Persistent low bone mineral density in adolescent idiopathic scoliosis: A longitudinal study.

BACKGROUND: Since osteopenia has been reported to potentially associated with the progression of scoliosis, bone mineral density (BMD) might have some influences on adolescent idiopathic scoliosis (AIS). However, little is known about longitudinal BMD changes in AIS patients. This study aimed to investigate whether osteopenia in preoperative AIS patients persist at bone maturity, and to evaluate the association between BMD and AIS severity. METHODS: We reviewed 61 AIS patients who underwent surgery when they were Risser grade 4 or below and less than 20 years old (16.6 ± 1.9 years), were followed until they were at least 18 years old and had a Risser grade of 5, and followed at least 2 years after the surgery (mean follow-up 4.9 ± 1.7 years). We evaluated radiographical parameters and proximal femur BMD before surgery and at the final follow-up. A BMD of less than the mean minus 1SD was considered as low BMD. Based on preoperative BMD, 37 patients were assigned to normal BMD (N) group (1.02 ± 0.08 g/cm2) and 24 patients to low BMD (L) group (0.82 ± 0.06 g/cm2). RESULTS: All patients in the N-group had normal BMD at the final follow-up. In the L group, 15 patients (62.5%) had low BMD at the final follow-up (L-L group; preoperative 0.79 ± 0.05 g/cm2 and final follow-up 0.78 ± 0.05 g/cm2). The mean preoperative Cobb angle was significantly larger in the L-L group (67.8 ± 11.2°) than in those with normal BMD at the final follow-up (L-N group, 55.6 ± 11.8°) or the N-N group (50.8 ± 7.6°). Preoperative BMD was significantly negative correlated with the preoperative Cobb angle. The age at surgery and mean preoperative BMI were similar in the L-N and L-L groups. CONCLUSIONS: Of AIS patients with low preoperative BMD, 62.5% still had low BMD after reaching bone maturity, and low BMD was associated with the severity of scoliosis.

Efficacy and safety of propranolol cream in infantile hemangioma: A prospective pilot study.

Infantile hemangioma (IH) is a common tumor in infants that gradually resolves and is often untreated. However, for cosmetic reasons, parents often opt for treatment. Oral propranolol, the first-line therapy for IH, is sometimes associated with several side effects, including hypotension, bradycardia, and hypoglycemia. No clinical studies on topical propranolol have been conducted using standardized procedures. We evaluated the efficacy and safety of topical propranolol in patients with IH. This multicenter, prospective pilot study was conducted from June 2019 to October 2020 and involved eight Japanese infants aged 35-150 days with proliferating IH. Patients were treated with 5% propranolol cream twice daily. We examined the efficacy rate based on central evaluation (complete or near-complete healing of the target hemangioma) at weeks 24 and 12, respectively, compared to baseline values. The efficacy rate at week 24 was 68.8% (95% confidence interval: 44.1-85.9%). The surface area, maximum diameter, and color intensity of the target IH decreased over time. Adverse event and drug-related adverse event rates were 87.5% and 0%, respectively. Propranolol cream may be effective and safe in Japanese patients with IH and may be considered a first-choice treatment for small and superficial IHs in cosmetically problematic areas.

Risk predictors of perioperative complications for the palliative surgical treatment of spinal metastasis.

BACKGROUND: The complication rate for palliative surgery in spinal metastasis is relatively high, and major complications can impair the patient's activities of daily living. However, surgical indications are determined based primarily on the prognosis of the cancer, with the risk of complications not truly considered. We aimed to identify the risk predictors for perioperative complications in palliative surgery for spinal metastasis. METHODS: A multicentered, retrospective review of 195 consecutive patients with spinal metastasis who underwent palliative surgeries with posterior procedures from 2001 to 2016 was performed. We evaluated the type and incidence of perioperative complications within 14 days after surgery. Patients were categorized into either the complication group (C) or no-complication group (NC). Univariate and multivariate analyses were used to identify potential predictors for perioperative complications. RESULTS: Thirty patients (15%) experienced one or more complications within 14 days of surgery. The most frequent complications were surgical site infection (4%) and motor weakness (3%). A history of diabetes mellitus (C; 37%, NC; 9%: p < 0.01) and surgical time over 300 min (C; 27%, NC; 12%: p < 0.05) were significantly associated with complications according to univariate analysis. Increased blood loss and non-ambulatory status were determined to be potential risk factors. Of these factors, multivariate logistic regression revealed that a history of diabetes mellitus (OR: 6.6, p < 0.001) and blood loss over 1 L (OR: 2.7, p < 0.05) were the independent risk factors for perioperative complications. There was no difference in glycated hemoglobin A1c between the diabetes patients with and without perioperative complications. CONCLUSIONS: Diabetes mellitus should be used for the risk stratification of surgical candidates regardless of the treatment status, and strict prevention of bleeding is needed in palliative surgeries with posterior procedures to mitigate the risk of perioperative complications.

