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Experimental Eye Research Jun 2024Aqueous humor (AQH) is a transparent fluid with characteristics similar to those of the interstitial fluid, which fills the eyeball posterior and anterior chambers and... (Review)
Review
Aqueous humor (AQH) is a transparent fluid with characteristics similar to those of the interstitial fluid, which fills the eyeball posterior and anterior chambers and circulates in them from the sites of production to those of drainage. The AQH volume and pressure homeostasis is essential for the trophism of the ocular avascular tissues and their normal structure and function. Different AQH outflow pathways exist, including a main pathway, quite well defined anatomically and referred to as the conventional pathway, and some accessory pathways, more recently described and still not fully morphofunctionally understood, generically referred to as unconventional pathways. The conventional pathway is based on the existence of a series of conduits starting with the trabecular meshwork and Schlemm's Canal and continuing with a system of intrascleral and episcleral venules, which are tributaries to veins of the anterior segment of the eyeball. The unconventional pathways are mainly represented by the uveoscleral pathway, in which AQH flows through clefts, interstitial conduits located in the ciliary body and sclera, and then merges into the aforementioned intrascleral and episcleral venules. A further unconventional pathway, the lymphatic pathway, has been supported by the demonstration of lymphatic microvessels in the limbal sclera and, possibly, in the uvea (ciliary body, choroid) as well as by the ocular glymphatic channels, present in the neural retina and optic nerve. It follows that AQH may be drained from the eyeball through blood vessels (TM-SC pathway, US pathway) or lymphatic vessels (lymphatic pathway), and the different pathways may integrate or compensate for each other, optimizing the AQH drainage. The present review aims to define the state-of-the-art concerning the structural organization and the functional anatomy of all the AQH outflow pathways. Particular attention is paid to examining the regulatory mechanisms active in each of them. The new data on the anatomy and physiology of AQH outflow pathways is the key to understanding the pathophysiology of AQH outflow disorders and could open the way for novel approaches to their treatment.
Topics: Aqueous Humor; Humans; Lymphatic System; Sclera; Trabecular Meshwork; Lymphatic Vessels; Veins; Uvea; Animals; Intraocular Pressure; Lymph; Ciliary Body
PubMed: 38642600
DOI: 10.1016/j.exer.2024.109904 -
Journal of Clinical Medicine Apr 2024: The surgical treatment of chronic limb-threatening ischemia and optimal conduit choice are extensively debated. The presence of suboptimal autologous material, such as...
: The surgical treatment of chronic limb-threatening ischemia and optimal conduit choice are extensively debated. The presence of suboptimal autologous material, such as varicosities or venous aneurysms, might impair long-term outcomes. Therefore, kink-resistant external supports have been advocated in the recent literature to improve the conduit quality and outcomes. This study analyzes the FRAME external support in venous ectasic grafts in patients with chronic limb-threatening ischemia. : From September 2017 to September 2023, a total of sixteen patients underwent CLTI surgery with FRAME external support for venous grafts. The inclusion criteria for FRAME applications were varicose or ectasic autologous material with a diameter ≥ 4.5 and ≤ 8 mm in an isolated segment or in the entire vein and a higher risk of bypass extrinsic compression (e.g., extra-anatomical venous bypass course). : Technical success and intraoperative patency were achieved in all cases. At 30 days, the limb salvage and survival rates were 100%. The primary bypass patency was 93.7% due to an early graft occlusion. No graft infection was registered. In one case, dehiscence of the surgical wound was treated by surgical debridement and antibiotic therapy. Minor amputation was required in four patients. Over a median follow-up of 32 months, two occlusions were observed; one was treated with reoperation and the other with major amputation. The primary patency was 68.7% and the assisted primary patency was 75%. Limb salvage rates observed during the entire follow-up period were 87.5%. No graft infections or dilatation of the reinforced veins were registered. : For patients with CLTI undergoing infrainguinal bypass, satisfactory results in terms of patency and limb salvage rates were achieved using the autologous venous material, even if ectasic or varicose, with the vascular external support FRAME.
PubMed: 38610860
DOI: 10.3390/jcm13072095 -
Journal of the Mechanical Behavior of... Jun 2024Despite polyester vascular grafts being routinely used in life-saving aortic aneurysm surgeries, they are less compliant than the healthy, native human aorta. This...
