Gut microbiota and fecal metabolites in sustained unresponsiveness by oral immunotherapy in school-age children with cow's milk allergy.

BACKGROUND: Oral immunotherapy (OIT) can ameliorate cow's milk allergy (CMA); however, the achievement of sustained unresponsiveness (SU) is challenging. Regarding the pathogenesis of CMA, recent studies have shown the importance of gut microbiota (Mb) and fecal water-soluble metabolites (WSMs), which prompted us to determine the change in clinical and gut environmental factors important for acquiring SU after OIT for CMA. METHODS: We conducted an ancillary cohort study of a multicenter randomized, parallel-group, delayed-start design study on 32 school-age children with IgE-mediated CMA who underwent OIT for 13 months. We defined SU as the ability to consume cow's milk exceeding the target dose in a double-blind placebo-controlled food challenge after OIT followed by a 2-week-avoidance. We longitudinally collected 175 fecal specimens and clustered the microbiome and metabolome data into 29 Mb- and 12 WSM-modules. RESULTS: During OIT, immunological factors improved in all participants. However, of the 32 participants, 4 withdrew because of adverse events, and only 7 were judged SU. Gut environmental factors shifted during OIT, but only in the beginning, and returned to the baseline at the end. Of these factors, milk- and casein-specific IgE and the Bifidobacterium-dominant module were associated with SU (milk- and casein-specific IgE; OR for 10 kUA/L increments, 0.67 and 0.66; 95%CI, 0.41-0.93 and 0.42-0.90; Bifidobacterium-dominant module; OR for 0.01 increments, 1.40; 95%CI, 1.10-2.03), and these associations were observed until the end of OIT. CONCLUSIONS: In this study, we identified the clinical and gut environmental factors associated with SU acquisition in CM-OIT.

[Sixteen Cases of Appendiceal Mucinous Neoplasm].

Appendiceal mucinous neoplasm is a relatively rare disease. It is classified as mucinous adenocarcinoma(MACA)and low- grade appendiceal mucinous neoplasm(LAMN). We retrospectively evaluated 16 cases of appendiceal mucinous neoplasm (LAMN: 13 cases, MACA: 3 cases)that were surgically resected in our hospital between January 2010 and July 2021. There were 7 men and 9 women, with a median age of 61 years(27-85 years). The most common chief complaint was abdominal pain(12 patients), while 3 cases were incidental findings following medical checkups for other diseases and without a chief complaint. Colonoscopy was performed for 9 cases. Of these, 5 revealed abnormal findings. The preoperative diagnosis was appendicitis in 7 patients and appendiceal tumor in 8 patients. The surgical procedures were planned for 8 cases and performed as emergencies in 8 cases. The procedures included laparoscopic surgery(n=6)and laparotomy(n=10). The resection range included appendectomy(n=9), partial cecal resection(n=4), and ileocecal resection(n=3). Surgical margins were negative in all cases. Metastases were not observed in patients who underwent lymph node dissections (2 patients with MACA and 1 patient with LAMN). The median follow-up was 17 months(1-43 months). Recurrence including peritoneal pseudomyxoma was not detected in any of the patients.

Anti-Ascaris IgE as a Risk Factor for Asthma Symptoms among 5-Year-Old Children in Rural Bangladesh with Even Decreased Ascaris Infection Prevalence.

