Single measurement of bowel wall thickness using intestinal ultrasonography in children with ulcerative colitis.

BACKGROUND: Endoscopic monitoring of disease activity in patients with ulcerative colitis (UC) is important. However, frequent colonoscopic examinations are difficult to perform because of their invasiveness, especially in children. Bowel wall thickness (BWT) measurement using intestinal ultrasonography and fecal calprotectin (FC) measurement are useful noninvasive evaluation methods. METHODS: We retrospectively analyzed BWT and FC levels and evaluated the Mayo endoscopic subscore (MES) using colonoscopy in pediatric patients with UC during the same period. The BWT was evaluated using the maximum BWT (mBWT), which was the maximum value of each colonic BWT; the sum of BWT (sBWT), which was the sum of each colonic BWT; and the sum of the adjusted BWT (saBWT), which was corrected using sBWT. RESULTS: In 54 procedures from 40 patients, FC, mBWT, sBWT, and saBWT were significantly different between MES 0-1 and MES 2. The agreement between BWT and MES 2 was 193 out of 216 segments (89.4%). Sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of FC were 68.8%, 84.2%, 64.7%, 86.5%, and 79.6% respectively, while those of saBWT were 81.2%, 89.5%, 76.5%, 91.9%, 87.0%, respectively. CONCLUSIONS: BWT in each colonic segment, particularly saBWT, was more useful than FC for detecting moderate colonic inflammation (MES 2) in pediatric patients with UC. Therefore, intestinal ultrasonography may be helpful in the less invasive management of pediatric patients with UC.

Survey on digital dependency, writing by hand, and group learning as learning styles among Japanese medical students: Assessing correlations between various accomplishments.

BACKGROUND: Although digital learning devices have become increasingly more common in medical education settings, it remains unclear how they influence medical student learning styles and various outcome measures. This study aimed to assess student learning styles, specifically as they relate to digital dependency, writing habits, and group learning practices among current medical students. MATERIALS AND METHODS: This questionnaire study was approved by the Research Ethics Committee of Osaka Medical and Pharmaceutical University. We conducted a questionnaire survey of 109 medical students who were 5th year students during the 2021 school year. Medical students were asked about their level of digital dependency, writing by hand, and group learning practices. We also analyzed the correlation between student learning styles and their respective outcomes on several summative evaluations. RESULTS: Of the 109 students targeted, we received responses from 62 (response rate, 56.8%). Among the respondents, digital dependency was 83.4 ± 18.6%, while hand writing ratio 39.8 ± 29.9% and group learning ratio 33.5 ± 30.5%. We also assessed correlations between these learning styles and scores on the CBT, OSCE, CC, and CC Integrative Test. Only writing by hand showed a small positive correlation with CC Integrative Test scores. CONCLUSION: Our questionnaire survey assessed the rates of digital dependency, writing by hand, and group learning practices, and analyzed the correlations between these learning styles and respective outcomes. Current medical students exhibited high digital dependency which was not correlated with performance outcomes.

Comparison of Younger and Older medical student performance outcomes: A retrospective analysis in Japan.

The present study examined the impact of age on medical student repeat-year experience and performance outcomes on the objective structured clinical examination (OSCE), Clinical Clerkship (CC), and other relevant examinations in the Japanese medical school system. This retrospective analysis examined the number of students with repeat-years and the years required to graduate, stratifying students by the age they entered medical school (Younger: within 4 years of high school graduation; Older: 5 or more years after high school graduation). Scores of the Pre-CC OSCE, Computer-based testing (CBT), CC performance, CC integrative test, and graduation exams were compared among those graduating from our medical school between 2018 and 2020, and examined correlations between student age and performance outcomes. From 2018 to 2020, 328 medical students graduated. Of these, 283 had entered within 4 years of high school graduation (Younger), while 45 did so 5 or more years after high school graduation (Older). The number of repeat-years did not differ significantly between groups. The average number of years required to graduate was slightly higher for the Older group and the Younger group scored significantly higher on the CC integrative test. No significant differences were found for the remaining tests. These results suggest that older medical students in general show no significant inferiority in their performance of most clinical skills and competencies relative to younger students in Japan.

