Involvement of Muscarinic M3 Receptor in the Development of M2 Macrophages in Allergic Inflammation.

INTRODUCTION: The muscarinic M3 receptor antagonist, tiotropium, has a bronchodilatory effect on asthma patients. Additionally, tiotropium inhibits allergic airway inflammation and remodeling in a murine asthma model. However, the underlying mechanisms of this M3 receptor antagonist remain unclear. Therefore, we investigated the effect of muscarinic M3 receptor blockage on M2 macrophage development during allergic airway inflammation. METHODS: BALB/c mice were sensitized and challenged with ovalbumin to develop a murine model of allergic airway inflammation mimicking human atopic asthma. During the challenge phase, mice were treated with or without tiotropium. Lung cells were isolated 24 h after the last treatment and gated using CD68-positive cells. Relm-α and Arginase-1 (Arg1) (M2 macrophage markers) expression was determined by flow cytometry. Mouse bone marrow mononuclear cell-derived macrophages (mBMMacs) and human peripheral blood mononuclear cells (PBMCs)-derived macrophages were stimulated with IL-4 and treated with a muscarinic M3 receptor antagonist in vitro. RESULTS: The total cells, eosinophils, and IL-5 and IL-13 levels in BAL fluids were markedly decreased in the asthma group treated with tiotropium compared to that in the untreated asthma group. The Relm-α and Arg1 expression in macrophages was reduced considerably in the asthma group treated with tiotropium compared to that in the untreated asthma group, suggesting that the development of M2 macrophages was inhibited by muscarinic M3 receptor blockage. Additionally, muscarinic M3 receptor blockage in vitro significantly inhibited M2 macrophage development in both mBMMacs- and PBMCs-derived macrophages. CONCLUSIONS: Muscarinic M3 receptor blockage inhibits M2 macrophage development and prevents allergic airway inflammation. Moreover, muscarinic M3 receptors might be involved in the differentiation of immature macrophages into M2 macrophages.

Baseline forced oscillation technique predicting lack of exacerbations in adult with asthma: A 12-month prospective.

BACKGROUND: The forced oscillation technique (FOT) is a minimally invasive test to evaluate asthma during resting ventilation. However, its role in longitudinal assessments, such as clinical remission, remains unclear. OBJECTIVE: This study aimed to longitudinally assess asthma clinical remission and identify parameters that predict clinical remission at 12 months from baseline FOT. METHODS: Adult patients with asthma at our university hospital between April 2022 and May 2023 were enrolled in this prospective observational study. They were evaluated for 12 months after enrollment to determine whether they met the clinical remission criteria: asthma control test score of ≥20 at enrollment and 12 months, no asthma exacerbations for 12 months, and no regular oral corticosteroid use during the 12 months. FOT parameters at enrollment were analyzed for associations with clinical remission. RESULTS: Ninety-four patients with asthma completed the study and were categorized into clinical and non-clinical remission groups. Comparison of pulmonary function tests, including the FOT, between the two groups revealed significant differences in resistance at 5 Hz and 20 Hz (R20) but not in FEV1. Multivariate logistic regression analysis showed that R20 was associated with clinical remission, with adjusted ORs of 0.32 (95% CI: 0.12-0.91, P=0.033) for R20. CONCLUSION: R20 can be a useful predictor of future exacerbations in patients with asthma. These findings may assist in evaluating adult patients with asthma and normal FEV1.

The Effect of Bronchoconstriction by Methacholine Inhalation in a Murine Model of Asthma.

