Background The clinical presentation of COVID-19 in patients admitted to hospital is heterogeneous. We aimed to determine whether clinical phenotypes of patients with COVID-19 can be derived from clinical data, to assess the reproducibility of these phenotypes and correlation with prognosis, and to derive and validate a simplified probabilistic model for phenotype assignment. Phenotype identification was not primarily intended as a predictive tool for mortality. MethodsIn this study, we used data from two cohorts: the COVID-19@Spain cohort, a retrospective cohort including 4035 consecutive adult patients admitted to 127 hospitals in Spain with COVID-19 between Feb 2 and March 17, 2020, and the COVID-19@HULP cohort, including 2226 consecutive adult patients admitted to a teaching hospital in Madrid between Feb 25 and April 19, 2020. The COVID-19@Spain cohort was divided into a derivation cohort, comprising 2667 randomly selected patients, and an internal validation cohort, comprising the remaining 1368 patients. The COVID-19@HULP cohort was used as an external validation cohort. A probabilistic model for phenotype assignment was derived in the derivation cohort using multinomial logistic regression and validated in the internal validation cohort. The model was also applied to the external validation cohort. 30-day mortality and other prognostic variables were assessed in the derived phenotypes and in the phenotypes assigned by the probabilistic model. Findings Three distinct phenotypes were derived in the derivation cohort (n=2667)-phenotype A (516 [19%] patients), phenotype B (1955 [73%]) and phenotype C (196 [7%])-and reproduced in the internal validation cohort (n=1368)phenotype A (233 [17%] patients), phenotype B (1019 [74%]), and phenotype C (116 [8%]). Patients with phenotype A were younger, were less frequently male, had mild viral symptoms, and had normal inflammatory parameters. Patients with phenotype B included more patients with obesity, lymphocytopenia, and moderately elevated inflammatory parameters. Patients with phenotype C included older patients with more comorbidities and even higher inflammatory parameters than phenotype B. We developed a simplified probabilistic model (validated in the internal validation cohort) for phenotype assignment, including 16 variables. In the derivation cohort, 30-day mortality rates were 2•5% (95% CI 1•4-4•3) for patients with phenotype A, 30•5% (28•5-32•6) for patients with phenotype B, and 60•7% (53•7-67•2) for patients with phenotype C (log-rank test p<0•0001). The predicted phenotypes in the internal validation cohort and external validation cohort showed similar mortality rates to the assigned phenotypes (internal validation cohort: 5•3% [95% CI 3•4-8•1] for phenotype A, 31•3% [28•5-34•2] for phenotype B, and 59•5% [48•8-69•3] for phenotype C; external validation cohort: 3•7% [2•0-6•4] for phenotype A, 23•7% [21•8-25•7] for phenotype B, and 51•4% [41•9-60•7] for phenotype C).Interpretation Patients admitted to hospital with COVID-19 can be classified into three...

Cilia are evolutionarily conserved hair-like structures with a wide spectrum of key biological roles, and their dysfunction has been linked to a growing class of genetic disorders, known collectively as ciliopathies. Many strides have been made towards deciphering the molecular causes for these diseases, which have in turn expanded the understanding of cilia and their functional roles. One recently-identified ciliary gene is ARL2BP , encoding the ADP-Ribosylation Factor Like 2 Binding Protein. In this study, we have identified multiple ciliopathy phenotypes associated with mutations in ARL2BP in human patients and in a mouse knockout model. Our research demonstrates that spermiogenesis is impaired, resulting in abnormally shaped heads, shortened and mis-assembled sperm tails, as well as in loss of axonemal doublets. Additional phenotypes in the mouse included enlarged ventricles of the brain and situs inversus. Mouse embryonic fibroblasts derived from knockout animals revealed delayed depolymerization of primary cilia. Our results suggest that ARL2BP is required for the structural maintenance of cilia as well as of the sperm flagellum, and that its deficiency leads to syndromic ciliopathy.

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Purpose: To evaluate ganglion cell layer (GCL) and ganglion cell complex (GCC) thickness manually by spectral-domain optical coherence tomography in subjects with early and intermediate age-related macular degeneration (AMD) in 12 locations on the horizontal meridian. Methods: A total of 450 eyes (specifically, 246 eyes classified as having early/intermediate AMD plus 204 control eyes) were studied. Mann-Whitney U and Kruskal-Wallis tests were used to compare values between the healthy controls and the AMD group and also between the subgroups under study. Diagnostic performance was also compared calculating the areas under the receiver operating characteristic curve. Results: The manual layer segmentation showed clear boundaries between the GCL and the GCC. It was in the temporal GCC that more changes were found. Conclusions: The GCC, especially in the temporal region, allowed the discrimination of differences between various subgroups that have faint variations as well as between early AMD and the first signs of aging.

