Investigation of Changes in Skeletal Muscle Mass and Muscle Quality and Factors Affecting Changes in Deceased Donor Liver Transplantation.

BACKGROUND: In Japan, there are very few cases of deceased donor liver transplantation (DDLT) and even fewer studies on the effects of DDLT on sarcopenia. This study examined the changes in skeletal muscle mass and quality in DDLT, the factors related to these changes, and survival rates. METHODS: Using computed tomography (CT), we retrospectively measured L3 skeletal muscle index (L3SMI) and intramuscular adipose tissue content (IMAC) at admission, discharge, and 1-year post-DDLT in 23 patients with DDLT from our hospital between 2011 and 2020. We investigated the relationships between changes in L3SMI and IMAC associated with DDLT and between various admission factors and survival. RESULTS: Patients with DDLT showed significant decreases in L3SMI during hospitalization (P < .05). Although L3SMI tended to increase postdischarge, in 11 (73%) cases, it was lower at 1-year post-DDLT than that on admission. Moreover, decreases in L3SMI during hospitalization were correlated to L3SMI on admission (r = 0.475, P < 0.05). Intramuscular adipose tissue content increased from admission to discharge and decreased 1-year post-DDLT. Admission L3SMI and IMAC were not significantly correlated with survival. CONCLUSIONS: This study suggests that the skeletal muscle mass of DDLT patients decreased during hospitalization and showed a slight tendency to improve after discharge, but the decrease tended to be prolonged. In addition, patients with higher skeletal muscle mass at admission tended to lose more skeletal muscle mass during hospitalization. Deceased donor liver transplantation was identified as a potential contributor to improved muscle quality, whereas skeletal muscle mass and quality on admission did not affect post-DDLT survival.

Predictors of Activities of Daily Living in Intensive Care Unit Survivors: A Propensity Score Matching Analysis.

Objectives: Increased long-term impairment is common among intensive care unit (ICU) survivors. However, predictors of activities of daily living (ADL) in ICU survivors are poorly understood. We aimed to focus on the trajectory of physical function and explore the clinical variables that affect ADL at hospital discharge. Methods: We enrolled 411 patients admitted to the ICU from April 2018 to October 2020. Physical function was evaluated at ICU admission, ICU discharge, and hospital discharge. We assessed physical function (grip strength, arm and calf circumference, quadriceps thickness, and Barthel index). Patients were assigned to the high or low ADL group based on their Barthel index at discharge. Propensity score matching analysis was performed to minimize selection biases and differences in clinical characteristics. Results: After matching propensity scores, 114 of the 411 patients (aged 65±15 years) were evaluated. The high ADL group showed better physical function at ICU discharge and hospital discharge than the low ADL group. An overall decreasing trend in muscle mass was observed over time; the rates of decline were lower in the high ADL group than in the low ADL group. The cutoff values for relative changes in calf circumference and quadriceps thickness to predict high ADL were -7.89% (sensitivity: 77.8%, specificity: 55.6%) and -28.1% (sensitivity: 81.0%, specificity: 58.8%), respectively. Conclusions: The relative decreases in calf circumference and quadriceps thickness during hospitalization were lower in patients who maintained their ADL. Assessment of the trajectory of physical function can predict ADL status at hospital discharge among ICU survivors.

Regulatory Roles of Estrogens in Psoriasis.

Psoriasis is a common chronic inflammatory skin disease of the interleukin (IL)-23/IL-17 axis. The severity of psoriasis has been reported as higher in men than in women. The immunoregulatory role of female sex hormones has been proposed to be one of the factors responsible for sex differences. Among female sex hormones, estrogens have been suggested to be significantly involved in the development of psoriasis by various epidemiological and in vitro studies. For example, the severity of psoriasis is inversely correlated with serum estrogen levels. In vitro, estrogens suppress the production of psoriasis-related cytokines such as IL-1ß and IL-23 from neutrophils and dendritic cells, respectively. Furthermore, a recent study using a mouse psoriasis model indicated the inhibitory role of estrogens in psoriatic dermatitis by suppressing IL-1ß production from neutrophils and macrophages. Understanding the role and molecular mechanisms of female sex hormones in psoriasis may lead to better control of the disease.

