Publications by authors named "Toshifumi Yodoshi"

30 Publications

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Sarcopenia is highly prevalent in children with autoimmune liver diseases and is linked to visceral fat and parent-perceived general health.

Liver Int 2021 Nov 24. Epub 2021 Nov 24.

Division of Gastroenterology, Hepatology and Nutrition, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, USA.

Background: Patients with autoimmune hepatitis (AIH) and primary or autoimmune sclerosing cholangitis are at nutritional risk; their body composition and has not been extensively studied. We aimed to describe their body composition and identify clinical links.

Methods: Using magnetic resonance imaging (MRI), two reviewers segmented total psoas muscle area (tPMSA), visceral fat area (VFA) and subcutaneous fat area (mm ) and measured visceral and subcutaneous thickness (mm). Clinical, laboratory and quality of life (QoL; using PedsQL) data were collected. Sarcopenia was defined as tPMSA ≤5th percentile. Analysis of variance, Wilcoxon rank test and multivariable modelling were performed. A paediatric cohort with non-alcoholic fatty liver disease (NAFLD) was used as a comparator following propensity score matching.

Results: Fifty-eight patients with autoimmune liver disease (AILD) (33 [57%] with AIH) were included: median age 16 years (interquartile range [IQR]: 13-18), 33 (57%) male. Median time from diagnosis to MRI was 15 months (IQR: 2-39 months). Two patients (3%) had a BMIz indicative of mild malnutrition. tPMSA was measurable in 52 subjects (90%). Of those, 25 (48%) had sarcopenia. Sarcopenic patients had a lower blood urea nitrogen compared to non-sarcopenic (median [IQR]: 9.5 [8.0, 12.0] vs 11 [10, 14] mg/dL; P = .023). There was no difference in corticosteroid use between groups. The VFA of sarcopenic patients was higher (3156 [2064, 7492]) vs 2084 [688, 3092]) mm ; P = .005). Patient-reported QoL negatively associated with VFA and general health negatively associated with VFA. Compared with NAFLD, the odds ratio for sarcopenia with AILD was 14.5 (95% confidence interval: 2.3-90.7).

Conclusion: In autoimmune liver diseases, sarcopenia is highly prevalent, associated with increased visceral fat and QoL.
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http://dx.doi.org/10.1111/liv.15108DOI Listing
November 2021

5-Aminosalicylic acid-induced pericarditis in pediatric Crohn's disease.

Pediatr Int 2021 Oct 3. Epub 2021 Oct 3.

Department of Pediatrics, Okinawa Chubu Hospital, Okinawa, Japan.

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http://dx.doi.org/10.1111/ped.14710DOI Listing
October 2021

Another Challenge of Family Medicine Residency Training in Japan.

Fam Med 2021 09;53(8):730-731

Department of Pediatrics, Okinawa Chubu Hospital Okinawa, Japan.

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http://dx.doi.org/10.22454/FamMed.2021.178064DOI Listing
September 2021

Impedance-based measures of muscle mass can be used to predict severity of hepatic steatosis in pediatric nonalcoholic fatty liver disease.

Nutrition 2021 Nov-Dec;91-92:111447. Epub 2021 Aug 10.

Division of Gastroenterology, Hepatology and Nutrition, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, USA; Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, Ohio, USA. Electronic address:

Objectives: The objective of this study was to investigate the association between measures of body composition based on bioelectrical impedance analysis (BIA) and histologic severity of liver disease in a pediatric cohort with nonalcoholic fatty liver disease (NAFLD).

Methods: This was a cross-sectional study of patients < 20 y old with histologically confirmed NAFLD followed in our Steatohepatitis Center from 2017 to 2019. Contemporaneous body-composition data were obtained using a multifrequency octopolar BIA device (InBody 370, InBody, Seoul, South Korea). BIA data collected were skeletal muscle mass, appendicular muscle mass, and percentage body fat. Skeletal and appendicular muscle mass were corrected for height (dividing by the square of height), generating their respective indices. Univariate linear and logistic regression, followed by multivariable logistic regression analyses, were used.

Results: Of the 79 children included (27% female, 73% male; 38% Hispanic; median age, 13 y; median body mass index Z-score, 2.43), the median NAFLD Activity Score was 4 (interquartile range, 3-5). In multivariable regression analyses, the skeletal muscle mass index was negatively associated with hepatic steatosis after controlling for confounders (odds ratio, 0.76; 95% confidence interval, 0.62-0.93). Similarly, the appendicular muscle mass index was negatively associated with severity of hepatic steatosis severity (odds ratio, 0.69; 95% confidence interval, 0.53-0.90). In contrast, percentage body fat was not associated with hepatic steatosis. NAFLD Activity Score, lobular inflammation, ballooning scores, and fibrosis stage were not associated with measures of body composition.

Conclusions: There is an inverse association between BIA-based measures of muscle mass and severity of hepatic steatosis in children with NAFLD. BIA data could further inform clinical decision making in this context.
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http://dx.doi.org/10.1016/j.nut.2021.111447DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8595713PMC
August 2021

Body composition measured by bioelectrical impedance analysis is a viable alternative to magnetic resonance imaging in children with nonalcoholic fatty liver disease.

JPEN J Parenter Enteral Nutr 2021 Apr 2. Epub 2021 Apr 2.

Division of Gastroenterology, Hepatology, and Nutrition, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, USA.

Objective: To determine the relationship between bioelectrical impedance analysis (BIA) and magnetic resonance imaging (MRI) obtained measures of body composition in children with nonalcoholic fatty liver disease (NAFLD).

Methods: Youth with obesity and NAFLD who had BIA and abdominal MRI testing were included. BIA measured skeletal muscle mass (SMM), appendicular lean mass (ALM), trunk muscle mass (TMM), and percent body fat. MRI measured total psoas muscle surface area (tPMSA) and fat compartments. Univariate analysis described the relationship between BIA- and MRI-derived measurements. Multivariable regression analyses built a model with body composition measured via MRI.