Spinal correction surgery improves asymmetrical trunk kinematics during gait in adolescent idiopathic scoliosis with thoracic major curve.

PURPOSE: To clarify the effect of posterior correction and fusion surgery on the trunk-pelvic kinematics during gait in adolescent idiopathic scoliosis (AIS) patients with single thoracic major curve. METHODS: Among preoperative AIS patients who planned correction surgery, 18 patients with Lenke type 1A or B were selected for this study. All patients were female. The patients' trunk and pelvic kinematics during gait were measured three-dimensionally and dynamically using reflective markers, optoelectronic motion capture system. The gait analysis was performed before and 1-2 years after surgery. The trunk and pelvic symmetry during gait was evaluated at coronal, sagittal, and transverse planes between concave and convex sides. RESULTS: The trunk and pelvic angles in sagittal and coronal planes were equivalent between concave and convex sides before and after surgery. Preoperatively, transverse trunk rotation angles were significantly deviated toward the concave (left) side during both static standing (4.3 ± 2.0°) and gait (8.8 ± 0.6°, p < 0.01). Preoperative transverse pelvic rotation angles were significantly deviated toward the convex side during static standing (4.0 ± 3.8°). However, pelvis displayed with symmetric rotational kinematics during gait. Postoperatively, the deviated transverse trunk rotation angle significantly decreased (1.6 ± 0.3°), and the transverse rotational kinematics of both trunk and pelvis improved to symmetric. CONCLUSIONS: Posterior correction and fusion surgery have improved preoperative asymmetric global rotational kinematics of trunk and pelvis in transverse plane to symmetric postoperatively in AIS patients with thoracic single major curve. These slides can be retrieved under Electronic Supplementary Material.

Embedding Bifurcations into Pneumatic Artificial Muscle.

Harnessing complex body dynamics has long been a challenge in robotics, particularly when dealing with soft dynamics, which exhibit high complexity in interacting with the environment. Recent studies indicate that these dynamics can be used as a computational resource, exemplified by the McKibben pneumatic artificial muscle, a common soft actuator. This study demonstrates that bifurcations, including periodic and chaotic dynamics, can be embedded into the pneumatic artificial muscle, with the entire bifurcation structure using the framework of physical reservoir computing. These results suggest that dynamics not present in training data can be embedded through bifurcation embedment, implying the capability to incorporate various qualitatively different patterns into pneumatic artificial muscle without the need to design and learn all required patterns explicitly. Thus, this study introduces a novel approach to simplify robotic devices and control training by reducing reliance on external pattern generators and the amount and types of training data needed for control.

Graft cell expansion from hiPSC-RPE strip after transplantation in primate eyes with or without RPE damage.

Clinical studies using suspensions or sheets of human pluripotent cell-derived retinal pigment epithelial cells (hiPSC-RPE) have been conducted globally for diseases such as age-related macular degeneration. Despite being minimally invasive, cell suspension transplantation faces challenges in targeted cell delivery and frequent cell leakage. Conversely, although the RPE sheet ensures targeted delivery with correct cell polarity, it requires invasive surgery, and graft preparation is time-consuming. We previously reported hiPSC-RPE strips as a form of quick cell aggregate that allows for reliable cell delivery to the target area with minimal invasiveness. In this study, we used a microsecond pulse laser to create a local RPE ablation model in cynomolgus monkey eyes. The hiPSC-RPE strips were transplanted into the RPE-ablated and intact sites. The hiPSC-RPE strip stably survived in all transplanted monkey eyes. The expansion area of the RPE from the engrafted strip was larger at the RPE injury site than at the intact site with no tumorigenic growth. Histological observation showed a monolayer expansion of the transplanted RPE cells with the expression of MERTK apically and collagen type 4 basally. The hiPSC-RPE strip is considered a beneficial transplantation option for RPE cell therapy.