Antenatal mgnesium sulfate and ritodrine increased potassium levels in preterm infants: A cohort study.

BACKGROUND: Ritodrine and magnesium sulfate are administered to prevent preterm labor. Magnesium sulfate is also administered to prevent preeclampsia. These drugs have been reported to increase potassium levels in pregnant women and neonates. The aim of this study was to investigate the relationship between potassium levels in preterm infants and antenatal treatment. METHODS: This prospective cohort study was conducted at Saiseikai Suita Hospital. Preterm infants born at <35 weeks' gestation between October 2012 and September 2014 were recruited and divided into four groups based on the antenatal treatment their mothers received. Serum and urine electrolyte levels at birth and serum potassium levels 1 day after birth were measured. RESULTS: The mothers of 16 infants received no antenatal treatment (condition C); the mothers of 29 infants received antenatal ritodrine (R); the mothers of seven infants received magnesium sulfate (M); and the mothers of 15 infants received both magnesium sulfate and ritodrine (M + R). At birth, potassium levels were similar among the four groups. However, potassium levels a day after birth were significantly higher in the M + R group than in the other groups: median (min.-max.) mEq/L 4.8 (3.8-6.2), 4.8 (3.6-6.0), and 4.4 (3.8-5.9) vs. 5.8 (4.9-7.2), in the C, R, and M groups versus the M + R group, respectively (P < 0.01). Significantly more infants in the M + R group exhibited a fractional excretion of potassium of <10% compared with those in the other groups. CONCLUSION: The increased potassium levels we observe in preterm infants of mothers who received antenatal magnesium sulfate and ritodrine administration on postnatal day 1 warrant monitoring by neonatologists.

Usefulness of ultrasonography for small intestinal evaluations in pediatric Crohn's disease.

BACKGROUND: Small bowel capsule endoscopy (SBCE) for Crohn's disease is useful; however, its use has some limitations, such as invasiveness when endoscopic assistance is required in patients who cannot swallow the capsule, and the burden of interpretation on a physician. In contrast, intestinal ultrasonography (IUS) is a non-invasive modality for children. The purpose of this study is to evaluate the accuracy of IUS for pediatric patients with established Crohn's disease. METHODS: Small bowel capsule endoscopy and IUS findings from the same period in pediatric patients with established Crohn's disease were analyzed retrospectively. First, we compared the Lewis score (LS), small bowel endoscopic activity, and IUS findings by small bowel wall thickness (SBWT) and mesenteric lymph node size (MLNS). Second, we compared the performance of IUS findings with those of some biomarkers. RESULTS: In 22 procedures, SBWT and MLNS were correlated with LS (r = 0.52, P < 0.05, and r = 0.45, P < 0.05, respectively). Small bowel wall thickness, erythrocyte sedimentation rate, and fecal calprotectin levels had the highest accuracy (81.8%, 81.8%, and 81.8%, respectively). The combination of SBWT and MLNS had the highest positive predictive value and negative predictive value (100% and 83.3%, respectively). CONCLUSIONS: Intestinal ultrasonography findings, including SBWT and MLNS, are useful for monitoring small bowel lesions in pediatric patients with established Crohn's disease. We suggest first evaluating small bowel inflammation by IUS in pediatric patients with Crohn's disease before SBCE because IUS is less invasive than SBCE.

A Case of Gorlin-Goltz Syndrome Without the Characteristic Physical Features That Was Diagnosed After the Development of a Fifth Cancer.

We present a case of Gorlin-Goltz syndrome (GGS) in a patient who developed medulloblastoma, osteosarcoma, myelodysplastic syndrome, basal cell carcinoma, and odontogenic keratocyst by the age of 19 years. He had no known family history and no characteristic physical features of GGS. A frameshift mutation in the PTCH1 gene was found in the oral mucosa as a low-frequency mosaicism, basal cell carcinoma, and normal skin by whole exome sequencing of cancer susceptibility genes. Setting a therapeutic strategy with regard to second cancer development is important for pediatric cancer patients who have a background of cancer predisposition. Advances in comprehensive multigenetic analysis are anticipated to aid in developing such a strategy.

Percentage of overweight is overestimated in children of short stature.

