Disease In Pediatric Patients Research Articles

Risk factors and incidence of cytomegalovirus viremia and disease in pediatric patients with allogeneic hematopoietic stem cell transplantation: An 8-year single-center experience in Latin America.

Cytomegalovirus infection represents a significant cause of morbidity and mortality after hematopoietic stem cell transplantation. This study aimed to evaluate the incidence of viremia and disease due to cytomegalovirus and the risk factors in pediatric patients with hematopoietic stem cell transplantation in our institution. This was a retrospective cohort of patients under 19 years of age who underwent allogeneic hematopoietic stem cell transplantation due to any indication between 2012 and 2019. The analysis included the diagnosis of cytomegalovirus viremia or disease during post-transplant follow-up, evaluation of risk factors, and outcomes. The statistical analysis included univariate and multivariate analyses, and the cumulative incidence of cytomegalovirus viremia was determined by the Kaplan-Meier method using STATA 14 statistical software. A total of 182 transplants were included. At 100 days, the cumulative incidence of cytomegalovirus viremia was 70.5%, and that of cytomegalovirus disease was 4.7%. Overall survival at 2 years was 74%, and event-free survival was 64%. The remaining demographic characteristics were not predictors of infection. There was no association between viremia and relapse or survival of the patients. Higher mortality was noted in cytomegalovirus disease. During the study period, the incidence of cytomegalovirus disease was similar to that of other pediatric reports, but the incidence of viremia was higher. Pre-emptive therapy has diminished disease rates and death due to infection. Viral load cutoff points should be standardized to guide treatment and avoid myelotoxicity.

Machine Learning-Based CT Radiomics Method for Identifying the Stage of Wilms Tumor in Children.

PurposeTo develop and validate a machine learning-based CT radiomics method for preoperatively predicting the stages (stage I and non-stage I) of Wilms tumor (WT) in pediatric patients.MethodsA total of 118 patients with WT, who underwent contrast-enhanced computed tomography (CT) scans in our center between 2014 and 2021, were studied retrospectively and divided into two groups: stage I and non-stage I disease. Patients were randomly divided into training cohorts (n = 94) and test cohorts (n = 24). A total of 1,781 radiomic features from seven feature classes were extracted from preoperative portal venous–phase images of abdominal CT. Synthetic Minority Over-Sampling Technique (SMOTE) was used to handle imbalanced datasets, followed by a t-test and Least Absolute Shrinkage and Selection Operator (LASSO) regularization for feature selection. Support Vector Machine (SVM) was deployed using the selected informative features to develop the predicting model. The performance of the model was evaluated according to its accuracy, sensitivity, and specificity. The receiver operating characteristic curve (ROC) and the area under the ROC curve (AUC) was also arranged to assess the model performance.ResultsThe SVM model was fitted with 15 radiomic features obtained by t-test and LASSO concerning WT staging in the training dataset and demonstrated favorable performance in the testing dataset. Cross-validated AUC on the training dataset was 0.79 with a 95 percent confidence interval (CI) of 0.773–0.815 and a coefficient of variation of 3.76%, while AUC on the test dataset was 0.81, and accuracy, sensitivity, and specificity were 0.79, 0.87, and 0.69, respectively.ConclusionsThe machine learning model of SVM based on radiomic features extracted from CT images accurately predicted WT stage I and non-stage I disease in pediatric patients preoperatively, which provided a rapid and non-invasive way for investigation of WT stages.

The diagnosis and management of Gaucher disease in pediatric patients: Where do we go from here?

Gaucher disease (GD) is an autosomal recessive inherited lysosomal storage disease that often presents in early childhood and is associated with damage to multiple organ systems. Many challenges associated with GD diagnosis and management arise from the considerable heterogeneity of disease presentations and natural history. Phenotypic classification has traditionally been based on the absence (in type 1 GD) or presence (in types 2 and 3 GD) of neurological involvement of varying severity. However, patient management and prediction of prognosis may be best served by a dynamic, evolving definition of individual phenotype rather than by a rigid system of classification. Patients may experience considerable delays in diagnosis, which can potentially be reduced by effective screening programs; however, program implementation can involve ethical and practical challenges. Variation in the clinical course of GD and an uncertain prognosis also complicate decisions concerning treatment initiation, with differing stakeholder perspectives around efficacy and acceptable cost/benefit ratio. We review the challenges faced by physicians in the diagnosis and management of GD in pediatric patients. We also consider future directions and goals, including acceleration of accurate diagnosis, improvements in the understanding of disease heterogeneity (natural history, response to treatment, and prognosis), the need for new treatments to address unmet needs for all forms of GD, and refinement of the tools for monitoring disease progression and treatment efficacy, such as specific biomarkers.