Results: 115 patients (82 (71%) male, 38 (33%) Hispanic, median age14 years) were included. There was a strong correlation between tPMSA and SMM, ALM, and TMM (correlation coefficients [CCs]: 0.701, 0.689, 0.708, respectively; all P < .001). Higher SMM, ALM, and TMM were associated with higher tPMSA. This association remained after controlling for age, sex, ethnicity, type 2 diabetes mellitus status, and body mass index z-score. Total fat mass by BIA and MRI-determined total, subcutaneous, and intraperitoneal fat area correlated significantly (CCs: 0.813, 0.808, 0.515, respectively; all P < .001). In univariate regression, higher total fat mass by BIA was associated with increased total fat area and increased fat in each of the four regions measured by MRI. After controlling for confounders, the association between total fat mass by BIA and total fat area by MRI persisted.

Conclusions: BIA measures of muscle and fat mass correlate strongly with MRI measures of tPMSA and fat areas in children with obesity and NAFLD.
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http://dx.doi.org/10.1002/jpen.2113DOI Listing
April 2021

Alternative Etiologies of Liver Disease in Children With Suspected NAFLD.

Pediatrics 2021 04;147(4)

Division of Gastroenterology, Hepatology and Nutrition, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio;

Objectives: To determine the prevalence of alternative causes of liver disease in a cohort of youth with overweight and obesity undergoing evaluation for suspected nonalcoholic fatty liver disease (NAFLD).

Methods: Multicenter, retrospective cohort study of patients aged ≤18 years with overweight and obesity and evidence of elevated serum aminotransferases and/or hepatic steatosis on imaging, referred for suspected NAFLD to Cincinnati Children's Hospital Medical Center (2009-2017) or Yale New Haven Children's Hospital (2012-2017). Testing was performed to exclude the following: autoimmune hepatitis (AIH), Wilson disease, viral hepatitis (B and C), thyroid dysfunction, celiac disease, α-1 antitrypsin deficiency, and hemochromatosis.

Results: A total of 900 children with overweight and obesity (63% boys, 26% Hispanic ethnicity) were referred, with a median age of 13 years (range: 2-18). Most had severe obesity ( = 666; 76%) with a median BMI score of 2.45 (interquartile range [IQR]: 2.2-2.7). Median alanine aminotransferase level at presentation was 64 U/L (IQR: 42-95). A clinically indicated liver biopsy was performed in 358 children (40%) at a median of 6 months (IQR: 1-14) post initial visit; of those, 46% had confirmed nonalcoholic steatohepatitis. Positive autoantibodies were observed in 13% of the cohort, but none met criteria for AIH. Only 19 (2%) were found to have other causes of liver disease, with no cases of viral hepatitis or Wilson disease detected.

Conclusions: In a large, multicenter cohort, the vast majority of children with overweight and obesity with presumed or confirmed NAFLD tested negative for other causes of liver disease. In contrast to a previous pediatric report, no patient was diagnosed with AIH.
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http://dx.doi.org/10.1542/peds.2020-009829DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8015155PMC
April 2021

Under-reporting of Hepatic Steatosis in Children: A Missed Opportunity for Early Detection.

J Pediatr 2021 07 19;234:92-98.e2. Epub 2021 Mar 19.

Division of Pediatric Gastroenterology, Hepatology, and Nutrition, Cincinnati Children's Hospital Medical Center, Cincinnati, OH; Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH. Electronic address:

Objective: To determine the prevalence of underreporting of hepatic steatosis found incidentally on computed tomography (CT).

Study Design: Retrospective cross-sectional study including patients <18 years of age who had undergone unenhanced abdominal CT for evaluation of nephrolithiasis. Hepatic and splenic attenuation were measured independently by 2 reviewers. Hepatic steatosis was defined using various previously established criteria (4 original criteria designed to detect moderate/severe steatosis and 3 secondary criteria designed to identify mild steatosis). Radiology reports and clinical notes were reviewed for documentation of steatosis. Serum alanine aminotransferase levels were collected. Kappa statistics were used to assess agreement between reviewers.

Results: A total of 584 patients were included. Agreement between reviewers' measurements for categorical classification of presence of steatosis was excellent (kappa statistic agreement >87%). The prevalence of hepatic steatosis ranged from 3% to 35%, depending on the criterion. Using absolute liver attenuation <48 Hounsfield units (most likely reflective of the truth, given alanine aminotransferase distribution and body mass index data), the prevalence was 7% (n = 42). Steatosis was reported for only 12 of 42 (28%) of these patients and was documented in clinical notes in only 3 of those cases.

Conclusions: Hepatic steatosis is underreported as an incidental finding of CT for nephrolithiasis. Given the prevalence and silent nature of nonalcoholic fatty liver disease, a high level of suspicion is needed, so as not to miss the opportunity to identify steatosis in childhood.
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http://dx.doi.org/10.1016/j.jpeds.2021.03.016DOI Listing
July 2021

Can Baseline Characteristics be Used to Predict Liver Disease Outcomes in Pediatric Nonalcoholic Fatty Liver Disease?

Obesity (Silver Spring) 2021 01 13;29(1):171-176. Epub 2020 Nov 13.

Division of Gastroenterology, Hepatology and Nutrition, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, USA.

Objective: Longitudinal studies on childhood predictors of nonalcoholic fatty liver disease (NAFLD) progression are lacking. The objective of this study was to determine whether baseline clinical or laboratory measures predict liver disease outcomes in a pediatric NAFLD cohort.

