A case of multifocal sclerosis angiomatoid nodular transformations of the spleen occurring after partial splenic infarction with transcatheter arterial embolization for splenic artery aneurysm.

A 48-year-old woman underwent transcatheter arterial embolization (TAE) for a splenic artery aneurysm, which resulted in a partial splenic infarction in the middle lobe. Five years after TAE, a 20-mm diameter mass in the noninfarcted area of the spleen was detected on imaging, which grew to 25 mm in diameter after 6 months. MRI after gadolinium administration showed a 35 × 34 mm mass within the superior pole and 15 × 12 mm mass within the inferior pole. The patient underwent laparoscopic splenectomy and had an uneventful postoperative recovery. No evidence of recurrence was observed during the 2-year follow-up period after surgery. The mass was pathologically confirmed to be sclerosing angiomatoid nodular transformation (SANT) of the spleen. While some studies hypothesize that SANT is a response to vascular injury or trauma, to the best of our knowledge, there have been no previous reports of SANT occurring after procedures directly affecting splenic blood flow. Additionally, multifocal SANTs are reported to be very rare, accounting for only 4.7% of all reported SANTs of the spleen. We highlight a rare course of SANT of the spleen and discuss the possible relationship between blood flow abnormalities and the appearance of SANT.

Relationship of immunonutritional factor with changes in liver volume after portal vein embolization.

Background: To identify predictors of changes in hepatic volumes after portal vein embolization, we examined the relationship with preoperative nutritional and immunological parameters. Patients and Methods: Ninety-three patients who underwent portal vein embolization were included. The control group comprised 13 patients who underwent right hepatectomy without portal vein embolization. Computed tomographic volumetric parameter was measured for changes in embolized and nonembolized liver. Correlation with various candidates of immunonutritional parameters was examined. Results: Difference in increased liver ratio was 9.1%. C-reactive protein levels significantly increased after portal vein embolization (P < .01), whereas albumin and total cholesterol levels significantly decreased, respectively (P < .01). The C-reactive protein/albumin ratio, prognostic nutritional index, Controlling Nutritional Status score, and modified Glasgow Prognostic Score were significantly different, respectively (P < .01). Prothrombin activity and total cholesterol level significantly correlated with the increased change in nonembolized liver (P < .05). The C-reactive protein and C-reactive protein/albumin ratio after portal vein embolization negatively correlated with hypertrophic ratio (P < .05). By comparing posthepatectomy outcomes between 64 patients undergoing portal vein embolization and 13 who did not, the prevalence of severe complications and mortality in the portal vein embolization group was not different from that in the non-portal vein embolization group. Liver activity at 15 minutes > 0.92 and increased liver volume ≥ 10% tended to correlate with lower prevalence of severe complications. Only increased intraoperative blood loss ≥ 1,500 mL was significantly associated with morbidity and mortality (P < .05). Conclusion: Contrary to our hypothesis, immunonutritional parameters, except C-reactive protein and C-reactive protein/albumin ratio, did not reflect hypertrophy after portal vein embolization. Although it is difficult to predict the hypertrophic degree, the strategy of scheduled hepatectomy should be switched in case of impaired inflammatory status after portal vein embolization.

Rare resected eight cases of duodenal adenocarcinomas.

INTRODUCTION: Duodenal adenocarcinoma is a rare malignancy; recently, it has been found to be accompanied by operative indications. METHODS: Nine consecutive rare cases were diagnosed with duodenal carcinoma (DC), in which clinicopathological characteristics were retrospectively examined. Age was ranged over middle-aged males and females. No clinical onset with severe symptoms was observed, and the specific treatment for accompanied diseases or habits was not found. OUTCOMES: One case of two T1 stage DCs that underwent pancreas-sparing duodenectomy. Stage II DC was diagnosed in three cases, and stage III DC was diagnosed in four cases. Pancreaticoduodenectomy (PD) mainly occurred in seven patients, and duodenectomy was limited in two patients. All operations were safely performed, and the postoperative course showed no severe morbidity. Histological findings showed R0 resection in eight cases and R1 at the retroperitoneal dissecting part in one case. Five patients with advanced-stage DC underwent adjuvant chemotherapy; however, four patients showed tumor recurrence within 12 months. With additional strong chemotherapy, eight patients survived up to 84 months, and one died of liver metastasis at 43 months after surgery. Three representative cases of mucosal invasion with widespread pancreas-sparing duodenectomy and advanced-stage DC cases undergoing duodenectomy or PD are shown. CONCLUSION: In the field of upper digestive tract surgery, duodenal adenocarcinoma and various applications of surgery or adjuvant chemotherapy for long-term survival are important.

