Digital clubbing without hypoxia for lysinuric protein intolerance.

Digital clubbing is characterized by bulbous enlargement of the terminal segments of the fingers. Hypotheses including hypoxia have been proposed for the pathogenesis of digital clubbing, but the exact pathogenesis of digital clubbing is still uncertain. Lysinuric protein intolerance (LPI) is caused by pathogenic variants in SLC7A7 and is often associated with interstitial lung disease. Previously two patients of LPI with digital clubbing but without hypoxia have been reported. It is unclear whether digital clubbing in LPI is secondary to hypoxia or directly related to SLC7A7 deficiency. Here we report a 6-year-old Japanese boy presented with digital clubbing without hypoxia. He had episodic vomiting, each episode consisting of a single vomiting event occurring once a month, and his growth had been delayed. He had interstitial lung disease and hepatomegaly. He had compound heterozygous pathogenic variants in the SLC7A7, leading to the diagnosis of LPI. Together with the two previously reported patients mentioned above, we conclude that digital clubbing can occur in the absence of hypoxia. Digital clubbing in the absence of hypoxia has been observed in two genetic disorders related to prostaglandin (PG) E2, HPGD and SLCO2A1. PGE2 synthesis is primarily regulated by the cyclooxygenase 2, which plays a critical role in the control of inflammation. A high urine PGE level in the patient was compatible with the notion that PGE2 production may be increased in LPI. The occurrence of digital clubbing in the absence of hypoxia in LPI patients with SLC7A7 may be attributed to the mechanism of increased PGE2 production.

Assessing clinical benefits of live-attenuated vaccination in post-liver transplant patients: Analysis of breakthrough infections and natural boosters.

Recently, live-attenuated measles, rubella, varicella, and mumps vaccines have been administered to carefully selected post-liver transplant patients. Although attention has been focused on post-vaccination antibody titers and adverse events, the real-life clinical benefits remain unclear. A comprehensive analysis of breakthrough infections and natural boosters (asymptomatic cases with significant elevation in virus antibody titers) following immunization post-liver transplantation was conducted from 2002-2023, exploring the timing, frequency, correlation with domestic outbreaks, and degree of antibody elevation. During the median 10-year observation period among 68 post-liver transplant patients, breakthrough infections occurred only in chickenpox, with 7 mild cases (1 episode/64 person-years). A total of 59 natural booster episodes (1, 5, 20, and 33 for measles, rubella, chickenpox, and mumps, respectively) were observed, with incidence rates of 1 per 569, 110, 22, and 17 person-years, respectively. The timing of natural boosters closely correlated with domestic outbreaks (P < .05 in chickenpox and mumps), influenced by local vaccine coverage. The degree of antibody elevation was significantly higher in individuals with breakthrough infections than in those with natural boosters (P < .05). These findings suggest that immunization with live-attenuated vaccines for post-liver transplant patients has demonstrated clinical benefits. Furthermore, mass vaccination has a positive impact on post-transplant patient outcomes.

An atypical surge in RSV infections among children in Saitama, Japan in 2021.

Background: In 2021, atypical seasonal respiratory syncytial virus (RSV) outbreaks were observed in several countries. However, the peak, duration, and severity of these outbreaks have not been assessed. Methods: Data were collected from almost all facilities with pediatric wards in Saitama Prefecture, Japan. Variables included the weekly number of patients admitted with RSV infection, their age, and the number of patients who required intubation. The average weekly admission rates (number of patients admitted divided by the number of hospitals) were compared by pre-pandemic year (2018 and 2019) and 2021, using analysis of variance. Results: In 2021, 1354 patients were admitted with RSV infection. The median age of the patients was < 12 months. The admission rate peaked around week 30. The slope of the peak in 2021 was markedly steeper than in the previous years. The mean weekly admission rate did not differ significantly between 2018, 2019, and 2021 (p = 0.77). The proportions of intubated patients did not differ significantly over the 4 years (2018-2021, p = 0.68). Conclusion: The overall number of RSV admissions and intubation rate in 2021 were similar to those in pre-pandemic years.

Total synthesis of (-)-domoic acid, a potent ionotropic glutamate receptor agonist and the key compound in oceanic harmful algal blooms.

The stereo-controlled total synthesis of (-)-domoic acid is described. The critical construction of the C1'-C2' Z-configuration was accomplished by taking advantage of an unsaturated lactam structure. The side chain fragment was introduced in the final stages of synthesis through a modified Julia-Kocienski reaction, aiming for its efficient derivatization.

Extended-Spectrum ß-Lactamase-Producing Escherichia coli in Neonates and Listeria monocytogenes in Young Children with Bacterial Meningitis in Japan.

