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Innate and adaptive resistance to cancer therapies, such as chemotherapies, molecularly targeted therapies, and immune-modulating therapies, is a major issue in clinical practice. Subpopulations of tumor cells expressing the receptor tyrosine kinase AXL become enriched after treatment with antimitotic drugs, causing tumor relapse. Elevated AXL expression is closely associated with drug resistance in clinical samples, suggesting that AXL plays a pivotal role in drug resistance. Although several molecules with AXL inhibitory activity have been developed, none have sufficient activity and selectivity to be clinically effective when administered in combination with a cancer therapy. Here, we report a novel small molecule, ER-851, which is a potent and highly selective AXL inhibitor. To investigate resistance mechanisms and identify driving molecules, we conducted a comprehensive gene expression analysis of chemoresistant tumor cells in mouse xenograft models of genetically engineered human lung cancer and human triple-negative breast cancer. Consistent with the effect of AXL knockdown, cotreatment of ER-851 and antimitotic drugs produced an antitumor effect and prolonged relapse-free survival in the mouse xenograft model of human triple-negative breast cancer. Importantly, when orally administered to BALB/c mice, this compound did not induce retinal toxicity, a known side effect of chronic MER inhibition. Together, these data strongly suggest that AXL is a therapeutic target for overcoming drug resistance and that ER-851 is a promising candidate therapeutic agent for use against AXL-expressing antimitotic-resistant tumors.

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Hypertrophic cardiomyopathy (HCM) is the primary cause of sudden cardiac death in children and adolescents. Patients with HCM frequently have ventricular tachycardia and ventricular fibrillation, although complete atrioventricular block (CAVB) is very rare. We report a case of HCM with CAVB in an 8-year-old girl who underwent transvenous implantable cardioverter-defibrillator placement after resuscitation. In this patient, we identified a de novo heterozygous missense variant, Arg406Trp (c.1216C > T), in the desmin (DES) gene. Pathogenic variants in the DES gene result in cardiomyopathy, conduction disorders, and skeletal muscle weakness. This recently identified variant may cause HCM with CAVB. Résumé: La cardiomyopathie hypertrophique (CMH) est la première cause de mort subite d'origine cardiaque chez les enfants et les adolescents. Les patients atteints de CMH présentent fréquemment une tachycardie ventriculaire et une fibrillation ventriculaire, bien que le bloc auriculo-ventriculaire complet (BAVC) soit très rare. Nous rapportons un cas de CMH avec BAVC chez une fillette de 8 ans qui a reçu un défibrillateur cardioverteur implantable par voie transveineuse après réanimation. Chez cette patiente, nous avons isolé un variant faux sens hétérozygote de novo, Arg406Trp (c.1216C > T), dans le gène de la desmine (DES). Les variants pathogènes du gène DES entraînent une cardiomyopathie, des troubles de la conduction et une faiblesse des muscles squelettiques. Ce variant récemment identifié peut causer une CMH avec BAVC.

Innate and adaptive resistance to cancer therapies, such as chemotherapies, molecularly targeted therapies, and immune-modulating therapies, is a major issue in clinical practice. Subpopulations of tumor cells expressing the receptor tyrosine kinase AXL become enriched after treatment with anti-mitotic drugs, causing tumor relapse. Elevated AXL expression is closely associated with drug resistance in clinical samples, suggesting that AXL plays a pivotal role in drug resistance. Although several molecules with AXL inhibitory activity have been developed, none have sufficient activity and selectivity to be clinically effective when administered in combination with a cancer therapy. Here, we report a novel small molecule, ER-001259851-000, which is a potent and highly selective AXL inhibitor. To investigate resistance mechanisms and identify driving molecules, we conducted a comprehensive gene expression analysis of chemo-resistant tumor cells in mouse xenograft models of genetically engineered human lung cancer and human triple-negative breast cancer. Consistent with the effect of AXL knockdown, co-treatment of ER-001259851-000 and antimitotic drugs produced an anti-tumor effect and prolonged relapse-free survival in the mouse xenograft model of human triple-negative breast cancer. Importantly, when orally administered to BALB/c mice, this compound did not induce retinal toxicity, a known side effect of chronic MER inhibition. Together, these data strongly suggest that AXL is a therapeutic target for overcoming drug resistance and that ER-001259851-000 is a promising candidate therapeutic agent for use against AXL-expressing anti-mitotic-resistant tumors.

