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Objective: Severe acute respiratory syndrome coronavirus 2 through angiotensin‐converting enzyme 2 receptor can harm testes function. The objectives were to analyse the prevalence of low serum testosterone (LT) and impaired fertility potential (Leydig and Sertoli cells dysfunction, respectively) in coronavirus disease 2019 (COVID‐19) male survivors and to evaluate acute infection‐related associated factors. Also, we explore its association with post‐acute COVID‐19 syndrome (PCS) and quality of life (QOL). Materials and Methods: Male adults recovered from polymerase chain reaction‐confirmed COVID‐19 were offered a structured evaluation 8–12 weeks after recovery. The main outcome measure(s) were as follows: LT, defined as total testosterone (TT) < 2 ng/ml or if TT levels 2–4 ng/ml as calculated free testosterone < 6.36 ng/dl; Sertoli cell dysfunction was defined as inhibin‐B < 89 pg/ml. Secondary outcome‐associated factors were analysed by multiple logistic regression (odds ratio; 95% confidence interval [CI]). QOL was evaluated by SF‐36 v.2. Results: One hundred and forty‐three patients were evaluated at a median (interquartile range) of 77 days (72–83) after disease onset; 72% of them recovered from severe pneumonia. LT was detected in 41 patients (28.7%; 95% CI: 21.8–36.5). Low levels of inhibin‐B were detected in 25 patients (18.1%; 95% CI: 12.5–25.3). After multivariate adjustment, obesity and hypokalaemia were associated with LT, whereas age more than 65 was an independent predictor of Sertoli cell dysfunction. LT or Sertoli cell dysfunction was not associated with PCS. Patients with LT had a lower score in four domains of QOL. Conclusions: Prevalence of male LT and impaired fertility potential in COVID‐19 survivors is high in the medium term. Traditional risk factors and severity markers for COVID‐19 could be predictive. [ABSTRACT FROM AUTHOR]

Objectives: Frailty can be used as a predictor of adverse outcomes in people with coronavirus disease 2019 (COVID‐19). The aim of the study was to analyse the prognostic value of two different frailty scores in patients hospitalised for COVID‐19. Material and Methods: This retrospective cohort study included adult (≥18 years) inpatients with COVID‐19 and took place from 3 March to 2 May 2020. Patients were categorised by Clinical Frailty Score (CFS) and Hospital Frailty Risk Score (HFRS). The primary outcome was in‐hospital mortality, and secondary outcomes were tocilizumab treatment, length of hospital stay, admission in intensive care unit (ICU) and need for invasive mechanical ventilation. Results were analysed by multivariable logistic regression and expressed as odds ratios (ORs), adjusting for age, sex, kidney function and comorbidity. Results: Of the 290 included patients, 54 were frail according to the CFS (≥5 points; prevalence 18.6%, 95% confidence interval [CI]: 14.4‐23.7) vs 65 by HFRS (≥5 points; prevalence: 22.4%, 95% CI 17.8‐27.7). Prevalence of frailty increased with age according to both measures: 50‐64 years, CFS 1.9% vs HFRS 12.3%; 65‐79 years, CFS 31.5% vs HFRS 40.0%; and ≥80 years, CFS 66.7% vs HFRS 40.0% (P <.001). CFS‐defined frailty was independently associated with risk of death (OR 3.67, 95% CI 1.49‐9.04) and less treatment with tocilizumab (OR 0.28, 95% CI 0.08‐0.93). HFRS‐defined frailty was independently associated with length of hospital stay over 10 days (OR 2.89, 95% CI 1.53‐5.44), ICU admission (OR 4.18, 95% CI 1.84‐9.52) and invasive mechanical ventilation (OR 5.93, 95% CI 2.33‐15.10). Conclusion: In the spring 2020 wave of the COVID‐19 pandemic in Spain, CFS‐defined frailty was an independent predictor for death, while frailty as measured by the HFRS was associated with length of hospital stay over 10 days, ICU admission and use of invasive mechanical ventilation. [ABSTRACT FROM AUTHOR]