Despite polyester vascular grafts being routinely used in life-saving aortic aneurysm surgeries, they are less compliant than the healthy, native human aorta. This mismatch in mechanical behaviour has been associated with disruption of haemodynamics contributing to several long-term cardiovascular complications. Moreover, current fabrication approaches mean that opportunities to personalise grafts to the individual anatomical features are limited. Various modifications to graft design have been investigated to overcome such limitations; yet optimal graft functionality remains to be achieved. This study reports on the development and characterisation of an alternative vascular graft material. An alginate:PEGDA (AL:PE) interpenetrating polymer network (IPN) hydrogel has been produced with uniaxial tensile tests revealing similar strength and stiffness (0.39 ± 0.05 MPa and 1.61 ± 0.19 MPa, respectively) to the human aorta. Moreover, AL:PE tubular conduits of similar geometrical dimensions to segments of the aorta were produced, either via conventional moulding methods or stereolithography (SLA) 3D-printing. While both fabrication methods successfully demonstrated AL:PE hydrogel production, SLA 3D-printing was more easily adaptable to the fabrication of complex structures without the need of specific moulds or further post-processing. Additionally, most 3D-printed AL:PE hydrogel tubular conduits sustained, without failure, compression up to 50% their outer diameter and returned to their original shape upon load removal, thereby exhibiting promising behaviour that could withstand pulsatile pressure in vivo. Overall, these results suggest that this AL:PE IPN hydrogel formulation in combination with 3D-printing, has great potential for accelerating progress towards personalised and mechanically-matched aortic grafts.
Topics: Humans; Printing, Three-Dimensional; Blood Vessel Prosthesis; Aortic Aneurysm; Aorta; Hydrogels
PubMed: 38588633
DOI: 10.1016/j.jmbbm.2024.106531 -
NMR in Biomedicine Apr 2024The central nervous system (CNS) lacks traditionally defined lymphatic vasculature. However, CNS tissues and barriers compartmentalize the brain, spinal cord, and...
The central nervous system (CNS) lacks traditionally defined lymphatic vasculature. However, CNS tissues and barriers compartmentalize the brain, spinal cord, and adjacent spaces, facilitating the transmittal of fluids, metabolic wastes, immune cells, and vital signals, while more conventional lymphatic pathways in the meninges, cervicofacial and paraspinal regions transmit efflux fluid and molecules to peripheral lymph and lymph nodes. Thus, a unique and highly organized fluid circulation network encompassing intraparenchymal, subarachnoid, dural, and extradural segments functions in unison to maintain CNS homeostasis. Pathways involved in this system have been under investigation for centuries and continue to be the source of considerable interest and debate. Modern imaging and microscopy technologies have led to important breakthroughs pertaining to various elements of CNS fluid circuitry and exchange over the past decade, thus enhancing knowledge on mechanisms of mammalian CNS maintenance and disease. Yet, to better understand precise anatomical routes, the physiology and clinical significance of these CNS pathways, and potential therapeutic targets in humans, fluid conduits, flow-regulating factors, and tissue effects must be analyzed systematically and in a global manner in persons across age, demographical factors, and disease states. Here, we illustrate the system-wide nature of intermixing CNS fluid networks, summarize historical and clinical studies, and discuss anatomical and physiological similarities and differences that are relevant for translation of evidence from mice to humans. We also review Cushing's classical model of cerebrospinal fluid flow and present a new framework of this "third circulation" that emphasizes previously unexplained complexities of CNS fluid circulation in humans. Finally, we review future directions in the field, including emerging theranostic techniques and MRI studies required in humans.
PubMed: 38584002
DOI: 10.1002/nbm.5149 -
Journal of Endovascular Therapy : An... Apr 2024To assess the feasibility and safety of intravascular lithotripsy (IVL) for enabling transfemoral abdominal (EVAR), thoracic (TEVAR), and thoracoabdominal (BEVAR)...
PURPOSE
To assess the feasibility and safety of intravascular lithotripsy (IVL) for enabling transfemoral abdominal (EVAR), thoracic (TEVAR), and thoracoabdominal (BEVAR) endovascular aneurysm repair in patients with narrow and calcified iliac arteries.
