Challenges of long-term vascular access in pediatric hemodialysis: Recommendations for practitioners

Kidney transplantation is the preferred treatment of end-stage renal disease in children. However, time to transplant varies, making a well-functioning long-term vascular access essential for performing hemodialysis efficiently and without disruption until a kidney becomes available. However, establishing long-term vascular access in pediatric patients can present distinct challenges due to this population's unique characteristics, such as smaller body size and lower-diameter blood vessels. There are three main pediatric long-term vascular access options, which include central venous catheters (CVC), arteriovenous fistula (AVF), and arteriovenous graft (AVG). CVC are currently the most widely used modality, although various studies and guidelines recommend AVF or AVG as the preferred option. Although AVF should be used whenever possible, it is crucial that clinicians consider factors such as patient size, physical exam findings, comorbidities, predicted duration of treatment to decide on the most optimal long-term vascular access modality. This article reviews the three long-term vascular access methods in children and the benefits and complications of each.     

An in vivo comparative study of the e-polytetrafluoroethylene vascular prostheses: Vitaflon and Gore-Tex

A comparative study was performed in order to validate new Russian e-PTFE vascular prostheses Vitaflon (St. Petersburg, Russia). The Gore-Tex prostheses were chosen as a referential model. The prostheses were implanted in the venous and arterial positions in 13 dog experiments. After the implantation time was over a comprehensive histological and histochemical examination of excized specimens was performed. It was demonstrated that there is no difference in healing and functional properties between the two studied prostheses.     

Cannulation and vascular access-related complications in hemodialysis: Factors determining successful cannulation

Little is known about cannulation of the vascular access (VA), such as the number of successful cannulation procedures, frequency of complications caused by cannulation, and VA failure. Incident patients were followed for 6 months, from the first successful cannulation with 2 needles—both used for the hemodialysis treatment. Data included patient characteristics, comorbidities, and medication. Vascular access characteristics included: type of VA and location, vein diameter assessed by Duplex ultrasound, length of the cannulation route, and maturation period. Longitudinal data were collected by dialysis nurses, using identical questionnaires, and a standardized method to register data from each dialysis session. Among 10 Dutch dialysis facilities, clinical data from 120 patients were collected from June 2005 to March 2007. The use of autogenous arteriovenous fistulae (P<0.001) and limited length of the cannulation route (P<0.003) negatively affect the outcome of cannulation and complications such as use of single-needle (SN) dialysis and central vein catheters (CVC). Previous use of CVC and SN hemodialysis were significant predictors for VA failure (P<0.0001). The present study demonstrated that during the first 6 months of a newly placed VA, a huge number of cannulation-related complications such as miscannulation, use of CVC, and SN dialysis are encountered. Despite the fact that guidelines recommended the arteriovenous fistulae as the preferred VA, cannulation-related complications can lead to increased morbidity. The length of the cannulation route positively correlates with successful cannulation. Therefore, adjusted cannulation techniques might be indicated to improve VA outcome.     

Feasibility of biodegradable PLGA common bile duct stents: An in vitro and in vivo study

The current study investigates the feasibility of using a biodegradable polymeric stent in common bile duct (CBD) repair and reconstruction. Here, poly(l-lactide-co-glycolide) (PLGA, molar ratio LA/GA = 80/20) was processed into a circular tube- and dumbbell-shaped specimens to determine the in vitro degradation behavior in bile. The morphology, weight loss, and molecular weight changes were then investigated in conjunction with evaluations of the mechanical properties of the specimen. Circular tube-shaped PLGA stents with X-ray opacity were subsequently used in common bile duct exploration (CBDE) and primary suturing in canine models. Next, X-ray images of CBD stents in vivo were compared and levels of serum liver enzymes and a histological analysis were conducted after stent transplantation. The results showed that the PLGA stents exhibited the required biomedical properties and spontaneously disappeared from CBDs in 4–5 weeks. The degradation period and function match the requirements in repair and reconstruction of CBDs to support the duct, guide bile drainage, and reduce T-tube-related complications.     

