Disease Progression In Children Research Articles

Quantitative Foot Muscle Magnetic Resonance Imaging Reliably Measures Disease Progression in Children and Adolescents with Charcot-Marie-Tooth Disease Type 1A.

Quantitative muscle fat fraction (FF) responsiveness is lower in younger Charcot-Marie-Tooth disease type 1A (CMT1A) patients with lower baseline calf-level FF. We investigated the practicality, validity, and responsiveness of foot-level FF in this cohort involving 22 CMT1A patients and 14 controls. The mean baseline foot-level FF was 25.9 ± 20.3% in CMT1A patients, and the 365-day FF (n = 15) increased by 2.0 ± 2.4% (p < 0.001 vs controls). Intrinsic foot-level FF demonstrated large responsiveness (12-month standardized response mean (SRM) of 0.86) and correlated with the CMT examination score (ρ = 0.58, P = 0.01). Intrinsic foot-level FF has the potential to be used as a biomarker in future clinical trials involving younger CMT1A patients. ANN NEUROL 2024;96:170-174.

Comprehensive Association Analyses of Extraintestinal Manifestations in Inflammatory Bowel Disease

Patients with inflammatory bowel disease (IBD) frequently develop extraintestinal manifestations (EIMs) that contribute substantially to morbidity. We assembled the largest multicohort data set to date to investigate the clinical, serologic, and genetic factors associated with EIM complications in IBD. Data were available in 12,083 unrelated European ancestry IBD cases with presence or absence of EIMs (eg, ankylosing spondylitis [ankylosing spondylitis and sacroiliitis], primary sclerosing cholangitis [PSC], peripheral arthritis, and skin and ocular manifestations) across 4 cohorts (Cedars-Sinai Medical Center, National Institute for Diabetes and Digestive and Kidney Diseases IBD Genetics Consortium, Sinai Helmsley Alliance for Research Excellence Consortium, and Risk Stratification and Identification of Immunogenetic and Microbial Markers of Rapid Disease Progression in Children with Crohn's Disease cohort). Clinical and serologic parameters were analyzed by means of univariable and multivariable regression analyses using a mixed-effects model. Within-case logistic regression was performed to assess genetic associations. Most EIMs occurred more commonly in female subjects (overall EIM: P= 9.0E-05, odds ratio [OR], 1.2; 95% CI, 1.1-1.4), with CD (especially colonic disease location; P= 9.8E-09, OR, 1.7; 95% CI, 1.4-2.0), and in subjects who required surgery (both CD and UC; P= 3.6E-19, OR, 1.7; 95% CI, 1.5-1.9). Smoking increased risk of EIMs except for PSC, where there was a "protective" effect. Multiple serologic associations were observed, including with PSC (anti-nuclear cytoplasmic antibody; IgG and IgA, anti-Saccharomyces cerevisiae antibodies; and anti-flagellin) and any EIM (anti-nuclear cytoplasmic antibody; IgG and IgA, anti-Saccharomyces cerevisiae antibodies; and anti-Pseudomonas fluorescens-associated sequence). We identified genome-wide significant associations within major histocompatibility complex (ankylosing spondylitis and sacroiliitis, P= 1.4E-15; OR, 2.5; 95% CI, 2.0-3.1; PSC, P= 2.7E-10; OR, 2.8; 95% CI, 2.0-3.8; ocular, P= 2E-08, OR, 3.6; 95% CI, 2.3-5.6; and overall EIM, P= 8.4E-09; OR, 2.2; 95% CI, 1.7-2.9) and CPEB4 (skin, P= 2.7E-08; OR, 1.5; 95% CI, 1.3-1.8). Genetic associations implicated tumor necrosis factor, JAK-STAT, and IL6 as potential targets for EIMs. Contrary to previous reports, only 2% of our subjects had multiple EIMs and most co-occurrences were negatively correlated. We have identified demographic, clinical, and genetic associations with EIMs that revealed underlying mechanisms and implicated novel and existing drug targets-important steps toward a more personalized approach to IBD management.