INTRODUCTION: Bronchoconstriction was recently shown to cause airway remodeling and induce allergic airway inflammation in asthma. However, the mechanisms how mechanical stress via bronchoconstriction could induce airway inflammation and remodeling remain unclear. OBJECTIVE: We investigated the effect of bronchoconstriction induced by methacholine inhalation in a murine model of asthma. METHODS: BALB/c female mice were sensitized and challenged with ovalbumin (OVA), followed by treatment with methacholine by a nebulizer twice a day for 7 days. Twenty-four hours after the last methacholine treatment, the bronchoalveolar lavage fluid (BALF) and lung tissues were collected. The BALF was analyzed for total and differential cell counts and cytokine levels. The lung tissues were analyzed for goblet cell metaplasia, thickness of the smooth muscle, and lung fibrosis. The expression of cytokines in the lung was also examined. RESULTS: OVA sensitization and challenge induced infiltration of total cells, macrophages, and eosinophils in the BALF along with goblet cell metaplasia and increased airway smooth muscle hypertrophy. Seven days after the last OVA challenge, untreated mice achieved reduction in airway inflammation, while methacholine maintained the number of BALF total cells, macrophages, and eosinophils. The percentage of goblet cells and the thickness of airway smooth muscle were also maintained by methacholine. Moreover, the treatment of methacholine induced the expression of transforming growth factor (TGF)-ß in the lung. This result indicates that the production of TGF-ß is involved in induction of airway remodeling caused by bronchoconstriction with methacholine. CONCLUSIONS: Repeated bronchoconstriction caused by methacholine inhalation elicited allergic airway inflammation and airway remodeling.

Exposure to intermittent hypoxia inhibits allergic airway inflammation in a murine model of asthma.

PURPOSE: Obesity increases the severity of asthma, and patients with severe asthma are often complicated with obstructive sleep apnea syndrome (OSAS), a concomitant disease of obesity. We investigated whether intermittent hypoxia (IH), which is a physiological feature of OSAS, modifies allergic airway inflammation in a murine model of asthma. METHODS: Balb/c mice were sensitized by ovalbumin (OVA) intraperitoneally twice (days 1 and 14) and challenged with intranasal OVA three times (days 21, 22, and 23). The mice were exposed to IH either from days 1 to 24 (long exposure) or only from days 21 to 24 (short exposure). The impact of IH exposure to allergic airway inflammation was investigated using these mice models by histologic, morphometric, and molecular techniques. Additionally, the airway responsiveness to acetylcholine was also assessed. RESULTS: OVA-sensitized and OVA-challenged mice exposed to room air (RA) showed increased total cell and eosinophil numbers in the BALF. The levels of interleukin (IL)-5 and IL-13 in the BALF also increased and goblet cell metaplasia was induced. In contrast, both long and short exposure to IH inhibited the increased total cell and eosinophil numbers. The levels of IL-5 and IL-13 in the BALF also decreased on exposure to IH. Moreover, the goblet cell hyperplasia and airway hyperresponsiveness were significantly reduced in mice exposed to IH compared to those exposed to RA. CONCLUSIONS: These results suggest that IH may not deteriorate the asthmatic condition in a murine model of asthma.

Inhibition of Virus-Induced Cytokine Production from Airway Epithelial Cells by the Late Addition of Budesonide.

BACKGROUND: Viral infection is the main cause of asthma and COPD (chronic obstructive pulmonary disease) exacerbation and accumulate inflammatory cells to airway tissue. We have reported poly I:C, a mimic product of the virus and ligand of toll-like receptor 3 (TLR3), induced inflammatory chemokines from airway epithelial cells and found prior incubation with corticosteroids diminishes the effect of TLR3 activation. In clinical practice, mild asthma is recommended as-needed budesonide (BUD) when symptoms occur following a viral infection, etc. However, many questions still surround BUD's usefulness if taken after a virus has already infected airway tissue. OBJECTIVE: The aim of this study was to investigate the inhibitory effects of BUD on inflammatory cytokines induced by viral infection. Methods: Normal human bronchial epithelial (NHBE) cells were stimulated with poly I:C or infected with human rhinovirus-16 (HRV16) and BUD was added after the initial stimulation. Expression of both thymic stromal lymphopoietin (TSLP) and CCL26/eotaxin-3 was quantified by real-time RT-PCR and enzyme-linked immunosorbent assay (ELISA), respectively. Knockdown study was performed. Results: Pre-or post-incubation with BUD inhibited both poly I:C- and HRV16-induced mRNAs and proteins of both thymic stromal lymphopoietin (TSLP) and CCL26 with significance. Knockdown of the glucocorticoid receptor diminished these effects of BUD. Under the same conditions of BUD's experiment, post-incubation with neither fluticasone propionate nor dexamethasone suppressed expression of both TSLP and CCL26, which induced by poly I:C. CONCLUSION: Post-addition of BUD inhibited the virus-induced TSLP and CCL26 from the airway epithelial cells. These results suggest that inhalation of BUD after viral infection has beneficial effects on asthma. CONCLUSION: Late addition of BUD may benefit among patient with viral infection and type 2 allergic airway disease such as asthma.

