Potential of Autologous Adipose-Derived Mesenchymal Stem Cells in Peritoneal Fibrosis:A Pilot Study

Background: We aimed to determine the effects of systemic therapy with autologous adipose tissue derived mesenchymal stem cells (AD-MSCs) on different parameters of peritoneal function and inflammation in peritoneal dialysis (PD) patients.Methods: We enrolled nine PD patients with ultrafiltration failure (UFF). Patients received 1.2 & PLUSMN; 0.1 x 106 cell/kg of AD-MSCs via cubital vein and were then followed for six months at time points of baseline, 3, 6, 12, 16 and 24 weeks after infusion. UNI-PET was performed for assessment of peritoneal characteristics at baseline and weeks 12 and 24. Systemic and peritoneal levels of tumor necrosis factor & alpha; (TNF-& alpha;), interleukin-6 (IL-6), IL-2 and CA125 (by ELISA) and gene expression levels of transforming growth factor beta (TGF-8), smooth muscle actin (������-SMA) and fibroblast-specific protein-1 (FSP-1) in PD effluent derived cells (by quantitative real-time PCR) were measured at baseline and weeks 3, 6, 12, 16 and 24.Results: Slight improvement was observed in the following UF capacity indices: free water transport (FWT, 32%), ultrafiltration -small pore (UFSP, 18%), ultrafiltration total (UFT, 25%), osmotic conductance to glucose (OCG, 25%), D/P creatinine (0.75 to 0.70), and Dt/D0 glucose (0.23 to 0.26). There was a slight increase in systemic and peritoneal levels of CA125 and a slight decrease in gene expression levels of TGF-8, & alpha;-SMA and FSP-1 that was more prominent at week 12 and vanished by the end of the study. Conclusion: Our results for the first time showed the potential of MSCs for treatment of peritoneal damage in a clinical trial. Our results could be regarded as hypothesis suggestion and will need confirmation in future studies

Comparison of endovascular strategy versus hybrid procedure in treatment of chronic venous obstructions involving the confluence of common femoral vein

OBJECTIVE: Treatment of extensive chronic venous obstruction (CVO) with post-thrombotic trabeculation involving the common femoral vein with extension into the femoral vein or deep femoral vein remains a challenge and the best treatment technique for such cases is not clear. In the present study, we compared the results of endovascular alone vs endovascular with additional endophlebectomy (hybrid) procedures for such patients. METHODS: The medical records of 102 consecutive patients (108 limbs) treated between 2015 and 2020 for iliofemoral CVO extending to the femoral confluence were retrospectively reviewed. The patients were divided into two groups: the hybrid procedure (HP) and endovascular treatment (EN) groups. The HP group consisted of those treated with stent implantation and endophlebectomy of the common femoral vein with creation of an arteriovenous fistula. The EN group included those who had undergone stent implantation alone. The patency rates, complications, and clinical outcomes were analyzed. RESULTS: Of the 102 patients, 47 (49 limbs) were in the EN group and 55 (59 limbs) were in the HP group. The demographics of the two groups were similar with no statistically significant differences in cumulative primary, assisted primary, or secondary patency rates at 36 months (33.7% vs 36.3%, P = .839; 59.8% vs 64%, P = .941; 69% vs 72.7%, P = .851; respectively). The patients in the EN group, however, had better clinical improvement with a lower postoperative complication rate (P = .012), shorter procedure duration (P < .001), and shorter hospital stay (P = .025). CONCLUSIONS: The EN and HP both provided similar patency rates for patients with CVO extending into the femoral confluence. The endovascular strategy has the benefit of fewer postoperative complications and a shorter procedure duration and hospital stay compared with the HP

Assessment of the lymphatic system by indirect lymphography in patients with post-thrombotic syndrome