Lipoprotein(a) and family history for cardiovascular disease in paediatric patients: A new frontier in cardiovascular risk stratification. Data from the LIPIGEN paediatric group

Background and aimsLittle is known about the role of Lp(a) in the assessment of cardiovascular risk in the paediatric population. Trying to clarify the clinical relevance of Lp(a) in risk stratification, the aim of the study is to evaluate the association between Lp(a) plasma levels in children with familial hypercholesterolaemia (FH) and positive family history for premature cardiovascular disease (pCVD) in first- and second-degree relatives. Methods653 Caucasian children and adolescents (334 females and 319 males), aged 2–17 years, with diagnosis of FH from a paediatric cohort included in the LIPIGEN Network, were selected. We compared family history of pCVD, lipid and genetic profile in two groups based on Lp(a) levels below or above 30 mg/dL. To determine the independent predictors of pCVD, a multivariate logistic regression was used, with all clinical characteristics and blood measurements as predictors. ResultsSubjects with Lp(a) > 30 mg/dl more frequently reported positive family history of pCVD compared to subjects with Lp(a)≤30 mg/dl (69.90% vs 36.66%, p < 0.0001), while did not show differences in terms of median [interquartile range] LDL-cholesterol level (153.00 [88.00 vs 164.50 [90.25] mg/dL, p = 0.3105). In the regression analysis, Lp(a) > 30 mg/dl was an independent predictor of family history of pCVD. Comparing subjects with or without family history of pCVD, we reported significant differences for Lp(a) > 30 mg/dl (46.25% vs 17.65%, p < 0.0001), FH genetic mutation (50.48% vs 40.75%, p = 0,0157), as well as for LDL-cholesterol (p = 0.0013) and total cholesterol (p = 0.0101). ConclusionsChildren/adolescents with FH and Lp(a) > 30 mg/dl where more likely to have a positive family history of pCVD. Lp(a) screening in children and adolescents with FH may enhance risk assessment and help identify those subjects, children and relatives, at increased pCVD risk.

Chronic lung disease in paediatric patients: Does magnetic resonance imaging has a role?

BackgroundPediatric chronic lung disease (CLD) refers to a range of distinct clinical and pathological disorders that affect children. High-resolution CT (HRCT) is critical for detecting and characterizing parenchymal abnormalities as well as determining their nature and distribution. Although magnetic resonance imaging (MRI) shows promising results, however, due to its poor spatial resolution and signal-to-noise ratio, imaging of the lung parenchyma remains a challenge. As a result, in addition to the initial CT, a follow-up MRI is required. The goal of this paper is to highlight the main imaging features of children with CLD and to evaluate the efficacy of MRI lungs in the diagnosis and monitoring of pediatric CLD.ResultsThere was a strong positive correlation between CT and MRI, with a significant P-value. Findings of HRCT and MRI showed a qualitative agreement of 78% complete agreement. MRI helped primary diagnosis in 54% of cases compared to CT in 91% of cases.ConclusionMRI lungs are an equivalent technique to HRCT in assessing pediatric CLD; using the modified Helbich–Bhalla score, a strong correlation is obvious between both in the overall assessment. MRI is beneficial for case surveillance rather than primary diagnosis.

