No association between inactivated influenza vaccination and influenza viral load at diagnosis among young Japanese children: An observational study of the 2013/2014 through 2017/2018 influenza seasons.

BACKGROUND: The association between inactivated influenza vaccination and viral load in young children remains unclear. METHODS: During the 2013/2014 to 2017/2018 influenza seasons in Japan, children under 6 years of age with pre-defined influenza-like illness and influenza-positive status by real-time RT-PCR were recruited at pediatric clinics for this observational study. Influenza viral load was measured for the most predominant subtype/lineage in each season. Using median dichotomized viral load as an outcome, a multilevel logistic regression model was applied to estimate the multivariable adjusted odds ratio (MOR) and 95% confidence interval (CI) for higher viral load. RESULTS: A total of 1,185 influenza-positive children were analyzed. The median log10 viral load copy number (copies per milliliter) was 5.5 (interquartile range, 4.6 to 6.1) and did not differ by vaccination status: 5.5 for unvaccinated, 5.7 for one dose, and 5.5 for two doses (p = 0.67). The MOR of vaccinated (one or two doses) versus unvaccinated children was 1.19 (95% CI: 0.86-1.64). Other factors showing significant associations with higher viral load were positive results for A(H1N1)pdm09 and A(H3N2) in comparison with B/Yamagata. The respective MORs were 3.25 (95% CI: 2.28-4.64) and 1.81 (95% CI: 1.32-2.49). Significantly elevated MORs against higher viral load were also observed for higher body temperature at influenza diagnosis and shorter duration from fever onset to specimen collection. CONCLUSION: No association was observed between inactivated-influenza vaccination and viral load at influenza-positive diagnosis. Influenza subtype/lineage, body temperature, and time elapsed since fever onset were significantly associated with viral load.

Acute and Postacute Clinical Characteristics of Coronavirus Disease 2019 in Children in Japan.

BACKGROUND: The clinical features of coronavirus disease 2019 (COVID-19) in children have been changing because of the emergence and rapid spread of variants of concern (VOC). The increase in cases infected with VOC has brought concern with persistent symptoms after COVID-19 in children. This survey aimed to analyze the clinical manifestations and persistent symptoms of pediatric COVID-19 cases in Japan. METHODS: We analyzed the clinical manifestations of pediatric COVID-19 cases reported between February 2020 and April 2022 in Japan, using a dedicated database updated voluntarily by the members of the Japan Pediatric Society. Using the same database, we also analyzed persistent symptoms after COVID-19 in children who were diagnosed between February 2020 and November 2021. RESULTS: A total of 5411 and 1697 pediatric COVID-19 cases were included for analyzing clinical manifestations and persistent symptoms, respectively. During the Omicron variant predominant period, the percentage of patients with seizures increased to 13.4% and 7.4% in patient groups 1-4 and 5-11 years of age, respectively, compared with the pre-Delta (1.3%, 0.4%) or Delta period (3.1%, 0.0%). Persistent and present symptoms after 28 days of COVID-19 onset were reported in 55 (3.2%). CONCLUSIONS: Our survey showed that the rate of symptomatic pediatric COVID-19 cases increased gradually, especially during the Omicron variant predominant period, and a certain percentage of pediatric cases had persistent symptoms. Certain percentages of pediatric COVID-19 patients had severe complications or prolonged symptoms. Further studies are needed to follow such patients.

The clinical characteristics of pediatric coronavirus disease 2019 in 2020 in Japan.

BACKGROUND: The COVID-19 pandemic has affected the lives of people of all ages. Most reports on pediatric cases suggest that children experience fewer and milder symptoms than do adults. This is the first nationwide study in Japan focusing on pediatric cases reported by pediatricians, including cases with no or mild symptoms. METHODS: We analyzed the epidemiological and clinical characteristics and transmission patterns of 840 pediatric (<16 years old) COVID-19 cases reported between February and December 2020 in Japan, using a dedicated database which was maintained voluntarily by members of the Japan Pediatric Society. RESULTS: Almost half of the patients (47.7%) were asymptomatic, while most of the others presented mild symptoms. At the time of admission or first outpatient clinic visit, 84.0% of the cases were afebrile (<37.5°C). In total, 609 cases (72.5%) were exposed to COVID-19-positive household members. We analyzed the influence of nationwide school closures that were introduced in March 2020 on COVID-19 transmission routes among children in Japan. Transmission within households occurred most frequently, with no significant difference between the periods before and after declaring nationwide school closures (70.9% and 74.5%, respectively). CONCLUSIONS: COVID-19 symptoms in children are less severe than those in adults. School closure appeared to have a limited effect on transmission. Controlling household transmission from adult family members is the most important measure for prevention of COVID-19 among children.

