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Assessment of frailty is important for risk stratification among the elderly with severe aortic stenosis (AS) when considering interventions such as surgical aortic valve replacement (SAVR) or transcatheter aortic valve replacement (TAVR). However, evidence of the impact of preoperative frailty on short-term postoperative outcomes or functional recovery is limited. This retrospective study included 234 consecutive patients with severe AS who underwent SAVR or TAVR at Kobe University Hospital between Dec 2013 and Dec 2019. Primary outcomes were postoperative complications, postoperative 6-min walking distance (6MWD), and home discharge rates. The mean age was 82 ± 6.6 years. There were 169 (SAVR: 80, TAVR: 89) and 65 (SAVR: 20, TAVR: 45) patients in the non-frail and frail groups, respectively (p = 0.02). The postoperative complication rates in the frail group were significantly higher than those in the non-frail group [30.8% (SAVR: 35.0%, TAVR: 28.9%) vs. 10.7% (SAVR: 15.0%, TAVR: 6.7%), p

Background: The COVID-19 pandemic has challenged healthcare systems, at times overwhelming intensive care units (ICUs). We aimed to describe the length and rate of ICU admission, and explore the clinical variables influencing ICU use, for COVID-19 patients with known cardiovascular diseases or their risk factors (CVDRF). Methods and Results: A post hoc analysis was performed of 693 Japanese COVID-19 patients with CVDRF enrolled in the nationwide CLAVIS-COVID registration system between January and May 2020 (mean [±SD] age 68.3±14.9 years; 35% female); 199 patients (28.7%) required ICU management. The mean (±SD) ICU length of stay (LOS) was 19.3±18.5 days, and the rate of in-hospital death and hospital LOS were significantly higher (P

Background: Poor oral health status can lead to a deteriorated level of general health and is common among patients undergoing cardiovascular surgery. However, the effect of oral health status on postoperative outcomes in cardiovascular surgery patients remains unclear. Thus, we investigated the effect of preoperative oral health status on postoperative complications and functional recovery after cardiovascular surgery. Methods: This single-centre retrospective cohort study included 884 inpatients undergoing elective cardiovascular surgery. Oral health status was assessed based on the number of remaining teeth, use of dentures, occlusal support, and periodontal status. We investigated postoperative complications related to surgery and postoperative functional recovery by measuring the reacquisition of walking ability, activities of daily living, and length of postoperative hospital stay. Results: In this cohort (age 66.9 ± 13.4 years), the mean number of remaining teeth was 18.7 ± 9.4. Patients were grouped based on tertiles of the data distribution of remaining teeth: ≥ 20 teeth (470 patients); 10-19 teeth (137 patients); < 10 teeth (185 patients). The number of missing teeth was associated with age (P < 0.001). The prevalence of postoperative pneumonia and reintubation after surgery was 3.2% and 2.5%, respectively, which was significantly higher in patients with severe tooth loss (P < 0.05 for both). After adjusting for age and other confounding factors, the number of remaining teeth was a statistically significant predictor of functional recovery (P < 0.05). Conclusions: Preoperative oral health status was related to postoperative respiratory complications and independently associated with functional recovery. Preoperative oral intervention may improve functional recovery after cardiovascular surgery. Résumé: Contexte: Une mauvaise santé buccodentaire peut avoir des répercussions néfastes sur la santé générale et est fréquemment observée chez les patients subissant une intervention chirurgicale cardiovasculaire. Cependant, l’effet de l’état de santé buccodentaire sur les issues postopératoires chez les patients ayant subi une telle intervention est mal connu. Nous avons donc étudié l’effet de l’état de santé buccodentaire avant l’intervention sur les complications postopératoires et le rétablissement fonctionnel après une intervention chirurgicale cardiovasculaire. Méthodologie: Cette étude de cohorte rétrospective menée dans un seul centre réunissait 884 patients subissant une intervention chirurgicale cardiovasculaire non urgente. L’état de santé buccodentaire des patients a été évalué en fonction du nombre de dents restantes, du recours à des prothèses dentaires, de la présence d’appuis occlusaux et de la santé parodontale. Nous avons examiné les cas de complications postopératoires liées à l’intervention chirurgicale ainsi que le rétablissement fonctionnel après l’intervention en évaluant la réacquisition de la capacité de marcher, la capacité d’accomplir les activités de la vie quotidienne et la durée du séjour à l’hôpital après l’intervention. Résultats: Dans cette cohorte (âge moyen : 66,9 ± 13,4 ans), les sujets avaient en moyenne 18,7 ± 9,4 dents restantes. Les patients ont été répartis en trois groupes en fonction du nombre de dents restantes : ≥ 20 dents (470 patients); de 10 à 19 dents (137 patients); < 10 dents (185 patients). Il y avait un lien entre le nombre de dents manquantes et l’âge (p < 0,001). La prévalence des cas de pneumonie postopératoire et de réintubation après l’intervention s’établissait à 3,2 % et à 2,5 %, respectivement, et était significativement plus élevée chez les patients à qui il restait très peu de dents (p < 0,05 dans les deux cas). Après correction pour tenir compte de l’âge et d’autres facteurs de confusion, le nombre de dents restantes s’est révélé être un facteur de prédiction statistiquement significatif du rétablissement fonctionnel (p < 0,05). Conclusions: L’état de santé buccodentaire avant l’intervention chirurgicale était lié à des complications respiratoires postopératoires et associé de manière indépendante au rétablissement fonctionnel. Des soins buccodentaires préopératoires pourraient améliorer le rétablissement fonctionnel après une intervention chirurgicale cardiovasculaire.

Background Oral health is important for maintaining general health and is associated with components of physical frailty among the elderly. Oral health problems are common in hospitalized patients; however, no reports on oral health problems pertain to patients with cardiovascular diseases (CVD). The present study aimed to evaluate the association between oral health and physical frailty in these patients. Methods In this retrospective cohort study, we included consecutive patients admitted for CVD to our hospital between May 2014 and December 2018. Physical frailty was assessed using the Short Physical Performance Battery (SPPB). Oral health characteristics, such as the number of remaining teeth, denture use, occlusal support, and periodontal status, were assessed. Results In our cohort (n = 457), 111 (24.3%) patients had physical frailty. Univariate linear regression showed that the number of teeth present and the prevalence of occlusal support were significantly lower in patients with than without physical frailty. Pearson correlation indicated that the number of teeth significantly correlated with the nutritional status (r = 0.27) and SPPB score (r = 0.24), grip strength (r = 0.33), and 6-minute walking distance (r = 0.26). Multiple linear regression analysis showed that the number of teeth was independently associated with physical frailty after adjusting for confounders. Conclusions Oral health was closely associated with physical frailty, and nutritional status in patients with CVD; thus, it could be an important screening marker for early frailty symptoms and a predictor of future malnutrition risk.

