Comparison of early versus late addition of granulocyte and monocyte adsorption for incomplete remission induction in ulcerative colitis.

Background and aim: Ulcerative colitis (UC) is characterized by repeated relapse and remission. Because no fundamental therapeutic strategy has been established, the treatment goal is generally to maintain the remission phase for a long period after rapid remission induction. Granulocyte and monocyte adsorption (GMA) for UC is reportedly quite safe because it does not affect immunosuppression. Moreover, it is useful in combination with other remission induction therapy. The aim of this study was to evaluate the difference in efficacy by the timing of the addition of GMA with corticosteroids, calcineurin inhibitors, and anti-cytokine therapy for active UC. Methods: The study included 59 patients. Patients who started GMA of 5-11 days were in the early GMA combination group. Patients who started GMA 12 days or more were in the late GMA combination group. The primary endpoint was difference in the effect of additional GMA according to the timing of the intervention. The secondary endpoint was difference in the time to remission induction between the two groups. Results: Of the 32 early GMA group patients, 24 achieved remission induction. Of the 27 late group patients, 18 achieved remission induction. No significant difference in induction rates was found (P = 0.481). The early group had shorter mean time to remission induction (P < 0.001). Conclusions: In conclusion, results suggest that early addition of GMA might lead to earlier remission in patients who have had an inadequate response to remission induction therapy with corticosteroids, calcineurin inhibitors, and anti-cytokine therapy.

Pseudohypoparathyroidism type 1B with involuntary movements: a case report and literature review.

Pseudohypoparathyroidism (PHP) is a rare disorder characterized by convulsions, tetany, and sensory abnormalities caused by hypocalcemia due to parathyroid hormone (PTH) resistance. Only few patients present with involuntary movements. We report the case of a 7-yr-old girl with PHP and involuntary movements triggered by running. Initially, she was suspected of having paroxysmal kinesigenic dyskinesia and was treated with carbamazepine (CBZ). Involuntary movements were reduced. However, 2 months post-treatment, she experienced convulsions during a fever. Blood tests and brain computed tomography revealed hypocalcemia, hyperphosphatemia, elevated intact PTH, and calcifications in the frontal cortex and basal ganglia. The patient showed no features of Albright's hereditary osteodystrophy. The involuntary movements disappeared after the discontinuation of CBZ and initiation of calcium and active vitamin D preparations. Methylation-specific multiplex ligation-dependent probe amplification for the GNAS region and microsatellite analysis of chromosome 20 led to the diagnosis of PHP1B caused by epimutation. In 15 reported cases, with or without intracranial calcification, PHP-associated involuntary movements disappeared or became less severe with treatment for hypocalcemia; in eight of 11 cases, they were triggered by exercise or movement. PHP-associated hypocalcemia can trigger exercise-induced involuntary movements owing to lowered serum ionized calcium levels. In such patients, early blood tests are vital for the differential diagnosis of PHP.

Effects of COVID-19 pandemic-associated reduction in respiratory infections on infantile asthma development.

Background: It is speculated that the coronavirus disease 2019 (COVID-19) pandemic-associated reduction in the prevalence of respiratory tract infections has influenced the incidence of asthma in young children. Objectives: We investigated an association between the reduction in viral infections and the reduction in asthma in young children. Methods: The subjects were infants born in the early stages of the COVID-19 pandemic in Japan, which began in February 2020. A questionnaire survey related to asthma and allergy was conducted at 18 months and 3 years of age. These results were compared to those of age-matched infants during the nonpandemic period. Results: There were no epidemics of viral infectious diseases until the target child was 18 months old. At 18 months, the incidence of asthma/asthmatic bronchitis diagnosed by physicians in pandemic children was significantly lower than that in nonpandemic children. In 3-year-olds, no marked difference was observed between nonpandemic infants and pandemic children, except for an increase in respiratory syncytial virus infection in pandemic children. In a comparative study of the same children at ages 18 months and 3 years, an increased prevalence of asthma/asthmatic bronchitis was observed in pandemic children. Furthermore, the incidence of asthma after respiratory syncytial virus infection in pandemic infants was significantly lower than that in nonpandemic children. Conclusion: The COVID-19 pandemic-associated reduction in respiratory tract infections may have reduced the incidence of asthma in early childhood, and respiratory syncytial virus infection after 18 months of age had little effect on the onset of asthma. These results indicate the importance of preventing respiratory tract infections in early infancy.

