Intramuscular Adipose Tissue Content Predicts Patient Outcomes after Allogeneic Hematopoietic Stem Cell Transplantation

移植の成功に重要なのは、「質の良い」筋肉 --コンピュータ断層撮影を用いて評価した骨格筋指標での検討--. 京都大学プレスリリース. 2022-07-12.During clinical courses involving allogeneic hematopoietic stem cell transplantation (allo-HSCT), multidisciplinary assessments for patients including physical functions are indispensable, and quantitative skeletal muscle loss is a poor prognostic marker. In addition, deteriorating quality of muscle due to intra-muscle adipose tissue degeneration can be important as well, because many patients are cachexic or sarcopenic before allo-HSCT, although this approach has not been employed yet. Therefore, we conducted a retrospective cohort study to evaluate the quality, as well as quantity of skeletal muscle using computed tomography (CT). Psoas muscle mass index (PMI) and radiographic density (RD) calculated by cross-sectional area and averaged CT values of the psoas major muscle at the umbilical level were used to determine the quantity and quality of muscle, respectively. In total, 186 adult patients, aged 17-68 years (median, 49) were included in this study, and 46 (24.7%) and 49 (26.3%) patients were assigned to the lower PMI and RG groups. Low RD was identified as an independent risk factor for poor overall survival after allo-HSCT (adjusted hazard ratio 2.54, p<0.01), while PMI was not significant. Decreased RD along with reduced 6-min walking distance before transplantation was also significant factor for increased non-relapse mortality (hazard ratio, 2.69, p=0.01). This study is the first to suggest the use of a qualitative skeletal muscle index to serve as a prognostic indicator following allo-HSCT. RD should be included in pre-transplant screening parameters, and approaches that include rehabilitation focused on improving both muscle quality and quantity may improve the prognosis of allo-HSCT

Molecular tumorigenesis of the skin

Skin tumors are supposed to develop through accumulations of genetic and/or epigenetic events in normal cells of the skin. Among them, we focus on common skin tumors, including benign, seborrheic keratosis, and malignant, squamous cell carcinoma and melanoma. Many important molecules have been detected on the molecular tumorigenesis of each of them to date, and some drugs targeted for their molecules have been already developed. We review updates on the molecular tumorigenesis of these tumors with our current works

Higher exercise tolerance early after allogeneic hematopoietic stem cell transplantation is the predictive marker for higher probability of later social reintegration

同種造血幹細胞移植後における社会復帰の予測因子を発見 --移植後リハビリテーションがもつ重要性--. 京都大学プレスリリース. 2021-04-09.As the proportion of long-term survivors after allogeneic hematopoietic stem cell transplantation (allo-HSCT) is on the rise, it is essential to consider the significance of quality of life (QOL), including reintegration with society (returning to school or work). This retrospective cohort study aims to illustrate the precise epidemiology of social reintegration later after allo-HSCT and determine its predictive indicators. We enrolled 56 patients, and 40 patients (71%) attained social reintegration at 2 years post-HSCT. Reintegration failure markedly correlated with an inferior performance status and concurrent chronic graft-versus-host disease. In non-reintegrated patients, the physical function at discharge measured by the 6-min walking distance (6MWD) was markedly decreased. On the multivariate risk analyses, sex (female; odds ratio (OR) 0.07; 95% confidence interval (CI) 0.01–0.54; p = 0.01), HCT-CI (≥ 2; OR 0.10; 95% CI 0.01–0.84; p = 0.03), and change in 6MWD (per 5% increase; OR 1.47; 95% CI 1.01–2.13; p = 0.04) were significant predictors of later social reintegration. This study suggests that a multidisciplinary strategy including rehabilitation is essential, especially in patients with poor predictive markers at an early phase, and we should consider suitable rehabilitation programs to prevent a decline in exercise tolerance and improve social reintegration and overall QOL in patients after allo-HSCT

Effect of the severity of acute graft-versus-host disease on physical function after allogeneic hematopoietic stem cell transplantation

Purpose: The purpose of this study was to retrospectively investigate the effect of the severity of acute graft-versus-host disease (GVHD) on physical function after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Methods: 76 patients were included as subjects of this study. Severity of acute GVHD was classified according to the method defined by Grucksberg. To evaluate physical function, the knee extensor strength and six-minute walk distance (6MWD) were performed. Results: Among these patients, 54% developed acute GVHD; of these, 32%, 54%, and 15% of patients had grade I, grade II, and grades III–IV GVHD, respectively. In the grade I–II groups, mild acute GVHD following allo-HSCT resulted in a gradual decline in physical function, which improved at discharge. However, in cases of severe acute GVHD, physical function deteriorated, implementation of rehabilitation became difficult, and the decline in physical function persisted even at discharge. Conclusion: These results indicate that severe acute GVHD negatively affects physical function leading to longer hospital days because of inadequate rehabilitation interventions