Objective: Joint contractures are a major complication following joint immobilization. However, no fully effective treatment has yet been found. Recently, carbon dioxide (CO(2)) therapy was developed and verified this therapeutic application in various disorders. We aimed to verify the efficacy of transcutaneous CO(2) therapy for immobilization-induced joint contracture. Method: Twenty-two Wistar rats were randomly assigned to three groups: caged control, those untreated after joint immobilization, and those treated after joint immobilization. The rats were treated with CO(2) for 20 min once a daily either during immobilization, (prevention) or during remobilization after immobilization (treatment). Knee extension motion was measured with a goniometer, and the muscular and articular factors responsible for contractures were calculated. We evaluated muscle fibrosis, fibrosis-related genes (collagen Type 1α1 and TGF-β1) in muscles, synovial intima's length, and fibrosis-related proteins (Type I collagen and TGF-β1) in the joint capsules. Results: CO(2) therapy for prevention and treatment improved the knee extension motion. Muscular and articular factors decreased in rats of the treatment group. The muscular fibrosis of treated rats decreased in the treatment group. Although CO(2) therapy did not repress the increased expression of collagen Type 1α1, the therapy decreased the expression of TGF-β1 in the treatment group. CO(2) therapy for treatment improved the shortening of the synovial membrane after immobilization and decreased the immunolabeling of TGF-β1 in the joint capsules. Conclusions: CO(2) therapy may prevent and treat contractures after joint immobilization, and appears to be more effective as a treatment strategy for the deterioration of contractures during remobilization.

Objective Chemotherapy-induced peripheral neuropathy (CIPN) is a common adverse event experienced by cancer patients. In general, CIPN is evaluated subjectively based on patient self-assessment or clinician-reported scales; evidence supporting the utility and validity of quantitative sensory tests (QST) is lacking in this patient population. The aim of this study was to objectively assess CIPN of lower extremities by QSTs, and to evaluate the concordance between QSTs and subjective assessments. Methods In this prospective cohort study, outpatients with cancer receiving chemotherapy were recruited at a single university hospital. We assessed CIPN at the lower extremities at baseline and three months after baseline. The QSTs were performed by applying a monofilament and a tuning fork to determine touch and vibration thresholds, respectively, at the affected site. Subjective assessments were performed based on the visual analog scale (VAS) and the National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) toxicity grade. Kappa coefficients were calculated to evaluate the concordance between QSTs and subjective assessments. Results After exclusion and drop-outs during follow-up, nineteen patients were included in the analysis. The prevalence of patients with abnormal sensation was 37% based on QSTs, 32% based on the VAS, and 14% based on CTCAE grading, respectively. Kappa coefficients were 0.32 between QSTs and VAS, and 0.28 between QSTs and CTCAE. Conclusions The concordance rates between quantitative and subjective assessments were low. CIPN should be assessed using both quantitative and subjective assessments.

Background: Carbon dioxide therapy has been reported to be effective in treating certain cardiac diseases and skin problems. Although a previous study suggested that transcutaneous carbon dioxide application accelerated fracture repair in association with promotion of angiogenesis, blood flow, and endochondral ossification, the influence of the duration of carbon dioxide application on fracture repair is unknown. The aim of this study was to investigate the effect of the duration of transcutaneous carbon dioxide application on rat fracture repair. Methods: A closed femoral shaft fracture was created in each rat. Animals were randomly divided into four groups: the control group; 1w-CO2 group, postoperative carbon dioxide treatment for 1 week; 2w-CO2 group, postoperative carbon dioxide treatment for 2 weeks; 3w-CO2 group, postoperative carbon dioxide treatment for 3 weeks. Transcutaneous carbon dioxide application was performed five times a week in the carbon dioxide groups. Sham treatment, where the carbon dioxide was replaced with air, was performed for the control group. Radiographic, histological, and biomechanical assessments were performed at 3 weeks after fracture. Results: The fracture union rate was significantly higher in the 3w-CO2 group than in the control group (p < 0.05). Histological assessment revealed promotion of endochondral ossification in the 3w-CO2 group than in the control group. In the biomechanical assessment, all evaluation items related to bone strength were significantly higher in the 3w-CO2 group than in the control group (p < 0.05). Conclusions: The present study, conducted using an animal model, demonstrated that continuous carbon dioxide application throughout the process of fracture repair was effective in enhancing fracture healing.

Context:Some studies have discussed postoperative quadriceps strength recovery after anterior cruciate ligament reconstruction (ACLR). However, the effect of preoperative quadriceps strength deficit on longitudinal postoperative quadriceps strength recovery after ACLR with hamstring autograft is unknown.Objective:To reveal the longitudinal postoperative quadriceps strength recovery after ACLR with hamstring autograft among patient groups stratified by preoperative quadriceps strength deficit.Design:Retrospective cohort study.Setting:Single center.Patients:In total, 420 patients (222 men and 218 women; age at the time of surgery 23.1 [8.9] y) who underwent ipsilateral ACLR with hamstring autograft and completed knee function tests preoperatively and 3, 6, and 12 months postoperatively were included in this study.Intervention:The authors measured quadriceps strength at 60°/s, tested 1-leg hop performance (distance and anxiety), and calculated the quadriceps strength index (QSI) and limb symmetry index for 1-leg hop distance. Patients were divided into the following 4 groups according to their preoperative QSI: >80% (Excellent group), 80% to 60% (Good group), 60% to 40% (Moderate group), and ≤40% (Poor group).Main Outcome Measures:Postoperative QSI at 3, 6, and 12 months and 1-leg hop performance at 12 months after the surgery.Results:The Excellent group had the highest postoperative QSI at all periods. Based on the 1-leg hop performance, the Poor group had the lowest limb symmetry index and significantly greater anxiety during jump performance in comparison with the Excellent and Good groups.Conclusion:The present study shows a longitudinal recovery process and the average postoperative quadriceps strength after ACLR with hamstring autograft in patient groups stratified by preoperative QSI. The results indicate that the difference in preoperative QSI affects not only the longitudinal postoperative QSI recovery but also high-level 1-leg hop performance after ACLR using hamstring autograft.

Background Muscle atrophy causes difficulty in resuming daily activities after a fracture. Because transcutaneous carbon dioxide (CO2) application has previously upregulated oxygen pressure in the local tissue, thereby demonstrating its potential in preventing muscle atrophy, here we investigated effects of CO2 application on muscle atrophy after femoral shaft fracture. Methods Thirty fracture model rats were produced and randomly divided into a no treatment (control group) and treatment (CO2 group) groups. After treatment, the soleus muscle was dissected at post-fracture days 0, 14, and 21. Evaluations were performed by measuring muscle weight and performing histological examination and gene expression analysis. Results Muscle weight was significantly higher in the CO2 group than in the control group. Histological analysis revealed that the muscle fiber cross-sectional area was reduced in both groups. Nevertheless, the extent of atrophy was lesser in the CO2 group. Muscle fibers in the control group tended to change into fast muscle fibers. Vascular staining revealed that more capillary vessels surrounded the muscle fibers in the CO2 group than in the control group. Messenger RNA (mRNA) analysis revealed that the CO2 group had a significantly enhanced expression of genes that were related to muscle synthesis. Conclusion Transcutaneous CO2 application may be a novel therapeutic strategy for preventing skeletal muscle atrophy after fracture.