The medium‐term serologic response of SARS‐CoV‐2 infection recovered individuals is not well known. The aims were to quantify the incidence of seropositive failure in the medium term in a cohort of patients with different COVID‐19 severity and to analyze its associated factors. Patients who had recovered from mild and severe forms of SARS‐CoV‐2 infection in an Academic Spanish hospital (March 12–May 2, 2020), were tested for total anti‐SARS‐CoV‐2 antibodies by electrochemiluminescence immunoassay (Elecsys Anti‐SARS‐CoV‐2 test; Roche Diagnostics GmbH). The non‐seropositive status (seropositive failure) incidence (95% CI) was determined. Associations were tested by multiple logistic regression in a global cohort and severe pneumonia subpopulation. Of 435 patients with PCR‐confirmed SARS‐CoV‐2, a serological test was carried out in 325: 210 (64.6%) had severe pneumonia (hospitalized patients), 51 (15.7%) non‐severe pneumonia (managed as outpatients), and 64 (19.7%) mild cases without pneumonia. After a median (IQR) of 76 days (70–83) from symptom onset, antibody responses may not consistently develop or reach levels sufficient to be detectable by antibody tests (non‐seropositive incidence) in 6.9% (95% CI, 4.4–10.6) and 20.3% (95% CI, 12.2–31.7) of patients with and without pneumonia, respectively. Baseline independent predictors of seropositive failure were higher leukocytes and fewer days of symptoms before admission, while low glomerular filtrate and fever seem associated with serologic response. Age, comorbidity or immunosuppressive therapies (corticosteroids, tocilizumab) did not influence antibody response. In the medium‐term, SARS‐CoV‐2 seropositive failure is not infrequent in COVID‐19 recovered patients. Age, comorbidity or immunosuppressive therapies did not influence antibody response. [ABSTRACT FROM AUTHOR]

Introduction: This study analyzed the impact of a categorized approach, based on patients' prognosis, on major outcomes and explanators in patients hospitalized for COVID-19 pneumonia in an academic center in Spain. Methods: Retrospective cohort study (March 3 to May 2, 2020). Patients were categorized according to the followed clinical management, as maximum care or limited therapeutic effort (LTE). Main outcomes were all-cause mortality and need for invasive mechanical ventilation (IMV). Baseline factors associated with outcomes were analyzed by multiple logistic regression, estimating odds ratios (OR; 95%CI). Results: Thirty-hundred and six patients were hospitalized, median age 65.0 years, 57.8% males, 53.3% Charlson index ≥3. The overall all-cause fatality rate was 15.0% (n = 46). Maximum care was provided in 238 (77.8%), IMV was used in 38 patients (16.0%), and 5.5% died. LTE was decided in 68 patients (22.2%), none received IMV and fatality was 48.5%. Independent risk factors of mortality under maximum care were lymphocytes <790/mm3, troponin T >15ng/L and hypotension. Advanced age, lymphocytes <790/mm3 and BNP >240pg/mL independently associated with IMV requirement. Conclusion: Overall fatality in the cohort was 15% but markedly varied regarding the decided approach (maximum care versus LTE), translating into nine-fold higher mortality and different risk factors. [ABSTRACT FROM AUTHOR]