There are no recommended diagnostic criteria for transient congenital hypothyroidism (CH) during early childhood. In this study, we aimed to identify the factors that distinguish permanent (P)- and transient (T)-CH. We retrospectively analyzed the clinical, biochemical, and imaging data of 42 children with a definitive diagnosis of P- or T-CH by re-evaluation tests at our institution from November 1986 to October 2019. Patients who continued levothyroxine (L-T4) treatment after the re-evaluation tests were classified as group P (n = 19), while patients who were diagnosed with T-CH and discontinued L-T4 treatment were classified as group T (n = 23). Initial testing performed during infancy showed that the mean serum TSH and free T4 (FT4) levels did not differ significantly between groups P and T. None of the patients in group T required an increased dosage of L-T4 at the age of 3 yr and above while 85% of the patients in group P required increased dosages of L-T4. Hence, T-CH was suspected in patients who did not require an increase in L-T4 dosage at the age of 3 yr and above.

Background Coronavirus disease 2019 (COVID‐19) pandemic has affected the lives of young and old people. Most reports on pediatric cases suggest that children experience fewer and milder symptoms than adults do. This is the first nationwide study that focused on pediatric cases reported by pediatricians, including those with no or mild symptoms, in Japan. Methods We analyzed the epidemiological and clinical characteristics, and transmission patterns of 840 pediatric (

Background: The influence of maternal psychological distress on infant congenital heart defects (CHDs) has not been thoroughly investigated. Furthermore, there have been no reports on the combined effect of maternal psychological distress and socioeconomic status on infant CHDs. This study aimed to examine whether maternal psychological distress, socioeconomic status, and their combinations were associated with CHD.Methods: We conducted a prospective cohort study using data from the Japan Environment and Children’s Study, which recruited pregnant women between 2011 and 2014. Maternal psychological distress was evaluated using the Kessler Psychological Distress Scale in the first trimester, while maternal education and household income were evaluated in the second and third trimesters. The outcome of infant CHD was determined using the medical records at 1 month of age and/or at birth. Crude and adjusted logistic regression analyses were performed to evaluate the association between maternal psychological distress and education and household income on infant CHD.Results: A total of 93,643 pairs of mothers and infants were analyzed, with 1.1% of infants having CHDs. Maternal psychological distress had a significantly higher odds ratio in the crude analysis but not in the adjusted analysis, while maternal education and household income were statistically insignificant. In the analysis of the combination variable of lowest education and psychological distress, the trend for p was statistically significant in the crude and adjusted analyses.Conclusions: The combination of maternal psychological distress and lower education may be a possible indicator of infant CHD.

Background Lower respiratory tract infections (LRTIs) are a cause of inpatient and outpatient care among children. Although orofacial clefts seem to be associated with LRTIs, epidemiological studies are scarce on this topic. This study aimed to examine whether infants with orofacial clefts were associated with LRTIs. Methods This prospective cohort study used data from the Japan Environment and Children's Study, whose baseline recruitment was conducted during 2011-2014. This study included 81,535 participants. The number of infants with cleft lip and palate (CLP), cleft lip (CL), and cleft palate only (CP) was 67, 49, and 36, respectively. We defined history of LRTIs until 12 months' age reported by their mothers as the dependent variable. Accumulated breastfeeding duration was used as potential mediators. Results The incidence proportion of LRTIs among the control group was 6.0%. The incidence proportion among infants with CLP, CL, and CP were 11.9%, 14.3%, and 5.6%, respectively. After adjusting for covariates, compared with the control group, infants with CLP and CL were associated with risk of LRTIs (incidence risk ratio [IRR] of CLP = 2.38 [95% confidence interval = 1.30, 4.36] and of CL = 2.73 [1.40, 5.33]) , but not ones with CP (1.08 [0.28, 4.15]). Accumulated breastfeeding duration decreased the IRR of CLP only (IRR of CLP = 2.16 [1.19, 3.93]). Conclusions Infants with orofacial clefts aged 1 year have a potentially high incidence proportion of LRTIs. Accumulated breastfeeding duration might mediate the associations of CLP.

