Role of CB1 Cannabinoid Receptors in Vascular Responses and Vascular Remodeling of the Aorta in Female Mice.

Both the endocannabinoid system (ECS) and estrogens have significant roles in cardiovascular control processes. Cannabinoid type 1 receptors (CB1Rs) mediate acute vasodilator and hypotensive effects, although their role in cardiovascular pathological conditions is still controversial. Estrogens exert cardiovascular protection in females. We aimed to study the impact of ECS on vascular functions. Experiments were performed on CB1R knockout (CB1R KO) and wild-type (WT) female mice. Plasma estrogen metabolite levels were determined. Abdominal aortas were isolated for myography and histology. Vascular effects of phenylephrine (Phe), angiotensin II, acetylcholine (Ach) and estradiol (E2) were obtained and repeated with inhibitors of nitric oxide synthase (NOS, Nω-nitro-L-arginine) and of cyclooxygenase (COX, indomethacin). Histological stainings (hematoxylin-eosin, resorcin-fuchsin) and immunostainings for endothelial NOS (eNOS), COX-2, estrogen receptors (ER-α, ER-ß) were performed. Conjugated E2 levels were higher in CB1R KO compared to WT mice. Vasorelaxation responses to Ach and E2 were increased in CB1R KO mice, attenuated by NOS-inhibition. COX-inhibition decreased Phe-contractions, while it increased Ach-relaxation in the WT group but not in the CB1R KO. Effects of indomethacin on E2-relaxation in CB1R KO became opposite to that observed in WT. Histology revealed lower intima/media thickness and COX-2 density, higher eNOS and lower ER-ß density in CB1R KO than in WT mice. CB1R KO female mice are characterized by increased vasorelaxation associated with increased utilization of endothelial NO and a decreased impact of constrictor prostanoids. Our results indicate that the absence or inhibition of CB1Rs may have beneficial vascular effects.

[Modern views of fever management - about the FeverFriendTM program]. / A láz kezelésének modern szemléletérol a LázBarátTM program elso eredményeinek fényében.

INTRODUCTION: A wealth of physiological, pathophysiological and clinical evidence of the beneficial effects of childhood fever exists already. Nevertheless, the public perception of fever has become persistently negative. Sociological research attributes this to a number of factors: unjustified fear, help-seeking behaviour, complex behavioural patterns of symptom avoidance and comfort-seeking. One of the keys to this change in attitudes, in the light of recent research, is linked to changes in the awareness and understanding of health among health professionals and lay people. The role of the young generation using media is crucial. OBJECTIVE: To establish a long-term research project to reduce the use of medication (antipyretics and antibiotics) and the number of medical consultations and to improve attitudes towards fever, using media-based e-health tools. METHOD: An observational, adaptive, prospective cohort study was conducted. The intervention under study is a publicly available application and linked knowledge base. We collect self-reported data from caregivers. The application takes these into account and provides a decision-supporting condition classification based on a differential diagnosis algorithm. RESULTS: 1) The parameters, primary and secondary criteria to be captured in the application as well as the data collection and data processing methodology for the assessment were defined by 100% consensus of the expert partners in a Delphi process. 2) Based on the available national and international guidelines, the above parameters were used to create the condition assessment, decision aid algorithm, which can be a starting point for machine learning in the long term. 3) We evaluated baseline data on demographics, febrile events and antipyretic use from 01/11/2020 to 15/06/2022. CONCLUSION: The FeverFriendTM project can contribute to reduce the burden of medicalisation and care burden on the existing healthcare system through evidence-based modern fever management in the care of children and adults with fever. The impact of the FeverFriendTM program on target behavioural change needs to be further investigated through data analysis. Orv Hetil. 2023; 164(5): 179-185.

Atrophy of retinal vessels in neovascular age-related macular degeneration following long-term treatment with 20 intravitreal anti-VEGF injections.