[Purpose] Low muscle mass and sleep disturbance are common among geriatric patients with cancer. In patients with gastrointestinal cancer, low muscle mass is considered an indicator of poor prognosis. In the recent years, sleep disturbance has attracted much attention as a factor for low muscle mass among community-dwelling elderly individuals; however, such associations are unclear in patients with cancer. The present study investigated the relationship between preoperative sleep disturbance and low muscle mass in patients with gastrointestinal cancer. [Participants and Methods] This cross-sectional survey enrolled 86 elderly patients (aged more than 60 years) with gastrointestinal cancer who were scheduled for curative surgery. Low preoperative muscle mass was defined according to Asian Working Group for Sarcopenia criteria. Sleep disturbance was assessed using the Japanese version of the Pittsburgh Sleep Quality Index, including the subscales. [Results] Twenty-seven patients (31%) were classified as having low muscle mass. After adjusting for confounding factors, bad sleep quality, determined by the subscales, was significantly associated with low muscle mass. [Conclusion] Our results suggest that the evaluation of sleep quality is imperative for addressing low preoperative muscle mass in patients with gastrointestinal cancer.

The aim of this study is to evaluate the rehabilitation of patients based on data related to gait. In this paper, we evaluated the rehabilitation of patients undergone total knee arthroplasty (TKA), total hip arthroplasty (THA) and hemiplegic patients based on gait data such as speed, cadence, stride, and gait cycle during gait training. Statistical analysis, including repeated measures analysis of variance, is employed to examine the characteristics of changes in the data over time. Based on the results of this analysis, the importance of each data is weighted by the paired comparison method. Thereby, we evaluated the effectiveness of patient rehabilitation quantitatively and comprehensively.

Objectives This study aimed to assess the effect of home-based preoperative pulmonary rehabilitation (HBPPR) on the incidence of postoperative complications, length of stay (LOS), and duration of intercostal catheterization in non-small cell lung cancer (NSCLC) patients who underwent lung resection. Materials and methods In this retrospective cohort study, 144 patients who underwent lung resection were recruited, 51 of whom received HBPPR, comprising respiratory muscle training and was supervised (for patients undergoing it for the first time). Patients continued these programs for 2-4 weeks during the preoperative waiting period, in their homes. Data on postoperative complications graded according to the Clavien-Dindo classification, LOS, and intercostal catheterization duration were collected from medical records. These outcomes were compared between the HBPPR and non-HBPPR groups using Fisher’s exact test and Wilcoxon rank sum test, after 1:1 propensity score matching to avoid selection bias. Results Forty-nine matched pairs were extracted using propensity score matching. HBPPR reduced the onset of postoperative complications (p = 0.04), with the relative ratio (RR) for Clavien-Dindo Class I postoperative complications showing a significant difference (RR 0.55, 95% CI 0.30¬-1.02; p = 0.05), whereas RRs for the other Clavien-Dindo classes were not statistically significant. There was no significant difference in LOS or the duration of intercostal catheterization. Conclusion HBPPR reduced the incidence of Clavien-Dindo Class I postoperative complications after lung resection. Implementing HBPPR practices in a clinical setting would benefit patients unable to receive supervised preoperative pulmonary rehabilitation due to access barriers, time, and financial constraints.

Background Elderly patients undergoing cardiac surgery often show poor nutritional status, muscle wasting, and sarcopenia, which are reported to affect postoperative functional recovery and incidence of complications. Amino acids are essential in maintaining nutritional status, synthesizing muscle protein, and promoting beneficial energy balance of the heart muscle. β-Hydroxy β-methylbutyric acid (HMB) is a leucine metabolite known to increase muscle protein synthesis and inhibit protein catabolism; it has been used to more effectively support patients with muscle wasting due to wearing diseases. However, the efficacy of amino acid administration comprising HMB in patients undergoing open heart surgery remains unclear. This study aims to examine whether preoperative short-term aggressive amino acid administration helps support postoperative recovery of physical function and prevent complications. Methods This is a single-center prospective randomized controlled trial (UMIN000030490). Patients aged ≥65 years who will be hospitalized for medical examination before cardiac surgery will be recruited. The participants will be randomly assigned to the experimental or control group. The experimental group will be administered with an amino acid supplement with HMB 1200 mg, l -glutamine 7000 mg, and l -arginine 7000 mg once or twice per day depending on the degree of renal dysfunction, for 14–28 days preoperatively. The control group will not receive any nutritional intervention. The main outcome will be a change in the 6-min walking test distance pre- and postoperatively as a sign of functional recovery. Secondary outcomes such as the incidence of complications; physical, nutritional, and psychological states; mortality; and length of hospital stay will also be evaluated. Conclusion This clinical study will determine the effects of preoperative short-term oral amino acid supplementation with HMB, l -glutamine, and l -arginine on postoperative physical function in elderly patients undergoing cardiac surgery.

Objective: To elucidate the roles of interleukin-6 (IL-6) and tumour necrosis factor-α (TNF-α) in cell cycle regulation and proliferation of rheumatoid arthritis fibroblast-like synovial cells (RA-FLSs). Methods: Under stimulation with IL-6/soluble interleukin-6 receptor (sIL-6R) and TNF-α, we examined the expression of cell cycle regulators [p16INK4a, p21Cip1, p27Kip1, cyclin-dependent kinase-4 (CDK4), CDK6, Cyclin D, Cyclin E, and retinoblastoma protein (pRB)] by quantitative polymerase chain reaction, Western blotting, and immunofluorescence staining. The expression of pRB, with or without 10% foetal bovine serum, was examined by Western blotting. DNA synthesis and cell viability were examined by the BrdU assay and WST-8 assay, respectively. After transfection with siRNA/p16INK4a, siRNA/p21Cip1, siRNA/p27Kip1, siRNA/CDK4, or siRNA/CDK6, RA-FLSs were successively stimulated with or without IL-6/sIL-6R or TNF-α to determine cell viability. Results: IL-6/sIL-6R significantly decreased the expression of p16INK4a, and increased p21Cip1, Cyclin E1, CYCLIN D, and pRB. TNF-α decreased the expression of CDK4, and significantly increased p27Kip1, CDK6, Cyclin E1/E2, CYCLIN D, CYCLIN E, pRB, and phosphorylated pRB (phospho-pRB). By immunofluorescence staining, CYCLIN D and phospho-pRB were simultaneously stained in the single cell. In serum-free culture, the expression of pRB was apparently decreased. DNA synthesis and cell viability were significantly increased by IL-6/sIL-6R and TNF-α. Silencing of CDK6 attenuated the cell viability induced by IL-6 and TNF-α. Conclusion: The results indicate that IL-6 and TNF-α interact with each other in regulating the cell cycle and accelerate the proliferation of RA-FLSs.