Influence of Prior Influenza Vaccination on Current Influenza Vaccine Effectiveness in Children Aged 1 to 5 Years.

BACKGROUND: Although annual influenza vaccination is an important strategy used to prevent influenza-related morbidity and mortality, some studies have reported the negative influence of prior vaccination on vaccine effectiveness (VE) for current seasons. Currently, the influence of prior vaccination is not conclusive, especially in children. METHODS: We evaluated the association between current-season VE and prior season vaccination using a test-negative design in children aged 1-5 years presenting at nine outpatient clinics in Japan during the 2016/17 and 2017/18 influenza seasons. Children with influenza-like illness were enrolled prospectively and tested for influenza using real-time RT-PCR. Their recent vaccination history was categorized into six groups according to current vaccination doses (0/1/2) and prior vaccination status (unvaccinated = 0 doses/vaccinated = 1 dose or 2 doses): (1) 0 doses in the current season and unvaccinated in prior seasons (reference group); (2) 0 doses in the current season and vaccinated in a prior season; (3) 1 dose in the current season and unvaccinated in a prior season; (4) 1 dose in the current season and vaccinated in a prior season; (5) 2 doses in the current season and unvaccinated in a prior season, and (6) 2 doses in the current season and vaccinated in a prior season. RESULTS: A total of 799 cases and 1196 controls were analyzed. The median age of the subjects was 3 years, and the proportion of males was 54%. Overall, the vaccination rates (any vaccination in the current season) in the cases and controls were 36% and 53%, respectively. The VEs of the groups were: (2) 29% (95% confidence interval: -25% to 59%); (3) 53% (6% to 76%); (4) 70% (45% to 83%); (5) 56% (32% to 72%), and (6) 61% (42% to 73%). The one- and two-dose VEs of the current season were significant regardless of prior vaccination status. The results did not differ when stratified by influenza subtype/lineage. CONCLUSION: Prior vaccination did not attenuate the current-season VE in children aged 1 to 5 years, supporting the annual vaccination strategy.

Effect of a vaccine information statement (VIS) on immunization status and parental knowledge, attitudes, and beliefs regarding infant immunization in Japan.

BACKGROUND: Because of the overabundance of vaccination information on the internet, in the media, and on social media, providing clear and correct information on immunization is critical for parental decision-making. In 2018, the Japan Pediatric Society created and distributed a Vaccine Information Statement (VIS) to provide appropriate immunization information to caregivers. The objectives of the present study were to evaluate the effect of the VIS on immunization rates, adherence to schedule, and parental understanding of immunization in Japan. METHODS: This cross-sectional study was conducted at 18 centers in 2 prefectures in Japan. Caregivers were assigned to an intervention group, which received the VIS and a questionnaire when their child reached the age of 1 month, and a control group, which received only the questionnaire. Using the self-reported questionnaires, we evaluated vaccination rates and schedule adherence at age 2 months, and parental knowledge, attitudes, and beliefs regarding immunization. Three months later, the questionnaires were returned, and the findings were compared between the 2 groups. RESULTS: We contacted 422 and 428 persons in the intervention and control groups, respectively, and 111/422 (26.3%) and 119/428 (27.8%) returned the surveys. Vaccination rates and adherence rates for the first dose of 4 recommended vaccines did not differ significantly (P > 0.25); however, there were some positive effects on items related to vaccine knowledge (P = 0.03), perceived benefits (P = 0.02), perceived barriers (P < 0.001), and perceived behavioral control (P = 0.01). CONCLUSION: The VIS improved parent comprehension of infant immunization. Future studies should examine if the effects of such an intervention persist and affect vaccine uptake throughout childhood.

The Comparison of the Efficacy of Baloxavir and Neuraminidase Inhibitors for Patients with Influenza A in Clinical Practice.