The fine-needle aspiration cytology and clinical findings of Kikuchi–Fujimoto disease in pediatric patients: a retrospective clinical study

Background Histological evaluation of lymph node is crucial for the definitive diagnosis of Kikuchi–Fujimoto disease (KFD). However, lymph node biopsy under local anesthesia is often difficult in pediatric patients. Objectives We evaluated cytological findings for pediatric patients with prolonged cervical lymphadenitis clinically suggestive of KFD and investigated the clinical characteristics of patients diagnosed with KFD by fine-needle aspiration cytology (FNAC). Methods This retrospective clinical study included 58 Japanese pediatric patients with cervical lymphadenitis who underwent FNAC. Results Cytological diagnosis was KFD for 22 and suspicion of KFD for 11 patients. The remaining 25 patients were diagnosed with non-specific lymphadenitis (NSL). Tenderness was independently associated with a higher frequency of both KFD in narrow and broad senses, compared with NSL (p = .009; p = .038). The percentage of patients who underwent FNAC within 28 days from symptom onset tended to be higher among patients with KFD in a narrow sense than those with NSL (p = .052). Conclusion This study indicated that the period from symptom onset to FNAC (<28 days) and the symptom of tenderness were associated with the cytological diagnosis of KFD.

Full recovery after prolonged resuscitation in a pediatric patient due to fulminant myocarditis: a case report with three-year follow-up

BackgroundFulminant myocarditis (FM) is a common life-threatening disease in pediatric patients, which can result in sudden cardiac arrest (CA). Whether prolonged cardiopulmonary resuscitation (CPR) is beneficial to FM induced CA is unknown.Case presentationWe reported the case of an 8-year-old child with FM. At 14:49 of the day after admission, the ECG monitoring indicated ventricular flutter. The patient was immediately given continuous external cardiac compression. Electric cardioversion (energy 30J) and electric defibrillation (energy 50 J, 100 J, 100 J) were given. Continuous chest compression was conducted until extracorporeal membrane oxygenation (ECMO) successfully placed at 19:30 P.M. The total duration of CPR was 291 min. Nine days later, the ECMO was removed; and 29 days later, the patient was discharged from hospital. In the three years of follow-up, the boy showed a full recovery without neurological sequela. At present, his daily activities have returned to normal and his academic performance at school is excellent.ConclusionsProlonged CPR can be used in FM induced in-hospital CA in pediatric patients, especially during preparation for ECMO after the failure of standard resuscitation measures.

Association between idiopathic pulmonary hemosiderosis and celiac disease in pediatric patients: A scoping review of the literature over the past 50 years.

Idiopathic pulmonary hemosiderosis (IPH) is a rare cause of diffuse alveolar hemorrhage, the mechanism of which is currently unknown. Nearly one-third of pediatric patients with IPH test positive for Celiac disease (CD) serology. Several hypothetical mechanisms have been proposed to unify the coexistence of these two entities, also referred to as Lane-Hamilton syndrome (LHS). This manuscript is a scoping review of the medical literature. Medline, Embase, and PubMed Central databases were searched between 1971 and 2021 with appropriate search words to identify all cases of pediatric LHS. A total of 20 manuscripts with 23 pediatric patients with LHS were identified. The mean age was 11 years, and 13/23 (56.5%) of the children were boys. Hemoptysis was present in 57% of patients during diagnosis. Bronchoscopy with bronchoalveolar lavage demonstrating hemosiderin laden macrophages was the primary mode of diagnostic confirmation. Only three patients underwent lung biopsy. Any significant GI symptom was reported in a minority of patients (22%). Iron deficiency anemia on presentation was described in 83% of children. The majority of patients were malnourished. Serology for CD was positive in all patients, as was the histopathologic analysis of the small bowel biopsy. No patients had any other autoantibody positivity. The introduction of gluten free diet (GFD) was associated with a positive response in 20/23 patients. All pediatric patients with IPH should undergo screening for CD. Low serum ferritin in patients with IPH could be suggestive of coexisting CD. Strict GFD should be tried as the initial therapy.

