Distribution of surgical smoke particles within a simulated laparoscopic cavity utilizing an AirSeal® system.

An exploratory study was performed to determine the distribution of surgical smoke particulate matter (SSPM) and evacuation times within an AirSeal® System and a traditional insufflation access system in various simulated surgical scenarios. Identified trends showed statistical significance when setting the AirSeal® System to Low smoke evacuation that it reduces the percentage of particulate matter at the Access Port opening. Additionally, it was observed that when utilising a laparoscopic tool a similar trend in particle distributions were seen between either insufflation and access system at the opening of the Access Port and trocar. Evacuation times for SSPM removal within the AirSeal® System showed an overall average to ≥95% reduction of 5.64 min within the surgical cavity, 3.69 min at the Access Port opening, and 3.61 min within the smoke evacuation line. The overall average for the traditional insufflation and access system was 9.38 min within the surgical cavity and 6.06 min at the trocar opening. Results showed that when using the traditional system compared to the AirSeal® System, it resulted in a percent change increase in evacuation times of 66.31% within the surgical cavity and 64.23% at the trocar opening.

Clinical outcomes of low-pressure pneumoperitoneum in minimally invasive urological surgery.

The adoption of minimally invasive laparoscopic techniques has revolutionised urological practice. This necessitates a pneumoperitoneum (PNP) and the impact the PNP pressure has on post-operative outcomes is uncertain. During the current COVID-19 era guidance has suggested the utilisation of lower PNP pressures to mitigate the risk of intra-operative viral transmission. Review the current literature regarding the impact of pneumoperitoneum pressure, within the field of urology, on post-operative outcomes. A search of the PubMed, Medline and EMBASE databases was undertaken to identify studies that met the inclusion criteria. The Preferred Reporting Items for Systematic Reviews (PRISMA) guidelines were adhered to. Ten studies, that included both randomised controlled trials and retrospective case series reviews, were identified that met the inclusion criteria. The effect of PNP pressure on outcomes following prostatectomy, live donor nephrectomy, partial nephrectomy and a variety of benign upper tract procedures were discussed. Low pressure PNP appears safe when compared to high pressure PNP, potentially reducing post-operative pain and rates of ileus. When compared to general surgery, there is a lack of quality evidence investigating the impact of PNP pressures on outcomes within urology. Low pressure PNP appears non-inferior to high pressure PNP. More research is required to validate this finding, particularly post-cystectomy and nephrectomy.

Neointimal hyperplasia and calcification in medium sized arteries in adult patients with chronic kidney disease.

The nature of arterial changes resulting in cardiovascular events and dialysis vascular access failures in adult predialysis patients is not well known. This study examined intimal changes, calcium deposition, and consequent stiffness in brachial and radial arteries of adult CKD patients. Ten brachial-artery and seven radial-artery specimens were obtained during fistula creation from nine predialysis and eight dialysis-dependent, nondiabetic patients; and age-gender matched controls undergoing coronary bypass grafts (6 radial) or kidney donation (6 renal). Arterial stiffness was measured at baseline. Vessel histology, morphometric analysis of intima-media, and direct quantification of calcium load was performed using standard techniques. Both predialysis and dialysis patients demonstrated significant arterial intimal hyperplasia with intima:media ratio higher than controls (0.13 ± 0.12 vs. 0.02 ± 0.05, p = 0.01). Calcium deposition was demonstrated on histology and the calcium content in patients was higher than controls (34.68 ± 26.86 vs. 10.95 ± 9.18 µg/µg, p = 0.003). The blood vessel calcium content correlated with arterial stiffness (r = 0.64, p = 0.018). This study for the first time describes, and suggests mechanistic linkage between, intimal hyperplasia, pathological calcium deposition, and increased functional arterial stiffness in dialysis and predialysis patients. Our research could serve as a unique window into the in vivo status of the uremic vasculature impacting fistula maturation and cardiovascular disease.

Influence of temporal variation in wall shear stress on intima-media thickening in arteriovenous fistulae.

