Venous Circulation Research Articles

An anatomically detailed arterial-venous network model. Cerebral and coronary circulation.

In recent years, several works have addressed the problem of modeling blood flow phenomena in veins, as a response to increasing interest in modeling pathological conditions occurring in the venous network and their connection with the rest of the circulatory system. In this context, one-dimensional models have proven to be extremely efficient in delivering predictions in agreement with in-vivo observations. Pursuing the increase of anatomical accuracy and its connection to physiological principles in haemodynamics simulations, the main aim of this work is to describe a novel closed-loop Anatomically-Detailed Arterial-Venous Network (ADAVN) model. An extremely refined description of the arterial network consisting of 2,185 arterial vessels is coupled to a novel venous network featuring high level of anatomical detail in cerebral and coronary vascular territories. The entire venous network comprises 189 venous vessels, 79 of which drain the brain and 14 are coronary veins. Fundamental physiological mechanisms accounting for the interaction of brain blood flow with the cerebro-spinal fluid and of the coronary circulation with the cardiac mechanics are considered. Several issues related to the coupling of arterial and venous vessels at the microcirculation level are discussed in detail. Numerical simulations are compared to patient records published in the literature to show the descriptive capabilities of the model. Furthermore, a local sensitivity analysis is performed, evidencing the high impact of the venous circulation on main cardiovascular variables.

Experience of Physical Examination as a Primary Tool for Surgical Access Planning in Hemodialysis Patients

Abstract: Background: Understanding the importance of pre-operative assessment is something nephrologists are probing for years to avoid any post-operative complication and AVF failure. Objective: To assess the physical examination as primary tool as compared to Ultrasound Doppler in assessment of AVF planning in hemodialysis patients. Materials and Methods: This was a Retrospective, Cross-sectional study. Secondary data was collected from the Urology Department of Liquate University of Medical and health sciences, Jamshoro starting from October 2021 to October 2022. For physical examination, both the arterial and venous circulation were evaluated. Arterial patency, pulse amplitude and Allen’s test were recorded. After collection of data, statistical Package for Social Science (SPSS) version 17. 0 statistical software was used for analysis. Results: A total of 105 participants with mean age of 42.9 ± 13.9 years, 78 (74.3%) males and 27 (25.7%) females were included. The physical examination findings indicated facial swelling as the most frequently reported sign in with 59 (56.2%) of patients, followed by generalized body edema reported in 22 (21%) of participants. The estimated analysis of Allen’s test indicated good results with a mean of 12.4 ± 2.8 seconds in all patients, indicating good blood flow of the ulnar artery. The mean duration of hemodialysis was 55.2 ± 23.4 days before AVF, while central venous line duration was 57.2 ± 20.5 days. After 6 days fistula maturation was assessed, while mean fistula maturation duration was 44 ± 7.1 days. Conclusion: To monitor functioning, the Physical Examination of vascular access is convenient, straightforward, and cost-effective. Physical examination (PE) has been validated with diagnostic techniques for detecting stenosis.

Cement pulmonary embolism as a complication of percutaneous vertebroplasty in a patient with follicular lymphoma

Vertebroplasty involves injecting a cement polymer, often polymethylmethacrylate (PMA), into the vertebral body under imaging guidance to increase stability. However, the high vascularization and anatomical network of the paravertebral and extradural venous plexuses can allow the migration of cement particles into the systemic venous circulation regardless of whether spinal compression or fractures occur during or are present prior to the treatment. This case report presents a 42-year-old female patient who visited the emergency room with symptoms of cough, nasal obstruction, rhinorrhea, and dyspnea and had a history of follicular non-Hodgkin’s lymphoma under rituximab treatment. Imaging revealed a cement embolism in the pulmonary artery tree, most likely caused by prior vertebroplasty. Anticoagulation was started despite the lack of hypoxemia due to the inorganic character of the embolic substance and the patient’s immunosuppressed status. The embolic debris was still present on subsequent imaging, but the patient’s condition remained stable, with some signs of illness remission. This case highlights the importance of considering cement embolism as a possible vertebroplasty complication and the importance of properly assessing and managing such cases, particularly in patients with underlying medical issues, as well as the need for the development of a standard protocol of sequential chest X-rays after the procedure and possible alternatives to PMA.

