Vascular Alterations Research Articles

P197 PULSE WAVE ANALYSIS IN POST COVID PATIENTS WITH AND WITHOUT DE NOVO ARTERIAL HYPERTENSION. HOSPITAL UNIVERSITARIO DE LOS ANDES (HULA) VENEZUELA. 2021-2023

Background and Objective: COVID 19 infection is characterized by an acute respiratory process that can range from mild to severe and has been related to short- and long-term complications. Post COVID 19 syndrome has been described among these long-term complications, where alterations in pulse wave velocity define vascular alteration, increasing risk of systemic arterial hypertension. The objective is analyze pulse wave velocity and arterial stiffness in post-COVID 19 patients with and without de novo arterial hypertension at the HULA, Venezuela between 2021-2023. Methods: Observational case-control study on pulse wave velocity in post-COVID-19 patients with and without de novo arterial hypertension in the HULA post-COVID-19 consultation, 2021-2023. Results: The sample consisted of 90 patients: 30 cases and 60 controls, there was no statistically significant difference in variables such as sex, body mass index (BMI) and abdominal circumference between both cohorts, with a predominance of the age group between 35 to 49 years with 33.3%, and less frequency at the extremes of life, where the group of 18-34 years and over 65 corresponded to 20%, there was a statistically significant association between syndrome post COVID 19 and arterial stiffness, the risk of de novo arterial hypertension was found to be 4.9 times and 7.9 times higher in the small and large vessel arterial stiffness group compared to the group without arterial stiffness, respectively. Conclusions: It is impressive that the age group between 35 and 49 years has a higher risk of developing arterial hypertension associated with COVID 19, the alteration of pulse wave analysis in the patients in the consultation post COVID 19 was associated with a higher risk of developing de novo arterial hypertension compared to those who did not present alterations.

Association of microaneurysms with retinal vascular alterations in patients with retinal vein occlusion

ObjectiveTo investigate the localization, distribution, and type of central microaneurysms (MAs) and their relationship with retinal vascular alterations in patients with retinal vein occlusion (RVO). MethodsIn this cross-sectional study, ultra-widefield color fundus photography (UWF-CF), standard and single-capture 65° widefield (WF) optical coherence tomography angiography (OCTA) were performed in consecutive patients with RVO treated at the Department of Ophthalmology and Optometry, Medical University of Vienna. UWF-CF, en face and B-Scans in 6 mm × 6 mm OCTA were examined for detection of MAs. Nonperfusion areas (NPA) and collateral vessels (CV) were evaluated on WF-OCTA, ghost vessels (GV), and tortuous vessels (TV) on UWF-CF. ResultsOne-hundred-and-twelve patients were included in the study, and data from 59 eyes of 59 patients with disease duration longer than 3 months, good image quality, and without relevant ocular comorbidities were eligible for statistical analysis. Fifty-six of 59 (94.9%) patients were previously treated with anti-vascular endothelial growth factor agents for macular edema, 31 of 59 (52.5%) patients presented with MAs in the central 6 mm and 60 MAs were found in total using multimodal imaging. There was no statistically significant difference in the greatest diameter of fluid-associated versus non-fluid-associated MAs (p = 0.53). Eyes with MAs were associated with CV, TV, and GV (χ2-test; p < 0.001, p = 0.0498, and p = 0.001). Median NPA was 27.3 mm2 (quartiles 1.3–62.8 mm2) in eyes with MAs and 0 mm2 (quartiles 0–36.2 mm2) in eyes without MAs (Mann-Whitney-U-test; p = 0.018). ConclusionMAs were associated with extensive NPA, the presence of CV, GV, and TV. There was no correlation between the diameter of the MA and the adjacent intraretinal fluid in our predominantly pretreated RVO study patients.

A gender-based analysis of retinal microvascular alterations in patients with diabetes mellitus using OCT angiography