BACKGROUND: The prevalence of overweight and obesity has increased, not just in adults but also in children. In Japan, the percentage of overweight (POW) is widely used for the estimation and assessment of percentage body fat (PBF) for children. We examine whether there is a difference between normal height and short stature children in terms of the relationship between POW and PBF. METHODS: A total of 321 children of normal height (163 boys, 158 girls) and 106 children with short stature (78 boys, 28 girls) were assessed according to sex. Percentage of overweight was used to represent the degree of obesity. The PBF of the total body was examined by dual energy X-ray absorptiometry. RESULTS: According to their PBF, normal height subjects of both sexes were classified as obese if they had a POW of more than 20%. However, short-stature subjects of both sexes were not classified as obese until the boys had a POW of 40%, and girls had a POW of 35%, respectively. Thus, overweight or obesity is overestimated in short stature children in both males and females with the rule "POW above 20% is recognized as obesity." CONCLUSIONS: Percentage of overweight is commonly considered as a good surrogate measure for determining overweight and obesity in children of both sexes. However, this study has clarified that body fat accumulation is overestimated in children with short stature when using the POW measurement.

Pharmacokinetics, Efficacy and Safety of Bosutinib in a Pediatric Patient With Chronic Myeloid Leukemia.

Bosutinib is a second-generation tyrosine kinase inhibitor indicated for treatment of chronic myeloid leukemia (CML) in adult patients. The safety and efficacy of bosutinib in patients younger than 18 years of age have not been established. We here report the case of a 4-year-old male with CML who was treated with bosutinib during coordination of human leukocyte antigen-matched unrelated bone-marrow transplantation because of insufficient responses to imatinib and dasatinib. The patient achieved a complete cytogenetic response immediately after starting bosutinib at 180 mg/day (290 mg/m2/day). Because toxicity was tolerable, the dose was increased to 200 mg/day (330 mg/m2/day). A complete cytogenetic response was maintained, but a major molecular response was not achieved 6 months after initiation of treatment with bosutinib. At steady state, maximum plasma concentration, minimum plasma concentration, and area under the plasma concentration-time curve were 89.2 ng/mL, 16.7 ng/mL, and 1017.4 ng·hr/mL, respectively, at 290 mg/m2/day; and 141.1 ng/mL, 18.9 ng/mL, and 1278.5 ng·hr/mL, respectively, at 330 mg/m2/day. To the best of our knowledge, this is the first case report to show the pharmacokinetics of bosutinib with efficacy and safety in a pediatric patient with CML. This rare case in a very young child with CML can also be valuable reference for clinical practice.

Policy statement of enteral nutrition for preterm and very low birthweight infants.

For preterm and very low birthweight infants, the mother's own milk is the best nutrition. Based on the latest information for mothers who give birth to preterm and very low birthweight infants, medical staff should encourage and assist mothers to pump or express and provide their own milk whenever possible. If the supply of maternal milk is insufficient even though they receive adequate support, or the mother's own milk cannot be given to her infant for any reason, donor human milk should be used. Donors who donate their breast milk need to meet the Guideline of the Japan Human Milk Bank Association. Donor human milk should be provided according to the medical needs of preterm and very low birthweight infants, regardless of their family's financial status. In the future, it will be necessary to create a system to supply an exclusive human milk-based diet (EHMD), consisting of human milk with the addition of a human milk-derived human milk fortifier, to preterm and very low birthweight infants.

Correlation of the endoscopic findings for small and large bowels in pediatric patients with established Crohn's disease.

Small bowel capsule endoscopy can detect subtle mucosal lesions in pediatric patients with Crohn's disease, and our aim was to evaluate its application in established ileocolonic Crohn's disease. Colonic inflammation was evaluated with the colonic Simple Endoscopic Score for Crohn's Disease (SES-CD) (excluding the score of the terminal ileum). Small bowel inflammation was evaluated with the Lewis score and/or Capsule Endoscopy Crohn's Disease Activity Index (CECDAI). A Lewis score <135 was defined as small bowel inactive. A colonic SES-CD of 0 (colonic inactive group) was observed in 22/42 procedures (52.4%), and active small bowel lesions were observed in 11/22 procedures (50.0%). The Lewis score was lower in the colonic inactive group compared to the colonic active group. Correlations between the colonic SES-CD, the Lewis score and CECDAI were weak. The Lewis score and CECDAI in the colonic inactive group had significant correlation with fecal calprotectin levels. We suggest that Crohn's disease patients without both colonic active lesions and elevation of fecal calprotectin levels may not need to receive small bowel capsule endoscopy due to low incidence of lesions in small bowel.

