Thrombin-anti-thrombin levels and patency of arterio-venous fistula in patients undergoing haemodialysis compared to healthy volunteers : a prospective analysis

Peer reviewedPublisher PD

A Prospective Study of Internal Carotid Artery Plication During Carotid Endarterectomy: Early Clinical and Duplex Outcome

AbstractObjective: internal carotid artery (ICA) plication prevents kinking and secures the distal intimal step following carotid endarterectomy (CEA). The aims of this prospective study were to quantify the proportion of patients in whom plication might be beneficial and determine whether plication is associated with an increased incidence of early restenosis and a reduction in postoperative thromboembolic complications. Methods: analysis of a prospectively gathered computerised database. Results: between 1 November 1992 and 31 December 1997, 228 consecutive CEAs were performed in 213 patients, of which 84 (37%) in 79 patients were plicated. Sixty endarterectomy sites have been examined by duplex ultrasonography at a median of 5 (range 1–44) months postoperatively. No abnormality was detected in 52 (87%), six (10%) had restenosis of <50% and two (3%) restenosis of 50–75%. All were asymptomatic. Three patients (3.6%), one of whom died, had an intraoperative neurological event and one patient (1.2%) had a postoperative cerebral haemorrhage. No patient suffered ICA thromboembolism. During the same time period 144 non-plicated CEAs were performed in 134 patients. Of these, one (0.7%) had an intraoperative and five (3.5%) had a postoperative neurological event. Five of these six complications were due to ICA thromboembolism. There was no mortality in the non-plicated group. Conclusion: ICA plication can be used to prevent kinking, secure the distal intimal step, has not, to date, been associated with increased early restenosis rate and has avoided postoperative ICA thromboembolism

Bypass or Angioplasty for Severe Limb Ischaemia? A Delphi Consensus Study

AbstractObjectives: to examine the level of agreement among vascular surgeons and interventional radiologists regarding their preference for the surgical or endovascular management of severe limb ischaemia.Design: Delphi consensus study using 596 different hypothetical patient scenarios.Participants: Delphi consensus group for the Bypass versus Angioplasty in Severe Ischaemia of the Leg (BASIL) trial.Methods: twenty consultant vascular surgeons and 17 interventional radiologists completed both rounds of the study. The scenarios detailed the anatomical extent of disease, whether the patients had rest pain only or had tissue loss, and whether or not a suitable vein for bypass was available. Panellists were asked to score their treatment preference for either surgery or angioplasty on an eight-point scale. Outliers (top 10% and bottom 10% responses) were removed. If the remaining 80% of responses fell within a 3-point range, this was defined as “agreement”. If they did not, this was considered “disagreement”.Results: there was substantial disagreement in 484 (81%) of scenarios in round 1 and 401 (67%) in round 2. This disagreement was greater among surgeon than radiologists in both round 1 (83 vs 65%) and round 2 (69 vs 42%). Surgeons also demonstrated less convergence between rounds.Conclusions: there is substantial disagreement between and among surgeons and radiologists with regard to the appropriateness of surgery or angioplasty for severe limb ischaemia. This lack of consensus stems from the absence of an evidence base and means that the same patient may receive entirely different treatment depending on which hospital and consultant they attend. Not only may this unexplained variation be clinically unsatisfactory, it has major implications for the planning and use of health service resources

Frailty Assessment in Vascular OUtpatients Review (FAVOUR) PROTOCOL – single-centre prospective cohort study comparing feasibility and prognostic value of commonly used frailty assessment tools