Background: Data of vitamin D sufficiency in Asian patients with osteoporotic fragility hip fractures are limited. This study aimed to obtain data from the Japanese population. Methods: Patients aged 60 years or older with hip fractures were prospectively enrolled. Serum 25-hydroxyvitamin D (25(OH)D) levels were measured. Levels were compared between patients receiving and not receiving treatment for osteoporosis, those with and without previous contralateral hip fractures, and those with femoral neck versus trochanteric fractures. Sex-based differences were also assessed. The serum levels in patients younger than 60 years with extremity fractures were assessed, and differences between elderly and younger patients were evaluated. The individual correlation between 25(OH)D levels and the ultraviolet (UV) index and age was analyzed in elderly patients with hip fractures. Results: The data of 360 patients (aged 84.7 ± 8.2 years), comprising 80 men and 280 women, were analyzed. The mean 25(OH)D level was 16.5 ± 7.2 ng/mL. The prevalence of vitamin D insufficiency (25(OH)D Conclusion: Perennial vitamin D insufficiency is prevalent in elderly Japanese patients with hip fractures.

BACKGROUND: Joint contractures are a major complication in patients with spinal cord injuries. Positioning, stretching, and physical therapy are advocated to prevent and treat contractures; however, many patients still develop them. Joint motion (exercise) is crucial to correct contractures. Transcutaneous carbon dioxide (CO(2)) therapy was developed recently, and its effect is similar to that of exercise. This therapy may be an alternative or complementary approach to exercise. QUESTION/PURPOSES: Using an established model of spinal cord injury in rats with knee flexion contractures, we sought to clarify whether transcutaneous CO(2) altered (1) contracture, as measured by ROM; (2) muscular and articular factors contributing to the loss of ROM; (3) fibrosis and fibrosis-related gene expression in muscle; and (4) the morphology of and fibrosis-related protein expression in the joint capsule. METHODS: Thirty-six Wistar rats were divided into three equal groups: caged control, those untreated after spinal cord injury, and those treated with CO(2) after spinal cord injury. The rats were treated with CO(2) from either the first day (prevention) or 15th day (treatment) after spinal cord injury for 2 or 4 weeks. The hindlimbs of rats in the treated group were exposed to CO(2) gas for 20 minutes once daily. Knee extension ROM was measured with a goniometer and was measured again after myotomy. We calculated the muscular and articular factors responsible for contractures by subtracting the post-myotomy ROM from that before myotomy. We also quantified histologic muscle fibrosis and evaluated fibrosis-related genes (collagen Type 1, α1 and transforming growth factor beta) in the biceps femoris muscle with real-time polymerase chain reaction. The synovial intima’s length was measured, and the distribution of fibrosis-related proteins (Type I collagen and transforming growth factor beta) in the joint capsule was observed with immunohistochemistry. Knee flexion contractures developed in rats after spinal cord injuries at all timepoints. RESULTS: CO(2) therapy improved limited-extension ROM in the prevention group at 2 weeks (22° ± 2°) and 4 weeks (29° ± 1°) and in the treatment group at 2 weeks (31° ± 1°) compared with untreated rats after spinal cord injuries (35° ± 2°, mean difference, 13°; 39° ± 1°, mean difference, 9°; and 38° ± 1°, mean difference, 7°, respectively) (95% CI, 10.50-14.86, 8.10-10.19, and 4.73-9.01, respectively; all p < 0.001). Muscular factors decreased in treated rats in the prevention group at 2 weeks (8° ± 2°) and 4 weeks (14°± 1°) and in the treatment group at 2 weeks (14 ± 1°) compared with untreated rats (15° ± 1°, 4.85-9.42; 16° ± 1°, 1.24-3.86; and 17° ± 2°, 1.16-5.34, respectively; all p < 0.05). The therapy improved articular factors in the prevention group at 2 weeks (4° ± 1°) and 4 weeks (6° ± 1°) and in the treatment group at 2 weeks (8° ± 1°) compared with untreated rats (10° ± 1°, 4.05-7.05; 12° ± 1°, 5.18-8.02; and 11° ± 2°, 1.73-5.50, respectively; all p < 0.05). CO(2) therapy decreased muscle fibrosis in the prevention group at 2 weeks (p < 0.001). The expression of collagen Type 1, α1 mRNA in the biceps femoris decreased in treated rats in the prevention group at 2 and 4 weeks compared with untreated rat (p = 0.002 and p = 0.008, respectively), although there was little difference in the expression of transforming growth factor beta (p > 0.05). CO(2) therapy did not improve shortening of the synovial intima at all timepoints (all p > 0.05). CO(2) therapy decreased transforming growth factor beta immunolabeling in joint capsules in the rats in the prevention group at 2 weeks. The staining intensity and Type I collagen pattern showed no differences among all groups at all timepoints. CONCLUSION: CO(2) therapy may be useful for preventing and treating contractures after spinal cord injuries. CO(2) therapy particularly appears to be more effective as a prevention and treatment strategy in early-stage contractures before irreversible degeneration occurs, as shown in a rat model. CLINICAL RELEVANCE: Our findings support the idea that CO(2) therapy may be able to improve the loss of ROM after spinal cord injury.

Chemotherapy-induced peripheral neuropathy (CIPN) frequently occurs in lymphoma patients receiving R-CHOP, a drug combination therapy. Although severe CIPN may lead to reduction and/or discontinuation of the medication, predictive factors of CIPN have not been investigated sufficiently to date. We performed a retrospective exploratory research to determine associations between prevalence of severe CIPN and socio-demographic data, health characteristics, and medical conditions such as anemia at initial diagnosis. Forty patients (indolent lymphoma, n = 9; diffuse large B-cell lymphoma; n = 31) received R-CHOP therapy from September 2009 to July 2014. The median age of patients was 58 years (range = 27–76 years). Statistical analy-ses were applied to the patients, who were divided into two groups: mild CIPN (no symptoms or grade 1 according to the CTCAE version 3.0 program) and severe CIPN patients (grade 2 or higher). Forward stepwise logistic regression analyses were performed using the following variables: sex, BMI, BSA, hyperglycemia, malnutrition, and anemia. Severe CIPN occurred in seven patients (17.5%). Gender and anemia remained following the stepwise procedure, and anemia predicted severe CIPN significantly (OR = 19.45, 95% confi-dence interval = 1.52–171.12). Our study suggests that anemia at initial diagnosis could be a predictive factor of R-CHOP-induced CIPN.

Objectives The aim of the present study was to investigate the impact of preoperative cachexia on postoperative length of stay (LOS) in elderly patients with gastrointestinal cancer. Methods This prospective cohort study enrolled 98 patients (≥60 y of age) with gastric or colorectal cancer who were scheduled to undergo curative surgery and were categorized as either having cachexia or as being in a non-cachexia group. The definition of cachexia was patients with >5% loss of stable body weight over the previous 6 mo, a body mass index (BMI) 2%, or sarcopenia and ongoing weight loss >2%. Multivariable Poisson regression analysis was performed with postoperative LOS as the dependent variable and the presence of cachexia as the independent variable, and age, sex, Eastern Cooperative Oncology Group performance status, education, cancer type, clinical stage, surgical approach, and the Charlson Comorbidity Index as confounding variables. Results Twenty-two patients (22.4%) were diagnosed with cachexia. Postoperative LOS was 17.1 ± 8.7 d in the non-cachexia group and 20.6 ± 10.8 d in the cachexia group. Multivariable Poisson analysis showed that preoperative cachexia was significantly associated with prolonged postoperative LOS after adjustment (2.41 d; 95% confidence interval, 0.28 to 4.55; P = 0.027). Conclusions Our results suggested that preoperative cachexia prolongs postoperative LOS in elderly patients with gastrointestinal cancer, implying that cachexia should be assessed and treated before surgery.