Arteriovenous fistula (AVF) failure is mainly due to venous stenosis characterized by significant amount of intima-media thickening (IMT), probably in the presence of negative (inward) remodeling. Our hypothesis is that the longitudinal changes in wall shear stress (WSS) within different configurations of AVF can influence remodeling factors (changes in luminal diameter (ΔDh ) and IMT) during its maturation process. Dh is an equivalent diameter for a noncircular conduit. A total of six AVFs with curved (C-AVF; n = 3) and straight (S-AVF; n = 3) configurations were created between the femoral artery and vein of three pigs, bilaterally. CT scans and ultrasounds were utilized to calculate local WSS at 2D (D: days), 7D, and 28D postsurgery. For each AVF, IMT was measured at four regions along the vein using morphometric analyses. At these regions, repeated measurements of WSS and luminal diameter of each AVF were obtained over time. The ΔD(h) between 7D and 28D was significantly larger for C-AVF than for S-AVF (2.27 ± 0.67 mm vs. 0.02 ± 0.55 mm; p < 0.05). Also, at 28D the amount of IMT in C-AVF (77.46 ± 7.10 units) was significantly greater (p < 0.05) when compared with S-AVF (53.71 ± 8.23 units). These structural changes were accompanied by significantly different gradients of WSS over time (τ') for C-AVF (-0.56 ± 0.60 dyne/cm(2)/day) in comparison with S-AVF (0.71 ± 0.39 dyne/cm(2)/day). Negative τ' for C-AVF corresponded to reduction in WSS level over time resulting in a physiological level of WSS at 28D (4.08 ± 5.08 dyne/cm(2)). In contrast, a positive τ' for S-AVF was associated with the increase in WSS levels over time causing high levels of WSS at 28D (36.68 ± 5.32 dyne/cm(2)). The decrease in WSS levels for the C-AVF over time was associated with outward remodeling of the venous wall (favorable to maturation). In contrast, for S-AVF, the increase in WSS levels over time was associated with inward remodeling and subsequently, venous stenosis. Thus, temporal gradients of WSS, which could be altered by the surgical configuration of AVF, may provide important information on the remodeling behavior of AVFs. Identification of an optimal AVF configuration, which results in a temporal decrease in WSS and an outward remodeling of the venous wall, may reduce AVF maturation failure.

Longitudinal assessment of hemodynamic endpoints in predicting arteriovenous fistula maturation.

Arteriovenous fistula (AVF) nonmaturation is currently a significant clinical problem; however, the mechanisms responsible for this have remained unanswered. Previous work by our group and others has suggested that anatomical configuration and the corresponding hemodynamic endpoints could have an important role in AVF remodeling. Thus, our goal was to assess the longitudinal (temporal) effect of wall shear stress (WSS) on remodeling process of AVFs with two different configurations. The hypothesis is that early assessment of hemodynamic endpoints such as temporal gradient of WSS will predict the maturation status of AVF at later time points. Two AVFs with curved (C-AVF) and straight (S-AVF) configurations were created between the femoral artery and vein of each pig. Three pigs were considered in this study and in total six AVFs (three C-AVF and three S-AVF) were created. The CT scan and ultrasound were utilized to numerically evaluate local WSS at 20 cross-sections along the venous segment of AVFs at 2D (D: days), 7D, and 28D postsurgery. These cross-sections were located at 1.5 mm increments from the anastomosis junction. Local WSS values at these cross-sections were correlated with their corresponding luminal area over time. The WSS in C-AVF decreased from 22.3 ± 4.8 dyn/cm(2) at 2D to 4.1 ± 5.1 dyn/cm(2) at 28D, while WSS increased in S-AVF from 13.0 ± 5.0 dyn/cm(2) at 2D to 36.7 ± 5.3 dyn/cm(2) at 28D. Corresponding to these changes in WSS levels, luminal area of C-AVF dilated (0.23 ± 0.14 cm(2) at 2D to 0.87 ± 0.14 cm(2) at 28D) with attendant increase in flow rate. However, S-AVF had minimal changes in area (0.26 ± 0.02 cm(2) at 2D to 0.27 ± 0.03 cm(2) at 28D) despite some increase in flow rate. Our results suggest that the temporal changes of WSS could have significant effects on AVF maturation. Reduction in WSS over time (regardless of initial values) may result in dilation (p < 0.05), while increase in WSS may be detrimental to maturation. Thus, creation of AVFs in a specific configuration which results in a decline in WSS over time may reduce AVF maturation failure.