BACKGROUND: The study aimed to evaluate the changes in retinal vascular density in exudative age-related macular degeneration (AMD) after long-term anti-VEGF treatment using optical coherence tomography angiography (OCT-A), and to compare these changes with the vascular density in AMD treated for one year and healthy eyes. METHODS: In our cross-sectional study OCT-A was performed on 60 eyes of 60 patients. Group AMD 20 × consisted of patients receiving long-term (minimum 20 injections) aflibercept therapy (n = 17), and Group AMD one year consisted of patients treated for one year with a treat & extend protocol (n = 25). The vascular density values obtained with OCT-A were compared with an age-matched control group of 18 healthy eyes. We examined the central retinal thickness (CRT), the vascular density of the fovea and parafovea in the superficial and deep retinal plexus, and evaluated the extent of the non-flow area and the foveal avascular zone (FAZ) on a 3 × 3 mm macular region. Kruskal-Wallis test was performed for statistical analysis. RESULTS: In Group AMD 20x, the vascular density of superficial retinal plexus in the fovea (p = 0.0022) and parafovea (p < 0.0001) was significantly lower compared to Group one year and control group. In the deep retinal plexus, vascular density in the fovea (p = 0.0033) was significantly lower in both AMD groups compared to the control group, with no difference in the parafoveal region (p = 0.0774). The extent of non-flow area (p = 0.0003) and FAZ (p = 0.0008) were significantly larger in both AMD groups compared to the control group. There was a significant difference in CRT between those treated for one year and control eyes (p = 0.0036). CONCLUSIONS: In our study, we demonstrated that macular vessel density was lower in the foveal area in the superficial retinal plexus in AMD patients after one year and long-term anti-VEGF treatment. These vascular density changes were absent in the parafoveal and whole areas of the deep retinal plexus. Our results indicate that long-term anti-VEGF treatment reduces the vascular density of the superficial retinal plexus to a greater extent compared to the deep retinal plexus.

Real-Time Analysis of Predictors of COVID-19 Infection Spread in Countries in the European Union Through a New Tool.

Objectives: Real-time data analysis during a pandemic is crucial. This paper aims to introduce a novel interactive tool called Covid-Predictor-Tracker using several sources of COVID-19 data, which allows examining developments over time and across countries. Exemplified here by investigating relative effects of vaccination to non-pharmaceutical interventions on COVID-19 spread. Methods: We combine >100 indicators from the Global COVID-19 Trends and Impact Survey, Johns Hopkins University, Our World in Data, European Centre for Disease Prevention and Control, National Centers for Environmental Information, and Eurostat using random forests, hierarchical clustering, and rank correlation to predict COVID-19 cases. Results: Between 2/2020 and 1/2022, we found among the non-pharmaceutical interventions "mask usage" to have strong effects after the percentage of people vaccinated at least once, followed by country-specific measures such as lock-downs. Countries with similar characteristics share ranks of infection predictors. Gender and age distribution, healthcare expenditures and cultural participation interact with restriction measures. Conclusion: Including time-aware machine learning models in COVID-19 infection dashboards allows to disentangle and rank predictors of COVID-19 cases per country to support policy evaluation. Our open-source tool can be updated daily with continuous data streams, and expanded as the pandemic evolves.

Association between retinal vessel density and postoperative time after primary repair of rhegmatogenous retinal detachment.

The study aimed at a quantitative evaluation of macular vasculature after primary repair of rhegmatogenous retinal detachment (RRD) in correlation with the elapsed postoperative time. Optical coherence tomography angiography (OCT-A) was performed in 66 eyes of 33 patients in a retrospective case-control study: superficial and deep retinal vessel density (VD) of the whole image, fovea, parafovea, non-flow area, and foveal avascular zone (FAZ) were measured. Data of eyes with RRD were compared to the healthy fellow eyes in 3 groups according to the elapsed time after surgery: RD1: 6-12 months (n = 10), RD2: 1-2 years (n = 10), and RD3: 2-10 years (n = 13). In RD1 VD was significantly lower in the superficial parafoveal, deep parafoveal, and deep whole area compared to the fellow eyes. In RD3 VD was significantly lower in the superficial fovea, parafovea, whole image, and deep fovea, the non-flow area was significantly enlarged. OCT-A demonstrated a significant reduction in the superficial and deep regions of the macular vasculature after the repair of RRD. The deep area is more affected in the early postoperative period and the superficial region and the extent of the non-flow area are more involved after a longer postoperative time.

Immunological biomarkers of the vitreous responsible for proliferative alteration in the different forms of retinal detachment.