MATERIALS AND METHODS
Consecutive patients treated with IVL for severe calcified and narrowed iliac access before EVAR, TEVAR, or BEVAR between November 2020 and June 2022 were retrospectively evaluated. All anatomical iliac characteristics were acquired by multi-planar reconstruction of preoperative computed tomography angiography (CTA). The hostility of the vascular accesses was classified based on Peripheral Arterial Calcium Scoring System (PACSS) and calcified access severity score (CASS), a new score considering both anatomical (calcium grade and length, minimum lumen diameter [MLD], and tortuosity index) and aortic stent-graft (SG/MLD index) parameters. Primary endpoint was technical success defined as successful aortic endograft delivery and deployment without iliac rupture. Freedom from complications and primary patency were additionally analyzed.
RESULTS
Twenty-eight iliac axes were treated with IVL (8 bilateral) in 20 patients (mean age 74.5±6.7 years) with a mean follow-up of 26.5±6.2 (range 17-36) months. Ten patients underwent EVAR: 3 TEVAR, and 7 BEVAR procedures. In 14 patients (70%), aneurysm disease was associated with symptomatic aorto-iliac occlusive disease (AIOD), with Rutherford class III to IV. The PACSS was grade IV in 89% of the cases and the CASS (mean 14±2) was grade III to IV in all cases. The stent-graft (SG) outer diameter (5.60±1.65 mm) was significantly larger by 50% than MLD (3.96±1.20 mm), with an SG/MLD index of 1.50±0.51 (p<0.001). Technical success was 100%. No dissection, rupture, or distal embolization occurred. One (3.4%) bail-out stenting was necessary as endoconduit after IVL treatment. One month CTA showed that postoperative luminal gain increased by 93% (p<0.001). An improvement of 2 Rutherford classes occurred in all AIOD patients with a primary patency of 100% at last follow-up.
CONCLUSIONS
This study shows the safety and feasibility of IVL as a valuable option to treat narrow and calcified iliac arteries to facilitate endograft delivery. Further studies will be useful to confirm these results.
CLINICAL IMPACT
In this article, the use of intravascular iliac artery lithotripsy to facilitate aortic endograft delivery is explored. The presence of iliac severe calcifications still represents a contraindication for aortic endovascular repair. Intravascular lithotripsy increases the feasibility and safety of endovascular aortic procedures, facilitating endograft delivery and reducing the risk of iliac rupture and/or dissections by improving vessel compliance and luminal gain. This novel vessel preparation could be an alternative to "paving and cracking" and/or iliac conduits. This study describes a new score to classify the severity of iliac calcifications, considering anatomical parameters and the profile of aortic endografts delivery system.
PubMed: 38561973
DOI: 10.1177/15266028241241246 -
Journal of Vascular Surgery Cases and... Jun 2024Renal artery access might not always be achieved due to anatomical reasons during the deployment of a branched stent graft in thoracoabdominal or juxtarenal abdominal...
Renal artery access might not always be achieved due to anatomical reasons during the deployment of a branched stent graft in thoracoabdominal or juxtarenal abdominal aortic aneurysms. Renal perfusion is maintained through the aneurysm sac until the iliac limbs are deployed. To preserve renal perfusion, a branched iliac limb would be needed. Such limbs with a side branch, a narrow (12-14 mm) proximal end, and a wide (16-20 mm) distal end are not commercially available. Due to the nature of their deployment mechanism, Gore Excluder distal limbs (W.L. Gore & Associates) have been used outside the instructions for use in reversed position. A traditional Gore Excluder main body can be reversed; however, the smallest proximal diameter is 23 mm, which could be too large to be deployed in a typically 16- to 18-mm common iliac artery. However, the smallest Gore Excluder Conformable endoprosthesis (W.L. Gore & Associates, Inc) main body is 20 mm in diameter, and the distal limb is 14.5 mm. This allows for a perfect fit when deployed in reversed position between an 11-mm unibody limb (Cook Medical Inc) and the common iliac artery, resulting in access to the renal artery from the side branch. We used a Gore Excluder Conformable main body graft in two such cases successfully. In these two patients, the iliac limbs and renal artery have stayed patent during a follow-up of 24 and 3 months. A Gore Excluder Conformable graft can be deployed in reversed position, using it as a conduit between the branched stent graft limb, common iliac artery, and renal artery.