Anatomic configuration affects the flow rate and diameter of porcine arteriovenous fistulae.

Although arteriovenous fistulae are currently the preferred form of vascular access, early failure is a significant problem. Since wall shear stress is thought to play an important role in the pathogenesis of early failure, and this stress varies markedly in different fistula configurations, we assessed the influence of configuration (curved or straight) on longitudinal changes of flow rate and lumen diameter in a porcine fistula model. Fistulae were created in eight pigs between the femoral artery and vein, with each animal having a curved and a straight configuration on opposite sides. Velocity measurements were obtained by ultrasound at the time of surgery and at intermediate time points up to 28 days. Quantification of both the configuration and the internal diameter of the fistulae was determined by CT scans. The overall rate of increased flow during each time interval (0 to 2 days, 2 to 7 days, and 7 to 28 days) was more pronounced with the curved fistulae. Moreover, the luminal diameter of curved fistulae had dilated more from the time of surgery to 28 days as compared to the straight fistulae. Thus, anatomical configuration of fistulae plays a major role in flow-mediated dilatation. Identifying the optimal configuration may result in increased diameter and consequently blood flow, and perhaps reduce the incidence of early failure.

Severe venous neointimal hyperplasia prior to dialysis access surgery.

BACKGROUND: Venous neointimal hyperplasia is the most common cause of arteriovenous (AV) fistula and graft dysfunction following dialysis access surgery. However, the pathogenetic impact of pre-existing venous neointimal hyperplasia at the time of AV access creation on final clinical success is currently unknown in the setting of advanced chronic kidney disease (CKD) and end-stage renal disease (ESRD) patients. The aim of this study was to perform a detailed histological, morphometric, and immunohistochemical analysis of vein specimens in advanced CKD and ESRD patients collected at the time of new vascular access placement. METHODS: Vein samples from 12 patients were collected at the time of AV access creation near the site of AV anastomosis. Histological, immunohistochemistry and morphometric studies were performed on these vein samples. RESULTS: Examination of the tissue specimens obtained at the time of surgery showed neointimal hyperplasia in 10 of 12 specimens, ranging from minimal to very severe. The majority of cells within the neointima were myofibroblasts with a minority of contractile smooth muscle cells present. CONCLUSION: Our work represents a detailed description of the morphometric and cellular phenotypic lesions present in the veins of CKD and ESRD patients, prior to dialysis access placement. These studies (i) suggest the future possibility of a new predictive marker (pre-existing venous neointimal hyperplasia) for AV dialysis access dysfunction and (ii) open the door for the future development of novel local therapies for optimization of the venous substrate on which the dialysis access is created.

Investigation of kinetics of methotrexate for therapeutic treatment of intraocular lymphoma.

PURPOSE: Primary intraocular lymphoma (PIOL) provides a therapeutic challenge because of its diverse clinical picture and variable clinical course. The main objective of this study was to evaluate the retinal permeability of methotrexate for rabbit and human eyes and then investigate its kinetics in a human eye following the standard induction-consolidation-maintenance (I-C-M) injection protocols for the treatment of PIOL. Additionally, the therapeutic release rate of a 90-day sustained-release methotrexate implant was also determined for the effective treatment of PIOL. METHODOLOGY: The 3-dimensional model of a rabbit eye was adapted from our previous studies and a human eye model was constructed based on its physiological dimensions. The retinal permeability of methotrexate was the only unknown parameter in the numerical calculations and was determined by comparing the model simulated vitreous concentrations for rabbit and human eyes with the available in vivo and clinical data, respectively. RESULTS: The retinal permeability values of methotrexate calculated for an albino rabbit and human eye were 1.1 × 10(-5) cm/s and 9.25 × 10(-6) cm/s, respectively. Given that the dosage above 0.1 µM is considered tumoricidal, the cytotoxic levels of methotrexate were consistently achieved only in the induction phase and the concentration levels dropped below the cytotoxic levels for part of the consolidation and maintenance phases of the treatment following the I-C-M protocols. A sustained-release implant with a mean release rate of 0.2 µg/day-2 µg/day should be designed in order to maintain tumoricidal levels of methotrexate inside the vitreous of the human eye for a period of 3 months. CONCLUSIONS: By making use of the results of this study, one could select a dosing interval for serial injections of methotrexate or establish a treatment schedule using a controlled release methotrexate implant for the treatment of PIOL.