Estradiol suppresses psoriatic inflammation in mice by regulating neutrophil and macrophage functions.

BACKGROUND: Psoriasis is a common inflammatory skin disease resulting from dysregulation of the IL-23/TH17 immune axis. The prevalence and severity of psoriasis is higher in men than in women, although the underlying reasons for this are unclear. OBJECTIVE: We studied whether estradiol, a female hormone, plays protective roles in imiquimod-induced psoriatic inflammation in mice by regulating neutrophil and macrophage functions. METHODS: Wild-type mice and conditional knockout mice were ovariectomized, supplemented with placebo or estradiol pellets, and an imiquimod-containing cream applied. RESULTS: Mice without endogenous ovarian hormones exhibited exacerbated psoriatic inflammation including increased production of IL-17A and IL-1ß, which was reversed by exogenously added estradiol. The suppressive effect of estradiol on the production of IL-1ß and IL-17A was abolished in mice lacking estrogen receptors in neutrophils and macrophages (Esr1f/fEsr2f/fLysM-Cre+ mice). IL-1ß, which is required for production of IL-17A in the psoriasis model, was mainly produced by neutrophils and inflammatory macrophages. Estradiol suppressed IL-1ß production from neutrophils and macrophages in mice both in vivo and in vitro and from human neutrophils in vitro. CONCLUSION: Our results suggest a novel mechanism for sex-dependent differences in psoriasis clinical phenotypes that may shed new light on the pathology of psoriasis.

Prolonged high-intensity exercise induces fluctuating immune responses to herpes simplex virus infection via glucocorticoids.

BACKGROUND: Epidemiologic studies have yielded conflicting results regarding the influence of a single bout of prolonged high-intensity exercise on viral infection. OBJECTIVE: We sought to learn whether prolonged high-intensity exercise either exacerbates or ameliorates herpes simplex virus type 2 (HSV-2) infection according to the interval between virus exposure and exercise. METHODS: Mice were intravaginally infected with HSV-2 and exposed to run on the treadmill. RESULTS: Prolonged high-intensity exercise 17 hours after infection impaired the clearance of HSV-2, while exercise 8 hours after infection enhanced the clearance of HSV-2. These impaired or enhanced immune responses were related to a transient decrease or increase in the number of blood-circulating plasmacytoid dendritic cells. Exercise-induced glucocorticoids transiently decreased the number of circulating plasmacytoid dendritic cells by facilitating their homing to the bone marrow via the CXCL12-CXCR4 axis, which led to their subsequent increase in the blood. CONCLUSION: A single bout of prolonged high-intensity exercise can be either deleterious or beneficial to antiviral immunity.

High fat diet exacerbates murine psoriatic dermatitis by increasing the number of IL-17-producing γδ T cells.

Psoriasis is a common, chronic inflammatory skin disease characterized by epidermal hyperplasia via the IL-23/IL-17 axis. Various studies have indicated the association between obesity and psoriasis, however, the underlying mechanisms remains unclarified. To this end, we focused on high-fat diet (HFD) in this study, because HFD is suggested as a contributor to obesity, and HFD-fed mice exhibit exacerbated psoriatic dermatitis. Using murine imiquimod (IMQ)-induced psoriasis and HFD-induced obesity models, we have revealed a novel mechanism of HFD-induced exacerbation of psoriatic dermatitis. HFD-fed mice exhibited aggravated psoriatic dermatitis, which was accompanied with increased accumulation of IL-17A-producing Vγ4+ γδ T cells in the skin. HFD also induced the increase of Vγ4+ γδ T cells in other organs such as skin draining lymph nodes, which preceded the increase of them in the skin. In addition, HFD-fed mice displayed increased expression of several γδ T cell-recruiting chemokines in the skin. On the other hand, ob/ob mice, another model of murine obesity on normal diet, did not exhibit aggravated psoriatic dermatitis nor accumulation of γδ T cells in the dermis. These results indicate that HFD is a key element in exacerbation of IMQ-induced psoriatic dermatitis, and further raise the possibility of HFD as a factor that links obesity and psoriasis.