PurposeTo assess the difference in microvascular changes between males and females with diabetes mellitus (DM) without diabetic retinopathy (NoDR) and with mild-to-moderate non-proliferative diabetic retinopathy (NPDR) using Optical Coherence Tomography Angiography (OCT-A). DesignRetrospective cross-sectional study. Methods267 DM patients, 133 females (49.81 %), 111 with NoDR (41.57 %) and 156 NPDR (58.43 %) were included. Foveal-centered 3 × 3 mm OCT-A images corresponding to the superficial (SCP), intermediate (ICP) and deep capillary plexus (DCP), and full retinal (RET) slab were used for analysis. For each slab, FAZ area, perimeter, and circularity index (CI) were determined, following manual delineation of the FAZ; perfusion (PD) and vessel density (VD), fractal dimension (FD), vessel length density (VLD), geometric perfusion deficits (GPD) were also computed. Flow voids (FV) were determined in the choriocapillaris plexus; and perfused capillary density (PCD) in the RET slab. ResultsFemales showed larger FAZ CI in SCP and greater FAZ area and perimeter than males in NPDR group. Males had higher central macular thickness than females in NPDR group. All density metrics at the level of ICP and DCP were affected in the NPDR group with no gender differences. Of note, the same significant findings were found in type 1 DM patients, and not in type 2 DM patients. ConclusionsOur OCT-A findings suggest significant microvascular changes in females with NPDR compared to males, but no such differences in patients without DR. Therefore, gender-related vascular alterations might be present in early stages of DR with potential role.

Geographic Atrophy-associated Intraretinal Neovascularization (GAIN): A novel clinical entity.

KEY MESSAGES : WHAT IS KNOWN : Geographic atrophy could be associated with MNV or other vascular alterations. Intraretinal fluid could be present in GA also without neovascularization. WHAT IS NEW : GAIN is a novel clinical entity characterized by GA and an intraretinal neovascular network. GAIN could be exudative or non-exudative.

Differential Analysis of Venous Sinus Diameters: Unveiling Vascular Alterations in Patients with Multiple Sclerosis.

Alterations in the cerebral venous system have been increasingly recognized as a significant component of the pathophysiology of multiple sclerosis (MS). This study aimed to explore the relationship between venous sinus diameter and MS to understand potential vascular alterations in MS patients compared with controls. We sought to determine whether these alterations were correlated with disease characteristics such as duration, lesion type, and disability score. This study included 79 MS patients diagnosed according to the 2017 McDonald criteria and 67 healthy individuals. Magnetic resonance imaging (MRI) scans via a 1.5 Tesla system provided measurements of the superior sagittal sinus, right and left transverse sinus, sinus rectus, and venous structures. Statistical analysis was conducted via SPSS, employing independent sample t tests, ANOVA, chi-square tests, and Pearson correlation analysis, with the significance level set at p < 0.05. This study revealed significant differences in venous sinus diameter between MS patients and controls, with MS patients exhibiting larger diameters. Specifically, patients with brainstem and spinal lesions had larger diameters in certain sinus regions. No significant correlations were found between venous sinus diameter and demographic factors, expanded disability status scale scores, or lesion counts. However, a significant increase in perivenular lesions was noted in patients with longer disease durations. The findings indicate notable vascular alterations in MS patients, particularly in venous sinus diameters, suggesting a potential vascular component in MS pathology. The lack of correlation with conventional clinical and MRI metrics highlights the complexity of MS pathology. These insights underscore the need for further research, particularly longitudinal studies, to elucidate the role of venous changes in MS progression and their potential as therapeutic targets.

Associations of Cerebral Blood Flow Patterns With Gray and White Matter Structure in Patients With Temporal Lobe Epilepsy.

Neuroimaging studies in patients with temporal lobe epilepsy (TLE) show widespread brain network alterations beyond the mesiotemporal lobe. Despite the critical role of the cerebrovascular system in maintaining whole-brain structure and function, changes in cerebral blood flow (CBF) remain incompletely understood in the disease. Here, we studied whole-brain perfusion and vascular network alterations in TLE and assessed its associations with gray and white matter compromises and various clinical variables. We included individuals with and without pharmaco-resistant TLE who underwent multimodal 3T MRI, including arterial spin labelling, structural, and diffusion-weighted imaging. Using surface-based MRI mapping, we generated individualized cortico-subcortical profiles of perfusion, morphology, and microstructure. Linear models compared regional CBF in patients with controls and related alterations to morphological and microstructural metrics. We further probed interregional vascular networks in TLE, using graph theoretical CBF covariance analysis. The effects of disease duration were explored to better understand the progressive changes in perfusion. We assessed the utility of perfusion in separating patients with TLE from controls using supervised machine learning. Compared with control participants (n = 38; mean ± SD age 34.8 ± 9.3 years; 20 females), patients with TLE (n = 24; mean ± SD age 35.8 ± 10.6 years; 12 females) showed widespread CBF reductions predominantly in fronto-temporal regions (Cohen d -0.69, 95% CI -1.21 to -0.16), consistent in a subgroup of patients who remained seizure-free after surgical resection of the seizure focus. Parallel structural profiling and network-based models showed that cerebral hypoperfusion may be partially constrained by gray and white matter changes (8.11% reduction in Cohen d) and topologically segregated from whole-brain perfusion networks (area under the curve -0.17, p < 0.05). Negative effects of progressive disease duration further targeted regional CBF profiles in patients (r = -0.54, 95% CI -0.77 to -0.16). Perfusion-derived classifiers discriminated patients from controls with high accuracy (71% [70%-82%]). Findings were robust when controlling for several methodological confounds. Our multimodal findings provide insights into vascular contributions to TLE pathophysiology affecting and extending beyond mesiotemporal structures and highlight their clinical potential in epilepsy diagnosis. As our work was cross-sectional and based on a single site, it motivates future longitudinal studies to confirm progressive effects, ideally in a multicentric setting.

