Biochemical assessment in a cohort of pediatric patients with cystic fibrosis.

Cystic fibrosis (CF) is a recessive inherited disorder caused by genetic mutations in the CF transmembrane conductance regulator (CFTR) gene. It is a multisystem condition that primarily induces abnormal mucus accumulation in the respiratory system and obstructs the intrapancreatic common bile duct, causing a reduction in the delivery of digestive enzymes to the small intestine. Thus, patients with CF are characterized by maldigestion, malabsorption, and recurrent airway bacterial infections. Clinical monitoring of the health status of patients with CF is mandatory for increasing the patients' lifespan. To assess the feasibility of monitoring life quality (LQ) in pediatric patients with cystic fibrosis (CF) and to explore the relationship between biochemical parameters and clinical symptoms, our study analyzed inflammatory responses related to CF, medication, and pulmonary bacterial infections in 52 patients diagnosed with CF. Blood, hypo-pharyngeal exudate, and fecal samples were analyzed using clinical biochemistry, hematology, and microbiology techniques at the Alessandrescu-Rusescu National Institute for Mother and Child Health central laboratory in Bucharest, Romania. All the participants adhered to their prescribed outpatient CF regimens and appeared clinically stable. The overall clinical status of patients with CF was observed and compared with that of a healthy control group, which consisted of individuals similar in number and age. The screened patients with CF presented an impaired lipid status and chronic infections with various bacteria, iron, and vitamin (A, D, and E) deficiencies. Our findings provide insights into the pathophysiological mechanisms of CF and suggest that tailored monitoring and personalized therapeutic strategies could improve patient management.

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.

Exploring the Role of Serum Osteonectin and Hsp27 in Pediatric MAFLD Diagnosis and Cardiometabolic Health.

BACKGROUND: Childhood obesity is one of the major challenges of public health policies. The problem of fatty liver in childhood, known as MAFLD (metabolic dysfunction-associated fatty liver disease), is of particular interest as the gold standard diagnosis technique is invasive (liver biopsy). Hence, efforts are made to discover more specific biomarkers for the MAFLD signature. Therefore, the aim of the study was to evaluate Osteonectin and Hsp27 as biomarkers for MAFLD diagnosis and to assess their links with auxological and biochemical profiles of overweight and obese pediatric subjects. METHODS: A cross-sectional study in which we (re)analyzed data from the MR PONy cohort comprising 71 pediatric subjects. Auxological data, liver ultrasonography and biochemical serum profile were recorded. Lipid-derived indices and body composition indices were calculated. Nevertheless, serum Osteonectin and Hsp27 levels were assessed using an ELISA approach. RESULTS: MAFLD prevalence was 40.8%. Higher Osteonectin levels were noted in MAFLD subjects versus non-MAFLD subjects and in dyslipidemic children regardless of their liver function status. Lipid-derived indices had good diagnostic capacity for MAFLD. CONCLUSIONS: We confirm Osteonectin as a MAFLD diagnosis biomarker in children. Also, lipid-derived indices are useful as metabolic-associated organ impairment markers in children even before the onset of obesity.

Current and Future Therapeutic Approaches of Exocrine Pancreatic Insufficiency in Children with Cystic Fibrosis in the Era of Personalized Medicine.

This review presents current updates of pancreatic enzyme replacement therapy in children with cystic fibrosis based on literature published in the last decade and some special considerations regarding pancreatic enzyme replacement therapy in the era of new therapies, such as cystic fibrosis transmembrane conductance regulator modulator therapies. Few articles evaluate the efficacy of pancreatic enzyme replacement therapy in the pediatric population, and most studies also included children and adults with cystic fibrosis. Approximately 85% of cystic fibrosis patients have exocrine pancreatic insufficiency and need pancreatic enzyme replacement therapy. Fecal elastase is the most commonly used diagnostic test for exocrine pancreatic insufficiency, although this value can fluctuate over time. While it is used as a diagnostic test, it cannot be used for monitoring the effectiveness of pancreatic enzyme replacement therapy and for adjusting doses. Pancreatic enzyme replacement therapy, the actual treatment for exocrine pancreatic insufficiency, is essential in children with cystic fibrosis to prevent malabsorption and malnutrition and needs to be urgently initiated. This therapy presents many considerations for physicians, patients, and their families, including types and timing of administration, dose monitoring, and therapy failures. Based on clinical trials, pancreatic enzyme replacement therapy is considered effective and well-tolerated in children with cystic fibrosis. An important key point in cystic fibrosis treatment is the recent hypothesis that cystic fibrosis transmembrane conductance regulator modulators could improve pancreatic function, further studies being essential. Pancreatic enzyme replacement therapy is addressed a complication of the disease (exocrine pancreatic insufficiency), while modulators target the defective cystic fibrosis transmembrane conductance regulator protein. Exocrine pancreatic insufficiency in cystic fibrosis remains an active area of research in this era of cystic fibrosis transmembrane conductance regulator modulator therapies. This new therapy could represent an example of personalized medicine in cystic fibrosis patients, with each class of modulators being addressed to patients with specific genetic mutations.

