Peginterferon alfa-2b plus weight-based ribavirin for 24 weeks in patients with chronic hepatitis C virus genotype 1 with low viral load who achieve rapid viral response.

In chronic hepatitis C (CHC), treatment duration may be individualized according to time to first undetectable hepatitis C virus (HCV) RNA, with patients who attain undetectable HCV RNA early in treatment being candidates for shorter regimens. The aim of this study was to determine the relapse rate in patients with CHC genotype (G) 1 infection and low baseline viral load who achieved undetectable HCV RNA by week 4 [rapid virologic response (RVR)] when treated for 24 weeks. This was an open-label, multicentre, noninterventional study. Adult patients with G1 CHC infection and baseline viral load <600,000 IU/mL who attained RVR were treated with peginterferon alfa-2b (1.5 µg/kg/week) plus ribavirin (800-1200 mg/day) for 24 weeks, then followed for a further 24 weeks. The primary endpoint was relapse rate, defined as the proportion of patients with undetectable HCV RNA at treatment week 24 and detectable HCV RNA at week 24 follow-up. The secondary efficacy endpoint was sustained virologic response (SVR). Overall, 170 patients were included in the efficacy-evaluable population. The relapse rate was 9.7% (16/165, 95% confidence interval: 0.06-0.15), and SVR was attained by 149 of 170 patients (87.6%). Virologic outcomes were consistent regardless of age, gender, body weight and genotype. Seven patients reported treatment-emergent serious adverse events (AEs), and four patients discontinued treatment because of an AE. This study further demonstrates that peginterferon alfa-2b plus weight-based ribavirin for 24 weeks is an effective treatment strategy for treatment-naive patients with G1 CHC and low viral load who attain RVR.

Keyhole technique for autologous brachiobasilic transposition arteriovenous fistula.

BACKGROUND: Autologous brachiobasilic transposition arteriovenous fistulas (AVFs) are desirable but require long incisions and extensive surgical dissection. To minimize the extent of surgery, we developed a catheter-based technique that requires only keyhole incisions and local anesthesia. METHODS: The technique involves exposure and division of the basilic vein at the elbow. A guidewire is introduced into the vein, and a 6F "push catheter" is advanced over the guidewire and attached to the vein with sutures. Gently pushing the catheter proximally inverts, or intussuscepts, the vein. Side branches that are felt as resistances when pushing the catheter forward are localized, clipped, and divided under direct vision. Throughout the procedure, the endothelium always remains intraluminal. The basilic vein is externalized at the axilla without dividing it proximally and is tunneled subcutaneously, where it is anastomosed to the brachial artery. RESULTS: Thirty-two patients underwent the procedure--31 as outpatients. The mean duration of operation was less than 90 minutes. All patients tolerated the procedure well, and 31 required only intravenous sedation and local anesthesia. At a mean follow-up of 8 months, the primary patency rate of AVFs in patients with basilic vein diameters of 4 mm or more on preoperative duplex ultrasonography was 80%, vs 50% for those with vein diameters less than 4 mm. Overall, 78% of patent AVFs were being successfully accessed and 22% were still maturing at last follow-up. CONCLUSIONS: Autologous brachiobasilic transposition AVFs can be created by using catheter-mediated techniques that facilitate the mobilization and tunneling of the basilic vein through small incisions. Medium-term data suggest that the inversion method results in acceptable maturation and functionality of AVFs created with this technique.

Limb salvage using high-pressure intermittent compression arterial assist device in cases unsuitable for surgical revascularization.

