Actinomycosis of the Middle Ear in Children: Case Report and Literature Review.

Actinomycosis of the middle ear is a rare infectious disease, characterized by a slowly progressive clinical course. We report the case of a 9-year-old girl with recurrent otitis media, who presented with clinical signs of a cholesteatoma. She underwent tympanoplasty and ossiculoplasty. After surgery, actinomycosis was diagnosed histologically. We also provide a review of 16 published pediatric cases.

Retropharyngeal abscess due to Staphylococcus aureus complicated by bilateral neck and intraabdominal abscesses in an immunocompetent infant.

Retropharyngeal abscess is a serious condition, with potentially high morbidity and mortality if not detected early. The patient, a previously healthy 10-month-old girl, was admitted due to retropharyngeal and bilateral cervical lymph node abscesses. The neck abscesses recurred, despite surgical drainage and treatment with intravenous ampicillin-sulbactam. Methicillin-susceptible Staphylococcus aureus was identified from the abscess culture. A mesenteric abscess was also found during treatment. Intravenous ampicillin-sulbactam was switched to intravenous cephazolin and metronidazole, and the patient was successfully treated without further surgical intervention. No recurrence was observed throughout the 1-year follow-up period. Immune function testing, especially neutrophil function, did not reveal any abnormality. Neck abscesses can spread to the deep or shallow neck spaces directly or through the lymph node chains, even in immunocompetent hosts. Clinicians should consider deep neck infection in patients with cervical lymph node abscess, even if they present without the typical signs and symptoms of retropharyngeal abscess.

Efficacy, safety, and pharmacokinetics of oral valganciclovir in patients with congenital cytomegalovirus infection.

OBJECTIVES: Valganciclovir (VGCV) has been shown to improve sensorineural hearing loss (SNHL) and neurological outcomes in patients with neonatal symptomatic congenital cytomegalovirus (cCMV) infection. However, reports on the pharmacokinetics, efficacy and safety of oral VGCV are limited. The aim of this study is to evaluate the pharmacokinetics of VGCV for use in the treatment of cCMV. METHODS: This was a single-center, retrospective observational study conducted at Saitama Children's Medical Center in Japan between 2012 and 2017. CMV DNA copy number, maximum plasma VGCV concentration (Cmax), and adverse events (ADEs) during treatment were evaluated. RESULTS: A total of 26 patients with cCMV who received VGCV were included in this study. The median age at VGCV initiation was 9.5 months (range 0-46). Twenty-one patients (81%) had SNHL at baseline. Of these, five patients (19%) presented with improved SNHL, and none experienced worsened SNHL during treatment. The mean VGCV Cmax was 3.5 µg/mL (range 2-5.3), with no significant variation among individual values, and the values were maintained during treatment. Furthermore, there were no correlations between the Cmax values and age, sex, SNHL improvement or ADEs. Neutropenia (<1000/mm3) was observed in six patients (23%); however, no serious ADEs occurred. CONCLUSIONS: VGCV prevented the progression of SNHL without serious ADEs due to its stable pharmacokinetics. This study provides safety and tolerability of VGCV for the treatment of cCMV patients.

Preventive Effect of Tonsillectomy on Recurrence of Henoch-Schönlein Purpura Nephritis after Intravenous Methylprednisolone Pulse Therapy.

