[JAPANESE TRANSLATION AND LINGUISTIC VALIDATION OF THE RECAP OF ATOPIC ECZEMA (RECAP)].

BACKGROUND: The Recap of atopic eczema (RECAP), a new core outcome of the atopic dermatitis trial, was translated into Japanese and linguistically validated. METHODS: Translation into Japanese was accomplished according to the ISPOR (International Society for Pharmacoeconomics and Outcome Research) guidelines and the basic guidelines for scale translation. The translation process included two forward translations, reconciliation with native English speakers, third-party back translation, cognitive debriefing, review and harmonization by the original authors. Twenty-seven atopic dermatitis and pediatric specialists from 21 centers in Japan participated in the translation process. Cognitive debriefing was conducted through face-to-face interviews using a think-aloud method with the interview guide including questions about comprehensibility, relevance, comprehensiveness, recall period and suggested improvements, based on the COSMIN methodology. RESULTS: No linguistic or cultural problems were encountered in the translation into Japanese. Cognitive debriefings were conducted with 10 adult patients and 10 parents of pediatric patients. Some minor modifications were made following discussion and approval by the research team and the original authors. The Japanese version of RECAP was considered to be understandable, comprehensive and relevant for adult patients and families of pediatric patients. CONCLUSION: The Japanese version of the RECAP, which has been validated as linguistically equivalent to the original version, is now available. Further evaluation of the measurement properties is needed in the future.

What are the factors that cause emergency home visit in home medical care in Japan?

BACKGROUND: In the home medical care setting, the factors causing emergency home visits (EHV) remain unclear. This study aimed to determine those factors and examine their relationship with EHV requests. METHODS: This is a single-center retrospective observational study from data obtained from a home medical care clinic. We assessed the association between frequency of EHV and age, gender, level of care-needed, cancer, and medical device in use with using Poisson regression analysis. RESULTS: A total of 608 EHV in 214 patients were analyzed. Common chief complaints were fever, death, and dyspnea. As factors that affect frequency of EHV because of fever, higher care-needed level (RR: 3.35; 95% CI: 1.95-5.74, P < .001), urinary catheter use (RR: 1.94; 95% CI: 1.22-3.08, P = .005), and central venous port use (RR: 2.39; 95% CI: 1.44-3.96, P = .001) showed significant correlation. Regarding EHV because of dyspnea, lung tumor (RR: 2.71; 95% CI: 1.26-5.84, P = .011) and home oxygen use (RR: 3.96; 95% CI: 2.05-7.68, P < .001) showed significant correlation. Regarding EHV because of all chief complaints, higher care-needed level (RR: 1.59; 95% CI: 1.12-2.26, P = .009), urinary catheter use (RR: 1.78; 95% CI: 1.13-2.93, P = .014), and central venous port use (RR: 1.75; 95% CI: 1.04-2.93, P = .034) showed positive correlation. CONCLUSION: The factors associated with frequency of EHV because of fever or all chief complaints were urinary catheter use, central venous port use, and higher care-needed level. As for dyspnea, they were lung cancer and home oxygen use. Our study suggests that the burdens on medical staffs, patients, and their families can be reduced through recognizing these risk factors.

Vitamin K2 Suppresses Proliferation and Inflammatory Cytokine Production in Mitogen-Activated Lymphocytes of Atopic Dermatitis Patients through the Inhibition of Mitogen-Activated Protein Kinases.