Rosacea in East Asian populations: Clinical manifestations and pathophysiological perspectives for accurate diagnosis.

Rosacea is a chronic inflammatory disorder primarily affecting the facial skin, prominently involving the cheeks, nose, chin, forehead, and periorbital area. Cutaneous manifestations encompass persistent facial erythema, phymas, papules, pustules, telangiectasia, and flushing. The pathogenesis of rosacea is associated with various exacerbating or triggering factors, including microbial infestation, temperature fluctuations, sunlight exposure, physical exertion, emotional stress, consumption of hot beverages and spicy foods, and exposure to airborne pollen. These environmental factors interact with genetic predispositions in the development of rosacea. The roles of the lipophilic microbiome, ultraviolet radiation, nociceptive responses, and vascular alterations have been proposed as significant factors in the pathogenesis. These insights contribute to understanding the anatomical specificity of facial involvement and the progressive nature of rosacea. East Asian skin, predominantly classified as Fitzpatrick skin phototypes III to IV, is characterized by relatively diminished skin barrier function and increased sensitivity to irritants. Airborne pollen exposure may particularly act as a trigger in East Asian individuals, possibly mediated through toll-like receptors. The lack of specificity in objective clinical and histopathological findings leads to diagnostic challenges for individuals with colored skin, including East Asians, particularly when erythema is the sole objective manifestation. An alternative diagnostic scheme may thus be necessary. A diagnostic approach emphasizing vascular manifestations and nociceptive symptoms potentially holds promise for individuals with darker skin tones. More research focusing on potential variations in skin physiology across different racial groups is essential to establish more effective diagnostic schemes applicable to both dark and light skin colors.

Unraveling the Complex Molecular Interplay and Vascular Adaptive Changes in Hypertension-Induced Kidney Disease.

Angiogenesis, the natural mechanism by which fresh blood vessels develop from preexisting ones, is altered in arterial hypertension (AH), impacting renal function. Studies have shown that hypertension-induced renal damage involves changes in capillary density (CD), indicating alterations in vascularization. We aimed to elucidate the role of the apelin receptor (APLNR), neuronal nitric oxide synthase (nNOS), and vascular endothelial growth factor (VEGF) in hypertension-induced renal damage. We used two groups of spontaneously hypertensive rats aged 6 and 12 months, representing different stages of AH, and compared them to age-matched normotensive controls. The kidney tissue samples were prepared through a well-established protocol. All data analysis was conducted with a dedicated software program. APLNR was localized in tubular epithelial cells and the endothelial cells of the glomeruli, with higher expression in older SHRs. The localization of nNOS and VEGF was similar. The expression of APLNR and nNOS increased with AH progression, while VEGF levels decreased. CD was lower in young SHRs compared to controls and decreased significantly in older SHRs in comparison to age-matched controls. Our statistical analysis revealed significant differences in molecule expression between age groups and varying correlations between the expression of the three molecules and CD.

Effects of SARS-COV-2 on molecules involved in vascularization and autophagy in placenta tissues

SARS-CoV-2 infection is considered as a multi-organ disease, and several studies highlighted the relevance of the virus infection in the induction of vascular injury and tissue morphological alterations, including placenta. In this study, immunohistochemical analyses were carried out on placenta samples derived from women with COVID-19 infection at delivery (SARS-CoV-2 PCR+) or women healed from a COVID-19 infection (SARS-CoV-2 negative at delivery, SARS-CoV-2 PCR-) or women who gave birth before 2019 (Control). Angiotensin Converting Enzyme 2 (ACE2) receptor, Cluster of differentiation 147 (CD147), endothelial CD34 marker, Vascular Endothelial Growth Factor (VEGF) and total Microtubule-associated protein 1 Light Chain 3B marker (LC3B) were investigated in parallel with SPIKE protein by standard IHC. Multiplexed Immunohistochemical Consecutive Staining on Single Slide (MICSSS) was used to examine antigen co-expression in the same specimen. SPIKE protein was detected in villi and decidua from women with ongoing infection, with no significant differences in SPIKE staining between both biopsy sites. VEGF was significantly increased in SARS-CoV-2 PCR + biopsies compared to control and SARS-CoV-2 PCR- samples, and MICSSS method showed the co-localization of SPIKE with VEGF and CD34. The induction of autophagy, as suggested by the LC3B increase in SARS-CoV-2 PCR + biopsies and the co-expression of LC3B with SPIKE protein, may explain one of the different mechanisms by which placenta may react to infection. These data could provide important information on the impact that SARS-CoV-2 may have on the placenta and mother-to-fetus transmission.

