 cells. Upon activation, allergen-specific Treg cells up-regulated CCR4, exhibited enhanced chemotactic responses to CCR4 ligands, and suppressed the proliferation of and cytokine production by polarized Th2 cells. Collectively, these results demonstrated that Treg cells are capable of suppressing Th2-driven airway inflammation even in allergen-presensitized mice in a manner dependent on their efficient migration into the inflammatory site and their regulation of Th2 cell activation and proliferation.

Intake frequency of vegetables or seafoods negatively correlates with disease activity of rheumatoid arthritis.

OBJECTIVE: To clarify the relationship between dietary habit and disease activity of rheumatoid arthritis (RA). METHODS: This study enrolled RA patients who met the ACR/EULAR 2010 classification criteria from Kyoto University Rheumatoid Arthritis Management Alliance (KURAMA) cohort in 2015. 22-item food frequency questionnaire (FFQ) was taken for the measurement of dietary habit in a single-institution cohort of RA (Kyoto University Rheumatoid Arthritis Management Alliance: KURAMA) in 2015. The disease activities of RA using the Disease Activity Score calculated based on the erythrocyte sedimentation rate (DAS28-ESR), Simplified Disease Activity Index (SDAI), Health Assessment Questionnaire (HAQ), and serum matrix metalloproteinase-3 (MMP-3) level, the use of disease-modifying anti-rheumatic drugs (DMARDs), disease duration, rheumatoid factor, anti-cyclic citrullinated antibody, and body mass index were also examined. All of them were combined and statistically analyzed. RESULTS: 441 RA patients (81% women; mean age 65 years; mean disease duration 15 years) were enrolled from the KURAMA cohort. Average Disease Activity Score-28 using the erythrocyte sedimentation rate (DAS28-ESR) was 2.7. Univariate analysis showed that intake frequency of vegetables had a statistically significant negative correlation with disease activity markers, such as DAS28-ESR (ρ = -0.11, p<0.01), Simplified Disease Activity Index (SDAI) (ρ = -0.16, p<0.001), matrix metalloproteinase-3 (MMP-3) (ρ = -0.21, p<0.0001), and Health Assessment Questionnaire (HAQ) (ρ = -0.13, p<0.01). Factor analysis with varimax rotation was done to simplify the relevance of disease activity to various food items. 22 foods were categorized into five dietary patterns: "seafoods", "vegetables/fruits", "meats/fried foods", "snacks", and "processed foods". The multivariate analysis adjusted for clinically significant confounders showed that "seafoods" had statistically significant negative correlations with DAS28-ESR (ß = -0.15, p<0.01), SDAI (ß = -0.18, p<0.001), MMP-3 (ß = -0.15, p<0.01), and HAQ (ß = -0.24, p<0.0001). "Vegetables/fruits" had statistically significant negative correlations with SDAI (ß = -0.11 p<0.05), MMP-3 (ß = -0.12, p<0.01), and HAQ (ß = -0.11, p<0.05). CONCLUSIONS: These results suggest that high intake frequency of vegetables/fruits and/or seafoods might correlate with low disease activity.

Effect of Physical State on Pain Mediated Through Emotional Health in Rheumatoid Arthritis.

OBJECTIVE: Pain is one of the main symptoms of patients with rheumatoid arthritis (RA). Pain in RA is caused by specific physical changes, such as joint destruction, and is therefore used as a disease activity marker. Although pain can also be influenced by emotional factors, neither the effect of emotional health nor the indirect effect of the physical state mediated by emotional health on pain has been quantified. METHODS: A total of 548 patients with RA participated. Emotional health was assessed using the Hospital Anxiety and Depression Scale (HADS). Measures routinely used in practice were used to evaluate the physical state and pain. To quantify the effects of the physical state on emotional health, and the effects of both physical and emotional health on pain, we used structural equation modeling, with emotional health, physical state, and pain as latent variables. RESULTS: The prevalence of anxiety and depression (HADS score ≥8 for each) among patients with RA was 18.7% and 29.4%, respectively. Emotional health was significantly influenced by the physical state (ß = 0.21). Pain was affected by physical (ß = 0.54) and emotional health (ß = 0.29). The effect of the physical state on pain was mediated by emotional health, with this mediation effect (ß = 0.06) accounting for 10.2% of the total effect. CONCLUSION: The magnitude of pain in RA is determined by the mediation effect of emotional health as well as the direct physical state. Our findings suggest that emotional factors should be taken into account when assessing RA disease activity.

Alloantigen-specific prolongation of allograft survival in recipient mice treated by alloantigen immunization following ultraviolet-B irradiation.

It is well documented that ultraviolet (UV) radiation present in sunlight suppresses immune responses. However, the majority of studies documenting the immunosuppressive effects of UV irradiation have been carried out in animals exposed to UV irradiation before immunization. Here, we report that recipient mice exposed to UV irradiation 7 days after immunization with a donor alloantigen exhibited prolongation of allograft survival in an alloantigen-specific manner. Recipient mice (H-2(b)) intravenously immunized with 2 x 10(7) allogeneic spleen cells (H-2(b/d)) 7 days before UV irradiation (40 kJ/m(2)) showed prolonged survival of allografts presenting the alloantigen used for sensitization (H-2(b/d)), but not third-party allografts (H-2(b/k)). Adoptive transfer experiments revealed that CD4(+) T cells in UV-irradiated recipients were responsible for this prolongation. CD4(+) T cells that could transfer the suppression produced large amounts of interleukin (IL)-10, but not IL-4. The effect of UV irradiation on alloantigen-specific immunosuppression was cancelled by administration of an anti-IL-10 monoclonal antibody. These results indicate that UV irradiation given after alloantigen immunization induces alloantigen-specific type 1 regulatory T cell-like regulatory T cells that prolong allograft survival and imply that the difficulties associated with predicting donor-related organ availability in transplantation can be dealt with, given the effectiveness of UV irradiation after immunization.

