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Electroporation technique induced by high-voltage pulses has been successfully used to ablate tumor cells while preserving the function of normal blood vessels. Generally, the tumor blood vessels can provide a pathway to draw nutrients for tumor growth and contribute to invasion and metastasis, which is an obstacle to tumor treatment. The electroporation study of the endothelial cell, which is important in the vasculature microenvironment, is helpful to investigate the influence on both tumor and normal blood vessels. This study built a multicell-layer model of the vascular microenvironment to investigate the discriminative electroporation effect between normal and tumor blood vessels by high-frequency bipolar pulses (HFBPs) and monopolar pulses (MPs). The simulation results showed that both pore number and electroporation region in normal blood vessels are significantly lower than those in tumor blood vessels. The rich vascular smooth muscle cells existed in the normal blood vessels play a protective function for endothelial cells, compared with tumor blood vessels. However, the differences in pore number and electroporation region between normal and tumor blood vessels are gradually smaller with an increased electric field, which demonstrates that the electroporation pulse with higher intensity damages both normal and tumor blood vessels. HFBPs generate a weaker electroporation effect on both normal and tumor blood vessels than traditional MP. However, HFBPs are more suitable to electroporate tumor blood vessels, while preserving the normal blood vessels. Moreover, this study could also provide a multicell-layer model that can be used to analyze the cell electroporation effect in the vascular microenvironment. [ABSTRACT FROM AUTHOR]

Purpose: To compare glycated multilayered membranes (OV) to a commercially available thin-layer membrane (OP) in a lateral ridge augmentation model in dogs. Materials and Methods: This was designed as a three-arm study, where one negative control (empty defect) was compared to two test arms: alveolar bone defects grafted with a mixture of 90% deproteinized bovine bone mineral and 10% porcine collagen, then covered with either a thick- (OV) or thin-layered (OP) membrane. Animals were randomly divided into three groups corresponding to the final sacrifice times of 4 weeks, 12 weeks, and 24 weeks. Sections underwent microCT, histology, histopathology, and histomorphometry. Results: No statistical differences were observed for OV compared to OP regarding the percentage of mineral volume and mean mineral density, amount of bone maturation, percentage of bone graft and membrane remaining in the grafted area, alveolar ridge width measurements, membrane mineralization, or ossification. Test groups presented significantly higher values compared to the empty control for all the endpoints. Conclusions: Within its limitations, this in vivo study highlighted that multilayered thick glycated membranes can serve as effective occlusive barriers for up to 6 months. [ABSTRACT FROM AUTHOR]

Diabetic Retinopathy (DR) is termed as ever-lasting retinal disorders which can cause loss of vision and even blindness in most of the cases. The procedure to classify the level of severity in DR and is complex process as lesion features are complex to examine. The task of screening needs an effectual detection technique for classifying the subtle pathologies in retina. The deep models is considered as an imperative domain treating the disease caused in eye and help the ophthalmologists to make timely decisions. A new LeNet model is developed with Chronological Rat Swarm Optimization (CRSO) for detecting DR. The first step is the capturing retinal images through fundus photography, which further undergoes pre-processing with median filter. The segmentation is then achieved wherein lesion segmentation is completed with U-Net and blood vessel segmentation is performed with Dense U-Net. From input fundus image, lesion segmented output, and blood vessel segmented output, extraction of essential feature is performed. Finally, DR detection is executed with CRSO-based LeNet. The CRSO-based LeNet attained superior performance with highest accuracy of 89%, NPV of 87.2%, PPV of 87.0%, TNR of 89.0% and TPR of 89.5%. The proposed method is useful in various applications, such as medical applications and healthcare applications. [ABSTRACT FROM AUTHOR]

Many withered leaves or flowers spontaneously curl and transform from flattened structures into tubular constructs upon dehydration. Inspired by this phenomenon, an innovative strategy is developed to design stimuli‐responsive scaffolds that are capable of programmable transformation from flattened 2D constructs into various curled 3D tissue‐mimicking structures. Specifically, Janus‐structured scaffolds consisting of a passive layer of polycaprolactone and an active, triggered‐transforming layer of methacrylate gelatin/alginate hydrogel are 3D‐printed, which replicate the asymmetrical structure of leaves and enabled on‐demand transformation into desired curvatures and shapes through mimicking the regulation mechanism of leaves curling behavior by mesophyll matrix stiffness and vein patterns. Particularly for vascular reconstruction, multi‐step transformation scaffolds capable of primary 2D‐to‐3D transformation into tubular constructs induced by dehydration, and secondary transformation to adapt to the local intravascular geometry in vivo, are successfully developed. In addition, the oriented polycaprolactone layer of the printed scaffold can enable the adhesion, proliferation, and orientation of endothelial cells, thus demonstrating a novel strategy for the design of tissue‐engineered blood vessels. In general, this study provides an innovative design strategy for programmable biomaterials capable of shape morphing and adaptation in physiological conditions, thereby opening up a new avenue for the design of intelligent biomaterials in regenerative medicine. [ABSTRACT FROM AUTHOR]

Background: Hepatocellular carcinoma (HCC) is the most frequent primary liver tumor globally and a leading cause of mortality in cirrhotic patients. Our study aimed to estimate the diagnostic performance of triphasic CT and inter-observer reliability in the preoperative detection of microvascular invasion (MVI) in HCC. Two independent radiologists accomplished a retrospective analysis for 99 patients with HCC to assess the CT features for MVI in each lesion. Postoperative histopathology was considered the gold standard. Results: Multivariate regression analysis revealed that incomplete or absent tumor capsules, presence of TTPV, and absence of hypodense halo were statistically significant independent predictors of MVI. There was excellent agreement among observers in evaluating peritumoral enhancement, identifying intratumoral arteries, hypodense halo, TTPV, and macrovascular invasion. Also, our results revealed moderate agreement in assessing the tumor margin and tumor capsule. Conclusion: Triphasic CT features of MVI are reliable imaging predictors that may be helpful for standard preoperative interpretation of HCC. [ABSTRACT FROM AUTHOR]

Vata Vyadhi is the term which is applied to the specific disorders produced by vata.. The individual whose body has uninterrupted vata( air) circulation, a person who has a natural Vata Dosha and all the vata( Prana, udana, Smana, Vyana, Apana vata) in their body are in their proper locations can live a hundred years1 Hence, there are five variations in vata Prana, Udana, Samana, Vyana and Apana. This air, which is divided into five sections, moves each portion of the body well and continuously in its designated location2 . The term used to describe the particular illnesses caused by vata is Vata Vyadhi. There exist two categories of diseases3 . Samanya: The all-encompassing one, resulting from a different Dosha Nanatmaja -The unique one, which is solely brought about by vata through certain anomalous qualities, Ruksha (Dryness), Laghu (Coldness), Shita (cold), khara (rough), Sukshma (subtle), Chala (constant), vishada (clearness) are characteristics of Vata4 . The term used to describe the particular illnesses caused by vata is Vata Vyadhi. The illnesses impair the functions of Sira (blood vessels), Sanayu (ligaments), and Kandara (tendons) and impact the Madhyma Roga marga (Marma, Asthi, and Sandhi) 5 . Panchakarma treatment to reduce the illness by reducing the Ekanga Vata symptoms. The primary complaints of a 50- year-old male patient were weakness in his Right upper and Right lower limb, unable to work by Right hand and Right leg, difficulty in speaking. He took therapy from many Allopathic medicines but he did not get much improvement. In the end, the patient was admitted to our institute for treatment and the patient experienced roughly 70% alleviation in his illness symptoms. [ABSTRACT FROM AUTHOR]

A systematic evaluation of vascular access device (VAD) selection incorporates patient, device, and infusate characteristics to ensure optimal device placement. This article explores VAD selection from the perspective of vessel health and preservation and describes VAD selection options and indications, VAD-related complications, and strategies to reduce those complications. [ABSTRACT FROM AUTHOR]

