The Snuffbox Arteriovenous Fistula for Vascular Access

AbstractObjectives to determine the applicability, patency rates and factors influencing patency of snuffbox arteriovenous fistulae for haemodialysis access. Design retrospective non-randomised study. Materials and methods patency was determined by reference to an ongoing database and dialysis records of 645 vascular access procedures between 1985 and 1997, including 210 snuffbox fistulae in 201 patients. Results snuffbox fistulae comprised 189/376 (50%) primary procedures. Records of 208 snuffbox fistulae were available for patency analysis by the life-table method. Twenty-two (11%) thrombosed within 24 hours of operation. After six weeks 80% were used for dialysis. Cumulative patency was 65% at 1 year and 45% at 5 years. After thrombosis of snuffbox fistulae, ipsilateral wrist fistulae could be constructed in 45%. Fistula patency was significantly better in men than women (p<0.001) and for left- than right-sided fistulae (p<0.001). Diabetes, age >70 years, and the prior commencement of haemodialysis did not significantly affect fistula survival. Conclusions the snuffbox AV fistula gives a long segment of arterialised vein for needling and preserves proximal vessels. It is feasible in 50% of patients requiring primary access and has good long-term patency, especially in men. A more proximal fistula may be preferable in women with smaller vessels

Fully automated on demand cell culture media preparation for perfusion

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Development of a highly concentrated perfusion medium supplement to decrease media demand leveraging a newly designed 250 mL single use perfusion bioreactor

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A highly selective purine-based inhibitor of CSF1R potently inhibits osteoclast differentiation

The colony-stimulating factor 1 receptor (CSF1R) plays an important role in the regulation of many inflammatory processes, and overexpression of the kinase is implicated in several disease states. Identifying selective, smallmolecule inhibitors of CSF1R may be a crucial step toward treating these disorders. Through modelling, synthesis, and a systematic structure-activity relationship study, we have identified a number of potent and highly selective purine-based inhibitors of CSF1R. The optimized 6,8-disubstituted antagonist, compound 9, has enzymatic IC50 of 0.2 nM, and displays a strong affinity toward the autoinhibited form of CSF1R, contrasting that of other previously reported inhibitors. As a result of its binding mode, the inhibitor shows excellent selectivity (Selectivity score: 0.06), evidenced by profiling towards a panel of 468 kinases. In cell-based assays, this inhibitor shows dose-dependent blockade of CSF1-mediated downstream signalling in murine bone marrow-derived macrophages (IC50 = 106 nM) as well as disruption of osteoclast differentiation at nanomolar levels. In vivo experiments, however, indicate that improve metabolic stability is needed in order to further progress this compound class

Saphenofemoral arteriovenous fistula as hemodialysis access

<p>Abstract</p> <p>Background</p> <p>An upper limb arteriovenous (AV) fistula is the access of choice for haemodialysis (HD). There have been few reports of saphenofemoral AV fistulas (SFAVF) over the last 10-20 years because of previous suggestions of poor patencies and needling difficulties. Here, we describe our clinical experience with SFAVF.</p> <p>Methods</p> <p>SFAVFs were evaluated using the following variables: immediate results, early and late complications, intraoperative and postoperative complications (up to day 30), efficiency of the fistula after the onset of needling and complications associated to its use.</p> <p>Results</p> <p>Fifty-six SFAVF fistulas were created in 48 patients. Eight patients had two fistulas: 8 patent (16%), 10 transplanted (20%), 12 deaths (24%), 1 low flow (2%) and 20 thrombosis (39%) (first two months of preparation). One patient had severe hypotension during surgery, which caused thrombosis of the fistula, which was successfully thrombectomised, four thrombosed fistulae were successfully thrombectomised and revised on the first postoperative day. After 59 months of follow-up, primary patency was 44%.</p> <p>Conclusion</p> <p>SFAVF is an adequate alternative for patients without the possibility for other access in the upper limbs, allowing efficient dialysis with good long-term patency with a low complication rate.</p

Second asymptomatic carotid surgery trial (ACST-2): a randomised comparison of carotid artery stenting versus carotid endarterectomy