Cellular phenotypes in human stenotic lesions from haemodialysis vascular access.

BACKGROUND: Haemodialysis vascular access dysfunction (due to venous stenosis and thrombosis) is a leading cause of hospitalization and morbidity. The aim of the current study was to identify the specific cell types present within stenotic tissue samples from patients with AV fistula and graft failure. METHODS: Discarded tissue segments were collected from the stenotic portions (usually near the graft-vein anastomosis or the AV anastomosis) of 23 dialysis grafts and 20 AV fistulae, and examined for expression of smooth muscle alpha actin, desmin, vimentin and a macrophage marker. RESULTS: The majority of cells within the venous neointima (both grafts and fistulae) were myofibroblasts, with a smaller number of desmin positive smooth muscle cells. The graft neointima had a similar cellular phenotype, albeit without any desmin positive contractile smooth muscle cells. The majority of cells within the PTFE graft material were macrophages. Analysis of sequential sections revealed the presence of fibroblasts within the venous neointima and intragraft region. CONCLUSIONS: Our results demonstrate that contractile smooth muscle cells, myofibroblasts, fibroblasts and macrophages all play a role in the pathogenesis of dialysis access dysfunction (grafts and fistulae). Targeting these specific cell types might result in the development of novel therapeutic paradigms for haemodialysis vascular access dysfunction.

Hemodynamic wall shear stress profiles influence the magnitude and pattern of stenosis in a pig AV fistula.

Venous stenosis is a significant problem in arteriovenous fistulae, likely due to anatomical configuration and wall shear stress profiles. To identify linkages between wall shear stress and the magnitude and pattern of vascular stenosis, we produced curved and straight fistulae in a pig model. A complete wall stress profile was calculated for the curved configuration and correlated with luminal stenosis. Computer modeling techniques were then used to derive a wall shear stress profile for the straight arteriovenous fistula. Differences in the wall shear stress profile of the curved and straight fistula were then related to histological findings. There was a marked inverse correlation between the magnitude of wall shear stress within different regions of the curved arteriovenous fistula and luminal stenosis in these same regions. There were also significantly greater differences in wall shear stress between the outer and inner walls of the straight as compared to curved arteriovenous fistula, which translated into a more eccentric histological pattern of intima-media thickening. Our results suggest a clear linkage between anatomical configuration, wall shear stress profiles, and the pattern of luminal stenosis and intima-media thickening in a pig model of arteriovenous fistula stenosis. These results suggest that fistula failure could be reduced by using computer modeling prior to surgical placement to alter the anatomical and, consequently, the wall shear stress profiles in an arteriovenous fistula.

Effect of retinal permeability, diffusivity, and aqueous humor hydrodynamics on pharmacokinetics of drugs in the eye.