An ultrasound imaging and computational fluid dynamics protocol to assess hemodynamics in iliac vein compression syndrome

ObjectiveElevated shear rates are known to play a role in arterial thrombosis; however, shear rates have not been thoroughly investigated in patients with iliac vein compression syndrome (IVCS) owing to imaging limitations and assumptions on the low shear nature of venous flows. This study was undertaken to develop a standardized protocol that quantifies IVCS shear rates and can aid in the diagnosis and treatment of patients with moderate yet symptomatic compression. MethodsStudy patients with and without IVCS had their iliac vein hemodynamics measured via duplex ultrasound (US) at two of the following three vessel locations: infrarenal inferior vena cava (IVC), right common iliac vein, and left common iliac vein, in addition to acquiring data at the right and left external iliac veins. US velocity spectra were multiplied by a weighted cross-sectional area calculated from US and computed tomography (CT) data to create flow waveforms. Flow waveforms were then scaled to enforce conservation of flow across the IVC and common iliac veins. A three-dimensional (3D), patient-specific model of the iliac vein anatomy was constructed from CT and US examination. Flow waveforms and the 3D model were used as a basis to run a computational fluid dynamics (CFD) simulation. Owing to collateral vessel flow and discrepancies between CT and US area measurements, flows in internal iliac veins and cross-sectional areas of the common iliac veins were calibrated iteratively against target common iliac flow. Simulation results on mean velocity were validated against US data at measurement locations. Simulation results were postprocessed to derive spatial and temporal values of quantities such as velocity and shear rate. ResultsUsing our modeling protocol, we were able to build CFD models of the iliac veins that matched common iliac flow splits within 2% and measured US velocities within 10%. Proof-of-concept analyses (1 subject, 1 control) have revealed that patients with IVCS may experience elevated shear rates in the compressed left common iliac vein, more typical of the arterial rather than the venous circulation. These results encourage us to extend this protocol to a larger group of patients with IVCS and controls. ConclusionsWe developed a protocol that obtains hemodynamic measurements of the IVC and iliac veins from US, creates patient-specific 3D reconstructions of the venous anatomy using CT and US examinations, and computes shear rates using calibrated CFD methods. Proof-of-concept results have indicated that patients with IVCS may experience elevated shear rates in the compressed left common iliac vein. Larger cohorts are needed to assess the relationship between venous compression and shear rates in patients with IVCS as compared with controls with noncompressed iliac veins. Further studies using this protocol may also give promising insights into whether or not to treat patients with moderate, yet symptomatic compression.

Emerging Role of GLP-1 Agonists in Obesity: A Comprehensive Review of Randomised Controlled Trials.

Obesity is a chronic disease with high prevalence and associated comorbidities, making it a growing global concern. These comorbidities include type 2 diabetes, hypertension, ventilatory dysfunction, arthrosis, venous and lymphatic circulation diseases, depression, and others, which have a negative impact on health and increase morbidity and mortality. GLP-1 agonists, used to treat type 2 diabetes, have been shown to be effective in promoting weight loss in preclinical and clinical studies. This review summarizes numerous studies conducted on the main drugs in the GLP-1 agonists class, outlining the maximum achievable weight loss. Our aim is to emphasize the active role and main outcomes of GLP-1 agonists in promoting weight loss, as well as in improving hyperglycemia, insulin sensitivity, blood pressure, cardio-metabolic, and renal protection. We highlight the pleiotropic effects of these medications, along with their indications, contraindications, and precautions for both diabetic and non-diabetic patients, based on long-term follow-up studies.