Strain amplification in bone mechanobiology: a computational investigation of the in vivo mechanics of osteocytes

The osteocyte is believed to act as the main sensor of mechanical stimulus in bone, controlling signalling for bone growth and resorption in response to changes in the mechanical demands placed on our bones throughout life. However, the precise mechanical stimuli that bone cells experience in vivo are not yet fully understood. The objective of this study is to use computational methods to predict the loading conditions experienced by osteocytes during normal physiological activities. Confocal imaging of the lacunar–canalicular network was used to develop three-dimensional finite element models of osteocytes, including their cell body, and the surrounding pericellular matrix (PCM) and extracellular matrix (ECM). We investigated the role of the PCM and ECM projections for amplifying mechanical stimulation to the cells. At loading levels, representing vigorous physiological activity (3000 µɛ), our results provide direct evidence that (i) confocal image-derived models predict 350–400% greater strain amplification experienced by osteocytes compared with an idealized cell, (ii) the PCM increases the cell volume stimulated more than 3500 µɛ by 4–10% and (iii) ECM projections amplify strain to the cell by approximately 50–420%. These are the first confocal image-derived computational models to predict osteocyte strain in vivo and provide an insight into the mechanobiology of the osteocyte.     

Biomechanical regulation of vascular smooth muscle cell functions: from in vitro to in vivo understanding

Vascular smooth muscle cells (VSMCs) have critical functions in vascular diseases. Haemodynamic factors are important regulators of VSMC functions in vascular pathophysiology. VSMCs are physiologically active in the three-dimensional matrix and interact with the shear stress sensor of endothelial cells (ECs). The purpose of this review is to illustrate how haemodynamic factors regulate VSMC functions under two-dimensional conditions in vitro or three-dimensional co-culture conditions in vivo. Recent advances show that high shear stress induces VSMC apoptosis through endothelial-released nitric oxide and low shear stress upregulates VSMC proliferation and migration through platelet-derived growth factor released by ECs. This differential regulation emphasizes the need to construct more actual environments for future research on vascular diseases (such as atherosclerosis and hypertension) and cardiovascular tissue engineering.     

An in vivo ratio control mechanism for phospholipid homeostasis: evidence from lipidomic studies

While it is widely accepted that the lipid composition of eukaryotic membranes is under homeostatic control, the mechanisms through which cells sense lipid composition are still the subject of debate. It has been postulated that membrane curvature elastic energy is the membrane property that is regulated by cells, and that lipid composition is maintained by a ratio control function derived from the concentrations of type II and type 0 lipids, weighted appropriately. We assess this proposal by seeking a signature of ratio control in quantified lipid composition data obtained by electrospray ionization mass spectrometry from over 40 independent asynchronous cell populations. Our approach revealed the existence of a universal ‘pivot’ lipid, which marks the boundary between type 0 lipids and type II lipids, and which is invariant between different cell types or cells grown under different conditions. The presence of such a pivot species is a distinctive signature of the operation in vivo, in human cell lines, of a control function that is consistent with the hypothesis that membrane elastic energy is homeostatically controlled.     

Formulation and optimisation of famotidine proniosomes: an in vitro and ex vivo study

The aim of the study was to develop a proniosomal system for famotidine (FAM), a potent H₂ receptor antagonist that could efficiently deliver entrapped drug over a prolonged period of time. The proniosomal system was formulated by selecting various ratios of Span 60 and cholesterol using a coacervation-phase separation method. The formulated systems were characterised for drug excipient compatibility studies by Fourier transform infrared spectroscopy (FTIR), vesicle size determination by the particle size analyser, % drug encapsulation, drug-release profiles, field emission scanning electron microscopy (FESEM) for surface morphology, X-ray diffraction (XRD) and vesicular stability at different storage conditions. By using this method, the % drug loading that resulted by the encapsulation of proniosome was found to be 78%–89%. Increase in cholesterol and surfactant concentration increases encapsulation efficiency, but further increment decreases encapsulation. In vitro drug-release studies showed prolonged release of entrapped famotidine. The highest % cumulative drug release was achieved in formulation FAM2 (96%) in 24 hours. The ex vivo data on the release of famotidine from proniosomal formulations have shown significantly increased per cent release and flux in comparison to the same dose of marketed preparation of famotidine. Stability studies were carried out in refrigerated conditions, and higher drug retention was observed. It is evident from this study that proniosomes are a promising prolonged delivery system for famotidine and have reasonably good stability characteristics.     

Both pelvic radiography and lateral abdominal radiography correlate well with coronary artery calcification measured by computed tomography in hemodialysis patients: A cross‐sectional study