Objective Baloxavir marboxil is a novel anti-influenza drug reported to have an early antiviral effect, although it also causes the appearance of variant viruses with a reduced susceptibility to baloxavir. In Japan, four neuraminidase inhibitors (NAIs) have been commonly used to treat patients with influenza. In clinical practice, the differences in the effects of baloxavir and NAIs have not been sufficiently examined. Our objective was to clarify the clinical differences in efficacy between baloxavir and NAIs. Methods A multicenter, observational study was conducted using postcard questionnaires during the 2018-19 influenza season. Patients who were prescribed anti-influenza drugs were provided postcard questionnaires asking about their background characteristics and their body temperatures. The factors associated with the early alleviation of the fever were analyzed, and the duration of the fever was compared between the baloxavir group and the NAI group. Results A total of 295 patients with influenza A, ranging in age from 0-91 years old, were enrolled in this study. A multivariate analysis showed that treatment with baloxavir and a duration from the onset to the start of treatment ≥2.5 days were factors contributing to the early alleviation of the fever from the start of treatment. The duration of the fever was significantly shorter in the baloxavir group than in the NAI group (p=0.002). Conclusion The present survey showed that baloxavir was significantly more effective than NAIs for treating patients with influenza A in clinical practice.

Effect of four neuraminidase inhibitors on influenza in Osaka, Japan: An eight-year survey.

BACKGROUND: After the A/H1N1 influenza pandemic in 2009, two new drugs against influenza, namely laninamivir and peramivir, were released in 2010 in Japan. We investigated prescription trends of four neuraminidase inhibitors (NAIs), which are laninamivir, peramivir, oseltamivir, and zanamivir, and assessed clinical data related to influenza for 8 years. METHODS: Patients living in Osaka Prefecture and diagnosed with influenza responded to a postcard questionnaire that collected data regarding their demographic characteristics, symptoms including fever, prescribed drugs, and influenza type. RESULTS: Laninamivir was most prescribed to patients aged ≥ 10 years, and oseltamivir was most prescribed to patients aged < 10 years. All four NAIs had similar effects on influenza. Patients with type A influenza experienced fever alleviation earlier than those with type B influenza. Older patients tended to have lower fever. Most seasons had similar results. CONCLUSIONS: Our descriptive epidemiologic study revealed the status of patients with influenza and their medication use.

Current usage and effectiveness of influenza medications and factors regarding the time taken to alleviate fever based on postcard questionnaire survey.

Background: After the A/H1N1 influenza pandemic in 2009, two new drugs against the influenza virus, laninamivir and peramivir, were released in 2010 in Japan. We investigated the current usage and effectiveness of influenza medications and factors related to the time taken to alleviate fever. Methods: Patients diagnosed with influenza during the 2012-2013 season in Osaka Prefecture answered a postcard questionnaire that collected data regarding their demographic characteristics, flu vaccination status, symptoms, prescribed drugs, and drug-related adverse events. Results: The use of laninamivir consistently increased over the 3-year period and was prescribed at a similar rate as oseltamivir during the last year (39% and 45%, respectively). None of the neuraminidase inhibitors had a significant effect on the fever or other symptoms of influenza infection (P=.59 and P=.70, respectively). Vaccinated influenza patients experienced fever for a significantly longer duration than the nonvaccinated patients (P=.04). However, multivariate analysis showed that only influenza virus type, but not vaccination status, was related to the alleviation of fever within 2 days. Conclusions: There were no significant differences of effects on fever and symptoms among neuraminidase inhibitors. Virus type was only related to the alleviation of fever.

[Significance of Urological Surgical Treatment for Viral Hemorrhagic Cystitis after Allogeneic Hematopoietic Stem Cell Transplantation].

This study investigated the significance of urological surgical intervention for viral hemorrhagic cystitis (HC) after allogeneic hematopoietic stem cell transplantation (allo-HSCT). A total of 1, 024 patients underwent allo-HSCT at our medical center between January 2006 and July 2014. In the 6 patients (0.58%) who required urological surgical treatment for viral HC, we retrospectively analyzed patient characteristics and outcomes. Two patients underwent nephrostomy for bilateral hydronephrosis due to bladder tamponade. One of these patients showed no improvement in renal function, graft versus host disease worsened and he died on postoperative day (POD) 5. The other patient displayed improved renal function but hematuria did not improve, and total cystectomy was required. To control bleeding, we performed transurethral electrocoagulation (TUC) on 3 patients, and total cystectomy was performed on 2 patients. All 3 patients who underwent TUC had BK virus HC. Two of these patients experienced marked improvement in hematuria from immediately after surgery. Hemostasis was only temporary in the other patient, who eventually died due to septicemia on POD 24. The 2 patients who underwent total cystectomy had adenovirus HC. Both experienced secondary hemorrhage postoperatively and required further surgery. Eventually, one died due to postoperative bleeding on POD 1, and one died due to postoperative pneumonia on POD 57. Urological surgical treatment for HC was effective in some cases, but the ultimate outcome greatly depends on the general condition of the patient and treatment of the underlying hematological disorder. TUC may be considered for HC (particularly BK virus HC), but total cystectomy (especially inaden ovirus HC) should be avoided.