Deep learning phase error correction for cerebrovascular 4D flow MRI

Background phase errors in 4D Flow MRI may negatively impact blood flow quantification. In this study, we assessed their impact on cerebrovascular flow volume measurements, evaluated the benefit of manual image-based correction, and assessed the potential of a convolutional neural network (CNN), a form of deep learning, to directly infer the correction vector field. With IRB waiver of informed consent, we retrospectively identified 96 MRI exams from 48 patients who underwent cerebrovascular 4D Flow MRI from October 2015 to 2020. Flow measurements of the anterior, posterior, and venous circulation were performed to assess inflow-outflow error and the benefit of manual image-based phase error correction. A CNN was then trained to directly infer the phase-error correction field, without segmentation, from 4D Flow volumes to automate correction, reserving from 23 exams for testing. Statistical analyses included Spearman correlation, Bland–Altman, Wilcoxon-signed rank (WSR) and F-tests. Prior to correction, there was strong correlation between inflow and outflow (ρ = 0.833–0.947) measurements with the largest discrepancy in the venous circulation. Manual phase error correction improved inflow-outflow correlation (ρ = 0.945–0.981) and decreased variance (p < 0.001, F-test). Fully automated CNN correction was non-inferior to manual correction with no significant differences in correlation (ρ = 0.971 vs ρ = 0.982) or bias (p = 0.82, Wilcoxon-Signed Rank test) of inflow and outflow measurements. Residual background phase error can impair inflow-outflow consistency of cerebrovascular flow volume measurements. A CNN can be used to directly infer the phase-error vector field to fully automate phase error correction.

Intrapericardial Blood Re-transfused to Venous Circulation Through a Closed Circuit: A Life- Saving Management of Hemopericardium.

Intrapericardial Blood Re-transfused to Venous Circulation Through a Closed Circuit: A Life- Saving Management of Hemopericardium.

Acute kidney injury in cardiac critical care: bringing the venous circulation out of the shadows.

Acute kidney injury in cardiac critical care: bringing the venous circulation out of the shadows.

Cerebral Outflow Discrepancies in Recurrent Benign Paroxysmal Positional Vertigo: Focus on Ultrasonographic Examination.

This prospective pilot study aimed to evaluate whether cerebral inflow and outflow abnormalities assessed by ultrasonographic examination could be associated with recurrent benign paroxysmal positional vertigo (BPPV). Twenty-four patients with recurrent BPPV, affected by at least two episodes, and diagnosed according to American Academy of Otolaryngology-Head and Neck Surgery (AAO-HNS) criteria, evaluated at our University Hospital, between 1 February 2020 and 30 November 2021, have been included. At the ultrasonographic examination, 22 of 24 patients (92%) reported one or more alterations of the extracranial venous circulation, among those considered for the diagnosis of chronic cerebrospinal venous insufficiency (CCSVI), although none of the studied patients were found to have alterations in the arterial circulation. The present study confirms the presence of alterations of the extracranial venous circulation in recurrent BPPV; these anomalies (such as stenosis, blockages or regurgitation of flow, or abnormal valves, as per the CCSVI) could cause a disruption in the venous inner ear drainage, hampering the inner ear microcirculation and then possibly causing recurrent otolith detachment.

Experience in complex therapy of lower limb trophic ulcers of venous and diabetic origin

Trophic ulcers (TU) associated with venous circulation pathology or diabetes mellitus are considered chronic wounds with all the attributes of the complex extracellular matrix (ECM) reorganization and tissue remodelling of the edges and bed of these wounds. It was therefore determined that only a comprehensive step-wise approach to the treatment of TU can produce a stable clinical result. The article presents the experience of comprehensive management of venous and diabetic TUs. Three clinical cases of management of patients with lower limb TUs are described. The treatment of patients was planned taking into account the accepted algorithms for the management of TU associated venous circulation pathology or diabetes mellitus. The topical therapy included advanced wound coverings. The choice of dressing was determined by the clinical course of wound process. Alginate dressings were used on stages I and II wounds; hydrocolloid dressings were used on stages II and III wounds. Effects resulting from treatment included almost complete healing or readiness of a TU for skin grafting. The topical therapy of venous and diabetic TUs is part of the comprehensive treatment. During phase 1 wound process, the topical drugs should have antimicrobial, necrolytic, draining, osmotic and analgesic action. During phase 2, the granulation tissue should be induced and the balanced moist environment should be created to promote tissue regeneration. The wound coverings specified in the above clinical examples are fully consistent with the principles of the TIME concept, their ease of use and comfort for the patient are pointed out.