In this study, a portable plasma generator produced large‐area air plasma for treating infected wounds in BALB/c mice. Different plasma treatment times (30 s, 1 min, 3 min, and 4.5 min) were applied daily until the wounds healed completely. Results showed reduced inflammation and increased vascular endothelial growth factor (VEGF) expression in tissues treated for 1 and 3 min, promoting blood vessel proliferation and collagen fiber synthesis. However, treatment for 30 s and 4.5 min worsened inflammation and decreased VEGF expression. Overall, a 1‐min treatment was the most effective in promoting wound healing. Cold plasma shows promise for healing infected wounds, with treatment duration being a crucial factor. [ABSTRACT FROM AUTHOR]

Objective: Disruptor of telomeric silencing 1-like (DOT1L) is the only known histone H3K79 methyltransferase essential for the development of the embryonic cardiovascular system, including the heart, blood vessels, and lymphatic vessels, through transcriptional regulation. Our previous study demonstrated that Dot1l deletion results in aberrant lymphatic development and function. However, its precise function in the postnatal cardiovascular system remains unknown. Methods: Using conditional and inducible Dot1l knockout (KO) mice, along with a reporter strain carrying the Geo gene at the Dot1l locus, DOT1L expression and its function in the vascular system during postnatal life were investigated. To assess vessel morphology and vascular permeability, we administered Latex or Evans blue dye to KO mice. In addition, in vitro tube formation and cell migration assays were performed using DOT1L-depleted human umbilical vein endothelial cells (HUVECs). Changes in the expression of vascular genes in HUVECs were measured by quantitative polymerase chain reaction. Results: Our findings demonstrate that conditional Dot1l knockout in the Tg (Tie2-cre) strain results in abnormal blood vessel formation and lymphatic anomalies in the intestine. In a mouse model of Rosa26-creER-mediated inducible Dot1l knockout, we observed vascular phenotypes, including increased vascular permeability and brain hemorrhage, when DOT1L was deleted in adulthood. Additionally, DOT1L depletion in cultured HUVECs led to impaired cell migration and tube formation, likely due to altered gene transcription. These findings highlight the essential role of DOT1L in maintaining vascular integrity and function during embryonic development and postnatal life. Conclusion: Our study revealed that DOT1L is required for the maintenance of adult vascular function through the regulation of gene expression. [ABSTRACT FROM AUTHOR]

Background Gentian violet ink is used as a skin marker in various surgical procedures, including neurosurgery. The dye is also used to visualize the edges of blood vessels during bypass surgery. However, gentian violet ink carries the risks of carcinogenicity and venous injury, which causes microvascular thrombosis. In this study, we compare the gentian violet–free dye C.I. Basic Violet 4 (BV4) and gentian violet. The usefulness, in terms of color, and formation of microvascular thrombosis in anastomosis were compared. Methods We used the gentian violet–free dye in 20 cases involving 3 vascular anastomoses. The bone cutting lines on the bone surface, superior temporal artery, and middle cerebral artery were drawn using BV4 and gentian violet ink. Results The colors of BV4 and gentian violet ink were similar. No thrombus formation was observed at the vascular anastomosis when using BV4. Conclusion BV4 can be used similarly to gentian violet ink. No adverse effects such as thrombus formation in microvascular anastomosis were experienced when BV4 was used. [ABSTRACT FROM AUTHOR]

Objective In neuroendovascular treatment, there are many opportunities to guide multiple catheters into the intracranial blood vessels. We report the relationship between two microcatheters according to the guiding order with experimental in vitro studies. Materials and Methods We hypothesize that in a bent blood vessel such as a paraclinoid region of the internal carotid artery, the catheter that was first guided tended to pass through the inside, and the catheter that was guided later tended to pass through the outside. The in vitro verification was performed using a microcatheter and a balloon catheter in a silicone vascular aneurysmal model. Results As a result, it was found that the two catheters were arranged according to our hypothesis. This finding was also observed during the actual operation of balloon-assisted coil embolization. Conclusion The positional relationship between the two catheters according to the navigation order is very important, in particular during balloon-assisted coiling and stent-assisted coiling via a jailed microcatheter. [ABSTRACT FROM AUTHOR]

Purpose: Vascular injuries are rarely associated with severe knee injuries; nonetheless, it is imperative to efficiently detect this condition and plan for either immediate or definitive treatment at later stages. The diagnosis and management of multiligament knee injuries still present unresolved issues, particularly in the early detection of vascular issues and the sequential stabilisation of ligaments. High-energy trauma is a frequently encountered cause, however, even low-energy trauma in those who are morbidly obese might pose a significant risk. Advancements in detection and management methods have greatly decreased the occurrence of vascular complications and amputation rates over time. MLKIs after transient knee dislocations are frequently misdiagnosed for vascular injuries, underscoring the necessity for improved diagnostic techniques to avoid avoidable amputations. Methods: This article is a new conceptual review of vascular injuries associated with MLKIs. It provides a full overview of these conditions and includes a review of the most recent literature. We have included pertinent citations from the literature, together with suggestions derived from the latest studies. This review article had additional evaluation by proficient specialists with commendable outcomes and more than a decade of expertise in surgical techniques. Results: This article offers a detailed overview of orthopaedic management, including new definitions and summaries of the causes, evaluation of patients, clinical assessment, identification of vascular injuries, and initial management in patients with vascular impairment following major limb and joint injuries (MLKIs). Conclusion: MLKIs (patients with lower limb ischaemia) who have vascular damage necessitate meticulous physical assessment and sophisticated treatments in order to decrease amputation rates. Prompt identification and timely treatment of vascular lesions, namely in the popliteal artery, can substantially reduce the occurrence of amputations. Emerging research suggests that there is a heightened risk in low-energy situations, particularly amongst individuals who are extremely obese. Progress in vascular intervention has led to a reduction in amputation rates, whilst the implementation of new guidelines has enhanced identification. Thorough patient assessment is essential, utilising physical examinations and imaging techniques such as Computed tomography angiography, magnetic resonance angiography (CTA or MRA) to guide treatment decisions. MRA, in particular, is capable of identifying both vascular and knee structural damage. Level of Evidence: Level IV, Literature reviews. [ABSTRACT FROM AUTHOR]

Angiomyomatous hamartoma (AMH) is a rare benign lesion of the lymph nodes. Angiomyomatous hamartoma tends to be found in inguinal lymph nodes, and usually in a single lymph node. We present a rare care case of a 53-year-old presenting with a neck lump, found to be AMH involving multiple lymph nodes in her neck. To our knowledge, this is the first case presenting with multiple nodes in this location. There are a limited number of case reports describing magnetic resonance imaging (MRI) features of AMH lesions located in inguinal and head and neck regions. Our MRI findings revealed the mass had intermediate T1 enhancement, high T2 signal enhancement, and high post-gadolinium enhancement and fat saturation of the lesion. Angiomyomatous hamartoma is a histological diagnosis, distinguished from other similar nodal vascular lesions by a number of key features: including the presence of central nodal distribution, muscular blood vessel walls, adipose tissue, and HMB45 negative staining. Early recognition of this benign lesion may have implications for a patient's clinical course and surgical requirements. [ABSTRACT FROM AUTHOR]