Case of pemphigus with immunoglobulin G and A antibodies, binding to both the intercellular spaces and basement membrane zone.

We report a case involving a 62-year-old woman with in vivo-bound immunoglobulin (Ig)G and IgA antibodies in both the intercellular space (ICS) and basement membrane zone (BMZ). Her clinical and histopathological features were identical with those of pemphigus vulgaris, while the immunopathological findings suggested IgG/IgA pemphigus. Direct immunofluorescence (IF) showed in vivo-bound IgG and IgA antibodies in the ICS and BMZ, whereas indirect IF showed circulating IgG but not IgA antibodies in the ICS and BMZ. The anti-ICS IgG bound to desmoglein-3, while the anti-BMZ antibodies bound to the epidermal side of 1 mol/L NaCl-split skin. To the best of our knowledge, only two similar cases have been reported so far. Furthermore, we also examined IgG subclass distribution of the in vivo-bound and circulating anti-ICS and BMZ antibodies, and found that IgG1, IgG2 and IgG4 bound to ICS of the lesional skins, while IgG1 and IgG3 bound to the BMZ. The circulating anti-ICS antibodies belonged to IgG1 and IgG4, while the circulating anti-BMZ antibodies to IgG1, IgG2 and IgG4. We report a case involving a 62-year-old woman with in vivo-bound immunoglobulin (Ig)G and IgA antibodies in both the intercellular space (ICS) and basement membrane zone (BMZ). Her clinical and histopathological features were identical with those of pemphigus vulgaris, while the immunopathological findings suggested IgG/IgA pemphigus. Direct immunofluorescence (IF) showed in vivo-bound IgG and IgA antibodies in the ICS and BMZ, whereas indirect IF showed circulating IgG but not IgA antibodies in the ICS and BMZ. The anti-ICS IgG bound to desmoglein-3, while the anti-BMZ antibodies bound to the epidermal side of 1 mol/L NaCl-split skin. To the best of our knowledge, only two similar cases have been reported so far. Furthermore, we also examined IgG subclass distribution of the in vivo-bound and circulating anti-ICS and BMZ antibodies, and found that IgG1, IgG2 and IgG4 bound to ICS of the lesional skins, while IgG1 and IgG3 bound to the BMZ. The circulating anti-ICS antibodies belonged to IgG1 and IgG4, while the circulating anti-BMZ antibodies to IgG1, IgG2 and IgG4.

Case of H syndrome with massive skin involvement, retroperitoneal fibrosis and Raynaud's phenomenon with a novel mutation in the SLC29A3 gene.

We describe a case of H syndrome with massive skin involvement, retroperitoneal fibrosis and Raynaud's phenomenon. A 48-year-old man with parents of a consanguineous marriage, first appeared with decreased urine output, skin sclerosis on his inner thighs and short stature (142 cm, 47 kg). The patient had suffered from hearing loss since the age of 1 year, and his secondary sexual characteristics had not developed. Computed tomography showed periaortic fibrosis, bilateral ureteral stenosis, hydronephrosis and sclerosis of the germinal cords. A biopsy from the retroperitoneal mass revealed remarkable fibrosis with chronic inflammatory cells. Biopsies from the skin lesion showed thick collagen bundles through the dermis and lymphohistiocytic infiltration with numerous plasma cells. Serum inflammatory markers, such as C-reactive protein, vascular endothelial factor, transforming growth factor-ß and soluble interleukin-2 receptor, were elevated. Prednisolone was effective in treating skin lesions and in lowering serum inflammatory markers. After a long period of follow up, genomic DNA of the patient was obtained, and we identified a homozygous mutation in exon 5, c.625G>A, which caused transition of glycine to arginine, p.Gly208Arg, in the patient, but not in DNA samples from another 50 healthy individuals. This is the first case of H syndrome with Raynaud's phenomenon and retroperitoneal fibrosis, and the first Japanese case of H syndrome reported in the English published work with a novel mutation in the SLC29A3 gene.