A pediatric case of Burkitt's lymphoma with bile duct obstruction requiring surgical biliary reconstruction.

BACKGROUND: Biliary obstruction due to compression by a B-cell solid tumor occurs rarely. A few reports have described biliary reconstruction surgery for obstructive jaundice caused by Burkitt's lymphoma. However, there are no detailed reports on pediatric cases. We report a pediatric case of obstructive jaundice due to malignant lymphoma treated with biliary reconstruction surgery. CASE PRESENTATION: A 5-year-old girl presented to our hospital with a massive abdominal tumor that caused biliary stricture. Chemotherapy was initiated after an open tumor biopsy. However, endoscopic biliary stent placement was performed owing to elevated bilirubin levels. We treated the patient with chemotherapy for 9 months while endoscopically replacing the biliary stent every few months. She achieved complete tumor remission. However, sclerotic lymph nodes were persistent on the dorsal side of the cholecystic duct junction, and biliary stricture at the same site had changed to stent-dependent biliary obstruction. Therefore, we performed choledochojejunostomy and retrocolic Roux-en-Y reconstruction 15 months after initial admission. There were no postoperative complications or tumor recurrences, and the bilirubin level remained low. Histopathologically, the resected bile duct wall was fibrotic and thick, and the bile duct lumen narrowed. CONCLUSIONS: Biliary reconstruction is effective to achieve long-term biliary patency in pediatric patients with stent-dependent biliary obstruction due to malignant lymphoma. However, the decision on when to stop biliary stent replacement and proceed to biliary reconstruction surgery is a matter of debate. Further case studies are required to address this issue.

Prevalence and causes of chronic cough in Japan.

BACKGROUND: Chronic cough is one of the most common symptoms of respiratory diseases and can adversely affect patients' quality of life and interfere with social activities, resulting in a significant social burden. A survey is required to elucidate the frequency and treatment effect of chronic cough. However, clinical studies that cover all of Japan have not yet been conducted. METHODS: Patients who presented with a cough that lasted longer than 8 weeks and visited the respiratory clinics or hospitals affiliated with the Japan Cough Society during the 2-year study period were registered. RESULTS: A total of 379 patients were enrolled, and those who did not meet the definition of chronic cough were excluded. A total of 334 patients were analyzed: 201 patients had a single cause, and 113 patients had two or more causes. The main causative diseases were cough variant asthma in 92 patients, sinobronchial syndrome (SBS) in 36 patients, atopic cough in 31 patients, and gastroesophageal reflux (GER)-associated cough in 10 patients. The time required to treat undiagnosed patients and those with SBS was significantly longer and the treatment success rate for GER-associated cough was considerably poor. CONCLUSIONS: We confirmed that the main causes of chronic cough were cough variant asthma, SBS, atopic cough, and their complications. We also showed that complicated GER-associated cough was more likely to become refractory. This is the first nationwide study in Japan of the causes and treatment effects of chronic cough.

Using a survey, analyzing the current situation of allergic March in elementary and junior high school students of oyama and tochigi cities, Japan.