Background and aim Among elderly patients undergoing cardiac surgery, malnutrition is very common and related to muscle wasting known as sarcopenia. Cardiac surgery causes a further decline of nutritional status due to reduced dietary intake (DI); however, the impact of postoperative DI on functional recovery is unclear. Methods and results We enrolled 250 consecutive patients undergoing cardiac surgery. Daily DI was measured between postoperative days 3 and 7. Patients were categorized as having sufficient or insufficient DI based on whether their DI met or was less than estimated total energy requirements. Functional capacity was measured using the 6-minute walking distance (6MWD) preoperatively and at discharge. Mean postoperative DI was 22.4 ± 3.0 kcal/kg/day, and postoperative DI was insufficient in 92 patients (36.8%). The prevalence of sarcopenia was not different by postoperative DI. Although there was no significant difference in preoperative 6MWD results (P = 0.65), the sufficient DI group had longer 6MWD at discharge than the insufficient DI group (P = 0.04). In multivariate regression analysis, preoperative poor nutritional status (β = −0.29), duration of surgery (β = −0.18), and postoperative DI (β = 0.40) remained statistically significant predictors for improvement of 6MWD (P Conclusions Postoperative DI was independently associated with functional recovery, but preoperative sarcopenia was not. Regardless of preoperative nutritional status or the presence of sarcopenia, aggressive nutritional intervention in the early stage after surgery helps support functional recovery.

Hyperglycemia impairs oxidative capacity in skeletal muscle. Muscle oxidative capacity is regulated by peroxisome proliferator-activated receptor-γ co-activator-1α (PGC-1α). Transcutaneous carbon dioxide (CO2) enhances PGC-1α expression in skeletal muscle. Therefore, the aim of this study was to clarify the effects of CO2 therapy on muscle oxidative capacity impaired by streptozotocin (STZ)-induced hyperglycemia. Eight-week-old male Wistar rats were randomly divided into 4 groups: control, CO2 treatment, STZ-induced hyperglycemia, and STZ-induced hyperglycemia treated with CO2. STZ-induced hyperglycemia resulted in a decrease of muscle oxidative capacity and decreased PGC-1α and cytochrome c oxidase subunit 4 (COX-4) expression levels; while, application of transcutaneous CO2 attenuated this effect, and enhanced the expression levels of endothelial nitric oxide synthesis (eNOS). These results indicate that transcutaneous CO2 improves impaired muscle oxidative capacity via enhancement of eNOS and PGC-1α-related signaling in the skeletal muscle of rats with hyperglycemia.

Background Few studies have examined patient satisfaction with playing pre-injury sports after anterior cruciate ligament (ACL) reconstruction. The purpose of this study was to investigate patient satisfaction with playing pre-injury sport and identify factors associated with satisfaction. Methods A total of 97 patients underwent unilateral ACL reconstruction using a hamstring autograft and returned to pre-injury sports 1 year after surgery. Patient satisfaction with playing pre-injury sport was assessed by a visual analog scale (VAS) and an ordinal four-grade scale. Problems related to the operated knee were also assessed. Knee muscle strength, single leg hop distance, knee laxity, subjective knee pain, and fear of movement/reinjury using Tampa Scale for Kinesiophobia-11 (TSK-11) were measured. Multivariate linear regression analysis was performed to determine the factors associated with patient satisfaction with playing pre-injury sport 1 year after surgery. Results The average VAS score for patient satisfaction with playing pre-injury sports 1 year after surgery was 77.8 ± 20.2. Of the 97 patients, 87 patients (89.7%) answered “satisfied” or “mostly satisfied”, whereas 51 patients (52.6%) had one or more problems. Multivariate linear regression analysis identified that the TSK-11 score was associated with patient satisfaction with playing a pre-injury sport 1 year after surgery. Conclusion Most of the patients who returned to pre-injury sports were satisfied with their outcomes. In contrast, approximately half of the patients had one or more problems after returning to play pre-injury sports. In particular, fear of movement/reinjury was significantly associated with patient satisfaction with playing pre-injury sport 1 year after surgery.

Carbon dioxide (CO2) treatment is reported to have an antitumor effect owing to the improvement in intratumoral hypoxia. Previous studies were based on histological analysis alone. In the present study, the improvement in intratumoral hypoxia by percutaneous CO2 treatment in vivo was determined using 18F-fluoromisonidazole positron emission tomography-computed tomography (18F-FMISO PET-CT) images. Twelve Japanese nude mice underwent implantation of LM8 tumor cells in the dorsal subcutaneous area 2 weeks before percutaneous CO2 treatment and 18F-FMISO PET-CT scans. Immediately after intravenous injection of 18F-FMISO, CO2 and room air were administered transcutaneously in the CO2-treated group (n=6) and a control group (n=6), respectively; each treatment was performed for 10 minutes. PET-CT was performed 2 h after administration of 18F-FMISO. 18F-FMISO tumor uptake was quantitatively evaluated using the maximum standardized uptake value (SUVmax), tumor-to-liver ratio (TLR), tumor-to-muscle ratio (TMR), metabolic tumor volume (MTV) and total lesion glycolysis (TLG). Mean ± standard error of the mean (SEM) of the tumor volume was not significantly different between the two groups (CO2-treated group, 1.178±0.450 cm3; control group, 1.368±0.295 cm3; P=0.485). Mean ± SEM of SUVmax, TLR, MTV (cm3) and TLG were significantly lower in the CO2-treated group compared with the control group (0.880±0.095 vs. 1.253±0.071, P=0.015; 1.063±0.147361 vs. 1.455±0.078, P=0.041; 0.353±0.139 vs. 1.569±0.438, P=0.015; 0.182±0.070 vs. 1.028±0.338, P=0.015), respectively. TMR was not significantly different between the two groups (4.520±0.503 vs. 5.504±0.310; P=0.240). In conclusion, 18F-FMISO PET revealed that percutaneous CO2 treatment improved intratumoral hypoxia in vivo. This technique enables assessment of the therapeutic effect in CO2 treatment by imaging, and may contribute to its clinical application.

It has recently been shown that the aging population is refractory to the maintenance of swallowing function, which can seriously affect quality of life. Singing and vocal training contribute to mastication, swallowing and respiratory function. Previous studies have shown that singers have better vocal cord health. No consensus has been reached as to how vocal training affects swallowing function. Our study was designed to establish evidence that singers are statistically superior at swallowing function. In an effort to test our hypothesis we undertook a clinical trial on 55 singers and 141 non-singers (mean age: 60.1 ± 11.7 years). This cross-sectional study with propensity score matching resulted in significant differences in the repetitive saliva swallowing test among singers: 7.1 ± 2.4, n =53 vs non-singers: 5.9 ± 1.9, n =53, p < 0.05. We therefore conclude that singing can serve an important role in stabilizing the impact of age-related disease on speech.