Effects of Rheum rhaponticum and Rheum rhabarbarum extracts on haemostatic activity of blood plasma components and endothelial cells in vitro

Ethnopharmacological relevanceTraditional medicine recommends the use of Rheum rhaponticum L. and R. rhabarbarum L. to treat over thirty complaints, including disorders related to the cardiovascular system such as heartache, pains in the pericardium, epistaxis and other types of haemorrhage, blood purification as well as disorders of venous circulation. Aim of the studyThis work was dedicated to examining for the first time the effects of extracts from petioles and roots of R. rhaponticum and R. rhabarbarum, as well as two stilbene compounds (rhapontigenin and rhaponticin) on the haemostatic activity of endothelial cells and functionality of blood plasma components of the haemostatic system. Materials and methodsThe study was based on three main experimental modules, including the activity of proteins of the human blood plasma coagulation cascade and the fibrinolytic system as well as analyses of the haemostatic activity of human vascular endothelial cells. Additionally, interactions of the main components of the rhubarb extracts with crucial serine proteases of the coagulation cascade and fibrinolysis (i.e. thrombin, the coagulation factor Xa and plasmin) were analyzed in silico. ResultsThe examined extracts displayed anticoagulant properties and significantly reduced the tissue factor-induced clotting of human blood plasma (by about 40%). Inhibitory effects of the tested extracts on thrombin and the coagulation factor Xa (FXa) were found as well. For the extracts, the IC50 was ranging from 20.26 to 48.11 μg/ml. Modulatory effects on the haemostatic response of endothelial cells, including the release of von Willebrand factor, tissue-type plasminogen activator and the plasminogen activator inhibitor-1, have been also found. ConclusionsOur results indicated for the first time that the examined Rheum extracts influenced the haemostatic properties of blood plasma proteins and endothelial cells, with the prevalence of the anticoagulant action. The anticoagulant effect of the investigated extracts may be partly attributed to the inhibition of the FXa and thrombin activities, the key serine proteases of the blood coagulation cascade.

BLIND-SIDED BY BLACK FUNGUS: CRAO IN CAM

Importance: There has been an outbreak of COVID-19 associated rhino-orbito-cerebral mucormycosis (CAM) in many parts of developing world. The clinical prole, mortality rate, risk factors associated with it has been studied. A case series highlighting association of Central Retinal Artery Occlusion (CRAO) in CAM has not been reported yet. To report a case series of Central Retinal Artery Occlusion (CRAO) in 15 pati Objective: ents with history of COVID19 infection associated mucormycosis (CAM). This is a retrospective observational study of Design: 15 cases of rhino-cerebroorbital mucormycosis (ROCM) which presented to our tertiary referral centre between March 2021 and June 2021. All patients had unilateral or bilateral CRAO. Tertiary care multispecialty hospital in western India. Setting: Participants: All patients diagnosed with CAM and having unilateral or bilateral CRAO. Main outcome measure: The COVID-19 disease induced inammatory homeostasis changes that predispose to thrombotic disease in both venous and arterial circulation in CAM. Overall prognosis appears to be poor with mortality rate of 14- 50% in various studies. Fifteen patients were studied of Results: which 13 were male and rest females. The mean age of patients was 55.6 + 12.13 years (Range: 39 –78 years). Majority had uncontrolled Type 2 Diabetes Mellitus. Tissue and radiological diagnosis of mucormycosis was made in all patients. Twelve patients had unilateral CRAO and 3 patients had bilateral CRAO. Diabetes and systemic ster Conclusions and relevance: oids have proven to be risk factors for development of CRAO in CAM. Early ophthalmic screening should be initiated in COVID-19 patients with systemic co-morbidities, to reduce the immediate and late sequelae.