Studies have shown cerebrovascular dysfunction in offspring with full‐gestational electronic cigarette (Ecig) exposure, but little is known about how individual trimester exposure impacts offspring health. This study aimed to determine if there is a critical window during gestation that contributes to vascular and anxiety‐like behavioural changes seen with full‐term exposure. To test this, rats were time‐mated, and the pregnant dams were randomly assigned to Ecig exposure during first trimester (gestational day, GD2–7), second trimester (GD8–14), third trimester (GD15–21) or full‐term gestation (GD2–21). We also assessed the effect of maternal preconception exposure. Both male and female offspring from all maternal exposure conditions were compared to offspring from dams under ambient air (control) conditions. Ecig exposure consisted of 60‐puffs/day (5 days/week) using either 5 or 30 watts for each respective exposure group. We found that maternal exposure to Ecig in the second and third trimesters resulted in a decrease (23–38%) in vascular reactivity of the middle cerebral artery (MCA) reactivity in 3‐ and 6‐month‐old offspring compared to Air offspring. Further, the severity of impairment was comparable to the full‐term exposure (31–46%). Offspring also displayed changes in body composition, body mass, anxiety‐like behaviour and locomotor activity, indicating that Ecigs influence neurodevelopment and metabolism. Maternal preconception exposure showed no impact on offspring body mass, anxiety‐like behaviour, or vascular function. Thus, the critical exposure window where Ecig affects vascular development in offspring occurs during mid‐ to late‐gestation in pregnancy, and both 5 W and 30 W exposure produce significant vascular dysfunction compared to Air. Key points: Exposure to electronic cigarettes (Ecigs) is known to increase risk factors for cardiovascular disease in both animals and humans.Maternal Ecig use during pregnancy in rodents is found to impair the vascular health of adolescent and adult offspring, but the critical gestation window for Ecig‐induced vascular impairment is not known.This study demonstrates Ecig exposure during mid‐ and late‐gestation (i.e. second or third trimester) results in impaired endothelial cell‐mediated dilatation (i.e. middle cerebral artery reactivity) and alters anxiety‐like behaviour in offspring.Maternal exposure prior to conception did not impact offspring's vascular or anxiety‐like behavioural outcomes.Rodent models have been a reliable and useful predictor of inhalation‐induced harm to humans. These data indicate maternal use of Ecigs during pregnancy should not be considered safe, and begin to inform clinicians and women about potential long‐term harm to their offspring. [ABSTRACT FROM AUTHOR]

Purpose: Early identification of hematoma enlargement and persistent hematoma expansion (HE) in patients with cerebral hemorrhage is increasingly crucial for determining clinical treatments. However, due to the lack of clinically effective tools, radiomics has been gradually introduced into the early identification of hematoma enlargement. Though, radiomics has limited predictive accuracy due to variations in procedures. Therefore, we conducted a systematic review and meta-analysis to explore the value of radiomics in the early detection of HE in patients with cerebral hemorrhage. Methods: Eligible studies were systematically searched in PubMed, Embase, Cochrane and Web of Science from inception to April 8, 2024. English articles are considered eligible. The radiomics quality scoring (RQS) tool was used to evaluate included studies. Results: A total of 34 studies were identified with sample sizes ranging from 108 to 3016. Eleven types of models were involved, and the types of modeling contained mainly clinical, radiomic, and radiomic plus clinical features. The radiomics models seem to have better performance (0.77 and 0.73 C-index in the training cohort and validation cohort, respectively) than the clinical models (0.69 C-index in the training cohort and 0.70 C-index in the validation cohort) in discriminating HE. However, the C-index was the highest for the combined model in both the training (0.82) and validation (0.79) cohorts. Conclusions: Machine learning based on radiomic plus clinical features has the best predictive performance for HE, followed by machine learning based on radiomic features, and can be used as a potential tool to assist clinicians in early judgment. [ABSTRACT FROM AUTHOR]

The article discusses the background and clinical implications of coronary computed (CT) tomography angiography (CCTA) and CT-based fractional flow reserve (CT-FFR). Topics covered include the practice of CCTA and CT-FFR, samples of CCTA and CT-FFR protocols and case studies involving CCTA and CT-FFR. It also cited the clinical relevance of CCTA and CT-FFR and the clinical effect of the PLATFORM trial on CT-FFR.

Hospitals frequently introduce new medical devices. However, the process of clinicians adapting to these new vascular access devices has not been well explored. The study aims to explore clinicians' experience with the insertion of a new guidewire peripheral intravenous catheter (PIVC) introduced in the emergency department (ED) setting. The study was conducted at two EDs in Queensland, Australia, utilising a qualitative explorative approach. Interviews were conducted with guidewire PIVC inserters, including ED doctors and nurses, and field notes were recorded by research nurses during insertions. Data analysis was performed using inductive content analysis, from which themes emerged. The study compiled interviews from 10 participants and field notes from 191 observation episodes. Five key themes emerged, including diverse experience, barriers related to the learning process, factors influencing insertion success, and recommendations to enhance clinicians' acceptance. These themes suggest that the key to successful adoption by clinicians lies in designing user-friendly devices that align with familiar insertion techniques, facilitating a smooth transfer of learning. Clinician adaptation to new devices is vital for optimal patient care. Emergency nurses and doctors prefer simplicity, safety, and familiarity when it comes to new devices. Providing comprehensive device training with diverse training resources, hands-on sessions, and continuous expert support, is likely to enhance clinician acceptance and the successful adoption of new devices in ED settings. [ABSTRACT FROM AUTHOR]

Shock is circulatory insufficiency, inadequate oxygen delivery, and cellular hypoxia. Intravenous fluids are essential for shock management. Despite treatment, patients can face persistent shock with ongoing hypotension, contributing to higher mortality. This analysis aims to quantify hypotensive non-traumatic cases in an Australian ambulance service, determine persistent hypotension prevalence, and assess paramedic-administered intravascular fluids' impact on blood pressure changes. This study is a retrospective analysis of prehospital fluid resuscitation by New South Wales Ambulance paramedics during 2022. Hypotension is defined as a systolic blood pressure of ≤ 90 mmHg, and persistent hypotension is a systolic blood pressure consistently below 90 mmHg across all observations, with a final blood pressure below 90 mmHg. This study aimed to determine the volume of fluid resuscitation at which a plateau in population-level systolic blood pressure response is observed, by calculating the derivative of the fitted logistic regression model. Moreover, this analysis identified the relative contribution of factors influencing the probability of an attempt at intravenous or intraosseous access using machine learning. Among 796,865 attendances, 23,049 (2.9%) involved non-traumatic patients with hypotension. In total 7,388 (32.1%) of the hypotensive cases resulted in persistent hypotension, of which 3,235 (43.8%) received Hartmann's solution and 1,745 (53.9%) received at least 500 ml of fluids but still had hypotension. The model showed that systolic blood pressure tends to stop increasing after 500–600 milliliters of fluid are given. This suggests that, on average, giving more fluid than this may not raise blood pressure further in a prehospital setting, though individual patient needs can differ. The top four factors from the machine learning shows that as initial respiratory rate goes up, the probability of intravascular access rises. Transport times less than 20 min are associated with a smaller chance of access and younger patients are less likely to receive an attempt. Finally, extremes of systolic blood pressure are more likely to receive access attempts. This study found that three percent of non-traumatic attendances have at least one episode of hypotension, and that more than half of these have persistent hypotension. Only 44% of persistently hypotensive received fluids, and half of persistently hypotensive patients stayed hypotensive despite a reasonable volume of prehospital crystalloids. [ABSTRACT FROM AUTHOR]

The optimal initial vascular access strategy for out-of-hospital cardiac arrest (OHCA) remains unknown. Our objective was to evaluate the association between peripheral intravenous (PIV), tibial intraosseous (TIO), or humeral intraosseous (HIO) as first vascular attempt strategies and outcomes for patients suffering OHCA. This was a secondary analysis of the Portland Cardiac Arrest Epidemiologic Registry, which included adult patients (≥18 years-old) with EMS-treated, non-traumatic OHCA from 2018–2021. The primary independent variable in our analysis was the initial vascular access strategy, defined as PIV, TIO, or HIO based on the first access attempt. The primary outcome for this study was the return of spontaneous circulation (ROSC) at emergency department (ED) arrival (a palpable pulse on arrival to the hospital). Secondary outcomes included survival to: admission, discharge, and discharge with a favorable outcome (Cerebral Perfusion Category score of ≤2). We conducted multivariable logistic regressions, adjusting for confounding variables and for clustering using a mixed-effects approach, with prespecified subgroup analyses by initial rhythm. We included 2,993 patients with initial vascular access strategies of PIV (822 [27.5%]), TIO (1,171 [39.1%]), and HIO (1,000 [33.4%]). Multivariable analysis showed lower odds of ROSC at ED arrival (adjusted odds ratio [95% CI]) with TIO (0.79 [0.64–0.98]) or HIO (0.75 [0.60–0.93]) compared to a PIV-first strategy. These associations remained in stratified analyses for those with shockable initial rhythms (0.60 [0.41–0.88] and 0.53 [0.36–0.79]) but not in patients with asystole or pulseless electrical activity for TIO and HIO compared to PIV, respectively. There were no statistically significant differences in adjusted odds for survival to admission, discharge, or discharge with a favorable outcome for TIO or HIO compared to the PIV-first group in the overall analysis. Patients with shockable initial rhythms had lower adjusted odds of survival to discharge (0.63 [0.41–0.96] and 0.64 [0.41–0.99]) and to discharge with a favorable outcome (0.60 [0.39–0.93] and 0.64 [0.40–1.00]) for TIO and HIO compared to PIV, respectively. TIO or HIO as first access strategies in OHCA were associated with lower odds of ROSC at ED arrival compared to PIV. [ABSTRACT FROM AUTHOR]

