A Classification System Specific for Recurrent Inguinal Hernia Following Open Hernia Surgery.

BACKGROUND/AIM: Currently, there is no classification system specializing in recurrent inguinal hernia (RIH) after open-surgery. For this reason, in this study we proposed one so as to understand the causes of RIH. PATIENTS AND METHODS: Recurrence of IH after suture-repair was classified either as the tissue-loosening (TL) or the tissue-disruption (TD) type. Recurrence after open-mesh-repair was classified according to the locational relation between the hernia-defect and the mesh, as follows: i) mesh-distant (MD), ii) para-mesh (PM), iii) mesh-migration (MM), and iv) unclassifiable (UC). Fifty-two RIHs in 48 patients were classified, using this system, and analyzed. RESULTS: This system-based classification led to the identification of: i) MM in 11 lesions, ii) PM in 11, iii) MD in 10, iv) TL in 7, v) TD in 5, and vi) UC in 8 lesions. The median time to recurrence (MTR) was significantly shorter in patients who had previously undergone a mesh-repair (n=34) compared to those who had undergone a suture-repair (n=13) [Mesh-repair vs. suture-repair MTR: 1.6 years (0.1-20) vs. 30 years (15-72), p<0.001]. MTR was significantly shorter in the following order: i) MM [0.5(0.1-2.0)]), ii) PM [2.6(0.2-15)]), iii) MD [11(0.5-20)], iv) TD [20(15-30)], and v) TL [40(30-72)] (p<0.001). CONCLUSION: This classification system helps understand the causes of RIH, leading to improved outcomes following open-surgery in the future.

Treatment of acute exacerbation of liver-cirrhosis-associated portal vein thrombosis with direct-acting oral anticoagulant, edoxaban, used as an initial treatment in the early postoperative period after abdominal surgery: a case report.

BACKGROUND: Cirrhosis-associated portal vein thrombosis (CA-PVT) has been reportedly observed in 5-30% of cirrhotic patients. Moreover, the acute exacerbation of CA-PVT is likely to occur after certain situations, such as a status after abdominal surgery. Safety and efficacy of the direct-acting oral anticoagulant (DOAC) used for cirrhotic patients have been being confirmed. However, use of the DOAC as an initial treatment for CA-PVT appears still challenging especially in the early postoperative period after major surgery in terms of unestablished efficacy and safety in such occasion. CASE PRESENTATION: We herein report a case of the acute exacerbation of CA-PVT in the early postoperative period after abdominal surgery, which was successfully treated with DOAC, edoxaban used as an initial treatment. The patient was a 79-year-old Japanese male with alcoholic cirrhosis. The patient suffered choledocholithiasis and had a mural chronic CA-PVT extending from the superior mesenteric vein to the portal trunk. He underwent open cholecystectomy and choledochotomy. Early postoperative clinical course was uneventful except for abdominal distension due to ascites diagnosed on postoperative day (POD)7 when hospital discharge was planned. Contrast enhancement computed tomography (CE-CT) taken on POD 7 revealed the exacerbation of the CA-PVT. Despite recommendation for extension of hospital admission with low molecular weight heparin treatment, the patient strongly hoped to be discharged. Unwillingly, we selected DOAC, edoxaban, as an initial treatment, which was commenced the day after discharge (POD8). As a result, the remarkable improvement of the exacerbated CA-PVT was confirmed by the CE-CT taken on POD21. Any bleeding complications were not observed. Although a slight residue of the CA-PVT remains, the patient is currently doing well 4 years after surgery and is still receiving edoxaban. Any adverse effects of edoxaban have not been observed for 4 years. CONCLUSIONS: A case of successful treatment of the acute exacerbation of CA-PVT with edoxaban was reported. Moreover, edoxaban has been safely administered in a cirrhotic patient for 4 years. The findings obtained from the present case suggest that DOAC can be used as an initial treatment for CA-PVT even in early postoperative period after major abdominal surgery.

Subcutaneous switching suture technique for hernia defect closure during laparoscopic ventral and incisional hernia repair.

