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

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

Radiation Myelopathy Caused by Palliative Radiotherapy and Intrathecal Methotrexate

Radiation myelopathy is a rare, late-stage adverse event that develops following irradiation at or above 50 Gy. Here, we report a case of irreversible paraplegia caused by palliative radiation (20 Gy in 5 fractions) to the spinal cord combined with intrathecal methotrexate (IT-MTX). A 69-year-old man presented with back pain, prompting a diagnosis of acute myeloid leukemia. At the first visit, he complained of muscle weakness and hypoesthesia in both legs; spinal magnetic resonance imaging (MRI) revealed an epidural mass compressing the spinal cord at the fifth to seventh level of the thoracic vertebrae. This was considered to be an extramedullary lesion of leukemia, and he received remission induction therapy including IT-MTX; palliative radiation (20 Gy in 5 fractions) of the epidural mass was initiated the following day. Then, during the course of consolidation therapy, a second IT-MTX was performed after 1 month and a third after 3 months. While the consolidation therapy was complete, yielding remission, he developed sudden paraplegia, as well as bladder and bowel dysfunction (BBD), 10 months later. Spinal MRI showed extensive intramedullary high signal intensity on T2-weighted image, including the irradiation field. It was thought myelopathy was due to irradiation of the spinal cord combined with IT-MTX. He immediately received steroid pulse therapy; however, the paraplegia and BBD did not improve. It is extremely rare for irreversible radiation myelopathy to occur with IT-MTX and palliative radiation to the spinal cord. We believe that even with low-dose palliative radiation, caution is required for combined use with IT-MTX

A Role of Staphyococcus aureus, Interleukin-18, Nerve Growth Factor and Semaphorin 3A, an Axon Guidance Molecule, in Pathogenesis and Treatment of Atopic Dermatitis

Staphylococcus aureus (SA) is usually present not only in the skin lesions of atopic dermatitis (AD) but also in the atopic dry skin. SA discharges various toxins and enzymes that injure the skin, results in activation of epidermal keratinocytes, which produce and release IL-18. IL-18 that induces the super Th1 cells secreting IFN-γ and IL-13 is supposed to be involved in development of AD and its pathogenesis. Indeed, the number of SA colonies on the skin surface and the serum IL-18 levels in patients with AD significantly correlated with the skin scores of AD lesions. Also, there is strong positive correlation between the skin scores and serum IL-18 levels in DS-Nh mice (P<0.0001, r=0.64), which develop considerable AD-like legions when they are housed under conventional conditions, but develop skin legions with less severity and less frequency under specific pathogens free (SPF) conditions. Therefore, they are well-known as model mice of AD, in which SA is presumed to be critical factor for the development of AD lesions. Also, theses DS-Nh mice pretreated with Cy developed more remarkable AD-like lesions in comparison with non-treated ones. The levels of INF-r and IL-13 in the supernatants of the lymph node cell cultures stimulated with staphylococcal enterotoxin B (SEB) or ConA were increased in the Cy-treated mice, although the serum levels of total IgE were not. In this experiment, we revealed that Cy-treated mice, to which CD25 +CD4 + reguratory T cells taken from non-treated ones had been transferred, developed the AD-like legions with less severity and less number of SA colonies on the skin surface. Therefore, it is presumed that CD25 +CD4 + reguratory T cells might be involved in the suppression of super Th1 cells which are induced by IL-18 and are involved in the development of AD-like lesions rather than IgE production. The efficient induction of CD25 +CD4 + reguratory T cells is expected for the new type of treatment of AD. We also found that farnesol (F) and xylitol (X) synergistically inhibited biofilm formation by SA, and indeed the ratio of SA in total bacteria at sites to which the FX cream containing F and X had been applied was significantly decreased 1 week later, accompanied with improvement of AD, when compared with that before application and at placebo sites. Therefore, the FX cream is a useful skin-care agent for atopic dry skin colonized by SA. The nerve growth factor (NGF) in the horny layer (the horn NGF) of skin lesions on the cubital fossa was collected by tape stripping and measured using ELISA in AD patients before and after 2 and 4 weeks treatments. Simultaneously, the itch and eruptions on the whole body and on the lesions, in which the horn NGF was measured, were recorded, and also the peripheral blood eosinophil count, serum LDH level and serum total IgE level were examined. The level of NGF was significantly higher in AD patients than in healthy controls, correlated with the severity of itch, erythema, scale/xerosis, the eosinophil count and LDH level, and also significantly decreased after treatments with olopatadine and/or steroid ointment for 2 and 4 weeks. Therefore, the measurement of the NGF by this harmless method seems to be useful to assess the severity of AD and the therapeutic effects on AD. In AD patients, C-fiber in the epidermis increase and sprout, inducing hypersensitivity, which is considered to aggravate the disease. Semaphorin 3A (Sema3A), an axon guidance molecule, is a potent inhibitor of neurite outgrowth of sensory neurons. We administered recombinant Sema3A intracutaneously into the skin lesions of NC/Nga mice, an animal model of AD, and investigated the effect of Sema3A on the skin lesions and their itch. Sema3A dose-dependently improved skin lesions and attenuated the scratching behavior in NC/Nga mice. Histological examinations revealed a decrease in the epidermal thickness, the density of invasive nerve fibers in the epidermis, inflammatory infiltrate including mast cells and CD4 +T cells, and the production of IL-4 in the Sema3A-treated lesions. Because the interruption of the itch-scratch cycle likely contributes to the improvement of the AD-like lesions, Sema3A is expected to become a promising treatment of patients with refractory AD

Association of Transition of Laboratory Markers with Transition of Disease Activity in Psoriasis Patients Treated with Biologics

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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