Prediabetes in children and adolescents:An updated review

Prediabetes,the precursor of type 2 diabetes mellitus,is an intermediate stage between normal glucose homeostasis and overt diabetes.This asymptomatic metabolic state is increasingly prevalent in pediatric population and is very difficult to detect without appropriate screening.Studies have shown that a certain proportion of children with prediabetes will develop diabetes in a few years.Even more alarming is the evidence that youth-onset diabetes has a more aggressive clinical course with progressive beta-cell decline and accelerated endorgan damage.Despite its importance,several aspects involving prediabetes in childhood are disputed or unknown.This review presents the latest insights into this challenging entity and outlines a simplified screening approach to aid clinical practice.In summary,childhood prediabetes is an important clinical condition indicating the need for proper screening and timely intervention.

Use of Complementary and Alternative Medicine in Siblings of Pediatric Cancer Patients in Germany.A Population-Based Survey

Use of complementary and alternative medicine (CAM) in children with cancer is common and probably increasing. However data concerning use of CAM in siblings of children with an oncologic disease are missing so far. We conducted a population-based survey over a one-year period with 233 participants. Of the 209 respondents (90% response rate) 20% reported CAM use from the time on when the sibling was diagnosed to have cancer, compared to a prevalence rate of 48% before cancer diagnosis. The most prevalent therapies were homeopathy, anthroposophic medicine and Bach flowers. The main reasons for use were to strengthen the immune system and to achieve physical stabilization. Socio-demographic factors associated with CAM use were higher parental education and higher family income. A majority of CAM users would recommend them. 66% of the users informed a physician about CAM use. No side effects were reported.Conclusions: There is a significant decrease in CAM use in siblings of pediatric cancer patients after ascertainment of cancer in the affected sibling. Being out of the focus seems to be the main reason for non-use. Nevertheless the 20% CAM users rate CAM as very effective and would recommend CAM use to other parents.

Superior antibody and membrane protein‑specific T‑cell responses to CoronaVac by intradermal versus intramuscular routes in adolescents

Background Optimising the immunogenicity of COVID-19 vaccines to improve their protection against disease is necessary.Fractional dosing by intradermal(ID)administration has been shown to be equally immunogenic as intramuscular(IM)administration for several vaccines,but the immunogenicity of ID inactivated whole severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)at the full dose is unknown.This study(NCT04800133)investigated the superiority of antibody and T-cell responses of full-dose CoronaVac by ID over IM administration in adolescents.Methods Participants aged 11–17 years received two doses of IM or ID vaccine,followed by the 3rd dose 13–42 days later.Humoral and cellular immunogenicity outcomes were measured post-dose 2(IM-CC versus ID-CC)and post-dose 3(IMCCC versus ID-CCC).Doses 2 and 3 were administered to 173 and 104 adolescents,respectively.Results Spike protein(S)immunoglobulin G(IgG),S-receptor-binding domain(RBD)IgG,S IgG Fcγreceptor IIIa(FcγRIIIa)-binding,SNM[sum of individual(S),nucleocapsid protein(N),and membrane protein(M)peptide pool]-specific interleukin-2(IL-2)+CD4+,SNM-specific IL-2+CD8+,S-specific IL-2+CD8+,N-specific IL-2+CD4+,N-specific IL-2+CD8+and M-specific IL-2+CD4+responses fulfilled the superior and non-inferior criteria for ID-CC compared to IM-CC,whereas IgG avidity was inferior.For ID-CCC,S-RBD IgG,surrogate virus neutralisation test,90%plaque reduction neutralisation titre(PRNT90),PRNT50,S IgG avidity,S IgG FcγRIIIa-binding,M-specific IL-2+CD4+,interferon-γ+CD8+and IL-2+CD8+responses were superior and non-inferior to IM-CCC.The estimated vaccine efficacies were 49%,52%,66%and 79%for IM-CC,ID-CC,IM-CCC and ID-CCC,respectively.The ID groups reported more local,mild adverse reactions.Conclusion This is the first study to demonstrate superior antibody and M-specific T-cell responses by ID inactivated SARSCoV-2 vaccination and serves as the basis for future research to improve the immunogenicity of inactivated vaccines.