Predictive biomarkers of rapidly developing insulin deficiency in children with type 1 diabetes

IntroductionThe rate of progression to complete insulin deficiency varies greatly in type 1 diabetes. This constitutes a challenge, especially when randomizing patients in intervention trials aiming to preserve beta cell...

Novel multispectral imaging to predict disease progression in pediatric morphea.

Morphea, or localized scleroderma, is an inflammatory, fibrosing skin disorder that can be progressive and debilitating. Infrared thermography frequently has false positive results. The aim of this study was to assess the ability of multispectral imaging to predict disease progression in children with morphea. Children with morphea were recruited between 2016 and 2022. Multispectral images of affected and matched contralateral unaffected sites were obtained using the Antera™ 3D camera. Clinical assessment was performed using the Localized Scleroderma Assessment Tool (LoSCAT). Children were followed up every 3 months for imaging and clinical review. The main outcome measurement was correlation of hemoglobin gradient between affected and matched contralateral unaffected tissue and progression. Of 17 children, the average age was 12 years (range 6-18 years); most were female (76.5%) and white (94.1%). Nearly two-thirds (64.7%) had linear morphea, 35.2% had plaque morphea; 58.8% had been treated with systemic agents. The average LoSCAT score was 20.6 (range 5-73). The average hemoglobin gradient between affected and matched contralateral unaffected skin was four times higher in those who had progression (average differential 0.3, range 0.1-0.4) compared to those who did not (average differential 0.08, range 0.02-0.15). Using a cut off of a 0.18 hemoglobin gradient between affected and unaffected skin, the sensitivity of multispectral imaging for detecting progression in pediatric morphea is 90% with specificity of 100%. Multispectral imaging is a novel assessment tool with promising accuracy in predicting progression as an adjunct to clinical assessment in pediatric morphea. Further research should examine its performance against thermography.

Abstract WP226: Perioperative Stroke and Cardiac Anomalies Associated With Posterior Cerebral Artery Stenosis in Children With Moyamoya

Introduction: Moyamoya is a progressive steno-occlusive arteriopathy of the intracranial circulation affecting the anterior circulation and less often the posterior circulation. Risk factors and severity of disease progression in children with moyamoya and posterior cerebral artery (PCA) stenosis have not been well described in the literature. Previous research has shown an association between PCA stenosis and increased risk of post-operative stroke. We wanted to further explore this relationship in children with moyamoya and delineate the associated risk factors. Methods: Children with moyamoya who underwent surgical revascularization at our institution between December 2015 and December 2022 were reviewed for presence of PCA stenosis. Clinical and radiographic features were compared between children with moyamoya with and without PCA involvement. Categorical variables were compared using Fisher's exact test and continuous variables using Wilcoxon rank-sum. Associations between perioperative stroke and PCA stenosis were analyzes using a multivariate logistic regression. Results: In our cohort of 160 children with moyamoya, 45 (28%) had PCA stenosis; 26 of these 45 (57%) had PCA stenosis at time of diagnosis. Of the 19 children who did not have PCA stenosis at time of diagnosis but developed it during follow up, the median time to development of PCA stenosis was 1.0 years. Children with moyamoya and PCA stenosis had significant more cardiac anomalies than those without (p=0.02). Other associated disorders were found in 13 (28%) including trisomy 21 (6, 13%), cranial radiation (2,4%) and NF1 (3,7%). Interestingly, we found no significant difference in age, sex or prevalence of bilateral disease between the groups. Children with moyamoya and PCA stenosis had a 3.5 higher odds of having a stroke within 2 weeks of surgery (p=0.049). Conclusion: Children with moyamoya and PCA stenosis had a 3 fold higher odds of perioperative stroke compared to those without PCA stenosis. Genetic evaluations may be warranted given association of PCA stenosis and cardiac anomalies.

Telomere length exhibits a strong association with non-alcoholic fatty liver disease progression in children

Telomere length exhibits a strong association with non-alcoholic fatty liver disease progression in children

Intravitreal enzyme replacement therapy to prevent retinal disease progression in children with neuronal ceroid lipofuscinosis type 2 (CLN2): Unilateral injection results

Intravitreal enzyme replacement therapy to prevent retinal disease progression in children with neuronal ceroid lipofuscinosis type 2 (CLN2): Unilateral injection results

Longitudinal profiling of the intestinal microbiome in children with cystic fibrosis treated with elexacaftor-tezacaftor-ivacaftor.