Biallelic neuroblastoma amplified sequence (NBAS) gene mutations have recently been identified to cause a reduction in its protein expression and a broad phenotypic spectrum, from isolated short stature, optic nerve atrophy, and Pelger-Huet anomaly (SOPH) syndrome or infantile liver failure syndrome 2 to a combined, multi-systemic disease including skeletal dysplasia and immunological and neurological abnormalities. Herein, we report a 34-year-old patient with a range of phenotypes for NBAS deficiency due to compound heterozygous variants; one is a SOPH-specific variant, p.Arg1914His, and the other is a novel splice site variant, c.6433-2A>G. The patient experienced recurrent acute liver failure until early childhood. Hypogammaglobulinemia, a decrease in natural killer cells, and optic nerve atrophy were evident from infancy to childhood. In adulthood, the patient exhibited novel phenotypic features such as hepatic cirrhosis complicated by portal hypertension and autoimmune hemolytic anemia. The patient also suffered from childhood-onset insulin-requiring diabetes with progressive beta cell dysfunction. The patient had severe short stature and exhibited dysmorphic features compatible with SOPH, intellectual disability, and epilepsy. NBAS protein expression in the patient's fibroblasts was severely low. RNA expression analysis for the c.6433-2A>G variant showed that this variant activated two cryptic splice sites in intron 49 and exon 50, for which the predicted consequences at the protein level were an in-frame deletion/insertion, p.(Ile2199_Asn2202delins16), and a premature termination codon, p.(Ile2199Tyrfs*17), respectively. These findings indicate that NBAS deficiency is a multi-systemic progressive disease. The results of this study extend the spectrum of clinical and genetic findings related to NBAS deficiency.

Effects of liposomal particles on immune function have not been adequately investigated. Earlier reports indicate that intravenous injection of rats with pegylated liposomes comprising chemically defined specific lipids produces myeloid derived suppressor-cell (MDSC)-like cells in the spleen. After liposome injection, we sought a cell surface marker expressed specifically on splenic macrophages. Then we assessed the immunosuppressive activity of macrophages positive for the marker. Furthermore, we investigated whether immunosuppression induction is an immunopharmacological action specific to this pegylated liposome, or not. After using a microarray system to screen genes enhanced by this liposome, we evaluated cell surface expression of gene products using flow cytometry. Liposomes of several kinds, each comprising one type of phospholipid, were prepared and evaluated for their ability to induce T-cell suppression. Microarray analysis indicated enhanced B7-H3 expression. Flow cytometry revealed that the B7-H3 molecule was expressed on splenic macrophages after liposome injection. B7-H3+ macrophages were positive for iNOS. Removing B7-H3+ cells restored T-cell proliferation. Similarly to this liposome, various liposomes with different long chain fatty acids induced T-cell suppression when accumulated in the spleen. Immunosuppressive cells induced by this pegylated liposome closely resemble MDSCs, especially B7-H3+ MDSCs. Immunosuppression induction is not a phenomenon specific to this liposome. Accumulation of long chain fatty acid in macrophages by internalization of liposomal nanoparticles might be related to macrophage acquisition of immunosuppressive activity in vivo.