Methods: A retrospective study of patients with presumed NAFLD was conducted using baseline and follow-up clinical and laboratory measures. Disease outcomes were defined using the mean serum alanine aminotransferase (ALT) levels from 24 to 36 months after the first visit. Logistic regression assessed the relationship between ALT progression/regression and predictor variables. Multivariable regression determined the best model for predicting the ALT outcome. Markov process modeling explored the likelihood for a patient to transition between ALT states.

Results: Of a total of 816 patients identified, 144 had sufficient data. Regression was seen in 26%, whereas 30% progressed. No baseline clinical or laboratory measurements had a significant effect on disease outcomes. Markov modeling demonstrated that subjects were more likely to either remain in their baseline ALT group or worsen rather than improve.

Conclusions: Routinely obtained baseline clinical or laboratory measures cannot help risk-stratify youth with presumed NAFLD in terms of long-term outcomes. Close clinical, radiographic, and histologic evaluation of patients is warranted to determine those at risk of progression.
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http://dx.doi.org/10.1002/oby.22999DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7902314PMC
January 2021

Muscle Mass Is Linked to Liver Disease Severity in Pediatric Nonalcoholic Fatty Liver Disease.

J Pediatr 2020 08;223:93-99.e2

Division of Gastroenterology, Hepatology, and Nutrition, University of Cincinnati College of Medicine, Cincinnati, OH; Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH. Electronic address:

Objective: To investigate the association between muscle mass and liver disease severity in pediatric patients with non-alcoholic fatty liver disease (NAFLD).

Study Design: This was a retrospective study of patients aged <20 years followed from 2009 to 2018. Muscle mass was estimated in all patients by measuring magnetic resonance imaging-based total psoas muscle surface area (tPMSA) and correcting for height (tPMSA index = tPMSA/height). Two cohorts were studied, one with histological confirmation of NAFLD (n = 100) and the other with magnetic resonance imaging (MRI) evidence of hepatic steatosis (n = 236). Histology was scored using Nonalcoholic Steatohepatitis Clinical Research Network (NASH CRN) criteria. MRI-measured proton density fat fraction (PDFF) and liver stiffness were collected. Demographic, clinical, and socioeconomic status (using a validated Community Deprivation Index [CDI]) were assessed as covariates. Univariate regression analyses, followed by multivariable regression analyses, were used to determine the relationships between tPMSA index and NAS, MRI-PDFF, and liver stiffness, adjusting for clinical, demographic, and CDI variables.

Results: In the multivariable regression analyses, higher steatosis score was associated with a lower tPMSA index (OR, 0.73; 95% CI, 0.56-0.96) and younger age (OR, 0.84; 95% CI, 0.73-0.97). Liver PDFF was also significantly associated with the tPMSA index (P = .029), sex (P = .019), and CDI (P = .005). In contrast, liver stiffness was not associated with tPMSA in multivariable analyses.

Conclusions: tPMSA index was independently associated with both imaging and histological features of hepatic steatosis severity in children. Future studies should directly explore the presence and directionality of causative links between muscle mass and steatosis, as well as whether interventions that enhance muscle mass can reduce disease severity in children with NAFLD.
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http://dx.doi.org/10.1016/j.jpeds.2020.04.046DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8017767PMC
August 2020

Significance of autoantibody seropositivity in children with obesity and non-alcoholic fatty liver disease.

Pediatr Obes 2021 01 8;16(1):e12696. Epub 2020 Jul 8.

Section of Gastroenterology and Hepatology, Department of Pediatrics, Yale University School of Medicine, New Haven, Connecticut.

Background: Autoantibodies are frequently positive in adults with nonalcoholic fatty liver disease (NAFLD) without concurrent autoimmune hepatitis (AIH). The clinical significance of this is unknown in children.

Objective: To determine the prevalence of autoantibody positivity in pediatric NAFLD and to evaluate its association with disease severity.

Methods: Multicenter, retrospective study of patients ≤18 years of age with biopsy-confirmed NAFLD. Descriptive statistics were used and groups were compared using Wilcoxon-Mann Whitney or χ testing, and multivariable logistic regression was used for binary or ordinal outcomes.

Results: One hundred and thirty six patients with a median age of 14 years were included. The median body mass index Z-score was 2.5 (interquartile range 2.2, 2.6). Positive antinuclear antibody (ANA), anti-smooth muscle antibody (ASMA), anti-liver-kidney microsomal antibody, or any combination of autoantibodies were observed in 22%, 14%, 0%, and 33% of patients, respectively. The proportion of patients with a steatosis score ≥2 was significantly higher in those with positive ANA (P = .045). In the multivariable regression analysis, positive ANA was associated with increased odds of steatosis score ≥2 (odds ratio, 5.91; 95% confidential interval, 1.50-23.26), after controlling for potential confounders. No other significant histology differences were seen between the groups.

Conclusions: Positive ANA and ASMA are common in children with NAFLD; however, anti-LKM positivity is not. ANA positivity is associated with more severe steatosis.
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http://dx.doi.org/10.1111/ijpo.12696DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8006542PMC
January 2021

Improving the feasibility of academic writing by pediatric residents.

Pediatr Int 2020 06;62(6):762

Department of Family and Community Medicine, Hamamatsu University School of Medicine, Shizuoka, Japan.

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http://dx.doi.org/10.1111/ped.14193DOI Listing
June 2020

Pediatric endoscopy training in a community hospital in Japan.

Pediatr Int 2020 06 19;62(6):740-741. Epub 2020 May 19.

International University of Health and Welfare, Tokyo, Japan.

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http://dx.doi.org/10.1111/ped.14165DOI Listing
June 2020

Glomerular Hyperfiltration Is Associated with Liver Disease Severity in Children with Nonalcoholic Fatty Liver Disease.

J Pediatr 2020 07 4;222:127-133. Epub 2020 May 4.