PubMed: 38510095
DOI: 10.1016/j.jvscit.2024.101452 -
Left atrial appendage occlusion: On the need of a numerical model to simulate the implant procedure.International Journal For Numerical... May 2024Left atrial appendage occlusion (LAAO) is a percutaneous procedure to prevent thromboembolism in patients affected by atrial fibrillation. Despite its demonstrated...
Left atrial appendage occlusion (LAAO) is a percutaneous procedure to prevent thromboembolism in patients affected by atrial fibrillation. Despite its demonstrated efficacy, the LAA morphological complexity hinders the procedure, resulting in postprocedural drawbacks (device-related thrombus and peri-device leakage). Local anatomical features may cause difficulties in the device's positioning and affect the effectiveness of the device's implant. The current work proposes a detailed FE model of the LAAO useful to investigate implant scenarios and derive clinical indications. A high-fidelity model of the Watchman FLX device and simplified parametric conduits mimicking the zone of the LAA where the device is deployed were developed. Device-conduit interactions were evaluated by looking at clinical indicators such as device-wall gap, possible cause of leakage, and device protrusion. As expected, the positioning of the crimped device before the deployment was found to significantly affect the implant outcomes: clinician's choices can be improved if FE models are used to optimize the pre-operative planning. Remarkably, also the wall mechanical stiffness plays an important role. However, this parameter value is unknown for a specific LAA, a crucial point that must be correctly defined for developing an accurate FE model. Finally, numerical simulations outlined how the device's configuration on which the clinician relies to assess the implant success (i.e., the deployed configuration with the device still attached to the catheter) may differ from the actual final device's configuration, relevant for achieving a safe intervention.
Topics: Humans; Atrial Appendage; Models, Cardiovascular; Atrial Fibrillation; Computer Simulation; Finite Element Analysis; Thromboembolism
PubMed: 38504482
DOI: 10.1002/cnm.3814 -
Structural Heart : the Journal of the... Mar 2024Transcatheter mitral valve-in-valve (MViV) replacement has emerged as an alternative to redo mitral valve (MV) surgery for the management of failed bioprosthetic MVs....
BACKGROUND
Transcatheter mitral valve-in-valve (MViV) replacement has emerged as an alternative to redo mitral valve (MV) surgery for the management of failed bioprosthetic MVs. The degree of cardiac remodeling assessed by echocardiography has been shown to have prognostic implications in degenerative mitral regurgitation patients undergoing MV surgery. The impact of transcatheter MViV in patients with degenerative bioprosthetic MV failure on cardiac remodeling and its associated prognosis remains undescribed.
OBJECTIVES
The aim of this study is to describe the early anatomic and functional changes of the left-sided chambers and right ventricle by echocardiography posttranscatheter MViV intervention and their impact on mortality outcomes. Additionally, we sought to analyze the outcome of heart failure in bioprosthetic MV failure patients undergoing transcatheter MViV replacement.
METHODS
We analyzed consecutive patients undergoing MViV intervention for symptomatic bioprosthetic MV failure. Echocardiograms before intervention and within 100 days postintervention were analyzed. A chart review was performed to obtain baseline characteristics, follow-up visits, 30-day heart failure and 1-year all-cause mortality outcomes.
RESULTS
A total of 62 patients (mean age 69 ± 13 years, 61% male) were included in the study. Most patients were undergoing MViV intervention for prosthetic mitral stenosis n = 48 (77.4%) and the rest for mitral regurgitation or mixed disease. Compared with baseline, significant reductions were observed in median left atrial volume (LAV; 103 [81-129] ml vs. 95.2 [74.5-117.5] ml, < 0.01) and mean (SD) left atrial conduit strain (9.1% ± 5.2% vs. 10.8% ± 4.8%, = 0.039) within 100 days postintervention. Early reduction in right ventricular free wall global longitudinal strain and fractional area change also occurred postintervention. No significant change in left ventricular chamber dimensions or ejection fraction was observed. During the 1-year follow up period, 5 (8%) patients died. While baseline LAV was not associated with 1-year all-cause mortality (OR 0.98 CI 0.95-1.01; = 0.27), a change in LAV in the follow up period was associated with all-cause mortality at 1 year (OR 1.06 CI 1.01-1.12; = 0.023). At 30 days postintervention, 65% of patients had an improvement in their New York Heart Association functional class.