A case report: Twin sisters with restrictive cardiomyopathy associated with rare mutations in the cardiac troponin I gene.

Restrictive cardiomyopathy (RCM) is a rare cardiomyopathy in children, and its prognosis until now, has been poor. Recently some sarcomeric mutations have been reported as disease-causing genes of RCM. However, the genotype-phenotype correlation is not fully understood. Additionally, prognostic factors including sudden death in patients with RCM have not been elucidated. We report our experience in treating twin sisters with RCM or hypertrophic cardiomyopathy with RCM phenotype, both carriers of the same mutation in TNNI3, which encodes one of the major sarcomeric proteins in myofibrils. They were both diagnosed with RCM by cardiac catheterization at the age of 11 years. Despite appropriate follow-up and medical treatment, one died suddenly at the age of 11 years and the other also died at the age of 15 years due to heart failure while awaiting heart transplantation. In addition to our cases, other reports of younger fatal cases with RCM carrying TNNI3 mutations may suggest it as one of the prognostic factors. Genetic diagnosis is important in the clinical diagnosis, management, and treatment of cardiomyopathy. .

Deep sequencing of hepatitis B surface antigen gene in the preserved umbilical cords in immunoprophylaxis failure against mother-to-child HBV transmission.

BACKGROUND: Vaccine escape mutants (VEMs) are one of the causes of breakthrough infections in the mother-to-child transmission of hepatitis B virus (HBV). We hypothesized that VEMs existing as minor populations in the maternal blood are associated with breakthrough infections in children. We sought to determine whether VEMs exist as minor populations in the preserved umbilical cords of children with breakthrough infections. CASE PRESENTATION: Two families (Family 1: three children, Family 2: two children) were enrolled. Despite immunoprophylaxis, a breakthrough infection occurred in two Family 1 children and two Family 2 children. Preserved umbilical cords, serum, and nails were used for the HBV DNA analysis. To detect VEMs, we performed direct and deep sequencing of hepatitis B surface antigen gene. The direct sequencing showed that there were no VEMs in the serum of the children or mother of Family 1 and family 2, but it identified a G145A mutant in the nails of the mother of Family 2. In Family 1, deep sequencing detected a T143S mutant as a minor population (1.7-2.0%) in the umbilical cords and serum of all three children and in the serum of the mother. A T126A mutant was also detected in the umbilical cord (9.2%) and serum (7.0%) of the first-born child of Family 1. In Family 2, the deep sequencing showed no VEMs in the umbilical cords, but it detected D144A (2.5%) and G145A (11.2%) mutants in the serum of the 2nd-born child. CONCLUSIONS: VEMs were present as minor populations in the preserved umbilical cords of children with breakthrough infections. The VEMs did not become major populations after the breakthrough infections. The evolution of VEMs from a minor form to a major form might not be a prerequisite for breakthrough infections in mother-to-child transmission.

Outbreak of aseptic meningitis caused by echovirus 30 in Kushiro, Japan in 2017.

BACKGROUND: Echovirus 30 (E30) is one of the most common causative agents for aseptic meningitis. OBJECTIVES: In the autumn of 2017, there was an outbreak caused by E30 in Kushiro, Hokkaido, Japan. The aim of this study was to characterize this outbreak. STUDY DESIGN: Fifty-nine patients were admitted to the Department of Pediatrics, Kushiro Red Cross Hospital (KRCH) with clinical diagnosis of aseptic meningitis. Among those, 36 patients were finally diagnosed as E30-associated aseptic meningitis by the detection of viral RNA using reverse transcription-polymerase chain reaction (RT-PCR) and/or the evidence of more than four-fold rise in neutralizing antibody (NA) titers in the convalescent phase relative to those in the acute phase. We investigated these 36 confirmed cases. RESULTS: The median age was 6 years (range: 6 months-14 years). The positive signs and symptoms were as follows: fever (100%), headache (94%), vomiting (92%), jolt accentuation (77%), neck stiffness (74%), Kernig sign (29%), and abdominal pain (28%). The median cerebrospinal fluid (CSF) white cell count, neutrophil count, and lymphocyte count were 222/µL (range: 3-1434/µL), 144/µL (range: 1-1269/µL), and 85/µL (range: 2-354/µL), respectively. Although the detected viral genes demonstrated same cluster, they were different from E30 strains observed in Japan between 2010 and 2014. CONCLUSION: We mainly showed clinical and virological features of the E30-associated aseptic meningitis outbreak that occurred in Kushiro. To prevent further spread of E30 infection, continuous surveillance of enterovirus (EV) circulation and standard precautions are considered essential.