BACKGROUND: Epidemiological studies have indicated that anti-Ascaris IgE enhances asthma and allergies under specific conditions although the association between them is still controversial. The association of anti-Ascaris IgE with increased asthma symptoms among children from a general population with a mild to moderate Ascaris infection prevalence was investigated. METHODS: A total of 126 children aged 5 years with wheezing during the previous year and 110 children who did not have wheezing were selected randomly from the rural service area of the International Centre for Diarrhoeal Disease Research, Bangladesh. Serum levels of total, anti-Ascaris, anti-Dermatophagoides pteronyssinus, and anti-cockroach IgEs were tested, and their risks for wheezing were analyzed. The wheezing children were then classified by hierarchical cluster analysis to investigate the contribution of anti-Ascaris IgE to wheezing. RESULTS: The anti-Ascaris IgE levels in wheezing and never-wheezing children were 1.07 and 0.65 UA/mL, and it contributed to 11% of wheezing in children. Anti-Ascaris IgE was significantly associated with wheezing (odds ratio [OR] per loge increment: 1.37 [95% CI: 1.01-1.87], p = 0.046). The ORs, which were adjusted for sex, parental asthma, pneumonia history, helminth infections, Haemophilus influenzae type B combination vaccination, antibiotic use during infancy, and total and specific IgE levels, increased even when only children with more specific symptoms of asthma were included in the analysis. Namely, the ORs for wheezing with sleep disturbance, four or more attacks, and wheezing with speech difficulties during the previous 1 year were OR = 1.44/loge increment [95% CI: 1.01-2.07], OR = 1.90/loge increment [95% CI: 1.11-3.25], and OR = 1.78/loge increment [95% CI: 1.01-3.14], respectively. CONCLUSIONS: The anti-Ascaris IgE levels in wheezing and never-wheezing children in the current study significantly decreased concurrently with Ascaris infection prevalence compared with their corresponding values in 2001. The contribution of anti-Ascaris IgE to wheezing also dropped from 26% in 2001 to 11% in the current study. Despite significant decreases in the levels and the seroprevalence and its contribution to wheezing, anti-Ascaris IgE remained significantly associated with increased risk of wheezing. Anti-Ascaris IgE significantly increased the risk of wheezing in a general population with a mild to moderate Ascaris infection prevalence, suggesting robustness as a risk factor and a possible dose-response relationship.

Impact of Haemophilus influenzae type b combination vaccination on asthma symptoms and pneumonia in 5-year-old children in rural Bangladesh: a longitudinal study and comparison with a previous cross-sectional study.

BACKGROUND: Although the prevalence of bronchial asthma has been increasing worldwide since the 1970's, the prevalence among 5-year-old children was significantly lower in 2016 than in 2001 in rural Bangladesh. We aimed to determine whether the Haemophilus influenzae type b (Hib) combination vaccination (without booster) started in 2009 contributed to this decrease. METHODS: A case-control study was conducted among 1658 randomly selected 5-year-old children from Matlab, Bangladesh. Data on wheezing were collected using the International Study of Asthma and Allergies in Childhood questionnaire. The vaccination data were collected from the records of the Matlab Health and Demographic Surveillance System, while data on pneumonia were obtained from the clinical records of Matlab Hospital. Adjusted odds ratios (aORs) were calculated for the risk for wheezing. The reduction rate was calculated to determine the impact of the vaccination on pneumonia history between the present study and our previous study conducted in 2001 by using the following formula: (percentage of pneumonia cases in 2001 - percentage of pneumonia cases in 2016)/(percentage of pneumonia cases in 2001) times 100 (%). RESULTS: Hib combination vaccination was a protecting factor against wheezing (aOR: 0.50; p = 0.010), while pneumonia at 1, 2, 3-4 years of age were risk factors for wheezing (aOR: 2.86, 3.19, 2.86; p = 0.046, 0.030, 0.030, respectively). The history of pneumonia was significantly lower in the 2016 study participants than those in 2001 both in the overall cohort and the wheezing group (paired t-test: p = 0.012, p < 0.001, respectively). Whereas the history of pneumonia decreased when the children grew older in the 2001 overall cohort, it peaked at the age of 2 years in 2016 wheezing group. The reduction rate decreased when children grew older in both the overall cohort and the wheezing group, however, it decreased faster in the wheezing group. CONCLUSIONS: Hib combination vaccination was a protective factor against wheezing in 0-year-old children. However, the effects of vaccination might have attenuated at the ages of 1-4 years, because no booster dose was administered. The addition of a booster dose might further decrease the prevalence of asthma and wheezing.

[Case Report of an Elderly Patient with Interstitial Pneumonia Caused by the Administration of Trastuzumab plus Anastrozole for the Treatment of Inflammatory Breast Cancer].