Division of Gastroenterology, Hepatology, and Nutrition, Cincinnati Children's Hospital Medical Center, Cincinnati, OH; Department of Pediatrics, University of Cincinnati School of Medicine, Cincinnati, OH. Electronic address:

Objectives: To determine the prevalence of renal impairment in a large cohort of youths with histologically confirmed nonalcoholic fatty liver disease (NAFLD), and to determine its association with liver disease severity.

Study Design: Clinical, laboratory, and histology data were collected retrospectively in a pediatric cohort with biopsy-confirmed NAFLD at a tertiary care center between 2010 and 2017. Histological NAFLD severity was scored using validated criteria. Glomerular filtration rate (GFR) was calculated and categorized as low (<90 mL/min/1.73 m), normal (90-136 mL/min/1.73 m), or high (>136 mL/min/1.73 m). Univariate and multivariate modeling were used to determine differences between the GFR groups and to control for confounders.

Results: The cohort comprised 179 patients (82% non-Hispanic; median age; 14 years; IQR, 12-16 years). One-third of the patients had abnormal renal function, including 36 (20%) with glomerular hyperfiltration and 26 (15%) with low GFR. In multivariable logistic regression, compared with normal GFR, hyperfiltration was independently associated with higher NAFLD activity score (aOR, 2.96; 95% CI, 1.49-5.87; P = .002), after adjusting for age, sex, ethnicity, obesity severity, presence of type 2 diabetes mellitus, and medications.

Conclusions: In this large cohort with histologically confirmed NAFLD, renal impairment was highly prevalent and associated with liver disease severity, independent of obesity severity. Screening patients with confirmed NAFLD for renal complication is recommended.
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http://dx.doi.org/10.1016/j.jpeds.2020.03.038DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8218655PMC
July 2020

Identifying Predictors of Response to Vitamin E for the Treatment of Pediatric Nonalcoholic Steatohepatitis.

JPEN J Parenter Enteral Nutr 2020 09 27;44(7):1301-1307. Epub 2020 Jan 27.

Division of Gastroenterology, Hepatology and Nutrition, Cincinnati Children's Hospital Medical Center, University of Cincinnati College of Medicine, Cincinnati, Ohio, USA.

Background: A subset of patients with nonalcoholic steatohepatitis (NASH) respond to treatment with vitamin E. The characteristics of responders are not known. The objective of this study was to investigate the outcomes of vitamin E use in clinical practice and to determine factors associated with response to treatment.

Methods: A pediatric cohort with NASH treated with vitamin E for 6-24 months was studied retrospectively. Vitamin E response was defined as alanine aminotransferase (ALT) normalization or >50% ALT reduction from baseline. Univariate and multivariate logistic regression was used to determine the predictors of response to vitamin E. Available paired liver biopsy data were analyzed to determine histologic response.

Results: Of the 151 children prescribed vitamin E, 73 met inclusion/exclusion criteria. Of those, 28 (38%) were vitamin E responders. Higher baseline serum alkaline phosphatase (ALP) levels, steatosis grade, and Nonalcoholic Fatty Liver Disease Activity Score (NAS) were associated with response to vitamin E (ALP: odds ratio [OR], 14.1; 95% CI, 1.7-118.6; steatosis: OR 2.5; 95% CI, 1.2-5.0; NAS: OR 1.6; 95% CI, 1.1-2.4). In a multivariate logistic regression model, ALP and steatosis grade rendered an area under the curve of 0.75 (P < .001) for the prediction of response to treatment. Ballooning, NAS, and portal inflammation improved significantly with vitamin E in the subcohort (n = 15) with paired liver biopsies.

Conclusions: Vitamin E treatment was associated with significant ALT response in 38% of children. Baseline serum ALP levels and steatosis grade were associated with response to treatment.
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http://dx.doi.org/10.1002/jpen.1766DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7590297PMC
September 2020

Severe obesity is associated with liver disease severity in pediatric non-alcoholic fatty liver disease.

Pediatr Obes 2020 02 27;15(2):e12581. Epub 2019 Oct 27.

Division of Gastroenterology, Hepatology and Nutrition, Cincinnati Children's Hospital Medical Center, Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, Ohio.

Background: Paediatric non-alcoholic fatty liver disease (NAFLD) is highly prevalent among children with obesity. The primary objective of this study was determining whether obesity severity is associated with NAFLD severity. By using paediatric classifications for severe obesity, clinicians may be able to better risk stratify patients, which in turn would guide more effective management and treatment.

Methods: Retrospective cohort study including patients followed at Cincinnati Children's Medical Center for NAFLD. Patients were categorized as overweight or class I, II, III obese based on established body mass index (BMI) cut-offs. Liver disease severity was determined using biochemical, imaging (magnetic resonance elastography [MRE]), and histologic evidence of liver injury.

Results: Three cohorts were studied individually based on the method used to assess disease severity (biochemical n = 767, imaging n = 366, and histology n = 249). Between the three cohorts, there were significant differences in age, proportion of patients with class II and class III obesity, and serum alanine transaminase (ALT) levels. In the biochemistry cohort, the odds of having ALT > 80 U/L were highest in patients with class III obesity (P = .026). In the imaging cohort, liver stiffness was significantly different between BMI groups of patients (P = .001). In the histology cohort, those with class III obesity had significantly higher odds of NAFLD activity score (NAS) ≥ 5 (P = .012).

Discussion: Obesity severity is associated with liver disease severity. Patients with more severe obesity are more likely to have more advanced liver disease, a finding that can assist in risk stratification, as well as monitoring and treatment approaches.
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http://dx.doi.org/10.1111/ijpo.12581DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8006543PMC
February 2020

Community Socioeconomic Deprivation and Nonalcoholic Fatty Liver Disease Severity.

J Pediatr Gastroenterol Nutr 2020 03;70(3):364-370

Division of Gastroenterology, Hepatology and Nutrition.

