Potential role of stem cells from human exfoliated deciduous teeth in inducing liver regeneration.

BACKGROUND AND AIM: Even with advancement of medical technologies, liver transplantation still faces several major challenges. Hence, other treatment modalities are urgently needed for patients with end-stage liver disease. Stem cells from human exfoliated deciduous teeth (SHED) was discovered to have highly proliferative and pluripotent properties; including differentiation into hepatocyte-like cells. This study aims to investigate the capability of intrasplenic transplanted SHED and SHED-Hep cells in inducing proliferation of stem cells and native hepatocytes in order to accelerate liver regeneration in liver fibrosis mice models. METHODS: Three carbon tetrachloride (CCl4)-injured male mice groups were used in this study. Two of those groups were transplanted with either SHED or SHED-Hep, while the other did not undergo transplantation. One age- and sex- matched healthy mice group was used as control. All specimens were immunohistochemically stained with anti-Ki-67 antibodies and anti-proliferating cell nuclear antigen (PCNA) antibodies before counter stained with hematoxylin-eosin. RESULTS: Anti-Ki-67 antibodies staining: at both 8 and 12 weeks, proliferating activity was predominantly seen on both SHED- and SHED-Hep-transplanted CCl4-injured mice groups, while control and non-transplanted CCl4-injured mice group showed little to no sign of proliferation activity. Anti-PCNA staining: at both 8 and 12 weeks, significant proliferating activity was detected by PCNA staining, mainly on stem cells population area on SHED- and SHED-Hep-treated group. CONCLUSIONS: In conclusion, this study has provided the evidence that transplantation of SHED or SHED-Hep on liver-injured mice induced proliferation of both transplanted stem cells and native liver cells in order to accelerate liver regeneration.

The role of cardiac power and lactate clearance as an indicator of resuscitation success among pediatric patients with shock in the intensive care unit of Cipto Mangunkusumo Hospital.

BACKGROUND: Shock in children remains the primary cause of mortality and morbidity worldwide. Furthermore, its management outcome is improved using many hemodynamic parameters, such as cardiac power (CP) and lactate clearance (LC). Cardiac power is a contractility index based on the measurement of flow and pressure, and it is a relatively new hemodynamic parameter with limited studies. In contrast, LC has been proven useful as a target outcome in shock resuscitation. This study aims to explore the values of CP and LC in pediatric shock and their association with clinical outcomes. METHODS: This prospective observational study was conducted on children (1 month-18 years old) with shock at Cipto Mangunkusumo Hospital, Indonesia, from April to October 2021. We measured CP using ultrasonic cardiac output monitoring (USCOM®) and serum lactate levels at 0, 1, 6, and 24 h post-initial resuscitation. Subsequently, the variables were described and analyzed with the resuscitation success, length of stay, and mortality. RESULTS: A total of 44 children were analyzed. There were 27 (61.4%), 7 (15.9%), 4 (9.1%), 4 (9.1%), and 2 (4.5%) cases of septic, hypovolemic, cardiogenic, distributive, and obstructive shock, respectively. Within the first 24 h post-initial resuscitation, CP and LC had an increasing trend. Compared to children who had successful resuscitation, those who did not have successful resuscitation had similar CP at all time points (p > 0.05) and lower LC at 1 and 24 h post-initial resuscitation (p < 0.05). Lactate clearance was an acceptable predictor of resuscitation success (area under the curve: 0.795 [95% CI: 0.660-0.931]). An LC of 7.5% had a sensitivity, specificity, positive predictive value, and negative predictive value of 75.00%, 87.5%, 96.43%, and 43.75%, respectively. Lactate clearance in the first hour post-initial resuscitation had a weak correlation (r=-0.362, p < 0.05) with hospital length of stay. We found no difference in CP and LC among survivors compared to nonsurvivors. CONCLUSIONS: We found no evidence that CP was associated with resuscitation success, length of stay, or mortality. Meanwhile, higher LC was associated with successful resuscitation and shorter length of stay at the hospital, but not mortality.

Endoscopic Primary Prophylaxis to Prevent Bleeding in Children with Esophageal Varices: A Systematic Review and Meta-Analysis.