Treatment of central precocious puberty by GnRH analogs： long-term outcome in men

In boys, central precocious puberty （CPP） is the appearance of secondary sex characteristics driven by pituitary gonadotropin secretion before the age of 9 years. In the last years, relevant improvements in the treatment of CPP have been achieved. Because CPP is rare in boys, the majority of papers on this issue focus on girls and do not address specific features of male patients regarding end results and safety. In the present paper, recent advances of CPP management with GnRH analogs in men are summarized. End results in untreated and treated patients are also reviewed by an analysis of the recently published literature on treatment of CPP in men. The available data indicate that therapy with GnRH analogs can improve final height into the range of target height without significant adverse short-term and long-term effects, but longer follow-up of larger series of patients is still required to draw definitive conclusions.

Chronic ulcerative gastroduodenitis as a first gastrointestinal manifestation of Hermansky-Pudlak syndrome in a 10-year-old child

A 10-year-old Chinese boy who had a history of congenital thrombocytopathy presented with severe iron deficiency anemia secondary to chronic gastric inflammation and duodenal ulcerations. Subtle oculocutaneous albinism led to the finding of diminished dense bodies in the platelets under electron microscopy, hence the diagnosis of Hermansky-Pudlak syndrome (HPS). Biopsies from the stomach and duodenum revealed a lymphocytic infiltration in the submucosa, but H pylori infection was absent. The gastroduodenitis responded to the treatment with omeprazole while iron deficiency anemia was corrected by oral iron therapy. HPS is a rare cause of congenital bleeding disorder with multisystemic manifestations. Upper gastrointestinal involvement is rare and should be distinguished from a mere manifestation of the bleeding diathesis.

Variable outcome in infantile-onset inflammatory bowel disease in an Asian cohort

AIM Infantile-onset inflammatory bowel disease(IO-IBD) with the onset of disease before 12 mo of age, is a different disease entity from childhood IBD. We aimed to describe the clinical features, outcome and role of mutation in interleukin-10(IL-10) and interleukin-10 receptors(IL-10R) in Asian children with IO-IBD. METHODS All cases of IO-IBD, defined as onset of disease before 12 mo of age, seen at University Malaya Medical Center, Malaysia were reviewed. We performed mutational analysis for IL10 and IL10 R genes in patients with presenting clinical features of Crohn's disease(CD).RESULTS Six [13%; CD = 3, ulcerative colitis(UC) = 2, IBDunclassified(IBD-U) = 1] of the 48 children(CD = 25; UC = 23) with IBD have IO-IBD. At final review [median(range) duration of follow-up: 6.5(3.0-20) years], three patients were in remission without immunosuppression [one each for post-colostomy(IBD-U), after standard immunosuppression(CD), and after total colectomy(UC)]. Three patients were on immunosuppression:one(UC) was in remission while two(both CD) had persistent disease. As compared with later-onset disease, IO-IBD were more likely to present with bloody diarrhea(100% vs 55%, P = 0.039) but were similar in terms of an associated autoimmune liver disease(0% vs 19%, P = 0.31), requiring biologics therapy(50% vs 36%, P = 0.40), surgery(50% vs 29%, P = 0.27), or achieving remission(50% vs 64%, P = 0.40). No mutations in either IL10 or IL10 R in the three patients with CD and the only patient with IBD-U were identified.CONCLUSION The clinical features of IO-IBD in this Asian cohort of children who were negative for IL-10 or IL-10 R mutations were variable. As compared to childhood IBD with onset of disease after 12 mo of age, IO-IBD achieved remission at a similar rate.

Efficacy and safety of granulocyte, monocyte/macrophage adsorptive in pediatric ulcerative colitis