The intestinal microbiome influences growth and disease progression in children with cystic fibrosis (CF). Elexacaftor-tezacaftor-ivacaftor (ELX/TEZ/IVA), the newest pharmaceutical modulator for CF, restores the function of the pathogenic mutated CF transmembrane conductance regulator (CFTR) channel. We performed a single-center longitudinal analysis of the effect of ELX/TEZ/IVA on the intestinal microbiome, intestinal inflammation, and clinical parameters in children with CF. Following ELX/TEZ/IVA, children with CF had significant improvements in body mass index and percent predicted forced expiratory volume in one second, and required fewer antibiotics for respiratory infections. Intestinal microbiome diversity increased following ELX/TEZ/IVA coupled with a decrease in the intestinal carriage of Staphylococcus aureus, the predominant respiratory pathogen in children with CF. There was a reduced abundance of microbiome-encoded antibiotic resistance genes. Microbial pathways for aerobic respiration were reduced after ELX/TEZ/IVA. The abundance of microbial acid tolerance genes was reduced, indicating microbial adaptation to increased CFTR function. In all, this study represents the first comprehensive analysis of the intestinal microbiome in children with CF receiving ELX/TEZ/IVA.IMPORTANCECystic fibrosis (CF) is an autosomal recessive disease with significant gastrointestinal symptoms in addition to pulmonary complications. Recently approved treatments for CF, CF transmembrane conductance regulator (CFTR) modulators, are anticipated to substantially improve the care of people with CF and extend their lifespans. Prior work has shown that the intestinal microbiome correlates with health outcomes in CF, particularly in children. Here, we study the intestinal microbiome of children with CF before and after the CFTR modulator, ELX/TEZ/IVA. We identify promising improvements in microbiome diversity, reduced measures of intestinal inflammation, and reduced antibiotic resistance genes. We present specific bacterial taxa and protein groups which change following ELX/TEZ/IVA. These results will inform future mechanistic studies to understand the microbial improvements associated with CFTR modulator treatment. This study demonstrates how the microbiome can change in response to a targeted medication that corrects a genetic disease.

Neurofilament light protein as a biomarker for spinal muscular atrophy: a review and reference ranges.

Spinal muscular atrophy (SMA) is the leading genetic cause of infant mortality, characterized by progressive neuromuscular degeneration resulting from mutations in the survival motor neuron (SMN1) gene. The availability of disease-modifying therapies for SMA therapies highlights the pressing need for easily accessible and cost-effective blood biomarkers to monitor treatment response and for better disease management. Additionally, the wide implementation of newborn genetic screening programs in Western countries enables presymptomatic diagnosis of SMA and immediate treatment administration. However, the absence of monitoring and prognostic blood biomarkers for neurodegeneration in SMA hinders effective disease management. Neurofilament light protein (NfL) is a promising biomarker of neuroaxonal damage in SMA and reflects disease progression in children with SMA undergoing treatment. Recently, the European Medicines Agency issued a letter of support endorsing the potential utilization of NfL as a biomarker of pediatric neurological diseases, including SMA. Within this review, we comprehensively assess the potential applications of NfL as a monitoring biomarker for disease severity and treatment response in pediatric-onset SMA. We provide reference ranges for normal levels of serum based NfL in neurologically healthy children aged 0-18 years. These reference ranges enable accurate interpretation of NfL levels in children and can accelerate the implementation of NfL into clinical practice.