Purpose: This systematic review and meta-analysis aimed to compare endoscopy as primary versus secondary prophylaxis to prevent future bleeding in children with esophageal varices. Methods: A systematic literature search using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses method was conducted using the Scopus, PubMed, and Cochrane databases for relevant studies on the outcome of rebleeding events after endoscopy in primary prophylaxis compared to that in secondary prophylaxis. The following keywords were used: esophageal varices, children, endoscopy, primary prophylaxis and bleeding. The quality of eligible articles was assessed using the Newcastle-Ottawa Scale and statistically analyzed using RevMan 5.4 software. Results: A total of 174 children were included from four eligible articles. All four studies were considered of high-quality based on the Newcastle-Ottawa Quality Assessment Scale. Patients who received primary prophylaxis had 79% lower odds of bleeding than those who received secondary prophylaxis (odds ratio, 0.21; 95% confidence interval [CI], 0.07-0.66; I2=0%, p=0.008). Patients in the primary prophylaxis group underwent fewer endoscopic procedures to eradicate varices than those in the secondary prophylaxis group, with a mean difference of 1.73 (95% CI, 0.91-2.56; I2=62%, p<0.0001). Conclusion: Children with high-risk varices who underwent primary prophylaxis were less likely to experience future bleeding episodes and required fewer endoscopic procedures to eradicate the varices than children who underwent secondary prophylaxis.

Diagnostic challenges of hypoganglionosis based on immunohistochemical method.

Background: Hypoganglionosis resembles Hirschsprung's disease as in both diseases, patients may present with severe constipation or pseudo-obstruction. To date, diagnosis of hypoganglionosis is still difficult to be established due to lack of international consensus regarding diagnostic criteria. This study aims to evaluate the use of immunohistochemistry to provide objective support for our initial subjective impression of hypoganglionosis as well as to describe the morphological features of this study. Methods: This is a cross-sectional study. Three resected intestinal samples from patients with hypoganglionosis at Kyushu University Hospital, Fukuoka, Japan were included in this study. One healthy intestinal sample was used as control. All specimens were immunohistochemically stained with anti-S-100 protein, anti-α-smooth muscle actin (α-SMA), and anti-c-kit protein antibodies. Results: (I) S-100 immunostaining: hypoplasia of the myenteric ganglia and marked reduction of intramuscular nerve fibers were observed in several segments of the intestine. (II) α-SMA immunostaining: the pattern of the muscular layers was almost normal in all segments; however, some areas showed hypotrophy of the circular muscle (CM) layers and hypertrophy of the longitudinal muscle (LM) layers. (III) C-kit immunostaining: a decreased in the number of interstitial cells of Cajal (ICCs) was observed in almost all segments of the resected intestine, even around the myenteric plexus. Conclusions: Each segment of intestine in hypoganglionosis had different numbers of ICCs, sizes, and distributions of ganglions, as well as patterns of musculature, which may range from severely abnormal to nearly normal. Further investigations regarding the definition, etiology, diagnosis, and treatment of this disease should be performed to improve the prognosis of this disease.

Development of clinical-based scoring system to diagnose tuberculous meningitis in children.

OBJECTIVE: Diagnosing tuberculous meningitis (TBM) in children is challenging due to the low sensitivity with time delay of bacterial culture techniques and the lack of brain imaging facilities in many low- and middle-income settings. This study aims to establish and test a scoring system consisting of clinical manifestations on history and examination for diagnosing TBM in children. DESIGN: A retrospective study was conducted using a diagnostic multivariable prediction model. PARTICIPANTS: 167 children diagnosed with meningitis (tuberculous, bacterial, viral and others) aged 3 months to 18 years who were hospitalised from July 2011 until November 2021 in a national tertiary hospital in Indonesia. RESULTS: Eight out of the 10 statistically significant clinical characteristics were used to develop a predictive model. These resulted in good discrimination and calibration variables, which divided into systemic features with a cut-off score of ≥3 (sensitivity 78.8%; specificity 86.6%; the area under the curve (AUC) value 0.89 (95% CI 0.85 to 0.95; p<0.001)) and neurological features with a cut-off score of ≥2 (sensitivity 61.2%; specificity 75.2%; the AUC value 0.73 (95% CI 0.66 to 0.81; p<0.001)). Combined together, this scoring system predicted the diagnosis of TBM with a sensitivity, specificity and positive predictive value of 47.1%, 95.1% and 90.9%, respectively. CONCLUSION: The clinical scoring system consisting of systemic and neurological features can be used to predict the diagnosis of TBM in children with limited resource setting. The scoring system should be assessed in a prospective cohort.

