Jan J.A.M. van den Dungen

Biomaterial-Associated Infection: Locating the Finish Line in the Race for the Surface

This Review discusses approaches to developing infection-reducing biomaterials that strike a balance between host tissue integration and prevention of microbial attachment. NONE Biomaterial-associated infections occur on both permanent implants and temporary devices for restoration or support of human functions. Despite increasing use of biomaterials in an aging society, comparatively few biomaterials have been designed that effectively reduce the incidence of biomaterial-associated infections. This review provides design guidelines for infection-reducing strategies based on the concept that the fate of biomaterial implants or devices is a competition between host tissue cell integration and bacterial colonization at their surfaces.

ROC analysis of noninvasive tests for peripheral arterial disease

The purpose of this study is to evaluate the diagnostic accuracy of selected noninvasive tests for assessing peripheral arterial disease. The ankle/brachial index (ABI) and the femoral and popliteal pulsatility indices (PI), and combinations of these tests, were evaluated using receiver operating characteristic (ROC) analysis to determine their diagnostic accuracy depending on the localization of the disease. Verification bias, introduced by the preferential selection of patients for angiography based on the noninvasive test results, was examined. This study suggests that, in assessing whether a patient has significant peripheral arterial disease (lesions > or = 50%), determining an ABI is justified (ROC area 0.95 +/- 0.02). For disease localized to the aortoiliac segment, performing a single test, the femoral PI, is sufficient (ROC area 0.80 +/- 0.04). For disease including the femoropopliteal and infrapopliteal segments, a combination of tests is necessary. Utilized threshold values need to be adjusted for verification bias.

The relevance of aortic endograft prosthetic infection

BACKGROUND Vascular prosthetic graft infection is a severe complication after open aortic aneurysm repair. Reports of infected endografts are scarce. General treatment consensus with infected graft material is that it should be removed completely. The objective of this study was to describe the incidence of endograft infection after endovascular repair of abdominal (EVAR) and thoracic aortic aneurysm (TEVAR) and to report treatment options and their outcome. METHODS A retrospective cohort study was performed of patients endovascularly operated for abdominal and thoracic aortic aneurysm in two large hospitals (one tertiary referral center and one large community hospital) between March 1996 and June 2009. Diagnosis of infected endograft was made based on clinical findings, blood tests and cultures, imaging studies (computed tomography, fludeoxyglucose positron emission tomography), and intraoperative findings at reoperation. RESULTS Eleven patients with an infected endograft were identified in 1431 endovascular procedures. One other patient was referred from another hospital. Patients were aged 68 ± 9 years, and all but one were male. The median time from initial TEVAR/EVAR to the diagnosis of infection was 115 days (range, 7-3748 days), with 42% of patients presenting within 3 months after TEVAR/EVAR. Seven patients were diagnosed with endograft infection after elective TEVAR/EVAR and five after emergency TEVAR/EVAR. The incidence was significantly higher in patients that were treated in an emergency setting (0.56% vs 2.79%; P = .002), while there was no significant difference between TEVAR and EVAR procedures (1.37% vs 0.77%). All patients were initially treated with antibiotic therapy, which was complemented with surgical intervention in six patients. In four patients, the infected graft material was completely explanted. Isolated microorganisms included Staphylococcus species (n = 4), Streptococcus species (n = 4), Enterobacter cloacae (n = 1), Escherichia coli (n = 1), Pseudomonas aeruginosa (n = 1), and Listeria monocytogenes (n = 1). Median time of follow-up was 201 days (range, 6-2023 days). During the study period, three out of 12 patients died, of which two were treated conservatively (P = ns). At their last follow-up visit, seven of nine patients still used antimicrobial therapy. CONCLUSIONS The incidence of endograft infection is below 1%, with a mortality rate of 25%. Although consensus is that infected graft material should always be removed, this study shows no significant difference in mortality between the conservatively- and the surgically-managed group, possibly related to the small sample size. There may be a role for conservative treatment in selected cases of patients with an infected endograft.

Conservative treatment of vascular prosthetic graft infection is associated with high mortality

BACKGROUND The aim of this study was to identify patient-related and/or disease-related factors that influence outcomes in patients with vascular prosthetic graft infections. METHODS Through the hospital patient administration system, between January 1997 and December 2007, a total of 44 patients were diagnosed with central prosthetic graft infections. Univariate and multivariate analyses were performed to define factors predictive of mortality. RESULTS Thirty-three men and 11 women (mean age, 71 years) were included. There was considerable comorbidity. Coagulase-negative Staphylococcus and S aureus were isolated in almost 50% of the patients. The mean follow-up duration was 5 years, during which 20 patients (46%) died. The main causes of death were related to vascular disease. Conservative treatment with antibiotics was the only variable with significant predictive value on multivariate analysis (hazard ratio, 3.62; 95% confidence interval, 1.17-11.24; P = .02). CONCLUSIONS Conservative treatment of prosthetic graft infections was associated with high mortality; therefore, it should be limited to a specific group. Patients who are not capable of undergoing open repair may benefit from conservative management. Otherwise, aggressive open treatment seems indicated.

