Risk of COVID-19 infection, hospitalization, and mortality in patients with psoriasis treated by interleukin-17 inhibitors.

BACKGROUND: The risk of the infection and its complications under this drug class remains to be determined. OBJECTIVE: To evaluate the risk of COVID-19, COVID-19-associated hospitalization, and mortality among patients with psoriasis treated by IL-17I. METHODS: A population-based cohort study was performed to compare psoriasis patients treated by IL-17I (n = 680) with those treated by methotrexate (n = 2153) and non-systemic/non-immunomodulatory treatments (n = 138,750) regarding the incidence of COVID-19 and its complications. RESULTS: The use of IL-17I was not associated with an increased risk of COVID-19 infection [adjusted HR for IL-17I vs. methotrexate: 0.91 (95% CI, 0.48-1.72); IL-17I vs. non-systemic/non-immunomodulatory treatments: 0.92 (95% CI, 0.54-1.59)]. IL-17I was associated with comparable risk of COVID-19-associated hospitalization [adjusted HR for IL-17I vs. methotrexate: 0.42 (95% CI, 0.05-3.39); IL-17I vs. non-systemic/non-immunomodulatory treatments: 0.65 (95% CI, 0.09-4.59)] and COVID-19-associated mortality [adjusted HR for IL-17I vs. methotrexate: 7.57 (95% CI, 0.36-157.36); IL-17I vs. non-systemic/non-immunomodulatory treatments: 7.05 (95% CI, 0.96-51.98)]. In a sensitivity analysis, neither secukinumab nor ixekizumab imposed an elevated risk of any of the outcomes of interests. CONCLUSIONS: IL-17I treatment does not confer an increased risk of COVID-19 infection or its complications in patients with psoriasis. Our findings support the continuation of IL-17I treatment during the pandemic.

Risk of COVID-19 and its complications in patients with atopic dermatitis undergoing dupilumab treatment-a population-based cohort study.

The risk of coronavirus disease (COVID-19) infection and its complications among patients with atopic dermatitis (AD) treated by dupilumab is yet to be determined. We aimed to assess the risk of SARS-CoV-2 infection, COVID-19-associated hospitalization, and mortality among patients with AD treated by dupilumab. A population-based cohort study was conducted to compare AD patients treated by dupilumab (n = 238) with those treated by prolonged systemic corticosteroids (≥ 3 months; n = 1,023), phototherapy (n = 461), and azathioprine or mycophenolate mofetil (MMF; n = 194) regarding the incidence of COVID-19 and its complications. The incidence rate of COVID-19, COVID-19-associated hospitalization, and mortality among patients treated by dupilumab was 70.1 (95% CI, 40.5-116.4), 5.0 (95% CI, 0.3-24.7), and 0.0 per 1,000 person-year, respectively. The use of dupilumab was not associated with an increased risk of SARS-CoV-2 infection [adjusted HR for dupilumab vs. prolonged systemic corticosteroids: 1.13 (95% CI, 0.61-2.09); dupilumab vs. phototherapy: 0.80 (95% CI, 0.42-1.53); dupilumab vs. azathioprine/MMF: 1.10 (95% CI, 0.45-2.65)]. Dupilumab was associated with a comparable risk of COVID-19-associated hospitalization [adjusted HR for dupilumab vs. prolonged systemic corticosteroids: 0.35 (95% CI, 0.05-2.71); dupilumab vs. phototherapy: 0.43 (95% CI, 0.05-3.98); dupilumab vs. azathioprine/MMF: 0.25 (95% CI, 0.02-2.74)]. When applicable, the risk of mortality was not elevated in patients with AD treated by dupilumab [HR for dupilumab vs. prolonged systemic corticosteroids: 0.04 (95% CI, 0.00-225.20)]. To conclude, dupilumab does not impose an increased risk of SARS-CoV-2 infection or COVID-19 complications in patients with AD. Dupilumab should be continued and considered as a safe drug for moderate-to-severe AD during the pandemic.

Rapid progression of aortic stenosis after initiation of teriparatide treatment: a case report.

INTRODUCTION: Teriparatide, a recombinant formulation of endogenous PTH, is indicated for the treatment of osteoporosis in patients at high risk for fracture including postmenopausal women, men with primary or hypogonadal osteoporosis and patients with glucocorticoid-induced osteoporosis. CASE REPORT: A 64-year-old Jewish osteoporotic woman initiated use of Teriparatide (FORTEOTM, 250 µg per 1 ml subcutaneously per day) in April 2018. Prior to therapy initiation, the patient has undergone eight echocardiograms with an aortic valve pressure gradient ranging between 29 and 39 mmHg, defined as mild aortic stenosis (AS), with no clear trend of progression. In two subsequent echo tests conducted 4 and 7 months after treatment initiation, there was a rapid progression of AS with gradient pressures of 55 and 58 mmHg, respectively. CONCLUSION: Intermittent exposure to PTH analogues may be one of the causes of rapid progression of AS. Studies with sizeable populations are required to assess causal relationship between PTH analogues use and progression of AS.

MicroRNAs are essential for differentiation of the retinal pigmented epithelium and maturation of adjacent photoreceptors.

