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THE JOURNAL OF THE JAPAN PEDIATRIC SOCIETY
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Vol.121, No.9, September 2017
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Review
Title
Advances in Understanding and Treatment of Sepsis
Author
Yu Inata
Department of Intensive Care Medicine, Osaka Women's and Children's Hospital
Abstract
Sepsis, a life-threatening organ dysfunction caused by a dysregulated host response to an infection, is a serious condition with high morbidity and mortality even in the current era of advanced medicine. The widespread adoption of sepsis definitions and guidelines and the implementation of sepsis bundles have led to a significant decrease in mortality. Further efforts are being made to implement even faster initiation of sepsis treatment, for example, by deploying prehospital treatment and rapid response systems. Moreover, the recent development of the Japanese Guidelines for the Management of Sepsis 2016, which include a pediatric chapter, holds promise for further improving the rapid recognition and treatment of sepsis in children. Drug development for sepsis, on the other hand, has been largely unsuccessful. One of the main reasons for this disappointment is the fact that sepsis is a highly heterogeneous condition; the pathophysiology of sepsis differs among the septic patients due to the heterogeneity in the individual host response to infection and it varies even in each individual due to the dynamic temporal change of transcriptomic response to infection. Given its heterogeneity, the sepsis field has increasingly seen the application of precision medicine, in which treatment strategy could be tailored based on the disease endotype defined by molecular-biological profiles and prognostic prediction. Furthermore, enrichment strategy, i.e., the selection of patients in whom an intervention is more likely to be effective, has begun to be applied to sepsis clinical trials. With the increase of sequelae and readmissions among pediatric sepsis survivors, pediatricians are expected to play a larger role in long-term as well as acute management of pediatric sepsis.
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Original Article
Title
Intravenous Metronidazole Usage in Japanese Children
Author
Takayuki Yamanaka1)2) Kenta Ito2)3) and Yuho Horikoshi2)
1)Niigata City General Hospital
2)Division of Infectious Diseases, Department of Pediatrics, Tokyo Metropolitan Children's Medical Center
3)Aichi Children's Health and Medical Center
Abstract
Although metronidazole is used for anaerobic infections among children in many countries, intravenous metronidazole is not approved for pediatric use in Japan. Moreover, intravenous metronidazole was recently approved in 2015 and pediatric experience is limited in Japan. We retrospectively assessed the use of intravenous metronidazole in Japanese children. Clinical efficacy and adverse events after metronidazole injection were evaluated. From October 2014 to July 2015, 29 hospitalized cases were included in the study. The clinical efficacy rate was 93% (27/29). One or more adverse events were identified in 45% of cases. The most common adverse event was laboratory abnormality (11/29, 38%), followed by gastrointestinal symptoms (9/29, 31%). Almost all adverse events were mild, but one adverse event required discontinuation of metronidazole because of leukopenia. In conclusion, intravenous metronidazole was effective in most of our pediatric cases without significant adverse events. This intravenous anti-anaerobic agent is a good alternative to avoid usage of broad spectrum antibiotics such as carbapenems.
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Original Article
Title
Antibody Response with Routine Two-dose Varicella Vaccination
Author
Takao Ozaki Naoko Nishimura Kensei Gotoh and Koji Takemoto
Department of Pediatrics, Konan Kosei Hospital
Abstract
In October 2014, the schedule of varicella vaccination in Japan was changed from a voluntary single dose to a routine two-dose vaccination. To verify the immunogenicity of the new two-dose vaccination schedule, we investigated the antibody response.
From October 2014 to February 2016, varicella vaccine was administered twice to 28 healthy children. The mean age at initial immunization was 1.4 years and the mean age at the time of the second dose was 2.0 years. The median interval between the two doses was 207 days. In the children vaccinated according to this two-dose schedule, antibody titers were measured using an IAHA assay and a gpELISA just before and 4-6 weeks after each inoculation.
The IAHA antibody positive rate was 0% before the initial dose of the vaccine and increased to 70.4% after vaccination, while the gpELISA antibody-positive rate was 7.1% before the first dose and rose to 78.6% after vaccination. Before the second dose of the vaccine, the IAHA antibody-positive rate was significantly lower than after the first dose, but the gpELISA antibody positive rate did not decline. After the second dose, the IAHA and gpELISA antibody positive rates were both 100% and were both significantly higher than after the first dose. After the second dose, the mean IAHA antibody titer (Log2) was 6.9 and the mean gpELISA antibody titer (Log10) was 4.0. These titers showed a significant increase compared with the mean antibody titers after the first dose. In conclusion, it was shown that the antibody response with the routine two-dose varicella vaccination was good.
