for the Gene Modifier Study Group C YSTIC FIBROSIS (CF) IS A REcessive monogenic disorder characterizedbymultiorganinvolvement and clinical heterogeneity that is incompletely explained by mutations within the cystic fibrosis transmembraneconductanceregulator(CFTR) gene (OMIM 602421). 1 Patients with CF, including those homozygous for DF508, smallfraction(Ϸ3%-5%)ofpatientswith CF develops severe liver disease characterized by cirrhosis with portal hypertension (CFLD) 1 ; thus, non-CFTR genetic variability may contribute to risk for severe liver disease. [14][15][16][17] To determine the association between non-CFTR genetic polymorphisms and CFLD, we studied 9 functional variants in 5 genes previously See also Patient Page.
More than 20 years of serological approach to diagnosis of celiac disease (CD) has deeply changed the classical clinical presentation of the disease, and some reports indicate that CD and obesity can coexist in both childhood and adolescence. We reviewed clinical records of 149 children with CD followed in our institution between 1991 and 2007, considering weight, height and body mass index (BMI), both at diagnosis and after at least 12 months of gluten-free diet (GFD). In all, 11% of patients had BMI z-score 4 þ 1 and 3% were obese (z-score 4 þ 2) at presentation. In our population, there was a significant (P ¼ 0.008) increase in BMI z-score after GFD and the percentage of overweight (z-score 4 þ 1) subjects almost doubled (11 vs 21%, P ¼ 0.03). Our data suggest the need for a careful follow-up of nutritional status after diagnosis of CD, especially addressing those who are already overweight at presentation.
The present data on Shwachman's syndrome diagnosed in infancy underline the possibility of improvement or normalization of exocrine pancreatic function with age, suggesting the need for periodic checks on pancreatic activity in these subjects. It also indicates the possibility of diagnosis of this syndrome in the absence of pancreatic insufficiency; decreasing frequency of infections over time; and the usefulness of early neuropsychological evaluation.
Purpose
To describe the clinical course of COVID-19 in patients with cystic fibrosis (CF) and to identify risk factors for severe COVID-19.
Methods
We conducted a prospective study within the Italian CF Society. CF centers collected baseline and follow-up data of patients with virologically confirmed SARS-CoV-2 infection between March 2020 and June 2021. Odds ratios (ORs) for severe SARS-CoV-2 (as defined by hospital admission) were estimated by logistic regression models.
Results
The study included 236 patients with positive molecular test for SARS-CoV-2. Six patients died, 43 patients were admitted to hospital, 4 admitted to intensive care unit. Pancreatic insufficiency was associated with increased risk of severe COVID-19 (OR 4.04, 95% CI 1.52; 10.8). After adjusting for age and pancreatic insufficiency, forced expiratory volume in one second (FEVp) < 40% (OR 4.54, 95% CI 1.56; 13.2), oxygen therapy (OR 12.3, 95% CI 2.91–51.7), underweight (OR 2.92, 95% CI 1.12; 7.57), organ transplantation (OR 7.31, 95% CI 2.59; 20.7), diabetes (OR 2.67, 95% CI 1.23; 5.80) and liver disease (OR 3.67, 95% CI 1.77; 7.59) were associated with increased risk of severe COVID-19, while use of dornase alfa was associated with a reduced risk (OR 0.34, 95% CI 0.13–0.88). No significant changes were observed in FEVp from baseline to a median follow-up of 2 months (median difference: 0, interquartile range: − 4; 5,
P
= 0.62).
Conclusion
Clinical features indicative of severe form of CF are associated with increased risk of COVID-19 hospitalization. SARS-CoV-2 infected patients do not experience a deterioration of respiratory function.
Supplementary Information
The online version contains supplementary material available at 10.1007/s15010-021-01737-z.
Isomorphic mutation of the SBDS gene causes Shwachman-Diamond syndrome (SDS). SDS is a rare genetic bone marrow failure and cancer predisposition syndrome. SDS cells have ribosome biogenesis and their protein synthesis altered, which are two high-energy consuming cellular processes. The reported changes in reactive oxygen species production, endoplasmic reticulum stress response and reduced mitochondrial functionality suggest an energy production defect in SDS cells. In our work, we have demonstrated that SDS cells display a Complex IV activity impairment, which causes an oxidative phosphorylation metabolism defect, with a consequent decrease in ATP production. These data were confirmed by an increased glycolytic rate, which compensated for the energetic stress. Moreover, the signalling pathways involved in glycolysis activation also appeared more activated; i.e. we reported AMP-activated protein kinase hyper-phosphorylation. Notably, we also observed an increase in a mammalian target of rapamycin phosphorylation and high intracellular calcium concentration levels ([Ca2+]i), which probably represent new biochemical equilibrium modulation in SDS cells. Finally, the SDS cell response to leucine (Leu) was investigated, suggesting its possible use as a therapeutic adjuvant to be tested in clinical trials.
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