CONCLUSION
In this retrospective study of patients undergoing transcatheter MViV intervention for failed bioprosthetic MVs, early reverse remodeling of the left atrium occurs within 100 days postintervention and reduction in LAV is associated with reduced all-cause mortality at 1 year. In addition, there is significant improvement in heart failure symptoms at 30 days following intervention but further investigation into the longitudinal remodeling changes and long-term outcomes is needed.
PubMed: 38481712
DOI: 10.1016/j.shj.2023.100264 -
BJU International Mar 2024To assess the safety of sub-urothelial injection of durvalumab and examine the impact on tissue and circulating immune cell populations.
OBJECTIVES
To assess the safety of sub-urothelial injection of durvalumab and examine the impact on tissue and circulating immune cell populations.
PATIENTS AND METHODS
The patients were chemotherapy and immunotherapy naïve (bacille Calmette-Guérin allowed) with non-metastatic muscle-invasive bladder cancer or non-muscle-invasive bladder cancer planned for radical cystectomy (RC). The study was a Phase Ib 3 + 3 dose-escalation design with sub-urothelial injection of durvalumab at three pre-determined doses (25, 75, 150 mg) diluted in 25 mL normal saline, injected at 25 locations (25 × 1 mL injections), at least 2 weeks before RC.
RESULTS
A total of 11 patients were recruited (10 male, one female). No significant changes were reported on American Urological Association Symptom Score or O'Leary Interstitial Cystitis Scale. In all, 14 adverse events (AEs) were reported (10 Grade 1, three Grade 2, one Grade 3), none considered immune-related. No Grade 4 or 5 AEs were recorded. All the patients underwent RC. Tissue immune populations changed following durvalumab injection (P = 0.012), with a statistically significant increase in M2-macrophage (CD163) when comparing the 25-150 mg dose (P = 0.021). Basal/mixed cancers showed a larger CD163 increase than luminal cancers (P = 0.033).
CONCLUSION
Sub-urothelial injection of durvalumab is feasible and safe without immune-related AEs and shows local immunological effects.
PubMed: 38469652
DOI: 10.1111/bju.16325 -
Journal of Plastic, Reconstructive &... Apr 2024Lack of adequate recipient vessels in certain anatomically unfavorable locations or in complex clinical situations is still a limitation to successful microsurgical...
BACKGROUND
Lack of adequate recipient vessels in certain anatomically unfavorable locations or in complex clinical situations is still a limitation to successful microsurgical transfer. To address such complex cases, advanced microsurgical techniques should be applied. In this paper, the authors describe their experience with the Extra-anatomical Pedicle Rerouting (EPR) technique, an alternative approach that was used in selected cases throughout the body to obtain healthy recipient vessels for microsurgical reconstruction in unfavorable clinical situations where suitable recipient vessels were difficult to find.
PATIENTS AND METHODS
Fifteen patients with defects of variable etiology (oncological resection, trauma, previous surgeries) located in the trunk or upper and lower extremities received EPR free flap reconstruction at our Institution. Operative data, postoperative course, and complications were recorded. Clinical and photographic follow-ups were also documented.
RESULTS
A total of 15 flaps (6 antero-lateral thigh (ALT), 6 latissimus dorsi/thoracodorsal artery perforator flap (LD/TDAP), 3 deep inferior epigastric artery perforator flap (DIEP)) were transferred adopting the EPR technique for oncological (11) and post-traumatic (4) defects. According to the different clinical scenarios, the rerouted vessels were the thoraco-acromial, posterior circumflex humeral, thoracodorsal, deep inferior epigastric, lateral circumflex femoral, anterior tibial, and medial sural pedicles. Mean length of the rerouted vascular conduits was 6.53 cm. Mean operative time was 420 minutes. No major complications were registered. Minor wound dehiscence was observed and managed conservatively in 3 patients.
CONCLUSIONS
The EPR technique proved to be useful in a reliable and reproducible manner in different regions of the body as an alternative solution to obtain healthy recipient vessels in anatomically and surgically unfavorable clinical situations.
Topics: Humans; Plastic Surgery Procedures; Surgical Flaps; Arteries; Lower Extremity; Thigh; Perforator Flap
PubMed: 38428230
DOI: 10.1016/j.bjps.2024.01.055