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Original Article
Title
Evaluation of the Rome III Criteria Questionnaire for Diagnosis of Functional Constipation in Japanese Children
Author
Maiko Tatsuki1) Reiko Hatori1) Miwako Nakano2) Takashi Ishige1) Yuki Ideno3) Takeshi Tomomasa4) and Hirokazu Arakawa1)
1)Department of Pediatrics, Gunma University Graduate School of Medicine
2)Department of Pediatric Surgery, Saitama City Hospital
3)Gunma University Initiative for Advanced Research
4)Pal Children's Clinic
Abstract
Accurate diagnosis and early intervention for patients with pediatric functional constipation (FC) is important to improve prognosis. The Rome III criteria have been widely used as a diagnostic tool in adult patients with functional gastrointestinal disorders but have not been validated in Japanese children. The aim of this study was to investigate the validity of the Rome III criteria for pediatric FC in Japan.
In this study, 398 children, aged 0-15 years, who were diagnosed as having FC by pediatric gastroenterologists through comprehensive history taking and physical examination were enrolled. A questionnaire was created by using the Rome III criteria for FC, Patients were defined as having FC when they had two or more symptoms described in the Rome III criteria. In addition, rectal bleeding at the time of defecation was also investigated on the patients in this study.
Seventy-six percent of the patients had painful defecation or hard bowel movements. Thirty-three percent of the patients had rectal bleeding from defecation. Fifty-three percent of infants (< 18 months), 77% of children between 18 months and 4 years, and 82% of children over 4 years fulfilled the Rome III diagnostic criteria for FC. When rectal bleeding was added to the criteria for FC, the diagnosis rates increased to 64%, 83%, and 85%, respectively.
In conclusion, the Rome III criteria questionnaire diagnosed 74% of the total constipated children. Rectal bleeding should also be taken into account in childhood FC.
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Original Article
Title
Lidocaine Adrenaline Tetracaine Compound Solution (LAT Solution) for Relief of Wound Pain: Its Efficacy and Safety
Author
Yusuke Tokida Yusuke Hagiwara and Nobuaki Inoue
Division of Pediatric Emergency Medicine, Tokyo Metropolitan Children's Medical Center
Abstract
Purpose: The efficacy of lidocaine-adrenaline-tetracaine compound solution (LAT solution) for relief from pain caused by lacerations has been reported worldwide. The present study is the first to assess the efficacy and safety of LAT solution in Japan.
Method: Patients aged 8 to 15 years who visited our emergency room between December 2014 and March 2016 for the treatment of lacerations requiring local anesthetic injection were prospectively enrolled. Cotton balls saturated with LAT solution formulated by our in-house pharmacy were applied to the wounds. The primary outcome was set as the difference in the degree of pain measured by a 100 mm Visual Analogue Scale before and after application of the solution. Adverse events occurring at the time of treatment and suture removal were also assessed.
Results: Fifty-one of 157 eligible patients (33%) were enrolled. The mean pain severity before and after application of the LAT solution was 45 mm (95% CI: 38 mm-51 mm) and 18 mm (95% CI: 13 mm-23 mm), respectively. The mean reduction in pain was statistically significant at 27 mm (95% CI: 20 mm-33 mm; p<0.0001). Application of the solution to wounds allowed physicians to complete treatment without additional injections of local anesthetics in 69% of the subjects. No obvious adverse event was observed in any of the subjects.
Conclusion: The LAT solution formulated by our in-house pharmacy was effective in relieving pain in patients with lacerations and was safe for use with children. Almost 70% of the subjects required no additional injection of local anesthetics.