Association Between Pediatric Gastroesophageal Reflux Disease Symptom and Quality of Life Questionnaire Score, Endoscopy and Biopsy in Children with Clinical Gastroesophageal Reflux Disease: A Prospective Study.

Purpose: Gastro esophageal reflux disease (GERD) is a burdensome disease affecting many children. A clinical examination is reported to be unreliable to diagnose GERD in children. This study aimed to investigate the relationship between the Pediatric Gastroesophageal Reflux Disease Symptom and Quality of Life Questionnaire (PGSQ) and endoscopic and histopathological findings in children with symptoms suggesting GERD. Changes in the PGSQ score in children with esophagitis as response to one month therapy were recorded as secondary outcome. Methods: This is a prospective cohort study in the pediatric outpatient clinic in an Indonesian tertiary hospital. Children aged 2-17 years old with clinical symptoms suspected of GERD are included in the study. Blinded endoscopic and histopathological examination was performed in all patients before one month proton pump inhibitors (PPI) therapy. The PGSQ information was collected at inclusion and after one month PPI treatment. Results: Fifty-eight subjects were included. Esophagitis was found in 60.9% of subjects according to endoscopy and 58.6% according to histology. There was no significant relationship between the PGSQ score and endoscopic (p=0.781) nor biopsy (p=0.740) examinations. The PGSQ showed a low diagnostic value compared to endoscopy and biopsy (area under the curve [AUC] 0.477, p=0.477, 95% confidence interval [CI] 0.326-0.629 and AUC 0.474, p=0.740 (95% CI 0.321-0.627 respectively). The PGSQ improved significantly post one month of PPI treatment. Conclusion: The PGSQ cannot be used to diagnose esophagitis in children with clinical symptoms suggesting GERD. However, the PGSQ can be used to monitor the treatment response in children with esophagitis.

Prevalence, Risk Factors, and Pediatrician Awareness of Infant Dyschezia in Indonesia.

Purpose: This study aimed to evaluate the prevalence and risk factors of infant dyschezia as well as pediatrician awareness regarding this disease in Indonesia. Methods: This is a two-part cross-sectional study, which was divided into study A and B. Study A: Parents whose infants were under 9 months old and attended well-baby clinics were recruited at two randomly selected primary health centers. Parents also provided information on the infant's previous medical history, and socio-demographic and family details. The Rome IV criteria was translated and validated to be used for diagnosis of infant dyschezia. Study B: Randomly selected pediatricians were surveyed by using a questionnaire to evaluate their knowledge regarding infant dyschezia. Results: The prevalence of infant dyschezia based on the result of this study was 11.8%. Three risk factors had a significant relationship with infant dyschezia i.e., the number of children in the family (odds ratio [OR], 5.619; 95% confidence interval [CI], 2.194-14.390; p<0.001), complementary food diet (OR, 4.238; 95% CI, 1.902-9.443; p<0.001), and social-emotional disturbance (OR, 5.670; 95% CI, 2.550-12.609; p<0.001). The percentage of pediatricians correctly diagnosed infant dyschezia was 71.5%. Most pediatricians agreed that they did not perform any diagnostic testing (79.7%) and only provided education in cases of infant dyschezia (58.5%). Conclusion: The prevalence of infant dyschezia identified in our study was higher than that in other neighboring Asian countries, with the highest prevalence observed in infants 7-9 months old. Being an only child, receiving complementary food diet, and sociao-emotional disturbances were significant risk factors of infant dyschezia.

Vascular Reactivity Index and PELOD-2 as a mortality predictor in paediatric septic shock: a single-centre retrospective study.