HYPOTHESIS: Intermittent compression therapy for patients with inoperable chronic critical ischemia with rest pain or tissue loss may have beneficial clinical and hemodynamic effects. STUDY DESIGN: Case series of 14 consecutive ischemic legs that underwent application of a 3-month treatment protocol during a 2(1/2)-year study. SETTING: Veterans Administration Hospital. PATIENTS: Thirteen patients with 14 critically ischemic legs (rest pain, n = 14; tissue loss, n = 13) who were not candidates for surgical reconstruction were treated with rapid high-pressure intermittent compression. The patients had a mean age of 76.2 years, 8 were diabetic, and they represented 10% of referrals for chronic critical ischemia. They were not amenable to revascularization owing to lack of outflow arteries (n = 7), lack of autogenous vein (n = 5), or poor general medical condition (n = 3). INTERVENTION: All patients were instructed to use the arterial assist device for 4 hours a day at home for a 3-month period. MAIN OUTCOME MEASURES: Limb salvage and calibrated pulse volume amplitude. RESULTS: After 3 months, 9 legs had a significant increase in pulse-volume amplitude (P< .05). These legs were salvaged, whereas the 4 amputated legs demonstrated no hemodynamic improvement. We noted a direct correlation between patient compliance and clinical outcome. Patients in whom limb salvage was achieved used their compression device for longer periods of time (mean time, 2.38 hours a day) compared with those who underwent amputation (mean time, 1.14 hours a day) (P< .05). These mean hours of use were derived from an hour counter built into the compression units. CONCLUSIONS: Intermittent high-pressure compression may allow limb salvage in patients with limb-threatening ischemia who are not candidates for revascularization. Further studies are warranted to assess intermittent compression as an alternative to amputation in an increasingly older patient population.

Endoleak after endovascular repair of abdominal aortic aneurysm.

PURPOSE: We sought to assess the role of endovascular techniques in the management of perigraft flow (endoleak) after endovascular repair of an abdominal aortic aneurysm. METHOD: We performed endovascular repair of abdominal aortic aneurysm in 114 patients, using a variety of Gianturco Z-stent-based prostheses. Results were evaluated with contrast-enhanced computed tomography (CT) at 3 days, 3 months, 6 months, 12 months, and every year after the operation. An endoleak that occurred 3 days after operation led to repeat CT scanning at 2 weeks, followed by angiography and attempted endovascular treatment. RESULTS: Endoleak was seen on the first postoperative CT scan in 21 (18%) patients and was still present at 2 weeks in 14 (12%). On the basis of angiographic localization of the inflow, the endoleak was pure type I in 3 cases, pure type II in 9, and mixed-pattern in 2. Of the 5 type I endoleaks, 3 were proximal and 2 were distal. All five resolved after endovascular implantation of additional stent-grafts, stents, and embolization coils. Although inferior mesenteric artery embolization was successful in 6 of 7 cases and lumbar embolization was successful in 4 of 7, only 1 of 11 primary type II endoleaks was shown to be resolved on CT scanning. There were no type III or type IV endoleaks (through the stent-graft). Endoleak was associated with aneurysm dilation two cases. In both cases, the aneurysm diameter stabilized after coil embolization of the inferior mesenteric artery. There were two secondary (delayed) endoleaks; one type I and one type II. The secondary type I endoleak and the associated aneurysm rupture were treated by use of an additional stent-graft. The secondary type II endoleak was not treated. CONCLUSIONS: Type I endoleaks represent a persistent risk of aneurysm rupture and should be treated promptly by endovascular means. Type II leaks are less dangerous and more difficult to treat, but coil embolization of feeding arteries may be warranted when leakage is associated with aneurysm enlargement.

Analysis of initial CT findings after endovascular repair of abdominal aortic aneurysm.

PURPOSE: To determine the spectrum and frequency of specific computed tomographic (CT) findings in the acute period after endovascular repair of abdominal aortic aneurysm (AAA). MATERIALS AND METHODS: CT images obtained 1--3 days after endograft placement were evaluated in 88 patients. The images were analyzed for stent position, appearance of endograft components, perigraft leak, and postoperative findings including air and acute thrombus within the aneurysm and air surrounding the femoral-femoral bypass graft. Findings that could be misinterpreted as perigraft leak were evaluated. RESULTS: Fifteen (17%) of 88 patients had perigraft leak in the acute postoperative period. The bare segment of the proximal self-expanding stent covered one or both renal arteries in 54 (61%) patients. One patient had CT evidence of renovascular compromise. Postoperative air was within the aneurysmal sac in 51 (58%) patients and surrounded the femoral-femoral bypass graft in 67 (94%) of 71 patients in whom the grafts were evaluated with CT. Mottled attenuation within the aneurysmal sac was seen in 50 (57%) patients. Forty-six (52%) patients had calcifications within longstanding thrombus. In 31 (35%) patients, findings that could have been misinterpreted as perigraft leak were identified. CONCLUSION: Accurate analysis of CT findings after endovascular AAA repair requires careful review of all available CT images (preprocedural and pre- and postcontrast) and clear understanding of specific stent-graft components and placement.