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Case Report
Title
Transient Symptomatic Thiamine Deficiency in Two Extremely Premature Infants
Author
Masakazu Egashira1) Tomoko Egashira1) Kayo Koga1) Akinori Shichijo1) Fumiya Miyamura1) Sayuri Nishikawa1) Etsuo Naito2) Yuki Hasegawa3) Seiji Yamaguchi3) and Toshimitsu Takayanagi1)
1)Department of Pediatrics, National Hospital Organization, Saga Hospital
2)Department of Pediatrics, Japanese Red Cross Tokushima Hinomine Rehabilitation Center for People with Disabilities
3)Department of Pediatrics, Shimane University Faculty of Medicine
Abstract
We reported two infants complicated with severe lactic acidosis beyond the early neonatal period. Their enteral feeding was established within 10 days after birth, but lactic acidosis was gradually aggravated. Crisis of lactic acidosis was recognized in both infants, showing pH 7.030, BE -20 mmol/l, lactate 112 mg/dl in case 1, pH 7.263, BE -12.2 mmol/l, lactate 105 mg/dl in case 2. Intravenous administration of compound vitamin B was effective. Urine gas-chromatography mass spectrometry in the acute condition demonstrated excessive excretion of branched-chain alpha-keto acid, 2-oxoglutaric acid as well as pyruvate and lactate. The findings suggested that these two cases had thiamine deficiency. Lactic acidemia did not relapse by daily thiamine supplementation. Finally, we made a diagnosis of transient thiamine deficiency in the two cases because lactic acidosis did not relapse after the cessation of thiamine administration. The pathophysiology of such a condition observed in ELBWI is still unknown. Possible mechanisms may include limited storage of thiamine during fetal growth restriction and insufficient supply of thiamine in the mother's breast milk, or insufficient activation enzyme of thiamine because of prematurity should be considered.
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Case Report
Title
A Case of Andersen-Tawil Syndrome Diagnosed by Taking a Disease-specific Medical History
Author
Mayumi Fusumae1)2) Chihiro Wada1)2) Yumi Daimon1)2) Kenichiro Tsunematsu1)2) Takashi Esaki1)2) Kenji Nanao1)2) and Hiroyuki Fukushima2)
1)Department of Pediatrics, Hino Municipal Hospital
2)Department of Pediatrics, Keio Universiy School of Medicine
Abstract
We encountered a 2-year-old girl diagnosed as having Andersen-Tawil syndrome after a chief complaint of gait disturbance. Andersen-Tawil syndrome is a rare, autosomal dominant inherited disorder characterized by the clinical triad of periodic paralysis, abnormal electrocardiogram with ventricular arrhythmias, and dysmorphic features. The phenotype and severity of this syndrome are known to be extremely variable.
The patient had a gait disturbance and hypokalemia, an abnormal electrocardiogram (abnormal U waves), and a dysmorphic face, suggesting the presence of Andersen-Tawil syndrome. With the possible diagnosis of this syndrome in mind, we repeated taking the patient's family history using specific key words. As a result, we discovered that her paternal aunt and grandmother had histories of a diagnosis of long QT syndrome. We confirmed the diagnosis using a gene analysis, in which a novel missense mutation in KCNJ2, the gene responsible for this syndrome, was identified in both the patient and her father.
In addition to the importance of a comprehensive medical history taking, this case report suggests that a careful history taking using specific key words could be useful for diagnosis, especially in cases suspected of having an inherited syndrome with low penetrance.
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Case Report
Title
Dysphonia and Dysphagia in a Patient with Juvenile Dermatomyositis
Author
Yutaro Imaichi Tetsuya Kibe and Takemasa Nomura
Department of Pediatrics, Seirei-Mikatahara General Hospital
Abstract
Dysphagia, which is a potentially life-threatening complication causing aspiration, reportedly occurs in 18-44% of pediatric patients with juvenile dermatomyositis (JDM). Nonetheless, there have been very few empirical reports [M2] in pediatric populations, probably due to the difficulty of assessing and managing dysphagia. Here, we report a 7-year-old boy with a diagnosis of JDM who developed dysphagia along with dysphonia after 10 days of prednisolone therapy, despite significant improvement of systemic muscular pain and weakness. A videofluoroscopic swallowing study (VFSS) revealed oropharyngeal contraction dysfunction, poor opening of the upper esophageal sphincter and silent aspiration while drinking thin liquids. We added a thickener to his drink along with additional pharmacotherapy, such as intravenous methylprednisolone pulse therapy, intravenous immunoglobulin, and methotrexate. His dysphagia improved gradually and thickener treatment was no longer necessary after about 3 months. Pediatricians should be aware that dysphagia and silent aspiration can occur in pediatric patients with JDM, and consider instrumental evaluation, such as VFSS, for the appropriate management of dysphagia.
