Autosomal dominant polycystic kidney disease (ADPKD) is a genetic disorder causing progressive renal cyst formation, increased kidney volume, and impaired function. The PCK rat is a preclinical model for investigating new treatments, requiring accurate quantification of total kidney volume (TKV), total cyst volume (TCV), and cyst count. We propose an automated segmentation pipeline of kidneys and cysts on µCT scans of excised rat kidneys, followed by automated cyst counting. For segmentation, a 3D U-Net ensemble was implemented using the nnU-Net framework with dual-channel input (raw µCT volumes, Sobel-filtered images). Models were trained on Dataset 1 subsets (D1, n = 5, 10, 15, 20), and evaluated on internal test set (n = 5) and independent external Dataset 2 (D2, n = 5). Segmentation achieved Dice Similarity Coefficients > 0.99 for kidney and > 0.98 for cysts on D1, with comparable performance on D2, exploring cross-scanner generalizability. For cyst counting, a morphological algorithm based on 3D distance transform and peak detection was optimized via genetic algorithm on 10 samples and evaluated on independent 10-sample set. The automated method achieved low variability, with operator-algorithm agreement exceeding inter-operator agreement across all metrics, drastically reducing processing time. The pipeline provides fast, accurate, and reproducible quantification of morphological biomarkers required for preclinical PKD research.

BACKGROUND:Fibromuscular dysplasia (FMD) is a potentially curable cause of renovascular hypertension, primarily affecting middle-aged women. Percutaneous angioplasty is the recommended treatment for patients with hemodynamically significant renal artery stenosis (RAS). However, no established non-invasive method currently exists to estimate the pressure drop across stenosis and assess its hemodynamic impact. This study aimed to assess the clinical applicability of an image-based computational fluid dynamic (CFD) pipeline, functioning as a digital twin of the renal vasculature, for non-invasive assessment of fractional flow reserve (FFR) and trans-stenotic pressure drop in patients with FMD-related RAS. METHODS:This retrospective study included 10 middle-aged women: six with FMD-related stenosis (two focal and four multifocal), two with atherosclerotic RAS and two healthy volunteers. For each subject, a patient-specific 3D surface model of the renal vasculature was reconstructed from medical images and CFD simulations were performed using Simvascular. FFR and trans-stenotic pressure drop were assessed across each renal artery. RESULTS:The imaged-based CFD pipeline was feasible for all 10 subjects. A wide range of FFR (0.57 - >0.95) and pressure drops (11-73 mmHg) was observed across subjects, depending on the phenotype and severity of stenosis. The computed pressure drops and FFR values were consistent with the clinical decision on revascularization (AUC = 0.988), supporting the diagnostic relevance of the model. CONCLUSION:The proposed pipeline represents a promising non-invasive approach to assess the hemodynamic significance of RAS due to FMD. As a digital twin for personalized cardiovascular medicine, it could serve as valuable tool for selecting patients requiring angioplasty and predicting revascularization outcomes.

BACKGROUND:Vascular access failure often makes hemodialysis treatment inefficient or impossible. This study investigates the potential of using recordings and acoustic analysis of arteriovenous fistula (AVF) sounds to i) distinguish between AVFs suitable for routine cannulation and those that are unsuitable and ii) detect possible complications in functional AVFs early. METHODS:A total of 154 AVF sounds were recorded and classified into functioning and non-functioning groups. Functioning AVFs were further categorized as optimally patent or as having complications like stenosis or aneurysm, based on ultrasound. After audio pre-processing, the high-low peak ratio (HLPR) and its natural logarithm (ln(HLPR)) were calculated using peak amplitudes in low and high-frequency ranges (100-250 Hz and 500-700 Hz respectively). RESULTS:The results revealed significant differences in acoustic metrics between functioning and non-functioning AVFs. Non-functioning AVFs exhibited higher frequency sounds, higher HLPR and ln(HLPR), and reduced amplitude in the low frequency range. In functioning AVFs, the presence of stenosis produced distinct acoustic patterns with higher frequencies and lower amplitude in the low-frequency range, while aneurysms exhibited prominent high frequencies but did not significantly affect acoustic metrics compared to sound recordings from optimally patent AVFs. Optimally patent AVFs had the highest amplitude in low frequency and the lowest high-frequency presence, exhibiting statistically significant differences compared to stenotic and non-functioning AVFs. Additionally, exploratory ROC analysis suggests a potential threshold in ln(HLPR) for identifying AVF function impairment, with good sensitivity and specificity. CONCLUSIONS:This study highlights the transformative potential of AVF sound analysis as a tool for identifying AVF complications and failure. By using the unique acoustic characteristics of AVFs, clinicians can improve their surveillance strategies, providing patients with timely interventions and better outcomes.