[A CASE OF ANAPHYLAXIS DUE TO STINGING OF A Brachyponera chinensis].

The case involved a man in his forties. While working at the restaurant that the patient runs, the patient experienced a stab-like pain on the left shoulder and developed systemic pruritic eruptions. He was diagnosed with anaphylaxis upon visiting our emergency department. Conjunctival hyperemia, lip swelling, cold sweats, and nausea presented later. A cap fluorescence enzyme immunoassay using the serum of the patient showed specific immunoglobulin E (IgE) positivity for wasps; therefore, we hypothesized that he had anaphylaxis caused by the insect's sting. Insects of the same species as that by which the patient had been stung were collected and finally identified as the Asian needle ant (Brachyponera chinensis). The freeze-dried insects' bodies were sonicated into powders and stored for following examinations. Next, a basophil activation test was performed using the patient's whole blood treated with the reagent above, which showed positivity. Furthermore, a skin prick test using the same reagent showed a positive result, and the reaction increased in a concentrationdependent manner. Based on these results, the patient was diagnosed with anaphylaxis after a sting by the ant. Based on the results of the allergen component specific IgE test, we speculated that the pathogens in this case was group5 allergen of the Asian needle ant. Anaphylaxis following insect stings by this ant has been reported frequently in South Korea. However, it is quite rare in Japan, although the ant is native to Japan. Clinicians should consider that this allergy can occur indoors, unlike allergies to other types of venom.

Beneficial Effect of Early Intervention with Garenoxacin for Bacterial Infection-Induced Acute Exacerbation of Bronchial Asthma and Chronic Obstructive Pulmonary Disease.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) and asthma have similar clinical features and are both exacerbated by airway infection. OBJECTIVE: To determine whether garenoxacin mesylate hydrate (GRNX) added to the standard care for bacterial infection-induced acute exacerbation of asthma or COPD in adults has clinical benefits. METHOD: This single-arm clinical trial was conducted from January 2015 to March 2016. Adults with a history of asthma or COPD for more than 12 months were recruited within 48 h of presentation with fever and acute deterioration of asthma or COPD requiring additional intervention. Participants were administered 400 mg GRNX daily for 7 days without additional systemic corticosteroids or other antibiotics. The primary outcome was efficacy of GRNX based on clinical symptoms and blood test results after 7 days of treatment. Secondary outcomes were: (1) comparison of the blood test results, radiograph findings, and bacterial culture surveillance before and after treatment; (2) effectiveness of GRNX after 3 days of administration; (3) analyzation of patient symptoms based on patient diary; and (4) continued effectiveness of GRNX on 14th day after the treatment (visit 3). RESULTS: The study included 44 febrile patients (34 asthma and 10 COPD). Frequently isolated bacteria included Moraxella catarrhalis (n = 6) and Klebsiella pneumoniae (n = 4). On visit 2, 40 patients responded, and no severe adverse events were observed. All secondary outcomes showed favorable results. CONCLUSION: GRNX effectively treated asthma and COPD patients with acute bacterial infection without severe adverse events. Further research with a larger study population is needed.