INTRODUCTION: A vertical penetration of the thread through the abdominal wall for the hernia defect closure in laparoscopic ventral/incisional hernia repair (LVIHR) is difficult especially in the large defect cases when applying the existing techniques. MATERIALS: Sixteen LVIHRs were performed using the suture technique for defect closure we newly developed. SURGICAL TECHNIQUE: With the subcutaneous switching, our technique only requires the suture-passer and easily enables the vertical penetration of the thread through the abdominal muscular wall even in the large defect cases. DISCUSSION: The defect closure in LVIHR tends to be complicated in the large defect cases. Thus, we devised this technique for the easy, reliable, and firm closure even in the large defect cases. Although the sample size was currently very small, we consider that the favorable outcomes have been obtained through our technique because any noticeable complications, such as mesh bulging or recurrence, have not been observed currently.

Completely laparoscopic repair for recurrent inguinal hernia that developed after open posterior mesh repair.

Surgeons tend to avoid performing completely laparoscopic repair (CLR) for recurrent inguinal hernia (RIH) that developed after the open posterior mesh repair (OPMR). For many, totally extraperitoneal repair or transabdominal preperitoneal repair after OPMR seems difficult because the previously placed mesh may pose an obstacle during the exfoliation of the parietal peritoneum. Moreover, these procedures could cause chronic pain if the "trapezoid of disaster" is injured. In this small case series, we describe our operative technique for CLR for RIH after OPMR, including modified transabdominal preperitoneal repair and modified intraperitoneal onlay mesh repair. The short-term and midterm outcomes of this procedure are also reported. Although we recognize the need for further analysis involving many more cases and a longer follow-up period, we will continue to perform CLR for RIH after OPMR because the results of this small case series were favorable.

Defining the Term "Elderly" in the Field of Surgery: A Retrospective Study Regarding the Changes in the Immunoinflammatory Indices During the Immediate Perioperative Period of the Elective Uncomplicated Laparoscopic Cholecystectomy.

BACKGROUNDS: The term "elderly" seems to have been used as "vulnerable to various stresses" but not well defined. To define the "elderly", we investigated whether the increased age causes unfavorable changes in several immunoinflammatory indices that indicate the increased vulnerability in the surgical field. PATIENTS AND METHODS: One-hundred forty-two patients undergoing an elective-uncomplicated laparoscopic cholecystectomy (within 60 min and without intraoperative-cholangiography, bile spillage, or open conversion) were retrospectively investigated. Before surgery, immediately after surgery, and on postoperative day (POD)1, whether the patient age correlated the following variables was examined: neutrophil-to-lymphocyte ratio (NLR), lymphocyte-to-monocyte ratio, platelet-to-lymphocyte ratio, lymphocyte-to-C-reactive-protein ratio (LCR), C-reactive-protein-to-albumin ratio (CAR), and others. RESULTS: The immunoinflammatory indices most unfavorably changed on POD1. The age correlated neither lymphocyte-to-monocyte ratio nor platelet-to-lymphocyte ratio on POD1, when NLR, LCR, and CAR showed the significant correlation with the age. Multiple regression analyses determined the following variables as the independent determinants of these 3 indices on POD1: age, intraoperative minimum body temperature ≥35.5°C (IntMinBT ≥35.5°C), maximum heart rate during POD0-1 (MaxHR) for NLR; age and IntMinBT ≥ 35.5°C for LCR; and age and MaxHR for CAR. The threshold of "elderly" was determined as 102-year-old for NLR, 94-year-old for LCR, and 97-year-old for CAR. CONCLUSIONS: The increased age causes the unfavorable changes in early postoperative immunoinflammatory indices after the uncomplicated laparoscopic cholecystectomy. Thus, the term "elderly" can be rephrased by the term "vulnerable to various surgical stresses." The thresholds for "elderly" defined herein seem impractical. Namely, the increased vulnerability caused by the aging seems modified by the individual surgical procedures.

Cardiofaciocutaneous syndrome with KRAS gene mutation presenting as chylopericardium.

A 12-year-old female patient with cardiofaciocutaneous syndrome in the presence of a KRAS gene mutation had episodes of pericardial effusion on ultrasound, later confirmed to be chylopericardium, which resolved after a lymphangiography. We discussed herein the pathophysiological background of this rare case and the efficacy of lymphangiography in the treatment of chylopericardium.

Mode of death and predictors of mortality in adult Fontan survivors: A Japanese multicenter observational study.