AIM: Retinal permeability is one of the important parameters that determine drug distribution during diseased retinal conditions, whose effect is still unclear. Thus, the main aim of this study was to understand the influence of varying retinal permeability (P) on drug distribution under normal (F1) and elevated vitreous outflow pathophysiologic conditions (F10) for a wide variety of drug diffusivities-high: D(-5) and low: D(-7). METHOD: A computational model of the rabbit eye was developed that took into account the varying effects of convection during normal and pathophysiologic conditions. RESULTS: High retinal permeability, P(-5), is associated with low peak macular concentration and a rapid clearance from the ocular chambers, with the retina as the major route of elimination. For low permeability, P(-7), there is very high peak macular concentration, slow elimination, and a buildup of drug concentration, which depends on vitreous outflow. The variation of t(1/2) with P was found to be of linear and nonlinear trends for F1 and F10 flow cases, respectively. Moreover, for D(-5) diffusivity, there was a 1.5-fold increase and a 1.6-fold decrease in t(1/2) values when the retinal permeability values were P(-5) and P(-7). On the contrary, for D(-7) diffusivity, there was a 2.5-fold decrease and a 1.4-fold increase in t(1/2) values for P(-5) and P(-7), with t(1/2) increasing for P(-6) during both high and low diffusivities. CONCLUSIONS: Thus, the combined effect of variables P, D, and F are important factors that should be considered in order to determine drug dosage. This study could be used to estimate the drug distribution and elimination for (1) wide range of physicochemical properties of drugs and (2) normal and abnormally elevated vitreous flows during the diseased condition of the eye. These results could help in obtaining essential information about the treatment protocol for targeted retinal diseases while simultaneously avoiding the toxic effects of these drugs.

Effect of blood viscosity on oxygen transport in residual stenosed artery following angioplasty.

The effect of blood viscosity on oxygen transport in a stenosed coronary artery during the postangioplasty scenario is studied. In addition to incorporating varying blood viscosity using different hematocrit (Hct) concentrations, oxygen consumption by the avascular wall and its supply from vasa vasorum, nonlinear oxygen binding capacity of the hemoglobin, and basal to hyperemic flow rate changes are included in the calculation of oxygen transport in both the lumen and the avascular wall. The results of this study show that oxygen transport in the postangioplasty residual stenosed artery is affected by non-Newtonian shear-thinning property of the blood viscosity having variable Hct concentration. As Hct increases from 25% to 65%, the diminished recirculation zone for the increased Hct causes the commencement of pO(2) decrease to shift radially outward by approximately 20% from the center of the artery for the basal flow, but by approximately 10% for the hyperemic flow at the end of the diverging section. Oxygen concentration increases from a minimum value at the core of the recirculation zone to over 90 mm Hg before the lumen-wall interface at the diverging section for the hyperemic flow, which is attributed to increased shear rate and thinner lumen boundary layer for the hyperemic flow, and below 90 mm Hg for the basal flow. As Hct increases from 25% to 65%, the average of pO(2,min) beyond the diverging section drops by approximately 25% for the basal flow, whereas it increases by approximately 15% for the hyperemic flow. Thus, current results with the moderate stenosed artery indicate that reducing Hct might be favorable in terms of increasing O(2) flux and pO(2,min), in the medial region of the wall for the basal flow, while higher Hct is advantageous for the hyperemic flow beyond the diverging section. The results of this study not only provide significant details of oxygen transport under varying pathophysiologic blood conditions such as unusually high blood viscosity and flow rate, but might also be extended to offer implications for drug therapy related to blood-thinning medication and for blood transfusion and hemorrhage.

Venous stenosis in a pig arteriovenous fistula model--anatomy, mechanisms and cellular phenotypes.

