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Introduction Imaging fibroid vascularity may predict fibroid growth and aid to determine most appropriate therapy. Microvascular (MV) flow imaging is relatively new and is able to detect slow flow in small vessels. Data on feasibility, reproducibility, and reliability of MV‐flow imaging in fibroids is lacking. The purpose of our study was to determine the reproducibility of MV‐flow imaging and to explore this technique for clinical practice for assessing blood flow in fibroids. Material and Methods Thirty patients with one or multiple fibroids (diameter 1.5–12.0 cm) were prospectively included. Transvaginal ultrasound scanning was performed in B‐mode, 2D MV‐Flow™, 2D and 3D power Doppler mode (HERA W10, Samsung) by two experienced gynecologists at a tertiary care clinic from February to December 2021. The primary outcome was intra‐ and interobserver agreement of the vascular index (VI) and color score (CS). The following parameters: ‘2D MV‐flow VI’, ‘3DPD VI’, ‘2D MV‐flow CS’ and ‘2DPD CS’ were measured offline in the center, pseudocapsule, and entire fibroid. Secondary offline outcomes for exploring 2D MV‐flow for clinical practice, included (1) ability to discern vascular structures, (2) assessing the degree of vascularity via CS and calculating a VI, and (3) determining penetration depth of the ultrasound signal in both power Doppler and MV‐flow imaging. Results All scans of the 30 included patients were of sufficient quality to analyze. Inter‐ and intra‐observer correlations of all studied parameters were good to excellent, both for 2D MV‐flow and 2D power Doppler (intercorrelation coefficient 0.992–0.996). Using 2D MV‐flow different vascular structures were visible in detail, in contrary to using 2D and 3D power Doppler. In significantly more fibroids central flow could be visualized using 2D MV‐flow (63%) than with 2D power Doppler (13%, p = 0.001). Finally, penetration of the ultrasound signal was deeper using 2D MV‐flow (3.92 cm) than with 2D power Doppler (2.95 cm, p = 0.001). Conclusions Using 2D MV‐flow imaging for determining vascularity is highly reproducible. It has potential added value for clinical practice as it depicts detailed vascular structures and the degree of vascularity, especially in the center of the fibroid. Microvascular flow imaging is relatively new and is able to detect slow flow in small vessels. In 30 patients, we showed good reproducibility between microvascular flow and conventional power Doppler imaging. Microvascular flow imaging is easy to use in clinical practice as it depicts detailed vascular structures and differences in tissue penetration, especially in the center of the fibroid.

There is evidence for increased angiogenesis in the (ectopic) endometrium of adenomyosis patients under the influence of vascular endothelial growth factor (VEGF). VEGF stimulates both angiogenesis and lymph-angiogenesis. However, information on lymph vessels in the (ectopic) endometrium of adenomyosis patients is lacking. In this retrospective matched case-control study, multiplex immunohistochemistry was performed on thirty-eight paraffin embedded specimens from premenopausal women who had undergone a hysterectomy at the Amsterdam UMC between 2001 and 2018 to investigate the evidence for (lymph) angiogenesis in the (ectopic) endometrium or myometrium of patients with adenomyosis versus controls with unrelated pathologies. Baseline characteristics of both groups were comparable. In the proliferative phase, the blood and lymph vessel densities were, respectively, higher in the ectopic and eutopic endometrium of patients with adenomyosis than in the endometrium of controls. The relative number of blood vessels without α-smooth muscle actinin (α SMA) was higher in the eutopic and ectopic endometrium of adenomyosis patients versus controls. The level of VEGF staining intensity was highest in the myometrium but did not differ between patients with adenomyosis or controls. The results indicate increased angiogenesis and lymphangiogenesis in the (ectopic) endometrium affected by adenomyosis. The clinical relevance of our findings should be confirmed in prospective clinical studies.

Apoptosis of endothelial cells related to homocysteine (Hcy) has been reported in several studies. In this study, we evaluated whether reactive oxygen species (ROS)-producing signaling pathways contribute to Hcy-induced apoptosis induction, with specific emphasis on NADPH oxidases. Human umbilical vein endothelial cells were incubated with 0.01–2.5 mM Hcy. We determined the effect of Hcy on caspase-3 activity, annexin V positivity, intracellular NOX1, NOX2, NOX4, and p47 phox expression and localization, nuclear nitrotyrosine accumulation, and mitochondrial membrane potential (Δ Ψ m ). Hcy induced caspase-3 activity and apoptosis; this effect was concentration dependent and maximal after 6-h exposure to 2.5 mM Hcy. It was accompanied by a significant increase in Δ Ψ m . Cysteine was inactive on these parameters excluding a reactive thiol group effect. Hcy induced an increase in cellular NOX2, p47 phox , and NOX4, but not that of NOX1. 3D digital imaging microscopy followed by image deconvolution analysis showed nuclear accumulation of NOX2 and p47 phox in endothelial cells exposed to Hcy, but not in control cells, which coincided with accumulation of nuclear nitrotyrosine residues. Furthermore, Hcy enhanced peri-nuclear localization of NOX4 coinciding with accumulation of peri-nuclear nitrotyrosine residues, a reflection of local ROS production. p47 phox was also increased in the peri-nuclear region. The Hcy-induced increase in caspase-3 activity was prevented by DPI and apocynin, suggesting involvement of NOX activity. The data presented in this article reveal accumulation of nuclear NOX2 and peri-nuclear NOX4 accumulation as potential source of ROS production in Hcy-induced apoptosis in endothelial cells.