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Case Report
Title
Pearson Syndrome with Hydrops Fetalis
Author
Tokiko Oshiro1) Satoru Hamada1) Yasutsugu Chinen1) Takeshi Yagi1) Jiro Miyamoto2) Nobuhiro Iida1) Hideki Goya1) Tomohide Yoshida1) and Nobuyuki Hyakuna1)
1)Department of Pediatrics, University of the Ryukyus
2)Osaka City General Hospital
Abstract
We report the case of a 3-month-old male infant who presented with hydrops fetalis and pancytopenia at birth, which was diagnosed as Pearson syndrome (PS). Although bone marrow cytological examination revealed hypocellularity alone on day 19 from birth, repeated bone marrow smear 3 months later showed dysplastic changes of megakaryocytes, ringed sideroblasts, and vacuolated progenitor cells. Based on the mitochondrial DNA analysis, resulting in a 4977-bp deletion, We definitively diagnosed PS. He needed frequent blood transfusions over a 14-month period, but eventually demonstrated spontaneous hematological improvement. As some reported PS cases were diagnosed with myelodysplastic syndrome or Diamond-Blackfan anemia at initial presentation, the findings of ringed sideroblasts and vacuolated progenitors in serial bone marrow evaluations are important. Although PS presenting with hydrops fetalis is rare, it should be differentiated from other congenital bone marrow failures. While hematological recovery with age has been reported, careful follow-up for potential failure of other organs is critical.
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Case Report
Title
A Female Child Diagnosed with Severe Hemophilia A Caused by Compound Heterozygosity for F8
Author
Ayumi Nogi1) Hiroshi Yoshihashi1)2) Tomu Kuchikata2) Yuya Saito3) Takashi Kaneko3) Masayo Kagami4) Tomoko Uehara5) Toshiki Takenouchi5) Kenjiro Kosaki5) and Hiroshi Hataya1)
1)Department of General Pediatrics, Tokyo Metropolitan Children's Medical Center
2)Department of Medical Genetics, Tokyo Metropolitan Children's Medical Center
3)Department of Hematology and Oncology, Tokyo Metropolitan Children's Medical Center
4)Department of Molecular Endocrinology, National Research Institute for Child Health and Development
5)Center for Medical Genetics, Keio University School of Medicine
Abstract
[Background] Most female carriers of hemophilia A, caused by pathogenic variants of the F8 gene inherited in an X-linked recessive manner, are commonly asymptomatic. However, a few symptomatic female carriers with severe hemophilia A have been reported. Herein, we present the clinical course and genetic analysis results in an affected female child.
[Case] A 4-year-old girl with no consanguinity was brought to the emergency department due to a large, subcutaneous, abdominal hematoma. Coagulation time was prolonged and coagulation factor VIII activity was significantly decreased, strongly suggesting severe hemophilia A. Genetic analysis of the F8 gene using next generation sequencing and Sanger validation, and an X chromosome inactivation assay based on Hpa II methylation analysis of a polymorphic short tandem repeat in the X-linked androgen receptor gene (AR) were performed. The genetic analysis results revealed pathogenic variants of F8 attributed to compound heterozygosity, including a paternal splicing variant (c.144-2A>G) and a maternal novel missense variant (c.1333G>C). We also found a skewed X chromosome inactivation pattern leading to preferential inactivation in the maternally-derived allele. The early, precise diagnosis of severe hemophilia A in females has contributed to good health care, provision of relevant information, and psychosocial support for both patients and their family. In females symptomatic for hemophilia A, the significance of patient education and genetic counseling for the future should also receive greater emphasis.
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Case Report
Title
Lysosomal Storage Disorders Presenting as Respiratory Problems: A Report of Two Cases
Author
Haruka Kuno1) Yuji Sugawara1) Takeshi Hasegawa1) Mika Okutsu1) Ryusuke Nambu2) Mitsuru Kubota3) Torayuki Okuyama4) and Shirou Tsuchiya1)
1)Department of Pediatrics, Soka Municipal Hospital
2)Devision of General Pediatrics, Saitama Children's Medical Center
3)Department of General Pediatrics, National Center for Child Health and Development
4)Center for Lysosomal Storage Disorder, Department of Clinical Laboratory Medicine, National Center for Child Health and Development
Abstract
Enzyme replacement therapy is reported to be effective for lysosomal storage disorders. However, early diagnosis and initiation of treatment are important because the therapy has poor efficacy in terms of reversing the changes in affected organs. We encountered two cases of lysosomal storage disorders presenting as respiratory problems. While one patient was given a diagnosis of type 2 Gaucher disease with inspiratory stridor, the other was given a diagnosis of mucopolysaccharidosis type 1 with snoring and obstructive sleep apnea. Lysosomal storage disorders present with diverse symptoms, and some patients present with chief complaints of nonspecific respiratory symptoms with a background of central nervous system symptoms and substrate accumulation. Herein, we provide information on this issue, with the aim of aiding general pediatricians in diagnosing this disorder.