An 83‒year‒old woman received trastuzumab plus anastrozole as first‒line chemotherapy for inflammatory breast cancer in her left breast. Following the treatment, the induration and redness in her breast gradually improved; however, 2 days after receiving the 5th course of chemotherapy, she developed dyspnea and was referred to the emergency room. Her SpO2 was 88%; her KL‒6 level had increased to 2,613 U/mL; and a chest CT scan showed ground‒glass opacity in the bilateral lung fields, yielding a diagnosis of interstitial pneumonia requiring steroid pulse therapy. The dyspnea improved immediately after steroid administration, and the patient was discharged 20 days after hospitalization. Thereafter, the steroid dosage was gradually lowered to 5 mg/day. We discontinued steroid therapy after a chest CT confirmed the reduction of ground‒glass opacity. However, she was later readmitted for interstitial pneumonia for which she was readministered steroid pulse therapy. Trastuzumab‒induced interstitial pneumonia is rare, but we must be aware of the possibility that patients may develop severe pulmonary disorders or experience cardiotoxic effects.

[A Case of an Elderly Patient with Multiple Lung Metastases of Postoperative Pancreatic Cancer in Whom Lung Metastases Were Controlled by Biweekly Dose-Down Administration of Gemcitabine].

An 80-year-old woman was diagnosed with pancreatic head cancer, and pancreaticoduodenectomy was performed. Twelve months after the operation, chest CT scans showed the presence ofmultiple nodules in both the lungs. Because ofthe potential negative side effects of anti-cancer drugs, the patient underwent chemotherapy with dose-down biweekly adminis- tration ofgemcitabine (1,000mg/day/body≒750mg/m2. Chest CT examination every 2-3 months revealed no rapid increase in multiple tumors. Nineteen months after starting gemcitabine therapy, there was an elevation in tumor marker and a gradual increase in lung metastases. We performed combination chemotherapy with nab-paclitaxel. However, owing to side effects, only 2 courses of nab-paclitaxel were administered, and the therapy was switched to only gemcitabine administration. Later, respiratory distress accompanied by pleural effusion developed, and the patient died of the original disease 27 months after recurrence. Here, we report a case ofan elderly patient with multiple lung metastases ofpancreatic cancer in whom lung metastases were controlled by biweekly dose-down administration of gemcitabine.

[A Case of Anastomotic Stage â Cecal Cancer Recurrence after Functional End-To-End Anastomosis].

An 83-year-old woman was referred to our hospital for cecal cancer, and ileocecal resection(D3 lymph node resection) with functional end-to-end anastomosis. Since the tumor was of histological Stage Ⅰ, no adjuvant chemotherapy was performed. One year and 9 months after the operation, an anastomotic recurrence was identified alongthe staple line using colonoscopy. We performed a resection of the anastomotic recurrence. At present, 6 months after the second operation, the patient remains in good health without evidence of recurrence. A few cases of anastomotic recurrence after surgery for Stage Ⅰcolon cancer have been reported in the literature available in Japanese. We report a rare case of an anastomotic recurrence of Stage Ⅰ cancer after functional end-to-end anastomosis.

[Usefulness of CT Colonography for a Patient with Three Synchronous Primary Descending Colon Cancers].

An 81-year-old woman presented with melena. Colonoscopy showed descending colon cancer, but the oral side of the tumor was excluded from observation because of easy bleeding related to the stenosis. CT colonography to evaluate the oral end of the intestine revealed 2 lesions in addition to the lesion observed on endoscopy. Before the surgery, the patient was suspected to have 3 synchronous primary descending colon cancers and underwent left hemicolectomy. Because CT colonography revealed synchronous multiple colon cancers in the patient, we performed surgery in one stage.

Desensitization to a whole egg by rush oral immunotherapy improves the quality of life of guardians: A multicenter, randomized, parallel-group, delayed-start design study.

BACKGROUND: Patients with food allergies and their families have a significantly reduced health-related quality of life (QOL). METHODS: We performed a multicenter, randomized, parallel-group, delayed-start design study to clarify the efficacy and safety of rush oral immunotherapy (rOIT) and its impact on the participants' daily life and their guardians (UMIN000003943). Forty-five participants were randomly divided into an early-start group and a late-start group. The early-start group received rOIT for 3 months, while the late-start group continued the egg elimination diet (control). In the next stage, both groups received OIT until all participants had finished 12 months of maintenance OIT. RESULTS: The ratio of the participants in whom an increase of the TD was achieved in the first stage was significantly higher in the early-start group (87.0%), than in the late-start group (22.7%). The QOL of the guardians in the early-start group significantly improved after the first stage (65.2%), in comparison to the late-start group (31.8%). During 12 months of rOIT, the serum ovomucoid-specific IgE levels, the percentage of CD203c+ basophils upon stimulation with egg white, and the wheal size to egg white were decreased, while the serum ovomucoid-specific IgG4 levels were increased. However, approximately 80% of the participants in the early-start group showed an allergic reaction during the first stage of the study, whereas none of the patients in the late-start group experienced an allergic reaction. CONCLUSIONS: rOIT induced desensitization to egg and thus improved the QOL of guardians; however, the participants experienced frequent allergic reactions due to the treatment.