Background: Among asymptomatic patients with severe carotid artery stenosis but no recent stroke or transient cerebral ischaemia, either carotid artery stenting (CAS) or carotid endarterectomy (CEA) can restore patency and reduce long-term stroke risks. However, from recent national registry data, each option causes about 1% procedural risk of disabling stroke or death. Comparison of their long-term protective effects requires large-scale randomised evidence. Methods: ACST-2 is an international multicentre randomised trial of CAS versus CEA among asymptomatic patients with severe stenosis thought to require intervention, interpreted with all other relevant trials. Patients were eligible if they had severe unilateral or bilateral carotid artery stenosis and both doctor and patient agreed that a carotid procedure should be undertaken, but they were substantially uncertain which one to choose. Patients were randomly allocated to CAS or CEA and followed up at 1 month and then annually, for a mean 5 years. Procedural events were those within 30 days of the intervention. Intention-to-treat analyses are provided. Analyses including procedural hazards use tabular methods. Analyses and meta-analyses of non-procedural strokes use Kaplan-Meier and log-rank methods. The trial is registered with the ISRCTN registry, ISRCTN21144362. Findings: Between Jan 15, 2008, and Dec 31, 2020, 3625 patients in 130 centres were randomly allocated, 1811 to CAS and 1814 to CEA, with good compliance, good medical therapy and a mean 5 years of follow-up. Overall, 1% had disabling stroke or death procedurally (15 allocated to CAS and 18 to CEA) and 2% had non-disabling procedural stroke (48 allocated to CAS and 29 to CEA). Kaplan-Meier estimates of 5-year non-procedural stroke were 2·5% in each group for fatal or disabling stroke, and 5·3% with CAS versus 4·5% with CEA for any stroke (rate ratio [RR] 1·16, 95% CI 0·86–1·57; p=0·33). Combining RRs for any non-procedural stroke in all CAS versus CEA trials, the RR was similar in symptomatic and asymptomatic patients (overall RR 1·11, 95% CI 0·91–1·32; p=0·21). Interpretation: Serious complications are similarly uncommon after competent CAS and CEA, and the long-term effects of these two carotid artery procedures on fatal or disabling stroke are comparable. Funding: UK Medical Research Council and Health Technology Assessment Programme

Analysis of interaction of murine 66cl4 and 67NR breast carcinomas with tumor-associated macrophages

Breast cancer is the most common cancer among women in the world, and death is usually caused by metastasis. A tumor is a heterogeneous mass of different cells, and the tumor microenvironment is complex with extensive communication between the different cell types. Tumor cells are able to polarize cells of the microenvironment, like macrophages, by secreting different compounds including members of the TGF-β superfamily. Macrophages can be polarized towards classically activated M1 macrophages or alternatively activated M2 macrophages. Tumor-associated macrophages (TAMs) are mainly M2 macrophages and support tumor growth by promoting tumor cell survival and proliferation, matrix remodeling, angiogenesis and metastasis. The number of macrophages in a tumor is correlated with poor prognosis in breast cancer patients. By utilizing the 4T1 breast cancer mouse model the communication between tumor cells and macrophages was studied. Transcriptome data of cell lines and primary tumors of the non-metastatic 67NR and the metastasizing 66cl4 showed a higher amount of M2 macrophage markers in 66cl4 primary tumors. 66cl4 cells also produce and secrete the TGF-β superfamily member BMP4, as well as its antagonist GREM1. GREM1 was produced even more in 168FARN cell lines, as well as found to be cell surface-associated. High amount of GREM1 is correlated to poor prognosis in breast cancer patients. By adding conditioned medium from the tumor cells to RAW 264.7 macrophages, it was seen that conditioned medium from 168FARN, 66cl4 and 4T1 potently inhibited both basal and rmBMP4-stimulated SMAD signaling. Conditioned medium from 66cl4 also upregulated the inflammatory signaling in RAW 264.7 macrophages by activating STAT1. In bone marrow-derived macrophages (BMDMs) it was seen that both conditioned medium from 67NR, 168FARN and 66cl4, as well as the presence of them in a transwell changed the morphology of the BMDMs. The presence of 67NR, 168FARN and 66cl4 cells also activated the SMAD pathway of the BMDMs. Further research is however needed to see if the regulation of the SMAD pathway in macrophages is related to the different functions of macrophages in tumors

Fully automated on demand cell culture media preparation for perfusion bioreactors

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