Background And Objectives: Nonalcoholic fatty liver disease (NAFLD) is linked to obesity. Obesity is associated with lower socioeconomic status (SES). An independent link between pediatric NAFLD and SES has not been elucidated. The objective of this study was to evaluate the distribution of socioeconomic deprivation, measured using an area-level proxy, in pediatric patients with known NAFLD and to determine whether deprivation is associated with liver disease severity.

Methods: Retrospective study of patients <21 years with NAFLD, followed from 2009 to 2018. The patients' addresses were mapped to census tracts, which were then linked to the community deprivation index (CDI; range 0--1, higher values indicating higher deprivation, calculated from six SES-related variables available publicly in US Census databases).

Results: Two cohorts were evaluated; 1 with MRI (magnetic resonance imaging) and/or MRE (magnetic resonance elastography) findings indicative of NAFLD (n = 334), and another with biopsy-confirmed NAFLD (n = 245). In the MRI and histology cohorts, the majority were boys (66%), non-Hispanic (77%-78%), severely obese (79%-80%), and publicly insured (55%-56%, respectively). The median CDI for both groups was 0.36 (range 0.15-0.85). In both cohorts, patients living above the median CDI were more likely to be younger at initial presentation, time of MRI, and time of liver biopsy. MRI-measured fat fraction and liver stiffness, as well as histologic characteristics were not different between the high- and low-deprivation groups.

Conclusions: Children with NAFLD were found across the spectrum of deprivation. Although children from more deprived neighborhoods present at a younger age, they exhibit the same degree of NAFLD severity as their peers from less deprived areas.
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http://dx.doi.org/10.1097/MPG.0000000000002527DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8054652PMC
March 2020

Vitamin D deficiency: prevalence and association with liver disease severity in pediatric nonalcoholic fatty liver disease.

Eur J Clin Nutr 2020 03 23;74(3):427-435. Epub 2019 Aug 23.

Division of Gastroenterology, Hepatology and Nutrition, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA.

Background/objectives: To determine associations between serum 25-hydroxyvitamin D (25(OH)-D) concentrations and histologic nonalcoholic fatty liver disease (NAFLD) severity.

Subjects/methods: Clinical, laboratory, and histology data were collected retrospectively in a pediatric cohort with biopsy-confirmed NAFLD. Serum 25(OH)-D concentrations were used to define vitamin D deficiency (≤20 ng/ml), insufficiency (21-30 ng/ml), and sufficiency (≥31 ng/ml).

Results: In all, 234 patients (78% non-Hispanic, median age 14 years) were included. The majority (n = 193) were either vitamin D insufficient (50%) or deficient (32%). Eighty-four patients (36%) reported taking vitamin D supplements at the time of biopsy; serum 25(OH)-D concentrations were not higher in those supplemented. There were no differences in the demographic, clinical, and laboratory characteristics of the three vitamin D status groups. Severity of steatosis, ballooning, lobular/portal inflammation, and NAFLD activity score were also not different between the groups. The proportion of patients with significant fibrosis (stage ≥ 2) was higher in those with insufficiency (29%) compared to those who were sufficient (17%) or deficient (15%, p = 0.04). After controlling for important covariates selected from age, body mass index, ethnicity, vitamin D supplementation, and season, the insufficient group had increased odds of a higher fibrosis score compared to the sufficient group (adjusted OR, 2.04; 95%CI, 1.02-4.08).

Conclusions: Vitamin D deficiency and insufficiency are common in children with NAFLD, but not consistently related with histologic disease severity. Prospective longitudinal studies are needed to determine optimal dosing strategies to achieve sufficiency and to determine whether adequate supplementation has an impact on histology.
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http://dx.doi.org/10.1038/s41430-019-0493-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8006544PMC
March 2020

Skin preparation for prevention of peripheral blood culture contamination in children.

Pediatr Int 2019 Jul 23;61(7):647-651. Epub 2019 Jul 23.

Division of Pediatric Emergency Medicine, Department of Pediatrics, BC Children's Hospital Research Institute, University of British Columbia, Vancouver, British Columbia, Canada.

Background: In Japan, blood cultures for children are performed by pediatric residents, and povidone-iodine (PI) is the recommended solution for skin preparation. Given that PI needs to be applied for 1.5-2 min before venipuncture, skin preparation may be suboptimal if this is not followed. In this study, we investigated the blood culture contamination rate after skin preparation with only 70% isopropyl alcohol (IPA) or IPA plus PI.

Methods: We performed a retrospective study of patients aged ≤6 years who provided blood cultures in the emergency department or pediatric ward. Patients with indwelling central venous catheter were excluded. We evaluated the impact of changing the method of skin preparation, comparing the traditional method using IPA plus PI between 2008 and 2010 (IPA + PI group) with the simplified method using only IPA between 2015 and 2017 (IPA group).

Results: A total of 5,365 blood culture samples were eligible for this study. Of these, 171 (3.2%) had an organism identified in blood culture. Of the blood culture-positive samples, 68 (1.3%) were true positive and 103 (1.9%) were contaminated. Thirty-eight (1.6%) of 2,407 cultures in the IPA group were contaminated, whereas 65 (2.2%) of 2,958 cultures in the IPA + PI group were contaminated (OR, 0.72; 95%CI: 0.48-1.07; P = 0.1). Coagulase-negative Staphylococcus grew significantly less in the IPA group (1.7% vs 1.0%, P = 0.02).

Conclusions: A single application of 70% IPA may be the optimal skin preparation method for obtaining peripheral blood cultures from children in Japan.
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http://dx.doi.org/10.1111/ped.13906DOI Listing
July 2019

Psychotropic Medications Are Associated With Increased Liver Disease Severity in Pediatric Nonalcoholic Fatty Liver Disease.

J Pediatr Gastroenterol Nutr 2019 09;69(3):339-343

Division of Gastroenterology, Hepatology and Nutrition.