Aims The prevalence and difference in risk factors for having thoracic aortic aneurysm (TAA) and abdominal aortic aneurysm (AAA) in men compared with women in the general population is not well described. This study aimed to test the hypotheses that (i) cardiovascular risk factors for TAA and AAA differ and (ii) the prevalence of TAA and AAA is sex specific. Methods and results Aortic examination using computed tomography angiography was performed in 11 294 individuals (56% women), with a mean age of 62 (range 40–95) years participating in the Copenhagen General Population Study. TAAs were defined as an ascending aortic diameter ≥45 mm and a descending aortic diameter ≥35 mm, while AAAs were defined as an abdominal aortic diameter ≥30 mm. Demographic data were obtained from questionnaires. Overall prevalence of aortic aneurysms (AAs) in the study population included: total population 2.1%, men 4.0% and women 0.7% (P -value men vs. women P < 0.001). AAs were independently associated with male sex, increasing age, and body surface area (BSA). While TAAs were associated with hypertension, odds ratio (OR) = 2.0 [95% confidence interval (CI): 1.5–2.8], AAAs were associated with hypercholesterolaemia and smoking, OR = 2.4 (95% CI: 1.6–3.6) and 3.2 (95% CI: 1.9–5.4). Conclusion Subclinical AAs are four times more prevalent in men than in women. In both sexes, increasing age and BSA are risk factors for AAs of any anatomical location. Whereas arterial hypertension is a risk factor for TAAs, hypercholesterolaemia and smoking are risk factors for AAAs. [ABSTRACT FROM AUTHOR]

Endothelial cells, which line the lumen of blood vessels, locally sense and respond to blood flow. In response to altered blood flow dynamics during early embryonic development, these cells undergo shape changes that directly affect vessel geometry: In the dorsal aorta of zebrafish embryos, elongation of endothelial cells in the direction of flow between 48 and 72 hours post fertilization (hpf) reduces the vessel's diameter. This remodeling process requires Endoglin; excessive endothelial cell growth in the protein's absence results in vessel diameter increases. To understand how these changes in vessel geometry emerge from morphological changes of individual endothelial cells, we developed a novel mathematical approach that allows 3D reconstruction and quantification of both dorsal aorta geometry and endothelial cell surface morphology. Based on fluorescently marked endothelial cell contours, we inferred cross-sections of the dorsal aorta that accounted for dorsal flattening of the vessel. By projection of endothelial cell contours onto the estimated cross-sections and subsequent triangulation, we finally reconstructed 3D surfaces of the individual cells. By simultaneously reconstructing vessel cross-sections and cell surfaces, we found in an exploratory analysis that morphology varied between endothelial cells located in different sectors of the dorsal aorta in both wild-type and Endoglin-deficient zebrafish embryos: In wild-types, ventral endothelial cells were smaller and more elongated in flow direction than dorsal endothelial cells at both 48 hpf and 72 hpf. Although dorsal and ventral endothelial cells in Endoglin-deficient embryos had similar sizes at 48 hpf, dorsal endothelial cells were much larger at 72 hpf. In Endoglin-deficient embryos, elongation in flow direction increased between 48 hpf and 72 hpf in ventral endothelial cells but hardly changed in dorsal endothelial cells. Hereby, we provide evidence that dorsal endothelial cells contribute most to the disparate changes in dorsal aorta diameter in wild-type and Endoglin-deficient embryos between 48 hpf and 72 hpf. Author summary: Endothelial cells, which form the innermost layer of each blood vessel, sense and respond to blood flow. During early embryonic development in zebrafish, endothelial cells of the dorsal aorta elongate in the direction of blood flow and hereby decrease the vessel's diameter. To understand how these changes in vessel geometry emerge from morphological changes of individual endothelial cells, it is critical to precisely quantify both vessel geometry and cell morphology. To this end, we developed a novel mathematical approach that leverages information from fluorescently marked endothelial cell contours to reconstruct the dorsal aorta's surface in 3D. In an exploratory analysis, we applied this method to wild-type and mutant zebrafish embryos lacking functional Endoglin that is required for the physiological vessel diameter decrease. By quantifying vessel geometry and cell morphology in these embryos, we found that size and elongation in the direction of blood flow varied between endothelial cells located in different vessel sectors. Notably, we determined a subgroup of endothelial cells that contributed most to the vessel diameter increases in the absence of Endoglin. Future studies can investigate whether variability in endothelial cell behavior also contributes to the onset of human vascular malformations occurring due to a loss of Endoglin. [ABSTRACT FROM AUTHOR]

Short-pulsed lasers can treat dermal pigmented lesions through selective photothermolysis. The irradiated light experiences multiple scattering by the skin and is absorbed by abnormal melanosomes as well as by normal blood vessels above the target. Because the fluence is extremely high, the absorbed light can cause thermal damage to the adjacent tissue components, leading to complications. To minimize radiant exposure and reduce the risk of burns, a model of the melanosome-disruption threshold fluence (MDTF) has been developed that accounts for the light-propagation efficiency in the skin. However, the light-propagation efficiency is attenuated because of multiple scattering, which limits the extent to which the radiant exposure required for treatment can be reduced. Here, this study demonstrates the principle of melanosome disruption with localized thermal damage through a turbid medium by ultralow radiant exposure of a short-pulsed laser. The MDTF model was combined with a wavefront-shaping technique to design an irradiation condition that can increase the light-propagation efficiency to the target. Under this irradiation condition, melanosomes were disrupted at a radiant exposure 25 times lower than the minimal value used in conventional laser treatments. Furthermore, almost no thermal damage to the skin was confirmed through a numerical simulation. These experimental and numerical results show the potential for noninvasive melanosome disruption and may lead to the improvement of the safety of short-pulsed laser treatment. [ABSTRACT FROM AUTHOR]

Mesoscopic photoacoustic imaging (PAI) enables label‐free visualization of vascular networks in tissues with high contrast and resolution. Segmenting these networks from 3D PAI data and interpreting their physiological and pathological significance is crucial yet challenging due to the time‐consuming and error‐prone nature of current methods. Deep learning offers a potential solution; however, supervised analysis frameworks typically require human‐annotated ground‐truth labels. To address this, an unsupervised image‐to‐image translation deep learning model is introduced, the Vessel Segmentation Generative Adversarial Network (VAN‐GAN). VAN‐GAN integrates synthetic blood vessel networks that closely resemble real‐life anatomy into its training process and learns to replicate the underlying physics of the PAI system in order to learn how to segment vasculature from 3D photoacoustic images. Applied to a diverse range of in silico, in vitro, and in vivo data, including patient‐derived breast cancer xenograft models and 3D clinical angiograms, VAN‐GAN demonstrates its capability to facilitate accurate and unbiased segmentation of 3D vascular networks. By leveraging synthetic data, VAN‐GAN reduces the reliance on manual labeling, thus lowering the barrier to entry for high‐quality blood vessel segmentation (F1 score: VAN‐GAN vs. U‐Net = 0.84 vs. 0.87) and enhancing preclinical and clinical research into vascular structure and function. [ABSTRACT FROM AUTHOR]