Nationwide surveillance of pediatric bacterial meningitis in Japan from 2019 to 2021 revealed two uncommon situations not covered by the recommended empiric treatment that were not rare in Japan, namely, extended-spectrum ß-lactamase-producing-producing Escherichia coli in neonates and Listeria monocytogenes in children older than 1 month.

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.

Periodic fever, aphthous stomatitis, pharyngitis, and cervical adenitis syndrome: Clinical characteristics and treatment outcomes - a single center study in Japan.

BACKGROUND: Periodic fever, aphthous stomatitis, pharyngitis, and cervical adenitis (PFAPA) syndrome is an autoinflammatory disease occurring in children. Although PFAPA is the most common periodic fever syndrome found in children, there are only a few studies defining the clinical characteristics and the efficacy of treatment strategies among Japanese children. This study aimed to clarify the demographic characteristics and clinical features of patients with PFAPA syndrome and to evaluate treatment efficacy. METHODS: We retrospectively reviewed the clinical features of children with PFAPA who visited Saitama Children's Medical Center between January and December 2019. We also evaluated treatment strategies and their efficacy; abortive treatment with corticosteroids, prophylaxis with cimetidine or colchicine, and surgical management with tonsillectomy. RESULTS: A total of 100 Japanese children (61% male) with PFAPA were included. Median age of onset was 3 years, median duration of fever episodes was 5 days, and median interval between episodes was 4 weeks. The symptoms (frequencies) were pharyngitis (89%), exudate on tonsils (71%), cervical adenitis (50%), and aphthous stomatitis (49%). Approximately 37% of patients took prednisolone for aborting fever attacks, showing a 100% response; 93% were treated with cimetidine, showing an 79.6% response, and 18% were treated with colchicine, showing a 66.7% response. Only one patient underwent tonsillectomy. CONCLUSIONS: Among Japanese children with PFAPA, 28% of them were ≥5 years with a male predominance. Pharyngitis is the most frequent symptom associated with fever. Cimetidine is suitable for initial therapy because of its safety and efficacy.

Clinical features and treatment strategies of febrile urinary tract infection caused by extended-spectrum beta-lactamase-producing Enterobacteriaceae in children: a multicenter retrospective observational study in Japan.

OBJECTIVES: The incidence of infections caused by extended-spectrum beta-lactamase (ESBL)-producing bacteria has increased. This study aimed to clarify the risk factors and treatment strategies for febrile urinary tract infection (fUTI) caused by ESBL-producing bacteria in Japanese children. METHODS: A retrospective observational study was conducted in 21 hospitals among children aged <16 years diagnosed with an fUTI between 2008 and 2017. Clinical data of children with fUTI caused by ESBL-producing and non-ESBL-producing bacteria were compared. RESULTS: Of the 2049 cases of fUTI, 147 (7.2%) were caused by ESBL-producing bacteria. Children in the ESBL group were more likely to have a history of recent antibiotic use or prophylactic antibiotic use, and experience recurrent UTIs (P <0.001) compared with those in the non-ESBL group. Of the 124 cases of fUTI due to ESBL-producing bacteria that were reviewed, 20 and 100 had concordant and discordant antibiotic use, respectively, and four had unknown antibiotic susceptibility. The median time from the start of treatment to fever resolution was 24 hours and did not differ significantly by therapy group (P = 0.39). CONCLUSION: ESBL-producing bacteria should be considered in children with recurrent UTIs and recent antibiotic use. Most children with fUTI experience clinical improvement regardless of the choice of antibiotic.

Prospective Study of the Detection of Bacterial Pathogens in Pediatric Clinical Specimens Using the Melting Temperature Mapping Method.

The melting temperature (Tm) mapping method is a novel technique that uses seven primer sets without sequencing to detect dominant bacteria. This method can identify pathogenic bacteria in adults within 3 h of blood collection without using conventional culture methods. However, no studies have examined whether pathogenic bacteria can be detected in clinical specimens from pediatric patients with bacterial infections. Here, we designed a new primer set for commercial use, constructed a database with more bacterial species, and examined the agreement rate of bacterial species in vitro. Moreover, we investigated whether our system could detect pathogenic bacteria from pediatric patients using the Tm mapping method and compared the detection rates of the Tm mapping and culture methods. A total of 256 pediatric clinical specimens from 156 patients (94 males and 62 females; median age, 2 years [<18 years of age]) were used. The observed concordance rates between the Tm mapping method and the culture method for both positive and negative samples were 76.4% (126/165) in blood samples and 79.1% (72/91) in other clinical specimens. The Tm mapping detection rate was higher than that of culture using both blood and other clinical specimens. In addition, using the Tm mapping method, we identified causative bacteria in pediatric clinical specimens quicker than when using blood cultures. Hence, the Tm mapping method could be a useful adjunct for diagnosing bacterial infections in pediatric patients and may be valuable in antimicrobial stewardship for patients with bacterial infections, especially in culture-negative cases. IMPORTANCE This study provides novel insights regarding the use of the melting temperature (Tm) mapping method to identify the dominant bacteria in samples collected from pediatric patients. We designed a new set of primers for commercial use and developed a database of different bacteria that can be identified using these primers. We show that the Tm mapping method could identify bacteria from blood samples and other clinical specimens. Moreover, we provide evidence that the Tm mapping method has a higher detection rate than that of the culture-based methods and can achieve a relatively high agreement rate. We believe that our study makes a significant contribution to this field because rapid identification of the source of bacterial infections can drastically improve patient outcomes and impede the development of antibiotic-resistant bacteria.