Comparison of the Clinical Courses of Patients with Influenza after Neuraminidase Inhibitors Treatment: A Postcard Survey of the 2013-2014 Influenza Season in Osaka.

Background In Japan, four neuraminidase inhibitors (NAIs) are currently prescribed to patients with influenza A and B. To know the backgrounds and clinical courses of patients with influenza who were treated with NAIs is important in the selection of appropriate medications. Methods We conducted a multicenter observational study in Osaka with postcard questionnaires. Patients who were prescribed NAIs were provided postcard questionnaires containing questions on their backgrounds, body temperatures, and durations of other influenza symptoms. We analyzed the factors that were associated with early fever alleviation using a logistic regression model. Results The postcard response rate was 31% (326 of 1050), and 307 patients were enrolled in this study [150 patients who were under 10 years old (type A, 118; and type B, 32) and 157 patients who were 10 or older (type A, 114; and type B, 43)]. In the patients under 10, the multivariate analysis showed that influenza type (Type B vs Type A; Odds Ratio, 0.13; 95% Confidence Interval: 0.04-0.38) was associated with early fever alleviation. However, NAIs were not related to early fever alleviation. Laninamivir tended to contribute more to early fever alleviation compared to oseltamivir in patients under 10 (Odds Ratio, 2.50;$95% Confidence Interval: 0.90-7.80). Conclusions The types,of prescibed NAIs were not significantly related to early fever alleviation. However, the fever durations of the patients under 10 who were prescribed laninamivir were shorter than those of patients under 10 who were prescribed oseltamivir or zanamivir.

Immunogenicity and reactogenicity of a monovalent inactivated 2009 influenza A vaccine in adolescents: with special reference to pre-existing antibody.

OBJECTIVE: To evaluate the immunogenicity and reactogenicity of a monovalent 2009 pandemic influenza vaccine in Japanese adolescents. STUDY DESIGN: A total of 111 junior high school and high school students aged 13 to 18 years participated. Subjects received two doses of a monovalent inactivated unadjuvanted 2009 influenza A vaccine. Immunogenicity of the vaccine was evaluated according to the international criteria. We also asked subjects to report adverse reactions. RESULTS: After the first dose of vaccine, the seroprotection rate was 91% (95% CI, 85%-96%), the seroconversion rate was 78% (70%-86%), and the geometric mean titer ratio was 11.9 in all subjects. Antibody titers achieved did not differ significantly after the first and the second doses. With multivariate analysis, an independent negative effect of a prevaccination titer of ≥1:40 on ≥4 fold antibody increase was indicated. No serious adverse reaction was reported. CONCLUSION: The monovalent pandemic vaccine generally was safe, and a single dose of the vaccine given to adolescents induced sufficient immunity. Pre-existing antibody showed substantial effect on antibody response. The effect of pre-existing titer should be considered when evaluating the immunogenicity of influenza vaccines, especially in studies conducted during pandemic waves.

[Initial division of the left renal vein before dissection of left renal vein occluded by intracaval tumor thrombus].

Between November 2008 and March 2010, we performed initial division of the left renal vein occluded by the tumor thrombus in six cases of left renal cancer at Toranomon Hospital. The left renal vein was completely occluded by the tumor thrombus in all cases. In order to ligate the left renal artery first behind the dilated left renal vein, we must dissect the left kidney with arterial blood flow. Massive bleeding from the numerous engorged collateral veins around the left kidney is inevitable. Furthermore, access to the left renal artery is difficult because of the large tumor. We therefore initially divided the left renal vein without arterial blood flow followed by division of the left renal artery. After nephrectomy by dissecting the tumor without blood flow we extirpated the intracaval tumor thrombus. The median time of the operation was 7 hours 35 minutes and the median amount of blood loss was 2,869 ml. The tumor stage was pT3b in four cases and pT3c in two cases. No complications were observed during and after surgery except for one case of lymphocele and another case of chylous ascites. The initial division of the left renal vein is considered to be a useful surgical approach in left renal cancer with occluded left renal vein, especially when the tumor is large.