Hypervascularized glioblastoma is naturally sensitive to anti‐angiogenesis but suffers from low efficacy of transient vasculature normalization. In this study, a lipid‐polymer nanoparticle is synthesized to execute compartmentalized Cas9 and sgRNA delivery for a permanent vasculature editing strategy by knocking out the signal transducer and activator of transcription 3 (STAT3). The phenylboronic acid branched cationic polymer is designed to condense sgRNA electrostatically (inner compartment) and patch Cas9 coordinatively (outer compartment), followed by liposomal hybridization with angiopep‐2 decoration for blood–brain barrier (BBB) penetration. The lipid‐polymer nanoparticles can reach glioblastoma within 2 h post intravenous administration, and hypoxia in tumor cells triggers charge‐elimination and degradation of the cationic polymer for burst release of Cas9 and sgRNA, accompanied by instant Cas9 RNP assembly, yielding ≈50% STAT3 knockout. The downregulation of downstream vascular endothelial growth factor (VEGF) reprograms vasculature normalization to improve immune infiltration, collaborating with interleukin‐6 (IL‐6) and interleukin‐10 (IL‐10) reduction to develop anti‐glioblastoma responses. Collectively, the combinational assembly for compartmentalized Cas9/sgRNA delivery provides a potential solution in glioblastoma therapy. [ABSTRACT FROM AUTHOR]

Background: Spatial and functional hepatic zonation, established by the heterogeneous tissue along the portal-central axis of the liver, is important for ensuring optimal liver function. Researchers have attempted to develop reliable hepatic models to mimic the liver microenvironment and analyze liver function using hepatocytes cultured in the developed systems. However, mimicking the liver microenvironment in vitro remains a great challenge owing to the lack of perfusable vascular networks in the model systems and the limitation in maintaining hepatocyte function over time. Methods: In this study, we established a microphysiological system that operated under continuous flush medium flow, thereby allowing the supply of nutrients and oxygen to liver organoids and the removal of waste and release of cytokines there from, similar to the function of blood vessels. Results: The application of microphysiological system to organoid culture was advantageous for reducing the differentiation time and enhancing the functional maturity of human liver organoid. Conclusion: Hence, our microphysiological culture system might open the possibility of the miniaturized liver model system into a single device to enable more rational in vitro assays of liver response. [ABSTRACT FROM AUTHOR]

Background: By controlling hypercapnia, respiratory acidosis, and associated consequences, extracorporeal CO2 removal (ECCO2R) has the potential to facilitate ultra-protective lung ventilation (UPLV) strategies and to decrease injury from mechanical ventilation. We convened a meeting of European intensivists and nephrologists and used a modified Delphi process to provide updated insights into the role of ECCO2R in acute respiratory distress syndrome (ARDS) and to identify recommendations for a future randomized controlled trial. Results: The group agreed that lung protective ventilation and UPLV should have distinct definitions, with UPLV primarily defined by a tidal volume (VT) of 4–6 mL/kg predicted body weight with a driving pressure (ΔP) ≤ 14–15 cmH2O. Fourteen (93%) participants agreed that ECCO2R would be needed in the majority of patients to implement UPLV. Furthermore, 10 participants (majority, 63%) would select patients with PaO2:FiO2 > 100 mmHg (> 13.3 kPa) and 14 (consensus, 88%) would select patients with a ventilatory ratio of > 2.5–3. A minimum CO2 removal rate of 80 mL/min delivered by continuous renal support machines was suggested (11/14 participants, 79%) for this objective, using a short, double-lumen catheter inserted into the right internal jugular vein as the preferred vascular access. Of the participants, 14/15 (93%, consensus) stated that a new randomized trial of ECCO2R is needed in patients with ARDS. A ΔP of ≥ 14–15 cmH2O was suggested by 12/14 participants (86%) as the primary inclusion criterion. Conclusions: ECCO2R may facilitate UPLV with lower volume and pressures provided by the ventilator, while controlling respiratory acidosis. Since recent European Society of Intensive Care Medicine guidelines on ARDS recommended against the use of ECCO2R for the treatment of ARDS outside of randomized controlled trials, new trials of ECCO2R are urgently needed, with a ΔP of ≥ 14–15 cmH2O suggested as the primary inclusion criterion. [ABSTRACT FROM AUTHOR]

Blood vessels show various COVID-19-related conditions including thrombosis and cytokine propagation. Existing in vitro blood vessel models cannot represent the consequent changes in the vascular structure or determine the initial infection site, making it difficult to evaluate how epithelial and endothelial tissues are damaged. Here, we developed a microphysiological system (MPS) that co-culture the bronchial organoids and the vascular bed to analyze infection site and interactions. In this system, virus-infected organoids caused damage in vascular structure. However, vasculature was not damaged or infected when the virus was directly introduced to vascular bed. The knockout of interferon-related genes and inhibition of the JAK/STAT pathway reduced the vascular damage, indicating the protective effect of interferon response suppression. The results demonstrate selective infection of bronchial epithelial cells and vascular damage by cytokines and also indicate the applicability of MPS to investigate how the infection influences vascular structure and functions. [ABSTRACT FROM AUTHOR]

Mechanically, the brain is characterized by both solid and fluid properties. The resulting unique material behavior fosters proliferation, differentiation, and repair of cellular and vascular networks, and optimally protects them from damaging shear forces. Magnetic resonance elastography (MRE) is a noninvasive imaging technique that maps the mechanical properties of the brain in vivo. MRE studies have shown that abnormal processes such as neuronal degeneration, demyelination, inflammation, and vascular leakage lead to tissue softening. In contrast, neuronal proliferation, cellular network formation, and higher vascular pressure result in brain stiffening. In addition, brain viscosity has been reported to change with normal blood perfusion variability and brain maturation as well as disease conditions such as tumor invasion. In this article, the contributions of the neuronal, glial, extracellular, and vascular networks are discussed to the coarse‐grained parameters determined by MRE. This reductionist multi‐network model of brain mechanics helps to explain many MRE observations in terms of microanatomical changes and suggests that cerebral viscoelasticity is a suitable imaging marker for brain disease. [ABSTRACT FROM AUTHOR]

Societal Impact Statement Summary Grapevine leaves are emblematic of the strong visual associations people make with plants. Leaf shape is immediately recognizable at a glance, and therefore, this is used to distinguish grape varieties. In an era of computationally enabled machine learning‐derived representations of reality, we can revisit how we view and use the shapes and forms that plants display to understand our relationship with them. Using computational approaches combined with time‐honored methods, we can predict theoretical leaves that are possible, enabling us to understand the genetics, development, and environmental responses of plants in new ways. Grapevine leaves are a model morphometric system. Sampling over 10,000 leaves using dozens of landmarks, the genetic, developmental, and environmental basis of leaf shape has been studied and a morphospace for the genus Vitis predicted. Yet, these representations of leaf shape fail to capture the exquisite features of leaves at high resolution. We measure the shapes of 139 grapevine leaves using 1672 pseudo‐landmarks derived from 90 homologous landmarks with Procrustean approaches. From hand traces of the vasculature and blade, we have derived a method to automatically detect landmarks and place pseudo‐landmarks that results in a high‐resolution representation of grapevine leaf shape. Using polynomial models, we create continuous representations of leaf development in 10 Vitis spp. We visualize a high‐resolution morphospace in which genetic and developmental sources of leaf shape variance are orthogonal to each other. Using classifiers, Vitis vinifera, Vitis spp., rootstock and dissected leaf varieties as well as developmental stages are accurately predicted. Theoretical eigenleaf representations sampled from across the morphospace that we call synthetic leaves can be classified using models. By predicting a high‐resolution morphospace and delimiting the boundaries of leaf shapes that can plausibly be produced within the genus Vitis, we can sample synthetic leaves with realistic qualities. From an ampelographic perspective, larger numbers of leaves sampled at lower resolution can be projected onto this high‐resolution space, or, synthetic leaves can be used to increase the robustness and accuracy of machine learning classifiers. [ABSTRACT FROM AUTHOR]