The effects of the administration of water soluble coenzyme Q10 (25 mg/kg per day) over 30 days, after 50 days feeding on a high-fat diet (3% lard + 1.3% cholesterol), were investigated in the plasma and liver mitochondria of rabbits. Results showed that this atherogenic diet enhanced lipid levels both in plasma and liver mitochondria, reduced plasma and mitochondrial concentrations of retinol and coenzyme Q10, led to higher DNA damage in peripheral blood lymphocytes and reactive oxygen species concentration in liver mitochondria. The treatment of animals with coenzyme Q10 reduced (to the healthy group levels) lipid concentration in liver mitochondria with no effect on plasma lipids, increased mitochondrial levels of alpha-tocopherol, restored mitochondrial coenzyme Q10 and improved alpha-tocopherol levels in plasma. Moreover, coenzyme Q10 supplementation reduced mitochondrial reactive oxygen species levels and decreased DNA damage in peripheral blood lymphocytes. The findings suggest that antioxidant therapy with coenzyme Q10 may be used in the treatment of liver pathologies associated to the intake of high-fat, atherogenic, diets.

OBJECTIVE: To compare clinical characteristics and risk factors of suppurative postsurgical mediastinitis according to its etiology. METHODS: Suppurative postsurgical mediastinitis developed in 45 (2.5%) of 1779 patients who underwent open-heart surgery at the Hospital Virgen del Rocío in Seville, Spain, from 1986 to 1996. Microbiological diagnosis was available in 42 patients. RESULTS: Gram-negative rods were isolated in 19 cases and Gram-positive cocci in 23 cases. Seventeen isolates (38%) were sensitive to the antimicrobial agent used perioperatively. Patients with Gram-negative rod infection had a longer duration of bypass (127plus minus36 min versus 96plus minus34 min, p<0.01), and a worse postoperative condition. Longer mechanical ventilation (4plus minus7 days versus 1plus minus2 days, p<0.05) and concomitant infection in a remote site (pulmonary and/or urinary infection) were more frequently observed in this group than in patients with Gram-positive infections (58% versus 22%, p<0.05). Twenty patients (51%) were bacteremic. The mortality rate was 20% (five of 45). CONCLUSIONS: Preventable postoperative remote-site infection may lead to mediastinitis, especially if Gram-negative rods are involved.

Purpose To evaluate quantitative parafoveal microvascular changes using Optical Coherence Tomography Angiography (OCTA) by comparing the area of foveal avascular zone (FAZ) and vessel density (VD) between nondiabetic controls and patients with different levels of Diabetic Retinopathy (DR). Methods A systematic review was performed according to the recommendations of the "Cochrane Handbook for Systematic Reviews of Interventions" and reported according to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines. Three electronic databases including PubMed, Web of Science and Cochrane Library were systematically retrieved by using key terms with Boolean operators. The data extracted from each study included: first author, year of publication, study design, sample size and participant characteristics (mean age, type of diabetes mellitus and mean duration of diabetic disease). Outcome variables included: VD and area of FAZ, in superficial and deep capillary plexuses of parafovea. Results 355 articles were identified from our search of databases and 10 studies were included in this systematic review. Patients with diabetes with or without clinical signs of DR have a significantly enlarged area of FAZ and decreased parafoveal VD compared to healthy controls, as well as an association between these microvascular changes and worsening DR. Conclusion OCTA can provide valuable information about early and subtle microvascular changes of parafoveal capillary plexuses in patients with diabetes and can identify preclinical DR before the manifestation of clinically apparent retinopathy. The non-invasive nature of OCTA allows routine imaging of the retinal vasculature, so this approach may be a promising tool for screening programmes of DR.

Purpose: To evaluate outer retina and choroidal thickness in subjects with intermediate age-related macular degeneration (iAMD) and to describe associations with the presence of reticular pseudodrusen (RPD). Methods: This was a retrospective, cross-sectional analysis of 157 consecutive eyes (specifically: 62 eyes classified as having RPD and 95 eyes with drusen ≥125 µm). Only cases with digital color fundus photographs, red-free, and infrared, obtained and graded according to the Age-Related Eye Disease Study to define iAMD, were used for this study. Outer retina and choroidal thickness were manually segmented and quantified at 12 locations in the horizontal meridian. Results: RPD appeared to be associated with thinning of the outer layers even after adjustment forgender and age. The presence of RPD in iAMD decreased with increase of choroidal thickness (total odds ratio [OR] 0.991, 95% confidence interval [CI] 0.985-0.996; nasal OR 0.992, 95% CI 0.986-0.997), with increased thickness of the myoid zone of the photoreceptors (total OR 0.812, 95% CI 0.688-0.958; nasal OR 0.863, 95% CI 0.755-0.987) and with increased thickness of the outer segment of the photoreceptors (total OR 0.850, 95% CI 0.731-0.989; nasal OR 0.857, 95% CI 0.736-0.989). Conclusions: The greatest differences between eyes with and without RPD are found at the level of the choroidal thickness and at the level of the photoreceptors.