Analysis of factors associated with patient-reported physical functioning scores at discharge of allogeneic hematopoietic stem cell transplantation patients: a cross-sectional study

Purpose: The purpose of this study was to clarify the independent factors related to patient-reported physical functioning (PF) scores at discharge of patients who underwent allogeneic hematopoietic stem cell transplantation (allo-HSCT). Methods: A total of 103 patients who underwent allo-HSCT were included in this cross-sectional study. As a screening method, a single regression analysis was conducted with the PF domain in the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 at discharge as the dependent variable, and body mass index, adverse events related to HSCT, and objective physical functions as independent variables. Multiple regression analysis was performed with PF as the dependent variable and variables that passed the screening by single regression analysis and confounders as independent variables. Results: The mean PF score at discharge of the patients was 76.5 (standard deviation: 15.2). Based on the results of screening by the single regression analysis, length of stay, infections (+/−), acute graft-versus-host disease grade, brief fatigue inventory score (BFI), knee extensor strength, and 6-min walk distance (6MWD) were included in the multiple regression analysis. BFI (B = − 11.94, p < 0.001) and 6MWD (per 10 m) (B = 0.56, p = 0.001) were extracted as significant independent variables governing the PF at discharge in the multiple regression model (adjusted R2 = 0.59). Conclusion: Higher exercise tolerance and lower fatigue in patients who underwent allo-HSCT were associated independently with patient-reported better PF scores at discharge

Elevated Brachial-Ankle Pulse Wave Velocity Is Associated with Left Ventricular Hypertrophy in Hypertensive Patients after Stroke

Brachial-ankle pulse wave velocity (baPWV) is widely used as a marker of arterial stiffness, but there are no data regarding the usefulness of measuring baPWV in hypertensive patients after stroke. The purpose of this study was to examine the clinical significance of baPWV by assessing its correlation with echocardiographic parameters in hypertensive patients after stroke. The study enrolled 61 hypertensives after stroke (24 patients with cerebral infarction and 37 with cerebral hemorrhage) and 61 age-matched hypertensives without stroke. Left ventricular (LV) hypertrophy was evaluated by measuring LV mass index (LVMI) and relative wall thickness (RWT), and LV diastolic function was evaluated by measuring peak early mitral annular velocities (E') using echocardiography. Concentric LV hypertrophy showing increased RWT (0.50 ± 0.12) was observed in hypertensives after stroke, but not in hypertensives without stroke. In hypertensives after stroke, elevated baPWV correlated with age (r = 0.60, p < 0.001), systolic blood pressure (r = 0.56, p < 0.001), increased LVMI (r = 0.47, p < 0.001), and decreased E' (r = -0.40, p = 0.002). Multiple regression analysis showed that age (β coefficient = 0.43, p < 0.001), systolic blood pressure (β coefficient = 0.40, p < 0.001), and LVMI (β coefficient = 0.25, p = 0.008) were independent determinants of elevated baPWV. In conclusion, elevated baPWV is more closely associated with LV hypertrophy than with LV diastolic dysfunction. Elevated baPWV is independently associated with the severity of LV hypertrophy adjusted with systolic blood pressure and age in hypertensive patients after stroke

Evaluation of indices for predicting recovery of exercise tolerance in patients surviving allogenic hematopoietic stem cell transplantation

[Purpose] Decline in physical function in the early stage after allogeneic hematopoietic stem cell transplantation (allo-HSCT) is a major challenge. Exercise tolerance tests, such as the 6-min walk test, are useful markers for predicting exercise tolerance and various other traits, including cardiometabolic risk and non-relapse mortality. This retrospective cohort study aimed to investigate and identify predictors of recovery of exercise tolerance in the early stage after allo-HSCT. [Methods] Ninety-eight patients were classified into recovery and non-recovery groups according to the median 6-min walk distance (6MWD) at discharge. [Results] Logistic regression analysis revealed that pre-post change in knee extensor strength (ΔKES) and hematopoietic cell transplantation comorbidity index were useful predictors of recovery of exercise tolerance at discharge and moderate predictors of 6MWD recovery in the early post-transplant period. Receiver operating characteristic analysis showed that pre-transplant ΔKES was an accurate predictor of 6MWD recovery in the early post-transplant period. The cutoff point for ΔKES calculated using the Youden index was − 1.17 Nm/kg. [Conclusions] The results of this study emphasize the importance of the need for programs designed to prevent muscle weakness in the early period after allo-HSCT. The results from markers of recovery of exercise tolerance are promising and can be used for patient education in rehabilitation programs after allo-HSCT