P338 Early proactive drug monitoring strategy of infliximab as monotherapy for inflammatory bowel disease in paediatric patients is associated with good sustained clinical remission

Abstract Background Monotherapy with infliximab (IFX) could be as efficient as combotherapy with immunomodulators in the treatment and maintenance of remission for children with inflammatory bowel disease (IBD) if a proactive therapeutic drug monitoring strategy is adequately performed. This strategy may allow optimization of blood levels of IFX in order to obtain a sustained clinical response. Methods A retrospective study was conducted amongst children with IBD, aged from, 2 to, 18 years old and diagnosed between January, 2018 and June, 2020. All patients were treated with IFX less than, 30 days after diagnosis. Data concerning disease activity was collected at diagnosis, at one year after diagnosis. Close monitoring of IFX blood levels were collected before the third and fourth dose and regularly thereafter. Adjustments in IFX dose per infusion were made according to blood levels and clinical response. The primary outcome was clinical remission, defined by a PUCAI or shortPCDAI score &amp;lt;, 10 without the need of corticosteroid, at one year after diagnosis. The secondary outcomes measured were the median (interquartile range (IQR)) dose of IFX (in mg/kg) after a year of treatment, the median (IQR) number of changes of IFX dose, the time intervals between IFX infusions over a year, and the median (IQR) number of blood levels of IFX done in a year. Results A total of, 91 patients were included (81% Crohn’s disease; mean age at diagnosis was, 13.2 years (IQR = 11.3 to, 15.15)). After one year of treatment, 76 patients (83.5%) reached clinical remission. IFX was discontinued in, 13 patients:, 6 due to antibody occurrence, 5 because of treatment failure, 1 due to psoriasis and, 1 due to autoimmune hepatitis. In total, 61.5% of patients needed two or more IFX dose/interval optimization over the course of a year. At one year after diagnosis, the median IFX dose per infusion was, 8.78 mg/kg (IQR = 7.5 mg/kg to, 9.9 mg/kg) with infusions given, 6 weeks apart or less in, 82% of the patients. Patients who were diagnosed before the age of, 10 had a median IFX dose of, 9.43 mg/kg. The median number of IFX blood level dosage was, 4 per patient over a year (IQR=, 3.5 to 6). Conclusion Early treatment for IBD with IFX as monotherapy and a proactive optimization strategy is associated with a good sustained steroid free clinical remission. Most patients needed an increase of IFX dose during the first year of treatment. We therefore recommend to proactively monitor blood levels of IFX before the third and fourth dose of IFX and thereafter, in order to lower the risk of treatment failure and anti-infliximab antibodies occurrence.

P186 Can transabdominal bowel ultrasound accurately detect both small and large bowel Crohn Disease in pediatric patients when compared to MRE?

Abstract Background Magnetic resonance enterography (MRE) has been the modality of choice to assess small bowel inflammation in patients with Crohn disease (CD). It can also assess large bowel when not feasible to assess endoscopically. Transabdominal bowel ultrasound (TABUS) is an attractive non-invasive tool to assess CD activity. Studies to date have focused on its correlation to large bowel endoscopic findings in adult CD. This study aimed to compare TABUS and MRE in identifying small and large bowel CD in pediatric patients. Methods Pediatric patients (≤18 years old) seen for suspected CD were prospectively enrolled and underwent baseline TABUS, endoscopy, MRE, blood work and stool studies. The Pediatric Crohn’s Disease Activity Index (PCDAI) and Simple Endoscopic Score for Crohn’s Disease (SES-CD) were used to assess disease activity. Bowel wall thickness (BWT) was assessed by TABUS and MRE. TABUS measurements were scored with the Simple Ultrasound Activity Score for Crohn Disease (SUS-CD) (0=≤3mm, 1=3–4.9mm, 2=5–7.9mm, 3=≥8mm). Pearson Chi-square was used to compare BWT between TABUS and MRE. Results 21 patients (71% male) were included, with a median age of 13 years (range 6–16). Median PCDAI was 40 (25–49) and SES-CD 15 (6.5–22). There was a high level of agreement between MRE and TABUS (Figure 1) with some disagreement in the jejunum (n=9/21, 43%). For terminal ileal (TI) disease where there was disagreement, endoscopy of TI was in agreement with TABUS in two patients and MRE in five patients. Endoscopic TI disease that was documented as normal on TABUS was mild (SES-CD 3). In patients with abnormal MRE, BWT was not significantly different between the two modalities (Table 1). In patients with normal MRE, TABUS SUS-CD scores were accurately 0 in almost all segments (score 1 in TI) (Table 2). TABUS correctly identified no fistulae and 2 small bowel strictures (identified at endoscopy), but did not detect 1 intra-abdominal abscess and 4 large bowel strictures (only 1 stricture seen on endoscopy). Excessive lymph nodes (&amp;gt;4) were successfully seen on TABUS in 10/16 patients. TABUS correctly identified 75% of patients with significant mesenteric fibrofatty proliferation. Hyperemia on TABUS corresponded to an abnormal MRE for that segment in 92–100% of small bowel and 50–86% of large bowel. Conclusion TABUS and MRE are comparable modalities in the assessment of small and large bowel disease in newly diagnosed pediatric CD patients. Assessment of proximal small bowel is complex, and MRE may over-call disease. MRE still plays an important role in assessing abscesses and mild large bowel narrowing. Hyperemia on TABUS is an important indicator of active bowel inflammation, and is particularly useful for endoscopically inaccessible small bowel.