Japanese clinical practice guidelines for allied disorders of Hirschsprung's disease, 2017.

BACKGROUND: Despite the presence of ganglion cells in the rectum, some patients have symptoms similar to those of Hirschsprung's disease. A consensus has yet to be established regarding the terminology for these diseases. We defined this group of diseases as "allied disorders of Hirschsprung's disease" and compiled these guidelines to facilitate accurate clinician diagnosis and provide appropriate treatment strategies for each disease. METHODS: These guidelines were developed using the methodologies in the Medical Information Network Distribution System (MINDS). Of seven allied disorders, isolated hypoganglionosis; megacystis-microcolon-intestinal hypoperistalsis syndrome; and chronic idiopathic intestinal pseudo-obstruction were selected as targets of clinical questions (CQ). In a comprehensive search of the Japanese- and English-language articles in PubMed and Ichu-Shi Web, 836 pieces of evidence related to the CQ were extracted from 288 articles; these pieces of evidence were summarized in an evidence table. RESULTS: We herein outline the newly established Japanese clinical practice guidelines for allied disorders of Hirschsprung's disease. Given that the target diseases are rare and intractable, most evidence was drawn from case reports and case series. In the CQ, the diagnosis, medication, nutritional support, surgical therapy, and prognosis for each disease are given. We emphasize the importance of full-thickness intestinal biopsy specimens for the histopathological evaluation of enteric ganglia. Considering the practicality of the guidelines, the recommendations for each CQ were created with protracted discussions among specialists. CONCLUSIONS: Clinical practice recommendations for allied disorders of Hirschprung's disease are given for each CQ, along with an assessment of the current evidence. We hope that the information will be helpful in daily practice and future studies.

[PROBLEMS ASSOCIATED WITH THE DIAGNOSIS OF PROLONGED/CHRONIC COUGH IN CLINICAL SETTINGS].

BACKGROUND: Many patients visit primary care clinics or local hospitals with a complaint of prolonged/chronic cough. Among the different types of chronic cough, cough variant asthma (CVA) and postinfectious cough may be the most common types, and their differential diagnosis is difficult. Some physicians tend to prescribe inhaled corticosteroids before establishing a definitive diagnosis. METHODS: We retrospectively investigated useful findings for diagnosis in 77 patients with a complaint of prolonged/ chronic cough to detect meaningful findings for differential diagnosis and to identify problems associated with diagnosis in clinical practice. RESULTS: CVA was diagnosed in 39 patients, and postinfectious cough was diagnosed in 19. Compared with postinfectious cough, CVA was associated with significant characteristics such as "diurnal variation of symptoms," "response to inhalation of short acting ß2 agonist (SABA)," and "recurrent episodes of symptoms." CVA was associated with high FeNO levels as well, and high FeNO levels were specific to CVA. However, these useful characteristics were not significant in the patients who had been prescribed ICS before visiting our hospital. CONCLUSIONS: Medical examination and determination of FeNO levels are useful for the differential diagnosis of prolonged/chronic cough, before treatment with ICS.

Evaluation of the association between sensitization to common inhalant fungi and poor asthma control.

