Mirza M. Idu

Impact of a color-flow duplex surveillance program on infrainguinal vein graft patency: A five-year experience

PURPOSE AND METHODS The contribution of color-flow duplex surveillance to improving vein graft patency was evaluated in two patient groups after 201 infrainguinal bypass procedures were performed during a 5-year period. Incidence of revision procedures and the primary and assisted primary patency rates were compared for 160 bypass grafts monitored during the first 2 years by use of color-flow duplex scanning of the vein graft and adjacent arterial segments (color-flow surveillance group) versus 41 bypass grafts monitored by use of clinical assessment alone (clinical follow-up group). Only grafts that were patent after the first postoperative month are considered. RESULTS The two groups were comparable with regard to most of the pertinent clinical factors. Stenotic lesions were identified in 58 bypass grafts, and severity was determined by use of intraarterial digital subtraction angiography. Eighteen bypass grafts with stenoses did not undergo a revision for reasons that were determined by the doctor, the hospital, or the patient. The occlusion rates of revised and nonrevised stenotic grafts were compared for lesions of different severity. None of the grafts for stenoses with 30% to 49% diameter reduction (DR) failed during follow-up. Occlusion occurred in 57% of the nonrevised and 9% of revised grafts (p = 0.047) for stenoses with 50% to 69% DR. Stenoses with 70% or greater DR were associated with graft failure in 100% of nonrevised bypasses and in 10% of revised grafts (p = 0.004). The assisted primary patency rate was higher in grafts that underwent color-flow surveillance compared with grafts with that underwent clinical follow-up (3-year patency rates of 91% and 72%, respectively; p = 0.004). The independent correlation of color-flow surveillance with higher patency rates was demonstrated in a proportional hazard analysis. The relative risk (probability of occlusion) in color-flow surveillance grafts is less than one third of the relative risk in bypass grafts that underwent clinical follow-up. CONCLUSIONS We conclude that revision procedures were more optimally used during color-flow surveillance, whereas asymptomatic stenotic graft lesions are missed with clinical follow-up, which results in a higher percentage of graft failures. Overall graft patency rates can be improved with use of color-flow duplex surveillance and repair of significant stenotic lesions.

Differential expression of interleukin-17 family cytokines in intact and complicated human atherosclerotic plaques†

In addition to the classical TH1 and TH2 cytokines, members of the recently identified IL‐17 cytokine family play an important role in regulating cellular and humoral immune responses. At present nothing is known about the role of these cytokines in atherosclerosis. Expression of IL‐17A, ‐E and ‐F was investigated in atherosclerotic tissue by rtPCR and immunohistochemistry. IL‐17E and its receptor were further studied in cultured smooth muscle cells and endothelial cells, using rtPCR and western blot. rtPCR showed that IL‐17A, ‐E and ‐F were expressed in the majority of plaques under investigation. IL‐17A/F was expressed by mast cells in all stages of plaque development. IL‐17A/F+ neutrophils were always observed in complicated plaques, but hardly in intact lesions. IL‐17A/F+ Tcells (‘TH17’) were never observed. IL‐17E was expressed by smooth muscle cells and endothelial cells in both normal and atherosclerotic arteries, and in advanced plaques also extensively by mature B cells. Cultured smooth muscle cells and endothelial cells were found to express both IL‐17E and its functional receptor (IL‐17RB). The constitutive expression of IL‐17E by resident plaque cells, and the additional presence of IL‐17E+ B cells and IL‐17A/F+ neutrophils in advanced and complicated plaques indicates a complex contribution of IL‐17 family cytokines in human atherosclerosis, depending on the stage and activity of the disease. Copyright

Collapse of a stent-graft following treatment of a traumatic thoracic aortic rupture.

Purpose: To report a collapsed stent-graft used to treat a traumatic aortic rupture. Case Report: A Gore TAG stent-graft was placed in a 20-year-old man with multiple injuries. Postimplantation computed tomographic angiography (CTA) demonstrated no contrast extravasation and total exclusion of the traumatic rupture. Routine CTA 3 months after implantation revealed a collapsed stent-graft located in the outer curve of the distal aortic arch. A Talent stent-graft was placed successfully within the collapsed prosthesis. Postimplantation CTA demonstrated no contrast extravasation and good apposition of the endograft to the aortic wall. At 6 months, the repair remains secure; there is no sign of graft collapse or endoleak. Conclusions: Collapse of stent-grafts can occur after treatment for traumatic aortic ruptures; endovascular methods can be used to restore a satisfactory luminal contour.