BACKGROUND: The mortality rate for children with septic shock is stil quite high in low-income and middle-income countries (31.7%). One of the most widely used scoring systems to assess mortality in sepsis or septic shock is Paediatric Logistic Organ Dysfunction 2 (PELOD-2). However, it requires various laboratory evaluations. A non-invasive, fast and easy method is needed to assess the mortality of children with septic shock at an early stage. Therefore, this study aims to evaluate the ability of Vascular Reactivity Index (VRI) compared with PELOD-2 score as a predictor of mortality in children with septic shock based on vascular response to vasoactive agents. METHODS: A retrospective cohort study was conducted using data from children aged 1 month to 18 years with septic shock treated in the ER and paediatric intensive care unit (PICU) of the tertiary hospital from 2017 to 2021. The serial haemodynamic data were analysed including Systemic Vascular Resistant Index (SVRI) and the cardiac index from ultrasound cardiac output monitoring device was recorded in the first and sixth hours after the diagnosis of septic shock. The VRI was determined by dividing SVRI/Vasoactive Inotropic Score (ie, accumulated doses of dopamine, dobutamine, epinephrine, milrinone, vasopressin and norepinephrine). The receiver operating curve was used to calculate the area under the curve (AUC), sensitivity and specificity of each cut-off point. RESULTS: A total of 68 subjects fulfilled the inclusion and exclusion criteria, the median age was 54 months with a range of 2-204 months and the mortality rate was 47%. The majority of the patients who died were found in the high cardiac index and low SVRI group (17.6%). Moreover, the optimum cut-off point of VRI was obtained to predict mortality in septic shock of 32.1, with 87.5% sensitivity and 88.9% specificity. The AUC for predicting death using VRI was 95% (95% CI 90% to 100%, p<0.001) and PELOD-2 92.6% (95% CI 96.4% to 98.8%, p<0.001). CONCLUSION: The VRI <32.1 may potentially be used to predict mortality in children with septic shock and its predictive ability is as good as PELOD-2. The assessment of VRI is faster and easier than PELOD-2.

Alopecia in Children Following Living Related Liver Transplantation.

INTRODUCTION: Alopecia is a common complication in patients following kidney transplantation; however, reports regarding liver transplantation patients are still few. METHODS: This study followed 111 children who underwent living related liver transplantation. Alopecia patients and its possible risk factors were analyzed. RESULTS: Alopecia occurred in 3 patients (2.7%). Underlying diseases were biliary atresia and Alagille syndrome. Clinically significant alopecia (universal alopecia) occurred in 1 patient with Alagille syndrome. All patients received tacrolimus as their immunosuppression drug. None of the patients who received cyclosporine experienced alopecia. The onset of alopecia ranged from 7 to 28 months after transplantation. Alopecia was treated with a topical corticosteroid and topical tacrolimus, but 1 patient with clinically severe alopecia required conversion from tacrolimus to cyclosporine A. CONCLUSIONS: Alopecia is 1 complication seen in children receiving tacrolimus therapy following living donor liver transplant. Prompt management of this cosmetic complication should be done to ensure patients' compliance to medication regimen.

Tenth year reenrollment randomized trial investigating the effects of childhood probiotics and calcium supplementation on height and weight at adolescence.

Microbiota and its modification with specific probiotics in early life could provide long term health benefits. Probiotics and calcium strengthen intestinal integrity and may support linear growth. This study investigated the long-term effects of childhood probiotics and calcium supplementation on growth in adolescence. We re-enrolled 238 adolescents aged 11-18 years from 494 children 10-years after 6-months of supplementation with either low-lactose milk fortified with low levels of calcium (LC, âˆ¼50 mg/day, n = 53/124), with regular levels of calcium (RC, ∼440 mg/day, n = 70/126), or with regular calcium + 5 x 108 CFU/day Lactobacillus reuteri DSM 17938 (Reuteri, n = 55/124), or regular calcium + 5 x 108 CFU/day L. casei CRL 431 (Casei, n = 60/120). Changes in height-for-age z-score (HAZ) and body mass index-for-age z-score (BMIZ) were determined from the end of intervention to re-enrollment. General linear models were used to assess the effects on HAZ and BMIZ of group, gender, living area, maternal education, family income, physical activity, diet quality, nutritional status, and gut integrity as determined by urinary lactulose/mannitol ratio (L:M). Adolescent mean age was 15.3 years, mean HAZ was - 1.11, mean BMIZ was - 0.2 and median L:M (n = 155) was 0.23. Changes in HAZ and BMIZ were not significantly different between Casei, Reuteri, LC compared to RC. However, a significant decrease in BMIZ was observed among female adolescents in the Casei compared to RC group (- 0.5 SD, 95% CI - 0.8 to - 0.003, p = 0.048). Childhood probiotic and calcium supplementation may therefore selectively affect female adolescents.Clinical trial registration: This follow-up study has been registered at www.clinicaltrials.gov , Registry name: Rina Agustina, Registration number: NCT04046289, First Registration Date 06/08/19. web link: https://www.clinicaltrials.gov/ct2/show/NCT04046289 .