Statin therapy in patients with early-stage autosomal dominant polycystic kidney disease: Design and baseline characteristics

BackgroundAutosomal dominant polycystic kidney disease (ADPKD) is characterized by the development and continued growth of multiple cysts in the kidneys leading to ultimate loss of kidney function in most patients. Currently, tolvaptan is the only agency approved therapy to slow kidney disease advancement in patients with faster progressing disease underscoring the need for additional ADPKD therapies suitable for all patients. We previously showed that pravastatin slowed kidney disease progression in children and young adults with ADPKD. However, the intervention has not been tested in an adult cohort. AimsThe aim of the study is to conduct a single center, randomized, placebo-controlled double-blinded clinical trial to determine the efficacy of pravastatin on slowing kidney disease progression in adult patients with early stage ADPKD. MethodsOne hundred and fifty adult patients with ADPKD and eGFR ≥60 ml/min/1.73m2 will be enrolled in the study and randomized to receive 40 mg/day pravastatin or placebo for a period of 2-years. OutcomesThe primary outcome of the trial is change in total kidney volume assessed by magnetic resonance imaging (MRI). Secondary outcomes include change in kidney function by iothalamate GFR and renal blood flow and markers of inflammation and oxidative stress. ConclusionThis study will assess the kidney therapeutic benefits of pravastatin in adult patients with ADPKD. The recruitment goal of 150 subjects was attained and the study is ongoing.Registration: This study is registered on Clinicaltrials.gov # NCT03273413

Home-spirometry exacerbation profiles in children with cystic fibrosis.

Pulmonary exacerbations (PEx) are strong predictors of respiratory disease progression in children with cystic fibrosis (CwCF) and may be associated with persistent decreased lung function after acute management. Telemonitoring devices can be used for early detection and monitoring of PEx, but its utility is debated. Which symptoms and telemonitoring spirometry characterics are related to outcome dynamics following initial PEx management? This retrospective study included CwCF followed at Bordeaux University Hospital, France. All severe PEx episodes treated with intravenous (IV) antibiotics (ATB) between 1 January 2017 and 31 December 2021 in CwCF using home telemonitoring were analyzed. Symptoms and home spirometry data were collected 45 days before and up to 60 days after each IV ATB course. We defined three response profiles based on terciles of baseline forced expiratory volume in 1 s (FEV1 ) recovery. A total of 346 IV ATB courses for PEx were administered to 65 CwCF during the study period. The drop in FEV1 became significant 8 days before IV ATB initiation. Forty-one percent of IV ATB courses failed to restore baseline FEV1 . The magnitude of FEV1 drop and a greater delay in the initiation of treatment correlated with a low response level. On the 14th day of the IV treatment, a FEV1 recovery less than 94% of baseline was associated with a nonresponder profile. Home spirometry may facilitate the early recognition of PEx to implement earlier interventions. This study also provides an outcome lung function threshold which identifies low responders to IV ATB.

Plasma Metabolomics of Dietary Intake of Protein-Rich Foods and Kidney Disease Progression in Children

Evidence regarding the efficacy of a low-protein diet for patients with CKD is inconsistent and recommending a low-protein diet for pediatric patients is controversial. There is also a lack of objective biomarkers of dietary intake. The purpose of this study was to identify plasma metabolites associated with dietary intake of protein and to assess whether protein-related metabolites are associated with CKD progression. Nontargeted metabolomics was conducted in plasma samples from 484 Chronic Kidney Disease in Children (CKiD) participants. Multivariable linear regression estimated the cross-sectional association between 949 known, nondrug metabolites and dietary intake of total protein, animal protein, plant protein, chicken, dairy, nuts and beans, red and processed meat, fish, and eggs, adjusting for demographic, clinical, and dietary covariates. Cox proportional hazards models assessed the prospective association between protein-related metabolites and CKD progression defined as the initiation of kidney replacement therapy or 50% eGFR reduction, adjusting for demographic and clinical covariates. One hundred and twenty-seven (26%) children experienced CKD progression during 5years of follow-up. Sixty metabolites were significantly associated with dietary protein intake. Among the 60 metabolites, 10 metabolites were significantly associated with CKD progression (animal protein: n=1, dairy: n=7, red and processed meat: n=2, nuts and beans: n=1), including one amino acid, one cofactor and vitamin, 4 lipids, 2 nucleotides, one peptide, and one xenobiotic. 1-(1-enyl-palmitoyl)-2-oleoyl-glycerophosphoethanolamine (GPE, P-16:0/18:1) was positively associated with dietary intake of red and processed meat, and a doubling of its abundance was associated with 88% higher risk of CKD progression. 3-ureidopropionate was inversely associated with dietary intake of red and processed meat, and a doubling of its abundance was associated with 48% lower risk of CKD progression. Untargeted plasma metabolomic profiling revealed metabolites associated with dietary intake of protein and CKD progression in a pediatric population.

