Summary Background For patients with end-stage renal disease who are not candidates for fistula, dialysis access grafts are the best option for chronic haemodialysis. However, polytetrafluoroethylene arteriovenous grafts are prone to thrombosis, infection, and intimal hyperplasia at the venous anastomosis. We developed and tested a bioengineered human acellular vessel as a potential solution to these limitations in dialysis access. Methods We did two single-arm phase 2 trials at six centres in the USA and Poland. We enrolled adults with end-stage renal disease. A novel bioengineered human acellular vessel was implanted into the arms of patients for haemodialysis access. Primary endpoints were safety (freedom from immune response or infection, aneurysm, or mechanical failure, and incidence of adverse events), and efficacy as assessed by primary, primary assisted, and secondary patencies at 6 months. All patients were followed up for at least 1 year, or had a censoring event. These trials are registered with ClinicalTrials.gov, NCT01744418 and NCT01840956. Findings Human acellular vessels were implanted into 60 patients. Mean follow-up was 16 months (SD 7·6). One vessel became infected during 82 patient-years of follow-up. The vessels had no dilatation and rarely had post-cannulation bleeding. At 6 months, 63% (95% CI 47–72) of patients had primary patency, 73% (57–81) had primary assisted patency, and 97% (85–98) had secondary patency, with most loss of primary patency because of thrombosis. At 12 months, 28% (17–40) had primary patency, 38% (26–51) had primary assisted patency, and 89% (74–93) had secondary patency. Interpretation Bioengineered human acellular vessels seem to provide safe and functional haemodialysis access, and warrant further study in randomised controlled trials. Funding Humacyte and US National Institutes of Health.

Our results suggest that podoplanin expression by CAFs could be an unfavourable prognostic marker for IDC.

Ectosomes (Ects) are a subpopulation of extracellular vesicles formed by the process of plasma membrane shedding. In the present study, we profiled ectosome-specific microRNAs (miRNAs) in patients with type 2 diabetes mellitus (T2DM) and analyzed their pro- and anti-angiogenic potential.Methods: We used different approaches for detecting and enumerating Ects, including atomic force microscopy, cryogenic transmission electron microscopy, and nanoparticle tracking analysis. Furthermore, we used bioinformatics tools to analyze functional data obtained from specific miRNA enrichment signatures during angiogenesis and vasculature development.Results: Levels of miR-193b-3p, miR-199a-3p, miR-20a-3p, miR-26b-5p, miR-30b-5p, miR-30c-5p, miR-374a-5p, miR-409-3p, and miR-95-3p were significantly different between Ects obtained from patients with T2DM and those obtained from healthy controls.Conclusion: Our results showed differences in the abundance of pro- and anti-angiogenic miRNAs in Ects of patients with T2DM, and are suggestive of mechanisms underlying the development of vascular complications due to impaired angiogenesis in such patients.

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Periostin (POSTN) is a secreted cell adhesion glycoprotein that plays an important role in proliferation, adhesion and migration processes, as well as in regulation of mechanisms related to epithelial-mesenchymal transition (EMT). It also plays a key role in angio- and lymphangiogenesis and in formation of distant metastases. The aim of this work was to determine expression of POSTN in invasive ductal breast carcinoma (IDC) and in non-invasive ductal carcinoma in situ (DCIS) and to correlate its expression with clinicopathological parameters. Material for immunohistochemical studies (IHC) comprise of 70 IDC cases, 44 DCIS cases and 21 cases of fibrocystic change (FC). Frozen (-80˚C) fragments of tumours taken from 41 patients with IDC were used for molecular studies (real-time PCR), including 11 cases of IDC subjected to laser capture microdissection (LCM). POSTN expression was shown mainly in tumour stromal cells, i.e. cancer-associated fibroblasts (CAFs). Statistically significant higher level of POSTN expression in CAFs in IDC as compared to FC (p<0.0001) was observed. Additionally, statistically elevated expression level of POSTN in CAFs in IDC relative to DCIS (p<0.0001) and significantly increased expression of POSTN in CAFs in DCIS in comparison to FC (p=0.0158) was also shown. High level of POSTN expression in CAFs in IDC (>8 IRS points) was significantly correlated with tumour malignancy grade (G) (p=0.0070). Moreover, higher POSTN expression by CAFs was associated with patient shorter overall survival. Significant increase of POSTN expression on mRNA and protein level in CAFs in IDC with the growing malignancy grade of the tumours (G) was shown. Furthermore, with the use of LCM method, statistically significant higher expression of mRNA POSTN in stromal cells relative to cancer cells (p<0.001) was noted. POSTN might be a factor playing an important role in the mechanism of IDC progression.