Burden of severe rotavirus diarrhea in indonesia.

Globally, rotavirus is the leading cause of diarrhea-related hospitalizations and deaths among young children, but the burden of rotavirus disease in Indonesia is poorly documented. From January through December 2006, we conducted prospective surveillance (inpatient and outpatient) among children aged <5 years at 6 hospitals in 6 provinces of Indonesia, using standardized methodology. Of 2240 enrolled children hospitalized for diarrhea, 1345 (60%) were rotavirus positive. Of 176 children enrolled in outpatient clinics in 3 hospitals, 73 (41%) were rotavirus positive. Among children hospitalized for diarrhea, dehydration was more common among those who tested positive for rotavirus than among those who did not (91% vs 82%; P < .05), as was vomiting (86% vs 67%; P < .05). Children aged 6-23 months experienced 72% of all rotavirus episodes. Rotavirus prevalence increased slightly in the cool, dry season. The most commonly detected genotypes were G9 (30%) and P[6] (56%). G1P[6] and G9P[6] accounted for 34% and 21% of strains, respectively. A high proportion of genotype P[6] was detected, in combination with the common G types G1 and G9. Available rotavirus vaccines would likely be efficacious against the most common circulating strains, but continued monitoring of uncommon genotypes is needed.

Effect of Supplementation of Zinc, Glutamine, Fiber, and Prebiotics in Presumed Healthy Indonesian Children Aged 1-3 Years.

PURPOSE: Impaired intestinal mucosal integrity may affect the gastrointestinal function, especially in relation to nutrition, absorption, and barrier function. The purpose of this study was to measure the prevalence of impaired intestinal mucosal integrity in presumed healthy children aged 1-3 years and assess the effects of zinc, glutamine, fiber, and prebiotic supplementation in them. METHODS: A cross-sectional study was conducted in 200 children aged 1-3 years in Pasar Minggu, South Jakarta, Indonesia. A randomized double-blind parallel group method clinical trial was then performed to assess the effects of zinc, glutamine, fiber, and prebiotic supplementation. RESULTS: Elevated calprotectin was found in 91/200 subjects (45.5%) at the onset of the study. After 10 months, 144 subjects completed the study: 72 subjects received the trial formula, whereas the other 72 received the standard formula. A transitory decrease in fecal calprotectin (FC) was observed after 6 months in the subgroup with normal FC levels, who were fed the test formula (p=0.012). CONCLUSION: The prevalence of impaired intestinal mucosal integrity in this group of Indonesian children aged 1-3 years was high. Supplementation with zinc, glutamine, fiber, and prebiotics during 6 months reduced FC only in those who had low levels at baseline but not in those with impaired integrity.

Natural evolution of regurgitation in healthy infants.

OBJECTIVES: To determine the natural history of infant regurgitation during the first year of life. METHODS: Parents recorded prospectively the frequency of regurgitation for 1 week before consultation during the first year of life. A sub-group analysis according to the method of feeding was planned. RESULTS: A total of 130 infants of an original sample of 163 (80%) newborns were followed up for 1 year. Daily spilling was highest during the first month of life (73%) and decreased gradually to 50% during the fifth month of life. During the first 2 months of life, 20% of the infants regurgitated more than four times per day. After the age of 12 months, only 4% of the infants had daily regurgitations. Exclusively breastfed infants did regurgitate less than partially breastfed infants. Weight gain was influenced by the frequency of regurgitation, especially in partially breastfed infants. CONCLUSION: Regurgitation in infancy is common, decreasing from birth, and tends to disappear by 12 months of age. Weight gain during the first 4 months of life is decreased in infants who regurgitate more than four times a day. Our data suggest that exclusively breastfed infants regurgitate less than partially breastfed babies.