BACKGROUND: Over the past few decades, allergic diseases have become more prevalent and impact around 20% of the global population. There is clinical significance of allergic march as it places a burden on the quality of life of children and their families. OBJECTIVES: To assess the current situation of allergy conditions experienced by children attending elementary and junior high schools in Oyama and Tochigi cities, Japan. METHODS: A letter was sent to parents informing them about an opt-in online survey concerning children's allergies along with a weblink and a QR code. A video explained the survey process and informed parents that their replies could not be retracted. Parents who had watched the explanation video and answered yes to participating were considered to have provided consent for the survey. RESULTS: A total of 2038 valid replies were gathered. Allergic Rhinitis was the most commonly diagnosed allergy, followed by Asthma, Food Allergy, and Atopic Dermatitis. Around 70% of the children were affected by the allergies, of whom half had been affected by multiple allergies. Most children affected by Atopic Dermatitis, Food Allergy or Asthma were affected by other allergies. Atopic Dermatitis and Food Allergy were mostly diagnosed before Asthma and Allergic Rhinitis. CONCLUSIONS: Children who are diagnosed with either Atopic Dermatitis or a Food Allergy will likely be affected by other allergies later in life. Allergic march perpetuated an earlier peak diagnosis incident rate for allergic rhinitis. Allergic Rhinitis can occur independently from other allergies compared to Atopic Dermatitis, Food Allergy and Asthma.

Acute Pancreatitis Leading to the Diagnosis of Presymptomatic Crohn's Disease: A Pediatric Case Report.

A 14-year-old boy presented with fever and abdominal pain and was diagnosed with acute pancreatitis based on computed tomography findings. The patient had neither diarrhea nor bloody stool but was diagnosed with microcytic anemia. Endoscopic examination revealed a cobblestone pattern and longitudinal ulcer scars in the jejunum. However, no abnormal findings were observed in the ileum or colon. Endoscopic ultrasound-guided fine-needle aspiration was performed from pancreatic body-tail. Pathological examination revealed no evidence of autoimmune pancreatitis (AIP). It was unclear from pathological examination whether idiopathic pancreatitis had self-limitedly improved or whether it was AIP localized to the pancreatic head. The patient was diagnosed with asymptomatic small-bowel Crohn's disease (CD), which may have been two unrelated events of acute pancreatitis. Acute pancreatitis may precede a diagnosis of inflammatory bowel disease. CD with only jejunal involvement (Montreal classification L4) is extremely rare, and we were able to diagnose it early.

Pediatric IgA-Dominant Infection-Related Glomerulonephritis.

The concept of infection-related glomerulonephritis (IRGN) has been introduced as adults diagnosed with glomerulonephritis often have coexisting active infections. Furthermore, IgA-dominant IRGN is associated with staphylococcal infections in adults with comorbidities, which often progress to end-stage renal disease. Little is known about IgA-dominant IRGN in children, and no consensus for a management strategy of this condition has been reached. We describe the case of a 9-year-old boy with IgA-dominant IRGN that was diagnosed using specific staining for nephritis-associated plasmin receptor (NAPlr)/plasmin activity and galactose-deficient IgA1 (Gd-IgA1), a marker of IgA nephropathy. The patient was successfully treated using a combination of prednisolone, mizoribine (an immunosuppressive drug), and lisinopril (an angiotensin-converting enzyme inhibitor) and three courses of methylprednisolone pulse therapy. The patient was admitted to our hospital with generalized edema, gross hematuria, proteinuria, hypertension, and renal dysfunction. Hypocomplementemia contributed to a diagnosis of IRGN, although the causative organism was unknown. A renal biopsy performed when the patient presented with nephrotic syndrome showed IgA deposition, positive staining for NAPlr, and negative staining for Gd-IgA1, in addition to findings consistent with IRGN, leading to a pathologic diagnosis of IgA-dominant IRGN. The histological staining for NAPlr/plasmin activity and Gd-IgA1, together with clinical symptoms, could be helpful for diagnosing IgA-dominant IRGN. Our findings indicate that otherwise healthy children can also develop IgA-dominant IRGN. Therefore, early diagnosis and aggressive treatment should be considered when IgA-dominant IRGN is suspected to avoid the possibility of incomplete recovery of renal function.

