Clinical manifestations and outcomes of coronavirus disease-19 in heart transplant recipients: a multicentre case series with a systematic review and meta-analysis

Available data on clinical presentation and mortality of coronavirus disease-2019 (COVID-19) in heart transplant (HT) recipients remain limited. We report a case series of laboratory-confirmed COVID-19 in 39 HT recipients from 3 French heart transplant centres (mean age 54.4 ± 14.8 years; 66.7% males). Hospital admission was required for 35 (89.7%) cases including 14/39 (35.9%) cases being admitted in intensive care unit. Immunosuppressive medications were reduced or discontinued in 74.4% of the patients. After a median follow-up of 54 (19–80) days, death and death or need for mechanical ventilation occurred in 25.6% and 33.3% of patients, respectively. Elevated C-reactive protein and lung involvement ≥50% on chest computed tomography (CT) at admission were associated with an increased risk of death or need for mechanical ventilation. Mortality rate from March to June in the entire 3-centre HT recipient cohort was 56% higher in 2020 compared to the time-matched 2019 cohort (2% vs. 1.28%, P = 0.15). In a meta-analysis including 4 studies, pre-existing diabetes mellitus (OR 3.60, 95% CI 1.43–9.06, I² = 0%, P = 0.006) and chronic kidney disease stage III or higher (OR 3.79, 95% CI 1.39–10.31, I² = 0%, P = 0.009) were associated with increased mortality. These findings highlight the aggressive clinical course of COVID-19 in HT recipients.     

Could FISH on buccal smears become a new method of screening in children suspect of HNF1B anomaly?

HNF1B gene anomalies include renal development defects associated with cysts and are well known by pediatric nephrologists that ask for molecular analysis of this gene. Two types of genomic rearrangements are reported: mutation and more frequently deletion. Using microsatellites or CGH array the size of the deletion was found to be at least of 1.2 Mb including 15 genes among which HNF1B, leading to the diagnosis of chromosomal microdeletion. Fluorescent In Situ Hybridization (FISH) is a simple routinely performed technique, considered as the referring tool to diagnose microdeletion in genetic practice. We performed interphasic FISH on buccal smears from 6 patients known to have HNF1B deletion to valid our technique and to determine the size of the 17q12 deletion. All the patients were found to present a 17q12 microdeletion. Our results showed that FISH is a rapid, reliable and specific technique to diagnose 17q12 microdeletion and might be performed as non invasive sampling procedure useful in pediatric practice. In conclusion we propose to use interphasic FISH to screen pediatric patients presenting with renal abnormalities possibly linked to HNF1B anomaly. Molecular analysis and MLPA (Multiplex Ligand Probe Analysis) could be performed in cases with normal interphasic FISH to detect a point mutation of the gene or more rarely a single exon deletion.     

Some are more equal than others

The microbial communities found in the mammalian large intestine and rumen efficiently degrade many recalcitrant substrates that are resistant to the host’s digestive enzymes. These communities are known from molecular profiling to be highly diverse at the species and strain level, but it may be that only certain specialized organisms (“keystone species”) have the ability to initiate degradation of such substrates, thus releasing energy on which the rest of the community depends. We have recently reported that Ruminococcus bromii has a superior ability to degrade certain forms of particulate resistant starch (RS) when compared with other highly abundant species of amylolytic bacteria found in the human colon and have presented evidence that this bacterium provides an example of a keystone species within the microbial community with respect to RS fermentation. The concept of keystone species can be equally relevant to other activities, e.g., those involved in stabilizing the community.     

L’acylation des protéines : une fonction cellulaire importante des acides gras saturés

Fatty acid acylation of proteins corresponds to the co- or post-translational covalent linkage of a fatty acid, activated in the form of acyl-CoA, to an amino acid residue of the substrate protein. The cellular fatty acids which are involved in protein acylation are mainly saturated fatty acids. Palmitoylation (S-acylation) corresponds to the reversible attachment of palmitic acid (C16:0) to the side chain of a cysteine residue via a thioester bond. N-terminal myristoylation refers to the covalent attachment of myristic acid (C14:0) by an amide bond to the N-terminal glycine of many eukaryotic and viral proteins. Octanoylation (O-acylation) typically concerns the formation of an ester bond between octanoic acid (caprylic acid, C8:0) and the side chain of a serine residue of the gut and brain peptide ghrelin. An increasing number of proteins (enzymes, receptors, oncogenes, tumor suppressors, proteins involved in signal transduction, eukaryotic and viral structural proteins) have been shown to undergo fatty acid acylation. The acyl moiety can mediate protein subcellular localization, protein–protein interaction or protein–membrane interaction. Therefore, through the covalent modification of proteins, saturated fatty acids exhibit emerging specific and important roles in modulating protein functions. This review provides an overview of the recent findings on the various classes of protein acylation leading to the biological ability of saturated fatty acids to regulate many pathways. Finally, the links between these elucidated biochemical mechanisms and the physiological roles of dietary saturated fatty acids are discussed.