Time to initiation of pre-emptive therapy for cytomegalovirus impacts overall survival in pediatric hematopoietic stem cell transplant recipients

Background aimsCytomegalovirus (CMV) reactivation is a significant complication following allogeneic hematopoietic stem cell transplant (HSCT) and affects upwards of 40% of pediatric HSCT patients. Pre-emptive therapy remains the only effective treatment strategy available for pediatric patients following CMV reactivation. Little is known about how the timing of induction treatment following CMV reactivation impacts outcomes in pediatric patients, especially following ex vivo T-cell-depleted (TCD) HSCT. MethodsThe authors evaluated how the timing of induction treatment after CMV reactivation impacts overall survival (OS) and CMV disease in pediatric patients undergoing TCD HSCT at a single institution. The authors retrospectively analyzed patients treated on the pediatric service who received an initial ex vivo TCD HSCT at Memorial Sloan Kettering Cancer Center (MSKCC) from January 2010 to June 2018. CMV reactivation was defined as ≥1 CMV polymerase chain reaction >500 copies/mL in whole blood or >137 IU/mL in plasma within the first 180 days after allogeneic HSCT. To analyze the impact of the timing of induction treatment, the authors’ primary study outcome was OS and secondary outcome was CMV disease. ResultsA total of 169 patients who underwent an initial allogeneic TCD HSCT on the pediatric service at MSKCC from January 2010 to June 2018 were included in the analysis. Thirty-seven (22%) patients reactivated CMV during the first 180 days following HSCT. Of those patients who reactivated CMV, CMV donor/recipient (D/R) serostatus was as follows: D+/R+ n = 28 (76%) and D–/R+ n = 9 (24%). There was no CMV reactivation observed among recipients who were CMV-seronegative irrespective of donor serostatus. In those patients who reactivated CMV, the median time from HSCT to CMV reactivation was 24 days (interquartile range, 20–31). Eleven patients ultimately developed CMV disease in addition to CMV viremia, whereas the remaining patients had only CMV viremia. The cumulative incidence of CMV reactivation at 60 days was 45.2% (95% confidence interval [CI], 32.8–57.5) in the D+/R+ subgroup and 31% (95% CI, 14.2–47.9) in the D–/R+ subgroup. For those patients who reactivated CMV, 30 (81%) received induction treatment with ganciclovir or foscarnet. To analyze the impact of the timing of induction treatment on clinical outcomes, the authors restricted the analysis to those patients who reactivated CMV and received induction treatment (n = 30). The timing of induction treatment was significantly associated with OS, with optimal timing of initiation within a week of CMV reactivation (P = 0.02). There was no significant impact on the timing of induction treatment and risk of CMV disease (P = 0.30). ConclusionsIn ex vivo TCD HSCT in pediatric patients, early initiation of induction treatment after CMV reactivation is associated with improved OS.

Association between Endocrine Disorders and Severe COVID-19 Disease in Pediatric Patients.