Objectives: The aim of the study was to determine whether pediatric patients with nonalcoholic fatty liver disease (NAFLD) exposed to psychotropic medications have more severe liver disease compared to their counterparts who are not on these medications. We hypothesize that use of psychotropic agents is associated with liver disease severity.

Methods: Children and adolescents with biopsy-confirmed NAFLD were included in this study. Histology data, detailed clinical information, and results of serum biochemistries performed within 3 months of the liver biopsy were collected retrospectively. Univariate and multivariate modeling was used to determine differences between the groups and to control for confounders.

Results: A total of 228 patients were included, 17 (8%) of whom where on psychotropic medications at the time of the liver biopsy. Patients on psychotropic medications were more likely to also be on metformin (53% vs 18%, P < 0.01) and antihypertensive medications (29% vs 8%, P < 0.01) compared to children with NAFLD who were not on psychotropic agents. There were no differences in regards to biochemical evidence of liver injury, insulin resistance, and dyslipidemia between the groups. On histology, however, the use of psychotropic medications was associated with increased steatosis severity (score 2.4 vs 1.9, P = 0.04) and increased likelihood of having an NAFLD Activity Score ≥5 (seen in 59% vs 35% or patients; P = 0.05, respectively).

Conclusions: In this large cohort of children with biopsy-confirmed NAFLD, the use of psychotropic medications was associated with increased liver disease severity. Exposure to psychotropic agents should be considered when risk stratifying children with NAFLD.
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http://dx.doi.org/10.1097/MPG.0000000000002401DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8525622PMC
September 2019

Utility of point-of-care Gram stain by physicians for urinary tract infection in children ≤36 months.

Medicine (Baltimore) 2019 Apr;98(14):e15101

Department of Pediatrics, Okinawa Chubu Hospital, Okinawa.

Urinary tract infection (UTI) in children requires early diagnosis and treatment to prevent repeated UTI and renal scarring. This study aimed to evaluate the usefulness of the point-of-care Gram stain by physicians for suspected UTI in children at Okinawa Chubu Hospital as a rapid diagnostic test.A single-center, retrospective study was undertaken between January 2011 and December 2015. Patients aged 36 months or younger who were reviewed had suspected UTI in the emergency room or outpatient clinic. Urine culture, urinalysis, and point-of-care Gram stain were performed on a single specimen. Patients with structural or functional urological defects requiring routine catheterization were excluded. We compared the diagnostic performance among the rapid diagnostic tests (i.e., pyuria, point-of-care Gram stain, or both). Kappa statistics were used to evaluate the agreement between the results of point-of-care Gram stain and morphotypes of urine culture with the 95% CI (bias corrected bootstrap interval). We also analyzed which antibiotics were more susceptible to the bacteria of urine culture results, selected by the results of point-of-care Gram stain or empirical treatment based on the Japanese guidelines by McNemar test.Of 1594 patients reviewed in the study, 1546 were eligible according to our inclusion criteria. Using urine culture as the gold standard for UTI, the sensitivity and specificity of pyuria were 73.2% and 95.1%, whereas those of the point-of-care Gram stain were 81.4% and 98.2%, respectively. The concordance rate between the morphotypes of bacteria detected by point-of-care Gram stain and those of urine culture was 0.784 (kappa coefficient) (95% CI 0.736-0.831). Furthermore, the proportion of "susceptible" in the minimum inhibitory concentration of pathogen-targeted treatment based on the point-of-care Gram stain was higher than that of empirical therapy (exact McNemar significance probability: .0001).Our analysis suggests that the point-of-care Gram stain is a useful rapid diagnostic tool for suspected UTI in young children. Pathogen-targeted treatment based on the point-of-care Gram stain would lead to better antibiotic selection compared with empirical therapy.
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http://dx.doi.org/10.1097/MD.0000000000015101DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6456128PMC
April 2019

Correlation of patient complexity with the burden for health-related professions, and differences in the burden between the professions at a Japanese regional hospital: a prospective cohort study.

BMJ Open 2019 02 21;9(2):e025176. Epub 2019 Feb 21.

Centre for Family Medicine Development, Japanese Health and Welfare Co-operative, Tokyo, Japan.

Objectives: An ageing society includes high patient complexity. Various biopsychosocial problems result in a high burden for health-related professionals. The direct relationship between the burden and patient complexity, however, has not been reported. We aimed to examine correlations between the burden for the attending physicians and nurses, and Patient Centred Assessment Method (PCAM) scores of patient complexity.

Design: Prospective cohort study.

Setting: A regional secondary care hospital in Japan.

Participants: We included all inpatients admitted to our acute care unit between 1 July 2014 and 30 September 2014. Exclusion criteria were age <20 years, refusal to participate in the study and length of stay fixed at the time of admission.

Main Predictor: PCAM total score in the initial phase of hospital admission.

Main Outcome: The burden for each profession (measured on a Visual Analogue Scale).

Results: In total, 201 inpatients participated [female/male=98/103, mean (SD) age of 77.4±11.9 years]. Spearman's rank correlation coefficients between the burden and the PCAM score ranged from 0.23 to 0.32. All p values were <0.05. Multivariate analysis was conducted using multilevel mixed-effects linear regression to determine the association between the burden and the PCAM score in two models. Model 1 used the total PCAM score as the predictive variable. Model 2 used the PCAM factors, patient-oriented complexity and medicine-oriented complexity, as predictive variables. In Model 2, with the burden of physicians, medicine-oriented complexity was statistically significant, whereas with the burden of nurses, both age and patient-oriented complexity were statistically significant.

Conclusions: PCAM scores correlated with the burden for physicians and nurses. Individual PCAM factors affected the burden for each profession differently.
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http://dx.doi.org/10.1136/bmjopen-2018-025176DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6398801PMC
February 2019

Giant Portomesenteric Venous Thrombosis Associated With Rectal Bleeding in a Child.