AIM: To investigate efficacy and safety for granulocyte, monocyte apheresis in a population of pediatric patients with ulcerative colitis.METHODS: The ADAPT study was a prospective, openlabel, multicenter study in pediatric patients with moderate, active ulcerative colitis with pediatric ulcerative colitis activity index(PUCAI) of 35-64. Patients received one weekly apheresis with Adacolumn granulocyte, monocyte/macrophage adsorptive(GMA) apheresis over 5 consecutive weeks, optionally followed by up to 3 additional apheresis treatments over 3 consecutive weeks. The primary endpoint was the change in mean PUCAI between baseline and week 12; the secondary endpoint was improvement in PUCAI categorized as(Significant Improvement, PUCAI decrease of ≥ 35), Moderate Improvement(PUCAI decrease of 20 < 35), Small Improvement(PUCAI decrease of 10 < 20) or No change(PUCAI decrease of < 10). RESULTS: Twenty-five patients(mean age 13.5 years; mean weight 47.7 kg) were enrolled. In the intention-to-treat set(ITT), the mean value for PUCAI improvement was 22.3 [95%CI: 12.9-31.6; n = 21]. In the per-protocol(PP) set, the mean improvement was 36.3 [95%CI: 31.4-41.1; n = 8]. Significant Improvement was recorded for 9 out of 20 patients(45%); 5 out of 20 patients(25%) had Moderate Improvement and one patient(5%) had No Change in PUCAI score at week 12. In the PP set, six out of eight patients(75%) showed Significant Improvement; and in two out of eight patients(25%) Moderate Improvement was recorded. The endoscopic activity index(EAI) decreased by 3 points on average. Seven(7) out of 21(33%) patients in ITT and 4 out of 8(50%) patients in PP have used steroids during the clinical investigation. The mean steroid dosage for these patients in the ITT set decreased from a mean 12.4 mg to 10 mg daily on average from Baseline to week 12.CONCLUSION: Adacolumn; GMA apheresis treatment was effective in pediatric patients with moderate active Ulcerative Colitis. No new safety signals were reported. The present data contribute to considering GMA apheresis as a therapeutic option in pediatric patients having failed first line therapy.

Clinical and epidemiological characteristics of norovirus gastroenteritis among hospitalized children in Lebanon

AIM To assess the burden of norovirus(No V) and to determine the diversity of circulating strains among hospitalized children in Lebanon. METHODS Stool samples were collected from children presenting with acute gastroenteritis to six major hospitals in Lebanon. A total of 739 eligible stool samples, testing negative for diarrhea caused by rotavirus as a possible viral pathogen, were collected between January 2011 and June 2013. A standardized questionnaire including demographic, epidemiological and clinical observations was used at the time of hospitalization of children presenting with diarrhea. Viral RNA was extracted from stool samples followed by reverse transcription polymerase chain reaction and nucleotide sequencing of a fragment of the viral protein 1 capsid gene. Multiple sequence alignments were carried out and phylogenetic trees were constructed using the MEGA 6 software.RESULTS Overall, 11.2% of stool samples collected from children aged < 5 years tested positive for No V genogroups Ⅰ(GⅠ) and Ⅱ(GⅡ). GⅡ accounted for 10.6% of the gastroenteritis cases with only five samples being positive for GⅠ(0.7%). The majority of hospitalized children showed symptoms of diarrhea, dehydration, vomiting and fever. Upon sequencing of positive samples and based on their clustering in the phylogenetic tree, 4/5 of GⅠ gastroenteritis cases were designated GⅠ.3 and one case as GⅠ.4. GⅡ.4 was predominantly detected in stool of our study participants(68%). We report a JB-15/KOR/2008 GⅡ.4 Apeldoorn 2008-like variant strain circulating in 2011; this strain was replaced between 2012 and 2013 by a variant sharing homology with the Sydney/NSW0514/2012/AUS GⅡ.4 Sydney 2012 and Sydney 2012/FRA GⅡ.4 strains. We also report the co-circulation of non-GⅡ.4 genotypes among hospitalized children. Our data show that No V gastroenteritis can occur throughout the year with the highest number of cases detected during the hot months.CONCLUSION The majority of No V-associated viral gastroenteritis cases among our participants are attributable to GⅡ.4, which is compatible with results reported worldwide.