OBJECTIVE: Alterations in lower extremity lymph drainage caused by chronic venous obstruction (CVO) are not well studied, partially due to a lack of standardized imaging modalities to assess the quality of lymphatic drainage in the lower extremities of patients with postthrombotic syndrome (PTS). However, these changes are likely to have an impact on the severity of disease and clinical outcomes of intervention. In the current study, we investigated the feasibility and diagnostic value of pre-intervention indirect lymphography in patients with CVO along with their pre and post intervention Villalta scores. METHODS: A total of 17 patients (21 limbs) with iliofemoral and caval CVO were included in the study between 2017 and 2018. The deep and superficial lymphatic vessels in both legs were assessed before venous recanalization and stenting. The quality of lymphatic flow was compared in legs with CVO and healthy legs. Moreover, the correlation between lymphatic changes and clinical severity of PTS was evaluated by the Villalta score and CEAP classification. RESULTS: The mean patient age was 44 ± 12 years and 10 (59%) patients were female. Patients were treated a mean 25 ± 6 months after their first deep venous thrombosis (DVT). Five patients (29%) suffered from recurrent DVT. Mean pre-interventional Villalta score was 10.5 ± 1.46, post-interventional Villalta was 9.27 ± 1.12 (p:0.0096). Regarding the CEAP classification, 4 legs were in class 5, seven legs were in class 4, three legs were in class 3 and 2 respectively. The primary patency rate was 70.5% and secondary patency rate 82.5% after a mean 18-months of follow-up. Indirect lymphography of the superficial and deep lymphatic system was completed prior to intervention in both legs of all patients. According to qualitative criteria, abnormal lymphatic vessel function was found in 35.2% of the superficial and 58.8% of the deep lymphatic vessels of the affected legs. Further analysis in patients showed abnormal function of deep lymphatic vessels in all patients with moderate to severe PTS according to the Villalta score. CONCLUSION: Indirect lymphography is a feasible diagnostic tool to evaluate the function of lymphatic vessels. Impaired drainage of the deep lymphatic system was found in all patients with moderate to severe PTS. The clinical meaning of these lymphatic changes is not clear, but an association with clinical severity and outcome is possible

Factors associated with difficulty in stenting the chronic iliofemoral venous obstruction

BACKGROUND: The main aim of this article is to investigate the causes of technical failure during endovascular recanalization in patients with post-thrombotic syndrome with occluded iliofemoral veins and to suggest alternative techniques to improve outcomes in such challenging cases. METHODS: Between November 2015 and August 2020, 230 patients (274 limbs) treated in our institution with symptomatic chronic iliofemoral venous obstruction underwent endovascular recanalization with angioplasty and stent placement. Overall, the initial attempt was unsuccessful in 15 limbs. We retrospectively analyzed the basic demographic and health characteristics of the involved patients and evaluated the endovascular procedures and techniques that resulted in a successful second intervention. RESULTS: The first attempts at endovascular intervention were unsuccessful in 15 of the 274 limbs (5.4%). Failures were attributed to hostile groin areas in intravenous drug abusers caused by multiple punctures in six cases. In addition, five interventions failed due to prior surgery at the site of venous occlusion and in retroperitoneal space, three patients due to severe stent deformity, and one patient due to congenital venous aplasia. Of the 15 patients, 11 underwent a subsequent attempt that included six successful recanalizations. The mean follow-up time of the six patients with successful recanalization was 27 months (5-62 months). The primary, assisted primary and secondary patency rates were 83.3%, 100%, and 100%, respectively. The remaining five patients, in whom the second recanalization attempt failed, received conservative treatment. CONCLUSIONS: Recanalization failure is rare in chronic venous obstruction patients. Severe stent deformities have the lowest chance of successful second intervention. Patients with a hostile groin or prior open surgeries at the occlusion site may be considered for reintervention with a success rate of nearly 50%

Quality of Life after Stenting for Iliofemoral Venous Obstruction:A Randomised Controlled Trial with One Year Follow Up