BACKGROUND: Fungi are well-known airborne allergens that are predisposing environmental factors to asthma. Few comparative studies have evaluated sensitization to common inhalant fungi in relation to poor asthma control in patients with asthma. OBJECTIVE: To evaluate the association between sensitization to individual fungi and asthma control and elucidate the characteristics of patients with poorly controlled asthma sensitized to fungi. METHODS: This cross-sectional study was performed at Showa University Hospital between September 2014 and December 2014. The specific IgE levels for several major aeroallergens, including house dust mites, Japanese cedar, various types of pollen, furry animals, or insects, were measured with a fluorescent enzyme immunoassay in 160 patients with adult asthma. RESULTS: Fungal sensitization was predominant in men with asthma, and it was associated with poor asthma control. Sensitization to house dust mites, Japanese cedar, pollen, furry animals, or insects was not associated with poor asthma control. Logistic regression analyses revealed that patients sensitized to Aspergillus and Penicillium had a significantly increased risk of poor asthma control. More Penicillium IgE-positive patients were men and pet owners compared with Penicillium IgE-negative patients; in addition, Penicillium IgE-positive patients had higher total IgE levels. The Asthma Control Test level was significantly higher in Penicillium IgE-positive patients than in Penicillium IgE-negative patients. However, there were no differences in fractional exhaled nitric oxide, forced vital capacity, and forced expiratory volume in 1 second. Finally, sensitization to Aspergillus, Cladosporium, and Trichophyton were positively correlated with sensitization to Penicillium. CONCLUSION: Sensitization to fungi is predominant in men, and it is associated with poor asthma control. In particular, sensitization to Penicillium and Aspergillus is a risk factor for asthma severity. These results have potential relevance in asthma management.

Effects of insistent screening for contralateral patent processus vaginalis in laparoscopic percutaneous extraperitoneal closure to prevent metachronous contralateral onset of pediatric inguinal hernia.

PURPOSE: Laparoscopic percutaneous extraperitoneal closure (LPEC) is known to reduce the incidence of metachronous contralateral hernia (MCH) compared to conventional hernia repair. We herein describe the effects of insistent screening for an irregular orifice of the contralateral patent processus vaginalis (CPPV). METHODS: All patients who underwent LPEC between 2003 and 2013 were reviewed. We started insistent screening for a CPPV in July 2010. The surgically treated cases before June 2010 were assigned to the former group, while those treated after July 2010 were in the latter group. The data were retrospectively collected from medical records. The statistical analysis was performed using the Mann-Whitney U test or Chi square test. A value of P < 0.05 was considered to be significant. RESULT: A total of 1113 patients (514 males and 599 females) ranging in age from 3 months old to 15 years old (median 4.6 years old), were reviewed. Of the 626 patients in the former group, a CPPV was detected in 227 patients. Of the 487 patients in the latter group, a CPPV was detected in 271 patients. The incidence of a CPPV significantly increased over time (P < 0.001). We encountered five cases of MCH, all of which belonged to the former group (P = 0.048). CONCLUSIONS: The increased detection of a CPPV by insistent screening seemed to cause a decrease in the incidence of MCH.

Incidence of contralateral patent processus vaginalis in relation to age at laparoscopic percutaneous extraperitoneal closure for pediatric inguinal hernia.

INTRODUCTION: Laparoscopic percutaneous extraperitoneal closure (LPEC) allows the surgeon to look for contralateral patent processus vaginalis (CPPV) directly. We investigated the incidence of CPPV in relation to age at LPEC. METHODS: Following Institutional Review Board approval, 1232 patients ranging in age from 2 months old to 15 years old (median 4.7 years), who underwent LPEC, were investigated retrospectively. Patients were divided into five groups based on their age at surgery: younger than 1, 1-2, 2-4, 4-6 years, and older than 6 years. The incidence of CPPV being detected by preoperative ultrasonography or laparoscopy was compared among these groups. Statistical analyses were performed using the Chi-square test or Cochran-Armitage trend test, and p < 0.05 was considered significant. RESULTS: The incidence of CPPV detected by ultrasonography decreased as the age increased (p < 0.0001), whereas the incidence of CPPV newly revealed by laparoscopy increased as age increased (p = 0.0001). There were no significant differences in the incidence of CPPV in patients with unilateral hernia among the five age groups (p = 0.74). CONCLUSIONS: These results showed that the incidence of CPPV in patients with unilateral inguinal hernia did not change in relation to their age.

[Treatment Strategy for Acute Type B Aortic Dissection with End-organ Malperfusion].