Kidneys from Donors after Cardiac Death Provide Survival Benefit

The continuing shortage of kidneys for transplantation requires major efforts to expand the donor pool. Donation after cardiac death (DCD) increases the number of available kidneys, but it is unknown whether patients who receive a DCD kidney live longer than patients who remain on dialysis and wait for a conventional kidney from a brain-dead donor (DBD). This observational cohort study included all 2575 patients who were registered on the Dutch waiting list for a first kidney transplant between January 1, 1999, and December 31, 2004. From listing until the earliest of death, living-donor kidney transplantation, or December 31, 2005, 459 patients received a DCD transplant and 680 patients received a DBD transplant. Graft failure during the first 3 months after transplantation was twice as likely for DCD kidneys than DBD kidneys (12 versus 6.3%; P=0.001). Standard-criteria DCD transplantation associated with a 56% reduced risk for mortality (hazard ratio 0.44; 95% confidence interval 0.24 to 0.80) compared with continuing on dialysis and awaiting a standard-criteria DBD kidney. This reduction in mortality translates into 2.4-month additional expected lifetime during the first 4 years after transplantation for recipients of DCD kidneys compared with patients who await a DBD kidney. In summary, standard-criteria DCD kidney transplantation associates with increased survival of patients who have ESRD and are on the transplant waiting list.

No Difference in Degree of Interstitial Sirius Red–Stained Area in Serial Biopsies from Area under Concentration-over-Time Curves–Guided Cyclosporine versus Tacrolimus-Treated Renal Transplant Recipients at One Year

Interstitial fibrosis is the main characteristic of chronic allograft nephropathy and long-term graft failure. Cyclosporin (CsA) is thought to be more fibrogenic than tacrolimus. In a prospective, randomized, multicenter trial using a calcineurin-sparing regimen, renal interstitial volume was compared in CsA- and tacrolimus-treated renal transplant recipients by image analysis of Sirius red (SR)-stained cortical areas in protocol biopsies obtained at 6 mo (n = 94) and 12 mo (n = 97) after transplantation. Immunosuppression consisted of CsA or tacrolimus, CD25 mAb, mycophenolate mofetil, and prednisolone. CsA therapy increased the 6-mo risk for subclinical rejection. The prevalence of subclinical rejection was 38.8% in the CsA-treated and 15.2% in the tacrolimus-treated patient group (P = 0.012). Strikingly, no difference in the degree of interstitial SR-stained area was detectable between the two treatment groups. In particular, previous subclinical rejection episodes did not influence the degree of interstitial volume. Also, no difference in GFR occurred at 1 yr, when the mean GFR mounted 63 ml/min. No significant differences in the degree of interstitial SR-stained area could be observed at 6 and 12 mo between CsA- and tacrolimus-treated renal transplant recipients. Although CsA-treated patients developed significantly more subclinical rejections at 6 mo, this did not influence the degree of SR staining or the change in renal function at 1 yr.

Human virus-specific effector-type T cells accumulate in blood but not in lymph nodes

It is believed that the size of the CD8(+) T-cell pool is fixed and that with every new viral challenge, the size of the pre-existing memory-cell population shrinks to make way for the new virus-specific cells. CMV-seropositive individuals have high numbers of CMV-specific resting-effector type CD8(+) T cells in their peripheral blood (PB). This prompted us to investigate whether CMV infection limits immunologic space at sites where immune reactions are initiated, such as in the lymph nodes (LNs). LN and paired PB samples were analyzed for CMV-, EBV-, and influenza-specific CD8(+) T cells. In marked contrast to blood, LNs contained significantly lower numbers of CX3CR1-expressing effector-type CD8(+) T cells, whereas the CMV-specific cells that were found in the LNs resembled polyfunctional memory-type cells. In contrast, EBV- and influenza-specific CD8(+) T cells were highly similar between PB and LNs both in number and function. Therefore, it is unlikely that CMV-specific CD8(+) T cells in the LNs restrain the immunologic space of other virus-specific cells.

Vein graft surveillance: Is graft revision without angiography justified and what criteria should be used?