OBJECTIVE: Deep venous obstruction (DVO) has a great burden on the healthcare system and patients' quality of life (QoL). Case series show stenting is safe and effective; however, most studies lack control groups and QoL changes have not been compared with conventional treatment. The aim was to assess the difference in QoL changes from baseline to 12 months between stent and conventionally treated patients with DVO. METHODS: Subjects &gt; 18 years old with DVO due to post-thrombotic (PTS) or non-thrombotic iliac vein lesions (NIVLs) in a tertiary hospital were prospectively randomised to best medical therapy (BMT) or stent placement with BMT in a ratio 2:1, stratified for PTS or NIVL. The primary outcome was the between group difference in VEINES-QoL scores change from baseline to 12 months after treatment. Secondary outcomes included the difference in scores change for EuroQoL 5-Dimension 5-Level (EQ-5D-5L), Pain Disability Index (PDI), Venous Clinical Severity Score (VCSS), and the Villalta score. STUDY REGISTRATION NUMBER: NCT03026049. RESULTS: After three years, the inclusion rate dropped to almost zero, therefore the study had to be stopped. Sixty-three patients were randomised to either the stent (n = 42) or control group (n = 21). Overall, 50 patients had available data for primary outcome analysis. The adjusted mean difference between 12 month scores for VEINES-QoL and VEINES-Sym was 8.07 (95% CI 3.04 - 13.09) and 5.99 (95% CI 0.75 - 11.24) (p = .026), respectively, in favour of the stent group. The differences were significant, but a predefined meaningful 14 point improvement in QoL was not reached. The mean difference between 12 month scores for VCSS was -2.93 (95% CI -5.71 - 0.16, p = .040), -11.83 (95% CI -20.81 - 2.86, p = .011) for PDI, 0.015 (95% CI -0.12 - 0.15, p = .82) for the EQ-5D index, and -2.99 (95% CI -7.28 - 1.30, p = .17) for the Villalta score. CONCLUSION: Symptomatic patients with DVO who received dedicated venous stents had significantly higher VEINES-QoL/Sym scores at 12 months compared with the control group, but the between group difference was lower than the pre-specified clinically relevant QoL difference of at least 14 points

Systemic Infusion of Autologous Adipose Tissue-Derived Mesenchymal Stem Cells in Peritoneal Dialysis Patients: Feasibility and Safety

Using mesenchymal stem cells (MSCs) is regarded as a new therapeutic approach for improving fibrotic diseases. The aim of this study to evaluate the feasibility and safety of systemic infusion of autologous adipose tissue-derived MSCs (AD-MSCs) in peritoneal dialysis (PD) patients with expected peritoneal fibrosis. Materials and Methods: This study was a prospective, open-label, non-randomized, placebo-free, phase I clinical trial. Case group consisted of nine eligible renal failure patients with more than two years of history of being on PD. Autologous AD-MSCs were obtained through lipoaspiration and expanded under good manufacturing practice conditions. Patients received 1.2 ± 0.1×106 cell/kg of AD-MSCs via cubital vein and then were followed for six months at time points of baseline, and then 3 weeks, 6 weeks, 12 weeks, 16 weeks and 24 weeks after infusion. Clinical, biochemical and peritoneal equilibration test (PET) were performed to assess the safety and probable change in peritoneal solute transport parameters. Results: No serious adverse events and no catheter-related complications were found in the participants. 14 minor reported adverse events were self-limited or subsided after supportive treatment. One patient developed an episode of peritonitis and another patient experienced exit site infection, which did not appear to be related to the procedure. A significant decrease in the rate of solute transport across peritoneal membrane was detected by PET (D/P cr=0.77 vs. 0.73, P=0.02). Conclusion: This study, for the first time, showed the feasibility and safety of AD-MSCs in PD patients and the potentials for positive changes in solute transport. Further studies with larger samples, longer follow-up, and randomized blind control groups to elucidate the most effective route, frequency and dose of MSCs administration, are necessary (Registration Number: IRCT2015052415841N2)

Quality of Life after Stenting for Iliofemoral Venous Obstruction: A Randomised Controlled Trial with One Year Follow Up.

OBJECTIVE: Deep venous obstruction (DVO) is a great burden on the healthcare system and patients\u27 quality of life (QoL). Case series show stenting is safe and effective, however most studies lack control groups and QoL changes have not been compared with conventional treatment. The aim was to assess the difference in QoL changes from baseline to 12 months between stent and conventionally treated patients with DVO. METHODS: Subjects \u3e 18 years old with DVO due to post-thrombotic (PTS) or non-thrombotic iliac vein lesions (NIVLs) in a tertiary hospital were prospectively randomised to best medical therapy (BMT) or stent placement with BMT in a ratio 2:1, stratified for PTS or NIVL. The primary outcome was the between group difference in VEINES-QoL scores change from baseline to 12 months after treatment. Secondary outcomes included the difference in score changes for EuroQoL 5-Dimension 5 Level (EQ-5D-5L), Pain Disability Index (PDI), Venous Clinical Severity Score (VCSS), and the Villalta score. STUDY REGISTRATION NUMBER: NCT03026049. RESULTS: After three years, the inclusion rate dropped to almost zero, therefore the study had to be stopped. Sixty-three patients were randomised to either the stent (n = 42) or control group (n = 21). Overall, 50 patients had available data for primary outcome analysis. The adjusted mean difference between 12 month scores for VEINES-QoL and VEINES-Sym was 8.07 (95% CI 3.04 - 13.09) and 5.99 (95% CI 0.75 - 11.24) (p = .026), respectively, in favour of the stent group. The differences were significant, but a pre-defined meaningful 14 point improvement in QoL was not reached. The mean difference between 12 month scores for VCSS was -2.93 (95% CI -5.71 - 0.16, p = .040), -11.83 (95% CI -20.81 - 2.86, p = .011) for PDI, 0.015 (95% CI -0.12 - 0.15, p = .82) for the EQ-5D index, and -2.99 (95% CI -7.28 - 1.30, p = .17) for the Villalta score. CONCLUSION: Symptomatic patients with DVO who received dedicated venous stents had significantly higher VEINES-QoL/Sym scores at 12 months compared with the control group, but the between group difference was lower than the pre-specified clinically relevant QoL difference of at least 14 points