Background: Arteriovenous fistula (AVF) is the preferred vascular access (VA) for hemodialysis, but it is still affected by high non-maturation and early failure rates due to stenosis development. Increasing evidence suggests that the presence of turbulent-like flow may play a key role, therefore, to stabilize the flow in the venous segment, an external support device (VasQ TM ) has been designed. The aim of this study was to provide preliminary evidence of VasQ TM impact on AVF hemodynamics as compared to AVFs created with conventional surgery. Methods: In this pilot single-center prospective randomized study six patients were enrolled, three in the VasQ group and three in the control group. Contrast-free magnetic resonance imaging (MRI) scans were acquired at 3 days, 3 months and 1 year after AVF surgery and were used to generate 3D patient-specific models. Computational fluid dynamic (CFD) simulations were performed using pimpleFoam, imposing patient-specific flow waveforms derived from ultrasound (US) examinations at the inlet of the proximal and distal artery, and a traction-free condition at the venous outflow. Morphologic and hemodynamic changes occurring over time were compared between VasQ and control AVFs. Results: Our MRI protocol provided high-quality images suitable for reliable segmentation and reconstruction of patient-specific 3D models of AVFs at all three timepoints in four out of six patients. The VasQ TM device maintained the angle between the artery and the vein almost unchanged over time, with a more stable flow in the AVFs supported by the device. In contrast, one of the AVFs of the control group evolved to an extreme dilatation of the vein and highly disturbed flow, while the other developed a stenosis in the juxta-anastomotic region. Conclusions: This study demonstrated the feasibility of characterizing the morphological and hemodynamic changes occurring over time in AVFs created using the VasQ TM device and provided preliminary evidence of the potential hemodynamic benefits of its use. Keywords Arteriovenous fistula , computational fluid dynamics , disturbed flow , external support device , longitudinal changes

Kidney fibrosis is a chronic physiomorphologic transformation of the renal parenchyma. Despite the known characteristics of the related structural and cellular changes, the mechanisms responsible for the initiation and progression of renal fibrosis are not completely understood. Development of efficient therapeutic drugs aimed at preventing the progressive loss of renal function requires an in-depth understanding of the complex phenomena associated with the pathophysiology of human diseases. The investigation of Li et al. provides novel evidence in this direction.

The mechanisms underlying vascular stenosis formation in the arteriovenous fistula (AVF) for hemodialysis (HD) remain mostly unknown. Several computational fluid dynamics (CFD) studies have suggested a potential role for unsteady flow in inducing intimal hyperplasia and AVF stenosis, but the majority of these observations have been limited to a single time point after surgical creation. The aim of the present study was to investigate the relation between hemodynamic conditions and AVF vascular remodeling through a CFD longitudinal study. Non contrast-enhanced MR images and Doppler Ultrasound (US) examinations were acquired at 3 days, 40 days, 6 months, 1 year, and 1.5 years after surgery in a 72-year male referred for native radio-cephalic AVF. Three-dimensional AVF models were generated and high fidelity CFD simulations were performed using pimpleFoam, setting patient-specific boundary conditions derived from US. Morphological and hemodynamic changes over time were then analyzed. Analysis of vessel morphology and hemodynamics during follow-up showed that the AVF had a successful maturation process, characterized by a massive arterial and venous dilatation within the 6 months after surgery, a corresponding increase in blood flow volume and important flow instabilities. Between 6 months and 1 year, a stenosis developed in the juxta-anastomotic vein and caused AVF failure at 1.5 years. The development of stenosis was paralleled by the regularization of blood flow velocity pattern and consequent decrease in the near-wall disturbed flow metrics. These results suggest that development of intimal hyperplasia and vessel stenosis, triggered by unsteady flow, could be the result of vascular inward remodeling toward regularization of turbulent-like flow.

