Myocardial localization of coronavirus in COVID‐19 cardiogenic shock

We describe the first case of acute cardiac injury directly linked to myocardial localization of severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) in a 69‐year‐old patient with flu‐like symptoms rapidly degenerating into respiratory distress, hypotension, and cardiogenic shock. The patient was successfully treated with venous‐arterial extracorporeal membrane oxygenation (ECMO) and mechanical ventilation. Cardiac function fully recovered in 5 days and ECMO was removed. Endomyocardial biopsy demonstrated low‐grade myocardial inflammation and viral particles in the myocardium suggesting either a viraemic phase or, alternatively, infected macrophage migration from the lung.     

Multiplex Ligation-Dependent Probe Amplification Analysis of GATA4 Gene Copy Number Variations in Patients with Isolated Congenital Heart Disease

GATA4 mutations are found in patients with different isolated congenital heart defects (CHDs), mostly cardiac septal defects and tetralogy of Fallot. In addition, GATA4 is supposed to be the responsible gene for the CHDs in the chromosomal 8p23 deletion syndrome, which is recognized as a malformation syndrome with clinical symptoms of facial anomalies, microcephaly, mental retardation, and congenital heart defects. Thus far, no study has been carried out to investigate the role of GATA4 copy number variations (CNVs) in non-syndromic CHDs. To explore the possible occurrence of GATA4 gene CNVs in isolated CHDs, we analyzed by multiplex ligation-dependent probe amplification (MLPA) a cohort of 161 non-syndromic patients with cardiac anomalies previously associated with GATA4 gene mutations. The patients were mutation-negative for GATA4, NKX2.5, and FOG2 genes after screening with denaturing high performance liquid chromatography. MLPA analysis revealed that normalized MLPA signals were all found within the normal range values for all exons in all patients, excluding a major contribution of GATA4 gene CNVs in CHD pathogenesis.     

The effect of enzyme replacement therapy on clinical outcomes in female patients with Fabry disease – A systematic literature review by a European panel of experts

BackgroundHeterozygous females with Fabry disease have a wide range of clinical phenotypes depending on the nature of their mutation and their X-chromosome inactivation pattern; it is therefore important to examine outcomes of enzyme replacement therapy (ERT) in the female patient population specifically. This paper presents the findings of a systematic literature review of treatment outcomes with ERT in adult female patients.MethodsA comprehensive systematic literature review was conducted through January 2017 to retrieve published papers with original data on ERT in the treatment of Fabry disease. The review included all original articles that presented ERT outcomes data on patients with Fabry disease, irrespective of the study type.ResultsClinical evidence for the efficacy of ERT in female patients was available from 67 publications including six clinical trial publications, and indicates significant reductions in plasma and urine globotriaosylceramide (GL-3) accumulation (in female patients with elevated pre-treatment levels) and improvements in cardiac parameters and quality of life (QoL). To date, data are insufficient to conclude on the effects of ERT on the nervous system, gastrointestinal manifestations, and pain in female patients with Fabry disease.ConclusionsThis review of available literature data demonstrates that ERT in adult female patients with Fabry disease has a beneficial effect on GL-3 levels and cardiac outcomes. The current evidence also suggests that ERT may improve QoL in this patient population, though further studies are needed to examine these results.     

Epidemiology of achondroplasia: A population‐based study in Europe

Achondroplasia is a rare genetic disorder resulting in short‐limb skeletal dysplasia. We present the largest European population‐based epidemiological study to date using data provided by the European Surveillance of Congenital Anomalies (EUROCAT) network. All cases of achondroplasia notified to 28 EUROCAT registries (1991–2015) were included in the study. Prevalence, birth outcomes, prenatal diagnosis, associated anomalies, and the impact of paternal and maternal age on de novo achondroplasia were presented. The study population consisted of 434 achondroplasia cases with a prevalence of 3.72 per 100,000 births (95%CIs: 3.14–4.39). There were 350 live births, 82 terminations of pregnancy after prenatal diagnosis, and two fetal deaths. The prenatal detection rate was significantly higher in recent years (71% in 2011–2015 vs. 36% in 1991–1995). Major associated congenital anomalies were present in 10% of cases. About 20% of cases were familial. After adjusting for maternal age, fathers >34 years had a significantly higher risk of having infants with de novo achondroplasia than younger fathers. Prevalence was stable over time, but regional differences were observed. All pregnancy outcomes were included in the prevalence estimate with 80.6% being live born. The study confirmed the increased risk for older fathers of having infants with de novo achondroplasia.     

Variations in the NMDA receptor subunit 2B gene (GRIN2B) and schizophrenia: a case-control study.

A well established model for the pathophysiology of schizophrenia postulates a role for the NMDA-mediated glutamate transmission. The human gene coding for the 2B subunit of the NMDA receptor (GRIN2B) is considered a candidate based on its selective expression in brain. To evaluate the hypothesis that GRIN2B acts as a major gene in determining susceptibility to schizophrenia, a case-control association study was performed. Five single nucleotide polymorphisms (SNPs) were genotyped in 188 Italian patients and 156 control subjects. The association study showed a marginally significant excess of homozygosity for the polymorphism located in the 3'UTR region (P = 0.04). No other difference in genotype and allele frequencies was found in schizophrenics as compared to the control series. The case-control study was also carried out on estimated haplotypes, confirming a trend for association (P = 0.04). These results suggest that GRIN2B variations might be linked with susceptibility to schizophrenia. Replication studies on larger samples are warranted to further test this hypothesis.     

Similar rapid onset of action and magnitude of effect of fexofenadine and cetirizine as assessed by inhibition of histamine-induced wheal-and-flare reaction.

BACKGROUND: Histamine-induced wheal-and-flare studies are useful, objective tests for determining differences in the peripheral H1-receptor blockade activities of antihistamines. OBJECTIVE: To evaluate the time of occurrence of 95% inhibition of histamine-induced wheal and flare after administration of fexofenadine hydrochloride, 180 mg, or cetirizine, 10 mg. METHODS: Forty-two volunteers (aged 18-60 years) were included in a randomized, double-blind, crossover study. Skin prick tests were undertaken using histamine (100 mg/mL) before treatment and 0.5, 1.0, 1.5, 2.0, 2.5, 3.0, 3.5, and 4.0 hours after treatment. Wheal and flare areas were evaluated, and the time to occurrence of 95% inhibition and the frequency of subjects exhibiting 95% inhibition before median time to 95% inhibition were calculated. RESULTS: Mean +/- SD time to 95% wheal inhibition was 2.46 +/- 0.71 hours with fexofenadine and 2.55 +/- 0.57 hours with cetirizine. The estimated mean difference between fexofenadine and cetirizine (-7 minutes in favor of fexofenadine; 2-sided 95% confidence interval, -21 to +7 minutes) was not statistically significant (P = .34). For wheal, 29% of subjects receiving fexofenadine and 24% receiving cetirizine achieved 95% inhibition before the median time of inhibition (2.5 hours). An exact permutation test yielded a P = .37. For flare, 26% of subjects receiving fexofenadine and 10% receiving cetirizine achieved 95% inhibition before the median time of inhibition (3 hours; P = .12 by exact permutation test). CONCLUSIONS: Fexofenadine and cetirizine have comparable onset of action times and similar frequencies of inhibition, as evaluated by the occurrence of 95% inhibition of histamine-induced wheal and flare.