Growth and bone health in paediatric patients with Crohn's disease receiving subcutaneous tumor necrosis factor antibody

AIM:To study whether adalimumab(ADA) was associated with improvement in growth,bone mineraldensity(BMD) and bone metabolism.METHODS:In children with Crohn's disease(CD) there is a high prevalence of growth failure and reduced BMD.Treatment with infliximab is associated with an improvement in growth.Anthropometry,paediatric CD activity index(PCDAI),bone markers and BMD was measured in 18 patients(72% females) one year before and after start of ADA with a median age of 14.4 years(range:5-19 years) at treatment start.Outcomes were indicators of growth with treatment as well as interval growth.RESULTS:Eleven(61%) children experienced catchup growth after ADA.PCDAI significantly decreased from 52.1 ± 16 to 30.4 ± 23(P ≤ 0.001).Post ADA,body mass index(BMI) standard deviation score(SDS) 0.1[range:2.7-(-0.8)] vs-1 [range:0.1-(-3.6)],P = 0.04 and △BMI SDS in children 0.3 [range:0.7-(-0.2)] vs-1.1 [range:1.2-(-2.3)],P = 0.01 in remission were significantly higher compared to those with moderate to severe inflammation.The main predictors for growth were 25-hydroxycholecalciferol and for bone mineralisation weight and height SDS.ADA had no significant influence on bone markers and BMD.CONCLUSION:Next to improvement of PCDAI,half of the children achieved a positive catch-up growth.A better nutritional status with improvement in BMI and weight is positive predictor for improved growth and bone mineralisation.

Hepatic veno-occlusive disease after hematopoietic stem cell transplantation: Prophylaxis and treatment controversies

Hepatic veno-occlusive disease(VOD), also known as sinusoidal obstruction syndrome, is a major complication of hematopoietic stem cell transplantation and it carries a high mortality. Prophylaxis for hepatic VOD is commonly given to transplant recipients from the start of conditioning through the early weeks of transplant. However, high quality evidence from randomized controlled trials is scarce with small sample sizes and the trials yielded conflicting results. Although various treatment options for hepatic VOD are available, most have not undergone stringent evaluation with randomized controlled trial and therefore it remains uncertain which treatment offers real benefit. It remains controversial whether VOD prophylaxis should be given, which prophylactic therapy should be given, who should receive prophylaxis, and what treatment should be offered once VOD is established.

Light and sound- emerging imaging techniques for inflammatory bowel disease

Patients with inflammatory bowel disease are known to have a high demand of recurrent evaluation for therapy and disease activity. Further, the risk of developing cancer during the disease progression is increasing from year to year. New, mostly non-radiant, quick to perform and quantitative methods are challenging, conventional endoscopy with biopsy as gold standard. Especially, new physical imaging approaches utilizing light and sound waves have facilitated the development of advanced functional and molecular modalities. Besides these advantages they hold the promise to predict personalized therapeutic responses and to spare frequent invasive procedures. Within this article we highlight their potential for initial diagnosis, assessment of disease activity and surveillance of cancer development in established techniques and recent advances such as wide-view full-spectrum endoscopy, chromoendoscopy, autofluorescence endoscopy, endocytoscopy, confocal laser endoscopy, multiphoton endoscopy, molecular imaging endoscopy, B-mode and Doppler ultrasound, contrast-enhanced ultrasound, ultrasound molecular imaging, and elastography.

Pediatric obesity prevention:From na?ve examination of energy imbalance towards strategies that influence the competition for nutrient resources among tissues

Current pediatric obesity interventions have collectively yielded relatively unsuccessful results. In this Field of Vision, we present plausible physiologic underpinnings fostering ineffectiveness of conventional strategies grounded in requisite induction of negative energy imbalance. Moreover, such recommendations exacerbate the underlying metabolic dysfunction by further limiting metabolic fuel availability, lowering energy expenditure, and increasing hunger(recapitulating the starvation response amid apparent nutritional adequacy) which precede and promote obesity during growth and development. The qualitative aspects of musculoskeletal system(i.e., endocrine response, muscle functional capacity) are likely to improve metabolic function and increase nutrient delivery and utilization. An intricate and complex system including multiple feedback mechanisms operates to homeostatically regulate energy balance and support optimal body composition trajectories and metabolic health, during growth and development. Thus, ignoring the interdependencies of regulatory growth processes initiates a nuanced understanding of energy regulation and thus misguided attempts at preventive strategies. Importantly, these gains are not dependent upon weight-loss, rather we suggest can be achieved through resistance training. Collectively, optimizing musculoskeletal health via resistance training elicits augmentation of competitive capacity across systems. Further, substantial gains can be achieved in skeletal muscle mass, strength, and functional capacity through resistance training in a relatively short period of time.