Therapeutic strategies for treating Stanford type B dissection with endo-organ malperfusion remain controversial, and whether surgery or conservative treatment should be performed is a matter of ongoing debate. In this study, we examined the treatment strategies used in cases of malperfusion in which treatment was initiated conservatively at the onset of symptoms without superior mesenteric artery (SMA) or limb artery obstruction. A total of 16 patients had organ ischemia in this series. The obstructed branches were the SMA in 5 patients, the artery of Adamkiewicz in 2, the bilateral renal arteries in 3, the celiac artery in 3 and limb arteries in 3. The surgical procedure included bypass grafting in 2 patients with SMA obstruction and extra-anatomical bypass in 2 patients with limb artery obstruction. A total of 11 patients were treated without surgery. Three patients died, including 2 patients with SMA obstruction. The remaining patient who died had limb artery obstruction and did not undergo surgery. The results suggest that patients with acute type B aortic dissection with endo-organ malperfusion who develop SMA or limb artery obstruction require early surgery.

Inorganic nitrite improves components of the metabolic syndrome independent of weight change in a murine model of obesity and insulin resistance.

Nitrite acts as an endocrine source of bioactive nitric oxide, impacting vascular reactivity, angiogenesis and cytoprotection. Nitrite has recently been shown to have a metabolic role although its effects and mechanisms of action in the obese insulin-resistant state are unknown. We examined glucose tolerance and insulin secretion using the frequently sampled intravenous glucose tolerance test and insulin sensitivity using the hyperinsulinaemic euglycaemic clamp in obese male ob(lep) mice administered nitrite (100 mg kg(-1) day(-1) ) or saline (control) for 7 days and compared responses to the known insulin-sensitizing effects of rosiglitazone (6 mg kg(-1) day(-1) ). Under weight-matched conditions, nitrite lowered blood pressure relative to saline and rosiglitazone, whereas only rosiglitazone was effective at reducing hepatic glucose output and basal blood glucose. Both nitrite and rosiglitazone produced improvements, relative to saline, in glucose tolerance (12,524 ± 602, 12,811 ± 692 vs.14,428 ± 335 mg (dl min)(-1) , respectively; P < 0.05) and insulin sensitivity (8.6 ± 0.7, 7.9 ± 0.3 vs. 6.6 ± 0.5 mg kg(-1) min(-1) , respectively; P < 0.001), but there was no effect on insulin secretion. Nitrite exhibited an uncoupling of mitochondrial respiration and a decrease in ATP generation in muscle that was independent of mitochondrial biogenesis or activation of uncoupling proteins. There was no insulin-stimulated phosphorylation of Akt, but nitrite increased the phosphorylation of AMP-activated protein kinase. We conclude that nitrite improves two key components of the metabolic syndrome, blood pressure and insulin sensitivity, independent of weight and with effectiveness comparable to rosiglitazone.

ß-catenin links hepatic metabolic zonation with lipid metabolism and diet-induced obesity in mice.

ß-catenin regulates the establishment of hepatic metabolic zonation. To elucidate the functional significance of liver metabolic zonation in the chronically overfed state in vivo, we fed a high-fat diet (HFD) to hepatocyte-specific ß-catenin transgenic (TG) and knockout (KO) mice. Chow-fed TG and KO mice had normal liver histologic findings and body weight. However, HFD-fed TG mice developed prominent perivenous steatosis with periportal sparing. In contrast, HFD-fed KO mice had increased lobular inflammation and hepatocyte apoptosis. HFD-fed TG mice rapidly developed diet-induced obesity and systemic insulin resistance, but KO mice were resistant to diet-induced obesity. However, ß-catenin did not directly affect hepatic insulin signaling, suggesting that the metabolic effects of ß-catenin occurred via a parallel pathway. Hepatic expression of key glycolytic and lipogenic genes was higher in HFD-fed TG and lower in KO mice compared with wild-type mice. KO mice also exhibited defective hepatic fatty acid oxidation and fasting ketogenesis. Hepatic levels of hypoxia inducible factor-1α, an oxygen-sensitive transcriptional regulator of glycolysis and a known ß-catenin binding partner, were higher in HFD-fed TG and lower in KO mice. KO mice had attenuated perivenous hypoxia, suggesting disruption of the normal sinusoidal oxygen gradient, a major determinant of liver carbohydrate and liver metabolism. Canonical Wnt signaling in hepatocytes is essential for the development of diet-induced fatty liver and obesity.