Skeletal pathology in mouse models of Gould syndrome is partially alleviated by genetically reducing TGFβ signaling

Skeletal defects are hallmark features of many extracellular matrix (ECM) and collagen-related disorders. However, a biological function in bone has never been defined for the highly evolutionarily conserved type IV collagen. Collagen type IV alpha 1 (COL4A1) and alpha 2 (COL4A2) form α1α1α2 (IV) heterotrimers that represent a fundamental basement membrane constituent present in every organ of the body, including the skeleton. COL4A1 and COL4A2 mutations cause Gould syndrome, a variable and clinically heterogenous multisystem disorder generally characterized by the presence of cerebrovascular disease with ocular, renal, and muscular manifestations. We have previously identified elevated TGFβ signaling as a pathological insult resulting from Col4a1 mutations and demonstrated that reducing TGFβ signaling ameliorate ocular and cerebrovascular phenotypes in Col4a1 mutant mouse models of Gould syndrome. In this study, we describe the first characterization of skeletal defects in Col4a1 mutant mice that include a developmental delay in osteogenesis and structural, biomechanical and vascular alterations of mature bones. Using distinct mouse models, we show that allelic heterogeneity influences the presentation of skeletal pathology resulting from Col4a1 mutations. Importantly, we found that TGFβ target gene expression is elevated in developing bones from Col4a1 mutant mice and show that genetically reducing TGFβ signaling partially ameliorates skeletal manifestations. Collectively, these findings identify a novel and unsuspected role for type IV collagen in bone biology, expand the spectrum of manifestations associated with Gould syndrome to include skeletal abnormalities, and implicate elevated TGFβ signaling in skeletal pathogenesis in Col4a1 mutant mice.

Changes in Blood Vessel Morphology in Erythematous Skin of Atopic Dermatitis Patients

Background: Atopic dermatitis is an inflammatory skin disease characterized by erythematous changes and abnormalities in microvasculature. Regarding the research questions, this cross-sectional study conducted from January 5 to July 5, 2019 at Watim Medical and Dental College, Rawat and the findings on observed vascular alterations supposed to present the mean age, standard deviation and p-value as follows: Objectives: , the morphology of the blood vessels in the erythematous skin of the patients with AD and controls matched based on their age will be examined. Study Design: A Cross-sectional study. Place and Duration of Study: from 05-Jan-2019 to 05-Jan-2020 in the Department Pathology, Watim Medical and Dental College Rawat, Pakistan. Methods: This descriptive cross sectional study recruited the patients from the Department of Pathology, Watim Medical and Dental College, Rawat over a period of six months from January 5, 2019 to July 5, 2019. Adult patients, comprising 100 in number, diagnosed to have atopic dermatitis were used in the study. The patient ages were noted down and dermoscopy of the morphological changes occurring in the blood vessels at erythematous lesions were observed. Descriptive statistics were used in a bid to calculate mean age, standard deviation as well as the p-value. This research study was reviewed and cleared by the Institution’s ethical committee before its conduct. Results: Patients 100 Patients were selected for the study, Moreover the patients diagnosed with atopic dermatitis were between the age group of 18-65 years with mean age of 35. 4 years (SD 12. 7), refer to the table 1. Morphological assessment of blood vessels in erythematous skin showed that 60% of the patients were having abnormal morphological pattern whereas 40% of patients demonstrated normal morphology (table 2). Co-relating and comparing the normal and altered Vascular architecture mathematical statistics revealed the fact with P-values equal to 0. 045 (Table 4). The findings of increased vascular alterations in lesions of atopic dermatitis evident from the results in Table 5 indicate that blood vessel alterations are associated with the severity of skin condition rashes. Conclusion: our study identify that extensive vascular changes at the skin of those with atopic dermatitis while stressing on the importance of these changes in disease progression. Targeted therapies for the aforementioned vascular changes could be promising in the future as compared to the ones that address mere clinical manifestations. Keywords: AMD, Vasculature, Redness of the Skin, Swelling.

