The gut microbiome is a critical modulator of host immunity and is linked to the immune response to respiratory viral infections. However, few studies have gone beyond describing broad compositional ...alterations in severe COVID-19, defined as acute respiratory or other organ failure.
We profiled 127 hospitalized patients with COVID-19 (n = 79 with severe COVID-19 and 48 with moderate) who collectively provided 241 stool samples from April 2020 to May 2021 to identify links between COVID-19 severity and gut microbial taxa, their biochemical pathways, and stool metabolites.
Forty-eight species were associated with severe disease after accounting for antibiotic use, age, sex, and various comorbidities. These included significant in-hospital depletions of Fusicatenibacter saccharivorans and Roseburia hominis, each previously linked to post-acute COVID syndrome or "long COVID," suggesting these microbes may serve as early biomarkers for the eventual development of long COVID. A random forest classifier achieved excellent performance when tasked with classifying whether stool was obtained from patients with severe vs. moderate COVID-19, a finding that was externally validated in an independent cohort. Dedicated network analyses demonstrated fragile microbial ecology in severe disease, characterized by fracturing of clusters and reduced negative selection. We also observed shifts in predicted stool metabolite pools, implicating perturbed bile acid metabolism in severe disease.
Here, we show that the gut microbiome differentiates individuals with a more severe disease course after infection with COVID-19 and offer several tractable and biologically plausible mechanisms through which gut microbial communities may influence COVID-19 disease course. Further studies are needed to expand upon these observations to better leverage the gut microbiome as a potential biomarker for disease severity and as a target for therapeutic intervention.
Archaeological evidence indicates that pig domestication had begun by ∼10,500 y before the present (BP) in the Near East, and mitochondrial DNA (mtDNA) suggests that pigs arrived in Europe alongside ...farmers ∼8,500 y BP. A few thousand years after the introduction of Near Eastern pigs into Europe, however, their characteristic mtDNA signature disappeared and was replaced by haplotypes associated with European wild boars. This turnover could be accounted for by substantial gene flow from local European wild boars, although it is also possible that European wild boars were domesticated independently without any genetic contribution from the Near East. To test these hypotheses, we obtained mtDNA sequences from 2,099 modern and ancient pig samples and 63 nuclear ancient genomes from Near Eastern and European pigs. Our analyses revealed that European domestic pigs dating from 7,100 to 6,000 y BP possessed both Near Eastern and European nuclear ancestry, while later pigs possessed no more than 4% Near Eastern ancestry, indicating that gene flow from European wild boars resulted in a near-complete disappearance of Near East ancestry. In addition, we demonstrate that a variant at a locus encoding black coat color likely originated in the Near East and persisted in European pigs. Altogether, our results indicate that while pigs were not independently domesticated in Europe, the vast majority of human-mediated selection over the past 5,000 y focused on the genomic fraction derived from the European wild boars, and not on the fraction that was selected by early Neolithic farmers over the first 2,500 y of the domestication process.
Although consensus documents on catheter and surgical ablation of atrial fibrillation (AF) suggest a uniform "blanking period" of 3 months, recent evidence suggested that early recurrences of atrial ...tachyarrhythmias (ERATs) are strongly associated with late recurrences (LRs), especially if ERATs occurred in the last part of the "blanking period".
The present study sought to assess the role of ERATs in predicting LRs in a large cohort of patients with paroxysmal AF who have undergone second-generation cryoballoon ablation.
Consecutive patients with drug-resistant paroxysmal AF who underwent pulmonary vein isolation using CB-A technology as the index procedure were retrospectively included in our analysis. The exclusion criteria were any contraindications for the procedure, including the presence of an intracavitary thrombus, uncontrolled heart failure, contraindications to general anesthesia, and persistent AF.
A total of 331 consecutive patients (104 women 31%; mean age 56.7 ± 13.3 years) were enrolled. Atrial tachyarrhythmias/AF recurrences were detected in 57 patients (17.2%). The highest prevalence of ERATs was observed in the first 2 weeks (55%) after pulmonary vein isolation. Of note, all the ERATs occurring 1.5 months after AF ablation relapsed after 3 months and were confirmed as definitive recurrences. Late recurrence of AF and atrial tachycardia occurred in 20 of 29 patients with ERATs (69.0%) and 28 of 302 patients without ERATs (9.3%) (P < .0001). A multivariate Cox regression analysis showed that the early recurrence within the blanking period was significantly and independently associated with an increased risk of developing a late recurrence (hazard ratio 6.79; 95% confidence interval 3.52-10.14; P < .0001).
Our findings reveal that ERATs are strongly associated with an LR after paroxysmal AF ablation using CB-A technology (hazard ratio 6.79; 95% confidence interval 3.52-10.14; P < .0001). Of note, when ERATs occurred later than 1.5 months, patients systematically experienced an LR.