During a haemodialysis (HD), because of the contact of blood with the surface of the dialyser, the immune system becomes activated and reactive oxygen species (ROS) are released into plasma. Particularly exposed to the ROS are lipids and proteins contained in plasma, which undergo peroxidation. The main breakdown product of oxidized lipids is the malondialdehyde (MDA). A common method for measuring the concentration of MDA is a thiobarbituric acid reactive substances (TBARS) method. Despite the formation of MDA in plasma during HD, its concentration decreases because it is removed from the blood in the dialyser. Therefore, this research proposes the Fourier Transform Infrared Attenuated Total Reflectance (FTIR-ATR) spectroscopy, which enables determination of primary peroxidation products. We examined the influence of the amount of hydrogen peroxide added to lipid suspension that was earlier extracted from plasma specimen on lipid peroxidation with use of TBARS and FTIR-ATR methods. Linear correlation between these methods was shown. The proposed method was effective during the evaluation of changes in the extent of lipid peroxidation in plasma during a haemodialysis in sheep. A measurement using the FTIR-ATR showed an increase in plasma lipid peroxidation after 15 and 240 minutes of treatment, while the TBARS concentration was respectively lower.

Cancer-associated fibroblasts (CAFs) are well-known to be part of the tumor microenvironment. This heterogeneous population of cells of the tumor microenvironment via secretion of various growth factors and cytokines was shown to contribute to increased cancer cell proliferation rate, migration, invasiveness and other key processes such as angiogenesis and lymphangiogenesis. Recent studies identified podoplanin as a marker of CAFs in various malignancies and its expression in these cells was shown to influence cancer progression. In some studies it yielded a prognostic impact on patient survival which was strongly dependent on the entity of the tumor. This review summarizes recent findings concerning the biology of podoplanin in cancer progression with particular emphasis on its expression in CAFs.

IntroductionEarly safe discharge is paramount for the success of ERAS following colorectal cancer resections. Anastomotic leakage (AL) has high morbidity, particularly if the patient has been discharged to the community.AimTo evaluate whether C-reactive protein (CRP) and procalcitonin (PCT) can predict AL before early discharge.Material and methodsFifty-five consecutive patients undergoing open and robotic colorectal cancer resections were included. C-reactive protein and PCT were measured pre-operatively, 8 h after incision, and on the first and third postoperative day. Thirty-day readmissions, re-operations and mortality were recorded.ResultsTwenty-nine patients underwent robotic and the remainder open (n = 26) resections. Five patients had AL. The mean CRP and PCT increased on postoperative day 1 (POD 1) and POD 3 in all patients. On POD 3, mean CRP was 114 mg/l in non-AL patients and 321 mg/l in AL patients (p = 0.0001). Mean PCT on POD 3 was 0.56 ng/ml in the non-AL group and 10.4 ng/ml in AL patients (p = 0.017). On analysis of ROC and AUC curves, the cut-off for CRP on POD 3 was 245.64 mg/l, with 100% sensitivity and 98% specificity for AL. The cut-off for PCT on POD 3 was 3.83 ng/ml, with 75% sensitivity and 100% specificity for AL.ConclusionsC-reactive protein and PCT measurement on POD 3 following colorectal cancer resection can positively identify patients at low risk of anastomotic leakage.