Introduction Lateral abdominal radiograph is suggested as an alternative to coronary artery computed tomography (CT) in evaluating vascular calcification. Simple scoring systems including pelvic radiograph scoring and abdominal scoring system were utilized to study their correlation with coronary artery calcification. Methods In 106 MHD patients, coronary artery CT, lateral abdominal, and pelvic radiograph were taken. The Agatston scoring system was applied to evaluate the degree of coronary artery calcification which was categorized according to Agatston coronary artery calcification score (CACS) ≥ 30, ≥100, ≥400, and ≥1000. Abdominal aortic calcification was scored by 4‐scored and 24‐scored systems. Pelvic artery calcification was scored by a 4‐scored system. Sensitivities and specificities of abdominal aortic calcification scores and pelvic artery calcification scores to predict different categories of coronary artery calcification were analyzed. We studied the diagnostic capability of abdominal aorta calcification and pelvic artery calcification to predict different CACS categories by calculating likelihood ratios. Receiver operator characteristic curves were used to determine the area under the curve for each of these testing procedures. Findings The prevalence was 48(45.3%), 15 (14.2%), 11 (10.4%), 11 (10.4%), and 11 (10.4%) for CACs > 0, ≥30, ≥100, ≥400, and ≥1000, respectively. The degree of CACs was positively correlated with patient age, prevalence of diabetes, abdominal aorta scores, and pelvic calcification scores. The areas under the curves for different CACS by all X‐ray scoring systems were above 0.70 except pelvic 4‐scored system for diagnosing CACS ≥30, without significant difference (P > 0.05). Discussion Both lateral abdominal and pelvic plain radiographs were demonstrated as acceptable alternatives to CT in evaluating vascular calcification.     

Comparison of standard forearm prosthetic loop grafts to composite semiloop forearm grafts (“semi‐grafts”) in hemodialysis patients: A prospective study

Introduction: To prospectively assess the performance of composite semiloop antebrachial grafts (“semi‐grafts,” SGs) in hemodialysis patients. Methods: Eighty‐five patients who received 67 loop antebrachial grafts (LG‐group) and 25 antebrachial semigrafts (SG‐group) were enrolled. SGs were defined as those originating from the brachial artery and anastomosed with the proximal mature mid‐antebrachial cephalic vein. Cephalic vein length should be at least 10 cm in length and of ≥5 mm in diameter for inclusion in the SG‐group. LG‐group included all possible outflow vein options of minimum diameter 3 mm. Kaplan‐Meier statistics was used for comparison of groups. Findings: Main indication for a SG was a failing radiocephalic fistula with extensive distal cephalic vein stenosis not amenable to correction or failed after endovascular repair or requiring long interposition grafting. The mean follow‐up period was 20.16 ± 22.6 and 29.6 ± 36.7 months for the LG‐ and SG‐group, respectively (P = 0.14). Forty‐two patients died during the follow‐up. Primary patency (up to first intervention or failure) at 6 and 12 months for LG‐ vs. SG‐group was 93.9% vs. 83.7% and 47% vs. 55.8% (P = 0.08). Secondary patency (up to abandonment) was 58.2% vs. 61.1% and 36% vs. 45.8% at 12 and 24 months (P = 0.18). Mortality at 48 months was 22.4% (LG‐group) and 24% (SG‐group) (P = 0.9). Discussion: There was a trend toward better primary and secondary patency rates for the SGs especially in the long‐term. This is a valuable option in selected patients that access surgeons and nephrologists should be aware of.     

Dynamics of angiogenesis during murine retinal development: a coupled in vivo and in silico study

The manner in which the superficial retinal vascular plexus (RVP) develops in neonatal wild-type mice is relatively well documented and poses an interesting challenge to the mathematical modelling community. Prior to birth, astrocyte sprouting and proliferation begin around the edge of the optic nerve head, and subsequent astrocyte migration in response to a chemotactic gradient of platelet-derived growth factor (PDGF)-A results in the formation of a dense scaffold on the surface of the inner retina. Astrocytes express a variety of chemotactic and haptotactic proteins that subsequently induce endothelial cell sprouting and modulate growth of the RVP. An experimentally informed, two-dimensional hybrid partial differential equation-discrete model is derived to track the outward migration of individual astrocyte and endothelial tip cells in response to the appropriate biochemical cues. Blood perfusion is included throughout the development of the plexus, and the evolving retinal trees are allowed to adapt and remodel by means of several biological stimuli. The resulting wild-type in silico RVP structures are compared with corresponding experimental whole mounts taken at various stages of development, and agreement between the respective vascular morphologies is found to be excellent. Subsequent numerical predictions help elucidate some of the key biological processes underlying retinal development and demonstrate the potential of the virtual retina for the investigation of various vascular-related diseases of the eye.     