Theoretical Study on the Open-Shell Electronic Structure and Electron Conductivity of [18]Annulene as a Molecular Parallel Circuit Model.

Herein, the electron conductivities of [18]annulene and its derivatives are theoretically examined as a molecular parallel circuit model consisting of two linear polyenes. Their electron conductivities are estimated by elastic scattering Green's function (ESGF) theory and density functional theory (DFT) methods. The calculated conductivity of the [18]annulene does not follow the classical conductivity, i.e., Ohm's law, suggesting the importance of a quantum interference effect in single molecules. By introducing electron-withdrawing groups into the annulene framework, on the other hand, a spin-polarized electronic structure appears, and the quantum interference effect is significantly suppressed. In addition, the total current is affected by the spin polarization because of the asymmetry in the coupling constant between the molecule and electrodes. From these results, it is suggested that the electron conductivity as well as the quantum interference effect of π-conjugated molecular systems can be designed using their open-shell nature, which is chemically controlled by the substituents.

Inhibition of common cold-induced aggravation of childhood asthma by leukotriene receptor antagonists.

BACKGROUND: Virus infection is an important risk factor for aggravation of childhood asthma. The objective of this study was to examine the effect of drugs on aggravation of asthma induced by a common cold. METHODS: Asthma control was examined in a survey of 1,014 Japanese pediatric patients with bronchial asthma. The occurrence of common cold, asthma control, and drugs used for asthma control were investigated using a modified Childhood Asthma Control Test (C-ACT) for patients aged <4 years old and 4 to 11 years old, and an Asthma Control Test (ACT) for patients aged 12 to 15 years old. RESULTS: The status of asthma control did not differ among the age groups. The prevalence of common cold and aggravation of asthma were significantly higher in patients aged <4 years old. Control of asthma following common cold-induced aggravation was significantly less effective in patients aged <4 years old compared to those aged ≥4 years old. In patients aged <4 years old with a common cold, asthma control was significantly more effective for those treated with leukotriene receptor antagonists (LTRAs) compared to treatment without LTRAs. Asthma control did not differ between patients who did or did not take inhaled corticosteroids or long-acting ß2 stimulants. CONCLUSIONS: These findings showed a high prevalence of common cold in younger patients with childhood asthma and indicated that common cold can induce aggravation of asthma. LTRAs are useful for long-term asthma control in very young patients who develop an asthma attack due to a common cold.

Robotic search for optimal cell culture in regenerative medicine.

Induced differentiation is one of the most experience- and skill-dependent experimental processes in regenerative medicine, and establishing optimal conditions often takes years. We developed a robotic AI system with a batch Bayesian optimization algorithm that autonomously induces the differentiation of induced pluripotent stem cell-derived retinal pigment epithelial (iPSC-RPE) cells. From 200 million possible parameter combinations, the system performed cell culture in 143 different conditions in 111 days, resulting in 88% better iPSC-RPE production than that obtained by the pre-optimized culture in terms of the pigmentation scores. Our work demonstrates that the use of autonomous robotic AI systems drastically accelerates systematic and unbiased exploration of experimental search space, suggesting immense use in medicine and research.

Inducing human retinal pigment epithelium-like cells from somatic tissue.

Regenerative medicine relies on basic research outcomes that are only practical when cost effective. The human eyeball requires the retinal pigment epithelium (RPE) to interface the neural retina and the choroid at large. Millions of people suffer from age-related macular degeneration (AMD), a blinding multifactor genetic disease among RPE degradation pathologies. Recently, autologous pluripotent stem-cell-derived RPE cells were prohibitively expensive due to time; therefore, we developed a faster reprogramming system. We stably induced RPE-like cells (iRPE) from human fibroblasts (Fibs) by conditional overexpression of both broad plasticity and lineage-specific transcription factors (TFs). iRPE cells displayed critical RPE benchmarks and significant in vivo integration in transplanted retinas. Herein, we detail the iRPE system with comprehensive single-cell RNA sequencing (scRNA-seq) profiling to interpret and characterize its best cells. We anticipate that our system may enable robust retinal cell induction for basic research and affordable autologous human RPE tissue for regenerative cell therapy.

Trends in effectiveness of inactivated influenza vaccine in children by age groups in seven seasons immediately before the COVID-19 era.