Introduction: Frailty has consistently demonstrated associations with poorer healthcare outcomes. Vascular guidelines have recognised the importance of frailty assessment. However, an abundance of frailty tools and a lack of prospective studies confirming suitability of routine frailty assessment in clinical practice has delayed the uptake of these guidelines. The Frailty Assessment in Vascular OUtpatients Review study speaks to this evidence gap. The primary aim is to assess feasibility of implementing routine frailty assessment in a reproducible outpatient setting. Secondary objectives include comparing prognostic values and interuser agreement across five frailty assessment tools. Methods and analysis: This single-centre prospective cohort study of feasibility is conducted in a rapid-referral vascular surgery clinic, serving a population of 2 million. Adults with capacity (&gt;18 years), attending a clinic for any reason, are eligible for inclusion. Five assessments are completed by patient (Rockwood Clinical Frailty Scale (CFS) and Frail NonDisabled Questionnaire), clinician (CFS, Healthcare Improvement Scotland FRAIL tool and ‘Initial Clinical Evaluation’) and researcher (11-item modified Frailty Index). Consistent with feasibility objectives, outcome measures include recruitment rates, frailty assessment completion rates, time-to-complete assessments and interuser variability. Electronic follow-up at 30 days and 1 year will assess home-time and mortality as prognostic indicators. Patients treated surgically/endovascularly will undergo additional 30-day and 1-year postoperative follow-up, outcome measures include: surgical procedure, mortality, complications (according to Clavien-Dindo Classification), length of stay, readmission rates, non-home discharge, home-time, higher social care requirements on discharge and amputation-free survival. Prognostic value will be compared by area under receiver operating characteristic curves. Continuous outcome variables will be analysed using Spearman’s rank correlation coefficient. Interuser agreement will be compared by percentage agreement in Cohen’s kappa coefficient.  Ethics and dissemination: The study is sponsored by National Health Service Greater Glasgow and Clyde (R&amp;IUGN23CE014). London-Riverside REC (23/PR/0062) granted ethical approval. Results will be disseminated through publication in peer-reviewed vascular surgery and geriatric medicine themed journals and presentation at similar scientific conferences. Trials registration number: NCT06040658. Stage of study: pre-results

Intratumoural and peripheral blood lymphocyte subsets in patients with metastatic renal cell carcinoma undergoing interleukin-2 based immunotherapy: association to objective response and survival

The aim of the present study was to analyse lymphocyte subsets in consecutive peripheral blood samples and consecutive tumour tissue core needle biopsies performed before and during interleukin-2 based immunotherapy, and to correlate the findings with objective response and survival. Twenty-six patients with metastatic renal cell carcinoma were treated with low dose s.c. interleukin-2, interferon-α and histamine. A total of 250 blood samples and 62 core needle biopsies from 23 and 19 of these patients, respectively, were analysed. After 2 weeks of treatment, a significant positive correlation between absolute number of peripheral blood lymphocytes (P=0.028), CD3 (P=0.017), CD57 (P=0.041) and objective response was demonstrated. There was no correlation between any peripheral blood leukocyte subsets and survival. Cytotoxicity of peripheral blood mononuclear cells was not correlated to objective response or survival. Within the tumour tissue at baseline, a significant positive correlation between CD4 (P=0.027), CD8 (P=0.028), CD57 (P=0.007) and objective response was demonstrated. After one month of immunotherapy, a significant positive correlation between intratumoral CD3 (P=0.026), CD8 (P=0.015), CD57 (P=0.009) and objective response was demonstrated. A significant positive correlation between intratumoral baseline CD4 (P=0.047), baseline CD57 (P=0.035), CD3 at one month (P=0.049) and survival was demonstrated. These data provide novel in vivo evidence of the possible contribution of lymphocyte subsets in the tumour reduction in responding patients during interleukin-2 based immunotherapy. Confirmation of the results requires further studies including a larger number of patients

Dysregulated Expression of Both the Costimulatory CD28 and Inhibitory CTLA-4 Molecules in PB T Cells of Advanced Cervical Cancer Patients Suggests Systemic Immunosuppression Related to Disease Progression

Cervical cancer (CC) occurs more frequently in women who are immunosuppressed, suggesting that both local and systemic immune abnormalities may be involved in the evolution of the disease. Costimulatory CD28 and inhibitory CTLA-4 molecules expressed in T cells play a key role in the balanced immune responses. There has been demonstrated a relation between CD28, CTLA-4, and IFN genes in susceptibility to CC, suggesting their importance in CC development. Therefore, we assessed the pattern of CD28 and CTLA-4 expression in T cells from PB of CC patients with advanced CC (stages III and IV according to FIGO) compared to controls. We also examined the ability of PBMCs to secrete IFN-gamma. We found lower frequencies of freshly isolated and ex vivo stimulated CD4 + CD28+ and CD8 + CD28+ T cells in CC patients than in controls. Loss of CD28 expression was more pronounced in the CD8+ T subset. Markedly increased proportions of CTLA-4+ T cells in CC patients before and after culture compared to controls were also observed. In addition, patients’ T cells exhibited abnormal kinetics of surface CTLA-4 expression, with the peak at 24 h of stimulation, which was in contrast to corresponding normal T cells, revealing maximum CTLA-4 expression at 72 h of stimulation. Of note, markedly higher IFN-gamma concentrations were shown in supernatants of stimulated PBMCs from CC patients. Conclusions: Our report shows the dysregulated CD28 and CTLA-4 expression in PB T cells of CC patients, which may lead to impaired function of these lymphocytes and systemic immunosuppression related to disease progression