Neonatal hyperoxia exposure leads to developmental programming of cardiovascular and renal disease in adult rats

Premature infants are often exposed to hyperoxia. However, there is limited data regarding the mechanistic underpinnings linking neonatal hyperoxia exposure and its contribution to cardio-renal dysfunction in adults born preterm. Our objective was to determine whether neonatal hyperoxia induces systemic vascular stiffness and cardio-renal dysfunction in adulthood. Newborn rats were randomly assigned to room air (RA) or hyperoxia (85% O2) from postnatal day 1 to 14, then recovered in RA until 1 year of life. Arterial stiffness, cardio-renal histomorphometry, and fibrosis in the aorta, heart, and kidney were assessed. RNA-sequencing (RNA-seq) of the aorta and kidney was also done. Adult rats exposed to neonatal hyperoxia had increased aortic and mesenteric artery stiffness as demonstrated by wire and pressure myography. They also had cardiomyocyte hypertrophy, glomerulomegaly, and tubular injury. Hyperoxia exposure altered the transcriptome profile associated with fibrosis and matrix remodeling in the aorta and kidney. There was also increased TGF-β1 levels and fibrosis in the aorta, left ventricle, and kidney. In conclusion, neonatal hyperoxia exposure was associated with systemic vascular and cardio-renal alterations in 1-year-old rats. Further studies to determine how targeted therapies could reprogram cardio-renal injury after neonatal hyperoxia exposure are indicated.

Evaluation of ophthalmic vascular and neuroretinal alterations in fibromyalgia syndrome: a cross-sectional comparative study

IntroductionFibromyalgia syndrome (FMS) is a prevalent rheumatic disorder, and its pathogenesis includes genetic, neuroendocrine, and autonomic abnormalities, which may impact ocular structures. The aim was to conduct a comparative analysis of the ophthalmic vasculature and the retinal nerve fiber layer (RNFL) thickness between FMS and control groups using optical coherence tomography (OCT) and OCT angiography (OCTA).MethodsThis cross-sectional comparative study included 43 FMS patients and 40 healthy controls recruited from a tertiary education and research hospital between January 2024 and May 2024. All patients satisfied the 2016 American College of Rheumatology criteria for FMS and consented. OCT and OCTA were used to assess the RNFL thickness and the retinal microvasculature structure. The Fibromyalgia Impact Questionnaire (FIQ) was performed to evaluate disease severity.ResultsThe study found significantly higher total retinal parafoveal thickness and foveal density in FMS patients (p = 0.017 and p = 0.044, respectively). Nevertheless, there were no significant differences among the groups concerning total retinal foveal thickness, foveal avascular zone characteristics, superficial and deep capillary plexus densities, choriocapillaris flow area, and outer retinal flow area values (p > 0.05). The RNFL thickness in all quadrants did not reveal significant differences between the groups (p > 0.05). Furthermore, there was no significant correlation between FIQ scores and OCTA parameters or RNFL thickness values (p > 0.05).ConclusionThe study revealed slight differences in retinal parafoveal thickness and foveal density in FMS patients, but no substantial vascular or neurodegenerative alterations were observed compared to healthy controls. These data indicate that FMS may not substantially affect ocular structures, contrary to earlier hypotheses.

SPECTRUM AND CHARACTERISTICS OF THE ELECTROCARDIOGRAPHIC CHANGES IN CHILDREN WITH TYPE I DIABETES MELLITUS

Introduction. Type I diabetes mellitus (T1D) is one of the most widespread and socially significant diseases. Well-known as a co-occurring condition with youth-onset type 1 diabetes mellitus, cardiovascular disease manifests early after initial diagnosis as signs of cardiovascular remodeling. Growing data indicates that type 1 diabetic children and young adults experience subclinical heart dysfunction, central aortic stiffening, and accelerated peripheral vascular disease. Increased morbidity and mortality in adults have been linked to peripheral artery, heart, and cerebrovascular diseases, and early vascular alterations have been demonstrated to exist since childhood. Little is known to date concerning the development of early cardiac structural and functional problems in children with T1D. Early diagnostic is of high importance. Aim. To assess the frequency and spectrum of electrocardiography (ECG) abnormalities in children with type 1 diabetes. Materials and methods. Records of 60 patients with type I diabetes included into the analysis. ECG data, main anamnestic, clinical and laboratory data analyzed. Results. So-called "small ECG abnormalities" were found. Incomplete left/right blockade bundle branch block found in 22.5% of children, shortened PQ interval in 15%, extrasystoles, tachycardia, bradycardia in 52.5%, T wave amplitude decrease in 60%. 87.5% of the examinees have a combination of 2–3 of the above changes on the ECG. Only 12% of the examined children had an ECG without pathological changes. All children with newly diagnosed type 1 DM had at least 1 of the described ECG abnormalities. Correlation analysis done. Substantial positive correlations between Hb1Ac levels and number of ECG changes, serum cholesterol levels and number of ECG changes were found. Conclusions. The results of the study indicate that the majority of children with type I diabetes have so-called "small ECG abnormalities." According to the type of disturbances, they can be classified as rhythm and conduction disturbances and combined changes. These findings are promising in terms of management tactics for children with type I diabetes, early detection and timely therapeutic correction of ECG abnormalities.