Portal Endovascular Rendezvous Catheterization (PERC): An innovative transabdominal technique of accessing the portal vein for large animal translational vascular research

Previously described techniques for portomesenteric venous wire access typically require specialized expertise, technical skills, and equipment. The aim of this paper is to describe Portal Endovascular Rendezvous Catheterization (PERC), a simpler approach to access the portal vein for large animal translational research purposes. Using Swine, this technique utilizes a hybrid approach with percutaneous access of the internal jugular vein and open transabdominal access of the portal vein. A through-and-through micropuncture of the portal vein into the inferior vena cava at the level of the hepatic parenchyma allows for the access wire to be snared and access sheath advanced into the portal venous system, which then allows for any indicated sampling or endovascular interventions in the portomesenteric venous circulation. PERC is more manageable than transjugular intrahepatic portosystemic shunt (TIPS) placement for portal venous access, and its use will allow a greater breadth of translational researchers to access the portal vein.

Analysis of the efficacy of microdissection of paravebous sinus meningiomas invading large venous sinuses

ObjectiveThe management of paravebous sinus meningiomas that invade major venous sinuses is a subject of debate, particularly concerning the necessity of complete resection of the tumor and reconstruction of the venous sinus. This article aims to demonstrate the outcomes of total removal of the lesion (including the invading venous sinus portion) and the effects of restoring or not restoring venous circulation in terms of recurrence of the tumor, mortality, and post-operative complications.MethodsThe authors conducted a study involving 68 patients with paravebous sinus meningiomas. Of the 60 parasagittal meningiomas, 23 were located in the anterior third, 30 in the middle third, and 7 in the posterior third. Additionally, 3 lesions were located in the sinus confluence area, and 5 in the transverse sinus. All patients underwent surgery, and the degree of venous sinus involvement was classified into six types. For type I meningiomas, the outer layer of the sinus wall was stripped off. For types II to VI, two strategies were employed: non-constitutional, wherein the tumor and affected venous sinuses were removed without repair, and reconstructive, wherein the tumor was completely removed and the venous sinuses were sutured or repaired. Karnofsky Performance Status (KPS) scale and Magnetic Resonance Venography (MRV) were utilized to assess the outcomes of the surgical procedures.ResultsThe study group of 68 patients underwent complete tumor resection in 97.1%, with sinus reconstruction attempted in 84.4% of cases with sinus wall and sinus cavity invasion. The recurrence rate of this group was 5.9%, with follow-up ranging from 33 to 57 months. It was found that the recurrence rate was significantly higher in cases with incomplete resection than in those with complete resection. The overall mortality rate was 4.4%, with all cases resulting from malignant brain swelling due to the failure to perform venous reconstruction after resectioning of the meningioma type VI. Furthermore, 10.3% of patients experienced worsening symptoms of neurological deficits or complete loss of neurological function, with a significantly higher incidence in those without venous reconstruction than in the venous reconstruction group (P < 0.0001, Fisher test). No statistically significant pre-operative and post-operative KPS differences were observed in patients with type I to V. However, in patients with type VI (who did not receive venous reconstruction), the post-operative KPS score was significantly worse.ConclusionThe results of this study suggest the necessity of a complete resection of the tumor, including the invasive venous sinus component, as the recurrence rate was found to be relatively low at 5.9%. Moreover, patients who did not undergo venous reconstruction showed significant deterioration in their clinical condition compared to other subgroups, thus highlighting the importance of venous sinus reconstruction.

The “forgotten circulation”: Sympathetic control of mesenteric venous capacity in conscious hypertensive rats

