Study identifies genetic cause for yellow nail syndrome

Embargoed for release until 5:00 p.m. ET on Monday 23 December 2024    

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Below please find summaries of new articles that will be published in the next issue of Annals of Internal Medicine. The summaries are not intended to substitute for the full articles as a source of information. This information is under strict embargo and by taking it into possession, media representatives are committing to the terms of the embargo not only on their own behalf, but also on behalf of the organization they represent.         
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1. Study identifies genetic cause for yellow nail syndrome

Abstract: https://www.acpjournals.org/doi/10.7326/ANNALS-24-01101

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An analysis of genetic sequencing data and gene and protein expression studies from patients with yellow nail syndrome (YNS) found that defects in the planar cell polarity (PCP) pathway play a significant role in the pathogenesis of YNS. According to the authors, this is the first demonstration of a mechanism explaining YNS development, especially in its congenital form. This study is published in Annals of Internal Medicine.

YNS is a rare disease characterized by the triad of yellow dystrophic nails, lymphedema, and chronic lung disease. The cause of YNS remains largely unknown, although some evidence points to lymphatic vessel development defects as a manifestation of the disease. The genetic cause of YNS, whether congenital or late-onset, remains unknown.

Researchers from the Genetics Institute and Genomics Center, Tel Aviv Sourasky Medical Center and colleagues studied genetic data from six patients with congenital YNS (cYNS) and five with sporadic YNS (sYNS) to determine the genetic mechanisms underlying the disease. Among the patients with cYNS, their first symptoms appeared prenatally or shortly after birth. The median age for onset of symptoms for those with sYNS was 12 years. Yellow nails and lung disease were the presenting symptoms in most patients with YNS. The researchers examined next generation sequencing data for all patients with YNS to identify and analyze genetic variants. CELSR1 was highlighted as the principal candidate disease-causing gene with autosomal recessive inheritance. The researchers found that all but one patient with cYNS had biallelic variants in CELSR1. The remaining patient had a heterozygous loss-of-function variant in FZD6. Both CELSR1 and FZD6 are core molecules in the Wnt/PCP pathway. None of the patients with sYNS had candidate variants in either CELSR1 or FZD6. The researchers then extracted RNA from all patients to assess the Wnt/PCP pathway expression, and found that the pathway is disrupted both in cYNS patients with genetic variants and, to a lesser degree, in sYNS patients without genetic defects. These results suggest a strong case for the involvement of Wnt/PCP signaling and PCP defects in the pathogenesis of YNS.

Media contacts: For an embargoed PDF, please contact Angela Collom at acollom@acponline.org. To speak with corresponding author Hagit Baris Feldman, MD, please email hagitbf@tlvmc.gov.il.

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2. Higher dosage of anticoagulation for COVID-19 patients leads to lower mortality risk

Abstract: https://www.acpjournals.org/doi/10.7326/ANNALS-24-00800

URL goes live when the embargo lifts         

A prospective metanalysis of clinical trials examined the effects of high and low doses of anticoagulation for hospitalized patients with COVID-19. The study found that administering therapeutic dose anticoagulation with heparins reduced mortality, need for invasive mechanical ventilation (IMV) and thromboembolic events compared with prophylactic dose heparins. The findings are published in Annals of Internal Medicine.

Researchers funded by the World Health Organization studied data from 18 randomized clinical trials which randomly assigned patients hospitalized for COVID-19 to higher versus lower doses of anticoagulants. The intensity of anticoagulant used was classified as prophylactic, intermediate, or therapeutic dosing. The objective of the study was to estimate intention-to-treat effects of therapeutic vs prophylactic; therapeutic vs intermediate; and intermediate vs prophylactic dose anticoagulation in hospitalized patients with suspected or confirmed COVID-19. The primary outcome was all-cause mortality by 28 days after randomization, and secondary outcomes were progression to IMV or death, thromboembolic events and major bleeding. The majority of trials studied evaluated heparins, including enoxaparin, tinzaparin or dalteparin, so the researchers focused their findings on anticoagulation using heparins. The researchers found that administering therapeutic vs prophylactic-dose anticoagulation to patients hospitalized for COVID-19 was associated with 23% lower 28-day mortality. Mortality was higher for therapeutic vs intermediate dose anticoagulation; however, the researchers note that this comparison was not estimated precisely. Mortality risk was similar for similar for intermediate vs prophylactic dose anticoagulation. Risk of progression to IMV or death was similar to mortality risk. Across all dosage comparisons, the risk for major bleeding was higher, but the risk for thromboembolic events was lower. The findings suggest a high certainty that therapeutic dose anticoagulation of heparin reduces 28-day mortality in hospitalized patients with COVID-19. 

Media contacts: For an embargoed PDF, please contact Angela Collom at acollom@acponline.org. To speak with corresponding author Srinivas Murthy, MD, MHSc, please email Srinivas.murthy@ubc.ca.

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