Lung sound analysis for predicting recurrent wheezing in preschool children.

Background: In young healthy children, assessing airflow limitation may be difficult because of narrowing of the airways, which is a pathology of asthma, and responsiveness to bronchodilators. Objective: We investigated whether lung sound analysis could predict the development of recurrent wheezing (RW), which is one of the signs of asthma. Methods: In healthy children aged 3 to 24 months, we recorded and analyzed lung sounds before and after inhalation of bronchodilators and conducted a questionnaire survey. The children were followed up and assessed for the development of RW at age 3 years. Results: Of the 62 patients analyzed, 19 (30.6%) developed RW. The parameters ratio of power and frequency at 50% of the highest frequency of the dB power spectrum (RPF50) and ratio of power and frequency at 75% of the highest frequency of the dB power spectrum (RPF75), calculated by lung sound analysis, were lower in the RW group, with odds ratios of 0.77 (95% CI = 0.61-0.98) and 0.81 (95% CI = 0.66-0.99), respectively. The rate of change of lung sound analysis parameters after bronchodilator inhalation did not differ among the participants as a group; however, in the subgroup of children with a history of atopic dermatitis, the fourth area under the curve (B4) divided by the total area under the curve of 100 Hz to the highest frequency of the dB power spectrum (AT) and difference between the values of the ratio of power and frequency at 50% of the highest frequency of the dB power spectrum (ΔRPF50) were elevated in the RW group (P = .015 and P = .041, respectively). In the subgroup of children with total a IgE level greater than 20 kUA/L, the sensitivities and specificities for predicting the development of RW were 85.7% (95% CI = 48.7-99.3) and 68.8% (95% CI = 44.4-85.8), respectively, when the cutoff value of ΔRPF50 was set at 10.5%. Conclusion: The method of lung sound analysis allows noninvasive assessment of the airway, including airway hypersensitivity, in young children and may predict the risk of development of RW.

Palivizumab prophylaxis in preterm infants and subsequent wheezing/asthma: 10-year follow-up study.

BACKGROUND: Respiratory syncytial virus (RSV) causes not only infantile recurrent wheezing but also the development of asthma. To investigate whether palivizumab, an anti-RSV monoclonal antibody, prophylaxis given to preterm infants during the first RSV season reduces the incidence of subsequent recurrent wheezing and/or development of asthma, at 10 years of age. METHODS: We conducted an observational prospective multicenter (52 registered hospitals in Japan) case-control study in preterm infants with a gestational age between 33 and 35 weeks followed for 6 years. During the 2007-2008 RSV season, the decision to administer palivizumab was made based on standard medical practice (SCELIA study). Here, we followed these subjects until 10 years of age. Parents of study subjects reported the patients' physician's assessment of recurrent wheezing/asthma, using a report card and a novel mobile phone-based reporting system using the internet. The relationship between RSV infection and asthma development, as well as the relationship between other factors and asthma development, were investigated. RESULTS: Of 154 preterm infants enrolled, 113 received palivizumab during the first year of life. At 10 years, although both recurrent wheezing and development of asthma were not significantly different between the treated and untreated groups, maternal smoking with aeroallergen sensitization of the patients was significantly correlated with physician-diagnosed asthma. CONCLUSIONS: In contrast to the prior study results at 6 years, by 10 years palivizumab prophylaxis had no impact on recurrent wheezing or asthma, but there was a significant correlation between maternal passive smoking with aeroallergen sensitization and development of asthma by 10 years of age.

Utility of MRI in diagnosis and treatment of acute focal bacterial nephritis with abscess formation in a paediatric patient.