The venous circulation is often “forgotten,” as cardiovascular research and therapeutic intervention focusses predominantly on arteries. However, systemic veins store two-thirds of blood volume at rest, with reservoir beds such as the mesenteric circulation receiving dense sympathetic innervation, suggesting a critical neurogenic role for the mobilization of blood. The impact of hypertension on sympathetic regulation of venous circulation remains unclear. We hypothesized that capacity of mesenteric vasculature is impaired in spontaneously hypertensive rats (SHR) and that reducing sympathetic drive will increase mesenteric buffering of excess volume.SHR (n=6) and Wistar rats (n=7) were instrumented with telemeters recording arterial and venous pressures, and an atrial balloon for assessment of mean circulatory filling pressure (MCFP). Arterial (inflow) and venous (outflow) mesenteric flow probes were implanted to measure total mesenteric volume fluctuation. Mesenteric vascular capacity was challenged with 20% volume load of intravenous saline. In SHR sympathetic drive was reduced via hexamethonium (10mg/kg) or via carotid body denervation (CBD).MCFP was elevated in SHR (+2.7±0.5mmHg, p&lt;0.01 vs Wistars). MCFP in SHR was reduced by hexamethonium (-2.6±0.6; p=0.01 vs Baseline, n=5) and CBD (‑2.0±0.7mmHg; p=0.04 vs Baseline, n=5). In normotensives volume load was accommodated by the mesenteric bed, with a net total influx of blood (+5.4±2.2ml; n=7). In contrast, SHR showed a counter-intuitive net efflux of blood from the mesenteric bed (-1.6±1.4ml; p=0.04 vs Wistars, n=6). Preliminary results indicate that hexamethonium and CBD tended to increase the ability of the mesenteric bed to accommodate volume (hexamethonium: +1.9±1.5, n=6; CBD: +0.8±0.6ml, n=3).We show that SHR have higher venous tone and reduced capacity to accommodate excess volume within the mesenteric vascular bed. Reductions in sympathetic drive reduced venous tone and improved the ability to accommodate volume load. Inhibiting sympathetic activity may provide a novel therapeutic opportunity to restore venous mesenteric capacity and potentially ameliorate hypertension. Marsden Fund, Royal Society of New Zealand; Health Research Council of New Zealand This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Comparative localization of the courses of superficial veins in rabbits' limbs using latex and VeinViewer systems.

The purpose of this study; It is to reveal whether the veinviewer device, which we have not encountered in animals, can be visualized in rabbits for thoracic and pelvic limb superficial veins. Therefore, the latex method was used as a "gold test" to verify VeinViewer precision. For this purpose, the project was designed with two stages. In the first stage, the extremities of 15 New Zealand white rabbits were imaged using the VeinViewer device, and the results were recorded. In the second stage, the latex injection method was applied to the same animals, the cadavers were dissected, and the obtained results were comparatively analysed. In the rabbits, it was determined that v. cephalica originated from v. jugularis or v. brachialis in the proximity of the insertion of m. omotransversarius and anastomosed with v. mediana at the middle 1/3 level of the antebrachium. It was found that the superficial venous circulation of the pelvic limbs was provided by the branches of v. iliaca externa and v. iliaca interna. The vena saphena medialis was determined to be present in pairs in 80% of the cadavers. All cadavers showed the presence of the ramus anastomoticus cum vena saphena mediali. Additionally, the superficial veins of both the thoracic limbs and pelvic limbs of the rabbits were imaged with the VeinViewer device, which provided results parallel with the results of the latex injection method. Considering that the findings obtained with the latex injection method and the VeinViewer device were compatible, the usage of this device can potentially be considered as an alternative to visualizing superficial veins in animals. Further morphological and clinical studies can prove that the method is applicable.

Recurrent Transient Ischemic Attacks in a Patient with Multiple Pacemaker Leads

Venous complications-specifically, stenosis and thrombosis-are both well-known complications of transvenous implantation of pacemakers and defibrillators. Although they are a well-recognized phenomenon, these complications are rarely of clinical significance. One of the most concerning complications is the development of superior vena cava (SVC) syndrome. Studies have found that the incidence of SVC syndrome varies from 1 in 3,100 to 1 in 650 patients. The azygos-hemiazygos venous system is the most commonly observed collateral. We report a case of a 71-year-old female patient who presented with stroke-like symptoms during the injection of agitated saline bubbles while performing an echo and was found to have an unusual venous collateral circulation formed as a result of brachiocephalic and SVC obstruction from multiple pacemaker leads. Our patient's clinical presentation was extremely unique, and we did not find any cases during our literature search reporting a similar presentation. Multiple collaterals formed between the brachiocephalic and subclavian veins, and bilateral pulmonary veins in our patient allowed the injected air bubbles from the venous system to reach the left side of the heart and eventually the cerebrovascular system, resulting in these transient ischemic attacks. These attacks eventually resolved as the air bubbles were dissolved and washed away by the continuous blood flow. It is advisable to monitor the patient for possible venous stenosis and SVC syndrome after any device insertion during regular device follow-up appointments.