Aims/Purpose: Alzheimer's disease (AD) is a degenerative neurological disorder characterized by the progressive loss of neurons and their synapses in the brain. Similar alterations have been observed in the retina even before they manifest in the brain. The retina has been proposed as a readily accessible biomarker for AD. In a previous work utilizing a murine model of AD (APPNL‐F/NL‐F), changes in retinal thickness, as measured by optical coherence tomography (OCT), were observed at 15 and 17 months. The objective of this study was to quantitatively assess the population of retinal ganglion cells (RGCs) in this same AD murine model over a specified time period and compare it with wild‐type (WT) mice. Methods: To quantitatively assess the population of retinal ganglion cells we used two study groups: the APPNL‐F/NL‐F model throughout the time period of (6, 9, 12, 17, and 20 months) and compared with wild‐type (WT) mice age matched (n = 30 in both groups). The quantification of retinal ganglion cells (RGCs) was conducted using immunohistochemical analysis with the Brn3a marker. This analysis was performed using a semi‐automatic algorithm implemented in the MatLab environment, which was developed by the Ramón Castroviejo Institute for Ophthalmic Research. For the analysis, the entire retina was considered and segmented into the peripapillary, intermediate, and peripheral zones. Results: A statistically significant decresase (p < 0.05) in the population of Brn3a + cells was observed in the APPNL‐F/NL‐F group compared to the WT group. This decreased was found in the total retina at 12 months, in the peripapillary zone at 9, 12, and 20 months, and in the intermediate zone at 12 months of the study. Conclusions: The APPNL‐F/NL‐F mouse model exhibits RGCs loss at 9, 12, and 20 months, mirroring the patterns observed in human cases. These findings suggest that the model holds promise for investigating and studying mechanisms related to RGC degeneration in Alzheimer's disease. [ABSTRACT FROM AUTHOR]

Aims/Purpose: In addition to advanced age, two of the most important risk factors for the development of Alzheimer's disease are having a family history of the disease (FH+) and being a carrier of at least one Ɛ4+ allele for the ApoE gene (ApoE Ɛ4+). AD generates changes in the retina and visual function when the disease is established, so the aim of the present work is to know if these changes appear in healthy subjects but with high genetic risk to develop the disease and to analyse if these changes evolve along 27 months of follow‐up. Methods: A retinal thickness analysis by optical coherence tomography and visual function by assessing visual acuity (VA), contrast sensitivity (CS), colour perception, perception digital test and visual field analysis was completed by all participants. For structural findings analysis subjects were divided into (FH+ ApoE Ɛ4+) and (FH‐ ApoE Ɛ4‐) groups and for functional analysis these subgroups were subdivided by ages between 40 and 60 years and subjects over 60 years. Results: After 27 months of follow‐up, the FH+ ApoE Ɛ4+ group experienced changes in the thickness of all retinal layers except the outer layers. In this group, the inner nuclear layer showed progressing changes, but there was no progression in visual function. However, compared to the FH‐ ApoE Ɛ4‐ group at 27 months, the improvement in visual acuity and contrast sensitivity (3 and 12 cpd) observed during the initial visit was maintained. Conclusions: In cognitively healthy individuals at high risk of developing AD structural changes in the retina continue to progress after 27 months, while functional changes detected at the beginning remain stable. [ABSTRACT FROM AUTHOR]

Introduction: The essence of Enhanced Recovery After Surgery (ERAS) programs is the multimodal approach, and many authors have demonstrated safety and feasibility in fast track bariatric surgery. According to this concept, a multidisciplinary ERAS program for bariatric surgery has been developed by the Spanish Fast Track Group (ERAS Spain). The aim of this study was to analyze the initial implementation of this Spanish National ERAS protocol in bariatric surgery, comparing it with a historical cohort receiving standard care. Material and methods: A multi-centric prospective study was performed, including 233 consecutive patients undergoing bariatric surgery during 2015 and following ERAS protocol. It was compared with a historical cohort of 286 patients, who underwent bariatric surgery at the same institutions between 2013 and 2014 and following standard care. Compliance with the protocol, morbidity, mortality, hospital stay and readmission were evaluated. Results: Bariatric techniques performed were Roux-en-Y gastric bypass and sleeve gastrectomy. There were no significant differences in complications, mortality and readmission. Postoperative pain and hospital stay were significantly lower in the ERAS group. The total compliance to protocol was 80%. Conclusion: The Spanish National ERAS protocol is a safe issue, obtaining similar results to standard care in terms of complications, reoperations, mortality and readmissions. It is associated with less postoperative pain and earlier hospital discharge. [ABSTRACT FROM AUTHOR]