The Outcome of Childhood Immunoglobulin A Nephropathy with Acute Kidney Injury at the Onset of the Disease-National Study.

Introduction: IgA nephropathy (IgAN) is the most common glomerulonephritis worldwide. Decreased glomerular filtration rate is a known risk factor for disease progression. Aim: We aimed to examine factors that may contribute to disease progression in children that present with impaired eGFR at the onset of IgAN. Materials and methods: Of the 175 patients with IgAN from the Polish Registry of Children with IgAN and IgAVN, 54 (31%) patients with IgAN who had an onset of renal function impairment (GFR < 90 mL/min) were eligible for the study. All of them were analyzed for initial symptoms (GFR according to Schwartz formula, creatinine, proteinuria, IgA, C3), renal biopsy result with assessment by Oxford classification, treatment used (R-renoprotection, P-prednisone+R, Aza-azathioprine+P+R, Cyc-cyclophosphamide+P+R, CsA-cyclosporine+P+R, MMF-mycophenolate mofetil+P+R), and distant follow-up. Based on the GFR score obtained at the end, patients were divided into two groups: A-GFR > 90 mL/min and B-GFR < 90 mL/min. Results: In the study group, the mean age of onset was 12.87 ± 3.57 years, GFR was 66.1 ± 17.3 mL/min, and proteinuria was 18.1 (0-967) mg/kg/d. Renal biopsy was performed 0.2 (0-7) years after the onset of the disease, and MESTC score averaged 2.57 ± 1.6. Treatment was R only in 39% of children, P+R in 20%, Aza+P+R in 28%, Cyc+P+R in 9%, CsA+P+R in 7%, and MMF+P+R in 3%. The length of the observation period was 2.16 (0.05-11) years. At the follow-up, Group A had 30 patients (56%) and Group B had 24 patients (44%). There were no significant differences in any of the other biochemical parameters (except creatinine) or proteinuria values between the groups and the frequency of the MESTC score ≥ 2 and <2 was not significantly different between Groups A and B. Patients with normal GFR at the follow-up (Group A) were significantly more likely to have received prednisone and/or immunosuppressive treatment than those in Group B (p < 0.05) Conclusions: In a population of Polish children with IgAN and decreased renal function at the onset of the disease, 56% had normal GFR in remote observation. The use of immunosuppressive/corticosteroids treatment in children with IgAN and impaired glomerular filtration rate at the beginning of the disease may contribute to the normalization of GFR in the outcome, although this requires confirmation in a larger group of pediatric patients.

THU140 Triglyceride Glucose-body Mass Index Is A Reliable Surrogate Marker To Predict Non-alcoholic Fatty Liver Disease In Children And Adolescents