BACKGROUND: Mortality rates may be high in adult Fontan patients; however, the clinical determinants remain unclear. PURPOSE: We conducted a prospective multicenter study of adult Fontan survivors to determine the 5-year mortality rate and clarify the determinants. METHOD AND RESULTS: We followed 600 adult Fontan survivors from 40 Japanese institutions (307 men, 28 ±â€¯7 years old, follow-up: 18 ±â€¯6 years). The New York Heart Association (NYHA) functional class I and II was 51% and 42%, respectively. During the follow-up period of 4.1 ±â€¯1.6 years, 33 patients died, and the 5-year survival rate was 93.5%. The mode of death was heart failure in 11 patients (34%), arrhythmia or sudden death in 8 (24%), cancer in 5 (15%), perioperative problems and hemostatic problems in 4 each (12% for each), and infection in 1 (3%). Left isomerism, prior hospitalization, protein losing enteropathy (PLE), pulmonary arteriovenous fistulae, NYHA functional class, impaired hemodynamics, hyponatremia, hepatorenal dysfunction, and use of diuretics were associated with a high mortality rate (p < 0.05-0.0001). Further, PLE (hazard ratio [HR]: 14.4), left isomerism (HR: 3.5), and NYHA (HR: 2.4) independently predicted a high 5-year high mortality (p < 0.05 for all). The incidence of cancer-related mortality increased markedly with age >40 years. CONCLUSIONS: Majority of the Japanese adult Fontan survivors had good functional status, with an acceptable 5-year survival rate. However, the significant prevalence of non-cardiac mortality highlights Fontan pathophysiology as a multi-organ disease that requires a multidisciplinary management strategy to improve the long-term outcome.

[Primary Pulmonary Vein Stenosis Developed after Bidirectional Glenn Procedure;Report of Two Cases].

We experienced 2 cases of primary pulmonary vein stenosis(PVS),which developed after a bidirectional Glenn procedure was performed for complex heart defects with normal pulmonary venous return. Although the patients successfully underwent primary sutureless repair for left PVS, restenosis of the affected pulmonary veins occurred several months after surgery in both patients. Stent implantation followed by balloon angioplasty was performed for stent stenosis in 1 patient without effect. However, the patient later underwent a successful fenestrated Fontan procedure. Catheter intervention was contraindicated in the 2nd patient due to almost complete obstruction of the left pulmonary veins with upstream hypoplasia. To improve the results of PVS treatment, earlier diagnosis by quantitative lung perfusion scintigraphy, magnetic resonance imaging, and close echocardiographic observation together with earlier, aggressive treatment combining surgery and catheter interventions are recommended.

Study design for control of HEART rate in inFant and child tachyarrhythmia with heart failure Using Landiolol (HEARTFUL): A prospective, multicenter, uncontrolled clinical trial.

BACKGROUND: Persistent tachycardia in pediatric patients after congenital heart surgery further deteriorates their hemodynamic condition, and may become fatal. Therefore, immediate control of the tachycardia is mandatory in these patients. For this purpose, quick-acting, short-acting, titratable intravenous agents are required. However, there are no agents with such characteristics among the drugs approved for control of pediatric arrhythmias in Japan, and thus novel and effective medications for these patients are awaited. Landiolol, an ultrashort-acting ß-blocker, was approved in 2013 for tachyarrhythmias in adult patients with heart failure. However, its efficacy and safety in pediatric patients remain unclear. The aim of this prospective, multicenter, open-label phase IIb/III study is to investigate the efficacy and safety of landiolol in pediatric patients with tachyarrhythmias as well as heart failure. METHODS: Eligible patients are aged ≥ 3 months and <15 years, and have tachyarrhythmia (atrial fibrillation, atrial flutter, supraventricular tachycardia) as well as heart failure. The primary endpoint of the study is ≥20% reduction from baseline heart rate or return to normal sinus rhythm within 2h after starting intravenous administration of landiolol. Patients will receive intravenous infusion of landiolol, starting at 1µg/kg/min. The dose will be increased by 1µg/kg/min every 15-20min until the tachycardia rate has decreased by >20% or tachycardia has terminated, and the dose will then be maintained or further increased depending on the patient's condition. The study was started in April 2015 and will end within a few years. CONCLUSIONS: The study was designed and designated the "HEARTFUL study" in the hope of establishing a basis for control of HEART rate in inFant and child tachyarrhythmia Using Landiolol in children with heart failure.

