A pediatric case of atypical hemolytic uremic syndrome (aHUS): Could any infection play a triggering role?

A 12-year-old boy was transferred to our pediatric department from a rural hospital for fever, cough, and vomiting associated with thrombocytopenia, non-immune hemolytic anemia, and acute kidney injury, leading to the diagnosis of hemolytic uremic syndrome (HUS). A nasopharyngeal swab and a lower respiratory sample detected Influenza A by polymerase chain reaction (PCR). The patient was treated with oseltamivir and intravenous fluids in addition to fresh frozen plasma (FFP). Enteropathogenic Escherichia coli (EPEC) was detected in a stool sample by PCR. Serum antibodies for Mycoplasma pneumoniae (IgM and IgG) and Helicobacter pylori (IgA and IgG) were increased. Further work-up revealed elevated serum C5b-9 suggesting a simultaneous viral and bacterial infection-mediated complement overactivation leading to the diagnosis of atypical HUS (aHUS). An association between aHUS and influenza A is reported in the literature, but the correlation of EPEC, Mycoplasma pneumoniae, and Helicobacter pylori with aHUS is not well-established. Fresh frozen plasma was administered for a total of 3 days, followed by clinical and laboratory improvement. The patient has remained asymptomatic until the latest follow-up, 5 months after discharge. This case demonstrates the potential triggering role of different pathogens in aHUS pathogenesis to raise awareness in the pediatric community.

Denosumab in a pediatric kidney transplant recipient with late, resistant hypercalcemia secondary to Pneumocystis jirovecii pneumonia.

Kidney transplant recipients (KTR) are at an increased risk of developing Pneumocystis jirovecii pneumonia (PCP), especially during the first year after transplantation. This is the first reported pediatric KTR, with chronic kidney disease (CKD) secondary to kidney dysplasia and vesicoureteral reflux, who developed refractory and symptomatic hypercalcemia 5 years after transplantation. The hypercalcemia was resistant to treatment with intravenous hyperhydration, furosemide, and a low-calcium diet. A respiratory tract infection due to PCP treated with trimethoprim-sulfamethoxazole did not improve calcium levels. Due to the hypercalcemic symptom burden for the patient, a single dose of subcutaneous denosumab was used to achieve sustained clinical and biochemical improvement, without any severe adverse events. This case highlights the potential use of denosumab as a treatment option in pediatric KTR with refractory hypercalcemia related to PCP. Further study of denosumab in young people with CKD or kidney transplants is needed before routine use can be recommended.

Beckwith-Wiedemann syndrome with multiple hepatic and cutaneous hemangiomas in a female patient of Albanian origin: Diagnostic and therapeutic considerations.

We describe a 2-month-old female infant with macroglossia, macrosomia, omphalocele, neonatal hypoglycemia, earlobe creases, low nasal bridge, midface retrusion, syndromic facies and multiple cutaneous and hepatic hemangiomas (HH). Genetic evaluation confirmed the diagnosis of Beckwith-Wiedemann Syndrome (BWS) with mosaic uniparental disomy 11 as the underlying genetic mechanism suggested by partial hypermethylation of H19/IGF2:IG-DMR and partial hypomethylation of KCNQ1OT1:TSS-DMR on chromosome 11p15.5. Pediatric endocrinology and cardiology assessments were normal. No malignant liver or renal tumors were detected during the follow-up period. Treatment with propranolol was started for the multiple HH, according to international recommendations. At 3-, 6-, and 9-month follow up, a gradual decrease in the size of the hemangiomas and AFP levels was observed, without side effects. This is the fifth case in the literature combining HH and BWS, and among these, the third case with this specific genetic defect suggesting a possible association between HH and BWS caused by 11 paternal uniparental disomy [upd(11)pat]. The case also highlights that if treatment is warranted, then oral propranolol can be used for the management of infantile HH in BWS patients similarly to non-BWS patients.

The benefit of metformin in the treatment of pediatric non-alcoholic fatty liver disease: a systematic review and meta-analysis of randomized controlled trials.