BACKGROUND AND OBJECTIVES There are few reports on renal dysfunction in the remote period after biventricular repair, and biomarkers for early detection of renal dysfunction are not well understood. We examined whether early fluctuation of biomarkers of renal function occurs in the remote period after biventricular repair in patients with congenital heart disease (CHD). METHODS Fourteen patients with CHD after biventricular repair were included. The examination values obtained by cardiac catheterization test and renal function indices based on blood and urine sampling were compared. RESULTS The median estimated glomerular filtration rate (eGFR) of creatinine was 113 mL/min/1.73 m², and the median eGFR of cystatin C was 117 mL/min/1.73 m². A urine albumin-to-creatinine ratio (UACR) ≥10 mg/gCr was considered a risk factor for cardiovascular disease in 6 (43%) patients. There was a significant difference in right ventricular ejection fraction and deviation in right ventricular end-diastolic volume from the normal value between the 2 groups divided by UACR. Cyanosis before biventricular repair was noted in 2 (25%) patients with UACR

The European Union has approved a new energy strategy for 2030, the target being to save the 27% of primary energy compared with the business-as-usual scenario and to reduce the CO2 emission of 40%. Each member state shall establish an indicator showing the energy efficiency contribution towards the Member State's 2030 target. Under such challenging target, the use of optimized energy management system has the potential to greatly contribute to the reduction of both the primary energy and the CO2 emission. Of course, the economic benefit for installing these systems is also an important issue from owner's point of view, and it has a big influence on the technical solution choice. The energy management systems are capable to optimize the schedule of boilers, electric chillers, and other kind of generators. In this latter case, the use of cogeneration systems is often applied, in order to increase the overall efficiency of the plant, often in combination with absorption chillers to make effective use of the heat also with large cooling loads and small heating duties. The fuel sources of all these pieces of equipment are represented by natural gas and electricity, so the result of optimized operations is greatly modified depending on the situation of gas and electricity prices, which are strictly dependent on the country which the analysis is referred to. The purpose of this study is to clarify the influence of the electricity price and the natural gas price of each country on the optimum operation of an energy management system, considering the acquired energy demand pattern and the configuration of a multi-generation production plant consisting in a small Italian factory. The energy price scenarios which will be analyzed are related to 7 countries with large GDP in the EU region, on which optimization algorithm will be applied. The results will be focused on the comparison of the economic benefit, primary energy saving and reduction of CO2 emissions for each country, applying different target function of the optimizer (minimum running costs, primary energy consumption, or GHGs emissions), in order to highlight the most relevant parameters determining the benefit of the energy management system.

The recent clinical application of perfusion technology for the machine preservation of donation after cardiac death (DCD) grafts has some advantages. Oxygenation has been proposed for the preservation of DCD liver grafts. The aim of this study is to clarify whether the use of HbV-containing preservation solution during the subnormothermic machine perfusion (SNMP) of the liver graft improves the graft function of DCD porcine livers in an ex vivo reperfusion model. Pig livers were excised after 60 minutes of warm ischemic time and were preserved under one of three preservation conditions for 4 hours. The preservation conditions were as follows: 4°C cold storage (CS group; N = 5), Hypothermic machine preservation (HMP) with UW gluconate solution (HMP group; N = 5), SNMP (21°C) with UW gluconate solution (SNMP group; N = 5), SNMP (21°C) with HbVs (Hb; 1.8 mg/dl) perfusate (SNMP+HbV group; N = 5). Autologous blood perfusion was performed for 2 hours in an isolated liver reperfusion model (IRM). The oxygen consumption of the SNMP and SNMP+HbV group was higher than the HMP groups (p < 0.05). During the reperfusion, the AST level in the SNMP+HbV group was lower than that in the CS, HMP and SNMP groups. The changes in pH after reperfusion was significantly lower in SNMP+HbV group than CS and HMP groups. The ultrastructural findings indicated that the mitochondria of the SNMP+HbV group was well maintained in comparison to the CS, HMP and SNMP groups. The SNMP+HbVs preservation solution protected against metabolic acidosis and preserved the liver function after reperfusion injury in the DCD liver.