Patient-Specific Human Induced Pluripotent Stem Cell Model Assessed with Electrical Pacing Validates S107 as a Potential Therapeutic Agent for Catecholaminergic Polymorphic Ventricular Tachycardia.

INTRODUCTION: Human induced pluripotent stem cells (hiPSCs) offer a unique opportunity for disease modeling. However, it is not invariably successful to recapitulate the disease phenotype because of the immaturity of hiPSC-derived cardiomyocytes (hiPSC-CMs). The purpose of this study was to establish and analyze iPSC-based model of catecholaminergic polymorphic ventricular tachycardia (CPVT), which is characterized by adrenergically mediated lethal arrhythmias, more precisely using electrical pacing that could promote the development of new pharmacotherapies. METHOD AND RESULTS: We generated hiPSCs from a 37-year-old CPVT patient and differentiated them into cardiomyocytes. Under spontaneous beating conditions, no significant difference was found in the timing irregularity of spontaneous Ca2+ transients between control- and CPVT-hiPSC-CMs. Using Ca2+ imaging at 1 Hz electrical field stimulation, isoproterenol induced an abnormal diastolic Ca2+ increase more frequently in CPVT- than in control-hiPSC-CMs (control 12% vs. CPVT 43%, p<0.05). Action potential recordings of spontaneous beating hiPSC-CMs revealed no significant difference in the frequency of delayed afterdepolarizations (DADs) between control and CPVT cells. After isoproterenol application with pacing at 1 Hz, 87.5% of CPVT-hiPSC-CMs developed DADs, compared to 30% of control-hiPSC-CMs (p<0.05). Pre-incubation with 10 µM S107, which stabilizes the closed state of the ryanodine receptor 2, significantly decreased the percentage of CPVT-hiPSC-CMs presenting DADs to 25% (p<0.05). CONCLUSIONS: We recapitulated the electrophysiological features of CPVT-derived hiPSC-CMs using electrical pacing. The development of DADs in the presence of isoproterenol was significantly suppressed by S107. Our model provides a promising platform to study disease mechanisms and screen drugs.

Randomized Comparison of Subcuticular Sutures Versus Staples for Skin Closure After Open Abdominal Surgery: a Multicenter Open-Label Randomized Controlled Trial.

BACKGROUND: The incisional surgical site infection (SSI) is an extremely common complication following open abdominal surgery and imposes a considerable treatment and cost burden. METHOD: We conducted a multicenter open-label randomized controlled trial at three Tokyo Metropolitan medical institutions. We enrolled adult patients who underwent either an elective or an emergency open laparotomy. Eligible patients were allocated preoperatively to undergo wound closure with either subcuticular sutures or staples. A central Web-based randomization tool was used to assign participants randomly by a permuted block sequence with a 1:1 allocation ratio and a block size of 4 before mass closure to each group. The primary endpoint was the occurrence of a superficial SSI within 30 days after surgery in accordance with the Centers for Disease Control and Prevention criteria. This trial was registered with UMIN-CTR as UMIN 000004836 ( http://www.umin.ac.jp/ctr ). RESULTS: Between September 1, 2010 and August 31, 2015, 401 patients were enrolled and randomly assigned to either group. One hundred and ninety-nine patients were allocated to the subcuticular suture and 202 patients to the staple groups (hereafter the "suture" and "staple" group, respectively). Three hundred and ninety-nine were eligible for the primary endpoint. Superficial SSIs occurred in 25 of 198 suture patients and in 27 of 201 staple patients. Overall, the rate of superficial SSIs did not differ significantly between the suture and staple groups. CONCLUSION: Subcuticular sutures did not increase the occurrence of superficial SSIs following open laparotomies mainly consisting of clean-contaminated surgical procedures. The applicability of the wound closure material and method is likely to depend on individual circumstances of the patient and surgical procedure.

Bowel strangulation caused by massive intraperitoneal adhesion due to effective chemotherapy for multiple peritoneal metastases originating from descending colon cancer.