Altered Expression of Retinol Metabolism-Related Genes in an ANIT-Induced Cholestasis Rat Model.

Cholestasis is defined as a reduction of bile secretion caused by a dysfunction of bile formation. Insufficient bile secretion into the intestine undermines the formation of micelles, which may result in the reduced absorption of lipids and fat-soluble vitamins. Here, we investigated the retinol homeostasis and the alterations of retinol metabolism-related genes, including ß-carotene 15,15' monooxygenase (BCMO), lecithin:retinol acyltransferase (LRAT), aldehyde dehydrogenase (ALDH), cytochrome P450 26A1 (CYP26A1), and retinoic acid receptors (RAR) ß, in a α-naphthyl isothiocyanate (ANIT)-induced cholestasis rat model. Moreover, we examined the expression of the farnesoid X receptor (FXR) target genes. Our results showed that plasma retinol levels were decreased in ANIT rats compared to control rats. On the contrary, hepatic retinol levels were not different between the two groups. The expression of FXR target genes in the liver and intestine of cholestasis model rats was repressed. The BCMO expression was decreased in the liver and increased in the intestine of ANIT rats compared to control rats. Finally, the hepatic expression of LRAT, RARß, and ALDH1A1 in cholestatic rats was decreased compared to the control rats, while the CYP26A1 expression of the liver was not altered. The increased expression of intestinal BCMO in cholestasis model rats might compensate for decreased circulatory retinol levels. The BCMO expression might be regulated in a tissue-specific manner to maintain the homeostasis of retinol.

Therapeutic experience with hepatoblastoma associated with trisomy 18.

Trisomy 18 is often fatal, but patients with this disease can now have longer survival due to proactive treatment intervention. However, hepatoblastomas may develop in these patients. In this study, we report four cases of hepatoblastoma associated with trisomy 18. All of the patients had congenital heart disease and three had undergone intracardiac surgical repair. Tumor growth was relatively slow in all cases, and there were no problems with chemotherapy tolerability and surgical resection. Three of the patients are currently disease-free and the fourth is alive with remaining of the tumor. These cases suggest that combined chemotherapy and surgical resection may be an option to treat hepatoblastoma associated with trisomy 18 when cardiac pulmonary function is relatively stable.

Microvascular endothelial function in Japanese early adolescents.

Endothelial dysfunction is the early predictive factor for the development of atherosclerosis and future cardiovascular diseases in adulthood. The prevalence of endothelial dysfunction in children and early adolescents is increasing worldwide. Peripheral arterial tonometry is a noninvasive technique for assessing peripheral microvascular function and is used as a validated marker of endothelial function. We assessed anthropometric parameters, blood pressure, arterial stiffness, and peripheral endothelial function in 157 Japanese early adolescents (75 boys and 82 girls). We measured peripheral endothelial function by using peripheral arterial tonometry to determine the reactive hyperemia index, and assessed the association of reactive hyperemia index with parameters of anthropometry and arterial stiffness. The mean reactive hyperemia index of all subjects was 1.85 ± 0.6, and there was no difference of reactive hyperemia index according to sex. Reactive hyperemia index was significantly associated with systolic and diastolic blood pressures, and had no correlation with anthropometric parameters and arterial stiffness markers. The reactive hyperemia index values among Japanese early adolescents were similar to those reported in previous studies on children and early adolescents. This noninvasive technique may be useful for the assessment of microvascular endothelial function among children and early adolescents.

Evaluation of uric acid levels, thyroid function, and anthropometric parameters in Japanese children with Down syndrome.