It has been largely documented that local hemodynamic conditions, characterized by low and oscillating wall shear stresses, play a key role in the initiation and progression of vascular atherosclerotic lesions. Thus, investigation of the flow field in the carotid bifurcation can lead to early identification of vulnerable plaques. In this scenario, the development of novel non-invasive imaging tools that can be used in routine clinical practice to identify disturbed and recirculating blood flow becomes crucial. In this context, Vector Flow Imaging is becoming a relevant tool as it provides an angle independent assessment of blood flow velocity and multidimensional flow vector visualization. The purpose of the present study was to validate, in several locations of the carotid bifurcation, the high-frame rate vector flow imaging (HiFR-VFI) technique by comparing with computational fluid dynamic simulations (CFD).In all eight carotid bifurcations, HiFR-VFI accurately detected regions of laminar flow as well as recirculation and unsteady flow areas. An accurate and statistically significant agreement was observed between velocity vectors obtained by HiFR-VFI and those computed by CFD, both for vector magnitude (R = 0.85) and direction (R = 0.74).Our study demonstrated that HiFR-VFI is a valid technique for rapid and advanced visual representation of velocity field in large arteries. Thus, it has a great potential in research-based clinical practice for the identification of flow recirculation, low and oscillating velocity gradients near vessel wall. The use of HiFR-VFI may provide a great improvement in the investigation of the role of local hemodynamics in vascular pathologies, as well in the assessment of the effect of pharmacological treatments.

BACKGROUND:With the spread of COVID-19, telemedicine solutions became crucial to release continuous and remote assistance to chronic patients. The rapid transition to telemedicine solutions did not allow a complete assessment of the user experience by both patients and medical personnel. Despite the well-known benefits in remote care, the lack of usability evaluation of already existing technologies for the vital signs measurement has emerged. A telemedicine platform must match video communication between patients and the medical staff with the possibility to measure vital parameters. Furthermore, technological assistance may overcome the unfamiliarity with telemedicine and drastically reduce the learning time for both patients and medical personnel.OBJECTIVES:The research work presents a method to improve the user experience of a telemedicine service based on the combination of televisits and telemonitoring with wearable sensors for heart failure patients. Skilled technological staff is proposed by the presented method to lead the learning process of both medical personnel and patients in order to reach a high level of usability in less than 6 months.METHODS:The proposed method is composed of 5 steps: identification of technological staff and end users; selection of the telemedicine platform; design of questionnaires for usability analysis; training of clinicians and patients; final usability evaluation of the telemedicine platform by means of customized satisfaction questionnaires and Post-Study System Usability Questionnaires (PSSUQs). The methodological approach has been tested in collaboration with a heart failure clinic by involving 5 physicians, 5 nurses, 15 heart failure patients, a research engineer and 4 technicians. A platform with 3 wearable sensors has been chosen: a wireless thermometer, a finger pulse-oximeter and an undershirt have been used for the detection of ECG trace. While these devices allowed asynchronous measurements of physiological data, scheduled televisits have been used for direct communication between physicians and patients.RESULTS:Satisfaction questionnaires of patients and clinicians reached respectively 65.18% and 65.83%, while PSSUQ scores were respectively 91.73% and 81.70%. Both groups of end users confirmed a good level of usability and their satisfaction about the ease of use and the perceived quality of the instrumentation. Moreover, 73% of patients did not require help from caregivers to use the kit of sensors. The results have been reached in 5.5 months according to the aim defined initially. Research engineers have played a crucial role in helping clinicians and patients to improve the user experience with the telemedicine platform.CONCLUSIONS:The high level of usability and satisfaction confirmed that the proposed methodological approach helps to learn the technological features of the telemedicine platforms, which are based on different types of technology, such as web applications, wearable sensors and virtual calls. The positive results with heart failure patients encouraged to plan further research studies by using the designed method with other categories of chronic patients.