Dysfunction of the retinal pigmented epithelium (RPE) results in degeneration of photoreceptors and vision loss and is correlated with common blinding disorders in humans. Although many protein-coding genes are known to be expressed in RPE and are important for its development and maintenance, virtually nothing is known about the in vivo roles of non-coding transcripts. The expression patterns of microRNAs (miRNAs) have been analyzed in a variety of ocular tissues, and a few were implicated to play role in RPE based on studies in cell lines. Here, through RPE-specific conditional mutagenesis of Dicer1 or Dgcr8 in mice, the importance of miRNAs for RPE differentiation was uncovered. miRNAs were found to be dispensable for maintaining RPE fate and survival, and yet they are essential for the acquisition of important RPE properties such as the expression of genes involved in the visual cycle pathway, pigmentation and cell adhesion. Importantly, miRNAs of the RPE are required for maturation of adjacent photoreceptors, specifically for the morphogenesis of the outer segments. The alterations in the miRNA and mRNA profiles in the Dicer1-deficient RPE point to a key role of miR-204 in regulation of the RPE differentiation program in vivo and uncover the importance of additional novel RPE miRNAs. This study reveals the combined regulatory activity of miRNAs that is required for RPE differentiation and for the development of the adjacent neuroretina.

ApoE4 induces synaptic and ERG impairments in the retina of young targeted replacement apoE4 mice.

The vertebrate retina, which is part of the central nervous system, is a window into the brain. The present study investigated the extent to which the retina can be used as a model for studying the pathological effects of apolipoprotein E4 (apoE4), the most prevalent genetic risk factor for Alzheimer's disease (AD). Immunohistochemical studies of retinas from young (4 months old) apoE4-targeted replacement mice and from corresponding mice which express the AD benign apoE3 allele, revealed that the density of the perikarya of the different classes of retinal neurons was not affected by apoE4. In contrast, the synaptic density of the retinal synaptic layers, which was assessed immunohistochemically and by immunoblot experiments, was significantly lower in the apoE4 than in the apoE3 mice. This was associated with reduced levels of the presynaptic vesicular glutamatergic transporter, VGluT1, but not of either the GABAergic vesicular transporter, VGaT, or the cholinergic vesicular transporter, VAChT, suggesting that the glutamatergic nerve terminals are preferentially affected by apoE4. In contrast, the post synaptic scaffold proteins PSD-95 and Gephyrin, which reside in excitatory and inhibitory synapses, respectively, were both elevated, and their ratio was not affected by apoE4. Electroretinogram (ERG) recordings revealed significant attenuation of mixed rod-cone responses in dark-adapted eyes of apoE4 mice. These findings suggest that the reduced ERG response in the apoE4 mice may be related to the observed decrease in the retinal nerve terminals and that the retina could be used as a novel model for non-invasive monitoring of the effects of apoE4 on the CNS.

Serum levels of 25-hydroxy-vitamin D3 among sun-protected outdoor workers in Israel.

The objective of this study was to evaluate the effect of reduced sun exposure of outdoor workers on vitamin D status using different modalities of sun protection, for primary prevention of skin cancer. 25-OH-D3 measurements were performed in two successive winters, 8 (interim) and 20 months after initiation of the study, in three groups of male outdoor workers, enrolled in either a complete, partial or minimal sun protection program. Ambient solar UVB radiation was monitored simultaneously. No intragroup or intergroup differences were observed between the interim- and postintervention measurements of mean 25-OH-D3, which were close to 30 ng mL(-1). Significant risk factors for postintervention 25-OH-D3 levels >33.8 ng mL(-1) (a surrogate for reduced sun protection) were: previous sunburn episodes (OR 2.5; 95% CI 1.01-6.3; P=0.05) and younger age (OR 0.92; 95 CI 0.86-0.98; P=0.009). Outdoor workers of Western, compared with those of Eastern paternal origin had a borderline significant risk (OR 2.4; 95% CI 0.9-6.3; P=0.07). A borderline significant effect (OR 2.9; 95% CI 0.97-10.1; P=0.085) was also noted for those in the minimal intervention group. In conclusion, sun protection among outdoor workers following a successful intervention did not suppress mean winter 25-OH-D3.

Increased electroretinogram a-wave amplitude after intravitreal bevacizumab injection for neovascular age-related macular degeneration.

PURPOSE: To assess the effect of bevacizumab (Avastin), a vascular endothelial growth factor inhibitor, on retinal function by full-field electroretinography (ERG) in patients with neovascular age-related macular degeneration (AMD). DESIGN: A prospective, nonrandomized, controlled interventional clinical trial. METHODS: Twelve patients (aged 50)85) with neovascular AMD each received one unilateral intravitreal injection of bevacizumab 1.25 mg/ 0.05 ml as part of the standard management for choroidal neovascular AMD. Before and 1 month after injection, all patients underwent bilateral full-field ERG scanning by a masked technician according to the ISCEV protocol, and their wave amplitudes were recorded. Untreated eyes served as controls. Scotopic responses were recorded at four incremental light intensities and photopic responses at two incremental light intensities. Changes in ERG-amplitude responses were calculated. Repeated-measures ANOVA was used for data analysis. RESULTS: Mean pre- and postinjection differences in a-wave amplitudes between the incremental light intensities in injected eyes were significantly higher than in controls (15.92 versus 1.33 lV for scotopic responses and 4.97 versus )1.06 lV for photopic responses; p = 0.057 and p = 0.01, respectively). Mean b-wave amplitudes in injected eyes were significantly higher than in controls for photopic responses (p = 0.048), but for scotopic responses, the difference between treated and untreated eyes was not significant (p = 0.23). CONCLUSIONS: Intravitreally injected bevacizumab improves both rod and cone functioning in patients with neovascular AMD, as demonstrated by the increase in the ERG a-wave responses of these patients. Other measured ERG parameters yielded no significant photoreceptor toxicity.