J Pediatr Gastroenterol Nutr 2019 08;69(2):e54

Department of Emergency Medicine, Mary Bridge Children's Hospital, Tacoma, WA.

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http://dx.doi.org/10.1097/MPG.0000000000002220DOI Listing
August 2019

Clinical Safety and Utility of Pediatric Balloon-assisted Enteroscopy: A Multicenter Prospective Study in Japan.

J Pediatr Gastroenterol Nutr 2019 03;68(3):306-310

Department of Pediatrics, Shinshu University School of Medicine, Matsumoto, Nagano Prefecture, Japan.

Objectives: The benefit of balloon-assisted enteroscopy (BAE) had been recently documented in pediatric patients, but previous reports are based on single institution experiences. We evaluated the feasibility of pediatric BAE in 8 tertiary referral hospitals throughout Japan.

Methods: This was a prospective, multi-institutional study. Patients younger than 18 years were enrolled between April 2014 and March 2017 to undergo double-balloon or single-balloon enteroscopy. Data were collected prospectively using a standardized questionnaire.

Results: We enrolled 79 pediatric patients (96 procedures, 70 boys, 26 girls; median age 12.7 years, range 1-17 years). Antegrade (oral-route) BAE was performed in 20 procedures (lowest body weight 12.9 kg, youngest age 3.7 years), and retrograde (anal-route) BAE in 76 (lowest body weight 10.8 kg, youngest age 1.6 years). Severe adverse events were associated with BAE in 2 patients: 1 with hemorrhage due to polypectomy and 1 with pancreatitis after double-balloon endoscopic retrograde cholangioscopy. No intestinal perforation was reported. Procedure duration of oral-route BAE for diagnosis was significantly longer than anal-route for diagnosis (P < 0.001). The overall diagnostic yield for rectal bleeding/positive fecal occult blood test and abdominal pain was 48%. Among 40 patients referred for diagnosis who did not undergo capsule endoscopy, diagnoses were confirmed in 17 (42.5%) patients after BAE.

Conclusions: This prospective multicenter observational study documents the efficacy of BAE in pediatric patients.
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http://dx.doi.org/10.1097/MPG.0000000000002181DOI Listing
March 2019

Fecal Microbiota Transplantation to Patients with Refractory Very Early Onset Ulcerative Colitis.

Pediatr Gastroenterol Hepatol Nutr 2018 Oct 10;21(4):355-360. Epub 2018 Oct 10.

Department of Emergency Medicine, Mary Bridge Children's Hospital, Tacoma, WA, United States.

Recently, fecal microbiota transplantation (FMT) has been attracting attention as a possible medical treatment of ulcerative colitis (UC). A randomized controlled trial of FMT for children with UC is currently underway. Therapeutic effects of FMT for adults with UC remain controversial. We report two cases of early-onset UC in children. A patient was diagnosed with UC at age 1-year 9-month and underwent FMT at age 2-year 3-month. He attained clinical remission for three weeks after FMT, but then relapsed at four weeks, ultimately undergoing a total colectomy. Another child was diagnosed with UC at 2-year 10-month and she underwent FMT at age 5 years. She has remained in clinical remission following FMT for 24 months and her UC has been maintained without complications with tacrolimus and azathioprine. We report that FMT for early-onset UC appears to be safe and potentially effective.
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http://dx.doi.org/10.5223/pghn.2018.21.4.355DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6182486PMC
October 2018

Avoiding diagnostic delay for mucopolysaccharidosis IIIB: do not overlook common clues such as wheezing and otitis media.

BMJ Case Rep 2018 Jul 25;2018. Epub 2018 Jul 25.

Department of Emergency Medicine, Mary Bridge Children's Hospital and Health Center, Tacoma, Washington, USA.

Mucopolysaccharidosis IIIB (MPS IIIB) is an autosomal recessive lysosomal storage disorder. In comparison to Hurler syndrome (MPS I) and Hunter syndrome (MPS II), characteristic facial and physical features tend to be milder and progression of neurological symptoms may initially be slower. Obvious neurological and behavioural symptoms may not appear until age 2-6 years, but once they begin, progression is relentless, leading to death by the early 20s. Although there is currently no known cure for MPS IIIB, enzyme replacement clinical trials are showing hope for delay in the progression of symptoms. Early diagnosis is therefore necessary before neurological symptoms have progressed. In our case, MPS IIIB was diagnosed at an early age because recurrent wheezing and otitis media in conjunction with hepatomegaly were recognised as more than trivial findings. A thorough examination and a definitive proactive decision to perform a liver biopsy resulted in early diagnosis of a rare disease.
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http://dx.doi.org/10.1136/bcr-2018-224412DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6067142PMC
July 2018

Gas in the right hemiscrotum? Amyand's hernia in a neonate.

BMJ Case Rep 2018 Apr 19;2018. Epub 2018 Apr 19.

Mary Bridge Children's Hospital and Health Center, Department of Emergency Medicine, Tacoma, Washington, USA.

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http://dx.doi.org/10.1136/bcr-2018-224598DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5911102PMC
April 2018

The effects of resistance training of swallowing muscles on dysphagia in older people: A cluster, randomized, controlled trial.

Nutrition 2018 04 27;48:111-116. Epub 2017 Nov 27.

Division of Clinical Epidemiology, Jikei University School of Medicine, Tokyo, Japan.

Objective: This study examined the effects of resistance training of swallowing muscles in community-dwelling older individuals with dysphagia.

Methods: A cluster randomized controlled trial was performed in day-service and day-care facilities. The participants were older (≥65 y) community-dwelling individuals with dysphagia. The intervention group performed a tongue resistance exercise and a head flexion exercise against manual resistance. Both groups received a brochure on dysphagia rehabilitation. The primary endpoint was an improvement in dysphagia assessed by the Eating Assessment Tool (EAT-10) score. Tongue pressure was the secondary endpoint.