Renal fibrosis, which is characterized by the progressive deposition and accumulation of excess extracellular matrix, 1 Bulow R.D. Boor P. Extracellular matrix in kidney fibrosis: more than just a scaffold. J Histochem Cytochem. 2019; 67: 643-661 Crossref PubMed Scopus (159) Google Scholar is a strong predictor of progression in chronic kidney disease (CKD). 2 Nath K.A. The tubulointerstitium in progressive renal disease. Kidney Int. 1998; 54: 992-994 Abstract Full Text Full Text PDF PubMed Scopus (162) Google Scholar ,3 Nangaku M. Chronic hypoxia and tubulointerstitial injury: a final common pathway to end-stage renal failure. J Am Soc Nephrol. 2006; 17: 17-25 Crossref PubMed Scopus (923) Google Scholar Recent advances in diagnostic imaging techniques, including ultrasonography and noncontrast-enhanced magnetic resonance imaging (MRI), have shown promise for noninvasive assessment of renal fibrosis both in animals and humans. 4 Jiang K. Ferguson C.M. Lerman L.O. Noninvasive assessment of renal fibrosis by magnetic resonance imaging and ultrasound techniques. Transl Res. 2019; 209: 105-120 Abstract Full Text Full Text PDF PubMed Scopus (43) Google Scholar However, the specificity of these techniques is controversial, because they indirectly assess renal fibrosis by evaluating the impact on mechanical or molecular properties of the tissue, and in the case of functional MRI, on kidney function. Moreover, these techniques are not sensitive to early fibrotic changes, which could be relevant for implementing timely interventions to halt CKD progression. Visualizing fibrosis—hope for ideal markers beyond imagingKidney InternationalVol. 97Issue 3PreviewHow do nephrologists, or physicians, evaluate chronic kidney disease (CKD) progression? Clinically, the progression of CKD is routinely assessed by the decrease in estimated glomerular filtration rate and histologically by expansion of the fibrotic area. Unfortunately, the level of estimated glomerular filtration rate does not always precisely reflect the extent of kidney fibrosis. The gap between the estimated glomerular filtration rate (the clinical indicator of the renal function of toxin excretion) and the interstitial fibrosis and tubular atrophy index (the histological index of collagen accumulation) complicates the precise understanding and evaluation of CKD progression. Full-Text PDF

Purpose. A large number of patients affected by the SARS-Cov-2 virus worldwide undergo recovery of symptoms in about one month. Among these patients, the healing process is still under observation, with some patients in need of careful clinical monitoring. While the radiological findings have been shown to regress almost completely, little knowledge is available at the moment about other complications in the lung and in other organs. We then investigated the lung perfusion conditions in patients affected by COVID- 19 during recovery. Method. We retrospectively studied 20 patients, from 14 to 60 days after resolution of the COVID-19 symptoms, using chest CT. In a subgroup of 5 patients contrasted CT was used. Beside normal radiological evaluation of lung tissue, perfusion conditions were evaluated by digital image processing in the lung volume automatically segmented. Results. Pulmonary lung evaluation showed that COVID-19 pneumonia almost completely regressed, with mild focal areas affected by fibrous stripes. In patients that reported dyspnea, lung CT showed complete resolution of interstitial changes. Quantification of lung perfusion condition by contrasted CT, showed that dyspnea in 3 patients was associated with areas of hypoperfusion, while in 2 patients not reporting dyspnea perfusion conditions were comparable to normal controls. Conclusions. Although we obtained preliminary data, this is the first report on quantitative evaluation of hypoperfused lung tissue detected in recovering COVID-19 patients. These results suggest the need to further investigate these patients and to redefine the role of CT evaluation for diagnostic purposes as well as for evaluation of potential treatments.