A perspective on partially hydrolyzed protein infant formula in nonexclusively breastfed infants.

The World Health Organization recommends that infants should be exclusively breastfed for the first 6 months of life to provide optimal nutrition in this critical period of life. After this, infants should receive nutritionally adequate and safe complementary foods while breastfeeding continues for up to 2 years of age or beyond. For nonbreastfed infants, infant formula is an available option to provide the nutrition needed. Infant formula is usually prepared from industrially modified cow's milk and processed to adjust for the nutritional needs of infants. However, cow's milk is one of the most common causes of food allergy, affecting 2%-5% of all formula-fed infants during their first year of life. One strategy to prevent cow's milk allergy in nonbreastfed infants is the use of partially hydrolyzed formula (pHF) in high-risk infants, which are infants born in families with atopic disease. However, based on an epidemiological study, approximately half of the infants who develop allergy are not part of the at-risk group. This is because the non-at-risk group is significantly larger than the at-risk group and the non-at-risk infants have approximately 15% risk of developing allergies. This study aimed to evaluate the effects of partially hydrolyzed whey formula (pHF-W) in nonbreastfed infants and determine whether pHF-W can prevent atopic disease in high-risk infants and can be used as routine starter formula regardless of the allergy risk status.

The Role of Two Human Milk Oligosaccharides, 2'-Fucosyllactose and Lacto-N-Neotetraose, in Infant Nutrition.

Human breast milk contains numerous biomolecules. Human milk oligosaccharides (HMOs) are the third most abundant component of breast milk, after lactose and lipids. Amongst the synthetized HMOs, 2'-fucosyllactose (2'-FL) and lacto-N-neotetraose (LNnT) are widely studied and are considered safe for infant nutrition. Several studies have reported the health benefits of HMOs, which include modulation of the intestinal microbiota, anti-adhesive effect against pathogens, modulation of the intestinal epithelial cell response, and development of the immune system. The amount and diversity of HMOs are determined by the genetic background of the mothers (HMO secretors or non-secretors). The non-secretor mothers secrete lower HMOs than secretor mothers. The breastfed infants of secretor mothers gain more health benefit than those of non-secretor mothers. In conclusion, supplementation of infant formula with 2'-FL and LNnT is a promising innovation for infant nutrition.

Improved growth of toddlers fed a milk containing synbiotics.

Bifidobacterium longum (BL999), Lactobacillus rhamonosus (LPR), prebiotics (inulin and fructo-oligosaccharides), and long-chain polyunsaturated fatty acids (LCPUFA) are believed to have health benefits. In a randomized, double-blind, controlled trial we compared growth and development of toddlers fed milk containing synbiotics (BL999, LPR, and prebiotics) and LCPUFA or a control milk. Three hundred and ninety three healthy, 12 month-old toddlers were fed approximately 400 mL/day for 12 months. Anthropometric measurements were taken at 12, 14, and 16 months. Toddlers' response to measles and hepatitis A vaccine was measured at 16 months, and Bayley scale for motor, cognitive, and behavioral functions made at 24 months. The primary outcome was weight gain between 12 and 16 months. Secondary outcomes were gain in length, head circumference, and body mass index, gastrointestinal tolerance (stool characteristics), stool bacterial counts, safety, anti-vaccine IgG, and neurodevelopment. Weight gain was greater in the synbiotics group (mean±SD, 7.57±4.13 g/day) compared with the control group (6.64±4.08 g/day). The difference of 0.93 g/day (with a 95% confidence interval of 0.12 to 1.75) is significant (p=0.025). The gain in the synbiotics group resulted in a change in z-score weight-for-age closer to WHO Child Growth Standard. There was a significant increase in lactobacilli and enterococci counts between 12 months and 16 months in the synbiotic group. We conclude that in healthy toddlers milk containing synbiotics and LCPUFA provides better growth and promotes favorable gut colonization, as shown by higher Lactobacillus counts.