Development of a prediction model for deep vein thrombosis in a retrospective cohort of patients with suspected deep vein thrombosis in primary care

OBJECTIVES: Early accurate prediction and diagnosis of deep-vein thrombosis (DVT) is essential to allow immediate treatment and reduce potential complications. However, all potential strong risk factors are not included in pretest probability assessments such as the Wells score. In addition, the Wells score may not be suitable in primary care since it was developed for secondary care. We hypothesized that by adding more risk factors for DVT, existing diagnostic approaches may improve DVT prediction. METHODS: All consecutive patients suspected of DVT (2004-2016) in a primary care setting were included in this retrospective study. All patients received a Wells score, D-dimer, and duplex. Available recorded data of patients were used to develop a model to predict DVT. RESULTS: Among 3381 eligible patients, 489 (14.5%) had confirmed DVT. The developed model based on D-dimer, Wells score, gender, anticoagulation use, age, and family history of venous thrombosis (VTE) was able to distinguish DVT patients from all suspected DVTs with a sensitivity of 82% (confidence interval [CI]: 78-86) and a specificity of 82% (CI: 80-83). CONCLUSIONS: The proposed model is able to predict the presence of DVT among all suspected DVT patients in a primary care setting with reasonable accuracy. Further validation in prospective studies is required

Additional file 2: Figure S1. of Safety and tolerability of autologous bone marrow mesenchymal stromal cells in ADPKD patients

Characterization of the patients’ bone mesenchymal stromal cells (MSCs). (DOCX 781 kb

Evaluation of safety and performance of a new prototype self-expandable nitinol venous stent in an ovine model

Objective: Our study was a prospective in vivo study performed on an animal model to evaluate the safety and performance of a novel venous stent designed specifically for venous applications. Methods: The novel stents were implanted in the inferior vena cava of nine sheep. The stents were deployed with different distances between the closed cell rings to test for if the segments might migrate after being deployed at maximal distance. Three different total lengths were 9, 11, and 13 cm. After 1, 3, and 6 months, vascular injury, thrombus, neointima coverage, and stent migration were evaluated through computed tomography venography and histopathology. Imaging, histology, and integration data were analyzed for each group. Results: All stents were deployed successfully, and all sheep survived until the time of harvesting. In all cases, the native blood vessel sections were intact. The segmented stent parts showed a differently pronounced tissue coverage, depending on the duration of the implantation. Conclusions: The new nitinol stent is safe and feasible to implant in the venous system with a rapid surface coverage. Alteration of stent length did not affect the development of neointimal formation and did not cause migration. : Clinical Relevance: The clinical relevance of our study titled ''Evaluation of Safety and Performance of a New Prototype Self-Expandable Nitinol Stent in an Ovine Model'' lies in its potential to advance the field of venous intervention. Stent implantation is a common procedure used to treat deep venous obstruction, and the use of self-expandable nitinol stents has been shown to be effective in improving the patency rates. However, the safety and efficacy of new stent prototypes must be evaluated thoroughly before they can be used in clinical practice. Our study contributes to the evaluation of a new prototype self-expandable nitinol stent by demonstrating its excellent mechanical properties, biocompatibility, and histopathological response in an ovine model. The results of our study may provide valuable insight for researchers and clinicians in developing and implementing new stent technologies, ultimately improving patient outcomes in the treatment of chronic venous obstruction