Henoch-Schönlein purpura (HSP) is regarded as a benign and self-limiting vasculitis characterized by purpura, arthritis, and gastrointestinal symptoms; however, about one third of the patients develop HSP nephritis (HSPN), the most serious long-term complication. Since 2013, we have proposed that tonsillectomy in addition to intravenous methylprednisolone pulse therapy (IVMP) be performed in all patients with HSPN, similar to immunoglobulin A nephropathy (IgAN) patients because both diseases are considered to a share common pathogenesis. Herein, we retrospectively reviewed the clinical courses of 71 Japanese children with HSPN (34 boys; median age at diagnosis, 6.7 years; median follow-up period, 5.6 years) who had received initial treatment with IVMP (15-20 mg/kg; on 3 consecutive days/week for 3 weeks) followed by oral prednisolone (initially 1 mg/kg; tapered off within 12 months) and achieved clinical remission (i.e., disappearance of both proteinuria and hematuria). The patients were divided into two groups: 31 patients receiving tonsillectomy after IVMP between 2013 and 2017 (tonsillectomy group) and 40 patients receiving IVMP monotherapy between 2003 and 2012 (IVMP group). For the 2 years after IVMP therapy, the rate of HSPN recurrence (i.e., persistent proteinuria combined with hematuria requiring additional treatments) after clinical remission was significantly lower in the tonsillectomy group than the IVMP group (0% vs. 19%, P < 0.05). Despite the short follow-up period in the tonsillectomy group, this study provides the evidence that tonsillectomy may be beneficial for preventing recurrence of HSPN from clinical remission with IVMP therapy in Japanese children.

10-year follow-up of congenital cytomegalovirus infection complicated with severe neurological findings in infancy: a case report.

BACKGROUND: Congenital cytomegalovirus (cCMV) infection leads to sensorineural hearing loss (SNHL) and neurodevelopmental delays. However, the long-term outcomes of cCMV infection with severe neurological manifestations in infancy remain unclear. CASE PRESENTATION: The patient was a one-month-old girl visited owing to abnormalities in neonatal hearing screening. Central nervous system involvement including intracranial calcification and extensive white matter abnormalities was identified. Right SNHL (50 dB) was detected by auditory brain response (ABR) testing. The cause of her hearing loss was determined to be cCMV infection by polymerase chain reaction (PCR) using a dried blood spot. At 1.5 months of age, the patient was treated with intravenous ganciclovir (GCV) for 5 weeks followed by oral valganciclovir (VGCV) for an additional 6 weeks. Cytomegalovirus (CMV) loads in her urine continued to be detected until she was 10 years old. Fortunately, during this time, her right hearing loss did not deteriorate, and her left hearing remained normal. Furthermore, the extensive abnormal areas of white matter observed at 1 month of age mostly disappeared by the time the patient was 9 years old. Her neurodevelopmental score was normal, and motor milestones were not delayed as of 10 years of age. CONCLUSIONS: Here, we report the 10-year follow-up of a patient with cCMV who showed normal neurodevelopment, no progression of hearing loss, and ameliorating magnetic resonance imaging (MRI) findings, despite having various complications and severe neurological findings during infancy.

Screening for seemingly healthy newborns with congenital cytomegalovirus infection by quantitative real-time polymerase chain reaction using newborn urine: an observational study.

OBJECTIVE: Approximately 8-10% of newborns with asymptomatic congenital cytomegalovirus (cCMV) infection develop sensorineural hearing loss (SNHL). However, the relationship between CMV load, SNHL and central nervous system (CNS) damage in cCMV infection remains unclear. This study aimed to examine the relationship between urinary CMV load, SNHL and CNS damage in newborns with cCMV infection. STUDY DESIGN: The study included 23 368 newborns from two maternity hospitals in Saitama Prefecture, Japan. Urine screening for cCMV infection (quantitative real-time PCR) and newborn hearing screening (automated auditory brainstem response (AABR) testing) were conducted within 5 days of birth to examine the incidence of cCMV infection and SNHL, respectively. CNS damage was assessed by MRI of cCMV-infected newborns. RESULTS: The incidence of cCMV infection was 60/23 368 (0.257%; 95% CI 0.192% to 0.322%). The geometric mean urinary CMV DNA copy number in newborns with cCMV was 1.79×106 copies/mL (95% CI 7.97×105 to 4.02×106). AABR testing revealed abnormalities in 171 of the 22 229 (0.769%) newborns whose parents approved hearing screening. Of these 171 newborns, 22 had SNHL (12.9%), and 5 of these 22 were infected with cCMV (22.7%). Newborns with both cCMV and SNHL had a higher urinary CMV DNA copy number than newborns with cCMV without SNHL (p=0.036). MRI revealed CNS damage, including white matter abnormalities, in 83.0% of newborns with cCMV. Moreover, newborns with CNS damage had a significantly greater urinary CMV load than newborns without CNS damage (p=0.013). CONCLUSIONS: We determined the incidence of cCMV infection and urinary CMV DNA copy number in seemingly healthy newborns from two hospitals in Saitama Prefecture. SNHL and CNS damage were associated with urinary CMV DNA copy number. Quantification of urinary CMV load may effectively predict the incidence of late-onset SNHL and neurodevelopmental disorders.