Aortic stent-grafts in patients with renal transplants.

PURPOSE: To report the endovascular treatment of abdominal aortic aneurysms (AAA) in 2 patients with pelvic renal transplants. METHODS AND RESULTS: Two men with multiple comorbidities and pelvic transplant kidneys underwent endovascular AAA repair using an aortomonoiliac system with femorofemoral bypass grafting. The arterial end-to-side anastomosis in both patients was to the external iliac artery. Tapered aortomonoiliac grafts were fashioned from Gianturco Z-stents covered with Dacron graft material and implanted with the distal attachment site in the iliac system ipsilateral to the transplant kidney arterial anastomosis. The body of the stent-graft was reinforcement with a Wallstent in each case before the contralateral common iliac artery was occluded and the cross-femoral bypass constructed. Both patients recovered uneventfully from the procedure and are free of endoleak or other complications related to their aneurysm repair at 7 and 34 months. CONCLUSIONS: The presence of a pelvic renal transplant in a patient undergoing endovascular AAA repair increases the complexity of procedural planning and endograft implantation, but a good outcome can be achieved.

Endovascular repair of a presumed aortoenteric fistula: late failure due to recurrent infection.

PURPOSE: To describe a case of presumed aortoduodenal fistula that was treated by endovascular implantation of a stent-graft. METHODS AND RESULTS: A 76-year-old man was transferred from another hospital where he had been treated for upper gastrointestinal hemorrhage over a 2-month period. Ten years previously, he had undergone aortobifemoral bypass, the right limb of which recently thrombosed. At the time of transfer, computed tomographic scanning showed a large false aneurysm between the aorta and the duodenum. Endoscopy disclosed mucosal erosions in the fourth portion of the duodenum. Following implantation of 2 overlapping stent-grafts, the bleeding ceased and the false aneurysm disappeared. At no time did the patient have a fever. The patient initially did well, but 8 months after treatment, he presented with fever and chills. Recurrent infection had caused erosion of the aorta so that a large portion of the stent-graft was visible from the duodenum. The infected graft and stent-grafts were removed in a two-part operation, from which the patient recovered satisfactorily. CONCLUSIONS: Endovascular stent-grafts may have a role to play in the management of aortoduodenal fistula, if only as a temporary measure to control bleeding.

Endovascular aneurysm repair in high-risk patients.

PURPOSE: The purpose of this study was to evaluate the role of endovascular aneurysm repair in high-risk patients. METHODS: The elective endovascular repair of infrarenal aortic aneurysm was performed in 116 high-risk patients with either custom-made or commercial stent grafts. The routine follow-up examination included contrast-enhanced computed tomography (CT) before discharge, at 3, 6, and 12 months, and annually thereafter. Patients with endoleak on the initial CT underwent re-evaluation at 2 weeks. Those patients with positive CT results at 2 weeks underwent endovascular treatment. RESULTS: Endovascular repair was considered feasible in 67% of the patients. The mean age was 75 years, and the mean aneurysm diameter was 6.3 cm. The American Society of Anesthesiologists grade was II in 3.4%, III in 65.5%, IV in 30.1%, and V in 0.9%. There were no conversions to open repair. Custom-made aortomonoiliac stent grafts were implanted in 77.6% of the cases, custom-made aortoaotic stent grafts in 11.2%, and commercial bifurcated stent grafts in 11.2%. The 30-day rates of mortality, major morbidity, and minor morbidity were 3.4%, 20.7%, and 12%, respectively, in the first 58 patients and 0%, 3.4%, and 3.4%, respectively, in the last 58. The late complications included five cases of stent graft kinking, two cases of femorofemoral graft occlusion, and three cases of proximal stent migration, one of which led to aneurysm rupture. At 2 weeks after repair, endoleak was present in 10.3% of the cases. All the type I (direct perigraft) endoleaks underwent successful endovascular treatment, whereas only one type II (collateral) endoleak responded to treatment. The technical success rate at 2 weeks was 86.2%, and the clinical success rate was 96.6%. The continuing success rate was 87.9%. Seventeen patients died late, unrelated deaths. CONCLUSION: Endovascular aneurysm repair is safe and effective in patients at high risk, for whom it may be the preferred method of treatment.