Abstract Disclosure: J. Yoon: None. K. Yi: None. Background: The triglyceride glucose (TyG) index is significantly associated with the presence of nonalcoholic fatty liver disease (NAFLD) and is a reliable insulin resistance (IR) surrogate marker. TyG index combined with body mass index (BMI) were reported to be superior to TyG index alone in predicting NAFLD in youths. Ultrasound fatty liver indicator (US-FLI) is proposed as a non-invasive, semi-quantitative method for predicting hepatitis in children with NAFLD. Objects: In this study, TyG-BMI detection ability was evaluated in children and adolescents with NAFLD diagnosed by US-FLI and compared with TyG index. We also analyzed the association between TyG-BMI and severity of NAFLD according to the US-FLI scores. Methods: Alanine aminotransferase (ALT) was used as the screening method for NAFLD (&amp;gt;26IU/L in boys and &amp;gt;22IU/L in girls), and US-FLI was performed on children who met these criteria. The US-FLI is a scoring system ranging 2-8 that evaluates based on intensity of liver/kidney contrast, posterior attenuation of ultrasound beam, vessel blurring, difficult visualization of gallbladder wall, difficult visualization of the diaphragm and areas of focal sparing. NAFLD is diagnosed by the minimum score ≥2. Healthy children of normal weight (body mass index 5-85th percentile) without metabolic comorbidities and no steatosis on ultrasound participated as a control group. TyG index was calculated as ln(fasting triglyceride (TG) [mg/dL] × fasting glucose [mg/dL]/2), and TyG-BMI were calculated as TyG × BMI. The diagnostic value of TyG-BMI for NAFLD detection was evaluated based on area under the receiver operating characteristic curve (AUC). Results: A total of 130 NAFLD patients (90 boys and 40 girls) included in this study, with mean age of 11.5±2.29 years. The control group consisted of a total of 28 subjects (17 boys and 11 girls) with mean age of 8.39±1.60 years. The TyG-BMI was significantly correlated with AST (r=0.282, p=0.005), ALT (r=0.395, p&amp;lt;0.001), HOMA-IR (r=0.444, p&amp;lt;0.001), and US-FLI (r=0.557, p&amp;lt;0.001) after controlling for sex and age. Multiple linear regression analysis showed that TyG-BMI were significantly associated with ALT (β=0.156, p=0.024), HOMA-IR (β =0.247, p&amp;lt;0.001), US-FLI (β=0.366, p&amp;lt;0.001) after adjusting for confounders. TyG-BMI was independent risk factor for NAFLD (odds ratio: 1.13, 95% confidence interval: 1.041-1.228) after controlling sex and age. In the receiver operating characteristic analysis, the TyG–BMI index (AUC=0.994, p&amp;lt;0.001) showed a better performance for detection of NAFLD than the TyG index (AUC=0.834, p&amp;lt;0.001). Conclusions: TyG-BMI is associated with insulin resistance and severity of US-FLI in NAFLD. In addition, TyG-BMI was superior to TyG index alone in detecting NAFLD. TyG-BMI is expected to be useful in detecting NAFLD and predicting disease progression in children and adolescents. Presentation: Thursday, June 15, 2023

Electrocardiographic Findings in Genotype-Positive and Non-sarcomeric Children with Definite Hypertrophic Cardiomyopathy and Subclinical Variant Carriers.

In children with hypertrophic cardiomyopathy (HCM), the genotype-phenotype association of abnormal electrocardiographic (ECG) features in the backdrop of gene positivity has not been well described. This study aimed to describe the abnormal ECG findings in children with HCM harboring who have genetic variants and determine the association with major adverse cardiac events (MACE). We retrospectively analyzed 81 variants-positive, phenotype-positive (V+P+), 66 variant-positive, phenotype-negative (V+P-), and 85 non-sarcomeric subjects. We analyzed ECG findings and clinical outcomes in the three groups of subjects. Repolarization abnormalities (ST and T wave changes) and pathologic Q waves were the most common abnormalities in variant and non-sarcomeric subjects. The V+P+ group showed higher occurrence of ST segment changes and T wave abnormalities compared to V+P- group. Independent predictors of MACE included ST segment changes (OR 3.54, CI 1.20-10.47, p = 0.022). T wave changes alone did not predict outcome (OR 2.13, CI 0.75-6.07, p = 0.157), but combined repolarization abnormalities (ST+T changes) were strong predictors of MACE (OR 5.84, CI 1.43-23.7, p = 0.014) than ST segment changes alone. Maximal wall z score by echocardiography was a predictor of MACE (OR 1.21, CI 1.07-1.37, p = 0.002). Despite the presence of significant myocardial hypertrophy (z score > 4.7), voltage criteria for LVH were much less predictive. In the non-sarcomeric group, RVH was significantly associated with MACE (OR 3.85, CI 1.08-13.73, p = 0.038). These abnormal ECG findings described on the platform of known genetic status and known myocardial hypertrophy may add incremental value to the diagnosis and surveillance of disease progression in children with HCM. Select ECG findings, particularly repolarization abnormalities, may serve as predictors of MACE in children.