Purpose: To analyse the anti‐inflammatory effect of saffron extract, by regulating the expression of cytokines and chemokines involved in the neuroinflammatory process leading to retinal ganglion cell (RGC) damage, in a mouse model of unilateral laser‐induced ocular hypertension (OHT). Methods: Three groups of Albino Swiss mice treated with saffron extract were used; saffron naïve group (SNG), saffron laser group 1 day (SLG1d) and saffron laser group 3 days (SLG3d). Both eyes with OHT (treated with laser photocoagulation) and their contralateral were analysed. Retinal samples were processed and multiarray kits (MILLIPLEX MAP Mouse Cytokine/Myokine Magnetic Bead Panel) were used to quantify the expression of: IL‐1β, IL‐4, IL‐6, IL‐10, IL‐17, IFN‐ϒ, TNF‐α, Brain‐derived Neurotrophic Factor (BDNF), Vascular Endothelial Growth Factor (VEGF) and Fractalkine. Immunohistochemical analysis was performed to locate cells expressing the factors and cytokines detected in the multiplex assay. Results: After saffron treatment, no significant differences were found, at 1 and 3 days after laser‐induced OHT, between the concentration of proinflammatory cytokines (IL‐1β, IFN‐γ, TNF‐α and IL‐17), anti‐inflammatory cytokines (IL‐4 and IL‐10), BDNF, VEGF, and fractalkine in both the OHT eye and its contralateral eye, compared to saffron naïve. IL‐6 levels increased significantly in the OHT eye in SLG1d, reaching normal values at SLG3d compared to SNG. These results are contrary to those found in OHT eyes and their contralateral not treated with saffron, in which changes in cytokine levels were observed. Conclusions: Saffron is effective in regulating the production of proinflammatory cytokines, VEGF, and fractalkine induced by increased IOP, thus protecting the retina from its related damage. Saffron could be beneficial as coadjutant therapies in the treatment of glaucoma, thus helping to decrease the inflammatory process that occurs in this pathology. [ABSTRACT FROM AUTHOR]

Purpose: In addition to advanced age, genetic inheritance is another predisposing factor for the development of Alzheimer's disease (AD). Retinal changes already exist in preclinical stages, so the aim of this study was to analyse possible retinal changes in subjects at high risk of developing AD using OCT and correlate them with brain areas analysed by magnetic resonance imaging (MRI). Methods: Macular and peripapillary OCT and brain MRI were performed in 64 cognitively healthy subjects. 30 controls were subjects with no family history of AD and carrying no ApoE ɛ4 allele (FH− ApoE ɛ4−), while 34 subjects had an affected first‐degree relative and at least one ɛ4 allele (FH+ ApoE ɛ4+). Results: We observed in the FH+ ApoE ɛ4+ group compared to the control group a significant volume reduction in the following macular areas: (i) macular RNFL (mRNFL), (ii) inner plexiform layer (IPL); (iii) inner nuclear layer (INL) and (iv) outer plexiform layer (OPL). Moreover, in the FH+ ApoE ɛ4+ group the retinal sectors that showed a statistically significant decrease in volume correlated with brain areas that are affected in the early stages of AD, such as the lingual gyrus, the hippocampal region and the entorhinal cortex. In the same group, no statistically significant changes in thickness were found in the peripapillary retinal nerve fibre layer (pRNFL) compared to the control group. However, correlations of these sectors with brain areas involved in this pathology were also found. Conclusions: In cognitively healthy subjects at high genetic risk of developing sporadic forms of AD, there are significant correlations between the changes observed in the retina and brain areas closely related to AD, such as the lingual gyrus, the hippocampal area and the entorhinal cortex. [ABSTRACT FROM AUTHOR]

