Assessment of inner retinal layers and choroidal thickness in type 1 diabetes mellitus: a cross-sectional study

Choroid; Diabetic retinopathy; Ganglion cell layerCoroides; Retinopatía diabética; Capa de células ganglionaresCoroide; Retinopatia diabètica; Capa de cèl·lules ganglionàriesRecent studies have shown that retinal neurodegeneration may precede visible vascular changes in diabetic retinopathy (DR). In addition, the relationship of choroidal thickness (CT) with DR stage is not well defined. To assess the inner retinal and choroidal structural changes in type 1 diabetic subjects (T1D), a cross-sectional study was conducted in 242 T1D patients and in 69 age-matched, non-diabetic individuals. The nasal retinal nerve fibre layer (RNFL) thickness was lower in T1D patients without DR (p < 0.001), with mild DR (p < 0.001), and with advanced DR (p < 0.001) compared to control subjects. The ganglion cell layer (GCL) thickness was lower in T1D patients with advanced DR compared to those with mild DR (p = 0.003) and without DR (p < 0.001) and compared to the control subjects (p < 0.001). T1D subjects with no DR and mild DR had higher CT than the control subjects, but the CT in T1D patients with advanced DR was lower (p = 0.038) than that in T1D subjects with mild DR and was not significantly different from that of the control subjects. In conclusion, T1D subjects showed a significant thinning of the nasal RNFL in the early stages of the disease, even before any vascular changes in the retina. A decrease in the GCL thickness during advanced DR stages was observed. Choroidal thickness was higher in T1D subjects without DR and in early DR stages but decreased in advanced stages.This research was supported by grants from the Spanish Ministry of Health, the Carlos III National Institute of Health (PI12/0183 and PI15/0625) and the European Regional Development Fund (ERDF). CIBER for Diabetes and Associated Metabolic Diseases (CIBERDEM) is an initiative of ISCIII, Spain. The Health Sciences Research Institute Germans Trias i Pujol is part of the CERCA Programme/Generalitat de Catalunya

Decreased quality of live and treatment satisfaction in patients with latent autoinmune diabetes of the adult

Objectives. Our main aim was to assess the quality of life (QoL) and treatment satisfaction (TS) of subjects with LADA (latent autoimmune diabetes of the adult) and compare these measures with those of patients with other diabetes types, i.e., type 1 (T1DM) and type 2 diabetes mellitus (T2DM). Methods. This was a cross-sectional study with a total of 48 patients with LADA, 297 patients with T2DM and 124 with T1DM. The Audit of Diabetes-Dependent Quality of Life (ADDQoL-19) questionnaire and the Diabetes Treatment Satisfaction Questionnaire (DTSQ) were administered. Relevant clinical variables were also assessed. The data analysis included comparisons between groups and multivariate linear models. Results. The LADA patients presented lower diabetes-specific QoL (p D 0:045) and average weighted impact scores (p D 0:007) than the T2DM patients. The subgroup of LADA patients with diabetic retinopathy (DR) who were treated with insulin had a lowerADDQoLaverage weighted impact score than the other diabetic groups. Although the overall measure of TS was not different between the LADA and T2DM (pD0:389) and T1DM (pD0:091) groups, the patients with LADA showed a poorer hyperglycemic frequency perception than the T2DM patients (p<0:001) and an improved frequency of hypoglycemic perception compared with the T1DM patients (pD0:021). Conclusions. The current findings suggest a poorer quality of life, especially in terms of DRand insulin treatment, among patients with LADA compared with those withT1DM and T2DM. Hyperglycemia frequency perception was also poorer in the LADA patients than in the T1DM and T2DM patients. Further research with prospective studies and a large number of patients is necessary.This study was supported by grant PS09/01035 and PI12/00183 from the Instituto de Salud Carlos III, Ministry of Economy and Competitiveness, Spain. CIBERDEM is an initiative from Instituto de Salud Carlos III (Plan Nacional de I+D+I and Fondo Europeo de Desarrollo Regional). MGC holds a predoctoral fellowship from the Ministerio de Educación, Cultura y Deporte (FPU15/03005)