Una supermatriz de nichos sinteticos que comprende al menos dos matrices de nichos sinteticos, en la que cada matriz comprende n x m nichos sinteticos, en la que n y m, identicos o diferentes entre si, tienen un valor >= 1, a condicion de que uno de m o n sea >= 2 y con un valor maximo de m y n que permite mantener la estructura del nicho sintetico individual intacta de modo que la retraccion del material no causa alteraciones significativas, y en la que la distancia (d) entre una matriz de nicho sintetico y la otra es superior a cero y en la que, en cada matriz, cada nicho sintetico tiene una o mas paredes en comun con el(los) otro(s) nicho(s) sintetico(s) de la matriz.

Combining 2D ultrasound High-frame rate Vector Flow (HiFR-VF) and 3D Computational Fluid Dynamics (CFD) on the carotid bifurcation (CB) may allow the clinical validation of a new approach to obtain a comprehensive assessment of the blood flow field. This initial study aimed at ensuring the effectiveness of a protocol designed for a future multicentric prospective study.

BACKGROUND:Autosomal dominant polycystic kidney disease (ADPKD) is the most frequent genetically determined renal disease. In affected patients, renal function may progressively decline up to end-stage renal disease (ESRD), and approximately 10% of those with ESRD are affected by ADPKD. The somatostatin analog octreotide long-acting release (octreotide-LAR) slows renal function deterioration in patients in early stages of the disease. We evaluated the renoprotective effect of octreotide-LAR in ADPKD patients at high risk of ESRD because of later-stage ADPKD. METHODS AND FINDINGS:We did an internally funded, parallel-group, double-blind, placebo-controlled phase III trial to assess octreotide-LAR in adults with ADPKD with glomerular filtration rate (GFR) 15-40 ml/min/1.73 m2. Participants were randomized to receive 2 intramuscular injections of 20 mg octreotide-LAR (n = 51) or 0.9% sodium chloride solution (placebo; n = 49) every 28 days for 3 years. Central randomization was 1:1 using a computerized list stratified by center and presence or absence of diabetes or proteinuria. Co-primary short- and long-term outcomes were 1-year total kidney volume (TKV) (computed tomography scan) growth and 3-year GFR (iohexol plasma clearance) decline. Analyses were by modified intention-to-treat. Patients were recruited from 4 Italian nephrology units between October 11, 2011, and March 20, 2014, and followed up to April 14, 2017. Baseline characteristics were similar between groups. Compared to placebo, octreotide-LAR reduced median (95% CI) TKV growth from baseline by 96.8 (10.8 to 182.7) ml at 1 year (p = 0.027) and 422.6 (150.3 to 695.0) ml at 3 years (p = 0.002). Reduction in the median (95% CI) rate of GFR decline (0.56 [-0.63 to 1.75] ml/min/1.73 m2 per year) was not significant (p = 0.295). TKV analyses were adjusted for age, sex, and baseline TKV. Over a median (IQR) 36 (24 to 37) months of follow-up, 9 patients on octreotide-LAR and 21 patients on placebo progressed to a doubling of serum creatinine or ESRD (composite endpoint) (hazard ratio [HR] [95% CI] adjusted for age, sex, baseline serum creatinine, and baseline TKV: 0.307 [0.127 to 0.742], p = 0.009). One composite endpoint was prevented for every 4 treated patients. Among 63 patients with chronic kidney disease (CKD) stage 4, 3 on octreotide-LAR and 8 on placebo progressed to ESRD (adjusted HR [95% CI]: 0.121 [0.017 to 0.866], p = 0.036). Three patients on placebo had a serious renal cyst rupture/infection and 1 patient had a serious urinary tract infection/obstruction, versus 1 patient on octreotide-LAR with a serious renal cyst infection. The main study limitation was the small sample size. CONCLUSIONS:In this study we observed that in later-stage ADPKD, octreotide-LAR slowed kidney growth and delayed progression to ESRD, in particular in CKD stage 4. TRIAL REGISTRATION:ClinicalTrials.gov NCT01377246; EudraCT: 2011-000138-12.