Ultrasound evaluation of inflammation in patients with chronic recurrent multifocal osteomyelitis involving the mandible: report of three cases.

Chronic recurrent multifocal osteomyelitis (CRMO) is aseptic and can be diagnosed by excluding other diseases, such as bacterial osteomyelitis, scurvy, metabolic disorders, and malignant diseases; therefore, bone biopsy is usually performed to confirm the diagnosis. To prevent misdiagnosis, the appropriate timing and location for biopsy should be determined from an active phase of inflammation. We presented 3 cases of CRMO involving the mandible: Case 1: A 2-year-old girl diagnosed with CRMO in the chronic phase. A sonogram showed a slightly low echoic area adjacent to the bone cortex. Pathological examination revealed a slight accumulation of leukocytes and plasma cells, as well as predominant fibrous stroma. Case 2: A 9-year-old girl diagnosed with CRMO with massive new osteoid formation. A sonogram showed a massive inhomogeneous low echoic area adjacent to the bone cortex. Pathological examination revealed massive osteoid formation and scattered inflammatory cells infiltration. Case 3: A 3-year-old girl diagnosed with CRMO in the active phase. A sonogram showed a massive hypoechoic area adjacent to the bone cortex and hyperechogenicity associated with a muscular and subcutaneous edema. Pathological examination revealed massive bone destruction and neutrophils infiltration within damaged osteoid. Ultrasound was able to visualize the degree of inflammation in the mandible corresponding to that of the surrounding soft tissue in all 3 cases. Therefore, ultrasound would be useful in determining the appropriate timing and location for bone biopsy.

Yersinia pseudotuberculosis Infection Accompanied by Intussusception and Incomplete Kawasaki Disease in a 7-year-old Girl.

Infection with Yersinia pseudotuberculosis, a known causal pathogen of human bacterial gastroenteritis, causes various symptoms and complications. A previously healthy 7-year-old girl was admitted because of fever and gastrointestinal symptoms. She was initially diagnosed with intussusception by abdominal ultrasonography. Although the patient was successfully treated by air enema, the fever persisted. The patient was then diagnosed with incomplete Kawasaki disease based on the presence of four principal clinical features. Intravenous immunoglobulin and oral aspirin were initiated. The patient defervesced and the other symptoms subsided after the treatment. Cardiac ultrasound results showed normal coronary arteries. Because of the gastrointestinal symptoms, stool samples were cultured repeatedly, only to yield normal flora. However, serum levels of anti-Y. pseudotuberculosis-derived mitogen antibody were elevated between the 7th and 18th days of the disease, thereby confirming Y. pseudotuberculosis infection. Because Y. pseudotuberculosis infection results in various clinical manifestations, we must be aware of each symptom and address them systematically.

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.

Influenza vaccine effectiveness against influenza A in children based on the results of various rapid influenza tests in the 2018/19 season.

During influenza epidemics, Japanese clinicians routinely conduct rapid influenza diagnostic tests (RIDTs) in patients with influenza-like illness, and patients with positive test results are treated with anti-influenza drugs within 48 h after the onset of illness. We assessed the vaccine effectiveness (VE) of inactivated influenza vaccine (IIV) in children (6 months-15 years old, N = 4243), using a test-negative case-control design based on the results of RIDTs in the 2018/19 season. The VE against influenza A(H1N1)pdm and A(H3N2) was analyzed separately using an RIDT kit specifically for detecting A(H1N1)pdm09. The adjusted VE against combined influenza A (H1N1pdm and H3N2) and against A(H1N1)pdm09 was 39% (95% confidence interval [CI], 30%-46%) and 74% (95% CI, 39%-89%), respectively. By contrast, the VE against non-A(H1N1)pdm09 influenza A (presumed to be H3N2) was very low at 7%. The adjusted VE for preventing hospitalization was 56% (95% CI, 16%-77%) against influenza A. The VE against A(H1N1)pdm09 was consistently high in our studies. By contrast, the VE against A(H3N2) was low not only in adults but also in children in the 2018/19 season.