We describe a case of bowel strangulation caused by massive peritoneal adhesion as a result of effective chemotherapy. A 71-year-old man, who had obstructive descending colon cancer with massive peritoneal metastases and, therefore, received palliative surgery consisting of diverting colostomy and sampling of peritoneal nodules, developed bowel strangulation on day 4 of the 2nd course of chemotherapy, including irinotecan, l-leucovorin, and 5-fluorouracil. Emergent celiotomy showed a massive intraperitoneal adhesion formed around several intestinal loops, which were not observed at the prior surgery. One loop was strangled, but recovered by adhesiotomy alone. Intestinal loops were formed around aggregates of peritoneal nodules as the centers, several of which were then sampled. We closed the abdomen after all intestinal loops were eradicated by total enterolysis. Fortunately, the patient has been doing well and received chemotherapy without recurrent bowel obstruction 10 months after the present episode. Histological findings of the aggregates causing intestinal loops demonstrated extensive necrosis of cancerous tissue surrounded by fibrosis with abundant lymphocyte infiltration. These findings were not observed in the specimen sampled before chemotherapy, suggesting that intestinal loops were caused by inflammatory adhesion occurring around the peritoneal metastases as a result of effectiveness of chemotherapy.

Hepatocellular carcinoma incidentally detected at second hepatectomy for repeated colorectal liver metastasis in a patient with hepatitis C virus-related cirrhosis: a case report.

BACKGROUND: It has been reported that liver metastasis rarely occurs in a cirrhotic/hepatitic liver. Thus, coexistence of liver metastasis and hepatocellular carcinoma has been scarcely reported. To the best of our knowledge, there are no cases with hepatocellular carcinoma, which developed during an observational period after hepatectomy for colorectal liver metastasis, in the worldwide English literature. Here we present a case of hepatocellular carcinoma which occurred during a period between the first and second hepatectomy for repeated colorectal liver metastasis. CASE PRESENTATION: A 65-year-old Japanese woman underwent rectal resection for advanced rectal cancer. Hepatitis C cirrhosis was diagnosed at that time and antiviral therapy was offered but rejected because of socioeconomic reasons. At the age of 68, she developed two colorectal liver metastases originating from the rectal cancer, which were treated by local ablation and partial hepatectomy. At the age of 71, solitary recurrent colorectal liver metastasis was observed adjacent to the previously ablated lesion in segment 4, and thus segmentectomy 4 was performed. During surgery, a small tumor in segment 8 was incidentally identified. Taking into account her history, the tumor was considered to be recurrent colorectal liver metastasis and it was extirpated by partial hepatectomy. However, the segment 4 tumor was diagnosed as recurrent colorectal liver metastasis on the basis of histological findings and the segment 8 tumor was diagnosed as hepatocellular carcinoma. Although she had a cut surface abscess postoperatively, she was discharged from hospital 21 days after the surgery and is currently doing well 18 months after the second hepatectomy. She is currently receiving interferon and ribavirin therapy to eliminate hepatitis C virus. CONCLUSIONS: If antiviral therapy was performed earlier for the present case and viral elimination was achieved, hepatocellular carcinoma might not have developed. This case reemphasizes the importance of antiviral therapy for preventing carcinogenesis of hepatocellular carcinoma in patients with viral hepatitis even if they have other cancers.

Incidence of and risk factors for severe acute kidney injury in children with heart failure treated with renin-angiotensin system inhibitors.