Deficit of oxygen and nutrients in the tumor microenvironment (TME) triggers abnormal angiogenesis that produces dysfunctional and leaky blood vessels, which fail to adequately perfuse tumor tissues. Resulting hypoxia, exacerbation of metabolic disturbances, and generation of an immunosuppressive TME undermine the efficacy of anticancer therapies. Use of carefully scheduled angiogenesis inhibitors has been suggested to overcome these problems and normalize the TME. Here, we propose an alternative agonist-based normalization approach using a derivative of the C-type natriuretic peptide (dCNP). Multiple gene expression signatures in tumor tissues were affected in mice treated with dCNP. In several mouse orthotopic and subcutaneous solid tumor models including colon and pancreatic adenocarcinomas, this well-tolerated agent stimulated formation of highly functional tumor blood vessels to reduce hypoxia. Administration of dCNP also inhibited stromagenesis and remodeling of the extracellular matrix and decreased tumor interstitial fluid pressure. In addition, treatment with dCNP reinvigorated the antitumor immune responses. Administration of dCNP decelerated growth of primary mouse tumors and suppressed their metastases. Moreover, inclusion of dCNP into the chemo-, radio-, or immune-therapeutic regimens increased their efficacy against solid tumors in immunocompetent mice. These results demonstrate the proof of principle for using vasculature normalizing agonists to improve therapies against solid tumors and characterize dCNP as the first in class among such agents. Editor's summary: Tumors often have abnormal and dysfunctional blood vessels that are in part responsible for poor drug delivery and thus reduced efficacy of treatment. Here, Lu et al. have developed a derivative of the C-type natriuretic peptide (dCNP) to normalize vascular structures of tumors to improve therapy efficacy. They demonstrated that this modified dCNP had superior pharmacokinetic and pharmacodynamic properties as compared with native CNP. In addition, administration of dCNP to multiple mouse models remodeled tumor blood vessels and improved antitumorigenic activity of standard monotherapies. This represents a promising compound that could improve therapeutic efficacy of multiple therapies for patients with cancer that requires further study. —Dorothy Hallberg [ABSTRACT FROM AUTHOR]

Globally, eye disorders have been a major issue, especially in developing nations where resources for technology and financing are limited. Due to its tremendous feature learning ability, CNN has obtained remarkable progress in the area of fundus images. Through appropriate analysis and examination of fundus images, computer-aided diagnosis may yield information with a standard value for experts in clinical diagnosis or screening. However, the majority of earlier investigations have focused on the identification of a particular fundus disease, and the accurate fast classification of multiple fundus diseases remains a major challenge. Extremely numerous retinal fundus images must be analyzed to achieve a categorization that is reliable, fast, and precise. As a result, this research aims to propose a novel classification model for eye illnesses based on four major steps: (a) Pre-processing, (b) segmentation of blood vessels, (c) Extracting features and (d) Multi-classification of eye disease. In order to accurately classify the images, it is necessary to extract the essential informational characteristics from the segmented blood vessels. The categorization of eye diseases is carried out using a hybrid classifier that integrates the SqueezeNet and Long-Term Recurrent Convolutional Network (LRCN). We trained and validated our models using tenfold cross-validation tests on a database of fundus images including five categories: Normal, Retinitis Pigmentosa, Pathological Myopia, Maculopathy and Glaucoma. The efficacy of the presented approach is evaluated based on specificity, F1-score, recall, precision and accuracy of 98%, 97.8%, 97.6%, 98.4% and 98% respectively. [ABSTRACT FROM AUTHOR]

It has been reported that the retinal vessel and macular region of the retina are displaced after macular hole (MH) surgery. However, there is no detailed information for correlations between retinal and choroidal displacements. We obtained optical coherence tomography angiography (OCTA) and en-face optical coherence tomography (OCT) images from 24 eyes to measure the retinal and choroidal vascular displacement before and after surgery. These images were merged into infrared images using blood vessel patterns. The same vascular bifurcation points were automatically selected for each follow-up image, and the displacements of the bifurcation points were analyzed as a vector unit for prespecified grid regions in a semi-automated fashion. The results showed displacements of the choroidal intermediate vessels and retinal vessels following MH surgery (p = 0.002, p < 0.001). The topographic changes showed inferior, nasal, and centripetal displacement of the retina and inferiorly displaced choroid. The ILM peeling size and basal MH size were significantly associated with the retinal displacement (p < 0.001 and p = 0.010). Additionally, changes in the amount of the choroidal displacement were significantly correlated with that of the retinal displacements (p = 0.002). Clinicians should keep in mind that there might be topographic discrepancies of the displacement between retina and choroid when analyzing them following surgery. [ABSTRACT FROM AUTHOR]

Blood vessel endothelial cells (EC) display heterogeneity across vascular beds, which is anticipated to drive site-specific vascular pathology. This heterogeneity is assessed using transcriptomics in vivo, and functional assays in vitro, but how proteomes compare across human in vitro cultured ECs remains incompletely characterized. We generated an in-depth human EC proteomic landscape (>8000 proteins) across six organs and two in vitro models in steady-state and upon IFNγ-induced inflammation. EC proteomes displayed a high similarity and organ-specific proteins were limited. Variation between ECs was mainly based on proliferation and differentiation processes in which Blood outgrowth endothelial cells (BOEC) and Human umbilical vein cells (HUVEC) represented the extremes of proteomic phenotypes. The IFNγ response was highly conserved across all samples. Harnessing dynamics in protein abundances we delineated VWF and VE-Cadherin correlation networks. This EC landscape provides an extensive proteomic addition in studying EC biology and heterogeneity from an in vitro perspective. Analysis of proteomic signatures of commercially acquired endothelial cells from different organs in steady state and after IFNγ inflammation in the context of understanding vascular heterogeneity. [ABSTRACT FROM AUTHOR]

Simple Summary: As breast cancer rates rise, more patients choose breast reconstruction. Autologous breast reconstruction (ABR) may be more cost-effective and offer superior patient quality of life compared to prosthetic implant-based reconstruction but it involves heightened surgical complexity and extended operative time. Imaging facilitates surgical planning, patient selection, and reduces the time spent in the operating room, thereby enhancing the likelihood of surgical success and decreasing complication rates. Advanced imaging has also spurred innovative surgical techniques aimed at improving aesthetic outcomes and minimizing donor-site morbidity, including robotic-assisted deep inferior epigastric flap perforator (DIEP) flap harvest and stacked microsurgical flaps. The evolution of imaging actively shapes clinical management in the field. Ultrasonography (US), computed tomography angiography (CTA), and magnetic resonance angiography (MRA) stand out as the most extensively researched imaging modalities for ABR. Ongoing advancements include "real-time" angiography and three-dimensional (3D) surface imaging, and future prospects incorporate augmented or virtual reality (AR/VR) and artificial intelligence (AI). These technologies may further enhance perioperative efficiency, reduce donor-site morbidity, and improve surgical outcomes in ABR. [ABSTRACT FROM AUTHOR]