BACKGROUND: We have reported the vaccine effectiveness of inactivated influenza vaccine in children aged 6 months to 15 years between the 2013/14 and 2018/19 seasons. Younger (6-11 months) and older (6-15 years old) children tended to have lower vaccine effectiveness. The purpose of this study is to investigate whether the recent vaccine can be recommended to all age groups. METHODS: The overall adjusted vaccine effectiveness was assessed from the 2013/14 until the 2020/21 season using a test-negative case-control design based on rapid influenza diagnostic test results. Vaccine effectiveness was calculated by influenza type and by age group (6-11 months, 1-2, 3-5, 6-12, and 13-15 years old) with adjustments including influenza seasons. RESULTS: A total of 29,400 children (9347, 4435, and 15,618 for influenza A and B, and test-negatives, respectively) were enrolled. The overall vaccine effectiveness against influenza A, A(H1N1)pdm09, and B was significant (44% [95% confidence interval (CI), 41-47], 63% [95 %CI, 51-72], and 37% [95 %CI, 32-42], respectively). The vaccine was significantly effective against influenza A and B, except among children 6 to 11 months against influenza B. The age group with the highest vaccine effectiveness was 1 to 2 years old with both influenza A and B (60% [95 %CI, 55-65] and 52% [95 %CI, 41-61], respectively). Analysis for the 2020/21 season was not performed because no cases were reported. CONCLUSIONS: This is the first report showing influenza vaccine effectiveness by age group in children for several seasons, including immediately before the coronavirus disease (COVID-19) era. The fact that significant vaccine effectiveness was observed in nearly every age group and every season shows that the recent vaccine can still be recommended to children for the upcoming influenza seasons, during and after the COVID-19 era.

Human iPS cell derived RPE strips for secure delivery of graft cells at a target place with minimal surgical invasion.

Several clinical studies have been conducted into the practicality and safety of regenerative therapy using hESC/iPSC-retinal pigment epithelium (RPE) as a treatment for the diseases including age-related macular degeneration. These studies used either suspensions of RPE cells or an RPE cell sheet. The cells can be injected using a minimally invasive procedure but the delivery of an intended number of cells at an exact target location is difficult; cell sheets take a longer time to prepare, and the surgical procedure is invasive but can be placed at the target area. In the research reported here, we combined the advantages of the two approaches by producing a quickly formed hiPSC-RPE strip in as short as 2 days. The strip readily expanded into a monolayer sheet on the plate, and after transplantation in nude rats, it showed a potency to partly expand with the correct apical/basal polarity in vivo, although limited in expansion area in the presence of healthy host RPE. The strip could be injected into a target area in animal eyes using a 24G canula tip.

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.

Migration of a Kirschner wire into the spinal cord: A case report and literature review.

CONTEXT: A Kirschner wire (K-wire) is a stainless steel pin with at least one sharpened tip that is mainly used for the internal fixation of bone fractures. While some cases of K-wire dislocation and migration have been reported as complications after fracture surgery, the intraspinal migration of a K-wire is rare. Herein, we report a case in which a K-wire used for sternal fixation 7 years earlier migrated into the spinal canal. FINDINGS: A 68-year-old male suddenly sustained severe radiating pain and numbness in his left upper extremity, and walked to our hospital. He had mild weakness in the left wrist extensor muscles and the left extensor digitorum. CT-myelography revealed a K-wire penetrating into the spinal cord at C5-6. There was no injury of the trachea, esophagus, or blood vessels. The patient had a history of surgical infection after cardiovascular surgery seven years before, and had undergone surgical debridement and sternum fixation with two K-wires. One K-wire had broken, and part of it migrated upward. Using an anterior approach, we detected the tip of K-wire below the left sternocleidomastoid muscle. We cut the K-wire into 1 to 2-cm pieces and removed it piece by piece. His postoperative course was uneventful and the symptoms improved markedly after the surgery. CONCLUSION: This is the first report of a K-wire that had been used for sternal fixation migrating into the spinal cord. This case illustrates that although rare, it is possible for a K-wire to migrate upward after sternal fixation.

Polarization-sensitive optical coherence tomography for estimating relative melanin content of autologous induced stem-cell derived retinal pigment epithelium.