Optimal systemic hemodynamic stability for successful clinical outcomes after adult living-donor liver transplantation: prospective observational study.

BACKGROUND AND AIM: Most living-donor liver transplantation (LDLT) recipients show characteristic systemic hemodynamics due to liver cirrhosis, and systemic hemodynamics after LDLT influenced postoperative graft function corresponding to outcomes. However, identities of optimal systemic hemodynamics for excellent outcomes and precise parameters for clinical strategy remain unclear. METHODS: Therefore, we performed prospective study in adult LDLT recipients from 2003. Hemodynamic parameters were prospectively recorded, and were analyzed in 40 recipients classified into three groups: cirrhotic (group I-C) or non-cirrhotic recipients (group I-NC) with good outcomes, and cirrhotic recipients (group II-C) without good outcomes. RESULTS: Group I-C retained characteristic hyperdynamics even after LDLT. However, absolute values of parameters revealed no significant differences between groups I-C and II-C, because group II-C also tended to show hyperdynamics. It is suggested that successful outcomes in cirrhotic recipients require maintenance of optimal hyperdynamic stability after LDLT, because cirrhotic vascular alterations still occurred. Because hemodynamic behaviors were different between groups I-C and I-NC, absolute values were also significantly different even in these successful two groups. Thus, absolute values themselves were not necessarily satisfactory for accurate evaluation of optimal hemodynamic stability. Cirrhotic hyperdynamics are symbolized in large blood volume (BV) circulated by high cardiac output (CO); therefore, we standardized CO against BV. CO/BV was significantly different between groups I-C and II-C, reflecting subtle variability of hyperdynamics in groups II-C, and was interestingly constant in the two successful groups. Therefore, CO/BV reliably evaluated optimal hemodynamic stability after LDLT, and accurately predicted outcomes. CONCLUSION: Identification of inappropriate hemodynamics after LDLT is advantageous to further improve LDLT outcomes.

Factors affecting walking ability in female patients with rheumatoid arthritis.

OBJECTIVE: To determine the factors associated with gait parameters in female patients with rheumatoid arthritis (RA). METHODS: The gait analysis was performed in a large cohort of RA patients, and three basic gait parameters (step length, cadence and gait speed) were calculated. Clinical and laboratory data were also collected. Factors associated with gait parameters were analyzed using multivariable linear regression in the three models with forced entry. Then, we divided those patients with Health Assessment Questionnaire disability index (HAQ) scores ≤ 0.5 into two groups according to their gait speed that were compared to identify the characteristics of patients with a good HAQ score but poor walking ability. RESULTS: A total of 318 female patients were analyzed. Knee extension strength had the strongest positive association with all three gait parameters (P < 0.0001), while methotrexate use was also positively associated with all three gait parameters (step length: P < 0.05, cadence: P < 0.05 in model 1 and 2; P < 0.01 in model 3, gait speed: P < 0.01). The disease activity score was negatively associated with step length and gait speed (step length, gait speed: P < 0.01 in model 1 and 2; P < 0.05 in model 3). 26% of patients with good HAQ scores showed slow gait speed. Patients with good HAQ scores and slow gait speed had higher disease activity scores (P < 0.05) and lower knee extension strength (P < 0.0001) than those with good HAQ scores and normal gait speed. CONCLUSIONS: High knee extension strength, low disease activity and administration of methotrexate were strongly associated with good walking ability in female patients with RA. And, even if patients showed good HAQ scores, about quarter of those patients had poor walking ability, and they showed higher disease activity, lower knee extension strength, compared to the patients with normal gait speed.

Stability of cirrhotic systemic hemodynamics ensures sufficient splanchnic blood flow after living-donor liver transplantation in adult recipients with liver cirrhosis.

AIM: To investigate the correlation between systemic hemodynamics and splanchnic circulation in recipients with cirrhosis undergoing living-donor liver transplantation (LDLT), and to clarify how systemic hemodynamics impact on local graft circulation after LDLT. METHODS: Systemic hemodynamics, indocyanine green (ICG) elimination rate (K ICG) and splanchnic circulation were simultaneously and non-invasively investigated by pulse dye densitometry (PDD) and ultrasound. Accurate estimators of optimal systemic hyperdynamics after LDLT [i.e., balance of cardiac output (CO) to blood volume (BV) and mean transit time (MTT), defined as the time required for half the administered ICG to pass through an attached PDD sensor in the first circulation] were also measured. Thirty recipients with cirrhosis were divided into two groups based on clinical outcomes corresponding to postoperative graft function. RESULTS: Cirrhotic systemic hyperdynamics characterized by high CO, expanded BV and low total peripheral resistance (TPR) were observed before LDLT. TPR reflecting cirrhotic vascular alterations was slowly restored after LDLT in both groups. Although no significant temporal differences in TPR were detected between the two groups, CO/BV and MTT differed significantly. Recipients with good outcomes showed persistent cirrhotic systemic hyperdynamics after LDLT, whereas recipients with poor outcomes presented with unstable cirrhotic systemic hyperdynamics and severely decreased K ICG. Systemic hyperdynamic disorders after LDLT impacted on portal venous flow but not hepatic arterial flow. CONCLUSION: We conclude that subtle systemic hyperdynamics disorders impact on splanchnic circulation, and that an imbalance between CO and BV decreases portal venous flow, which results in critical outcomes.