BACKGROUND: The purpose of the study was to explore the immunological components that are responsible for the proliferative alterations in the different forms of retinal detachment (RD). METHODS: Vitreous fluids were collected during 23G pars plana vitrectomy from 54 eyes of 54 patients with different RD types, such as rhegmatogenous RD (RRD) without proliferative vitreoretinopathy (PVR) (n = 30), PVR (n = 16) and proliferative diabetic retinopathy (PDR) with tractional RD (n = 8). Vitreous fluids were obtained from 19 eyes with epiretinal membrane (ERM), which were used as control samples. A multiplex chemiluminescent immunoassay was performed to evaluate the concentrations of 48 cytokines, chemokines and growth factors. RESULTS: The expression levels of eotaxin, IFN-gamma, IL-6, IL-8, IL-16, MCP-1, MIF and MIP-1 beta were significantly higher in all RD groups than in the ERM group. The levels of CTACK, IP-10, SCGF-beta, and SDF-1 alpha were significantly higher in patients with diabetic tractional RD and PVR than in other patients. The upregulation of VEGF and IL-18 was detected in PDR. CONCLUSIONS: Our results indicate that complex and significant immunological mechanisms are associated with the pathogenesis of different forms of RD: selected cytokines, chemokines and growth factors are upregulated in the vitreous of eyes with RD. The detected proteins are present in different concentrations both in RRD and PVR. In the presence of PVR and PDR, the majority of cytokines are upregulated; thus, they may serve as biomarkers to estimate the progression or severity level of proliferation and later to develop personalized therapeutic strategies to slow down or prevent pathological changes.

Position of macula lutea and presence of proliferative vitreoretinopathy affect vitreous cytokine expression in rhegmatogenous retinal detachment.

Our purpose was to evaluate the concentrations of vitreous cytokines in patients with rhegmatogenous retinal detachment (RRD). We hypothesized that patients with macula on RRD have lower levels of cytokines compared to patients with macula off RRD and proliferative vitreoretinopathy (PVR). Vitreous fluids were collected during 23G pars plana vitrectomy from 58 eyes of 58 patients. Indication for vitrectomy included macula off and macula on RRD, PVR, and idiopathic epiretinal membrane (ERM). A multiplex chemiluminescent immunoassay was performed to measure the concentrations of 48 cytokines, chemokines, and growth factors. Levels of HGF, IL-6, IL-8, IL-16, IFN-gamma, MCP-1, and MIF were significantly higher in all groups of retinal detachment compared to ERM. Levels of CTACK, eotaxin, G-CSF, IP-10, MIG, SCF, SCGF-beta, SDF-1alpha were significantly higher in PVR compared to macula on RRD and ERM. Levels of IL-1ra, IL-5, IL-9, M-CSF, MIP-1alpha, and TRIAL were significantly higher in PVR compared to macula on RRD. Our results indicate that the position of macula lutea and the presence of PVR significantly influence vitreous cytokine expression. The detected proteins may serve as biomarkers to estimate the possibility of PVR formation and may help to invent personalized therapeutic strategies to slow down or prevent PVR.

Vascular density in age-related macular degeneration after one year of antiVEGF treatment with treat-and-extend and fixed regimens.

Treatment of neovascular age-related macular degeneration (nAMD) with VEGF can be performed with several posologies. The purpose of our cross-sectional study was to analyze retinal vessel density by quantitative OCT-angiography (OCT-A) and to compare treat-and-extend (T&E) and fixed treatment protocols to a control group with dry AMD. Altogether 48 patients were enrolled: 13 eyes with T&E protocol ranibizumab treatment (group A) and 17 eyes with fixed regimen aflibercept therapy (group B), the control group comprised 18 eyes with dry AMD (group C). One year after the start of the treatment, quantitative OCT-A (AngioVue-Optovue, Fermont, USA) was performed: superficial and deep retinal vessel densities were analyzed in the foveal and parafoveal regions. Our results show, that the density of retinal superficial vasculature in the fovea was not different between the treatment groups (A: 25.9±9.1%; B: 24.3%±8.9), neither from group C (25.6±4.8%). Superficial parafoveal vascular density of the retina, however, was decreased in both treated groups (A: 46.7±9.1%, B: 42.9±6.1%, C: 49.7±4.9%). In the deep retinal plexus, vascular density was lower in both treatment groups compared to that of in controls in both the foveal and parafoveal area (A: 29.8±6.3%, B: 32.5±6.9%, C: 36.4±1.7% and A: 46.3±3.8%, B: 47.1±5.3%, C: 49.7±4.9%, foveal and parafoveal respectively). Our data suggest, that after one year of anti-VEGF treatment, reduced macular vessel density in three of the four examined vascular regions can be found independent of the treatment regimen.