IntroductionThough severe illness due to COVID-19 is uncommon in children, there is an urgent need to better determine the risk factors for disease severity in youth. This study aims to determine the impact a preexisting endocrine diagnosis has on severity of COVID-19 presentation in youth.MethodsThe cross-sectional chart review study included all patients less than 25 years old with a positive SARS-CoV-2 PCR at St. Louis Children's Hospital between March 2020 and February 2021. Electronic medical record data for analysis included patient demographics, BMI percentile, inpatient hospitalization or admission to the pediatric intensive care unit (PICU), and the presence of a preexisting endocrine diagnosis such as diabetes mellitus (type 1 and type 2), adrenal insufficiency, and hypothyroidism. Two outcome measures were analyzed in multivariate analysis: inpatient admission and PICU admission. Adjusted odds ratios with a 95% CI were calculated using binary logistic regression, along with p values after Wald χ² analysis.Results390 patients were included in the study. Mean age was 123.1 (±82.2) months old. 50.3% of patients were hospitalized, and 12.1% of patients were admitted to intensive care. Preexisting diagnoses of diabetes mellitus, obesity, and hypothyroidism were associated with an increased risk of hospital and ICU admission, independent of socioeconomic status.Discussion/ConclusionThis study provides evidence that unvaccinated youth with a preexisting diagnosis of obesity, hypothyroidism, or diabetes mellitus infected with COVID-19 are more likely to have a more severe clinical presentation requiring inpatient hospital admission and/or intensive care.

Особенности клинических и лабораторных изменений у подростков в динамике развития новой коронавирусной инфекции

The relevance of research on a novel coronavirus infection is associated with an increase in the incidence among children since 2021, which may be due to the accumulation of mutations in the virus genome and its evolution towards increased contagiousness, replicative ability, and evasion of immune protection. While there are many studies in adults, data analyzing the clinical course of the disease in pediatric patients infected with SARS-CoV-2 are limited, particularly regarding adolescents. Objective. To study the clinical and laboratory features of the course of a novel coronavirus infection in hospitalized adolescents in Novosibirsk during the first, second and third waves of the pandemic. Мaterials and methods. A retrospective analysis of case histories of 125 children treated at Novosibirsk Children's Clinical Hospital No 6 with a confirmed diagnosis of coronavirus infection during three pandemic waves was carried out (June–August 2020, October–December 2020, June–August 2021). Based on these time intervals, three groups of adolescents admitted to the hospital during the first, second, and third waves of coronavirus infection were formed. SARS-CoV-2 RNA in nasopharyngeal and oropharyngeal scrapings was determined using the PCR-RT method. Biochemical and general clinical studies were performed in accordance with the guidelines of the Ministry of Health of the Russian Federation. Statistical processing was carried out using the Satistika 7.0 software package (StatSoft, USA). Differences between the groups were assessed using the Z-test and the Mann–Whitney U test. Differences between the compared series were considered statistically significant with a probability level of 95%. Results. It was shown that during three pandemic waves (June 2020 – August 2021), more than half of the hospitalized children were adolescents. At the same time, regardless of the pandemic wave, intoxication, catarrhal and intestinal syndromes predominated in hospitalized adolescents. CNS injury symptoms were significantly less frequent in the first wave, as were skin rashes. Cough in the third wave was observed in 100% of hospitalized adolescents. The average values of the parameters of complete blood count, as well as CRP, D-dimer and ferritin had no statistically significant differences in different pandemic waves, but there was a significant variation in individual values within the groups in each wave. Key words: adolescents, coronavirus infection, COVID-19, clinical manifestations, laboratory parameters

Acute disseminated encephalomyelitis in children and adolescents - 20-year single-center experience in Serbia

Introduction/Objective. Acute disseminated encephalomyelitis (ADEM) is the most common demyelinating disease of the central nervous system in pediatric patients. We aimed to evaluate the clinical profile of children with ADEM and to discern prognostic factors for disease outcome. Methods. A 20-year retrospective?prospective study was conducted in a cohort with the diagnosis of ADEM. Results. The study included 36 patients, with range of follow-up period of 6?120 months (median of 26 months). Prior infection was reported in 72.2% of the patients. In the clinical presentation of the disease, motor deficit was most common (81.1%), followed by ataxia (77.8%). More than a third of patients had back and limb pain or abdominal visceral pain, which highly correlated with MRI findings of myelitis. Abnormal brain CT findings were evident in 22.2% of the patients, and this was associated with higher Expanded Disability Status Scale (EDSS) and quicker progression of the disease. Median EDSS was 0 at the most recent follow-up visit, in all the patients. EDSS 0?2.5 was verified in 29 (80.6%) of the patients, while three (8.3%) patients scored 7?9.5 at the last visit. Two patients had a lethal outcome. Conclusions. ADEM is a serious disease in pediatric patients, but with a good prognosis, which is illustrated by the fact that 80.6% of our patients had a complete or almost complete recovery.