This is the first meta-analysis of the available literature about the efficacy of metformin exclusively in pediatric patients with non-alcoholic fatty liver disease (NAFLD). We conducted a systematic literature search through major electronic databases till March 12, 2023, investigating the efficacy and safety of metformin in pediatric NAFLD. Weighted mean difference (WD) and standard deviation (SD) were used for continuous outcomes. In total, 4 randomized controlled trials (RCTs) with 309 pediatric patients with NAFLD were included in the meta-analysis. Metformin could not reach a statistically significant improvement in alanine aminotransferase (ALT) levels [(ALT: WMD = - 1.55 IU/L, 95% CI: - 5.38 to 2.28, I2 = 16%, p = 0.43), but had a statistically significant impact (p < 0.05) in insulin and HOMA-IR regulation, triglycerides, and high-density lipoprotein level improvement.   Conclusion: According to the data of this meta-analysis, treatment with metformin failed to statistically improve liver enzymes but may be beneficial in the improvement of lipid parameters and insulin metabolism regulation in pediatric patients with NAFLD. As there are not enough available studies in the literature, the influence of metformin on liver ultrasonography or histology in pediatric NAFLD should be further analyzed in future studies. What is Known: • Lifestyle modification with weight loss through physical activity and dietary modification is the recommended treatment option for pediatric NAFLD. • Metformin may reduce steatosis on ultrasound and may have a beneficial role in liver histology collated with insulin resistance improvement. What is New: • Metformin may improve insulin sensitivity and lipid parameters in children with obesity and NAFLD. • Metformin does not have a significant effect on transaminase levels in children with obesity and NAFLD.

Α rare case of myopathy, lactic acidosis, and severe rhabdomyolysis, due to a homozygous mutation of the ferredoxin-2 (FDX2) gene.

Mitochondrial myopathy is a severe metabolic myopathy related to nuclear or mitochondrial DNA dysfunction. We present a rare case of mitochondrial myopathy, presented with multiple episodes of proximal muscle weakness, lactic acidosis, and severe rhabdomyolysis (CPK 319,990 U/L, lactic acid 22.31 mmol/L, and GFR 3.82 mL/min/1.73m2 ). She was hospitalized in the pediatric intensive care unit due to acute kidney injury, elevated blood pressure, and deterioration of respiratory and cardiac function. Investigation for inherited metabolic disorders showed elevated levels of ammonia, lactic acid to pyruvic acid ratio, and urine ketone bodies. Exome sequencing detected a homozygous pathogenic variant in FDX2 (ENST00000541276:p.Met4Leu/c.10A > T) and a heterozygous variant of uncertain significance in MSTO1 (ENST00000538143:p.Leu137Pro/c.410 T > C). After Sanger sequencing, the p.Met4Leu pathogenic variant in FDX2 (ENST00000541276:p.Met4Leu/c.10A > T) was identified in a heterozygous state in both her parents and sister. Recently, pathogenic variants in the FDX2 gene have been associated with mitochondrial myopathy, lactic acidosis, optic atrophy, and leukoencephalopathy. Only four reports of FDX2-related rhabdomyolysis have been described before, but none of the previous patients had hyperammonemia. This is a rare case of severe mitochondrial myopathy in a pediatric patient related to a pathogenic FDX2 variant, suggesting the need for genetic analysis of the FDX2 gene in cases of suspicion of mitochondrial myopathies.

The efficacy of automated insulin delivery systems in children and adolescents with type 1 diabetes Mellitus: A systematic review and meta-analysis of randomized controlled trials.

AIMS: Insulin administration is the treatment of choice for people with type 1 diabetes mellitus (T1D). Technological advances have led to the development of automated insulin delivery (AID) systems, aiming to optimize the quality of life of patients with T1D. We present a systematic review and meta-analysis of the current literature about the efficacy of AID systems in children and adolescents with T1D. METHODS: We conducted a systematic literature search for randomized controlled trials (RCTs) until August 8th, 2022, investigating the efficacy of AID systems in the management of patients < 21 years of age with T1D. A priori subgroup and sensitivity analyses based on different settings (free-living settings, type of AID system, parallel group or crossover design) were also conducted. RESULTS: In total, 26 RCTs reporting a total of 915 children and adolescents with T1D were included in the meta-analysis. AID systems revealed statistically significant differences in the main outcomes, such as the proportion of time in the target glucose range (3.9-10 mmol/L) (p < 0.00001), in hypoglycemia (<3.9 mmol/L) (p = 0.003) and mean proportion of HbA1C (p = 0.0007) compared to control group. CONCLUSIONS: According to the present meta-analysis, AID systems are superior to insulin pump therapy, sensor-augmented pumps and multiple daily insulin injections. Most of the included studies have a high risk of bias because of allocation, blinding of patients and blinding of assessment. Our sensitivity analyses showed that patients < 21 years of age with T1D can use AID systems, after proper education, following their daily activities. Further RCTs examining the effect of AID systems on nocturnal hypoglycemia, under free-living settings and studies examining the effect of dual-hormone AID systems are pending.