Association between specific IgE to Staphylococcus aureus enterotoxins A and B and asthma control.

BACKGROUND: Recent studies have found that serum levels of Staphylococcus aureus enterotoxin (SE)-IgE are higher in patients with severe asthma compared with patients with nonsevere asthma. However, the association between SE-IgE and asthma control is not fully understood. Furthermore, SEA and SEB were the first reported SEs and subdivided into different groups. The influences of SEA-IgE and SEB-IgE on asthma control have not been elucidated. OBJECTIVE: To determine the relevance of SEA- and SEB-IgE in patients with adult asthma and to investigate the association of SEA-IgE, SEB-IgE, and asthma control, respectively. METHODS: The serum concentrations of SEA- and SEB-IgE in 172 adults with asthma were measured with a fluorescent enzyme immunoassay. RESULTS: The prevalence of SEA- and SEB-IgE was 16.2% and 22.1%, respectively. Total IgE levels and the prevalence of atopic dermatitis were higher in SEA-IgE- and SEB-IgE-positive patients than in SEA-IgE- and SEB-IgE-negative patients, respectively; more SEA-IgE- and SEB-IgE-positive patients owned pets. Sensitization to SEA was associated with a younger mean age and a younger mean age at asthma onset. Multiple regression analysis indicated an association between total IgE levels and SEB-IgE. The prevalence of poorly uncontrolled asthma was significantly higher in SEA-IgE-positive patients than in SEA-IgE-negative patients. In addition, fractional exhaled nitric oxide levels were higher in SEA-IgE-positive patients than in SEA-IgE-negative patients. Logistic regression analysis also identified an association between SEA-IgE and poor asthma control. CONCLUSION: Our findings indicate that sensitization to SE, in particular SEA rather than SEB, is associated with poor asthma control in adults with asthma.

Early jejunostomy creation in cases of isolated hypoganglionosis: verification of our own experience based on a national survey.

PURPOSE: Isolated hypoganglionosis (IH) is a rare disease, with few well-established therapeutic strategies. This study aims to verify our preliminary therapeutic strategies developed to date in a comparison with data obtained from a nationwide survey of congenital-type IH. METHODS: Of the 90 registered IH cases assessed in a survey of Japanese pediatric surgical departments, 40 patients who had initially undergone jejunostomy (JE) and 41 treated with ileostomy (IL) were analyzed. Thirteen patients with JE sites located less than 50 cm from the ligament of Treitz were defined as having undergone upper jejunostomy (UJE). Postsurgical plain abdominal X-ray findings and survival rates, estimated using the Kaplan-Meier method, were used to evaluate improvements following stoma creation. RESULTS: Improvements in bowel obstruction were observed in significantly more UJE patients (9/13) than non-UJE patients [20/63 (22 JE and 41 IL cases); p = 0.01]. Furthermore, the JE patients demonstrated a significantly higher survival rate than the IL patients (p = 0.01). Following the completion of the 10-year follow-up period, three JE patients died after undergoing massive bowel resection. CONCLUSIONS: To manage IH successfully, patients should undergo JE less than 50 cm from the ligament of Treitz during the neonatal period. Properly managing the distal intestines is important for achieving long-term survival.

Longitudinal increase in total IgE levels in patients with adult asthma: an association with poor asthma control.