Results: Participants included 47 men and 57 women, with a mean age ± standard deviation of 80 ± 7 y. At baseline, the median EAT-10 score was 7 (interquartile range, 5-12). A total of 91 patients, 43 in the intervention group (8 clusters) versus 48 in the control group (11 clusters), were assessed postintervention. The percentage of participants with EAT-10 scores <3 was not statistically significantly different between the two groups (intervention group, 23% versus control group, 19%, P = 0.598). Postintervention median EAT-10 scores were 6 (interquartile range, 3-10) in each group (P = 0.665) and mean tongue pressure was 23.9 ± 10.0 versus 25.9 ± 10.9 kPa (P = 0.376). The intervention did not significantly affect the EAT-10 score or tongue pressure in a mixed effects random intercept model. The Mini Nutritional Assessment Short Form score correlated significantly with the postintervention EAT-10 score.

Conclusions: Resistance training of swallowing muscles did not improve dysphagia in this study. Better nutritional status correlated independently with improved swallowing function.
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http://dx.doi.org/10.1016/j.nut.2017.11.009DOI Listing
April 2018

A Case of Delayed Interval Delivery with a Successful Hospital Move.

Case Rep Pediatr 2015 30;2015:802097. Epub 2015 Aug 30.

Department of Neonatology, United States Naval Hospital Okinawa, Camp Foster, Futenma, Ginowan, Okinawa, Japan.

This report is the first case of delayed interval twin delivery in which the first infant and mother survived without major morbidity following transport to another facility. In addition, this case is only the second report of asynchronous delivery in which both twins survived and neither suffered any major morbidity. A 30-year-old G5P1031 African American female with a diamniotic/dichorionic twin pregnancy presented to U.S. Naval Hospital Okinawa, Japan, at 22 + 5 weeks due to vaginal bleeding. At 23 + 2 weeks, Twin A was born secondary to advanced cervical dilation. Twin A's birth weight was 650 g with APGAR scores of 6 (1 min) and 7 (5 min). Following delivery of Twin A, Placenta A was left in utero with high ligation of the umbilical cord. Due to a scheduled hospital move, the mother and Twin A were transported to the new facility at Camp Foster. Three weeks later, Twin B was delivered at 26 + 4 weeks. Twin B's birth weight was 930 g with APGAR scores of 3 (1 min) and 7 (5 min). Both twins were discharged without IVH, PVL, ROP, or CLD. This case demonstrates the possibility of transporting both the mother and surviving infant A to a higher level of care prior to delivery of subsequent fetuses.
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http://dx.doi.org/10.1155/2015/802097DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4568053PMC
September 2015

A Case of Mild Encephalopathy with a Reversible Splenial Lesion Associated with G5P[6]Rotavirus Infection.

Case Rep Pediatr 2013 13;2013:197163. Epub 2013 Nov 13.

Division of Pediatric Neurology & General, Okinawa Prefectural Nanbu Medical Center & Children's Medical Center, Japan.

We report a case of mild encephalopathy with a reversible splenial lesion (MERS) associated with acute gastroenteritis caused by rotavirus (RV) infection. The patient (male, 4 years and 3 months old) was admitted to our hospital for diarrhea and afebrile seizures. Head MRI revealed a hyperintense signal in the splenium of the corpus callosum on DWI and a hypointense signal on the ADC-map. After awakening from sedation, the patient's disturbance of consciousness improved. On day 5 after admission of the illness, the patient was discharged from the hospital in a good condition. Electroencephalography on day 2 after admission was normal. On day 8 of admission, head MRI revealed that the splenial lesion had disappeared. RV antigen-positive stools suggested that RV had caused MERS. This RV genotype was considered to be G5P[6]; it may have spread to humans as a strain reassortment through substitution of porcine RV into human RV gene segments. This extremely rare genotype was detected first in Japan and is not covered by existing vaccines; this is the first sample isolated from encephalopathy patients. Few reports have investigated RV genotypes in encephalopathy; we believe that this case is valuable for studying the relationship between genotypes and clinical symptoms.
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http://dx.doi.org/10.1155/2013/197163DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3845239PMC
December 2013

Whole genomic analysis of a porcine-like human G5P[6] rotavirus strain isolated from a child with diarrhoea and encephalopathy in Japan.

J Gen Virol 2013 Jul 20;94(Pt 7):1568-1575. Epub 2013 Mar 20.

Department of Virology and Parasitology, Fujita Health University School of Medicine, Toyoake, Aichi 470-1192, Japan.

An unusual rotavirus strain, Ryukyu-1120, with G5P[6] genotypes (RVA/Human-wt/JPN/Ryukyu-1120/2011/G5P[6]) was identified in a stool specimen from a hospitalized child aged 4 years who showed diarrhoea and encephalopathy. In this study, we sequenced and characterized the complete genome of strain Ryukyu-1120. On whole genomic analysis, this strain was found to have a unique genotype constellation: G5-P[6]-I5-R1-C1-M1-A8-N1-T1-E1-H1. The VP6 and NSP1 genotypes I5 and A8 are those commonly found in porcine strains. Furthermore, phylogenetic analysis indicated that each of the 11 genes of strain Ryukyu-1120 appeared to be of porcine origin. Thus, strain Ryukyu-1120 was found to have a porcine rotavirus genetic backbone and is likely to be of porcine origin. To our knowledge, this is the first report of whole-genome-based characterization of the emerging G5P[6] strains in Asian countries. Our observations will provide important insights into the origin of G5P[6] strains and the dynamic interactions between human and porcine rotavirus strains.
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http://dx.doi.org/10.1099/vir.0.051011-0DOI Listing
July 2013
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