First Case of COVID-19 Treated with Monoclonal Anti-Spike Antibodies in a Patient with Cystic Fibrosis in Romania.

Patients with chronic lung conditions, including cystic fibrosis, may be prone to severe COVID-19. Therefore, therapeutic intervention should be prompt and tailored to all associated comorbidities. We report the case of a 17-year-old male adolescent with cystic fibrosis and multiple chronic conditions (bronchiectasis, exocrine pancreatic insufficiency, chronic multidrug resistant Pseudomonas aeruginosa colonization, nasal polyposis, chronic sinusitis, ventricular extrasystoles and multiple drug allergies), who presented with an acute episode of productive cough, and was confirmed with moderate COVID-19 based on positive RT-PCR for SARS-CoV-2 and lung imaging showing isolated foci of interstitial pneumonia. Intravenous treatment with the monoclonal antibody cocktail casirivimab and imdevimab was administered. The evolution was favorable, with rapid remission of the inflammatory syndrome and gradual decrease of cough, without progression to severe or critical COVID-19, but with complications such as repeated hemoptysis, which was due to the patient's underlying conditions, and which required close monitoring for timely adjustment of the patient's chronic treatment.

Endocan and Lumican in Relation to Cardiometabolic Risk in a Pediatric Overweight and Obese Cohort: A Cross-Sectional Study.

The aim of the study was to evaluate serum Endocan and Lumican levels as biomarkers for pediatric Nonalcoholic Fatty Liver Disease (NAFLD) and to explore their associations with pediatric cardiometabolic risk factors. We conducted a cross-sectional study on 68 pediatric obese and overweight (O&O) patients. Ten healthy controls were recruited. Serum Lumican and Endocan levels were analyzed using ELISA kits. O&O patients had lower levels of Endocan compared to healthy controls (p < 0.001). There were no differences between serum Endocan levels in O&O patients with NAFLD and those without (p = 0.53). Patients considered having Nonalcoholic Steatohepatitis (NASH) had lower Endocan levels compared to O&O patients without NASH (p = 0.026). Patients with metabolic syndrome had lower levels of Endocan (p = 0.003). There were no significant differences between serum Lumican levels in O&O children compared to healthy controls. Lumican levels were higher in patients with hypertension (p = 0.04). In O&O patients, Lumican levels were negatively correlated with Endocan levels (r = -0.37, p = 0.002). Endocan seems a promising biomarker for the evaluation of pediatric NASH. Lumican was not confirmed as a biomarker for NAFLD in our cohort but was associated with higher arterial pressure. Low Endocan levels are accompanied by high serum Lumican levels, and this could be an early signature of cardiometabolic risk.

[The family practitioner's role in the management of patients with cystic fibrosis]. / Rolul medicului de familie în îngrijirea pacientului cu fibroza chistica.

Cystic fibrosis ormucoviscidosis (CF) is the most frequent monogenic genetic disease with autosomal dominant transmision in caucasians. Currently, the typical approach is referring the CF patient to specialized centers with multidisciplinary teams. The inherent questions appear: which is then the role of the general practitioner (GP)? Should the GP be confined to the pasive role of exchanging medical letters with the specialist, or should he take active part in monitoring the disease? Is it ethicallyand professionally correct for the GP to simply copy the treatment of a patient that hedidn't actually see for years, or to assume the palliative care in final stages of a patient who was actually taken care of only by the specialist? What are the families' expectations and what is the level of competence they expect from the GP? These are some of the questions we will try to answer, considering the expertise we accumulated in the regional center in "Alfred Rusescu" lnstitute for Protection of Mother and Child, where 16.22% (60 out of 370) of CF patients in Romania are monitored, and based on a questionnaire addressed to the CF patient's families.