[A Case of a One-Stage Resection and Anastomosis Procedure for a Descending Colon Cancer Ileus after Decompression with a Trans-Nasal Ileus Tube].

A 72-year-old man presented to our hospital with a chief complaint of constipation and hiccup. Computed tomography revealed a colonic obstruction due to descending colon cancer, and a transnasal ileus tube was inserted. On the 2nd day of hospitalization, we attempted transanal drainage, but it was difficult to cannulate. Abdominal findings and inflammatory response were normal; thus, the transanal drainage procedure was followed by only decompression with a transnasal ileus tube. On the 13th day of hospitalization, the tip of the ileus tube reached the vicinity of the occluded area. We performed a one-stage resection and anastomosis procedure. The patient was discharged from the hospital on the 16th postoperative day. Patients with left-sided colorectal cancer ileus are often immediately treated with colostomy when trans-anal decompression is difficult. We report a case of one-stage resection and anastomosis procedure for a descending colon cancer ileus after decompression with a transnasal ileus tube.

[A Case of Intractable Pain Caused by Retroperitoneal Primary Unknown Cancer Recurrence That Was Improved by Palliative Cyberknife Therapy].

A 79-year-old man was diagnosed with retroperitoneal primary unknown cancer recurrence who underwent open fenestration and drainage(because radical cure resection is difficult). Two years after the fenestration, the patient developed severe hip pain and numbness of the right lower limb. Abdominal CT revealed a cystic tumor recurrence extending from the lower abdomen to the right perineum. We selected a palliative cyberknife therapy for pain control. Fractionated radiation using a cyberknife was administered for 5 days(25 Gy in 5 fractions). The hip pain was relieved, and a CT scan showed a reduction in size of the perineal tumor after the cyberknife treatment. The cyberknife therapy may be an effective and promising palliative treatment for patients with pelvic recurrence.

Surgical outcome of laparoscopic hepatic resection for hepatocellular carcinoma: A matched case-control study with propensity score matching.

BACKGROUND: Although the number of reports on laparoscopic hepatic resection (LHR) has increased, studies of long-term outcomes regarding tumor recurrence and patient survival compared to the conventional open approach are limited. We evaluated the long-term survival and feasibility of LHR in patients with hepatocellular carcinoma (HCC). PATIENTS AND METHODS: A retrospective analysis was performed on the clinical data of patients who underwent hepatic resection for primary HCC between August 2000 and December 2013. The patients were divided into the LHR or open hepatic resection (OHR) groups. To control for selection bias in the two groups, propensity score matching was used at a 1:1 ratio based on the following covariates: Child-Pugh grade, tumour size, tumour number and tumour location. Following propensity score matching, thirty patients were included in the LHR group and thirty were included in the OHR group. RESULTS: The respective disease-free survival rates at 1 year, 3 years and 5 years were 78.4%, 61.1% and 38.9%, respectively, for the LHR group, and 89.3%, 57.5% and 47.9%, respectively, for the OHR group (P = 0.89). Also, the overall survival rates at 1 year, 3 years and 5 years were 96.4%, 68.2% and 62.5%, respectively, for the LHR group and 100.0%, 95.8% and 72.3%, respectively, for the OHR group (P = 0.44). CONCLUSIONS: According to our study, using propensity score matching, LHR for HCC is safe, feasible and comparative, with good oncologic results.

Eosinophilic gastroenteritis in a patient with Bruton's tyrosine kinase deficiency.