Background The incidence of late liver complications such as fibrosis or cirrhosis has increased among patients who have undergone the Fontan procedure. Magnetic resonance elastography (MRE) recently emerged as a technique to clinically evaluate liver fibrosis. However, few reports have described its use in evaluating liver fibrosis in children with congenital heart disease (CHD). Methods and results Fifty-seven children were examined and divided into four groups: 27 with CHD who underwent intracardiac repair (ICR); 16 with CHD who underwent the Fontan procedure (Fontan); 14 in a control group (control); and two with cirrhosis (cirrhosis). Liver stiffness (LS) was measured using MRE. Other assessments included central venous pressure (CVP) as determined by cardiac catheterization. Circulating biomarker levels were also determined. There were no significant differences in biomarker levels among the groups. However, the LS degree was significantly higher in the Fontan group than in the control group. On stepwise multivariate analysis, only the CVP level was a statistically significant independent predictor of LS. There was also a strong correlation between LS and CVP and between LS and time interval since Fontan surgery. Conclusions This study clearly demonstrated that LS was significantly increased after the Fontan procedure and that CVP was a predictor of LS. MRE is a highly sensitive tool that can evaluate liver fibrosis in children who undergo the Fontan procedure and enable earlier detection of LS than biomarkers.

Background We previously showed that glycated albumin (GA) is a useful glycemic control indicator in patients with neonatal diabetes mellitus (NDM), and that age-adjusted GA (Aa-GA) can reflect more accurately glycemic control status. Here, we investigated whether the age at diagnosis influences Aa-GA at diagnosis of NDM. Methods Eight patients with NDM whose GA was measured at diagnosis (age at diagnosis: 39 ± 18 days; GA: 31.3 ± 7.6%; Aa-GA: 47.1 ± 10.3%; plasma glucose: 525 ± 194 mg/dl) were included. Aa-GA was calculated as follows: Aa-GA = GA × 14.0/[1.77 × log-age (days) + 6.65]. Correlations of GA or Aa-GA at diagnosis with its logarithmically transformed age in days (log-age), plasma glucose, and their product were investigated. Results GA at diagnosis was not significantly correlated with log-age or plasma glucose. On the other hand, Aa-GA at diagnosis was significantly positively correlated with plasma glucose (R = 0.75, P = 0.031) and was more strongly positively correlated with the product of plasma glucose and log-age (R = 0.82, P = 0.012) although it was not correlated with log-age. Conclusion Aa-GA at diagnosis is influenced by both age in days and plasma glucose. This finding is likely to show the aspect that age in days is almost equal to diabetes duration because glycemic control indicators including GA reflect the weighted mean of plasma glucose.

Protein-losing enteropathy (PLE) is a rare and life-threatening complication that occurs after the Fontan procedure. We herein report the case of an 11-year-old Japanese boy who developed PLE six times after undergoing the Fontan procedure. High-dose spironolactone therapy has been effective for 2 years. His high level of serum aldosterone decreased to a nearly normal range and spironolactone may have a diuretic and anti-inflammatory potential.

Published by Elsevier B.V. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/)., Introduction Moyamoya disease (MMD) is characterized by progressive stenosis and occlusion in the terminal portion of both internal carotid arteries (ICAs) and the formation of an abnormal vascular network. Because of the fragile structure of the collateral vessels, MMD is frequently accompanied by intracranial aneurysms that are mainly located within the abnormal basal network or the circle of Willis. However, the association between MMD and aneurysms of the ICAs has never been reported previously. Case report A 1-month-old infant presented with a decreased level of consciousness and arterial infarction in the right frontal and temporal lobes. Brain computed tomography angiography results showed aneurysms in both ICAs and occlusions of the distal part of the aneurysms without moyamoya collateral vessels. Aspirin therapy was initiated, and his clinical status stabilized. At 12 months of age, collateral networks of small vessels were found in the distal part of both ICAs, and MMD had evolved. At 24 months of age, he remains on aspirin therapy, and no further ischemic events have occurred. Conclusions This is the first report of MMD in which ICA aneurysms and occlusions developed bilaterally in early infancy without moyamoya collateral vessels. Our case indicates that angiogenesis at the base of the brain may occur following extracellular matrix remodeling at the terminal portion of the ICAs.