UNLABELLED: No large cohort study has yet determined the incidence of acute kidney injury (AKI) in children with heart failure treated with renin-angiotensin system (RAS) inhibitors. We thus retrospectively analyzed the incidence and risk factors for severe AKI (stages 2-3 according to the Kidney Disease Improving Global Outcomes (KDIGO) guidelines) at our institutions from 2008 to 2011. Among 312 children (162 boys; median age, 7.3 months), 59 cases of AKI occurred in 45 children. The incidence of AKI was 14.3 cases per 100 person-years overall (follow-up 413.6 person-years), or 27.3, 16.8, and 4.5 cases per 100 person-years in children aged <1, 1-3, and ≥4 years, respectively. Among them, 23 (39.0 %) children had metabolic acidosis and 14 (23.7 %) had hyperkalemia. Younger age, myocardial disease, cyanotic congenital heart disease, use of spironolactone, and cardiac surgery were independent risk factors for AKI. Furthermore, 37.3 % of children suffered dehydration during AKI. CONCLUSION: AKI incidence is relatively high in children, particularly younger children, with heart failure treated using RAS inhibitors. Careful monitoring of renal function and serum electrolytes is essential. Proper management of fluid balance after infection and cardiac surgery may reduce the risk of AKI. Temporary discontinuation in RAS inhibitors should be considered during dehydration or surgery. WHAT IS KNOWN: • Angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) are the two main classes of renin-angiotensin system (RAS) inhibitors used to treat hypertension, heart failure, and chronic kidney disease. Acute kidney injury (AKI) and hyperkalemia are potentially life-threatening complications associated with the use of ACEIs and ARBs. Some reports have suggested that dehydration and cardiac surgery are risk factors for AKI in children. However, no large-scale cohort studies have determined the incidence of AKI, its risk factors, and its outcomes in children with heart failure treated with ACEIs and/or ARBs. What is new: • In this retrospective cohort study, we determined the incidence, severity, and risk factors for severe AKI in children with heart failure treated with ACEIs and/or ARBs. The incidence of AKI in these children was relatively high (14.3 episodes per 100 person-years). In addition, younger age, myocardial disease, cyanotic congenital heart disease, concomitant use of spironolactone, and cardiac surgery were risk factors for AKI. Furthermore, 37.3 % of children had dehydration during AKI episodes. • Our results suggested that appropriate fluid balance after infection and cardiac surgery might reduce the risk of AKI and its complications. Temporary discontinuation or reductions in the levels of ACEIs and/or ARBs during dehydration or before surgery may also be warranted in these patients.

A case with neonatal hyperinsulinemic hypoglycemia: It is a characteristic complication of Sotos syndrome.

Sotos syndrome (SoS, OMIM #117550) is an overgrowth syndrome. Deletions or intragenic mutations of the NSD1 , which is located at chromosome 5q35, are responsible for more than 75% of SoS. Conventionally, neonatal hypoglycemia was reported briefly as one of the infrequent symptoms of SoS. However, Matsuo et al. published a report describing five patients with SoS who presented with transient hyperinsulinemic hypoglycemia (HIH) in the neonatal period. We report on an additional patient of SoS, who presented transient HIH in the neonatal period. All of this patient and previous patients have microdeletions at the 5q35 chromosome. Therefore, we examined the following three in considering the possibility that other factor than NSD1 caused HIH. 1) This patient had no mutation of four currently known HIH related genes, ABCC8, KCNJ11, GLUD1, and GCK. 2) He had no further deletion than commonly observed region encompassing NSD1 by comparative genomic hybridization to DNA microarrays. 3) He had no mutation in the 5q35 region in the non-deleted chromosome using exsome sequence analysis. In conclusion, our patient supported that HIH could be one of the characteristic symptoms of SoS in the neonatal period, and could be useful for early diagnosis.

HRAS mutants identified in Costello syndrome patients can induce cellular senescence: possible implications for the pathogenesis of Costello syndrome.

Costello syndrome (CS) is a congenital disease that is characterized by a distinctive facial appearance, failure to thrive, mental retardation and cardiomyopathy. In 2005, we discovered that heterozygous germline mutations in HRAS caused CS. Several studies have shown that CS-associated HRAS mutations are clustered in codons 12 and 13, and mutations in other codons have also been identified. However, a comprehensive comparison of the substitutions identified in patients with CS has not been conducted. In the current study, we identified four mutations (p.G12S, p.G12A, p.G12C and p.G12D) in 21 patients and analyzed the associated clinical manifestations of CS in these individuals. To examine functional differences among the identified mutations, we characterized a total of nine HRAS mutants, including seven distinct substitutions in codons 12 and 13, p.K117R and p.A146T. The p.A146T mutant demonstrated the weakest Raf-binding activity, and the p.K117R and p.A146T mutants had weaker effects on downstream c-Jun N-terminal kinase signaling than did codon 12 or 13 mutants. We demonstrated that these mutant HRAS proteins induced senescence when overexpressed in human fibroblasts. Oncogene-induced senescence is a cellular reaction that controls cell proliferation in response to oncogenic mutation and it has been considered one of the tumor suppression mechanisms in vivo. Our findings suggest that the HRAS mutations identified in CS are sufficient to cause oncogene-induced senescence and that cellular senescence might therefore contribute to the pathogenesis of CS.