Vitamin K2 is suggested to have a suppressive effect on the peripheral blood mononuclear cells (PBMCs) of pediatric atopic dermatitis patients. We examined the molecular targets of vitamin K2 to suppress proliferation and cytokine production in T-cell mitogen-activated PBMCs of atopic dermatitis patients from the viewpoint of mitogen-activated protein kinase signaling molecules. The study population included 16 pediatric vitamin K2 patients and 21 healthy subjects. The effect of vitamin K2 on concanavalin A-activated PBMC proliferation was evaluated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and cell counting assays. T-helper (Th)1/Th2/Th17 cytokine profiles in plasma and PBMC-culture supernatants were analyzed by a cytometric beads array assay. Mitogen-activated protein kinase signaling molecules in concanavalin A-activated PBMCs were examined by enzyme-linked immunosorbent assay (ELISA) assays. At 10-100 µM, vitamin K2 significantly suppressed the proliferation of mitogen-activated PBMCs derived from atopic dermatitis patients and healthy subjects (p < 0.05). The interleukin (IL)-10 concentrations in plasma and the PBMC culture supernatants of atopic dermatitis patients were significantly higher than those of healthy subjects (p < 0.05). The IL-2 concentrations in the culture supernatants of atopic dermatitis PBMCs were significantly lower than those of healthy PBMCs (p < 0.05). Vitamin K2 significantly inhibited the IL-17A, IL-10, and tumor necrosis factor α (TNF-α) production (p < 0.05), and increased the IL-2 production (p < 0.01) in the culture supernatant of atopic dermatitis PBMCs. At 10-100 µM, vitamin K2 markedly decreased the of Mek1, extracellular signal-regulated kinases (ERK)1/2 mitogen-activated protein kinase, and SAPK/c-Jun N-terminal kinase (JNK) expression in atopic dermatitis PBMCs (p < 0.05). Vitamin K2 is suggested to attenuate activated T-cell immunity in atopic dermatitis patients through the inhibition of mitogen-activated protein kinase-Mek1-ERK1/2 and SAPK/JNK signaling pathways.

Vitamin K2 immunosuppressive effect on pediatric patients with atopic dermatitis.

BACKGROUND: Over 20 kinds of steroids, tacrolimus ointments, and cyclosporine capsules are usually recommended for the treatment of atopic dermatitis (AD), depending on the symptoms of patients. However, several side effects sometimes occur with the extensive use of these agents for the treatment of pediatric AD patients. The purpose of this study was to explore whether vitamin K2 could be a new immunosuppressive candidate for pediatric patients with AD. METHODS: The immunosuppressive efficacy of vitamin K2 was evaluated through a cell-culture procedure using mitogen-activated peripheral blood mononuclear cells (PBMCs) obtained from pediatric AD patients. RESULTS: The mean (SD) IC50 value of vitamin K2 for the proliferation of concanavalin A-activated PBMCs was 15.37 (30.05) µmol/L, while the value for tacrolimus was 0.10 (0.28) ng/mL (0.12 (0.35) nmol/L). There was a significant correlation between the IC50 values for vitamin K2 and those for tacrolimus (P = 0.0001, r = 0.8871). However, there was no significant correlation between the IC50 values of vitamin K2 and those of cyclosporine A or methylprednisolone. A significant correlation between the IC50 values of vitamin K2 or tacrolimus and blood eosinophil counts (P = 0.0099, r = 0.7086 and P = 0.0032, r = 0.7722, respectively) was observed. CONCLUSION: Vitamin K2 -inhibited T-cell mitogen stimulated proliferation of PBMCs from pediatric AD patients in a dose-dependent manner. The PBMCs from pediatric AD patients were more sensitive to the immunosuppressive efficacy of vitamin K2 than the PBMCs from healthy subjects. The individual immunosuppressive pharmacological efficacy of vitamin K2 and of tacrolimus could be inferred from the blood eosinophil count of pediatric AD patients.

[THE ANALYSIS OF ANAPHYLAXIS DIAGNOSED AT DERMATOLOGY OF TOKYO MEDICAL UNIVERSITY HOSPITAL].

OBJECTIVE: There are few epidemiological reports of anaphylaxis since childhood. We herein examined cases of anaphylaxis diagnosed in our department. METHODS: One hundred-thirty-two patients who were examined at the Dermatology Department of Tokyo Medical University Hospital between January 2011 and March 2017 and were prescribed epinephrine autoinjector (EpiPen®) for treatment were enrolled. The referral institution if any, severity of anaphylaxis, diagnostic method, causative antigen, and recurrence rate was examined. RESULTS: The referral rate was 54% while 46% of patients requested examination of their own accord. Anaphylaxis severity was mild to moderate in 75% of cases. Food allergy accounted for 71% of the symptoms, with wheat as the most common causative antigen, followed by Anisakis allergy. After diagnosis only 37% of patients continued periodic consultations, and 16 patients recurred anaphylaxis of the diagnosis. CONCLUSION: Wheat and WDEIA were the most frequent causes of anaphylaxis diagnosed in our department. We also found that as many as 15% of patients had Anisakis allergy, suggesting that it may be an important item in antigen testing.