Assessment of Inner Retinal Layers and Choroidal Thickness in Type 1 Diabetes Mellitus: A Cross-Sectional Study

Recent studies have shown that retinal neurodegeneration may precede visible vascular changes in diabetic retinopathy (DR). In addition, the relationship of choroidal thickness (CT) with DR stage is not well defined. To assess the inner retinal and choroidal structural changes in type 1 diabetic subjects (T1D), a cross-sectional study was conducted in 242 T1D patients and in 69 age-matched, non-diabetic individuals. The nasal retinal nerve fibre layer (RNFL) thickness was lower in T1D patients without DR (p < 0.001), with mild DR (p < 0.001), and with advanced DR (p < 0.001) compared to control subjects. The ganglion cell layer (GCL) thickness was lower in T1D patients with advanced DR compared to those with mild DR (p = 0.003) and without DR (p < 0.001) and compared to the control subjects (p < 0.001). T1D subjects with no DR and mild DR had higher CT than the control subjects, but the CT in T1D patients with advanced DR was lower (p = 0.038) than that in T1D subjects with mild DR and was not significantly different from that of the control subjects. In conclusion, T1D subjects showed a significant thinning of the nasal RNFL in the early stages of the disease, even before any vascular changes in the retina. A decrease in the GCL thickness during advanced DR stages was observed. Choroidal thickness was higher in T1D subjects without DR and in early DR stages but decreased in advanced stages.This research was supported by grants from the Spanish Ministry of Health, the Carlos III National Institute of Health (PI12/0183 and PI15/0625) and the European Regional Development Fund (ERDF). CIBER for Diabetes and Associated Metabolic Diseases (CIBERDEM) is an initiative of ISCIII, Spain. The Health Sciences Research Institute Germans Trias i Pujol is part of the CERCA Programme/Generalitat de Catalunya

Role of the Scavenger Receptor CD36 in Accelerated Diabetic Atherosclerosis

Diabetes mellitus entails increased atherosclerotic burden and medial arterial calcification, but the precise mechanisms are not fully elucidated. We aimed to investigate the implication of CD36 in inflammation and calcification processes orchestrated by vascular smooth muscle cells (VSMCs) under hyperglycemic and atherogenic conditions. We examined the expression of CD36, pro-inflammatory cytokines, endoplasmic reticulum (ER) stress markers, and mineralization-regulating enzymes by RT-PCR in human VSMCs, cultured in a medium containing normal (5 mM) or high glucose (22 mM) for 72 h with or without oxidized low-density lipoprotein (oxLDL) (24 h). The uptake of 1,1'-dioctadecyl-3,3,3',3-tetramethylindocarbocyanine perchlorate-fluorescently (DiI) labeled oxLDL was quantified by flow cytometry and fluorimetry and calcification assays were performed in VSMC cultured in osteogenic medium and stained by alizarin red. We observed induction in the expression of CD36, cytokines, calcification markers, and ER stress markers under high glucose that was exacerbated by oxLDL. These results were confirmed in carotid plaques from subjects with diabetes versus non-diabetic subjects. Accordingly, the uptake of DiI-labeled oxLDL was increased after exposure to high glucose. The silencing of CD36 reduced the induction of CD36 and the expression of calcification enzymes and mineralization of VSMC. Our results indicate that CD36 signaling is partially involved in hyperglycemia and oxLDL-induced vascular calcification in diabetes

Poorer Quality of Life and Treatment Satisfaction is Associated with Diabetic Retinopathy in Patients with Type 1 Diabetes without Other Advanced Late Complications

