Impact of CFTR Modulator Therapies on Liver Function in Cystic Fibrosis Patients: A Systematic Review of Hepatic Biomarkers.

BACKGROUND AND AIMS: Cystic fibrosis transmembrane conductance regulator (CFTR) modulators, including elexacaftor/ivacaftor/tezacaftor (ETI) and lumacaftor/ivacaftor (LI), have revolutionized the treatment of cystic fibrosis. However, their impact on liver function remains unclear, with varying effects reported across studies. The aim of this study was to systematically review the effects of CFTR modulators on liver function in cystic fibrosis patients by evaluating changes in key hepatic biomarkers. METHODS: A comprehensive literature search was conducted in Europe PubMed Central and PubMed databases for studies published between January 1, 2010, and December 31, 2023. Eligible studies included those assessing the impact of CFTR modulators on liver biomarkers in cystic fibrosis patients. Meta-analyses were performed where possible. RESULTS: Six studies encompassing 195 patients were included, with significant heterogeneity in study design, population, and outcomes. The review found mixed results for alanine aminotransferase (ALT), aspartate aminotransferase (AST), and gamma glutamyltransferase (GGT) levels, with some studies reporting increases and others decreases. LI therapy was associated with significant reductions in GGT and alkaline phosphatase (AP) levels, while ETI therapy showed significant increases in bilirubin levels. Albumin levels increased significantly with both therapies. CONCLUSIONS: CFTR modulators have varying effects on liver function biomarkers in cystic fibrosis patients, with LI therapy generally showing more favorable outcomes on liver health. The significant heterogeneity among studies underscores the need for more standardized research to better understand these effects and guide clinical management.

Neurological Manifestations of Acute SARS-CoV-2 Infection in Pediatric Patients: A 3-Year Study on Differences between Pandemic Waves.

This study analyzed the neurological manifestation profiles of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection across pandemic waves in pediatric patients. The study collected data on patients aged between 0 and 18 years, diagnosed with acute SARS-CoV-2 infection, admitted to a pediatric tertiary hospital between 1 March 2020 and 28 February 2023. This study included 1677 patients. Neurological manifestations were noted in 10% (n = 168) of patients with a median age of 3.2 years (interquartile range: 1-11.92). Neurological manifestations were significantly associated with the pandemic waves (p = 0.006) and age groups (p < 0.001). Seizures were noted in 4.2% of cases and reached an increasing frequency over time (p = 0.001), but were not associated with age groups. Febrile seizures accounted for the majority of seizures. Headache was reported in 2.6% of cases and had similar frequencies across the pandemic waves and age groups. Muscular involvement was noted in 2% of cases, reached a decreasing frequency over time (p < 0.001), and showed different frequencies among the age groups. Neurological manifestations of acute SARS-CoV-2 infection exhibit distinct patterns, depending on the pandemic wave and patient age group. The Wuhan and Omicron waves involved the nervous system more often than the other waves.

Hybrid Immunity and the Incidence of SARS-CoV-2 Reinfections during the Omicron Era in Frontline Healthcare Workers.

During the coronavirus disease (COVID-19) pandemic healthcare workers (HCWs) acquired immunity by vaccination or exposure to multiple variants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Our study is a comparative analysis between subgroups of HCWs constructed based on the number of SARS-CoV-2 infections, vaccination, and the dominant variant of SARS-CoV-2 in the population. We collected and analyzed data using the χ2 test and density incidence of reinfections in Microsoft Excel for Mac, Version 16.84, and MedCalc®, 22.026. Of the 829 HCWs, 70.1% (581) had only one SARS-CoV-2 infection and 29.9% (248) had two infections. Of the subjects with two infections, 77.4% (192) worked in high-risk departments and 93.2% (231) of the second infections were registered during Omicron dominance. The density incidence of reinfections was higher in HCWs vaccinated with the primary schedule than those vaccinated with the first booster, and the incidence ratio was 2.8 (95% CI: 1.2; 6.7). The probability of reinfection was five times lower (95% CI: 2.9; 9.2) in HCWs vaccinated with the primary schedule if the first infection was acquired during Omicron dominance. The subjects vaccinated with the first booster had a density incidence of reinfection three times lower (95% CI: 1.9; 5.8) if the first infection was during Omicron. The incidence ratio in subgroups constructed based on characteristics such as gender, age group, job category, and department also registered significant differences in density incidence. The history of SARS-CoV-2 infection by variant is important when interpreting and understanding public health data and the results of studies related to vaccine efficacy for hybrid immunity subgroup populations.

Benzalkonium Chloride Poisoning in Pediatric Patients: Report of Case with a Severe Clinical Course and Literature Review.

The use of disinfectants, particularly those containing quaternary ammonium compounds (QUACs), has dramatically escalated globally since the coronavirus disease 2019 pandemic. We report a case that highlights the risks associated with ingesting low-concentration QUAC solutions and emphasize the importance of effective management in resolving severe lesions without sequelae. A 17-month-old boy experienced severe respiratory failure after ingesting a disinfectant containing benzalkonium chloride (BAC). The child was initially treated at a local emergency department and was subsequently transferred to a pediatric poison center. Upon evaluation, the child was found to have grade III-A corrosive esophageal lesions and chemical pneumonitis. Several complications, including massive pneumothorax and candidemia, occurred during the clinical course of the disease. However, with timely medical intervention and appropriate supportive care, the patient completely recovered without any long-term sequelae. The properties of BAC and the comprehensive management approach may have been responsible for the patient's full recovery, despite the potentially life-threatening effects of ingesting disinfectants.