The effects of vitamin K1 and vitamin K2 on the proliferation, cytokine production and regulatory T-cell frequency in peripheral blood mononuclear cells of paediatric atopic dermatitis patients.

We estimated the pharmacological efficacy of vitamin K1 (VK1 ) and VK2 on the mitogen-activated peripheral blood mononuclear cells (PBMCs) of paediatric atopic dermatitis (AD) patients. VK2 suppressed the in vitro proliferation of T-cell mitogen-activated PBMCs of AD patients. In contrast, VK1 had little effect on the PBMC proliferation. The IL-2 production from the activated PBMCs of AD patients significantly increased (P < .05), while the production significantly decreased by 100 µmol L-1 VK2 (P < .01). In addition, 100 µmol L-1 VK2 reduced the percentage of CD4+ and CD4+CD25+ cells in PBMCs. These results suggest that VK2 can modulate T-cell function in PBMCs of AD patients.

Follow-up of patients with uncertain symptoms during an oral food challenge is useful for diagnosis.

BACKGROUND: Uncertain symptoms often emerge during an oral food challenge (OFC), and Open-OFCs with those uncertain mild symptoms are ordinarily regarded as positive. Double-blind placebo-controlled food challenges should be conducted to determine these associations. Nevertheless, studies regarding the diagnosis of uncertain food allergy symptoms are lacking. We examined the diagnostic decision for a food allergy based on uncertain symptoms during an Open-OFC. METHODS: We conducted an Open-OFC between August 2005 and April 2012 with 2271 cases who suspected as allergic to hen's eggs, cow's milk, or wheat. For the primary diagnosis, Open-OFCs with obvious symptoms were classified as "positive," no symptoms as "negative," and uncertain, indeterminate symptoms as "uncertain." We encouraged the children in the uncertain group to consume the causative foods at home more than twice; if any definitive symptoms were induced, children were classified as "intolerant," and children without any symptoms were classified as "tolerant," for the final diagnosis. RESULTS: We analyzed 454 uncertain cases excluding 781 positive cases and 1036 negative cases. The symptoms that occurred for the uncertain cases included slight abdominal pain, localized skin rash, and an isolated cough. Of these cases, 362 (79.7%) were considered tolerant at the final diagnosis. Of the intolerant children at the final diagnosis, the induced symptoms at home were not serious. CONCLUSIONS: Monitoring of recurring symptoms following consumption of causative foods at home by patients with uncertain symptoms improves the diagnostic accuracy of an Open-OFC.

Spontaneous pneumomediastinum in young women: Comparison between anorexia nervosa and nonanorexic patients.

Spontaneous pneumomediastinum is a benign, self-limited condition that mainly affects young people. In this report, we present four cases of this uncommon condition and a review of the current literature. Two cases had no prior significant medical history: one had a history of asthma and the other underwent regular outpatient treatment for anorexia nervosa. The three patients who were not anorexic spontaneously improved within a few days. However, the patient with anorexia nervosa took 2 months to recover. It appears that spontaneous pneumomediastinum is an intractable complication of anorexia nervosa, and the improvement of nutritional status in the patient is essential to manage this condition.

In vitro quantitative determination of the concentration of the polymerization agent methyl 2-benzoylbenzoate in intravenous injection solution and the cytotoxic effects of the chemical on normal human peripheral blood mononuclear cells.