Transplantation of autologous human induced pluripotent stem cell-derived retinal pigment epithelial (hiPSC-RPE) sheets is a promising therapy for age-related macular degeneration (AMD). As melanin content is a representative feature of healthy RPE, we used polarization-sensitive optical coherence tomography (PS-OCT) to estimate the relative melanin content of RPE in diseased and non-diseased area, and in human iPSC-RPE sheets in vitro and in vivo by evaluating the randomness of polarization (entropy). Two aged Japanese women, one with neovascular AMD that underwent transplantation of an autologous hiPSC-RPE cell sheet and another with binocular dry AMD, were selected for this study. Entropy value was minimal in cells containing no melanin, whereas that of human RPE and hiPSC-RPE sheets was high. En face entropy of the cultured hiPSC-RPE sheet was compared with its grey-scale photo and its values were found to be inversely correlated with the extent of absence of pigmentation in vitro. En face entropy maps were compared to colour fundus photographs, fundus autofluorescence images, and fluorescein angiography images from patients. Entropy values of intact and defective RPEs and of iPSC-RPE transplant areas were determined in vivo using PS-OCT B-scan images. PS-OCT was found to be applicable in the estimation of relative melanin content of cultured and transplanted RPEs in regenerative medicine.

HLA-Matched Allogeneic iPS Cells-Derived RPE Transplantation for Macular Degeneration.

Immune attacks are key issues for cell transplantation. To assess the safety and the immune reactions after iPS cells-derived retinal pigment epithelium (iPS-RPE) transplantation, we transplanted HLA homozygote iPS-RPE cells established at an iPS bank in HLA-matched patients with exudative age-related macular degeneration. In addition, local steroids without immunosuppressive medications were administered. We monitored immune rejections by routine ocular examinations as well as by lymphocytes-graft cells immune reaction (LGIR) tests using graft RPE and the patient's blood cells. In all five of the cases that underwent iPS-RPE transplantation, the presence of graft cells was indicated by clumps or an area of increased pigmentation at 6 months, which became stable with no further abnormal growth in the graft during the 1-year observation period. Adverse events observed included corneal erosion, epiretinal membrane, retinal edema due to epiretinal membrane, elevated intraocular pressure, endophthalmitis, and mild immune rejection in the eye. In the one case exhibiting positive LGIR tests along with a slight fluid recurrence, we administrated local steroid therapy that subsequently resolved the suspected immune attacks. Although the cell delivery strategy must be further optimized, the present results suggest that it is possible to achieve stable survival and safety of iPS-RPE cell transplantation for a year.

A simple and static preservation system for shipping retinal pigment epithelium cell sheets.

The ability to move cells and tissues from bench to bedside is an essential aspect of regenerative medicine. In this study, we propose a simple and static shipping system to deliver tissue-engineered cell sheets. Notably, this system is electronic-device-free and simplified to minimize the number of packing and opening steps involved. Shipping conditions were optimized, and application and verification of the system were performed using human iPS cell-derived or fetal retinal pigment epithelium (RPE) cell sheets. The temperature of the compartments within the insulated container was stable at various conditions, and filling up the cell vessel with medium effectively prevented turbulence-induced mechanical damage to the RPE cell sheets. Furthermore, no abnormal changes were observed in RPE morphology, transepithelial electrical resistance, or mRNA expression after transit by train and car. Taken together, our simple shipping system has the potential to minimize the costs and human error associated with bench to bedside tissue transfer. This specially designed regenerative tissue shipping system, validated for use in this field, can be used without any special training. This study provides a procedure for easily sharing engineered tissues with the goal of promoting collaboration between laboratories and hospitals and enhancing patient care.

Epithelioid Hemangioma of the Thoracic Spine: A Case Report and Review of the Literature.

Context: Osseous epithelioid hemangioma is uncommon, and reports of epithelioid hemangiomas of the spine are especially rare.Study Design: Case report.Findings: A 43-year-old male was referred to our department with progressive gait disturbance. CT scans showed a lucent mass in the vertebral body at the T3 level. MRI of the thoracic spine showed a strongly enhanced mass compressing the spinal cord. The patient underwent laminectomy from T2 to T4, debulking of the tumor, and posterior fusion from T1 to T5. After the operation, the patient's neurological status improved significantly, and he was able walk without assistance. Histological examination determined that the tumor was an epithelioid hemangioma. The patient was treated with 40 Gy radiation for local control of the tumor. The patient could walk without difficulty 12 months after the surgery.Conclusion: This is a rare example of an epithelioid hemangioma that developed in the thoracic spine and compressed the spinal cord, and was treated successfully.