Diabetic retinopathy (DR) may potentially cause vision loss and affect the patient's quality of life (QoL) and treatment satisfaction (TS). Using specific tools, we aimed to assess the impact of DR and clinical factors on the QoL and TS in patients with type 1 diabetes. This was a cross-sectional, two-centre study. A sample of 102 patients with DR and 140 non-DR patients were compared. The Audit of Diabetes-Dependent Quality of Life (ADDQoL-19) and Diabetes Treatment Satisfaction Questionnaire (DTSQ-s) were administered. Data analysis included bivariate and multivariable analysis. Patients with DR showed a poorer perception of present QoL (p = 0.039), work life (p = 0.037), dependence (p = 0.010), and had a lower average weighted impact (AWI) score (p = 0.045). The multivariable analysis showed that DR was associated with a lower present QoL (p = 0.040), work life (p = 0.036) and dependence (p = 0.016). With regards to TS, DR was associated with a higher perceived frequency of hypoglycaemia (p = 0.019). In patients with type 1 diabetes, the presence of DR is associated with a poorer perception of their QoL. With regard to TS, these subjects also show a higher perceived frequency of hypoglycaemia.This study was supported by the Catalan Diabetes Association (Beca d’Educació Terapèutica 2015), Spain. Additional support from grants PI12/00183 and PI15/00625 from the Instituto de Salud Carlos III (Ministry of Economy and Competitiveness, Spain) to DM is acknowledged. CIBERDEM is an initiative from the Instituto de Salud Carlos III (Plan Nacional de I + D + I and Fondo Europeo de Desarrollo Regional). M.G.-C. holds a predoctoral fellowship from the Ministerio de Educación, Cultura y Deporte, FPU15/03005

Calcium phosphate product is associated with subclinical carotid atherosclerosis in type 2 diabetes

Aims. To assess whether circulating 25-hydroxyvitamin D3 (25OHD) and mineral metabolism-related factors (serum phosphate, calcium, and parathormone) are associated with subclinical carotid atherosclerosis (SCA), defined as the presence of carotid atherosclerotic plaques (main study outcome), in patients with type 2 diabetes mellitus (T2DM) without kidney disease or previous cardiovascular disease. Methods. We undertook a post hoc analysis of a cross-sectional study in adults with T2DM in whom we evaluated SCA. A total of 303 subjects with T2DM were included. Clinical variables and carotid ultrasound imaging were obtained. Results. We found no association of 25OHD with the presence of SCA. However, calcium phosphate (CaP; mg2/dL2) product was positively associated with the presence of carotid plaques (ORadj = 1.078; 95% CI: 1.017–1.142). An inverse association was observed between higher levels of 25OHD (≥30 ng/mL versus <20 ng/mL concentrations) and common carotid intima-media thickness (cIMT; mm) (βadj ± SE = −0.055 ± 0.024). We conclude that the CaP product is independently associated with the presence of established subclinical carotid atherosclerosis in patients with T2DM.This study was supported by Grants PS09/01035 and PI15/ 00625 from Instituto de Salud Carlos III, Ministry of Economy and Competitiveness, Spain. CIBERDEM is an initiative from Instituto de Salud Carlos III (Plan Nacional de I+D+I and Fondo Europeo de Desarrollo Regional). Minerva Granado-Casas holds a predoctoral fellowship from Ministerio de Educación, Cultura y Deporte, FPU15/03005

High-titre methylene blue-treated convalescent plasma as an early treatment for outpatients with COVID-19: a randomised, placebo-controlled trial.