The emerging role of cardiovascular magnetic resonance in the evaluation of cardiac involvement in systemic sclerosis

Abstract Systemic sclerosis (SSc) is an autoimmune rheumatic disease, characterized by vascular, inflammatory and fibrotic alterations. Cardiac involvement is the « fatal tip of the iceberg» in SSc, as it leads to high morbidity/mortality. Cardiovascular imaging modalities play an important role in the early diagnosis and treatment assessment of cardiac involvement. Echocardiography is the corner stone for evaluation of cardiac involvement, providing information about function, wall motion, pulmonary pressure, pericardium and valvular disease. It is a low-cost modality, widely available, without radiation and with great experience among cardiologists. However, it is a window and operator dependent modality and cannot provide tissue characterization information, absolutely necessary for diagnosis and treatment of cardiac involvement in SSc. Cardiovascular magnetic resonance (CMR) can perform myocardial function and tissue characterization in the same examination without radiation, has excellent reproducibility and is window and operator independent. The great advantage of CMR is the capability to assess peri- myo-vascular inflammation, myocardial ischemia and presence of replacement and diffuse myocardial fibrosis in parallel with ventricular function assessment. The modified Lake Louise criteria including T2, native T1 mapping and extracellular volume fraction (ECV) has been recently used to diagnose inflammatory cardiomyopathy. According to expert recommendations, myocardial inflammation should be considered if at least 2 indices, one T2 and one T1 parameter are positive, whereas native T1 mapping and ECV assess diffuse fibrosis or oedema, even in the absence of late gadolinium enhancement (LGE). Moreover, transmural/subendocardial LGE following the distribution of coronary arteries and diffuse subendocardial fibrosis not related with epicardial coronary arteries are indicative of epicardial and micro-vascular coronary artery disease, respectively. To conclude, CMR can overcome the limitations of echocardiography by identifying acute/active or chronic myocardial inflammation/fibrosis, ischemia and myocardial infarction using classic and parametric indices in parallel with biventricular function assessment

Retinal Vascular and Structural Changes in the Murine Alzheimer's APPNL-F/NL-F Model from 6 to 20 Months.

Alzheimer's disease (AD) may manifest retinal changes preceding brain pathology. A transversal case-control study utilized spectral-domain OCT angiography (SD-OCTA) and Angio-Tool software 0.6a to assess retinal vascular structures and OCT for inner and outer retina thickness in the APPNL-F/NL-F AD model at 6, 9, 12, 15, 17, and 20 months old. Comparisons to age-matched wild type (WT) were performed. The analysis focused on the three vascular plexuses using AngiooTool and on retinal thickness, which was represented with the Early Treatment Diabetic Retinopathy Study (ETDRS) sectors. Compared to WT, the APPNL-F/NL-F group exhibited both vascular and structural changes as early as 6 months persisting and evolving at 15, 17, and 20 months. Significant vascular alterations, principally in the superficial vascular complex (SVC), were observed. There was a significant decrease in the vessel area and the total vessel length in SVC, intermediate, and deep capillary plexus. The inner retina in the APPNL-F/NL-F group predominantly decreased in thickness while the outer retina showed increased thickness in most analyzed time points compared to the control group. There are early vascular and structural retinal changes that precede the cognitive changes, which appear at later stages. Therefore, the natural history of the APPNL-F/NL-F model may be more similar to human AD than other transgenic models.

The relationship of visceral adiposity with endothelial functions and subclinical atherosclerosis in obese individuals.