[The initial division of left renal vein in left renal cancer with intracaval tumor thrombus: a case report].

A 30-year-old female was admitted to our hospital with a 3-month history of general fatigue and one month history of left flank mass. Computed tomography revealed a huge left renal tumor (20 × 13 × 10 cm) with intracaval tumor thrombus. The tumor thrombus extended into the right atrium. The left renal vein (lt-RV) was expanded 3.5 cm in diameter by the tumor thrombus. The tumor was surrounded by a tortuous dilated capsular vein. The strategic issue was how to ligate the left renal artery (lt-RA) behind the expanded lt-RV. We first divided the lt-RV occluded by the tumor thrombus using a Linear Cutter® and then divided the lt-RA before the dissection of the tumor to avoid excessive bleeding. Even transarterial embolization of lt-RA were to be performed,the tumor was too large to dissect without division of lt-RV and lt RA. After the left kidney was removed,the lower half of the tumor thrombus was excised,clamping the inferior vena cava,three right renal arteries,two right renal veins,and the lumber vein. Finally,we removed the upper half of the tumor thrombus extending to the right atrium through atriotomy and cavotomy under an extracorporeal cardiovascular bypass. Operation time was 9 h 22 m,and total blood loss was 1670 ml. Convalescence was uneventful except for abdominal lymphocele.

An office-based prospective study of deafness in mumps.

BACKGROUND: Deafness is a rare but important complication of mumps virus infection. Its incidence has been estimated at 0.5 to 5.0 per 100,000 cases of mumps, but recent reports from Japan, where mumps is endemic, suggest that the incidence might be higher. OBJECTIVE: Prospective office-based study to determine the incidence of hearing loss in children with mumps. METHODS: Forty pediatric practices participated in this survey. The study population consisted of patients < or =20 years old with mumps seen between January 2004 and December 2006. Clinical diagnosis of mumps was made by experienced pediatricians. Among those from whom written consent was obtained, parents were asked to conduct hearing screening tests by rubbing fingers near the ears twice daily for 2 weeks. Patients suspected with hearing loss were further examined by an otolaryngologist. RESULTS: Among 7400 children who underwent hearing ability assessment after clinical onset of mumps, 7 had confirmed hearing loss; none had been previously vaccinated against mumps. In all cases, hearing loss was unilateral but severe and did not improve over time. CONCLUSIONS: The incidence of hearing loss in children due to mumps was 7/7400 (approximately 1/1000 cases), which is higher than previously suggested. Prevention of deafness is another important reason for assuring universal immunization against mumps.

Risk of missing colorectal cancer during laparoscopic cholecystectomy.

PURPOSE: The increased number of patients undergoing laparoscopic cholecystectomy (LC) is associated with a risk of missing concomitant colorectal cancers; however, the incidence and cause have not yet been well recognized. Our aim, therefore, was to evaluate these factors. METHODS: This retrospective study evaluated data on 473 patients with benign gallbladder diseases, who underwent LC between January 1991 and December 1999. Among these 473 patients, 2 (0.4%) were thought to have had detectable cancer at LC. RESULTS: The first patient was a 59-year-old woman who underwent palliative resection for ascending colon cancer associated with liver and pulmonary metastases 10 months following LC when laboratory data showed a low hemoglobin level (10.0 g/dl). The other patient, a 50-year-old man, underwent resection for Dukes' C sigmoid colon cancer 6 months following LC. At LC, the patient did not present with any symptoms suggesting the existence of colorectal cancer and the laboratory data were normal. CONCLUSIONS: These results indicate that although an extremely low incidence of missed colorectal cancers does not justify routine screening for colorectal cancer before LC in terms of cost-effectiveness, careful attention to preoperative physical findings and laboratory data as well as meticulous techniques and full diagnostic visualization of the large-bowel intraoperatively may reduce the potential risk of missing coexisting colorectal cancers during LC.