Isolated cases of monomorphic ventricular tachycardia (MVT) in patients with Brugada syndrome (BrS) have been reported.
We aimed to describe the incidence and characteristics of MVT in a cohort of ...patients with BrS who had received an implantable cardioverter-defibrillator (ICD).
Data from 834 patients with BrS implanted with an ICD in 15 tertiary hospitals between 1993 and 2014 were included.
The mean age of enrolled patients was 45.3 ± 13.9 years; 200 patients (24%) were women. During a mean follow-up of 69.4 ± 54.3 months, 114 patients (13.7%) experienced at least 1 appropriate ICD intervention, with MVT recorded in 35 patients (4.2%) (sensitive to antitachycardia pacing in 15 42.8%). Only QRS width was an independent predictor of MVT in the overall population. Specifically, 6 (17.1%) patients presented with right ventricular outflow tract tachycardia (successfully ablated from the endocardium in 4 and epicardial and endocardial ablation in 1), 2 patients with MVT arising from the left ventricle (1 successfully ablated in the supra lateral mitral annulus), and 2 (5.7%) patients with bundle branch reentry ventricular tachycardia. Significant structural heart disease was ruled out by echocardiography and/or cardiac magnetic resonance imaging.
In this retrospective study, 4.2% of patients with BrS implanted with an ICD presented with MVT confirmed as arising from the right ventricular outflow tract tachycardia in 6, patients with MVT arising from the left ventricle in 2, and patients with bundle branch reentry ventricular tachycardia in 2. Endocardial and/or epicardial ablation was successful in 80% of these cases. These data imply that the occurrence of MVT should not rule out the possibility of BrS. This finding may also be relevant for ICD model selection and programming.
NextGen's tools for the future Kruger, Matthew; Hussey, Brendan J.; Wang, Wei ...
Science (American Association for the Advancement of Science),
04/2015, Letnik:
348, Številka:
6230
Journal Article
In pediatric patients, triggering of digits other than the thumb is uncommon and can have unique etiology. We present a juvenile patient whose trigger finger was associated with a solid calcified ...nodule on the flexor digitorum superficialis tendon.
AMPA receptors (AMPARs) are tetrameric ligand-gated channels made up of combinations of GluA1-4 subunits encoded by GRIA1-4 genes. GluA2 has an especially important role because, following ...post-transcriptional editing at the Q607 site, it renders heteromultimeric AMPARs Ca
-impermeable, with a linear relationship between current and trans-membrane voltage. Here, we report heterozygous de novo GRIA2 mutations in 28 unrelated patients with intellectual disability (ID) and neurodevelopmental abnormalities including autism spectrum disorder (ASD), Rett syndrome-like features, and seizures or developmental epileptic encephalopathy (DEE). In functional expression studies, mutations lead to a decrease in agonist-evoked current mediated by mutant subunits compared to wild-type channels. When GluA2 subunits are co-expressed with GluA1, most GRIA2 mutations cause a decreased current amplitude and some also affect voltage rectification. Our results show that de-novo variants in GRIA2 can cause neurodevelopmental disorders, complementing evidence that other genetic causes of ID, ASD and DEE also disrupt glutamatergic synaptic transmission.
The high costs of direct-acting antiviral (DAA) agents to treat chronic hepatitis C virus (HCV) infection have resulted in denials of treatment, but it is not clear whether patients' access to these ...therapies differs with their type of insurance.
We conducted a prospective cohort study among all patients who had a DAA prescription submitted between November 1, 2014 and April 30, 2015 to Burman's Specialty Pharmacy, which provides HCV pharmacy services to patients in Delaware, Maryland, New Jersey, and Pennsylvania. We determined the incidence of absolute denial of DAA prescription, defined as a lack of approval of a prescription fill by the insurer, according to type of insurance (US Medicaid, US Medicare, or commercial insurance). Multivariable Poisson regression was used to estimate adjusted relative risks of absolute denial associated with patient characteristics.
Among 2321 patients prescribed a DAA regimen (503 covered by Medicaid, 795 covered by Medicare, and 1023 covered by commercial insurance), 377 (16.2%) received an absolute denial. The most common reasons for absolute denial were insufficient information to assess medical need (134 35.5%) and lack of medical necessity (132 35.0%). A higher proportion of patients covered by Medicaid received an absolute denial (233 46.3%) than those covered by Medicare (40 5.0%; P < .001) or commercial insurance (104 10.2%; P < .001). Medicaid insurance (adjusted relative risk, 4.14; 95% confidence interval, 3.38-5.08) and absence of cirrhosis (adjusted relative risk, 1.96; 95% confidence interval, 1.53-2.50) were associated with absolute denial.
There are significant disparities in access to DAA-based treatments for HCV infection among patients with different types of insurance. Nearly half of Medicaid beneficiaries in Delaware, Maryland, New Jersey, and Pennsylvania were denied access to these drugs for chronic HCV infection.
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