Re: Deep Learning Imaging Features Derived from Kidney Ultrasounds Predict Chronic Kidney Disease Progression in Children with Posterior Urethral Valves

Re: Deep Learning Imaging Features Derived from Kidney Ultrasounds Predict Chronic Kidney Disease Progression in Children with Posterior Urethral Valves

The impact of changes in gadolinium-enhancement on disease progression in children with neurofibromatosis type 1-associated optic pathway glioma: a retrospective analysis.

There has been limited investigation of imaging features associated with visual acuity (VA) decline and initiation of treatment for patients with neurofibromatosis type 1 (NF1) and optic pathway glioma (OPG). To evaluate the association of increased gadolinium enhancement with decline in VA, initiation of chemotherapy, and tumor growth, we performed a retrospective cohort study of children diagnosed with NF1-OPG between January 2006 to June 2016. Two cohorts were defined: a new diagnosis and a longitudinal cohort. Outcomes were examined at 1 and 2 years from initial diagnosis, and 1 and 2 years from initial increase in enhancement in the longitudinal cohort. Eighty patients were eligible; all 80 contributed to the new diagnosis cohort and 73 to the longitudinal cohort. Fifty-six patients (70%) demonstrated enhancing NF1-OPG at diagnosis. 39% of patients in the new diagnosis cohort and 45% of those in the longitudinal cohort developed increased enhancement during the study period. There was no significant association between increases in enhancement and VA decline in the newly diagnosed or longitudinal cohorts, as well as with initiation of treatment in the longitudinal cohort. Although there was an association of enhancement increase with treatment in the new diagnosis cohort, this association was not maintained when stratified by concurrent change in tumor size. Increased gadolinium-enhancement independent of a concurrent increase in tumor size on MRI should not be used as a marker of NF1-OPG progression and does not appear to be associated with visual decline or initiation of chemotherapy.

Clinical significance of IgM and C3 deposition in children with primary immunoglobulin A nephropathy.

Mesangial IgM and C3 deposition is commonly observed in patients with primary immunoglobulin A nephropathy (IgAN), but its characteristics and prognosis have rarely been reported. The aim of this study was to investigate the relationship between combined mesangial IgM and C3 deposition and disease progression in children with IgAN. One hundred sixteen children diagnosed with IgAN between 2016 and 2020 were selected. Renal biopsies were scored by Oxford classification including the presence of mesangial hypercellularity, endocapillary hypercellularity, segmental glomerulosclerosis, tubular atrophy/interstitial fibrosis and crescents.The primary renal outcome was an event of either ≥ 50% reduction of eGFR from the baseline value or the onset of end-stage renal disease within the follow-up period.Cox regression analysis was performed to examine the effect of the combined mesangial IgM and C3 deposition on renal outcomes. Forty-seven (40.52%) patients presented combined mesangial IgM and C3 deposition. Compared with children without combined IgM and C3 deposition, children with combined IgM and C3 deposition presented higher mesangial hypercellularity, endocapillary hypercellularity and cresentic lesions in kidney biopsies, and higher prevalence of renal dysfunction (19.15% versus 2.90%; P = 0.007). Renal outcome was alsosignificantly worse as revealed by Kaplan-Meier curves (P = 0.0034). Multivariable Cox analysis identified tubular atrophy/interstitial fibrosis lesions [hazard ratio (HR) 14.843, 95% CI, 3.497-62.997, P < 0.001] and intensity of IgM deposition (HR 2.838, 95% CI, 1.321-6.094, P = 0.007) as independent risk factors for poor renal function. Combined mesangial IgM and C3 deposition was associated with unfavorable histopathological features. Mesangial IgM deposition was an independent risk factor for poor renal outcomes in children with primary IgAN.

Lipoprotein(a) and subclinical vascular disease progression in children with familial hypercholesterolaemia

Lipoprotein(a) and subclinical vascular disease progression in children with familial hypercholesterolaemia

Butyrate-Producing Bacteria as Microbiomarkers of Chronic Kidney Disease Progression in Children.

Butyrate-Producing Bacteria as Microbiomarkers of Chronic Kidney Disease Progression in Children.