On the cardiovascular system, obesity accelerates atherosclerosis progression, inducing pathophysiological changes that are detectable already from young adults. Endothelial dysfunction is one of the earliest vascular alterations observed in obesity. In this study, we aimed to determine endothelial functions and carotid intima-media thickness in patients with obesity without overt cardiovascular disease. The study was conducted with 112 individuals with obesity without overt cardiovascular disease and any chronical diseases (BMI>30 kg/m2) (84 female, 28 male, mean age: 46.3±11.2 years) and 49 healthy individuals with no diseases (33 female, 16 male, mean age: 44.6±10.2 years). All patients were examined for endothelial functions by the flow-mediated dilatation (FMD) method and carotid intima-media thicknesses (CIMT). All measurements were performed by the same imaging specialist, averaging 3 different measurements. In addition to the body mass index and waist circumference visceral adiposity index (VAI) and triponderal mass index (TPI) also calculated. The percentage of FMD obtained by brachial artery ultrasound was significantly lower, visceral adipose tissue, perirenal adipose tissue thicknesses measured by abdominal ultrasound and CIMT were significantly thicker in Group 1 compared to Group 2. FMD had a negative significant correlation with body mass index, visceral adipose tissue thickness, perirenal adipose tissue thickness, and waist and hip circumferences, and carotid intima-media thickness and CIMT had a significant correlation with visceral adipose tissue thickness, perirenal adipose tissue thickness, VAI, TPI and waist, hip circumferences. Individuals with obesity have impaired endothelial functions and greater carotid intima-media thicknesses compared to healthy individuals. This impairment in endothelial functions is proportional to the amount of visceral and perirenal fat accumulation. Parameterss reflecting visceral fat distribution such as VAI and TPI are also related with these impairment.

Revealing the mechanisms of blood-brain barrier in chronic neurodegenerative disease: an opportunity for therapeutic intervention.

The brain microenvironment is tightly regulated, and the blood-brain barrier (BBB) plays a pivotal role in maintaining the homeostasis of the central nervous system. It effectively safeguards brain tissue from harmful substances in peripheral blood. However, both acute pathological factors and age-related biodegradation have thepotential to compromise the integrity of the BBB and areassociated with chronic neurodegenerative diseases such as Alzheimer's disease (AD) and Parkinson's disease (PD), as well as Epilepsy (EP). This association arises duetoinfiltration of peripheral foreign bodies including microorganisms, immune-inflammatory mediators, and plasma proteins into the central nervous system when the BBB is compromised. Nevertheless, these partial and generalized understandings do not prompt a shift from passive to active treatment approaches. Therefore, it is imperative to acquire a comprehensive and in-depth understanding of the intricate molecular mechanisms underlying vascular disease alterations associated with theonset and progression of chronic neurodegenerative disorders, as well as the subsequent homeostatic changes triggered by BBB impairment. The present article aims to systematically summarize and review recent scientific workwith a specific focus on elucidating the fundamental mechanisms underlying BBB damage in AD, PD, and EP as well as their consequential impact on disease progression. These findings not only offer guidance for optimizing thephysiological function of the BBB, but also provide valuable insights for developing intervention strategies aimed at early restoration of BBB structural integrity, thereby laying a solid foundation for designing drug delivery strategies centered around the BBB.

Implications of von Willebrand Factor in Inflammatory Bowel Diseases: Beyond Bleeding and Thrombosis.

Inflammatory bowel disease (IBD) displays an increased venous and arterial thrombotic risk despite the common occurrence of intestinal bleeding. While some of the mechanisms leading to these thrombotic complications have been studied, other specific changes in the hemostasis profile of IBD patients have been less explored. One such example relates to von Willebrand factor (VWF) whose plasma levels have been reported to be modulated in IBD. Von Willebrand factor is a plasma glycoprotein crucial for hemostatic functions via roles both in platelet function and coagulation. High plasma VWF is a known risk factor for venous thromboembolism. In addition to its canonical roles in hemostasis, VWF is known to be directly or indirectly involved in other vascular processes such as maintenance of endothelial barrier integrity or proliferation of vascular smooth muscle cells. The purpose of this review is to recapitulate and update the existing data about VWF biology in IBD and to highlight its role both in the existing procoagulant phenotype and in vascular alterations that may occur in IBD.