Simple Summary: Pancreatic cancer is a significant challenge due to its aggressive nature, complex management, high mortality rate, and low 5-year survival rate. Approximately 85% of cases are adenocarcinomas, while endocrine tumors comprise less than 5%. Borderline reresections andcally advanced pancreatic cancers are difficult to treat due to frequent vascular involvement, complicating complete resections, and increasing morbidity. Various therapeutic modalities aim to improve patient outcomes. Traditionally, upfront surgery was the standard for resectable tumors, with multimodal chemotherapy being central to treatment. Understanding surgical anatomy is pivotal for enhancing outcomes. Classification systems like the MD Anderson Criteria assess tumor involvement with major blood vessels. Neoadjuvant therapy addresses micro-metastatic disease early, increasing R0 resection chances. Dr. Sanjay S. Reddy's insights highlight the importance of a multidisciplinary approach to advancing therapy and improving prognosis. Pancreatic cancer is a significant challenge in oncology due to its aggressive nature and complex management, leading to high mortality rates and a dismally low 5-year survival rate. Approximately 85% of cases manifest as adenocarcinoma, while endocrine tumors constitute less than 5%. Borderline resectable and locally advanced pancreatic cancers are particularly difficult to treat due to vascular involvement, which complicates complete resections and increases morbidity. Various therapeutic modalities aim to overcome these challenges and improve patient outcomes. Traditionally, upfront surgery was the standard for resectable tumors, with multimodal chemotherapy being central to treatment. Understanding surgical anatomy is pivotal in enhancing surgical outcomes and patient survival. Resectability challenges are several when seeking to achieve R0 resections, particularly for borderline resectable tumors. Various classification systems—the MD Anderson criteria, the NCCN criteria, the AHPA/SSAT/SSO consensus statement, and the Alliance definition—assess tumor involvement with major blood vessels, with the first of these systems being broadly accepted. Vascular staging integration is also important, with the Ishikawa staging system using preoperative imaging to assess venous involvement. Furthermore, neoadjuvant therapy enhances treatment effectiveness by addressing micro-metastatic disease early, increasing R0 resection chances, and downstaging tumors for optimal surgery. Insights from the Fox Chase Cancer Center's neoadjuvant treatment approach highlight the importance of a multidisciplinary strategy when advancing therapy and improving patient prognosis. This commentary, inspired by Dr. Sanjay S. Reddy's Keynote Conference during MedNews week, highlights current advancements and ongoing challenges in the treatment of pancreatic cancer, emphasizing the need for a comprehensive, multidisciplinary approach to improve outcomes. [ABSTRACT FROM AUTHOR]

Simple Summary: This research investigates the effectiveness and safety of totally implantable vascular access devices (TIVADs) used for delivering treatments such as chemotherapy. Over a five-year period, 70 patients received TIVADs through a standardized surgical method under local anesthesia. The study found very low complication rates, with only two notable incidents: one device needed adjustment due to a flipped catheter, and one infection occurred after over three years of use. The procedural success rate was 100%, with devices typically lasting around 22 months, and some even up to five years. These findings suggest that TIVADs are a reliable and safe option for long-term venous access, significantly benefiting routine clinical practices. Background: Daily clinical practice requires repeated and prolonged venous access for delivering chemotherapy, antibiotics, antivirals, parenteral nutrition, or blood transfusions. This study aimed to investigate the performance and the safety of totally implantable vascular access devices (TIVADs) over a 5-year follow-up period through a standardized well-trained surgical technique and patient management under local anesthesia. Methods: In a retrospective, observational, and monocentric study, 70 patients receiving POLYSITE® TIVADs for chemotherapy were included. The safety endpoints focused on the rate of perioperative, short-term, and long-term complications. The performance endpoints included vein identification for device insertion and procedural success rate. Results: The study demonstrated no perioperative or short-term complications related to the TIVADs. One (1.4%) complication related to device manipulation was identified as catheter flipping, which led to catheter adjustment 56 days post-placement. Moreover, one (1.4%) infection due to usage conditions was observed, leading to TIVAD removal 3 years and 4 months post-surgery. Catheter placement occurred in cephalic veins (71.4%), subclavian veins (20%), and internal jugular veins (8.6%). The procedural success rate was 100%. Overall, the implantable ports typically remained in place for an average of 22.4 months. Conclusions: This study confirmed the TIVADs' performance and safety, underscored by low complication rates compared to published data, thereby emphasizing its potential and compelling significance for enhancing routine clinical practice using a standardized well-trained surgical technique and patient management. [ABSTRACT FROM AUTHOR]

Simple Summary: Breast cancer typically originates and metastasizes from the mammary fat pad. The tumor within the fat pad is supported by enriched lymphatic vessels, to a greater degree than that of blood vessels. Recently, we have successfully co-formulated two physically disparate cancer drugs, water-soluble gemcitabine (G) and water-insoluble paclitaxel (T), into a drug combination nanoparticle (DcNP) referred to as GT-in-DcNP. This GT-in-DcNP dosage form is stable and scalable. When it is given to mice, it enables synchronized delivery of GT into tumors via enriched lymph vessels. A single dose of GT-in-DcNP in mice has been found to suppress breast tumor growth in the mammary fat pad more effectively than an equivalent dose of the free GT combination. We observed tumor regression and restoration of mammary fat tissue at higher doses of GT-in-DcNP. This concept has been extended to demonstrate the ability to suppress human breast cancer in a xenograft model. With these observations, GT-in-DcNP may be considered for clinical development to treat breast cancer. Early diagnosis, intervention, and therapeutic advancements have extended the lives of breast cancer patients; however, even with molecularly targeted therapies, many patients eventually progress to metastatic cancer. Recent data suggest that residual breast cancer cells often reside in the lymphatic system before rapidly spreading through the bloodstream. To address this challenge, an effective drug combination composed of gemcitabine (G) and paclitaxel (T) is administered intravenously in sequence at the metastatic stage, but intravenous GT infusion may limit lymphatic GT drug accessibility and asynchronous drug exposure in cancer cells within the lymph. To determine whether co-localization of intracellular gemcitabine and paclitaxel (referred to as GT) could overcome these limitations and enhance the efficacy of GT, we have evaluated a previously reported GT drug-combination formulated in nanoparticle (referred to as GT-in-DcNP) evaluated in an orthotopic breast tumor model. Previously, with indocyanine green-labeled nanoparticles, we reported that GT-in-DcNP particles after subcutaneous dosing were taken up rapidly and preferentially into the lymph instead of blood vessels. The pharmacokinetic study showed enhanced co-localization of GT within the tumors and likely through lymphatic access, before drug apparency in the plasma leading to apparent long-acting plasma time-course. The mechanisms may be related to significantly greater inhibitions of tumor growth—by 100 to 140 times—in both sub-iliac and axillary regions compared to the equivalent dosing with free-and-soluble GT formulation. Furthermore, GT-in-DcNP exhibited dose-dependent effects with significant tumor regression. In contrast, even at the highest dose of free GT combination, only a modest tumor growth reduction was notable. Preliminary studies with MDA-231-HM human breast cancer in an orthotopic xenograft model indicated that GT-in-DcNP may be effective in suppressing human breast tumor growth. Taken together, the synchronized delivery of GT-in-DcNP to mammary tumors through the lymphatic system offers enhanced cellular retention and greater efficacy. [ABSTRACT FROM AUTHOR]

Background and Purpose: The single layer of cells lining all blood vessels, the endothelium, is a sophisticated signal co‐ordination centre that controls a wide range of vascular functions including the regulation of blood pressure and blood flow. To co‐ordinate activities, communication among cells is required for tissue level responses to emerge. While a significant form of communication occurs by the propagation of signals between cells, the mechanism of propagation in the intact endothelium is unresolved. Experimental Approach: Precision signal generation and targeted cellular manipulation was used in conjunction with high spatiotemporal mesoscale Ca2+ imaging in the endothelium of intact blood vessels. Key Results: Multiple mechanisms maintain communication so that Ca2+ wave propagation occurs irrespective of the status of connectivity among cells. Between adjoining cells, regenerative IP3‐induced IP3 production transmits Ca2+ signals and explains the propagated vasodilation that underlies the increased blood flow accompanying tissue activity. The inositide is itself sufficient to evoke regenerative phospholipase C‐dependent Ca2+ waves across coupled cells. None of gap junctions, Ca2+ diffusion or the release of extracellular messengers is required to support this type of intercellular Ca2+ signalling. In contrast, when discontinuities exist between cells, ATP released as a diffusible extracellular messenger transmits Ca2+ signals across the discontinuity and drives propagated vasodilation. Conclusion and Implications: These results show that signalling switches underlie endothelial cell‐to‐cell signal transmission and reveal how communication is maintained in the face of endothelial damage. The findings provide a new framework for understanding wave propagation and cell signalling in the endothelium. [ABSTRACT FROM AUTHOR]