Adenomyosis is characterized by abnormal uterine bleeding, dysmenorrhea and subfertility. Increased expression of angiogenesis markers in adenomyosis presents a treatment opportunity and was studied in an adenomyosis mouse model. Mice were administered tamoxifen (1 mg/kg) on neonatal days 2–5. At six weeks of age, mice received oral treatment with axitinib 3 mg/kg (‘dose I/AX3’, n = 34), axitinib 25 mg/kg (‘dose II/AX25’ n = 34), or with vehicle-only (‘placebo’, n = 34). The prevalence and severity of adenomyosis were assessed. An adenomyosis severity index was calculated by multiplying mean grade/mouse by the percentage affected surface area. Angiogenesis-related gene expression was evaluated using real-time quantitative PCR. 101 mice completed adenomyosis induction and could be analyzed. The prevalence of adenomyosis was 30/33 (90.0%) in dose I, 29/34 (85.3%) in dose II, and 30/34 (88.2%) in placebo treated mice (p = 0.78). High grade (2/3) adenomyosis was significantly less prevalent in mice treated with axitinib dose II (n = 19, 55.9%) than in the placebo group (n = 27, 79.4%, p < 0.05). The adenomyosis severity index was reduced by 48% in the axitinib-treated groups (dose I, p < 0.05). The expression of angiogenic growth factors was reduced in the dose I and II axitinib-treated groups compared to the placebo-treated group. Following these promising first results, further research should focus on commonality among different angiostatic drugs, potential side effects, as well as the method and timing of application.

Infectious myocarditis is the result of an immune response to a microbial infection of the heart. The blood vessels of the heart, both the intramyocardial microvasculature and the large epicardial coronary arteries, play an important role in the pathogenesis of infectious myocarditis. First of all, in addition to cardiomyocytes, endothelial cells of the cardiac (micro)vasculature are direct targets for infection. Moreover, through the expression of adhesion molecules and antigen presenting Major Histocompatibility Complex molecules, the blood vessels assist in shaping the cellular immune response in infectious myocarditis. In addition, damage and dysfunction of the cardiac (micro)vasculature are associated with thrombus formation as well as aberrant regulation of vascular tone including coronary vasospasm. These in turn can cause cardiac perfusion abnormalities and even myocardial infarction. In this review, we will discuss the role of the cardiac (micro)vasculature in the pathogenesis of infectious myocarditis.

Abstract Background It is unknown whether lung-protective ventilation is applied in burn patients and whether they benefit from it. This study aimed to determine ventilation practices in burn intensive care units (ICUs) and investigate the association between lung-protective ventilation and the number of ventilator-free days and alive at day 28 (VFD-28). Methods This is an international prospective observational cohort study including adult burn patients requiring mechanical ventilation. Low tidal volume (VT) was defined as VT ≤ 8 mL/kg predicted body weight (PBW). Levels of positive end-expiratory pressure (PEEP) and maximum airway pressures were collected. The association between VT and VFD-28 was analyzed using a competing risk model. Ventilation settings were presented for all patients, focusing on the first day of ventilation. We also compared ventilation settings between patients with and without inhalation trauma. Results A total of 160 patients from 28 ICUs in 16 countries were included. Low VT was used in 74% of patients, median VT size was 7.3 [interquartile range (IQR) 6.2–8.3] mL/kg PBW and did not differ between patients with and without inhalation trauma (p = 0.58). Median VFD-28 was 17 (IQR 0–26), without a difference between ventilation with low or high VT (p = 0.98). All patients were ventilated with PEEP levels ≥5 cmH2O; 80% of patients had maximum airway pressures <30 cmH2O. Conclusion In this international cohort study we found that lung-protective ventilation is used in the majority of burn patients, irrespective of the presence of inhalation trauma. Use of low VT was not associated with a reduction in VFD-28. Trial registration Clinicaltrials.gov NCT02312869. Date of registration: 9 December 2014.