Contrast-enhanced CT is the gold standard for the diagnosis of acute focal bacterial nephritis (AFBN). However, owing to radiation exposure and the possibility of contrast agent-induced side effects, contrast-enhanced CT is not always recommended for children. A paediatric patient presenting with a 1-week history of fever was admitted to our hospital. After a urine culture detected Escherichia coli, antimicrobials were administered; however, the fever had not resolved by the third day of hospitalisation. Renal diffusion-weighted MRI was performed and showed multiple wedge-shaped areas of high signal intensity in the right kidney. Additionally, the same site showed an area of low signal intensity in the apparent diffusion coefficient, and a diagnosis of AFBN with abscess was made. A chronic-phase technetium-99m-labelled dimercaptosuccinic acid renal scintigraphy was performed, but there was no renal scarring. MRI may be a more suitable tool for diagnosing AFBN given no radiation exposure.

Natural history of eosinophil­derived neurotoxin levels and the onset of allergic airway disease in preschool children.

'Atopic march' is the progression of allergic conditions through infancy and childhood. The present study investigated the association between blood eosinophil-derived neurotoxin (EDN) levels in preschool children with food allergy (FA) or atopic dermatitis (AD) and the onset of allergic airway disease [bronchial asthma (BA), allergic rhinitis (AR)]. A total of 123 children below the age of 1 year were enrolled in the present study, along with controls (n=37). Blood specimens were taken, serum EDN levels were measured and immunoglobulin E was quantified. Finally, a total of 86 subjects were analyzed. EDN values were measured at 3 time-points: before 1 year of age, before 2 years of age and before 3 years of age. The EDN levels were initially similar between those patients who did and those who did not develop allergic airway disease but then markedly diverged at the 2-year time-point (226.6 vs. 65.0 ng/ml; P<0.01) and remained divergent at the 3-year time-point (173.9 vs. 62.7 ng/ml; P<0.01). EDN levels prior to diagnosis were compared between the two groups and they were much higher in the Onset group (n=10) compared to the Non-onset group (n=67) (171.2±34.28 vs. 81.3±10.02 ng/ml; P=0.003), with 4 cases of BA and 6 cases of AR in the Onset group. After diagnosis, EDN levels were compared twice: i) At 1 and 2 years of age; and ii) 1 and 3 years of age. A significant difference was found only in the comparison at 2 years (P=0.001). In conclusion, young children with elevated EDN levels during the FA/AD disease period were more likely to develop allergic airway disease (BA, AR) in their first three years of life. A factor leading to this progression may be increased eosinophil activity.

Association between residents' scholarly activities and publication requirement policy.

BACKGROUND: Scholarship is recognized as important in residency training worldwide. The Japan Pediatric Society (JPS) enacted a reform in 2017 to require publication of an article as a prerequisite for taking the board certification test, with the goal of increasing scholarly activity. METHODS: The purpose of this study was to provide a detailed description of the trends in residents' scholarly activities related to the JPS reform. A secondary analysis was performed on the cross-sectional database of pediatrics residents who took the certification test in 2015-2018. RESULTS: The enrolled participants were 2399 residents of which 79.7% passed the test. Publication of any type of article increased significantly (21%-22% to 100%; 0.1 to 0.3/person-year) after the implementation of the JPS reform, whereas academic presentations did not (89% to 91%; 1.2 to 1.3/person-year), both in terms of the percentage of the number of those who created them and the average rate of research production. Not only Japanese articles (11%-13% to 49%-53%; 0.04 to 0.15-0.17/person-year) or case reports (10%-14% to 51%-52%; 0.03-0.05 to 0.16-0.17/person-year), but also English articles (4%-5% to 15%-16%; 0.01-0.02 to 0.05/person-year) and original articles (5% to 11%-17%; 0.01 to 0.03-0.05/person-year) increased significantly. The number of each type of article publication was correlated with success in the board certification test (odds ratio 1.5-1.8). CONCLUSIONS: Scholarly activities of pediatrics residents were enhanced by the JPS implementation of the article requirement policy, which is crucial to fostering a scholarly culture. The most efficient measures to promote scholarship need to be persistently investigated.