Cisplatin-induced hearing loss: the need for a long-term evaluating system.

Cisplatin is an effective chemotherapeutic agent against pediatric cancers; however, ototoxicity is a concern. This study describes the frequency, severity, and clinical course of hearing loss in Japanese pediatric patients treated with cisplatin-based multimodal therapy. A total of 55 children who received cisplatin-based therapy from 1983 to 2012 underwent audiologic evaluations. Data were analyzed to determine the onset, time-to-progression, and severity of hearing loss. Thirty-five patients, 12 of 16 older patients (4 y or older), and 23 of 39 younger patients (under 4 y), including 7 of 8 patients treated with cisplatin, carboplatin, and radiotherapy, developed hearing loss. Ten of 18 patients who received a cumulative cisplatin dose of <360 mg/m developed hearing loss at a minimum dose of 200 mg/m. Median time to onset after the last cisplatin dose was 71 days; 6 patients developed hearing loss after ≥2 years. Four patients required hearing aids, 6 patients developed progressive hearing loss with time, and 4 patients exhibited persistent hearing failure at low frequencies. Risk factors for acquired hearing loss and its severity may be associated with a combination of factors such as cisplatin and carboplatin therapy, radiotherapy, age at diagnosis, and genetic background. Our results suggested that all pediatric patients treated with cisplatin would have their hearing evaluated regularly, irrespective of the cumulative cisplatin dose as a suggestion, and that further prospective studies regarding ototoxicity including genetic polymorphisms analysis were required.

Effects of oral care in Down syndrome children with obstructive sleep apnea.

Down syndrome (DS) children with sleep apnea often present with oral breathing associated with nasal obstruction. This causes the oral cavity and pharynx to become dry. We describe the treatment of three DS children with sleep apnea who were treated using products for oral dryness. Snoring disappeared after treatment in two of the children and apnea disappeared in all three. The symptoms of a reddened oral mucosa and coated tongue disappeared in all three DS children. Saliva pH testing demonstrated that the pH value increased in all of the children after treatment. These results indicate that oral care can improve the oral hygiene status of DS children, and that proper oral care can help prevent oral mucosal dryness and thereby reduce sleep apnea symptoms.

Mycophenolic acid inhibits syncytium formation accompanied by reduction of gp120 expression.

Mycophenolic acid (MPA) was identified as an inhibitor of syncytium formation during the screening of human immunodeficiency virus (HIV) entry inhibitors. MPA is a well-known inhibitor of inosine monophosphate dehydrogenase and anti-HIV activity has been reported in vitro and in vivo. MPA inhibited syncytium formation in T cell-tropic and macrophage-tropic systems with IC50 values of 0.1 and 0.5 microM, respectively. The reduction of HIV gp120 expression by MPA (1.0 microM) was observed by use of Western blot analysis. Furthermore, the addition of guanosine restored both syncytium formation and gp120 expression in the presence of MPA. These results suggest that MPA inhibits not only reverse transcription by depletion of a substrate, GTP, as has been reported, but also syncytium formation through a predominant reduction in the amount of gp120 that is vigorously expressed in the above transformed cells and may be in HIV-infected cells.