Eosinophilic gastrointestinal diseases (EGID) are relatively rare diseases characterized by eosinophilic infiltration of the gastrointestinal tract resulting in various gastrointestinal symptoms. EGID are often caused by allergic reactions or systemic eosinophilic disorders, but their comorbidity with Bruton's tyrosine kinase (BTK) deficiency has not been previously documented. Here, we report a case of eosinophilic gastroenteritis (EG) in a patient with BTK deficiency. Despite adequate replacement immunoglobulin (Ig) therapy, trough serum IgG was not maintained. To identify the underlying cause of the low trough level and chronic diarrhea, the intestine was investigated on endoscopy. We also screened for the variable number of tandem repeat polymorphism in FCGRT. Genetic analysis could not explain the low trough IgG, but endoscopy indicated eosinophilic enterocolitis. EG may be an important differential diagnosis when primary immunodeficiency patients have chronic diarrhea or continued low serum IgG.

Anti-Ascaris immunoglobulin E associated with bronchial hyper-reactivity in 9-year-old rural Bangladeshi children.

BACKGROUND: Studies have addressed the immunomodulatory effects of helminths and their protective effects upon asthma. However, anti-Ascaris IgE has been reported to be associated with an increased risk of asthma symptoms. We examined the association between serum levels of anti-Ascaris IgE and bronchial hyper-responsiveness (BHR) in children living in rural Bangladesh. METHODS: Serum anti-Ascaris IgE level was measured and the BHR test done in 158 children aged 9 years selected randomly from a general population of 1705 in the Matlab Health and Demographic Surveillance Area of the International Centre for Diarrhoeal Disease Research, Bangladesh. We investigated wheezing symptoms using a questionnaire from the International Study of Asthma and Allergies in Childhood. BHR tests were successfully done on 152 children (108 'current wheezers'; 44 'never-wheezers'). We examined the association between anti-Ascaris IgE level and wheezing and BHR using multiple logistic regression analyses. RESULTS: Of 108 current-wheezers, 59 were BHR-positive; of 44 never-wheezers, 32 were BHR-negative. Mean anti-Ascaris IgE levels were significantly higher (12.51 UA/ml; 95% confidence interval (CI), 9.21-17.00) in children with current wheezing with BHR-positive than in those of never-wheezers with BHR-negative (3.89; 2.65-5.70; t test, p < 0.001). A BHR-positive test was independently associated with anti-Ascaris IgE levels with an odds ratio (OR) = 7.30 [95% CI, 2.28-23.33], p = 0.001 when adjusted for total IgE, anti-Dermatophagoides pteronyssinus IgE, pneumonia history, parental asthma, Trichuris infection, forced expiratory volume in one second, eosinophilic leukocyte count, and sex. CONCLUSIONS: Anti-Ascaris IgE level is associated with an increased risk of BHR among 9-year-old rural Bangladeshi children.

[A Case of Gastric Cancer Associated with Sjögren's Syndrome and Interstitial Pneumonia].

A 77-year-old man presented with poor appetite and dyspnea. A gastroendoscopy showed an advanced gastric cancer and a CT scan demonstrated diffuse interstitial infiltrative shadows in both lungs. Laboratory data showed high level of anti-SSA and anti-SSB antibodies, suggestive of interstitial pneumonia associated with Sjögren's syndrome. Although the levels of KL-6 and SP-D, markers of interstitial pneumonia, decreased after steroid and immunosuppressive therapy, the CT findings of interstitial pneumonia showed no remarkable change. Surgery was performed 2 months after the administration of prednisolone since the respiratory function had improved, allowing the administration of general anesthesia. A CT scan revealed remarkable improvement of the lung lesions after the surgery. Therefore, it is likely that Sjögren's syndrome and interstitial pneumonia manifested as paraneoplastic syndromes in the presented case.

Risks and prevention of severe RS virus infection among children with immunodeficiency and Down's syndrome.