Development of novel monoclonal antibodies directed against catechins for investigation of antibacterial mechanism of catechins.

Catechins are major polyphenolic compounds of green tea. To investigate mechanism for antibacterial action of catechins, 11 monoclonal antibodies (MAbs) were raised against a 3-succinyl-epicatechin (EC)-keyhole limpet hemocyanin (KLH) conjugate. Amino acid sequences of variable regions determined for MAbs b-1058, b-1565, and b-2106 confirmed their innovative character. MAb b-1058 strongly interacted with its target substances in the following order of magnitude: theaflavin-3,3'-di-O-gallate (TFDG)>theaflavin-3-O-gallate (TF3G)≥theaflavin-3'-O-gallate (TF3'G)>gallocatechin gallate (GCg)>penta-O-galloyl-ß-d-glucose (PGG)>epigallocatechin gallate (EGCg), as determined using surface plasmon resonance (SPR) on MAb-immobilized sensor chips. The affinity profiles of MAbs b-1058 and b-2106 to the various polyphenols tested suggested that flavan skeletons with both carbonyl oxygen and hydroxyl groups are important for this interaction to take place. S. aureus cells treated with EGCg showed green fluorescence around the cells after incubation with FITC-labeled MAb b-1058. The fluorescence intensity increased with increasing concentrations of EGCg. These MAbs are effective to investigate antibacterial mechanism of catechins and theaflavins.

Lung Transplant for Pulmonary Arterial Hypertension After Arterial Switch Operation.

Pulmonary arterial hypertension after arterial switch operation for transposition of the great arteries is an infrequent but life-threatening complication. We report successful lung transplantation in a case of pulmonary hypertension after arterial switch operation. Cardiopulmonary bypass outflow was established through the right subclavian and femoral arteries because of the previous arterial switch operation. Abnormal anatomy and severe pleural and pericardial adhesions as a result of previous operations resulted in prolonged graft ischemic and operation times. Despite delayed left heart adaptation and primary graft dysfunction requiring prolonged extracorporeal membrane oxygenation, the recipient was eventually discharged without activity limitations.

A rare association between Rathke's cyst and hypophysitis in a patient with delayed sex development and growth failure.

We report an 18-year-old Japanese male with a lack of secondary sex characterization and growth failure caused by a rare association between Rathke's cyst and hypophysitis. He was referred to us because of delayed secondary sex characterization. Endocrinological examination showed panhypopituitarism, and the replacement of hydrocortisone, levothyroxine, and desmopressin acetate (DDAVP) was initiated. Brain magnetic resonance imaging (MRI) showed a suprasellar region and a swollen pituitary stalk. The mass was partially resected using the transsphenoidal approach. The pathological diagnosis was hypophysitis and Rathke's cyst. Follow-up MRI performed 1 year after surgery showed that the size of sellar region had not changed. After surgery, in addition to pre-operative hormonal replacement, growth hormone and testosterone were initiated. Two years later, the size of sellar region remains unchanged. In conclusion, while an association between Rathke's cyst and hypophysitis is rare, we suggest that this condition should be included in differential diagnosis of the sellar region, even in adolescents.

Somatic mosaicism in two unrelated patients with X-linked chronic granulomatous disease characterized by the presence of a small population of normal cells.

X-linked chronic granulomatous disease (X-CGD) is a primary immunodeficiency disease of phagocytes caused by mutations in the cytochrome b(558)ß (CYBB) gene. We, for the first time, detected somatic mosaicism in two unrelated male patients with X-CGD caused by de novo nonsense mutations (p.Gly223X and p.Glu462X) in the CYBB gene. In each patient, a small subset of granulocytes was normal in terms of respiratory burst (ROB) activity, gp91(phox) expression, and CYBB sequences. Cells with wild-type CYBB sequence were also detected in buccal swab specimens and in peripheral blood mononuclear cells. The normal cells were shown to be of the patient origin by fluorescent in situ hybridization analysis of X/Y chromosomes, and by HLA DNA typing. Two possible mechanisms for this somatic mosaicism were considered. The first is that the de novo disease-causing mutations in CYBB occurred at an early multicellular stage of embryogenesis with subsequent expansion of the mutated cells, leaving some unmutated cells surviving. The second possibility is that the de novo mutations occurred in oocytes which was followed by reversion of the mutations in a small subset of cells in early embryogenesis.