Asplenia syndrome is frequently complicated by a total anomalous pulmonary venous connection. Pulmonary venous obstruction, following total anomalous pulmonary venous connection surgery, is one of the risk factors for morbidity and mortality. In some patients, the pulmonary vasculature is abnormal even in the absence of clinical evidence of pulmonary venous obstruction. We hypothesized that a change in the pulmonary hemodynamics could indicate the abnormality of pulmonary vein in a patient with asplenia, single right ventricle, and total anomalous pulmonary venous connection, following Fontan procedure. Here, we present a case of asplenia, single right ventricle, total anomalous pulmonary venous connection, and right pulmonary venous obstruction in which evidence of a potential left pulmonary venous obstruction was obtained following the administration of inhaled nitric oxide and oxygen.

Inflammatory bowel disease (IBD), including ulcerative colitis and Crohn’s disease, is a chronic intestinal inflammatory condition initiated by integrins-mediated leukocyte adhesion to the activated colonic microvascular endothelium. Calreticulin (CRT), a calcium-binding chaperone, is known as a partner in the activation of integrin α subunits (ITGAs). The relationship between their interaction and the pathogenesis of IBD is largely unknown. Here we show that a small molecule, orally active ER-464195-01, inhibits the CRT binding to ITGAs, which suppresses the adhesiveness of both T cells and neutrophils. Transcriptome analysis on colon samples from dextran sodium sulfate-induced colitis mice reveals that the increased expression of pro-inflammatory genes is downregulated by ER-464195-01. Its prophylactic and therapeutic administration to IBD mouse models ameliorates the severity of their diseases. We propose that leukocytes infiltration via the binding of CRT to ITGAs is necessary for the onset and development of the colitis and the inhibition of this interaction may be a novel therapeutic strategy for the treatment of IBD., Inflammatory bowel disease (IBD) is initiated by integrins-mediated leukocyte adhesion to the activated colonic microvascular endothelium. Here, the authors show that inhibition of the calreticulin binding to integrin α subunits ameliorates the severity of IBD in animal models.

Background Basal meningoceles are rare congenital defects and often clinically occult until they result in life-threatening complications. Therefore, it is important to know the diagnostic clues to early diagnosis. Case presentation We describe three cases of congenital basal meningocele in a 3-year-old Japanese boy, a 1-month-old Japanese baby boy, and a 10-month-old Japanese baby girl. One of our patients died of sepsis due to traumatic rupture of the meningocele during nasal suction. His meningocele remained undiagnosed until it resulted in the fatal complication. The other patients underwent surgical repair without any complications. Their meningoceles were complicated by midfacial anomalies including cleft palate and hypertelorism, or a sign of nasal obstruction such as snoring. Conclusions These clinical features may be a clue to the early diagnosis of congenital basal meningocele, which enables its safe preoperative management and provides an opportunity for surgical repair before the condition results in serious complications.