Purpose: To analyse morphological changes in retinal vascular network in 103 subjects with a high genetic risk of developing Alzheimer's Disease (AD) ((family history of AD(FH) and ApoE ɛ4 characterization (ApoE ɛ4)). Methods: OCTA images were analysed with two imaging software programs: AngioTool and Erlangen‐Angio‐Tool (EA‐Tool). Participating subjects were classified according to HF into HF− or HF+ and ApoE ɛ4 characterization into ApoE ɛ4− or ApoE ɛ4+. Vascular density was analysed considering two vascular risk factors: hypercholesterolemia (HCL) and arterial hypertension (HBP). Results: Taking account FH and allelic characterization, vascular changes were observed mainly in the peripapillary zone. In this zone, Angio‐Tool showed in the FH+ ApoE ɛ4− group a statistically significant higher of vessels surface area percentage compared to the FH+ ApoE ɛ4+ group. EA‐Tool showed in the C3 annulus in the FH+ ApoE ɛ4+ group, statistically significant higher vascular densities compared to the groups: (i) FH− ApoE ɛ4− in sectors H3, H4, H10, and H11; and (ii) FH+ ApoE ɛ4− in sectors H4, and H12. In participants with vascular risk factors (LCH and BPH), statistically significant changes were found especially with EA‐Tool, both in the macular area, mainly in the deep plexus, and in the peripapillary area. Conclusions: In subjects with two genetic risk factors for the development of AD, OCTA is able to show an apparent increase in vascular density in some sectors of the retina, probably caused by the opening of arteriovenous shunts. This finding is one of the first vascular changes detectable by OCTA in this type of high‐risk subjects for the development of AD. This constitutes a promising biomarker to monitor the progression of the disease. [ABSTRACT FROM AUTHOR]

Purpose: To study whether saffron extract supplementation can decrease microglial activation signs and reduce retinal ganglion cells (RGCs) loss in a glaucoma model. Methods: Albino Swiss mice groups; naïve (NG n = 6), saffron naïve (SNG n = 8), laser 3 days (LG3d n = 8), laser 7 days (LG7d n = 6), saffron laser 3 days (SLG3d n = 8) and saffron laser 7 days (SLG7d n = 6). In laser groups, unilateral ocular hypertension (OHT) was induced by OI laser photocoagulation. OHT and contralateral eyes were analysed. Retinal whole‐mounts were processed: (1) Anti Iba‐1 to quantify: Iba‐1 + cells number (Ibacn) in outer segments (OS), outer plexiform layer (OPL) and inner plexiform layer (IPL); Area of retina occupied by Iba‐1 + cells (Iba‐1 RA) in the nerve fiber layer‐ganglion cell layer (NFL‐GCL); Cell body area of Iba‐1+ cells (CbIbac) in OPL, IPL and NFL‐GCL; and Arbor area of Iba‐1+ cells (AAIbac) in OPL and IPL. (2) Anti‐P2RY12 for resident microglia. 3) Anti‐Brn3a to quantify Brn3a+ RGCs number. Results: No differences were found between naïve groups. LG3d OHT eyes showed significant: increase of Ibacn, Iba‐1 RA and CbIbac and decrease of AAIbac compared to NG. In SLG3d, OHT and contralateral eyes showed a significant reduction of microglial activation signs compared to LG3d. In NG all Iba‐1 + cells were P2RY12+. Compared to NG, in LG3d OHT eyes, the P2RY12 expression was down‐regulated. In SLG3d OHT eyes, saffron extract led to a smaller decrease. In contralateral eyes of LG3d and SLG3d, P2RY12 expression was similar to NG. In LG7d OHT eyes, a significant reduction in the number of Brn3a+ RGCs compared to NG was observed. Saffron extract counteracted this reduction and a significant different were found in SLG7d OHT eyes respect to LG7d OHT eyes. No differences were found between LG7d and SLG7d contralateral eyes. Conclusions: Saffron extract decreases the morphological signs of microglial activation, down‐regulation of P2RY12 and counteract the RCGs loss. Thus, they reduce neuroinflammation associated with IOP increase and protect RGCs. [ABSTRACT FROM AUTHOR]