For patients with severe kidney or liver failure the best solution is currently organ transplantation. However, not all patients are eligible for transplantation and due to limited organ availability, most patients are currently treated with therapies using artificial kidney and artificial liver devices. These therapies, despite their relative success in preserving the patients' life, have important limitations since they can only replace part of the natural kidney or liver functions. As blood detoxification (and other functions) in these highly perfused organs is achieved by specialized cells, it seems relevant to review the approaches leading to bioengineered organs fulfilling most of the native organ functions. There, the culture of cells of specific phenotypes on adapted scaffolds that can be perfused takes place. In this review paper, first the functions of kidney and liver organs are briefly described. Then artificial kidney/liver devices, bioartificial kidney devices, and bioartificial liver devices are focused on, as well as biohybrid constructs obtained by decellularization and recellularization of animal organs. For all organs, a thorough overview of the literature is given and the perspectives for their application in the clinic are discussed.

Autologous arteriovenous fistula (AVF) is the preferred choice for providing vascular access to hemodialysis (HD) patients, but it is still affected by high incidence of non-maturation or early failure. After creation, AVF must undergo vascular remodeling, a process characterized by an increase in blood vessel diameter and wall thickness, to allow efficient and adequate HD. A growing body of evidence indicates that AVF maturation is related to the response of endothelial cells (ECs) to changes in wall shear stress (WSS), and in particular, to changes of its peak value. The reasons why important number of AVFs are affected by non-maturation or early failure still remain to be elucidated, but it has been suggested that local hemodynamic conditions with highly disturbed flow patterns may play an important role. In the present contribution, we addressed the role of WSS on AVF maturation, clarifying mechanisms that affect the clinical outcome of AVF creation. We also pointed out the need of non-invasive longitudinal studies, with repeated observations of hemodynamic parameters and structural changes during time, to obtain evidence of a cause-and-effect relationship between the presence of disturbed flow and AVF maturation failure. This understanding may be fundamental in the future to ameliorate clinical outcome of AVF creation, with a great impact on the clinical management of HD patients and their quality of life.

Although our understanding of the failure mechanism of vascular access for hemodialysis has increased substantially, this knowledge has not translated into successful therapies. Despite advances in technology, it is recognized that vascular access is difficult to maintain, due to complications such as intimal hyperplasia. Computational studies have been used to estimate hemodynamic changes induced by vascular access creation. Due to the heterogeneity of patient-specific geometries, and difficulties with obtaining reliable models of access vessels, idealized models were often employed. In this review we analyze the knowledge gained with the use of computational such simplified models. A review of the literature was conducted, considering studies employing a computational fluid dynamics approach to gain insights into the flow field phenotype that develops in idealized models of vascular access. Several important discoveries have originated from idealized model studies, including the detrimental role of disturbed flow and turbulent flow, and the beneficial role of spiral flow in intimal hyperplasia. The general flow phenotype was consistent among studies, but findings were not treated homogeneously since they paralleled achievements in cardiovascular biomechanics which spanned over the last two decades. Computational studies in idealized models are important for studying local blood flow features and evaluating new concepts that may improve the patency of vascular access for hemodialysis. For future studies we strongly recommend numerical modelling targeted at accurately characterizing turbulent flows and multidirectional wall shear disturbances.