PURPOSE The objective of this study was to assess the accuracy of color-flow duplex surveillance parameters to detect infrainguinal vein graft stenoses and to investigate whether graft revision without angiography is justified. METHODS In a prospective study in which three centers participated, the data of graft surveillance in 300 patients were analyzed. For the evaluation of surveillance criteria all patients underwent a digital subtraction angiography if a graft stenosis was suspected. To create a control group, in patients with normal grafts a consented digital subtraction angiography was performed also. From these data the accuracy of seven duplex and three ankle blood pressure-derived variables was assessed. The relation between various surveillance criteria and continued graft patency was determined with life table analysis with the transient state method. RESULTS The mean follow-up period was 20 months (range, 1 to 40 months). At univariate and multivariate analysis the peak systolic velocity (PSV) ratio provided the best correlation with angiographic stenoses > or = 70% (PSV ratio cutoff 3.0: sensitivity 80%, specificity 84%). This finding did not differ between the participating centers. With life table methods it was demonstrated that the best combination of efficacy (limitation of the number of unnecessary revisions), safety (minimal number of correctable lesions missed), and reduction of angiograms was obtained by a two-parameter surveillance algorithm. This algorithm included a PSV ratio < 2.5 to delineate patients in whom a conservative approach without angiography or revision was appropriate, a PSV ratio > or = 4.0 to indicate patients in whom vein graft revision without angiography could be scheduled, and a group with PSV ratios between 2.5 and 4.0 in whom angiography was to be performed to determine clinical management on the basis of the stenosis severity. This algorithm had a positive predictive value of 93% and a negative predictive value of 89%. In addition, it resulted in a reduction of the number of angiograms of 49% compared with a policy of angiographies in all patients with a PSV ratio > or = 2.5. CONCLUSIONS The best criterion to identify a failing graft is the PSV ratio. With a two-parameter algorithm for vein graft surveillance, the incidence of unnecessary revisions and of missed high-grade lesions was acceptably low, whereas the number of angiograms was reduced by one half.

Left or right kidney in hand-assisted donor nephrectomy? A randomized controlled trial.

Background. There is an ongoing discussion in living renal transplantation whether the right or the left donor nephrectomy is to be preferred if both kidneys are equal, due to the lack of prospective studies. Methods. A prospective single-center randomized trial was conducted from April 2002 to September 2006, in which 60 eligible consecutive donors were randomized to either left-sided or right-sided hand-assisted laparoscopic donor nephrectomy (HALDN). Primary endpoint was operation time. Secondary endpoints were donor morbidity, warm ischemia time, delayed graft function, urological complications, quality of life, and graft survival. Results. Median operating time for left-sided HALDN (180 min) was significantly longer compared with right-sided HALDN (150 min; P=0.021). There were no conversions in both groups. There were no major intra- or postoperative complications. One-year graft survival rate was 96% in the left group versus 93% in the right group (P=0.625, log rank). Conclusions. Operating time of HALDN of the right kidney is significantly shorter than HALDN of the left kidney. No differences were detected in complication rates and graft survival between left and right-sided donor nephrectomy.

Maintenance immunosuppressive therapy with everolimus preserves humoral immune responses

While the guidelines for vaccination in renal transplant recipients recommend the use of pneumococcal polysaccharide (PPS) and tetanus toxoid (TT), their efficacy in immunocompromised renal transplant recipients is not known. Here we tested the effect of everolimus on immune responses after vaccination by measuring the capacity of 36 stable renal transplant recipients to mount cellular and humoral responses after vaccination. Twelve patients in each treatment arm received immunosuppressive therapy consisting of prednisolone (P) plus cyclosporine (CsA), mycophenolate sodium (MPA), or everolimus. Patients were vaccinated with the T-cell-dependent antigens immunocyanin and TT, and the T-cell-independent PPS. Treatment with CsA partially inhibited and MPA completely abolished the capacity to mount a primary humoral response, whereas everolimus left this largely intact. Recall responses were inhibited by MPA only. All drug combinations inhibited cellular responses against TT. In patients treated with MPA, B-cell numbers were severely reduced. Thus, combined with P, treatment with MPA completely disturbed primary and secondary humoral responses. Everolimus or CsA allowed the boosting of T-cell-dependent and -independent secondary humoral responses. Treatment with everolimus allowed a primary response.

B cells in cluster or in a scattered pattern do not correlate with clinical outcome of renal allograft rejection.

Background. The role of CD20+ B cells in renal allograft rejection has been reappreciated. Importantly, recent studies suggest a relation between CD20+ B cell aggregates and poorer clinical outcome. In the present study, we attempted to confirm these early reports in a tightly controlled patient population and to differentiate between scattered infiltrates and clusters of B cells. Methods. Fifty-four biopsies from renal transplant recipients with acute rejection were immunostained for CD20, CD3, and C4d. All patients received similar immunosuppressive therapy. Response to therapy was defined as a decrease in serum creatinine level within 2 weeks to 125% or less of the value before the clinically diagnosed episode of allograft rejection. Late clinical outcome was defined in creatinine clearance between 8 and 12 months after the episode of acute rejection or in graft failure. Results and Conclusion. A significant correlation was observed between interstitial infiltrates of CD20+ cells and CD3+ cells (r=0.720, P<0.001) suggesting that if B-cell infiltrates are present during rejection, they occur with T-cell infiltrates in a concurrent fashion. In contrast to previous reports, no relation was found between the number of CD20+ cells, in aggregates or in a scattered interstitial pattern, and response to conventional therapy. Remarkably, CD3+T cell aggregates did predict a favorable renal outcome.