Purpose: To quantify different morphological signs of microglial cells activation, as well as to analyze the P2RY12, MHC‐II and CD68 expression in 15‐month old mice , an early stage of aging (aged naïve) in comparison with a young adult mice (young naïve). Methods: Young naïve (n = 6) and aged naïve (n = 6) mice were analyzed. Retinal whole‐mounts were immunolabeled with: 1) anti Iba‐1 to quantify: i) Iba‐1 + cells number (Ibacn) in outer segments (OS), outer plexiform layer (OPL) and inner plexiform layer (IPL); ii) area of retina occupied by Iba‐1 + cells (Iba‐1 RA) in the nerve fiber layer‐ ganglion cell layer (NFL‐GCL) iii) cell body area of Iba‐1+ cells (CbIbac) in OPL, IPL and NFL‐GCL; iv) arbor area of Iba‐1+ cells (AAIbac) in OPL and IPL; number of vertical processes of Iba‐1+ cells (VPIbac) beetween the OS and OPL. 2) anti‐P2RY12 to identify resident microglia, anti‐CD68 and anti‐MHC‐II as a microglial activation marker. Results: In aged naïve with respect to young naïve the quantitative analysis showed: i) a non‐significant increase in the Ibacn in OS; ii) a non‐significant decrease in the AAIbac in OPL; iii) a significant increase in the CbIbac in OPL, IPL and NFL‐GCL and iv) a significant increase in the VPIbac. When we analyzed the expression of P2RY12, CD68 and MHC‐II we observed: i) in young naïve all Iba‐1+ cells were P2RY12+, except perivascular and dendritic cells, but in the aged naïve some cells were Iba‐1+/P2RY12‐; ii) in aged naïve numerous amoeboid‐like CD68+ cells were found while in the young naïve the expression of CD68 practically was absent, and iii) in both young naïve and aged naïve no expression of MHC‐II was observed. Conclusions: In 15‐month‐old mice, morphological changes and in the expression of P2RY12, CD68 and MHC‐II occurs in the microglial cells compared to young adult mice. These signs show a non‐pathological state of microglial activation that could influence of retinal age‐related disorders. [ABSTRACT FROM AUTHOR]

Purpose: Alzheimer's diseases (AD) is the most common cause of dementia characterized by a progressive decline in cognitive function, especially in the memory domain. It is known that its signs can appear decades before to clinical symptoms. In addition to age, genetic studies have identified an association between the presence of the Apoliprotein (ApoE) ɛ4 allele and family history of disease with the late‐onset AD. The aim of the present study was analyzed the possible changes that may occur in visual acuity (VA) and contrast sensitive test (CST) in young subjects with two marked genetic factors risk of developing Alzheimer's (AD): a first‐degree family history of the disease and being carrier of at least one e4 allele for the ApoE gene. Methods: A case‐control study was conducted in 28 subjects with family history of AD (FH+), ApoE ɛ4 carriers and with a mean age of 53.39 years and 16 age‐matched control subjects without a family history of AD (FH‐), ApoE ɛ4 non‐carriers and with a mean age of 53.94 years. A complete eye examination was performed in all participants, who were free of ocular pathology. Results: We found statistical significant increase (p < 0.05) in FH+ ApoE ɛ4 carriers compared to FH‐ ApoE ɛ4 non‐carriers in: I) VA (1.04 ± 0.10, FH+ vs 0.98 ± 0.04, FH‐) and II) CS in the spatial frequency (SF) of 12 cycles/degree (1.68 ± 0.18, FH+ vs 1.54 ± 0.17, FH‐). Conclusions: In FH+ ApoE ɛ4 carriers, the VA and CST registered changes compared to FH‐ ApoE ɛ4 non‐carriers. In young subjects at high genetic risk of developing AD, an increase of VA and CS in the 12 cicles/degree SF could be the first functional changes to appear. [ABSTRACT FROM AUTHOR]

A letter to the editor is presented discussing the strategies of preventing preanalytical false-positive increases of cardiac troponin I on the Unicel Dxl 800 analyzer.