Ataxia telangiectasia (A-T) is a devastating multi-system disorder characterized by progressive cerebellar ataxia, immunodeficiency, genetic instability, premature aging and growth retardation. Due to better care the patients get older than in the past and new disease entities like disturbed glucose tolerance and liver disease emerge. The objective of the present investigation is to determine the evolution of liver disease and its relation to age and neurological deterioration. The study included 67 patients aged 1 to 38 years with classical A-T. At least two measurements of liver enzymes were performed within a minimum interval of 6 months in 56 patients. The median follow-up period was 4 years (1–16 years). A total of 316 liver enzyme measurements were performed. For analysis, patients were divided into two age groups (Group 1: <12 years; group 2: ≥12 years). In addition, ultrasound of the liver and Klockgether Ataxia Score (KAS) were analyzed. We found significantly higher levels of alpha-fetoprotein (AFP) (226,8 ± 20.87 ng/ml vs. 565,1 ± 24.3 ng/ml, p < 0.0001), and liver enzymes like ALT (23.52 ± 0.77 IU/L vs. 87.83 ± 5.31 IU/L, p < 0.0001) in patients in group 2. In addition, we could show a significant correlation between age and AFP, GGT, and KAS. Ultrasound revealed hepatic steatosis in 11/19 (57.9%) patients in group 2. One female patient aged 37 years died due to a hepato-cellular carcinoma (HCC). Liver disease is present in the majority of older A-T patients. Structural changes, non-alcoholic fatty liver disease and fibrosis are frequent findings. Progress of liver disease is concomitant to neurological deterioration.

A high incidence of thromboembolic events associated with high mortality has been reported in severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) infections with respiratory failure. The present study characterized post-transcriptional gene regulation by global microRNA (miRNA) expression in relation to activated coagulation and inflammation in 21 critically ill SARS-CoV-2 patients. The cohort consisted of patients with moderate respiratory failure (n = 11) and severe respiratory failure (n = 10) at an acute stage (day 0–3) and in the later course of the disease (>7 days). All patients needed supplemental oxygen and severe patients were defined by the requirement of positive pressure ventilation (intubation). Levels of D-dimers, activated partial thromboplastin time (aPTT), C-reactive protein (CRP), and interleukin (IL)-6 were significantly higher in patients with severe compared with moderate respiratory failure. Concurrently, next generation sequencing (NGS) analysis demonstrated increased dysregulation of miRNA expression with progression of disease severity connected to extreme downregulation of miR-320a, miR-320b and miR-320c. Kyoto encyclopedia of genes and genomes (KEGG) pathway analysis revealed involvement in the Hippo signaling pathway, the transforming growth factor (TGF)-β signaling pathway and in the regulation of adherens junctions. The expression of all miR-320 family members was significantly correlated with CRP, IL-6, and D-dimer levels. In conclusion, our analysis underlines the importance of thromboembolic processes in patients with respiratory failure and emphasizes miRNA-320s as potential biomarkers for severe progressive SARS-CoV-2 infection.

Introduction. Bronchiolitis obliterans (BO) is a chronic disease in which persistent inflammation leads to obstruction and obliteration of the small airways. The aim of this study was to evaluate the value of calprotectin as an inflammatory marker in induced sputum. Methods. Twenty-eight patients suffering from BO and 18 healthy controls were examined. Lung function was measured by spirometry, body plethysmography, and lung clearance index (LCI). The induced sputum was obtained, cell counts were performed, and cytokines were measured using cytometric bead array (CBA). Calprotectin was quantified in the sputum and serum samples using commercially available sandwich ELISA. Results. Spirometry parameters including forced vital capacity (FVC), forced expiratory volume in 1 second (FEV1), and maximum expiratory flow rate at 25% vital capacity (MEF25) were significantly lower in BO patients than in healthy controls, whereas the reserve volume (RV), RV to total lung capacity ratio (RV/TLC), and LCI were significantly increased. In sputum, calprotectin levels, neutrophils, and IL-8 were significantly elevated. Calprotectin levels correlated strongly with IL-8 and other biomarkers, neutrophils FEV1 and MEF25. In serum, calprotectin was significantly diminished in BO patients compared to controls. Conclusion. Lung function is severely impaired in BO patients. Calprotectin is significantly elevated in the sputum of BO patients and reflects ongoing neutrophilic inflammation.

Ataxia telangiectasia (A-T) is a progressive and life-limiting disease associated with cerebellar ataxia due to progressive cerebellar degeneration. In addition to ataxia, which is described in detail, the presence of chorea, dystonia, oculomotor apraxia, athetosis, parkinsonism, and myoclonia are typical manifestations of the disease. The study aimed to evaluate the specificity and sensitivity of neurofilament light chain (NfL) as a biomarker of neurodegeneration in relation to SARA score. In this prospective trial, one visit of 42 A-T patients aged 1.3–25.6 years (mean 11.6 ± 7.3 years) was performed, in which NfL was determined from serum by ELISA. Additionally, a neurological examination of the patients was performed. Blood was collected from 19 healthy volunteers ≥ 12 years of age. We found significantly increased levels of NfL in patients with A-T compared to healthy controls (21.5 ± 3.6 pg/mL vs. 9.3 ± 0.49 pg/mL, p ≤ 0.01). There was a significant correlation of NfL with age, AFP, and SARA. NfL is a new potential progression biomarker in blood for neurodegeneration in A-T which increases with age.