著者最終原稿版, BACKGROUND/AIMS: Atomoxetine (ATX), a selective norepinephrine reuptake inhibitor, is the first approved non-stimulant drug for treatment of attention deficit/hyperactivity disorder (AD/HD). The present study examined the effects of long-term treatment with ATX on prefrontal hemodynamic activity in AD/HD children during a continuous performance task (CPT) using near-infrared spectroscopy (NIRS). METHODS: Prefrontal hemodynamic activity was measured in 12 children with AD/HD during experimental sessions conducted before and 6 months or more after starting ATX treatment. The average maintenance dose of ATX was 1.6 mg/kg/day. Fourteen age-matched typically developing children participated as a control group. RESULTS: In the control group, the CPT induced a significant increase in oxygenated hemoglobin (oxy-Hb) concentration in the bilateral dorsolateral prefrontal cortex (DLPFC). In the AD/HD group in the pre-ATX condition, the CPT did not induce a significant increase in oxy-Hb concentration in any of the NIRS channels, but induced a significant decrease in oxy-Hb concentration in the left ventrolateral prefrontal cortex (VLPFC). In the AD/HD group in the post-ATX condition, significant activation was observed in the right DLPFC and the decrease in oxy-Hb concentration in the left VLPFC disappeared. CONCLUSIONS: These results suggest that long-term treatment with ATX improved prefrontal hemodynamic activity in AD/HD children, and NIRS may be useful for assessment of the prefrontal hemodynamic response to ATX treatment.

Context: Myeloid-derived suppressor cells (MDSCs) are a subset of immature myeloid cells that function as immunosuppressive cells in various pathological conditions. Membrane-derived microvesicles are thought to be involved in MDSC induction. Earlier reports have described that injection of considerable amount of liposome into rat can suppress Con A-induced splenic T-cell proliferation. Liposome-internalized cells expressing CD11b/c suppress T-cell proliferation. Nitric oxide (NO) appears to be involved in the suppression. We speculated that, similarly to membrane-derived microvesicles, liposomal microparticles can induce MDSC-like cells in vivo. Objectives: To confirm our speculation we investigated dose-dependency of the suppressive effect, the effect of liposome on the induction of inducible NO synthase (iNOS), and anti-CD3 antibody-stimulated T-cell proliferation and cytokine production. Materials and methods: Liposome particles of 250 nm diameter were prepared and suspended in saline. Then, various amounts of liposomal suspension were injected intravenously into rats. After 24 h, rat spleens were removed and concanavalin A (or anti-CD3 antibody) stimulated-splenic T-cell proliferation and the production of iNOS, NO and cytokines were evaluated. Results: T-cell proliferation was suppressed dose-dependently by liposome injection. The immunosuppressive cell exerts its suppressive activity in a dose-dependent manner. The suppression was eliminated by iNOS inhibitor. iNOS was detected in liposome-loaded splenocytes. Anti-CD3 antibody-stimulated T-cell proliferation was also inhibited. Enhanced production of IL-10 was observed. Conclusions: Liposomal microparticles can induce MDSC-like cells in vivo. The lipids which comprise liposomes might serve an important role in the induction of MDSCs in vivo.

Juvenile-onset systemic sclerosis (jSSc) is a rare condition, having unique characteristic features compared to adult-onset SSc. Although cardiac involvement (CI) is known as a leading cause of mortality overall in SSc, the importance of CI in jSSc has not been emphasized. Here we present a 13-year-old female with jSSc overlapped with dermatomyositis (DM) complicated CI. She developed skin thickness and induration, Raynaud’s phenomenon, digital pitting scars in fingertips, and skeletal myositis. Oral prednisolone and pulse methotrexate treatment led to the improvement of skin findings; however two weeks after the initiation she suddenly presented with muscle pain and dyspnea within a few days. Cardiac investigations then showed pericardiac effusion and diastolic dysfunction due to significant biventricular hypertrophy causing heart failure. As pericardiac effusion and exacerbation of skeletal myositis were evident, steroid pulse therapy was initiated. Unexpectedly, not only the myositis but also the CI including diastolic dysfunction was improved. She thereafter followed a favorable clinical course without reactivation of the CI or cardiac fibrosis. As a conclusion, close attention to CI must be paid in jSSc patients, especially when skeletal muscle involvement is evident and immunosuppressive therapy may be effective for CI in jSSc in cases where it occurs abruptly.