In previous studies, we detected the photoinitiators 1-hydroxycyclohexyl phenyl ketone (1-HCHPK) and 2-methyl-4'-(methylthio)-2-morpholinopropiophenone (MTMP) in an intravenous injection solution. Importantly, 1-HCHPK and MTMP have been demonstrated to be cytotoxic to normal human peripheral blood (PB) mononuclear cells (MNC). Cell death (apoptosis) pathways can be classified into two modes, caspase-dependent and -independent pathways. However, it is unclear whether methyl 2-benzoylbenzoate (MBB) induces the caspase-dependent and/or -independent pathway in normal human PBMNC. In the present in vitro study, we examined the levels of MBB in a solution from an intravenous fluid bag and the cytotoxicity of MBB towards normal human PBMNC via the caspase-8-, caspase-9-, or apoptosis-inducing factor (AIF)-mediated apoptosis pathways. We found that extracts from the injection solution had been contaminated with approximately 80 µM of the photoinitiator MBB. In addition, MBB induced apoptosis in the high concentration range in normal human PBMNC in vitro. Moreover, we found that MBB-induced apoptosis occurs via the caspase-9 pathway, but not the AIF pathway. In conclusion, we suggest that MBB has cytotoxic effects on normal human PBMNC in vitro, which are mediated via the caspase-dependent pathway.

Photoinitiator-Initiated Estrogenic Activity in Human Breast Cancer Cell Line MCF-7.

A recent in vitro study reported that the photoinitiator 2-isopropylthioxanthone (2-ITX) is an endocrine-disrupting compound (EDC). However, it is not clear whether other photoinitiators such as 1-hydroxycyclohexyl phenyl ketone (1-HCHPK) and 2-methyl-4'-(methylthio)-2-morpholinopropiophenone (MTMP) produce endocrine-disrupting effects. The purpose of this study was thus to assess the association between estrogenic activity and exposure to photoinitiators. For estimation of the proliferative effect of the photoinitiators, the E-screen assay was used. Six photoinitiators, 2,2-dimethoxy-2-phenylacetophenone (2,2-DMPAP), 2-ethylhexyl 4-(dimethylamino)benzoate (2-EHDAB), 1-HCHPK, 2-ITX, methyl-2-benzoylbenzoate (MBB), and MTMP, significantly increased number of MCF-7 cells, an estrogen-sensitive human breast cancer cell line. In addition, pretreatment with estrogen receptor (ER) antagonists such as clomiphene, tamoxifen, or fulvestrant, significantly reversed the proliferative effect of each photoinitiator. Data demonstrated that the six photoinitiators produced endocrine-disrupting effects and that these photoinitiators interacted with ER as agonists. Evidence indicates that the six photoinitiators demonstrated estrogenic activity via ER as agonists.

Differential combined effect of COX inhibitors on cell survival suppressed by sorafenib in the HepG2 cell line.

Hepatocellular carcinoma (HCC) is one of the leading causes of cancer-related deaths worldwide. Sorafenib, a molecular-targeted drug, is a multi-target oral anti-neoplastic drug that is used as a first-line treatment for patients with advanced Human HCC. An increase in the expression of the cyclooxygenase-2 (COX-2) protein and sequential production of prostaglandin (PG) E2 were previously shown to significantly enhance carcinogenesis. Although the synergistic and/or additive effects of various COX inhibitors have been demonstrated in HCC, those of a combination of sorafenib and COX inhibitors remain unclear. The aim of the present study was to examine the antitumor effects of a combination of sorafenib and COX inhibitors on HCC HepG2 cells. Various COX inhibitors suppressed HepG2 cell survival, and exhibited a combined effect with sorafenib. However, COX-2 selectivity had little relevance. The co-administration of COX inhibitors and sorafenib increased the frequency of apoptosis. Moreover, the combination of sorafenib and diclofenac significantly increased Bax protein expression levels. The results of the present study indicate that COX inhibitors can be administered in combination with sorafenib for HCC therapy.

Extreme efficiency of airway pressure release ventilation (APRV) in a patient suffering from acute lung injury with pandemic influenza A (H1N1) 2009 and high cytokines.

The authors report a Japanese boy with severe pandemic influenza A(H1N1) 2009-associated pneumonia and deteriorating oxygenation. He dramatically recovered after the use of Airway Pressure Release Ventilation (APRV) mode. There was no improvement by using any conventional ventilation, however, APRV immediately led to an improvement of his clinical symptoms and laboratory findings.