Techniques,indications and complications of corneal debridement

The cornea is the most exposed surface of the eye and, as such, is vulnerable to external trauma and the risk of infection. Many corneal diseases alter shape, surface, and transparency and thus result in reduced vision. The external position of the cornea, however, lends itself to diagnostic and therapeutic maneuvers that are commonly performed and readily done in the clinic. More sophisticated techniques require the use of complex equipment such as excimer and femtosecond laser. Complications that develop from poor healing and/or secondary infection are best avoided with appropriate technique, antisepsis, and modification of wound healing. We review corneal debridement in the management of corneal disease.     

Predictive phenotyping of inherited ichthyosis by next‐generation DNA sequencing

Basal cell naevus syndrome (BCNS) is an autosomal dominant disorder most commonly caused by a germline mutation in the Drosophila homologue of patched‐1 gene (PTCH1). Here we describe a patient with clinical signs of BCNS, caused by postzygotic mosaicism of a PTCH1 mutation. We performed restriction fragment length polymorphism analysis and Droplet Digital polymerase chain reaction to determine the degree of mosaicism in different tissues of this patient. Our case shows that a relatively low‐grade mosaicism can lead to clinical signs reminiscent of those caused by a germline mutation. This finding has important implications for genetic counselling and therefore is pivotal to recognize for dermatologists, as well as for clinical geneticists and clinical laboratory geneticists.     

Multiple variants aggregate in the neuregulin signaling pathway in a subset of schizophrenia patients

Despite the strongly held view that schizophrenia (SZ) shows substantial genetic heterogeneity, pathway heterogeneity, as seen in cancer where different pathways are affected in similar tumors, has not been explored. We explore this possibility in a case-only study of the neuregulin signaling pathway (NSP), which has been prominently implicated in SZ and for which there is detailed knowledge on the ligand- and receptor-processing steps through β- and γ-secretase cleavage. We hypothesize that more than one damaging variants in the NSP genes might be necessary to cause disease, leading to an apparent clustering of such variants in only the few patients with affected NSP. We analyze linkage and next-generation sequencing results for the genes encoding components of the pathway, including NRG1, NRG3, ERBB4, β-secretase and the γ-secretase complex. We find multiple independent examples of supporting evidence for this hypothesis: (i) increased linkage scores over NSP genes, (ii) multiple positive interlocus correlations of linkage scores across families suggesting each family is linked to either many or none of the genes, (iii) aggregation of predicted damaging variants in a subset of individuals and (iv) significant phenotypic differences of the subset of patients carrying such variants. Collectively, our data strongly support the hypothesis that the NSP is affected by multiple damaging variants in a subset of phenotypically distinct patients. On the basis of this, we propose a general model of pathway heterogeneity in SZ, which, in part, may explain its phenotypic variability and genetic complexity.     

The association between the etiology of a spinal cord injury and time to mortality in the United States: A 44-year investigation

Objective: To determine the association between spinal cord injury (SCI) etiology categories and mortality, and examine the association between etiology sub-categories and mortality.

Design: Prospective cohort study.

Setting: Model Systems and Shriners Hospital SCI units.

Participants: Data were analyzed from 42,627 cases in the SCI Model System Collaborative Survival Study Database from 1973 to 2017. Those with SCI etiologies categorized as vehicular, violent, sports, falls, pedestrian, and medical were included.

Interventions: Not applicable.

Outcome Measure: Time to mortality after SCI.

Results: Relative to the sports related etiology category, those with medical, pedestrian, violence, falls, and vehicular related SCIs had a 2.00 (95% confidence intervals (CIs): 1.79–2.24), 1.57 (CIs: 1.34–1.83), 1.54 (CIs: 1.41–1.68), 1.35 (CIs: 1.25–1.45), and 1.26 (CIs: 1.17–1.35) higher hazard for mortality, respectfully. Persons with SCIs from automobile crashes had a 1.38 (CIs: 1.23–1.56) higher hazard for mortality, whereas those with SCIs from motorcycle crashes had a 1.21 (CIs: 1.04–1.39) higher hazard for mortality, relative to other etiologies within the vehicular category. Those with SCIs from diving had a 1.37 (CIs: 1.18–1.59) higher hazard for mortality relative to other etiologies within the sports category.

Conclusions: Injury etiology categories and certain sub-categories were associated with a higher risk for early mortality. Understanding how additional factors such as socioeconomic status, co-occurring injuries, medical co-morbidities, and environmental aspects interact with SCI etiologies may provide insights for how etiology of injury impacts survival. These findings may serve as a development for extending long-term life expectancy by informing SCI prevention programs and care post-injury.