Down syndrome, caused by trisomy 21, is characterized by congenital abnormalities as well as mental retardation. From the neonatal stage through adolescence, patients with Down syndrome often have several complications. Thus, it is important to attain knowledge of the prevalence of these comorbidities in children with Down syndrome. We, therefore, evaluated the biochemical data, thyroid function, and anthropometric parameters, and analyzed the association among them in Japanese children and early adolescents with Down syndrome. There was no difference in the prevalence of obesity and overweight between boys and girls. The level of uric acid was higher in boys than in girls. Moreover, the prevalence of hyperuricemia was also higher in boys than in girls (approximately 32% and 10%, respectively). The prevalence of subclinical hypothyroidism in children with Down syndrome was approximately 20%, with no significant sex differences. The levels of uric acid and dehydroepiandrosterone-sulfate were positively associated with age, while the levels of thyroid-stimulating hormone and free thyroxine had a negative association with age. Overall, children with Down syndrome, exhibit a higher incidence of hyperuricemia. Therefore, uric acid levels, as well as thyroid function, from childhood to early adulthood should be monitored in this patient cohort.

Dehydroepiandrosterone alters vitamin E status and prevents lipid peroxidation in vitamin E-deficient rats.

In humans, dehydroepiandrosterone and its sulfate ester metabolite DHEA-S are secreted predominantly from the adrenal cortex, and dehydroepiandrosterone is converted to steroid hormones, including androgens and estrogens, and neurosteroid. Dehydroepiandrosterone exerts protective effects against several pathological conditions. Although there are reports on the association between dehydroepiandrosterone and vitamins, the exact relationship between dehydroepiandrosterone and vitamin E remains to be determined. Therefore, we attempted to elucidate the effect of dehydroepiandrosterone on vitamin E status and the expression of various vitamin E-related proteins, including binding proteins, transporters, and cytochrome P450, in vitamin E-deficient rats. Plasma α-tocopherol levels in vitamin E-deficient rats increased in response to dehydroepiandrosterone administration. The expression of hepatic α-tocopherol transfer protein was repressed in vitamin E-deficient rats compared to that in control rats; however, dehydroepiandrosterone administration significantly upregulated this expression. Hepatic expression of CYP4F2, an α-tocopherol metabolizing enzyme, in vitamin E-deficient rats was decreased by dehydroepiandrosterone administration, whereas hepatic expression of ATP-binding cassette transporter A1, an α-tocopherol transporter, was not altered following dehydroepiandrosterone administration. Dehydroepiandrosterone repressed lipid peroxidation in the liver of vitamin E-deficient rats. Therefore, adequate dehydroepiandrosterone supplementation may improve lipid peroxidation under several pathological conditions, and dehydroepiandrosterone may modulate α-tocopherol levels through altered expression of vitamin E-related proteins.

Dehydroepiandrosterone Alters Retinol Status and Expression of the ß-Carotene 15,15'-Monooxygenase and Lecithin:Retinol Acyltransferase Genes.

Dehydroepiandrosterone (DHEA) and its sulfate ester DHEA-sulfate (DHEA-S) are the most abundant adrenal steroids in humans. DHEA has a critical role as a steroidal precursor of androgens and/or estrogens, and in human studies and animal experiments, both DHEA and DHEA-S have multiple beneficial effects. However, there are few reports regarding the relationship between DHEA and nutrient status, especially for vitamins. Therefore, we elucidated the effect of DHEA administration on retinol status. Wistar rats were fed with a standard diet containing 0.4% (wt/wt) DHEA for 2 wk. We assessed retinol status and the expression of retinol-related proteins, including metabolic enzymes, binding proteins, cytochrome P450 (CYP) enzymes, and antioxidant enzymes. Retinol levels in the plasma and the liver of DHEA-fed rats were lower than those of controls. Expression of ß-carotene 15,15'-monooxygenase (BCMO) in the liver and intestine of DHEA-fed rats was lower, whereas BCMO expression in the testes of DHEA-fed rats was higher than that of controls. Expression of the retinol-metabolizing aldehyde dehydrogenase (ALDH) enzyme ALDH1A2 was repressed in the liver of DHEA rats, whereas ALDH1A1 expression was unaltered. Hepatic expression of lecithin:retinol acyltransferase (LRAT) and CYP26A1 was lower in DHEA-fed rats than in controls. Retinol status in DHEA-fed rats might be affected by altered BCMO expression in the liver and intestine and hepatic LRAT expression, whereas BCMO expression in peripheral tissues may be regulated in a tissue-specific manner. We have shown that DHEA administration may influence retinol status and the expression of retinol-related proteins.