High‐depth next‐generation sequencing panel testing in the evaluation of arteriovenous malformations

Arteriovenous malformations (AVMs) are vascular lesions in which an overgrowth of blood vessels of varying sizes develops with one or more direct connections between the arterial and venous circulation. We performed a retrospective review of a cohort of 54 patients with AVMs referred to our clinical genomic laboratory for high-depth next-generation sequencing (NGS) panel of Disorders of Somatic Mosaicism (DoSM). Thirty-seven of 54 patients were female (68.5%). Among the 54 cases, 37 (68.5%) cases had pathogenic and/or likely pathogenic (P/LP) variants identified, two cases (3.7%) had variants of uncertain clinical significance, and the remaining 15 cases (27.8%) had negative results. MAP2K1 variants were found in 12 cases, followed by eight cases with KRAS variants and seven with TEK variants, and the remainder being identified in several other genes on the panel. Among the 37 positive cases, 32 cases had somatic alterations only; the remaining five cases had at least one germline P/LP variant, including four cases with PTEN and one with RASA1. Of note, two cases had the unexpected co-existence of two P/LP variants. In summary, this study illustrated the molecular diagnostic yield (68.5%) of this cohort of patients with a clinical indication of AVMs by our high-depth DoSM NGS panel.

The in vivo study of cardiac mechano-electric and mechano-mechanical coupling during heart development in zebrafish.

In the adult heart, acute adaptation of electrical and mechanical activity to changes in mechanical load occurs via feedback processes known as "mechano-electric coupling" and "mechano-mechanical coupling." Whether this occurs during cardiac development is ill-defined, as acutely altering the heart's mechanical load while measuring functional responses in traditional experimental models is difficult, as embryogenesis occurs in utero, making the heart inaccessible. These limitations can be overcome with zebrafish, as larvae develop in a dish and are nearly transparent, allowing for in vivo manipulation and measurement of cardiac structure and function. Here we present a novel approach for the in vivo study of mechano-electric and mechano-mechanical coupling in the developing zebrafish heart. This innovative methodology involves acute in vivo atrial dilation (i.e., increased atrial preload) in larval zebrafish by injection of a controlled volume into the venous circulation immediately upstream of the heart, combined with optical measurement of the acute electrical (change in heart rate) and mechanical (change in stroke area) response. In proof-of-concept experiments, we applied our new method to 48h post-fertilisation zebrafish, which revealed differences between the electrical and mechanical response to atrial dilation. In response to an acute increase in atrial preload there is a large increase in atrial stroke area but no change in heart rate, demonstrating that in contrast to the fully developed heart, during early cardiac development mechano-mechanical coupling alone drives the adaptive increase in atrial output. Overall, in this methodological paper we present our new experimental approach for the study of mechano-electric and mechano-mechanical coupling during cardiac development and demonstrate its potential for understanding the essential adaptation of heart function to acute changes in mechanical load.

Conservative Surgery -Bilateral Uterine Artery Ligation for Uterine Av Fistula

An important but rare differential diagnosis for abnormal uterine bleeding is Uterine Arteriovenous fistula. The bleeding in these patients is due to abnormal vasculature in uterus, where is congenital or acquired connection between the arterial and venous circulation of the uterus. Acquired AVM is seen following Endometrial damage. Symptoms can vary from menorrhagia, metrorahgia to acute severe bleeding episode. Treatment options usually offered is uterine artery embolization and in failed cases of embolization, hysterectomy. This case report describes a conservative surgical management by Laparoscopic uterine artery ligation as a treatment option for Uterine AV fistula in young women who desire to retain fertility