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Case Report
Title
A Pediatric Case of Subglottic Laryngeal Abscess
Author
Shigeki Ishii1) Yuka Mihara1) Keigo Nakatani1) Kazunari Takamura2) Masako Harada2) and Kyouhei Kondo2)
1)Department of Pediatrics, Miyazaki Prefectural Miyazaki Hospital
2)Division of Pediatrics, Miyazaki University Hospital
Abstract
A 10-year-old healthy Chinese girl presented with a five-day history of fever, progressive swallowing pain, stridor, cough and mild respiratory distress at our emergency ward. Chest X-ray showed a steeple sign and infiltration on the left lower lung. Flexible laryngoscopy demonstrated mild narrowing of the airway, and slightly red and edematous arytenoid region without swelling of the epiglottis, vocal cord paralysis, tumor, nor foreign body. She was admitted to the hospital and received oxygen, inhalation of epinephrine, intravenous dexamethasone and antibiotics immediately under the clinical diagnosis of croup accompanied by pneumonia. Despite initial treatment, her upper respiratory symptoms progressed to respiratory distress. Computed tomography (CT) of the neck revealed the unexpected finding of narrowing of the airway oppressed by laryngeal mass. The patient was emergently transferred to a higher level of intensive care unit at the university hospital, and subglottic laryngeal abscess was subsequently diagnosed by contrast-enhanced CT. She received oral intubation to prevent airway obstruction and the abscess ultimately subsided with only administration of antibiotics for total 17 days without requiring drainage or incision. She was extubated on hospital day 7 and discharged on hospital day 14 without any sequelae.
Subglottic laryngeal abscess is extremely rare in the pediatric population and difficult to diagnose. However, pediatricians should be aware of this rare disease as one of the causes of upper airway obstruction. Rapid and accurate evaluation are needed because delayed diagnosis may cause suffocation and become fatal.
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Case Report
Title
Chronic Esophageal Foreign Bodies: Chief Presentation and Clinical Course
Author
Shoichiro Shirane1) Nao Tachibana2) Takatsugu Murakoshi2) Koji Komori3) Tomoo Miyakawa4) Naoki Shimizu5) and Hiroshi Hataya1)
1)Department of General Pediatrics, Tokyo Metropolitan Children's Medical Center
2)Department of Gastroenterology, Tokyo Metropolitan Children's Medical Center
3)Department of Surgery, Tokyo Metropolitan Children's Medical Center
4)Department of Respirology, Tokyo Metropolitan Children's Medical Center
5)Department of Emergency and Critical Care Medicine, Tokyo Metropolitan Children's Medical Center
Abstract
Most ingested foreign bodies are eventually excreted. In some cases, however, the object may remain in the esophagus and lead to severe, chronic complications. Chronic esophageal foreign bodies (CEFB), as such cases are known, are rare and not well-documented. We performed a review of 4 children presenting with CEFB who were admitted to Tokyo Metropolitan Children's Medical Center, to elucidate this condition's chief presentation and clinical course. Age at diagnosis ranged from 15 months to 67 months, while the interval from the first episode to diagnosis ranged from 6 months to 43 months. One patient presented an esophageal duplication cyst as an underlying illness. Three patients presented with a primary complaint of respiratory symptoms such as a wheeze or cough. One patient presented mainly with vomiting. All patients presented localized mediastinitis or a mediastinal abscess as a complication. There were 2 cases of tracheal perforation, 1 of which resulted in cardiopulmonary arrest due to severe tracheal stenosis. All of the foreign bodies were radiolucent plastic objects. Tracheal stenosis [o1] and deviation to the right were observed on a chest X-ray at diagnosis in 3 cases.
Patients with CEFB frequently present respiratory symptoms leading, erroneously, to treatment for asthma. Despite this unremarkable manifestation, CEFB can result in severe complications. When a patient with CEFB presents respiratory symptoms, a tracheal stenosis and deviation to the right on a chest X-ray may provide a diagnostic clue.
When patients presenting with respiratory symptoms have a chronic course or accompanying gastrointestinal symptoms, CEFB should be considered. If CEFB is suspected, a chest X-ray should be performed to determine if tracheal stenosis and deviation are present.
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