Association between haploidentical hematopoietic stem cell transplantation combined with an umbilical cord blood unit and graft-versus-host disease in pediatric patients with acquired severe aplastic anemia.

Haploidentical hematopoietic stem cell transplantation (haplo-HSCT) based on granulocyte colony-stimulating factor plus anti-thymocyte regimens ('Beijing Protocol') provides a salvage treatment for patients of acquired severe aplastic anemia (SAA) in China. However, graft-versus-host disease (GVHD) is a major impediment of haplo-HSCT due to human leukocyte antigen disparity. Recently, haplo-HSCT combined with umbilical cord blood (UCB) (haplo-cord HSCT) is performed in clinical trials to potentially reduce the risk of severe GVHD. Nevertheless, studies comparing GVHD in pediatric patients receiving haplo and haplo-cord HSCT for SAA are limited. The objective of this study was to investigate the impact of UCB co-infusion on GVHD in pediatric patients receiving haplo-HSCT for SAA. We conducted a retrospective study of 91 consecutive SAA children undergoing haploidentical transplantation based on the 'Beijing Protocol' with or without co-infusion of UCB in our center. All patients received uniform non-myeloablative conditioning and GVHD prophylaxis. We compared baseline characteristics and transplant outcomes between the haplo (n = 35) and haplo-cord (n = 56) recipients. All 91 patients achieved hematopoietic recovery from haploidentical donors, with a higher incidence of peri-engraftment syndrome observed with the haplo-cord group as compared with the haplo group (75.0% versus 48.6%, p = 0.029). Notably, the haplo-cord group showed a lower incidence of II-IV acute GVHD (aGVHD) than the haplo group (16.1% versus 42.9%, p = 0.002). Observed incidences of chronic GVHD (cGVHD) and moderate to severe cGVHD in the haplo-cord group were also lower than that in the haplo group (25.6% versus 51.3%, p = 0.019; 16.2% versus 41.3%, p = 0.016, respectively). Haplo-cord HSCT was identified as the only factor associated with a lower incidence of II-IV aGVHD and cGVHD in multivariate analysis. However, no differences were observed between the two groups for infections and survival outcomes. Our data indicated that co-infusion of UCB in 'Beijing Protocol'-based haplo-HSCT may be effective for reducing the risk of severe GVHD in SAA children.

Gallstones in patients with severe motor and intellectual disability.

Asymptomatic gallbladder stones may be detected with ultrasound; some gallstones produce symptomatic diseases, such as cholecystitis, cholangitis, or pancreatitis. Identifying the clinical features of symptomatic gallstones may help prevent severe complications by providing intervention for asymptomatic gallstones. We aimed to investigate risk factors associated with developing symptomatic disease in pediatric patients with severe motor and intellectual disabilities (SMID). This retrospective study enrolled 30 patients with SMID who were treated at the Nara Medical University between March 2016 and March 2019. We examined the prevalence of gallstones, and the rate at which associated symptoms of gallstones were observed in patients. Furthermore, we compared the clinical features of patients with and without gallstones. Among 30 patients with SMID, 7 (23%) had gallstones, with 6 (86%) of them being symptomatic: 3 patients had acute pancreatitis and 3 had cholecystitis or cholangitis. Among 23 patients without gallstones, 2 had acute pancreatitis and 2 had biliary sludge. Patients with gallstones had significantly lower daily calorie intake than those without gallstones (P = 0.042). Furthermore, the incidence of gallstones was higher in patients who received total parenteral nutrition than in those who did not (P = 0.031). Comparative analysis between symptomatic and asymptomatic patients was not performed because almost all cases were symptomatic. Gallstones were detected in 23% of patients with SMID. The gallstones were symptomatic at a very high rate. Considering this fact, patients with SMID should be surveyed for gallstones; careful management may be needed in such patients.

Recommendations for the diagnosis and management of Fabry disease in pediatric patients: a document from the Rare Diseases Committee of the Brazilian Society of Nephrology (Comdora-SBN).