Coffee polyphenols modulate whole-body substrate oxidation and suppress postprandial hyperglycaemia, hyperinsulinaemia and hyperlipidaemia.

Postprandial energy metabolism, including postprandial hyperglycaemia, hyperinsulinaemia and hyperlipidaemia, is related to the risk for developing obesity and CVD. In the present study, we examined the effects of polyphenols purified from coffee (coffee polyphenols (CPP)) on postprandial carbohydrate and lipid metabolism, and whole-body substrate oxidation in C57BL/6J mice. In mice that co-ingested CPP with a lipid-carbohydrate (sucrose or starch)-mixed emulsion, the respiratory quotient determined by indirect calorimetry was significantly lower than that in control mice, whereas there was no difference in VO2 (energy expenditure), indicating that CPP modulates postprandial energy partitioning. CPP also suppressed postprandial increases in plasma glucose, insulin, glucose-dependent insulinotropic polypeptide and TAG levels. Inhibition experiments on digestive enzymes revealed that CPP inhibits maltase and sucrase, and, to a lesser extent, pancreatic lipase in a concentration-dependent manner. Among the nine kinds of polyphenols (caffeoyl quinic acids (CQA), di-CQA, feruloyl quinic acids (FQA)) contained in CPP, di-CQA showed more potent inhibitory activity than CQA or FQA on these digestive enzymes, suggesting a predominant role of di-CQA in the regulation of postprandial energy metabolism. These results suggest that CPP modulates whole-body substrate oxidation by suppressing postprandial hyperglycaemia and hyperinsulinaemia, and these effects are mediated by inhibiting digestive enzymes.

Structure-based design of dipeptide derivatives for the human neutral endopeptidase.

Neutral endopeptidase (NEP) plays a key role in the metabolic inactivation of various bioactive peptides such as atrial natriuretic peptide (ANP), endothelins, and enkephalins. Furthermore, NEP is known to work as elastase in skin fibroblast. Therefore, effective inhibitors of NEP offer significant therapeutic interest as antihypertensives, analgesics, and skin anti-aging agents. Recently, the X-ray crystal structure of human NEP complexed with phosphoramidon has been reported and provided insights into the active site specificity of NEP. Here, we designed new inhibitors by using in silico molecular modeling and synthesized them by short steps. Expectedly, we found highly effective inhibitors with sub-nanomolar levels of IC(50) values. These results indicate that our structure-based molecular designing program is useful for obtaining novel NEP inhibitors. Furthermore, these inhibitors may be attractive leads for the generation of new pharmaceuticals for NEP-related diseases.

Coffee polyphenols suppress diet-induced body fat accumulation by downregulating SREBP-1c and related molecules in C57BL/6J mice.

The prevalence of obesity is increasing globally, and obesity is a major risk factor for type 2 diabetes and cardiovascular disease. We investigated the effects of coffee polyphenols (CPP), which are abundant in coffee and consumed worldwide, on diet-induced body fat accumulation. C57BL/6J mice were fed either a control diet, a high-fat diet, or a high-fat diet supplemented with 0.5 to 1.0% CPP for 2-15 wk. Supplementation with CPP significantly reduced body weight gain, abdominal and liver fat accumulation, and infiltration of macrophages into adipose tissues. Energy expenditure evaluated by indirect calorimetry was significantly increased in CPP-fed mice. The mRNA levels of sterol regulatory element-binding protein (SREBP)-1c, acetyl-CoA carboxylase-1 and -2, stearoyl-CoA desaturase-1, and pyruvate dehydrogenase kinase-4 in the liver were significantly lower in CPP-fed mice than in high-fat control mice. Similarly, CPP suppressed the expression of these molecules in Hepa 1-6 cells, concomitant with an increase in microRNA-122. Structure-activity relationship studies of nine quinic acid derivatives isolated from CPP in Hepa 1-6 cells suggested that mono- or di-caffeoyl quinic acids (CQA) are active substances in the beneficial effects of CPP. Furthermore, CPP and 5-CQA decreased the nuclear active form of SREBP-1, acetyl-CoA carboxylase activity, and cellular malonyl-CoA levels. These findings indicate that CPP enhances energy metabolism and reduces lipogenesis by downregulating SREBP-1c and related molecules, which leads to the suppression of body fat accumulation.