Association of thyroid hormones with obesity and metabolic syndrome in Japanese children.

Obesity is associated with health consequences, and thyroid dysfunction may be an adaption to the increased energy expenditure in obesity. With the rising prevalence of obesity in childhood, the prevalence of metabolic syndrome may also increase. In the current study, we have shown gender differences in the association of thyroid hormones with obesity, and attempted to elucidate the relationship between thyroid hormones and anthropometric parameters and biochemical data in obese Japanese children. We analyzed anthropometric measurements, blood pressure, body composition, thyroid hormones, and lipid profiles in 283 obese children. The association between thyroid hormones and several parameters differed by gender. The free T3 to free T4 ratio (fT3/fT4) in boys was negatively associated with the quantitative insulin sensitivity check index, whereas in girls, thyroid-stimulating hormone levels were positively correlated with levels of glucose, diastolic blood pressure, and non-high density lipoprotein-cholesterol, and fT3/fT4 was positively correlated with uric acid levels. FT3/fT4 in boys with metabolic syndrome was relatively higher than in those without metabolic syndrome. The cause of gender differences is unknown. Therefore, further studies with larger sample sizes and a long-term follow-up period are needed to address the influence of thyroid hormones on various parameters.

Altered retinol status and expression of retinol-related proteins in streptozotocin-induced type 1 diabetic model rats.

Diabetes is a metabolic disorder characterized by chronic hyperglycemia. Advanced diabetes is associated with severe complications and impaired nutritional status. Here, we assessed the expression of retinol-associated proteins, including ß-carotene 15,15'-monooxygenase (BCMO), lecithin:retinol acyltransferase (LRAT), aldehyde dehydrogenase (ALDH), and cytochrome P450 26A1 (CYP26A1), and measured retinol levels in the plasma and liver of streptozotocin (STZ)-induced type 1 diabetic model rats. Compared to the levels in the control rats, retinol levels in the plasma and liver of STZ rats were decreased and increased, respectively. Hepatic expression of the LRAT gene in STZ rats was lower than that in the controls. In the liver of STZ rats, the expression of ALDH1A1, a retinal metabolizing enzyme was higher, whereas ALDH1A2 expression was lower than in the controls. Hepatic CYP26A1 expression in STZ rats was significantly higher than in the control rats. BCMO expression levels in the liver and intestine of STZ rats were much lower than those of the controls. Altered BCMO expression might affect retinol status. It is considered that the metabolic availability of retinol was lessened despite the accelerated catabolism of retinol; therefore, retinol mobilization may be unbalanced in the liver of rats in the type 1 diabetic state.

Retinol status and expression of retinol-related proteins in methionine-choline deficient rats.

Retinol and its derivative, retinoic acid, have pleiotropic functions including vision, immunity, hematopoiesis, reproduction, cell differentiation/growth, and development. Non-alcoholic fatty liver disease (NAFLD) is one of the most common diseases in developed countries and encompasses a broad spectrum of forms, ranging from steatosis to steatohepatitis, which develops further to cirrhosis. Retinol status has an important role in liver homeostasis. The purpose of this study was to evaluate the retinol status and expression of retinol-related proteins, including enzymes and binding proteins, in methionine-choline deficient (MCD) rats as a model of NAFLD. We examined retinol levels in the plasma and liver and gene expression for ß-carotene 15,15'-monooxygenase (BCMO), lecithIn: retinol acyltransferase (LRAT), aldehyde dehydrogenase 1A1 (ALDH1A1), ALDH1A2, and cellular retinol binding protein (CRBP)-I in MCD rats. The plasma retinol levels in MCD rats were lower than those in the controls, whereas hepatic retinol levels in MCD rats were higher. BCMO expression in the intestine and liver in MCD rats was lower, whereas that in the testes and the kidneys was higher than in control rats. Expression of LRAT, CRBP-I, ALDH1A1, and ALDH1A2 in the liver of MCD rats was also higher. Altered expression of retinol-related proteins may affect retinol status in NAFLD.