BACKGROUND: Immunoglobulin (Ig) E is well-known to play a critical role in allergic diseases. We investigated the association between longitudinal change in total IgE level and the asthma control in patients with adult asthma. METHODS: For this retrospective study, 154 patients with asthma aged 21-82 years were recruited from the allergy and pulmonary units of the Showa University Hospital. Data on longitudinal changes in IgE over the preceding 10 years were collected and logarithmically transformed. Associations between longitudinal change in IgE and clinical characteristics including asthma control test (ACT) score, asthma control, pulmonary function test, and antigen specific IgE, were assessed. RESULTS: Patients with increased IgE tended to have significantly higher mean age, more episodes of acute exacerbation within a year, lower ACT scores, and used oral corticosteroids more frequently than those with decreased or unchanged IgE. The prevalence of uncontrolled asthma was higher in patients with increased IgE than in those with decreased or unchanged IgE. Mean %FEV1 and FEV1% were lower in patients with increased IgE than in those with decreased or unchanged IgE. Moreover, the prevalence of Aspergillus-specific IgE was higher in patients with increased IgE than in those with decreased or unchanged IgE. CONCLUSIONS: These data suggest that a longitudinal increase in total IgE is associated with both poor asthma control and Aspergillus-specific IgE in patients with adult asthma.

Cinematic magnetic resonance enterography for non-organic abdominal pain in infants and children.

BACKGROUND: Recurrent non-organic abdominal pain is the most commonly diagnosed medical problem in children. However, excluding small bowel disease remains a challenge. We evaluated our exclusion criteria for organic small intestinal diseases in pediatric patients with recurrent non-organic abdominal pain using cinematic magnetic resonance (cine-MR) enterography. METHODS: The non-intestinal organic (non-IO) group as classified by the Rome III criteria system and the intestinal organic (IO) group consisted of 81 and 19 patients, with 35 and 12 male and 46 and 7 female patients with an age range of 5-18 and 4-15 years (average 10.5 and 10.5 years), respectively. Cine-MR enterography was performed by dynamically balanced first-field-echo imaging with thick-slice water-selective excitation without breath holding. In our original small intestinal motility test, cine-MR enterography was taken at three different times (fasting state [P1], immediately after [P2] and 30 min after [P3] drinking liquid material), with images taken sequentially for 5 min at each time-point to evaluate the motion of water in the gastrointestinal tract. Positive findings for organic intestinal problems were concluded when persistent visible intestinal loops appeared in both the P1 and P2 phases. RESULTS: Cine-MR enterography showed 6/81 (7.4%) and 18/19 (94.7%) (P < 0.01) positive cases of organic intestinal problems in the non-IO and IO groups, respectively. Positive and negative predictive values of this examination were 78.3% and 97.4%, respectively. CONCLUSIONS: The unique capabilities of cine-MR enterography technology in this clinical setting render it an important additional diagnostic tool when specific disease management issues must be addressed.

Catheter-related bloodstream infection in patients with motility disorder of the alimentary tract.

PURPOSE: Catheter-related bloodstream infection (CRBSI) is a serious complication associated with parenteral nutrition (PN). We retrospectively examined the features of CRBSI in patients with motility disorder (MD) by reviewing medical records. METHODS: Patients who received PN for more than 100 days in our hospital between January 2009 and September 2013 were reviewed. They were divided into two groups based on the presence or absence of MD. The frequency of CRBSI and the pathogenic organisms detected were compared. Statistical analysis was performed with the Mann-Whitney U test or Fisher's exact test. P < 0.05 was considered significant. RESULTS: Six patients had MD (MD group) and four patients had short bowels without MD (SB group). The median frequencies of CRBSI were 12.6 per 1,000 catheter-days in the MD group and 2.3 in the SB group (P = 0.027). The percentage of Gram-negative bacilli in all pathogenic organisms was 61% in the MD group and 22% in the SB group (P = 0.036). CONCLUSION: We found CRBSI was more frequent and Gram-negative bacilli were more common in patients with MD. Stasis in the alimentary tract and subsequent bacterial overgrowth appear to be risk factors for CRBSI. Therefore, it is crucial to seek treatments not to cause intestinal stasis.