O-228 Do myomectomies decrease third trimester pregnancy complications when compared to women without myomectomies and uterine fibroids in situ? A study of an American population database

Abstract Study question Myomectomies are performed to decrease pregnancy complications, among other indications, however, do myomectomies decrease third trimester pregnancy complications? Summary answer Post-myomectomy, pregnancies experienced more complications including hypertensive disorders, premature-pre-term-rupture of membranes, preterm-delivery, placenta-previa, cesareans, uterine ruptures, wound complications, transfusions, and small for gestational age infants. What is known already Patients with fibroid uterus experience reduced fertility rates and increased in obstetrical complications compared to patients without fibroids. If the removal of fibroids improves fertility is controversial for intramural fibroids, it is recommended for submucosal fibroids by the American College Of Gynaecology guidelines. It is a common, untested belief that myomectomies may reduce the risks of certain obstetrics complications. While rates of mal-placentation and hypertensive disorders may increase post-myomectomy as shown by the literature comparing myomectomy vs. control groups without fibroids, other complications may be anticipated to decrease. However, no population-based studies have attempted to answer this question. Study design, size, duration Retrospective cohort study, using the Healthcare Cost and Utilization Project Nationwide Inpatient Sample between 2004 and 2014, inclusively, based on International Classification of Diseases, 9th edition, diagnoses (ICD-9). Data collected from 48 states and the District of Columbia, representing 20% of annual hospital admissions in the United States. Population-based study, including 89,025 with uterine fibroids: 7508 pregnancies with previous abdominal myomectomy (AM) or laparoscopic myomectomy (LM), and 81,517 controls with uterine fibroids in-situ, without myomectomies. Participants/materials, setting, methods We included patients delivery discharge diagnoses or maternal deaths, and with either uterine fibroids (ICD-9 codes 218.0, 218.1, 218.2, 218.9) or AM or LM prior to the pregnancy, (ICD-9 codes 68.29 and 68.19 or CPT procedure code 58140, 58145, 58146, 58545 and 58546). Binomial logistic regression was used and adjusted for age, race, income quartiles, smoking, previous cesarean section, chronic and pregnancy-induced hypertension, obesity, multiple gestations, pre-gestational and gestational diabetes mellitus. Main results and the role of chance The myomectomy group was characterized by older patients, higher rates of Caucasian race, chronic hypertension, previous cesarean delivery, and multiple gestations, and lower, income quartiles, rates of obesity, compared to the fibroid in-situ group (P &amp;lt; 0.05). There was no difference for rates of medical insurance plan type, tobacco smoking, pregestational diabetes, illicit drug use, thyroid disease, or in vitro fertilization use (P &amp;gt; 0.05, all). The myomectomy group had increased rates of pregnancy-induced hypertension (adjusted odd ratios(aOR)-1.15, 95% confidence intervals(CI):1.06-1.26), preeclampsia (aOR:1.25 95%CI:1.12-1.41), preterm delivery (aOR:1.4, 95%CI:1.27-1.53), preterm premature rupture of membranes (aOR:1.29, 95%CI:1.05-1.58), placenta previa (aOR:1.59, 95%CI:1.32-1.92), cesarean delivery (aOR:37.1, 95%CI:27.35-50.4), uterine rupture (aOR:2.1, 95%CI:1.06-4.16), blood transfusion (aOR:1.21, 95%CI:1.68-2.24), wound complications (aOR:1.44, 95%CI:1.1-1.9), disseminated intravascular coagulation (aOR:1.58, 95%CI:1.1-2.27), and small for gestational age (SGA) infants (aOR:0,19, 95%CI:1.05-1.39) compared to the fibroid in-situ group. The myomectomy group had a lower rate of gestational diabetes mellitus (aOR:0,88, 95%CI:0,79-0,97), chorioamnionitis (aOR:0,74, 95%CI:0,6-0,93), maternal infection (aOR:0.79, 95%CI:0.65-0.95), spontaneous (aOR:0.03, 95%CI:0.02-0.04) and operative vaginal delivery (aOR:0.87, 95%CI:0.75-0.99), and postpartum hemorrhage (aOR:0.73, 95%CI:0.62-0.87). There was no significant differences for rates of gestational hypertension, eclampsia, preeclampsia or eclampsia superimposed on pre-existing hypertension, abruptio placenta, hysterectomy, maternal death, deep venous thrombosis, pulmonary embolism and venous thromboembolism events (P &amp;gt; 0.05, all). Limitations, reasons for caution The retrospective nature of the study may mask undetected bias. Moreover, although the rate of uterine rupture was increased in the myomectomy group, it was rare and requires confirmation. Further prospective studies are needed to evaluate the outcomes in pregnancy after myomectomy. Wider implications of the findings The complications seen after myomectomies were likely related to uterine-incisions and alteration of myometrial vascularization, impairing trophectoderm invasion and leading to hypertensive disorders, mal-placentation, and abnormalities of fetal growth. Patients should be counselled regarding these potential risks. Increased understanding of the role of myomectomies on reproductive outcomes needs further study. Trial registration number not applicable