Objectives Frailty is a multidimensional syndrome. However, typical frailty scales used in oncology clinics assess physical impairment and/or malnutrition but do not consider the social domain. Our study aimed to clarify the relationship between preoperative social frailty and overall survival (OS) and cancer-specific survival (CSS) among older patients with gastrointestinal cancer. Design This was a prospective cohort study. Setting and Participants This single-center study recruited 195 patients with gastrointestinal cancer scheduled for curative surgery and aged >60 years. Methods The outcomes considered were the OS and CSS of surgery. Primary associated factors included frailty defined as a Geriatric 8 score ≤14; social frailty defined as 2 or more of the following—going out less frequently, rarely visiting friends, feeling unhelpful to friends or family, living alone, and not talking with someone daily, and combinations therein [no frailty without social frailty (−/−), frailty without social frailty (+/−), no frailty with social frailty (−/+), and frailty with social frailty (+/+)]. We used the Cox proportional hazards model and the Fine and Gray proportional subdistribution hazard model adjusting for confounding factors. Results Of the 195 patients, 181 (mean age, 72.0 years) were included for analysis. The median follow-up time was 994 days. Social frailty (hazard ratio 3.10) and their combinations [6.35; frailty with social frailty (+/+) vs no frailty without social frailty (−/−)] were significant predictors of OS. Social frailty (subdistribution hazard ratio 3.23) and their combinations (7.57) were significant predictors of CSS. Conclusions and Implications Preoperative social frailty is a predictor of OS and CSS in older patients with gastrointestinal cancer. Screening for social frailty, frailty, and their combinations in older patients with cancer is important.

We developed a registration system between OpenPose and Motion Analysis, that is a gold standard of human motion analysis, to evaluate the accuracy of human joint position. We took the data of the both for walking ten healthy persons: five males and five females. The registration result was evaluated by comparing with their obtained data. As a result, OpenPose had an error of 63.4mm on horizontal axis, 30.2mm on vertical axis in videos taken from the side view, and 29.2mm on horizontal axis, 34.1mm on vertical axis in videos taken from the front view with comparison to Motion Analysis.

Background MicroRNAs (miRNAs) are a class of small non-coding RNA molecules that regulate gene expression. There is increasing evidence that some miRNAs are involved in the pathology of diabetes mellitus (DM) and its complications. We hypothesized that the functions of certain miRNAs and the changes in their patterns of expression may contribute to the pathogenesis of impaired fractures due to DM. Methods In this study, 108 male Sprague–Dawley rats were divided into DM and control groups. DM rats were created by a single intravenous injection of streptozotocin. Closed transverse femoral shaft fractures were created in both groups. On post-fracture days 5, 7, 11, 14, 21, and 28, miRNA was extracted from the newly generated tissue at the fracture site. Microarray analysis was conducted with miRNA samples from each group on post-fracture days 5 and 11. The microarray findings were validated by real-time polymerase chain reaction (PCR) analysis at each time point. Results Microarray analysis revealed that, on days 5 and 11, 368 and 207 miRNAs, respectively, were upregulated in the DM group, compared with the control group. The top four miRNAs on day 5 were miR-339-3p, miR451-5p, miR-532-5p, and miR-551b-3p. The top four miRNAs on day 11 were miR-221-3p, miR376a-3p, miR-379-3p, and miR-379-5p. Among these miRNAs, miR-221-3p, miR-339-3p, miR-376a-3p, miR-379-5p, and miR-451-5p were validated by real-time PCR analysis. Furthermore, PCR analysis revealed that these five miRNAs were differentially expressed with dynamic expression patterns during fracture healing in the DM group, compared with the control group. Conclusions Our findings will aid in understanding the pathology of impaired fracture healing in DM and may support the development of molecular therapies using miRNAs for the treatment of impaired fracture healing in patients with DM.

Summary Introduction Skin flap procedures are widely used to reconstruct skin and soft tissue defects. Skin flap necrosis is a serious postoperative complication. Many researchers have introduced pharmacological agents to improve flap ischemia in experimental studies. However, outcomes of these studies remain controversial. We previously demonstrated that transcutaneous CO2 application improves hypoxia in fracture repair. In this study, we hypothesized that improving hypoxia by transcutaneous CO2 application can improve the blood flow in skin flaps and increase angiogenesis. We investigated whether transcutaneous CO2 application can increase the survival of random-pattern skin flaps. Materials and methods Six-week-old male Sprague-Dawley rats were divided into two equal groups: the control group (n = 6) and CO2 group (n = 6). A random-pattern skin flap was constructed in these rats. Topical CO2 was applied using a hydrogel every day for 5 days in the CO2 group. The flap survival area was measured on postoperative days 1, 3, and 5. The vessel density and expression of vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF), and hypoxia-inducible factor-1α (HIF-1α) were evaluated on postoperative day 5. Results A statistically significant difference was found in the percentage of the flap survival area between the two groups on postoperative days 3 and 5 (p Conclusions Transcutaneous CO2 application can improve the blood flow in skin flaps and increase angiogenesis, thus increasing the survival of random-pattern skin flaps.

ObjectivesDiabetes mellitus (DM) is known to impair fracture healing. Increasing evidence suggests that some microRNA (miRNA) is involved in the pathophysiology of diabetes and its complications. We hypothesized that the functions of miRNA and changes to their patterns of expression may be implicated in the pathogenesis of impaired fracture healing in DM.MethodsClosed transverse fractures were created in the femurs of 116 rats, with half assigned to the DM group and half assigned to the control group. Rats with DM were induced by a single intraperitoneal injection of streptozotocin. At post-fracture days five, seven, 11, 14, 21, and 28, miRNA was extracted from the newly generated tissue at the fracture site. Microarray analysis was performed with miRNA samples from each group on post-fracture days five and 11. For further analysis, real-time polymerase chain reaction (PCR) analysis was performed at each timepoint.ResultsMicroarray analysis showed that there were 14 miRNAs at day five and 17 miRNAs at day 11, with a greater than twofold change in the DM group compared with the control group. Among these types of miRNA, five were selected based on a comparative and extended literature review. Real-time PCR analysis revealed that five types of miRNA (miR-140-3p, miR-140-5p, miR-181a-1-3p, miR-210-3p, and miR-222-3p) were differentially expressed with changing patterns of expression during fracture healing in diabetic rats compared with controls.ConclusionsOur findings provide information to further understand the pathology of impaired fracture healing in a diabetic rat model. These results may allow the potential development of molecular therapy using miRNA for the treatment of impaired fracture healing in patients with DM. Cite this article: S. Takahara, S. Y. Lee, T. Iwakura, K. Oe, T. Fukui, E. Okumachi, T. Waki, M. Arakura, Y. Sakai, K. Nishida, R. Kuroda, T. Niikura. Altered expression of microRNA during fracture healing in diabetic rats. Bone Joint Res 2018;7:139–147. DOI: 10.1302/2046-3758.72.BJR-2017-0082.R1.