By the age of two years, almost all infants are infected with the Respiratory syncytial virus (RSV). One of the main causes of hospitalizations for bronchiolitis and pneumonia at this age is RSV infection. In addition to well-known risks for severe RSV disease, such as prematurity, bronchopulmonary dysplasia and congenital heart disease, immunodeficiencies, chromosomal abnormalities such as Down's syndrome or neuromuscular diseases have also been identified as risks. While the medical needs for RSV prevention in these risk groups are high, clinical evidence to support this is limited. Palivizumab was recently approved in Japan for prophylaxis in children with immunodeficiency or Down's syndrome. A clinical guidance protocol for the prevention of RSV infection using Palivizumab in these risk groups is provided here on the basis of a review of the available literature and on expert opinion. Thus, the present article reviews the published literature related to RSV infections in infants and children with immunodeficiencies or Down's syndrome in order to outline the risks, pathology and physiology of severe RSV disease in these patient groups. The purpose of this article is to facilitate understanding of the medical scientific bases for the clinical guidance.

Japanese pediatric guideline for the treatment and management of bronchial asthma 2012.

A new version of the Japanese pediatric guideline for the treatment and management of bronchial asthma was published in Japanese at the end of 2011. The guideline sets the pragmatic goal for clinicians treating childhood asthma as maintaining a "well-controlled level" for an extended period in which the child patient can lead a trouble-free daily life, not forgetting the ultimate goal of obtaining remission and/or cure. Important factors in the attainment of the pragmatic goal are: (i) appropriate use of anti-inflammatory drugs; (ii) elimination of environmental risk factors; and (iii) educational and enlightening activities for the patient and caregivers regarding adequate asthma management in daily life. The well-controlled level refers to a symptom-free state in which no transient coughs, wheezing, dyspnea or other symptoms associated with bronchial asthma are present, even for a short period of time. As was the case in the previous versions of the guideline, asthmatic children younger than 2 years of age are defined as infantile asthma patients. Special attention is paid to these patients in the new guideline: they often have rapid exacerbation and easily present chronic asthmatic conditions after the disease is established.

Immunization of rabbits with nematode Ascaris lumbricoides antigens induces antibodies cross-reactive to house dust mite Dermatophagoides farinae antigens.

There are controversial reports on the relationship between helminthic infection and allergic diseases. Although IgE cross-reactivity between nematode Ascaris antigens and house dust-mite allergens in allergic patients have been reported, whether Ascaris or the mite is the primary sensitizer remains unknown. Here we found that immunization of naïve animals with Ascaris lumbricoides (Al) antigens induced production of antibodies cross-reactive to mite antigens from Dermatophagoides farinae (Df). Sera from Bangladeshi children showed IgE reactivity to Ascaris and mite extracts. IgG from rabbits immunized with Al extract exhibited reactivity to Df antigens. Treatment of the anti-Al antibody with Df antigen-coupled beads eliminated the reactivity to Df antigens. In immunoblot analysis, an approximately 100-kDa Df band was the most reactive to anti-Al IgG. The present study is the first step towards the establishment of animal models to study the relationship between Ascaris infection and mite-induced allergic diseases.

Hospitalizations associated with pandemic influenza A (H1N1) 2009 in asthmatic children in Japan.

BACKGROUND: The pandemic influenza A (H1N1) 2009 [pdm (H1N1) 2009] spread through the world in 2009, producing a serious epidemic in Japan. Since it was suggested early that asthma is a risk factor for an increased severity of the infection, the Japanese Society of Pediatric Allergy and Clinical Immunology (JSPACI) organized a working group for countermeasures, and investigated asthmatic children admitted to the hospitals for pdm (H1N1) 2009 infection. METHODS: An appeal was made on the home page of the JSPACI to medical practitioners to input clinical information about asthmatic and non-asthmatic children (0-19 years) admitted to the hospital with pdm (H1N1) 2009 infection. RESULTS: A total of 862 children (390 with asthma, and 472 without asthma) from 61 medical centers were registered, and the data of 333 asthmatic children and 388 non-asthmatic children in all were entered in the analyses. The mean age was 7.4 ± 2.9 years in the asthma group and 6.9 ± 3.8 years in the non-asthma group. The percentage of children admitted for respiratory symptoms was significantly higher in the asthma group than in the non-asthma group (p < 0.001). There was no significant difference in the frequency of admission to the ICU or need for mechanical ventilation support between the two groups. No definite trend was detected in the relationship between the severity of asthma and the intensity of asthma attack. Antiviral drugs were administered within 24 hours in about 85% of the patients in both groups. CONCLUSIONS: Asthma may not be a risk factor for severe pdm (H1N1) 2009 infection in children.