Fat-soluble vitamin deficiency remains a challenge in cystic fibrosis (CF), chronic pancreatitis, and biliary atresia. Liposomes and cyclodextrins can enhance their bioavailability, thus this multi-center randomized placebo-controlled trial compared three-month supplementation of fat-soluble vitamins in the form of liposomes or cyclodextrins to medium-chain triglycerides (MCT) in pancreatic-insufficient CF patients. The daily doses were as follows: 2000 IU of retinyl palmitate, 4000 IU of vitamin D3, 200 IU of RRR-α-tocopherol, and 200 µg of vitamin K2 as menaquinone-7, with vitamin E given in soybean oil instead of liposomes. All participants received 4 mg of β-carotene and 1.07 mg of vitamin K1 to ensure compliance with the guidelines. The primary outcome was the change from the baseline of all-trans-retinol and 25-hydroxyvitamin D3 concentrations and the percentage of undercarboxylated osteocalcin. Out of 75 randomized patients (n = 28 liposomes, n = 22 cyclodextrins, and n = 25 MCT), 67 completed the trial (89%; n = 26 liposomes, n = 18 cyclodextrins, and n = 23 MCT) and had a median age of 22 years (IQR 19–28), body mass index of 20.6 kg/m² [18.4–22.0], and forced expiratory volume in 1 s of 65% (44–84%). The liposomal formulation of vitamin A was associated with the improved evolution of serum all-trans-retinol compared to the control (median +1.7 ng/mL (IQR −44.3–86.1) vs. −38.8 ng/mL (−71.2–6.8), p = 0.028). Cyclodextrins enhanced the bioavailability of vitamin D3 (+9.0 ng/mL (1.0–17.0) vs. +3.0 ng/mL (−4.0–7.0), p = 0.012) and vitamin E (+4.34 µg/mL (0.33–6.52) vs. −0.34 µg/mL (−1.71–2.15), p = 0.010). Liposomes may augment the bioavailability of vitamin A and cyclodextrins may strengthen the supplementation of vitamins D3 and E relative to MCT in pancreatic-insufficient CF but further studies are required to assess liposomal vitamin E (German Clinical Trial Register number DRKS00014295, funded from EU and Norsa Pharma).

NALCN mutations lead to complex neurodevelopmental syndromes, including infantile hypotonia with psychomotor retardation and characteristic facies (IHPRF) and congenital contractures of limbs and face, hypotonia, and developmental delay (CLIFAHDD), which are recessively and dominantly inherited, respectively. We present a patient in whom congenital myasthenic syndrome (CMS) was suspected due to the occurrence of hypotonia and apnea episodes requiring resuscitation. For this reason, treatment with pyridostigmine was introduced. After starting the treatment, a significant improvement was observed in reducing the apnea episodes and slight psychomotor progress. In the course of further diagnostics, CMS was excluded, and CLIFAHDD syndrome was confirmed. Thus, we try to explain a possible mechanism of clinical improvement after the introduction of treatment with pyridostigmine in a patient with a mutation in the NALCN gene.

Background and Aim. Neurogenic inflammation underlies the pathogenesis of allergic diseases. Interactions between neurons with the immune cells and structural cells (airway epithelium, nasal mucosa, skin keratinocytes) undergo altered regulation during chronic inflammation. Therefore, we hypothesized that the expression of neuroinflammatory genes may be altered allergic diseases, including atopic dermatitis and allergic rhinitis, and that, compared to atopic asthma, the expression pattern may be disease‐specific in pediatric patients. Methods. In the study, we included 86 children diagnosed with atopic asthma (n = 25), allergic rhinitis (n = 20), and atopic dermatitis (n = 20) and healthy control subjects (n = 21) of Caucasian origin from the Polish population. The blood leukocyte expression of 31 genes involved in neuroinflammatory response (neurotrophins, their receptors, neuropeptides, and histamine signaling pathway) was analysed using TaqMan low‐density arrays. The relative expression of selected proteins from plasma was done using TaqMan Protein Assays. Statistical analysis was done using Statistica. Results. Blood expression of 31 genes related to neuroimmune interactions showed significant increase in both allergic diseases, allergic rhinitis and atopic dermatitis, in comparison to the control group. We found 12 genes significantly increased in allergic rhinitis and 9 genes in which the expression was elevated in atopic dermatitis. Moreover, 9 genes with changed expression in atopic dermatitis overlapped with those in allergic rhinitis. Atopic asthma showed 5 genes with altered expression. The peripheral expression of neuroinflammatory genes in the human study was verified in target tissues (nasal epithelium and skin) in a rat model of allergic inflammation. Conclusions. A common pattern of neuroinflammatory gene expression between allergic rhinitis and atopic dermatitis may reflect similar changes in sensory nerve function during chronic allergic inflammation.

Copeptin was found to be a stable biomarker of inflammation and stress response in cardiac, renal, metabolic, and respiratory conditions such as pneumonia. The aim of this study was to investigate the copeptin levels in biological fluids (serum and sputum supernatant) of cystic fibrosis pediatric patients during pulmonary exacerbation and remission and to investigate the possible influence of copeptin levels on disease severity and quality of life. Copeptin serum concentrations were measured in 28 pediatric cystic fibrosis (CF) patients: 13 in stable condition and 15 during pulmonary exacerbation. In 10 CF patients, copeptin was also measured in the sputum. In all the patients, we assessed complete blood count, BMI, sputum culture, lung function, and chest imaging (with Brasfield score). The severity of symptoms was assessed using the Shwachman-Kulczycki (SK) score, and the quality of life was assessed with the Cystic Fibrosis Quality of Life Questionnaire-Revised (CFQ-R). Copeptin concentrations in serum and sputum supernatant was measured using an ELISA kit. Statistical analysis was done in Statistica v.12. Serum and sputum copeptin levels were higher in CF patients during pulmonary exacerbation than in a stable period, but the differences were not significant (p=0.58 and p=0.13, respectively). Copeptin did not correlate significantly with any clinical, laboratory, or spirometry markers of exacerbation. There was, however, a significant inverse correlation between the serum copeptin level and symptoms severity (r=‐0.77, p=0.008) and radiological changes (r=‐0.5626, p=0.036) during pulmonary exacerbation in pediatric CF patients. Copeptin also inversely correlated with the quality of life domains in CF patients: vitality and eating habits, mostly loss of appetite (p=0.031 and p=0.016, respectively). Copeptin may be useful to identify patients with a higher risk of deterioration to improve their outcomes.