Background Few studies have addressed the impact of palliative surgery for cervical spine metastasis on patients’ performance status (PS) and quality of life (QOL). We investigated the surgical outcomes of patients with cervical spine metastasis and the risk factors for a poor outcome with a focus on the PS and QOL. Methods We prospectively analyzed patients with cervical spine metastasis who underwent palliative surgery from 2013 to 2018. The Eastern Cooperative Oncology Group PS (ECOGPS) and EuroQol 5-Dimension (EQ5D) score were assessed at study enrollment and 1, 3, and 6 months postoperatively. Neurological function was evaluated with Frankel grading. Univariate and multivariate analyses were performed to identify the risk factors for a poor surgical outcome, defined as no improvement or deterioration after improvement of the ECOGPS or EQ5D score within 3 months. Results Forty-six patients (mean age, 67.5 ± 11.7 years) were enrolled. Twelve postoperative complications occurred in 11 (23.9%) patients. The median ECOGPS improved from PS3 at study enrolment to PS2 at 1 month and PS1 at 3 and 6 months postoperatively. The mean EQ5D score improved from 0.085 ± 0.487 at study enrolment to 0.658 ± 0.356 at 1 month and 0.753 ± 0.312 at 3 months. A poor outcome was observed in 18 (39.1%) patients. The univariate analysis showed that variables with a P value of P = 0.025). Conclusions Palliative surgery for cervical spine metastasis improved the PS and QOL, but a cervicothoracic junction lesion could be a risk factor for a poor outcome.

The acceleration of nerve regeneration remains a clinical challenge. We previously demonstrated that transcutaneous CO2 application using a novel hydrogel increases the oxygen concentration in local tissue via an "artificial Bohr effect" with the potential to prevent muscle atrophy. In this study, we investigated the effect of transcutaneous CO2 administration on limb function after peripheral nerve injury in a rat sciatic nerve injury model. In total, 73 Sprague-Dawley rats were divided into a sham group, a control group (crush injury to sciatic nerve and no treatment) or a CO2 group (crush injury with transcutaneous CO2 application). CO2 was administered percutaneously for 20 min five times per week. Scores for the sciatic function index and pinprick test were significantly higher in the CO2 group than control group. The muscle wet weight ratios of the tibialis anterior and soleus muscles were higher in the CO2 group than control group. Electrophysiological examination showed that the CO2 group had higher compound motor action potential amplitudes and shorter distal motor latency than the control group. Histological examination of the soleus muscle sections at postoperative week 2 showed shorter fiber diameter in the control group than in the CO2 group. The mRNA expression of Atrogin-1 and MuRF-1 was lower, mRNA expression of VEGF and myogenin and MyoD was higher in CO2 group at postoperative week 2 compared to the control group. Clinical significance Transcutaneous CO2 application has the therapeutic potential to accelerate the recovery of muscle atrophy in peripheral nerve injury. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 36:1653-1658, 2018.

Background One of the main complications in patients with muscular dystrophies is cardiac dysfunction. The literature on cardiac involvement in patients with Fukuyama congenital muscular dystrophy (FCMD) is limited. Aim To compare cardiac involvement between patients with FCMD and Duchenne muscular dystrophy (DMD). Methods We compared cardiac involvement between 30 patients with FCMD and 181 patients with DMD using echocardiography and serum biomarkers. All patients were receiving regular checkups at Kobe University Hospital. We used single regression analysis to compare echocardiographic parameters, age, and serum biomarkers. Results Almost all clinical and echocardiographic parameters were lower in patients with FCMD than DMD. The brain natriuretic peptide concentration in patients with FCMD showed no correlation with age or left ventricular ejection fraction ( r = 0.231, p = 0.22 and r = 0.058, p = 0.76, respectively). A log-rank test revealed that the risk of left ventricular systolic dysfunction was lower in patients with FCMD than DMD ( p = 0.046, hazard ratio = 0.348). Conclusion The clinical progression of cardiac dysfunction is significantly milder in patients with FCMD than DMD, while skeletal muscle involvement is significantly worse in patients with FCMD. These data suggest that the pathophysiological findings of FCMD can be explained by less severe cardiac dysfunction in FCMD than DMD.

Pulmonary arterial hypertension (PAH) and chronic thromboembolic pulmonary hypertension (CTEPH) are the main subgroups of pulmonary hypertension (PH). Despite differences in their etiologies, both diseases are characterized by vascular remodeling, resulting in progressive right heart failure. Noninvasive periodic evaluation of exercise tolerance has become increasingly important. Cardiopulmonary exercise testing (CPET) and a 6-minute walk test (6MWT) are now both recommended for evaluating exercise tolerance, but there is insufficient knowledge about possible differences in the associations of exercise tolerance with right heart catheterization (RHC) data for patients with PAH and CTEPH.A retrospective study was performed with 57 patients with PH (24 with PAH and 33 with CTEPH) all of whom underwent echocardiography, CPET, 6MWT, and RHC.For both patients with PAH and CTEPH, peak heart rate during CPET was significantly higher than that from 6MWT, whereas minimum peripheral oxygen saturation during CPET and 6MWT was similar. For patients with PAH, significant correlations were observed between peak (Equation is included in full-text article.)O2 and cardiac index (CI) (r = 0.59; P = .002) and between (Equation is included in full-text article.)E/(Equation is included in full-text article.)CO2 slopes and CI (r =-0.46, P = .02), as well as a nonsignificant correlation tendency for peak (Equation is included in full-text article.)O2 and pulmonary vascular resistance (PVR) and for (Equation is included in full-text article.)E/(Equation is included in full-text article.)CO2 and PVR (r =-0.39; P = .05; and r = 0.39; P = .06, respectively). For patients with CTEPH, however, a significant correlation was observed only between (Equation is included in full-text article.)E/(Equation is included in full-text article.)CO2 slopes and CI (r =-0.38; P = .02).PH etiology should be considered when assessing exercise tolerance, whereas CPET can be effective in addition to hemodynamic assessment by means of RHC for periodic evaluation during followup.

Carbon dioxide (CO2) therapy can be applied to treat a variety of disorders. We previously found that transcutaneous application of CO2 with a hydrogel decreased the tumor volume of several types of tumors and induced apoptosis via the mitochondrial pathway. However, only one condition of treatment intensity has been tested. For widespread application in clinical antitumor therapy, the conditions must be optimized. In the present study, we investigated the relationship between the duration, frequency, and treatment interval of transcutaneous CO2 application and antitumor effects in murine xenograft models. Murine xenograft models of three types of human tumors (breast cancer, osteosarcoma, and malignant fibrous histiocytoma/undifferentiated pleomorphic sarcoma) were used to assess the antitumor effects of transcutaneous CO2 application of varying durations, frequencies, and treatment intervals. In all human tumor xenografts, apoptosis was significantly induced by CO2 treatment for ≥10 min, and a significant decrease in tumor volume was observed with CO2 treatments of >5 min. The effect on tumor volume was not dependent on the frequency of CO2 application, i.e., twice or five times per week. However, treatment using 3- and 4-day intervals was more effective at decreasing tumor volume than treatment using 2- and 5-day intervals. The optimal conditions of transcutaneous CO2 application to obtain the best antitumor effect in various tumors were as follows: greater than 10 min per application, twice per week, with 3- and 4-day intervals, and application to the site of the tumor. The results suggest that this novel transcutaneous CO2 application might be useful to treat primary tumors, while mitigating some side effects, and therefore could be safe for clinical trials.