BACKGROUND: Haemodialysis vascular access dysfunction is currently a huge clinical problem. Although arteriovenous (AV) fistulae are the preferred mode of dialysis access, they have significant problems with both early (failure to mature) and late fistula failure. Both are characterized radiologically as a stenosis of the venous segment. Despite the magnitude of the clinical problem, the exact pathogenesis of AV fistula failure remains unclear. The aim of this study was to develop and validate a pig model of AV fistula stenosis and then use it to dissect out the mechanisms responsible for this lesion. METHODS: AV fistulae were created between the femoral artery and vein of Yorkshire Cross pigs. Animals were sacrificed at 2 days, 7 days, 28 days and 42 days post-surgery. At the time of sacrifice the entire specimen was divided into four regions; the arterial (AV-A) and venous (AV-V) portions of the AV anastomosis, the juxta-anastomotic segment (JA) and the proximal vein (PV), and assessed for the degree of intima-media thickening and the presence of specific cellular phenotypes. Haemodynamic parameters were not measured in this set of experiments. RESULTS: Significant luminal stenosis and intima-media thickening were present as early as 28 days and 42 days post-surgery in the pig model. In addition, within specimens from a single time point, these two parameters were maximal within the proximal vein and juxta-anastomotic segment as compared to the AV anastomosis (P < 0.0001). The vast majority of cells within the region of intima-media thickening were myofibroblasts. CONCLUSIONS: These studies suggest that early and aggressive intima-media thickening (which is made up primarily of myofibroblasts) plays an important role in AV fistula stenosis in a pig model of AV fistula placement. Interventions that target the mechanisms and cellular phenotypes described in this model, may be effective in reducing the very significant morbidity and economic costs currently associated with AV fistula failure.

Neointimal hyperplasia in early arteriovenous fistula failure.

BACKGROUND: Hemodialysis vascular access dysfunction currently is a huge clinical problem. Although arteriovenous fistulas (AVFs) are the preferred form of permanent dialysis access, they continue to have significant problems with early AVF failure. Although inadequate dilatation of the venous segment was believed to have a role in early AVF failure, the exact pathogenesis of early AVF failure is unknown despite the magnitude of the clinical problem. STUDY DESIGN: Case series. SETTING & PARTICIPANTS: Hemodialysis patients. OUTCOMES & MEASUREMENTS: Stenotic venous segments from 4 patients with early AVF failure were subjected to a detailed histological, morphometric, and immunohistochemical analysis. RESULTS: All 4 patients had significant luminal stenosis, primarily as a result of eccentric neointimal hyperplasia. This was confirmed through morphometric analysis, which documented intima-media area and thickness ratios that were greater than unity. Cellular phenotyping studies showed that the majority of cells within the region of neointimal hyperplasia were myofibroblasts, with smaller numbers of contractile smooth muscle cells. LIMITATIONS: We described only a limited number of specimens. CONCLUSIONS: We show for the first time that aggressive neointimal hyperplasia is present in venous segment specimens from patients with early AVF failure. Future therapies to address this problem will need to target this pathogenetic pathway.

Perivascular paclitaxel wraps block arteriovenous graft stenosis in a pig model.

BACKGROUND: Haemodialysis vascular access dysfunction is currently a huge clinical problem. In an attempt to reduce the morbidity associated with haemodialysis vascular access dysfunction, we have previously developed and validated a local perivascular paclitaxel release system that has been shown to release paclitaxel for at least 3 weeks. The aim of the current study was to evaluate the in vivo use of these perivascular wraps (for both safety and efficacy) at different time points in our pig model of arteriovenous graft stenosis. METHODS: Paclitaxel-loaded ethylene vinyl acetate wraps were placed around the graft-vein anastomosis on one side, with control polymers being placed on the contralateral side in our pig model of arteriovenous graft stenosis. Animals were sacrificed at early (10-11 days), middle (23-24 days) and late (32-38 days) time points. The entire graft-vein anastomosis was removed at the time of sacrifice and assessed for the extent of luminal stenosis using histomorphometric techniques. RESULT: Graft-vein anastomoses treated with the paclitaxel-loaded polymers had an almost complete absence of luminal stenosis at the middle (23-24 days) and late (32-38 days) time points (when one would expect the development of neointimal hyperplasia) as compared with the contralateral control graft-vein anastomoses (37.90% luminal stenosis in the controls vs 0.10% in the paclitaxel group). There were minimal local side effects from this procedure. CONCLUSIONS: Our results demonstrate the safety and efficacy of paclitaxel-loaded perivascular wraps in the setting of a pig model of arteriovenous graft stenosis. We believe that such a local approach which could be easily applied at the time of surgery is ideally suited for use in the clinical setting of haemodialysis vascular access dysfunction. It is likely that this novel approach could result in a significant reduction in the huge economic and health morbidity costs currently associated with this recalcitrant clinical problem.