Dysphagia after arteria lusoria dextra surgery: Anatomical considerations before redo-surgery

Aberrant right subclavian artery(arteria lusoria) is the most common congenital root anomaly, remaining asymptomatic in most cases. Nevertheless, some of the 20%-40% of those affected present tracheo-esophageal symptoms. We report on a 6-year-old previously healthy girl presenting with progressive dysphagia over 4 wk. Diagnostics including barium swallow, echocardiography and magnetic resonance angiography(MRA) revealed a retro-esophageal compression by an aberrant right subclavian artery. Despite the successful, uneventful transposition of this arteria lusoria to the right common carotid via right-sided thoracotomy, the girl was suffering from persisting dysphagia. Another barium swallow showed the persistent compression of the esophagus on the level where the arteria lusoria had originated. As MRA showed no evidence of a significant re-obstruction by the transected vascular stump, we suspected a persisting ligamentum arteriosum. After a second surgical intervention via left-sided thoracotomy consisting of transecting the obviously persisting ligamentum and shortening the remaining arterial stump of the aberrant right subclavian artery, the patient recovered fully. In this case report we discuss the potential relevance of a persisting ligamentum arteriosum for patients with leftaortic arch suffering from dysphagia lusoria and rational means of diagnosing, as well as the surgical options to prevent re-do surgery.

Limitations and opportunities of non-invasive liver stiffness measurement in children

Changes in liver structure are an important issue in chronic hepatopathies.Until the end of the 20 th century,these changes could only be determined by histological analyses of a liver specimen obtained via biopsy.The well-known limitations of this technique(i.e.,pain,bleeding and the need for sedation) have precluded its routine use in follow-up of patients with liver diseases.However,the introduction of non-invasive technologies,such as ultrasound and magnetic resonance imaging,for measurement of liver stiffness as an indirect marker of fibroses has changed this situation.Today,several noninvasive tools are available to physicians to estimate the degree of liver fibrosis by analysing liver stiffness.This review describes the currently available tools for liver stiffness determination that are applicable to follow-up of liver fibrosis/cirrhosis with established clinical use in children,and discusses their features in comparison to the "historical" tools.

Optimal stem cell source for allogeneic stem cell transplantation for hematological malignancies

Hematopoietic stem cell transplant(HSCT) is a standard treatment for many hematological malignancies.Three different sources of stem cells, namely bone marrow(BM), peripheral blood stem cells(PBSC) and cord blood(CB) can be used for HSCT, and each has its own advantages and disadvantages. Randomized controlled trials(RCTs) suggest that there is no significant survival advantage of PBSC over BM in Human Leukocyte Antigen-matched sibling transplant for adult patients with hematological malignancies. PBSC transplant probably results in lower risk of relapse and hence better disease-free survival, especially in patients with high risk disease at the expense of higher risks of both severe acute and chronic graft-versus-host disease(GVHD).In the unrelated donor setting, the only RCT available suggests that PBSC and BM result in comparable overall and disease-free survivals in patients with hematological malignancies; and PBSC transplant results in lower risk of graft failure and higher risk of chronic GVHD.High level evidence is not available for CB in comparison to BM or PBSC. The risks and benefits of different sources of stem cells likely change with different conditioning regimen, strategies for prophylaxis and treatment of GVHD and manipulation of grafts. The recent success and rapid advance of double CB transplant and haploidentical BM and PBSC transplants further complicate the selection of stem cell source. Optimal selection requires careful weighing of the risks and benefits of different stem cell source for each individual recipient and donor. Detailed counseling of patient and donor regarding risks and benefits in the specific context of the patient and transplant method is essential for informed decision making.