Aortomonoiliac endovascular grafting combined with femorofemoral bypass: an acceptable compromise or a preferred solution?

The relative merits of aortomonoiliac and bifurcated stent-graft configurations depend on the patient's arterial anatomy and clinical status. Aortomonoiliac stent-grafts are simple to make, simple to insert, and versatile. They are most useful when the iliac artery anatomy is severely distorted and the patient is old, sick, and inactive. The main problems with this approach are all consequences of femorofemoral bypass. The bifurcated stent-graft is the preferred alternative in healthy patients, because it ensures flow to both common iliac arteries, thereby eliminating the need for femorofemoral bypass. However, bifurcated stent-grafts and their delivery systems are difficult to make and difficult to deploy, especially when the iliac anatomy is distorted or emergency circumstances preclude preoperative sizing. This article addresses the advantages and disadvantages of the aortomonoiliac graft.

Endovascular repair of abdominal aortic aneurysm using a pararenal fenestrated stent-graft.

PURPOSE: To report an unusual case of endovascular abdominal aortic aneurysm (AAA) exclusion in which a fenestrated stent-graft was used to seal a proximal Type I endoleak. METHODS AND RESULTS: An 84-year-old man with a 6.0-cm AAA underwent an aortomonoiliac aneurysm exclusion procedure that was complicated by a proximal endoleak. Because the patient had no right kidney, an additional stent-graft was designed to cover the right renal artery stump while preserving left renal perfusion through a fenestration in the graft material. This approach was successful in obliterating the endoleak around the proximal attachment site, but flow through the lumbar arteries remained. CONCLUSIONS: The use of a fenestrated stent-graft is feasible, but the type of fenestration in this case has limited applicability owing to the rarity of patients with suitable anatomy.

Distinct mechanisms for N-acetylcysteine inhibition of cytokine-induced E-selectin and VCAM-1 expression.

We have examined the effects of N-acetyl-L-cysteine (NAC), a well-characterized, thiol-containing antioxidant, on agonist-induced monocytic cell adhesion to endothelial cells (EC). NAC inhibited interleukin-1 (IL-1 beta)-induced, but not basal, adhesion with 50% inhibition at approximately 20 mM. Monocytic cell adhesion to EC in response to tumor necrosis factor-alpha (TNF-alpha), lipopolysaccharide (LPS), alpha-thrombin, or phorbol 12-myristate 13-acetate (PMA) was similarly inhibited by NAC. Unlike published studies with pyrrolidinedithiocarbamate, which specifically inhibited vascular cell adhesion molecule 1 (VCAM-1), NAC inhibited IL-1 beta-induced mRNA and cell surface expression of both E-selectin and VCAM-1. NAC had no effect on the half-life of E-selectin or VCAM-1 mRNA. Although NAC reduced nuclear factor-kappa B (NF-kappa B) activation in EC as measured by gel-shift assays using an oligonucleotide probe corresponding to the consensus NF-kappa B binding sites of the VCAM-1 gene (VCAM-NF-kappa B), the antioxidant had no appreciable effect when an oligomer corresponding to the consensus NF-kappa B binding site of the E-selectin gene (E-selectin-NF-kappa B) was used. Because NF-kappa B has been reported to be redox sensitive, we studied the effects of NAC on the EC redox environment. NAC caused an expected dramatic increase in the reduced glutathione (GSH) levels in EC. In vitro studies demonstrated that whereas the binding affinity of NF-kappa B to the VCAM-NF-kappa B oligomer peaked at a GSH-to-oxidized glutathione (GSSG) ratio of approximately 200 and decreased at higher ratios, the binding to the E-selectin-NF-kappa B oligomer appeared relatively unaffected even at ratios > 400, i.e., those achieved in EC treated with 40 mM NAC. These results suggest that NF-kappa B binding to its consensus sequences in the VCAM-1 and E-selectin gene exhibits marked differences in redox sensitivity, allowing for differential gene expression regulated by the same transcription factor. Our data also demonstrate that NAC increases the GSH-to-GSSG ratio within the EC suggesting one possible mechanism through which this antioxidant inhibits agonist-induced monocyte adhesion to EC.