BACKGROUND: Convalescent plasma has been proposed as an early treatment to interrupt the progression of early COVID-19 to severe disease, but there is little definitive evidence. We aimed to assess whether early treatment with convalescent plasma reduces the risk of hospitalisation and reduces SARS-CoV-2 viral load among outpatients with COVID-19. METHODS: We did a multicentre, double-blind, randomised, placebo-controlled trial in four health-care centres in Catalonia, Spain. Adult outpatients aged 50 years or older with the onset of mild COVID-19 symptoms 7 days or less before randomisation were eligible for enrolment. Participants were randomly assigned (1:1) to receive one intravenous infusion of either 250-300 mL of ABO-compatible high anti-SARS-CoV-2 IgG titres (EUROIMMUN ratio ≥6) methylene blue-treated convalescent plasma (experimental group) or 250 mL of sterile 0·9% saline solution (control). Randomisation was done with the use of a central web-based system with concealment of the trial group assignment and no stratification. To preserve masking, we used opaque tubular bags that covered the investigational product and the infusion catheter. The coprimary endpoints were the incidence of hospitalisation within 28 days from baseline and the mean change in viral load (in log10 copies per mL) in nasopharyngeal swabs from baseline to day 7. The trial was stopped early following a data safety monitoring board recommendation because more than 85% of the target population had received a COVID-19 vaccine. Primary efficacy analyses were done in the intention-to-treat population, safety was assessed in all patients who received the investigational product. This study is registered with ClinicalTrials.gov, NCT04621123. FINDINGS: Between Nov 10, 2020, and July 28, 2021, we assessed 909 patients with confirmed COVID-19 for inclusion in the trial, 376 of whom were eligible and were randomly assigned to treatment (convalescent plasma n=188 [serum antibody-negative n=160]; placebo n=188 [serum antibody-negative n=166]). Median age was 56 years (IQR 52-62) and the mean symptom duration was 4·4 days (SD 1·4) before random assignment. In the intention-to-treat population, hospitalisation within 28 days from baseline occurred in 22 (12%) participants who received convalescent plasma versus 21 (11%) who received placebo (relative risk 1·05 [95% CI 0·78 to 1·41]). The mean change in viral load from baseline to day 7 was -2·41 log10 copies per mL (SD 1·32) with convalescent plasma and -2·32 log10 copies per mL (1·43) with placebo (crude difference -0·10 log10 copies per mL [95% CI -0·35 to 0·15]). One participant with mild COVID-19 developed a thromboembolic event 7 days after convalescent plasma infusion, which was reported as a serious adverse event possibly related to COVID-19 or to the experimental intervention. INTERPRETATION: Methylene blue-treated convalescent plasma did not prevent progression from mild to severe illness and did not reduce viral load in outpatients with COVID-19. Therefore, formal recommendations to support the use of convalescent plasma in outpatients with COVID-19 cannot be concluded. FUNDING: Grifols, Crowdfunding campaign YoMeCorono

Prospective individual patient data meta-analysis of two randomized trials on convalescent plasma for COVID-19 outpatients

Data on convalescent plasma (CP) treatment in COVID-19 outpatients are scarce. We aimed to assess whether CP administered during the first week of symptoms reduced the disease progression or risk of hospitalization of outpatients. Two multicenter, double-blind randomized trials (NCT04621123, NCT04589949) were merged with data pooling starting when = 50 years and symptomatic for <= 7days were included. The intervention consisted of 200-300mL of CP with a predefined minimum level of antibodies. Primary endpoints were a 5-point disease severity scale and a composite of hospitalization or death by 28 days. Amongst the 797 patients included, 390 received CP and 392 placebo; they had a median age of 58 years, 1 comorbidity, 5 days symptoms and 93% had negative IgG antibody-test. Seventy-four patients were hospitalized, 6 required mechanical ventilation and 3 died. The odds ratio (OR) of CP for improved disease severity scale was 0.936 (credible interval (CI) 0.667-1.311); OR for hospitalization or death was 0.919 (CI 0.592-1.416). CP effect on hospital admission or death was largest in patients with <= 5 days of symptoms (OR 0.658, 95%CI 0.394-1.085). CP did not decrease the time to full symptom resolution

Motivation for Vaccination against COVID-19 in Persons Aged between 18 and 60 Years at a Population-Based Vaccination Site in Manresa (Spain)

Our purpose was to identify the reasons why members of the population, aged 18–60 years, are vaccinated against COVID-19 at the mass vaccination point in Bages, Spain. This is 1 of 42 provisional spaces outside of health centres which have been set up in Catalonia in the context of the COVID-19 pandemic, and where people from all over Catalonia could go to be vaccinated by appointment. Methodology: We performed a cross-sectional study of users attending mass vaccination points in Bages during the months of July, August, and September 2021. Results: A total of 1361 questionnaires were statistically analysed. The most common reasons for vaccination were fear of infecting family (49.52%) and fear of self-infection (39.45%), followed by socialising (31.00%) and travel (30.56%). However, by applying a logistic regression model to each reason for vaccination, it was possible to estimate the associations regarding age, sex, marital status, educational level, production sector, mass vaccination point, previous COVID-19 infection, and COVID-19 infection of a family member. Relevance: The data generated will inform decisions and formulations of appropriate campaigns that will promote vaccination in specific population groups