The efficacy and safety of corticosteroids in pediatric kidney scar prevention after urinary tract infection: a systematic review and meta-analysis of randomized clinical trials.

BACKGROUND: Acute pyelonephritis (APN) in pediatric patients may lead to kidney scarring and is one of the main causes of permanent kidney damage. The incidence of kidney scarring after one febrile urinary tract infection (UTI) is reported to range from 2.8 to 15%, with the percentage rising to 28.6% after ≥ 3 febrile UTIs. Corticosteroids may have a role in the reduction of kidney scar formation and urine cytokine levels. The possible benefit of adjuvant corticosteroid administration in the reduction of kidney scar formation in children with APN has been recently examined in randomized controlled trials (RCTs). OBJECTIVES: The aim of this meta-analysis was to provide a summary of the current literature about the efficacy and safety of adjuvant corticosteroid administration in the reduction of kidney scar formation in children with APN. DATA SOURCES: An extensive literature search through major databases (PubMed/MEDLINE and Scopus) was carried out for RCTs from inception until October 12, 2022, investigating the efficacy and safety of adjuvant corticosteroids in preventing kidney scarring in children with APN. A risk ratio with 95% CI was used for dichotomous outcomes. RESULTS: In total, 5 RCTs with 918 pediatric patients with APN were included in the study. Adjuvant corticosteroid treatment revealed a statistically significant reduction in kidney scarring (95% CI 0.42-0.95, p = 0.03), without increasing the risk of adverse events like bacteremia, prolonged hospitalization, or recurrence of UTI. LIMITATIONS: There were limitations regarding sample size (n = 498 children), different classes of corticosteroids (methylprednisolone or dexamethasone), different routes of corticosteroid administration (intravenous or oral), and different day courses (3-day or 4-day course). CONCLUSIONS: Adjuvant corticosteroid administration seems to have a beneficial effect on kidney scar reduction in children with APN. Future studies should focus on the evaluation of the efficacy and safety of corticosteroids in kidney scarring reduction after APN to strengthen the results of our study. A higher resolution version of the Graphical abstract is available as Supplementary information.

Can omega-3 fatty acids be beneficial in pediatric NAFLD? A systematic review and meta-analysis.

Nonalcoholic fatty liver disease (NAFLD) has become the most common chronic liver disease in children and no medications or supplements are currently recommended. The role of omega-3 (n-3) fatty acids has been investigated in clinical trials with promising results. The aim of this study is to provide a detailed summary of the evidence about the efficacy of n-3 in the treatment of pediatric NAFLD. A systematic literature search was performed through major electronic databases up to September 20, 2021 for randomized placebo-controlled trials, investigating the efficacy of n-3 fatty acids in children with NAFLD. The primary outcomes were changes in serum transaminases concentration, Body Mass Index (BMI) and improvement of ultrasonographic liver steatosis. The secondary outcomes were changes in the patients' serum lipid profile, γ-glutamyl transferase (GGT), fasting blood glucose (FBG), homeostatic model assessment of insulin resistance (ΗΟΜΑ-ΙR) and waist circumference (WC). Results were expressed as mean differences for continuous outcomes and odds ratios for dichotomous outcomes with 95% confidence intervals. Six RCTs (n = 378 patients) were included. Treatment with n-3, compared to placebo, resulted in a statistically significant reduction in transaminases concentration. In addition, a significant improvement in liver steatosis assessed by ultrasonography and a decrease in BMI were observed. N-3 fatty acids supplementation seems to be an effective alternative treatment in pediatric NAFLD by improving liver biochemistry, ultrasonographic steatosis and BMI. Further research is required concerning the effect of n-3 fatty acids in liver histology.