Pediatric Application of Dynamic Contrast-Enhanced MR Imaging (DCE-MR) in the Management of Extra-Cranial Tumor: Experience in Routine Clinical Practice

Background: Dynamic contrast-enhanced MR imaging (DCE-MR) is becoming a widely accepted complementary method for diagnosing breast cancer and other cancers in adults. It is useful to predict tumor response to anticancer therapy and monitor the tumor response to the therapy. This form of imaging techniques has not been adequately explored in pediatric oncology patients. Objective: To determine the potential role of dynamic contrast-enhanced MR imaging (DCE-MR) in the diagnosis and treatment response monitoring of childhood and young adult extra-cranial tumors in routine clinical setting. Methods: Children with suspected extra-cranial solid tumors, including newly diagnosed or follow-up cases of confirmed tumors, were recruited. DCE-MR was performed with intravenous injection of 0.1 mmol/kg contrast. The enhancement time curves were plotted and the enhancement patterns were categorized into type 1, 2 and 3 curves. Enhancement curve patterns and maximal enhancement intensity were compared with types of tumor in newly diagnosed cases. The preoperative percentiles of inactive area on the colour map were compared with the necrotic areas on histologic sections of the resected specimens in follow-up cases. Pearson Chi-square test and Unpaired two-sample t-test were used for statistical analysis. Results: There were 36 patients, involving 28 malignant and 8 benign cases. There were 14 type 3 curves, (all of them were malignant tumors), 6 type 2 curves and 16 type 1 curves. All the benign cases (n = 8) demonstrated type 1 curve (accuracy & negative predictive value = 100%). All the malignant cases after treatment showed type 2 or 1 curve. For those cases with operation done afterwards, the extent of tumor necrosis was correlated closely with pathology findings (accuracy = 93.3%). Conclusion: Type 1 curve was a good predictor of benign lesion. DEC-MR may have a role to play in the monitoring of the progress of treatment and extent of tumor necrosis.

Indirect determination of serum creatinine reference intervals in a Pakistani pediatric population using big data analytics

BACKGROUND The indirect methods of reference intervals(RI)establishment based on data mining are utilized to overcome the ethical,practical challenges and the cost associated with the conventional direct approach.AIM To generate RIs for serum creatinine in children and adolescents using an indirect statistical tool.METHODS Data mining of the laboratory information system was performed for serum creatinine analyzed from birth to 17 years for both genders.The timeline was set at six years from January 2013 to December 2018.Microsoft Excel 2010 and an indirect algorithm developed by the German Society of Clinical Chemistry and Laboratory Medicine’s Working Group on Guide Limits were used for the data analysis.RESULTS Data were extracted from 96104 samples and after excluding multiple samples for the same individual,we calculated RIs for 21920 males and 14846 females,with stratification into six discrete age groups.CONCLUSION Serum creatinine dynamics varied significantly across gender and age groups.

Targeted molecular therapy (modified RIST regimen) in relapsed high risk stage Ⅳ neuroblastoma: two cases report

The prognosis for children with recurrent or refractory neuroblastoma remains a significant clinical challenge,and currently there are no known curative salvage regimens.In this paper we investigated the effect of imatinib with rapamycin and the chemotherapeutic agents temozolomide and irinotecan.We treated two children with recurrent neuroblastoma with this so called RIST protocol.Both patients,off therapy for 15 and 31 months,respectively are well,and developing normally,without any complications.These findings suggest that a combination regimen of RIST may provide a therapeutic benefit with a favorable toxicity profile to a unfortunate subset of patients with neuroblastoma.

Conservation of T cell epitopes between seasonal influenza viruses and the novel influenza A H7N9 virus

A novel avian influenza A(H7N9) virus recently emerged in the Yangtze River delta and caused diseases, often severe, in over 130 people. This H7N9 virus appeared to infect humans with greater ease than previous avian influenza virus subtypes such as H5N1 and H9N2. While there are other potential explanations for this large number of human infections with an avian influenza virus, we investigated whether a lack of conserved T-cell epitopes between endemic H1N1 and H3N2 influenza viruses and the novel H7N9 virus contributes to this observation. Here we demonstrate that a number of T cell epitopes are conserved between endemic H1N1 and H3N2 viruses and H7N9 virus. Most of these conserved epitopes are from viral internal proteins. The extent of conservation between endemic human seasonal influenza and avian influenza H7N9 was comparable to that with the highly pathogenic avian influenza H5N1. Thus, the ease of inter-species transmission of H7N9 viruses(compared with avian H5N1 viruses) cannot be attributed to the lack of conservation of such T cell epitopes. On the contrary, our findings predict significant T-cell based cross-reactions in the human population to the novel H7N9 virus. Our findings also have implications for H7N9 virus vaccine design.