Osteogenic differentiation and mineralization in fibre-reinforced tubular scaffolds: theoretical study and experimental evidences

The development of composite scaffolds with well-organized architecture and multi-scale properties (i.e. porosity, degradation) represents a valid approach for achieving a tissue-engineered construct capable of reproducing the medium- and long-term in vitro behaviour of hierarchically complex tissues such as spongy bone. To date, the implementation of scaffold design strategies able to summarize optimal scaffold architecture as well as intrinsic mechanical, chemical and fluid transport properties still remains a challenging issue. In this study, poly ɛ-caprolactone/polylactid acid (PCL/PLA) tubular devices (fibres of PLA in a PCL matrix) obtained by phase inversion/salt leaching and filament winding techniques were proposed as cell instructive scaffold for bone osteogenesis. Continuous fibres embedded in the polymeric matrix drastically improved the mechanical response as confirmed by compression elastic moduli, which vary from 0.214 ± 0.065 to 1.174 ± 0.143 MPa depending on the relative fibre/matrix and polymer/solvent ratios. Moreover, computational fluid dynamic simulations demonstrated the ability of composite structure to transfer hydrodynamic forces during in vitro culture, thus indicating the optimal flow rate conditions that, case by case, enables specific cellular events—i.e. osteoblast differentiation from human mesenchymal stem cells (hMSCs), mineralization, etc. Hence, we demonstrate that the hMSC differentiation preferentially occurs in the case of higher perfusion rates—over 0.05 ml min^–1—as confirmed by the expression of alkaline phosphate and osteocalcin markers. In particular, the highest osteopontin values and a massive mineral phase precipitation of bone-like phases detected in the case of intermediate flow rates (i.e. 0.05 ml min^–1) allows us to identify the best condition to stimulate the bone extracellular matrix in-growth, in agreement with the hydrodynamic model prediction. All these results concur to prove the succesful use of tubular composite as temporary device for long bone treatment.     

A novel application of electrospinning technique in sublingual membrane: characterization,permeation and in vivo study

Isosorbide dinitrate–polyvinylpyrrolidone (ISDN–PVP) electrospinning fibers were formulated and explored as potentially sublingual membrane. The addition of polyethylene glycol (PEG) to the formulation improved flexibility and reduced fluffiness of the fiber mat. The scanning electron microscopy (SEM) demonstrated that the fibers tended to be cross-linking, and the crosslinking degree increased with the increase of PEG amount. The differential scanning calorimetry (DSC) indicated that ISDN existed in non-crystalline state in the fibers (except at the highest drug content). The infrared spectroscopy suggested that ISDN had better compatibility with the ingredients owing to the hydrogen bonding (or hydrophobic interactions). The fibers were highly favorable for the fabrication of sublingual membrane due to neutral pH, large folding endurance and rapid drug release (complete dissolution within 120 s). The permeation study of ISDN through both dialysis membrane (DM) and porcine sublingual mucosa (SM) were carried out. A significant relationship of drug permeation rate through DM and SM was built up, which indicated that DM could be used to partly simulate SM and assess formulation. The pharmacokinetic study in rats demonstrated that the electrospinning fiber membrane had a higher C_max and lower T_max compared to the reference preparation, and the relative bioavailability of the fiber membrane was 151.6%.     

Topical delivery of tetrahydrocurcumin lipid nanoparticles effectively inhibits skin inflammation: in vitro and in vivo study

Tetrahydrocurcumin (THC) also referred to as ‘white curcumin’, is a stable colorless hydrogenated product of curcumin with superior antioxidant and anti-inflammatory properties. The present study is an attempt to elevate the topical bioavailability of THC, post-incorporation into a nano-carrier system with its final dosage as a hydrogel. Lipid nanoparticles of THC (THC-SLNs) prepared by microemulsification technique were ellipsoidal in shape (revealed in transmission electron microscopy) with a mean particle size of 96.6?nm and zeta potential of ?22?mV. Total drug content and entrapment efficiency of THC-SLNs was 94.51%?±?2.15% and 69.56%?±?1.35%, respectively. Differential scanning calorimetry and X-ray diffraction studies confirmed the formation of THC-SLNs. In vitro drug release studies showed the drug release from THC-SLNs gel to follow Higuchi’s equation revealing a Fickian diffusion. Ex vivo permeation studies indicated a 17 times (approximately) higher skin permeation of THC-SLNs gel as compared with the free THC gel. Skin irritation, occlusion, and stability studies indicated the formulation to be nonirritating, and stable with a desired occlusivity. Pharmacodynamic evaluation in an excision wound mice model clearly revealed the enhanced anti-inflammatory activity of THC-SLNs gel and was further confirmed using biochemical and histopathological studies. It is noteworthy to report here that THC-SLNs gel showed significantly better (p?≤?0.001) activity than free THC in gel. As inflammation is innate to all the skin disorders, the developed product opens up new therapeutic avenues for several skin diseases. To the best of our knowledge, this is the first paper elaborating the therapeutic usefulness of white curcumin-loaded lipidic nanoparticles for skin inflammation.