Vitrectorhexis in penetrating eye injuries in adults.

INTRODUCTION: Vitrectorhexis is an alternative for manual continuous curvilinear capsulorhexis originally developed for paediatric cataract surgery. The aim of our study was the evaluation of the technique in adult patients with penetrating ocular injury and traumatic cataracts. METHODS: Eight eyes of 8 patients (23-41 years, all males) had penetrating mechanical corneal trauma. Anterior lens capsule was penetrated in all cases and additional posterior capsule defect in five cases. Intraocular foreign body was detected in one case in the crystalline lens and in two cases in the posterior segment. Standard 23G infusion cannula and vitreous cutter were applied to perform anterior capsule opening, removal of lens material, anterior vitrectomy and pars plana vitrectomy if needed. No phacoemulsification or irrigation/aspiration probe was used. RESULTS: Vitrectorhexis could be performed in 7 out of 8 cases with the preservation of peripheral anterior capsule; primary implantation of posterior chamber intraocular lens was possible in all cases (in the bag in three eyes and into the sulcus in five eyes). Anterior chamber was stable in all cases intraoperatively, and no dropped nucleus or lens fragment loss was observed. Surgery was combined with pars plana vitrectomy in three cases, with foreign body removal (when necessary). No postoperative complication occurred. CONCLUSION: Vitrectorhexis was found to be an effective and safe alternative method in the management of complex anterior segment trauma cases. With its use, traditional cataract surgical devices can be substituted and additional benefits of vitreous cutter can be utilized in selected cases, especially in young adults.

[Angiography of the ocular fundus without dye: Optical coherence tomography based angiography in exsudative age-related macular degeneration]. / Szemfenéki érfestés festék nélkül: Az optikai koherencia tomográfia alapú angiográfia exsudativ típusú idoskori maculadegenerációban.

INTRODUCTION: Vascular endothelial growth factor antibody therapy is an established treatment of exsudative age-related macular degeneration. AIM: The morphologic characterisation of the macular microvasculature after longstanding treatment. METHOD: Forty-eight patients (34 women and 14 men; age, 74.4 ± 8.0 years) were enrolled in the study. During follow-up time (53.8 ± 31.0 months), 7.6 ± 4.9 injections were administered in 56 eyes. Optical coherence tomography angiographic examination was performed with AngioVue (Optovue Inc. Fremont, CA, USA). RESULTS: Distortion of the superficial retinal plexus and foveal avascular zone enlargement were noted in 5/56 eyes, deep retinal plexus defect was detected in 9/56 cases. Destruction of the choriocapillaries and the former neovascularisation could be found in 4 different patterns: 1. pigment epithelium and choriocapillary atrophy, 2. submacular scar, 3. active leaking choroidal neovascularisation, 4. intraretinal cysts. CONCLUSION: Optical coherence tomography angiography is a novel non-invasive method, which enables the follow up of macular degeneration. Orv. Hetil., 2016, 157(42), 1683-1690.

High rate of neoplastic cells with genetic abnormalities in proliferation centers of chronic lymphocytic leukemia.

In lymph nodes, chronic lymphocytic leukemia (CLL) cells (prolymphocytes and paraimmunoblasts) form proliferation centers (PCs), which are also known as pseudofollicles. To reveal whether PCs play a role in the accumulation of genetic alterations in CLL, we compared deletion at 11q22.3, 13q14.3, and 17p13.1 loci and trisomy 12 by the fluorescence in situ hybridization (FISH) technique in PCs versus surrounding small lymphocytes (SLs) in 12 formalin-fixed paraffin-embedded (FFPE) lymph nodes. The FFPE sections were stained with methylene blue and PCs were marked by laser beam. Subsequent FISH analysis was performed, relocalizing the previously defined regions. Loss of 11q was detected in five cases, loss of 13q in two cases, loss of 17p in two cases, and trisomy 12 in one case. In seven cases PCs contained a significantly higher ratio of cells with genetic alterations compared with the surrounding SLs. Our results show that CLL cells with genetic alterations tend to accumulate in PCs. The clonal expansion of the cell population carrying genetic alterations within PCs may contribute to CLL progression.