Volume 28: Issue 6

OBJECTIVE

This study aims to clarify the risk of nephrotoxicity with intravenous use of acyclovir (ACV) for the treatment of neonates (ages <3 months) and children (ages ≥3 months to <12 years) with herpes simplex virus (HSV) infections and to identify gaps in knowledge that could be further investigated.

METHODS

Multiple databases were searched to identify studies on risk of nephrotoxicity with ACV use for treatment of invasive HSV infections, defined as any neonatal infection or HSV encephalitis (HSE) in children.

RESULTS

There were 5 and 14 studies that evaluated the risk of ACV-associated nephrotoxicity in neonates and children, respectively. The US Food and Drug Administration (FDA) delayed the approval of high (HD; 60 mg/kg/day) ACV in neonates secondary to risk of toxicity. Based on our review, the risk of ACV-associated nephrotoxicity was lower in the neonatal compared with the pediatric population. Acyclovir dose >1500 mg/m², older age, and concomitant use of nephrotoxic drugs were identified as variables that increased the risk of ACV nephrotoxicity in children. Although the FDA has approved the use of HD ACV for the treatment of HSE in children, the American Academy of Pediatrics recommends a lower dose to minimize the risk of toxicity. The efficacy and safety of high vs lower doses of ACV for the management of HSE in children has yet to be evaluated.

CONCLUSIONS

The risk of ACV-associated nephrotoxicity was lower among neonates compared with older children. Future studies are needed to identify the optimal dosage that minimizes toxicities and maximizes the efficacy of ACV in children with HSE.

OBJECTIVE

Proton pump inhibitors (PPIs) are commonly used to manage children with upper gastrointestinal symptoms and without a formal diagnosis. We investigated the effect of PPIs on esophageal mucosal transcriptome and active microbiota in children with normal esophagi. Furthermore, we examined whether the differences in host esophageal mucosal gene expression were driven by an underlying esophageal epithelial cell type composition.

METHODS

Using metatranscriptomics, the host transcriptional and active microbial profiles were captured from 17 esophageal biopsy samples (PPI naïve [PPI−], n = 7; PPI exposed [PPI+], n = 10) collected from children without any endoscopic and histologic abnormalities in their esophagus (normal esophagus). Deconvolution computational analysis was performed with xCell to assess if the observed epithelial gene expression changes were related to the cell type composition in the esophageal samples.

RESULTS

The median (IQR) age of our cohort was 14 years (12–16) with female (63%) preponderance. Both groups were similar in terms of their demographics and clinical features. Compared with PPI−, the PPI+ had upregulation of 27 genes including the MUC genes. The cell type composition was similar between the PPI− and PPI+ groups. Prevotella sp and Streptococcus sp were abundant in PPI+ group.

CONCLUSIONS

In children with normal esophagus, PPI exposure can be associated with upregulation of esophageal mucosal homeostasis and epithelial cell function genes in a cell-type independent manner, and an altered esophageal microbiome. Additional studies are warranted to validate our findings and to investigate the causal effect of PPIs on the normal esophageal epithelium and microbial communities.

OBJECTIVE

Management of anemia of chronic kidney disease (CKD) often includes subcutaneous or intravenous administration of erythropoietin-stimulating agents (ESAs). Mircera, a pegylated continuous erythropoietin receptor agonist, has a longer duration of action and requires less frequent administration than other ESAs. Pediatric experience with Mircera is limited. We retrospectively reviewed our long-term experience of Mircera in a national pediatric nephrology center.

METHODS

Patients were identified via an electronic patient record database. Data collected included demographics (sex, age, etiology of CKD, CKD stage, dialysis modality), dosing information, and laboratory data—hemoglobin (Hb), parathormone (PTH), ferritin, hematinics prior to commencing Mircera and all subsequent values associated with dose adjustments.

RESULTS

Seventy-seven patients aged 2 to 18 years, with CKD stages 2 to 5T had received at least 1 dose of Mircera, with 75 patients having sufficient data and a total of 1473 doses. No patients discontinued Mircera owing to adverse effects. One patient experienced a potential severe adverse drug reaction. Mircera was effective in improving or maintaining Hb ≥10.0 g/dL in most (58/75, 77.3%) patients. The median dose to achieve Hb ≥10.0 g/dL was 2.1 µg/kg/4 wk. Most doses (1039, 71.5%) were administered 4-weekly. The doses (161, 11.1%) that were administered 6-weekly remained efficacious. Thirty-two patients started Mircera with Hb <10.0 g/dL; 26 (81%) achieved Hb ≥10.0 g/dL within a median time of 4 months. Mircera was less effective if given every 8 weeks, or in the presence of hyperparathyroidism or hyperferritinemia.

CONCLUSION

Mircera appears safe and effective in pediatric patients with CKD.

Introduction

This commentary provides a concise step-by-step guide on using ChatGPT, an advanced natural language processing (NLP) model, for research and publication purposes. The guide assesses crucial aspects, including data preprocessing, fine-tuning techniques, prompt engineering, and ethical considerations. By addressing challenges related to biases, interpretability, and plagiarism, this commentary offers insights and recommendations for the responsible and ethical use of ChatGPT. The guide empowers researchers to ethically integrate ChatGPT effectively into their workflows, enhancing productivity and improving the quality of their scientific publications. Through clear instructions and guidelines, researchers can tap into the transformative potential of ChatGPT, driving scientific progress