Spinal fractures in diffuse idiopathic skeletal hyperostosis: Advantages of percutaneous pedicle screw fixation.

PURPOSE: To validate the effectiveness of percutaneous pedicle screw (PPS) fixation for spinal fractures associated with diffuse idiopathic skeletal hyperostosis (DISH) by comparing surgical outcomes for PPS fixation and conventional open posterior fixation. Patients with DISH are vulnerable to unstable spinal fractures caused by trivial trauma, and these fractures have high rates of delayed paralysis, postoperative complications, and mortality. METHODS: This retrospective study assessed surgical outcomes for 16 patients with DISH (12 men; mean age 76.1 ± 9.4 years) who underwent PPS fixation for spinal fractures (pedicle screw (PS) group), and for a control group of 25 patients with DISH (18 men; mean age 77.9 ± 9.9 years) who underwent conventional open fixation (O group) at our affiliated hospitals from 2007 to 2017. We evaluated the preoperative physical condition (American Society of Anesthesiologists (ASA) classification), neurological status (Frankel grade), and improvement after surgery, fusion length, operating time, estimated blood loss, and perioperative complications. RESULTS: Preoperatively, the PS group consisted of one ASA-1 patient, eight ASA-2 patients, six ASA-3 patients, and one ASA-4 patient; by Frankel grade, there were 2 grade B patients, 13 grade C, 4 grade D, and 6 grade E patients. The O group had 2 ASA-1 patients, 13 ASA-2, 9 ASA-3, and 1 ASA-4 patients. Frankel grades in the O group reflected severe neurological deficits, with 3 grade C patients, 2 grade D, and 11 grade E ( p = 0.032) patients. The two groups had similar rates of neurological improvement (33.3% of PS and 40.0% of O patients; p = 0.410) and mean fusion length (PS 5.1 ± 0.8 segments; O 4.9 ± 1.2). The mean operating time and estimated blood loss were 168.1 ± 46.7 min and 133.9 ± 116.5 g, respectively, in the PS group, and 224.6 ± 49.8 min and 499.9 ± 368.5 g in the O group. Three O-group patients died of hypovolemic shock, respiratory failure, and pneumonia, respectively, within a year of surgery. CONCLUSION: Conventional open posterior fixation and PPS fixation for DISH-related spinal fractures were similar in fusion length and neurological improvement. However, PPS fixation was less invasive and had lower complication rates.

Effectiveness of inactivated influenza vaccine in children by vaccine dose, 2013-18.

OBJECTIVES: We assessed the vaccine effectiveness (VE) of inactivated influenza vaccine (IIV) by vaccine dose in children aged 6 months to 12 years for whom two doses are recommended in Japan to ascertain the appropriate vaccine doses. METHODS: VE was assessed according to a test-negative case-control design based on rapid influenza diagnostic test (RIDT) results. Children aged 6 months to 12 years with a fever ≥38 °C who had received an RIDT in outpatient clinics of 24 hospitals were enrolled for all five seasons since 2013/14. VE by vaccine dose (none vs. once or twice, and once vs. twice) was analyzed. RESULTS: In the dose analysis, 20,033 children were enrolled. Both one- and two-dose regimens significantly reduced cases in preventing any influenza, influenza A, and influenza B, but there was no significant difference in adjusted VE between one- and two-dose regimens overall (adjusted OR, 0.560 [95% CI, 0.505-0.621], 0.550 [95% CI, 0.516-0.586]), 0.549 [95% CI, 0.517-0.583], and 1.014 [95% CI, 0.907-1.135], for none vs. once, none vs. twice, none vs. once or twice, and once vs. twice for any influenza, respectively). Both one- and two-dose regimens significantly reduced cases with any influenza and influenza A every season. Also, both regimens significantly reduced cases of any influenza, influenza A, and influenza B among children aged 1-12 years, especially among those aged 1-5 years. In the 2013/14, 2015/16, and 2016/17 seasons, however, only the two-dose regimen was significantly effective in preventing influenza B. Both one- and two-dose regimens significantly reduced cases involving hospitalization due to any influenza and influenza A. CONCLUSIONS: Both one- and two-doses regimens of IIV were effective in preventing influenza for children aged 6 months to 12 years. The two-dose regimen was more effective against influenza B in some seasons.