Alpha-tocopherol inhibits agonist-induced monocytic cell adhesion to cultured human endothelial cells.

Antioxidants have been proposed to be anti-atherosclerotic agents; however, the mechanisms underlying their beneficial effects are poorly understood. We have examined the effect of alpha-tocopherol (alpha-tcp) on one cellular event in atherosclerotic plaque development, monocyte adhesion to stimulated endothelial cells (ECs). Human umbilical vein ECs were pretreated with alpha-tcp before stimulation with known agonists of monocyte adhesion: IL-1 (10 ng/ml), LPS (10 ng/ml), thrombin (30 U/ml), or PMA (10 nM). Agonist-induced monocytic cell adhesion, but not basal adhesion, was inhibited in a time- and concentration-dependent manner by alpha-tcp. The IC50 of alpha-tcp on an IL-1-induced response was 45 microM. The inhibition correlated with a decrease in steady state levels of E-selectin mRNA and cell surface expression of E-selectin which is consistent with the ability of a monoclonal antibody to E-selectin to inhibit monocytic cell adhesion in this system. Probucol (50 microM) and N-acetylcysteine (20 mM) also inhibited agonist-induced monocytic cell adhesion; whereas, several other antioxidants had no significant effect. Protein kinase C (PKC) does not appear to play a role in the alpha-tcp effect since no suppression of phosphorylation of PKC substrates was observed. Activation of the transcription factor NF-kappa B is reported to be necessary but not sufficient for E-selectin expression in EC. Electrophoretic mobility shift assays failed to show an alpha-tcp-induced decrease in activation of this transcription factor after cytokine stimulation. It has been hypothesized that alpha-tcp acts as an anti-atherosclerotic molecule by inhibiting generation of oxidized LDL--a putative triggering molecule in the atherosclerotic process. Our results point to a novel alternative mechanism of action of alpha-tcp.

Use of calcium alginate to pack abscess cavities: a controlled clinical trial.

Many conventional dressings are painful when removed, and may be detrimental to healing. In a pilot study ten consecutive abscesses, requiring incision and drainage, were packed with a calcium alginate dressing: this was well tolerated, its removal causing minimal pain. No adverse effects were attributable to its use. A controlled trial was therefore carried out to compare calcium alginate with the more traditional saline-soaked gauze for packing abscess cavities, following incision and drainage. Patients were randomized to receive either calcium alginate (16 patients) or gauze dressing (18 patients). At the first dressing change the patient marked on a linear analogue scale the pain experienced; the nurse noted similarly the ease of removal of the dressing. Calcium alginate was significantly less painful to remove after operation (P less than 0.01), and also easier to remove (P less than 0.01) than gauze dressings. If abscess cavities are packed after incision and drainage, calcium alginate appears to be an improvement on conventional dressings.

An audit of surgical emergencies in the very old.

The surgical emergency admissions of patients over the age of 80 years at the hospitals of the West Berkshire Health Authority during 1989 have been analysed. The results were then compared with those of 1976 and 1966 in an attempt to identify any changing trends. The total number of admissions increased by almost 37% from 248 in 1976 to 339 in 1989. There was a dramatic increase in those patients admitted with gastrointestinal problems. The average length of stay was less in 1989, being 9 days compared with 15 days in 1976; this was despite the fact that the average length of stay for all ages was comparable for the 2 years in question. The overall mortality rate has not appreciably altered being 21.8% in 1976 and 22.4% in 1989. Excluding terminal disease the mortality rates were 12.5% and 15.9% for 1976 and 1989 respectively. Despite the increased numbers of patients admitted the total beds occupied by the over 80s has actually fallen between 1976 and 1989, due to their shorter hospital stay. Figures for the year 2000 predict a continuing increase in the number of elderly patients in the community. It is unlikely that we will be able to reduce hospital stay much further and therefore the total number of beds occupied by the very old in the acute surgical ward will rise steadily.