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.

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.

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.

Verification of blood volume for blood culture and detection rate in pediatrics.

PURPOSE: This study was conducted to estimate the blood culture volume that should be collected from pediatric patients to improve diagnostic abilities. METHODS: Blood cultures from neonates and children aged up to 18 years were collected and the volume was measured for over a 1-year period. During the intervention period, examiners were instructed to draw 3 mL of blood for culture, if possible. The pre-intervention period was from June 1 to August 31, 2016. The post-intervention period was from September 1, 2016, to May 30, 2017. The rate of positive detections was calculated and compared between pre and post-intervention periods. RESULTS: We collected 1352 samples and measured 1327 bottles. During the pre-intervention period, 340 cases were collected with a median blood volume of 1.64 mL; 9 cases (2.7%) were true-positive. During the intervention period, 1012 cases were ordered with a median blood volume of 2.41 mL; 19 cases (1.9%) were true-positive. After intervention, blood volume was increased significantly (p < 0.01). However, there was no significant difference in the rate of positive detections during the study periods (p = 0.254). CONCLUSIONS: In the pediatric clinical setting in a Japanese municipal hospital, the positive detection rate did not improve even when the collected blood volume was increased. One milliliter of blood volume may be adequate for the pediatric bottle in children.

One-month-old boy with group B streptococcal meningitis, subdural effusion, and high levels of interleukin-6.

Meningitis is associated with elevated levels of inflammatory cytokines in the blood, cerebrospinal fluid (CSF), and subdural fluid. Subdural effusion prolongs fever in patients with meningitis. However, the reason for this remains unclear. A healthy one-month-old boy was admitted after presenting with bacterial meningitis. He was administered meropenem, cefotaxime, and dexamethasone intravenously. On the 3rd day, blood and CSF cultures revealed the presence of Group B Streptococcus from samples collected on day 1. Subsequently, ampicillin and gentamicin replaced the previous combination of antimicrobials used. On the 4th day, brain magnetic resonance imaging with contrast showed bilateral cerebral ventriculitis and left subdural effusion. On the 11th day, since the subdural effusion had worsened, we performed a subdural puncture from the anterior fontanelle. Owing to the prolonged fever, he was intravenously injected immunoglobulin on day 13. He was afebrile on day 23. Antimicrobials were administered for 28 days. Levels of interleukin-6 (IL-6) in the serum and CSF were the highest on the 1st day at 20,600 pg/mL and 170,000 pg/mL, respectively, and decreased upon treatment. IL-6 concentration in the subdural fluid (30,000 pg/mL) was much higher than that in the serum (9 pg/mL) and CSF (2600 pg/mL). To the best of our knowledge, this is the first report on the cytokines in subdural fluid in patients with group B Streptococcal meningitis. Subdural effusion maintained high levels of IL-6 even after the levels in the blood and CSF decreased dramatically. This could explain why subdural effusion prolongs fever in patients with meningitis.

Purulent lymphadenitis caused by Staphylococcus argenteus, representing the first Japanese case of Staphylococcus argenteus (multilocus sequence type 2250) infection in a 12-year-old boy.

Staphylococcus argenteus is a novel species separated from a strain of coagulase-positive, non-pigmented S. aureus. Although S. argenteus has been reported to occur globally, multilocus sequence type (ST) 2250 is mainly found in Northeastern Thailand. Because conventional biochemical testing misidentifies this pathogen as S. aureus, multilocus sequence typing (MLST) or nucA sequencing is recommended to distinguish between S. argenteus and S. auereus. The patient was a previously healthy 12-year-old boy who was admitted because of right inguinal lymphadenitis and cellulitis. Although intravenous cefazolin was administered, his lymphadenitis worsened and formed an abscess on day 6 of hospitalization. Incision and drainage were performed on day 7 of hospitalization. Cefazolin was changed to oral cefaclor, and the patient was successfully treated over a period of 5 weeks. No recurrence was observed throughout 12-months of follow-up. He had a history of right axillary lymph node abscess 2 months before this admission, which was successfully treated with incision, drainage, and antibiotic therapy. He has lived in Japan since birth and never traveled abroad. He had no opportunity to interact with foreigners. His immune function, especially neutrophil function, was tested and we did not find any dysfunction. First, methicillin-sensitive S. aureus was misidentified from the abscess culture. Subsequently, the causative agent was re-identified as S. argenteus ST2250 based on MLST. To our knowledge, this is the first case of S. argenteus ST2250 infection in Japan. This pathogen should be taken into consideration in the diagnosis if the patient has atypical non-pigmented S. aureus.

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.

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.

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.

Detection of Torque teno virus DNA in exhaled breath by polymerase chain reaction.

To determine whether exhaled breath contains Torque teno virus (TTV) or not, we tested exhaled breath condensate (EBC) samples by semi-nested PCR assay. We detected TTV DNA in 35% (7/20) of EBC samples collected from the mouth of one of the authors, demonstrating that TTV DNA is excreted in exhaled breath with moderate frequency. TTV DNA was detected also in oral EBC samples from 4 of 6 other authors, indicating that TTV DNA excretion in exhaled breath is not an exception but rather a common phenomenon. Furthermore, the same assay could amplify TTV DNA from room air condensate (RAC) samples collected at distances of 20 and 40cm from a human face with 40 (8/20) and 35% (7/20) positive rates, respectively. TTV transmission has been reported to occur during infancy. These distances seem equivalent to that between an infant and its household members while caring for the infant. Taken together, it seems that exhaled breath is one of the possible transmission routes of TTV. We also detected TTV DNA in 25% (10/40) of RAC samples collected at a distance of more than 180cm from any human face, suggesting the risk of airborne infection with TTV in a room.

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.

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.

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.