Effects of methylprednisolone pulse on cytokine levels in Kawasaki disease patients unresponsive to intravenous immunoglobulin.

This study aimed to determine the effects of intravenous methylprednisolone pulse (IVMP) therapy on cytokine levels in patients with acute Kawasaki disease (KD) unresponsive to initial intravenous immunoglobulin (IVIG) therapy. Fifteen KD patients unresponsive to initial IVIG, 2 g/kg/day, were randomized to receive IVMP (n = 7), 30 mg/kg/day for 3 days or additional IVIG (n = 8), 2 g/kg/day, and plasma cytokine levels were compared. The fraction of febrile patients was significantly lower in the IVMP group than in the additional IVIG group on day 2 (0/7 vs. 3/8, p = 0.03), but not on day 4 and later (3/7 vs. 4/8, p = 1.00) because of recurrent fever. The prevalence of coronary lesions was similar between the two groups (2/7 vs. 2/8, p = 1.00). The ratios of plasma levels of tumor necrosis factor-alpha and monocyte chemoattractant protein-1 to those at enrollment (defined as day 1) were significantly lower in the IVMP group on day 4 (0.50 +/- 0.27 vs. 1.01 +/- 0.46, 0.53 +/- 0.39 vs. 0.93 +/- 0.44, p = 0.02 and 0.045, respectively), but not on day 7 (0.54 +/- 0.34 vs. 0.88 +/- 0.39, 0.76 +/- 0.39 vs. 0.61 +/- 0.17, p = 0.07 and 0.83, respectively). The ratios of interleukin-2 receptor, interleukin-6, and vascular endothelial cell growth factor to those at enrollment did not differ significantly between the two groups. In conclusion, for KD patients unresponsive to initial IVIG, IVMP suppresses cytokine levels faster, but subsequently similarly, compared with additional IVIG.

[Sensory evaluation test: odor component analysis and endotoxin content of Krestin and Carbocrin (generic drug) to compare palatability].

We conducted a sensory evaluation test to demonstrate the difference in palatability between Krestin and Carbocrin (generic drugs). In addition,we analyzed the odorous components and endotoxin contents of the two products to clarify the difference in physicochemical properties. In the sensory evaluation test, questions were asked on the odor, taste, feeling on the tongue, and overall evaluation, to find out which is easier to swallow. Krestin is significantly superior to Carbocrin, showing a clear difference in palatability between the two products. In odor component analysis, chemicals estimated to be n-heptane and 4-methyl-3-penten-2-one or its isomer (ketone containing 6-carbon double bonding) were detected. In addition, endotoxin content was also different between the two products. According to the above results, Carbocrin is definitely different from Krestin. Prior to administration, it is necessary to give this information to patients and obtain consent before use.

CD40 ligand gene and Kawasaki disease.

Kawasaki disease (KD) is an acute systemic vasculitis syndrome of infants and young children. Although its etiology is largely unknown, epidemiological findings suggest that genetic factors play a role in the pathogenesis of KD. To identify genetic factors, affected sib-pair analysis has been performed. One of the identified peaks was located on the Xq26 region. A recent report of elevated expression of CD40 ligand (CD40L), which maps to Xq26, during the acute-phase KD, and its relationship to the development of coronary artery lesions (CAL) prompted us to screen for polymorphism of CD40L and to study the association of the gene to KD. A newly identified SNP in intron 4 (IVS4+121 A>G) is marginally over-represented in KD patients as compared to controls (109/602, 18.1 vs 111/737, 15.1%). When male KD patients with CAL were analyzed as a patient group, the SNP was significantly more frequent than in controls (15/58, 25.9%, vs 111/737, 15.1%, OR=2.0, 95% CI=1.07-3.66; P=0.030). Interestingly, this variation was extremely rare in a control Caucasian population (1/145, 0.7%). Our results suggest a role of CD40L in the pathogenesis of CAL and might explain the excess of males affected with KD.