An infant boy underwent hip disarticulation for infantile fibrosarcoma immediately after birth. His rehabilitation began when he was 4 mos old and involved training with his left (residual) leg. He could stand with support at 12 mos. His initial prosthesis fitting was performed at the age of 13 mos. He could stand and walk with support at 15 mos of age and could walk with no additional support and go up and down stairs at 2 yrs. A single-axis prosthetic knee joint was introduced at the age of 2 yrs 3 mos. His first gait using a hip prosthesis was successful, and his prosthesis was replaced at appropriate intervals with no major problems. The authors believe that the key to achieving a successful prosthetic gait in children is good communication among the medical team, which should comprise an orthopedic doctor, rehabilitation doctor, nurse, physical therapist, prosthetist/orthotist, and the patient's parents.

To examine the association of physical activity (PA) with bone health among patients with breast cancer receiving adjuvant aromatase inhibitor (AI) treatment. In this single-center observational study, we enrolled postmenopausal women with primary hormone receptor-positive breast cancer who were receiving adjuvant AI treatment. We assessed patient bone health [bone mineral density (BMD) and biomarkers of bone turnover] as main outcomes. PA was assessed using Baecke physical activity questionnaires (BPAQ) and an accelerometer. Multiple regression analysis was performed after adjustment for age, body mass index, smoking history and duration of AI treatment. For missing data, multiple imputation analysis was adapted. The mean age of the 53 enrolled patients was 67.4 ± 8.4 years. The mean duration of AI administration was 25.7 ± 18.9 months. The most frequently administered AI was anastrozole (73.6%). Although not related to BMD, PA was related to bone turnover. Serum collagen type I amino-terminal propeptide, a bone formation marker, was associated with only light PA (t = − 2.55, p = 0.015), while tartrate-resistant acid phosphatase 5b, a bone absorption marker, was associated with work index in the BPAQ subscale and light PA (t = − 2.28, p = 0.028, t = − 2.26, p = 0.031, respectively). The results for all patients were similar to those observed in the multiple imputation analysis. PA was significantly associated with bone turnover among cancer patients receiving AI treatment. Light PA and PA in the work domain were the most important factors among various PA intensities and PA domains.

BackgroundClinicians have very limited options to improve fracture repair. Therefore, it is critical to develop a new clinically available therapeutic option to assist fracture repair biologically. We previously reported that the topical cutaneous application of carbon dioxide (CO2) via a CO2absorption-enhancing hydrogel accelerates fracture repair in rats by increasing blood flow and angiogenesis and promoting endochondral ossification. The aim of this study was to assess the safety and efficacy of CO2therapy in patients with fractures.MethodsPatients with fractures of the femur and tibia were prospectively enrolled into this study with ethical approval and informed consent. The CO2absorption-enhancing hydrogel was applied to the fractured lower limbs of patients, and then 100% CO2was administered daily into a sealed space for 20 min over 4 weeks postoperatively. Safety was assessed based on vital signs, blood parameters, adverse events, and arterial and expired gas analyses. As the efficacy outcome, blood flow at the level of the fracture site and at a site 5 cm from the fracture in the affected limb was measured using a laser Doppler blood flow meter.ResultsNineteen patients were subjected to complete analysis. No adverse events were observed. Arterial and expired gas analyses revealed no adverse systemic effects including hypercapnia. The mean ratio of blood flow 20 min after CO2therapy compared with the pre-treatment level increased by approximately 2-fold in a time-dependent manner.ConclusionsThe findings of the present study revealed that CO2therapy is safe to apply to human patients and that it can enhance blood flow in the fractured limbs.Trial registrationThis study has been registered in the UMIN Clinical Trials Registry (Registration number:UMIN000013641, Date of registration: July 1, 2014).

Objectives The provision of inpatient programs that reduce the incidence of readmission after cardiac surgery remains challenging. Investigators have focused on multidisciplinary cardiac rehabilitation (CR) because it reduces the postoperative readmission rate; however, most previous studies used outpatient models (phase II CR). We retrospectively investigated the effect of comprehensive multidisciplinary interventions in the acute inpatient phase (phase I CR) on unplanned hospital readmission. Methods In a retrospective cohort study, we compared consecutive patients after cardiac surgery. We divided them into the multidisciplinary CR (multi-CR) group or conventional exercise-based CR (conv-CR) group according to their postoperative intervention during phase I CR. Multi-CR included psychological and educational intervention and individualized counseling in addition to conv-CR. The primary outcome was unplanned readmission rates between the groups. A propensity score–matching analysis was performed to minimize selection biases and the differences in clinical characteristics. Results In our cohort (n = 341), 56 (18.3%) patients had unplanned readmission during the follow-up period (median, 419 days). Compared with the conv-CR group, the multi-CR group had a significantly lower unplanned readmission rate (multivariable regression analysis; hazard ratio, 0.520; 95% confidence interval, 0.28-0.95; P = .024). A Kaplan–Meier analysis of our propensity score–matched cohort showed that, compared with the conv-CR group, the multi-CR group had a significantly lower incidence of readmission (stratified log-rank test, P = .041). Conclusions In phase I, compared to conv-CR alone, multi-CR reduced the incidence of unplanned readmission. Early multidisciplinary CR can reduce hospitalizations and improve long-term prognosis after cardiac surgery.

Objectives: Rheumatoid Arthritis (RA) is the autoimmune disease representing the circadian variations of symptoms such as morning stiffness of joints or increased production of cytokines around midnight. Clock genes have been reported to affect on the pathogenesis of RA, however, the detailed relation between clock genes and disease activities of RA has remained unclear. Methods: In this study, 15 RA patients treated with biological disease modifying anti-rheumatic drugs (bDMARDs) were enrolled (TNF inhibitor, 5; IL-6 inhibitor, 5; CTLA4-IgG, 5). Blood samples were collected from RA patients before treatment and at the study end-point fulfilling DAS28-ESR < 3.2. Total RNA was extracted from leukocytes to examine the expressions of the clock genes. We then evaluated the correlation of the clock gene expression with disease activity and the diagnostic values of the clock genes. Results: The expressions of the clock genes were significantly modulated by bDMARDs treatments. Disease activities were significantly correlated with the clock genes expressions, and disease remission/low disease activity could be distinguished from moderate/high disease activity due to the sensitivities, the specificities and the areas under the curves of that. Conclusion: The expressions of the clock genes in leukocytes could be useful as novel biomarkers predicting disease activities and therapeutic efficacies for bDMARDs in RA treatments.