Fabry disease (FD) is a genetic disease, with X-chromosome linked inheritance, due to variants in the GLA gene that encodes the α-galactosidase A (α-GAL) enzyme. The purpose of the present study was to create a consensus aiming to standardize the recommendations regarding the renal involvement of FD with guidelines on the diagnosis, screening, and treatment of pediatric patients. This consensus is an initiative of the Rare Diseases Committee (Comdora) of the Brazilian Society of Nephrology (SBN). Randomized controlled clinical studies and studies with real-life data added to the authors' experience were considered for this review. The result of this consensus was to help manage patient and physician expectations regarding treatment outcomes. Thus, this consensus document recommends the investigation of the pediatric family members of an index case, as well as cases with suggestive clinical signs. From the diagnosis, assess all possible FD impairments and grade through scales. From an extensive review of the literature including pediatric protocols and particularly evaluating pediatric cases from general studies, it can be concluded that the benefits of early treatment are great, especially in terms of neuropathic pain and renal impairment parameters and outweigh the possible adverse effects that were mainly manifested by infusion reactions.

A Novel Surgical Treatment for Pediatric Fulminant Clostridium Difficile Colitis.

Pediatric patients rarely present with severe, complicated Clostridium difficile colitis. The medical and surgical management of pediatric patients is primarily based on evidence from adult populations, in which standard therapy often includes subtotal colectomy and end ileostomy. New evidence in adults suggests that a diverting loop ileostomy and colonic lavage is an effective alternative for the management of refractory severe, complicated C difficile colitis. We report the case of a 15-year-old female patient who developed severe, complicated C difficile colitis. After failing medical management, she underwent a diverting loop ileostomy with antegrade colonic lavage and recovered uneventfully. There is limited literature on the medical management of C difficile–associated disease in pediatric patients and even less information on the medical or surgical management of severe, complicated C difficile colitis in pediatrics. Diverting loop ileostomy and colonic lavage should be considered as an alternative to subtotal colectomy and end ileostomy in a pediatric patient with severe, complicated C difficile colitis.

Differences in presentation between paediatric- and adult-onset primary Sjögren's syndrome patients.

Primary Sjögren's syndrome (pSS) is a rare disease in paediatric patients. Presenting symptoms differ from those in adult patients. The aim of this study was to evaluate presenting symptoms, classification criteria and clinical assessments, including salivary gland ultrasonography (SGUS), at disease onset in paediatric and adult patients with pSS. Data of 23 paediatric- and 33 adult-onset patients with pSS were obtained from our standardised multidisciplinary REpSULT and RESULT cohorts, respectively. Clinical, patient-reported, serological, functional, biopsy and SGUS parameters were compared. In paediatric-onset pSS (pedSS) patients, recurrent parotid gland swelling (91% vs. 49%, p<0.001) and fever (30% vs. 3%, p=0.006) were more often present than in adult-onset patients. In contrast, sicca symptoms of mouth (52% vs. 79%, p=0.046) and eyes (26% vs. 73%, p<0.001) were less common in pedSS patients. In paediatric patients, the entry criteria of the ACR/EULAR classification were most often met due to activity in the glandular domain of the ESSDAI. When applying the ACR/EULAR classification criteria, only 78% of pedSS fulfilled these criteria compared to 100% of adult patients. Abnormal glandular function tests had a greater contribution to fulfilling the criteria in adults, while the biopsy had a greater contribution in paediatric patients. Anti-SSA/Ro serology had similar contribution for both cohorts. SGUS Hocevar score was significantly higher in paediatric compared to adult patients (median 25 vs. 18, p=0.004). PedSS has a different presentation than adult-onset pSS. Recurrent parotid gland swelling in paediatric patients should alert clinicians to the potential presence of pSS.

The effect of probiotics on the treatment of non-alcoholic fatty liver disease in pediatric patients: a systematic review and meta-analysis

Rationale: Non-alcoholic fatty liver disease (NAFLD) is nowadays the most common chronic pediatric liver disease. Recently, clinical studies have been conducted investigating the impact of probiotics’ supplementation in the management of pediatric NAFLD. We conducted a meta-analysis in order to examine the role of probiotics in pediatric NAFLD.