Lymphatic vessels are essential for preventing the accumulation of harmful components within peripheral tissues, including the artery wall. Various endogenous mechanisms maintain adequate lymphatic function throughout life, with platelets being essential for preserving lymphatic vessel integrity. However, since lymph lacks platelets, their impact on the lymphatic system has long been viewed as restricted to areas where lymphatics intersect with blood vessels. Nevertheless, platelets can also exert long range effects through the release of extracellular vesicles (EVs) upon activation. We observed that platelet EVs (PEVs) are present in lymph, a compartment to which they could transfer regulatory effects of platelets. Here, we report that PEVs in lymph exhibit a distinct signature enabling them to interact with lymphatic endothelial cells (LECs). In vitro experiments show that the internalization of PEVs by LECs maintains their functional integrity. Treatment with PEVs improves lymphatic contraction capacity in atherosclerosis-prone mice. We suggest that boosting lymphatic pumping with exogenous PEVs offers a novel therapeutic approach for chronic inflammatory diseases characterized by defective lymphatics. This work shows that platelet extracellular vesicles play a role in regulating lymphatic endothelial cell integrity and improving lymphatic function. [ABSTRACT FROM AUTHOR]

Physiologically relevant concentrations in biological tissue, in the in vivo, state are of the order of μmol L−1 and mmol L−1. Up to the present, mapping the major elements in the matrix and its thickness has been neglected, despite their importance for quantification of lesser and trace element concentrations. Ryan and Jamieson's dynamic analysis, statistical spectral decomposition approach, is developed to quantitatively measure ex vivo tissue sections cut using a cryomicrotome. This mitigates the problem that physical analysis methods require a vacuum environment. This approach is used to quantitatively image the major matrix elements H, C, N, and O as well as trace maps of Ca, Fe, and Zn in a tissue section of porcine intestine. This sample is selected as it exhibits a complex morphology with multiple tissue compartments (such as muscle and mucosa, as well as void areas from blood vessels, lymph ducts, sinuses crypts, and villi. In the results, it is demonstrated that different tissue types can have a different matrix composition and thickness. Using this information, quantitative maps and elemental molarities for the lesser and trace elements Ca, Fe, and Zn are obtained. [ABSTRACT FROM AUTHOR]

Osteogenesis is tightly coupled with angiogenesis spatiotemporally. Previous studies have demonstrated that type H blood vessel formed by endothelial cells with high expression of CD31 and Emcn (CD31hi Emcnhi ECs) play a crucial role in bone regeneration. The mechanism of the molecular communication around CD31hi Emcnhi ECs and bone mesenchymal stem cells (BMSCs) in the osteogenic microenvironment is unclear. This study indicates that exosomes from bone mesenchymal stem cells with 7 days osteogenic differentiation (7D-BMSCs-exo) may promote CD31hi Emcnhi ECs angiogenesis, which was verified by tube formation assay, qRT-PCR, Western blot, immunofluorescence staining and µCT assays etc. in vitro and in vivo. Furthermore, by exosomal miRNA microarray and WGCNA assays, we identified downregulated miR-150-5p as the most relative hub gene coupling osteogenic differentiation and type H blood vessel angiogenesis. With bioinformatics assays, dual luciferase reporter experiments, qRT-PCR and Western blot assays, SOX2(SRY-Box Transcription Factor 2) was confirmed as a novel downstream target gene of miR-150-5p in exosomes, which might be a pivotal mechanism regulating CD31hi Emcnhi ECs formation. Additionally, JC-1 immunofluorescence staining, Western blot and seahorse assay results showed that the overexpression of SOX2 could shift metabolic reprogramming from oxidative phosphorylation (OXPHOS) to glycolysis to enhance the CD31hi Emcnhi ECs formation. The PI3k/Akt signaling pathway might play a key role in this process. In summary, BMSCs in osteogenic differentiation might secrete exosomes with low miR-150-5p expression to induce type H blood vessel formation by mediating SOX2 overexpression in ECs. These findings might reveal a molecular mechanism of osteogenesis coupled with type H blood vessel angiogenesis in the osteogenic microenvironment and provide a new therapeutic target or cell-free remedy for osteogenesis impaired diseases. [ABSTRACT FROM AUTHOR]

A novel NIR-II nanoprobe was developed through regulating the steric effect of an A–DA′D–A dye. The probe features the properties of strong fluorescence, high stability, and a large Stokes shift, thereby serving as a remarkable contrast agent for the fluorescence imaging of hindlimb vasculature and tumors in live mice. [ABSTRACT FROM AUTHOR]

Infective endocarditis (IE) poses a significant clinical challenge, especially among patients with end-stage renal disease (ESRD) undergoing dialysis, and is associated with high morbidity and mortality rates. This review provides a contemporary discussion of the epidemiology, risk factors, diagnostic challenges, and management strategies for IE among ESRD patients, including a literature review of recent studies focused on this vulnerable population. The review highlights the multifactorial nature of IE risk in ESRD patients, emphasizing the roles of vascular access type, dialysis modality, and comorbid conditions. It also explores the diagnostic utility of different imaging modalities and the importance of a multidisciplinary approach in managing IE, including both medical and surgical interventions. The insights from this review aim to contribute to the improvement of patient outcomes through early recognition, appropriate antimicrobial therapy, and timely surgical intervention when necessary. [ABSTRACT FROM AUTHOR]

Takotsubo syndrome (TTS) was first described in postmenopausal women with transient regional wall motion abnormalities. The trigger is usually an emotional or physical stress. The catecholamine hypothesis seems to be the most prevailing. The main difference between TTS and acute coronary syndromes is that there is no obstructive coronary disease to explain the regional abnormalities. In this form, the left ventricle resembles the fishing jar which is used to trap octopus in Japan. However, to date more atypical forms are recognized. Also, the syndrome is not limited to older women. Nowadays, TTS is presented even in pregnancy and postpartum females. Our experience revealed cases of patients during these periods and some of them suffered from reverse Takotsubo. Additionally, the initial diagnosis in some patients was other than TTS. Due to these findings, we suggest that this type of TTS is not very rare but underestimated. For this reason, further studies are needed to support and explain this condition. [ABSTRACT FROM AUTHOR]

Alzheimer's disease is the most prevalent form of dementia. Apart from its traditional clinical diagnostic methods, novel ocular imaging biomarkers have the potential to significantly enhance the diagnosis of Alzheimer's disease. Ophthalmologists might be able to play a crucial role in this multidisciplinary approach, aiding in the early detection and diagnosis of Alzheimer's disease through the use of advanced retinal imaging techniques. This systematic literature review the utilization of optical coherence tomography angiography biomarkers, specifically vessel density and the foveal avascular zone, for the diagnosis of Alzheimer's disease. A comprehensive search was performed across multiple academic journal databases, including 11 relevant studies. The selected studies underwent thorough analysis to assess the potential of these optical coherence tomography angiography biomarkers as diagnostic tools for Alzheimer's disease. The assessment of vessel density and the foveal avascular zone have emerged as a promising avenue for identifying and diagnosing Alzheimer's disease. However, it is imperative to acknowledge that further targeted investigations are warranted to address the inherent limitations of the existing body of literature. These limitations encompass various factors such as modest sample sizes, heterogeneity among study populations, disparities in optical coherence tomography angiography imaging protocols, and inconsistencies in the reported findings. In order to establish the clinical utility and robustness of these biomarkers in Alzheimer's disease diagnosis, future research endeavors should strive to overcome these limitations by implementing larger-scale studies characterized by standardized protocols and comprehensive assessments. [ABSTRACT FROM AUTHOR]

Calcification has significant influence over cardiovascular diseases and interventions. Detailed characterization of calcification is thus desired for predictive modeling, but calcium deposits on cardiovascular structures are still often manually reconstructed for physics-driven simulations. This poses a major bottleneck for large-scale adoption of computational simulations for research or clinical use. To address this, we propose an end-to-end automated image-to-mesh algorithm that enables robust incorporation of patient-specific calcification onto a given cardiovascular tissue mesh. The algorithm provides a substantial speed-up from several hours of manual meshing to ~1 min of automated computation, and it solves an important problem that cannot be addressed with recent template-based meshing techniques. We validated our final calcified tissue meshes with extensive simulations, demonstrating our ability to accurately model patient-specific aortic stenosis and Transcatheter Aortic Valve Replacement. Our method may serve as an important tool for accelerating the development and usage of personalized cardiovascular biomechanics. [ABSTRACT FROM AUTHOR]