Endovascular repair of acute AAAs under local anesthesia with bifurcated endografts: a feasibility study.

Purpose: To evaluate endovascular repair of abdominal aortic aneurysms (AAA) under local anesthesia in the acute setting. Methods: Between 1998 and 2001, 47 patients with an acute AAA were evaluated for endovascular repair after informed consent, provided they were in a stable, albeit hypotensive condition. The patients underwent urgent computed tomography to assess suitability for endovascular repair; 16 were eligible for stent-graft repair: 9 were frank ruptures and 7 were symptomatic aneurysms. Complications and outcome of endovascular repair were evaluated; mortality was compared to a contemporaneous surgical cohort. Results: Seven (23%) of 31 patients having a standard surgical procedure died in the study period compared to 1 (6%) of 16 patients undergoing endovascular repair (following conversion to surgery because of calcified access vessels). Twelve (75%) of the endovascular repairs were performed under local anesthesia; no complications with this mode of anesthesia were encountered. The median duration of the endovascular procedures was 110 minutes (range 75–240); median blood loss was 250 mL (range 100–2800 mL). Only 4 patients required blood transfusion, and only 8 patients required admission to the intensive care unit. There were 3 postoperative complications (1 ischemic colitis, 1 renal failure, 1 groin hematoma). During follow-up, 3 endograft patients received stent-graft extensions in uneventful procedures. Two patients died at 9 and 16 months from cardiac causes. Conclusions: This study demonstrates the feasibility and possible advantages of endovascular repair under local anesthesia in selected acute AAA patients. Further studies are needed to prove the advantages over open repair.

Stent fractures in the Hemobahn/Viabahn stent graft after endovascular popliteal aneurysm repair.

OBJECTIVE During the last decade, endovascular repair of popliteal artery aneurysms (PAAs) has become a valid alternative to open repair. This study analyzes the incidence and origin of stent graft fractures after endovascular repair, its impact on patency, and strategies to prevent fractures. METHODS Data of 78 atherosclerotic PAAs in 64 patients were gathered in a prospectively-held database from 1998 to 2009. All x-rays were reviewed to detect stent fractures. Only circumferential fractures were included for analysis; localized strut fractures were excluded. Clinical endpoints were circumferential stent fracture, occlusion, and clinical status of the patient. RESULTS Mean follow-up time was 50 months (range, 1-127 months). Fifteen circumferential stent fractures occurred in 13 (16.7%) patients. The majority of stent fractures (93.3%) were associated with the use of multiple stent grafts. At univariate analysis, younger age was identified as the only significant predictor for stent fracture (P = .007). The cumulative stent fracture-free survival was estimated at 78% and 73% at 5- and 10-year follow-up, respectively. The cumulative primary patency rate, defined as time to occlusion, was not different for the fracture group compared with the nonfracture group (P = .284). CONCLUSIONS The incidence of stent fractures after endovascular PAA repair is probably underreported in the literature. Stent graft fractures mainly occur at overlap zones and are associated with younger age of the patient. Fracture of the stent did not significantly influence patency of the stent graft.

Mortality of ruptured abdominal aortic aneurysm treated with open or endovascular repair

OBJECTIVES The study defined the selection criteria used for treatment of ruptured abdominal aortic aneurysms (RAAAs) and reviewed results during a 5-year period. METHODS From 2002 on, our tertiary referral center adopted a protocol of selective use of endovascular repair for RAAAs. The study included all patients with a proven RAAA who were admitted to our hospital from 2002 to 2006. The primary outcome measure was surgical mortality. RESULTS A total of 187 patients were admitted with an acute AAA, and an RAAA was confirmed 135 (72%) by computed tomography scanning or at laparotomy, and 125 (93%) were treated, 89 by open means and 36 by endovascular means. The overall mortality rate was 24% and the mortality rate was 13.9% for endovascular repair. Endovascular repair was consistently used more often in patients with favorable anatomy and in patients who were hemodynamically more stable. There were considerable differences in approach between the four consultant vascular surgeons. The overall evaluation and inclusion for endovascular treatment increased during the study period. CONCLUSIONS A strict protocol for admission, evaluation, and treatment of RAAA, with selective use of endovascular repair, resulted in low mortality rates in our center.

Treatment of popliteal artery aneurysms with the Hemobahn stent-graft

Purpose: To report a prospective study to ascertain the results of popliteal aneurysm treatment with a self-expanding stent-graft. Methods: In a recent 3-year period, 21 patients (18 men; median age 67 years, range 52–82) with 23 popliteal aneurysms were treated with Hemobahn stent-grafts. Follow-up evaluation included duplex scanning, ankle-brachial index (ABI) measurements, and radiographic examination of the knee. Outcome measures were occlusion of the stent-graft and limb loss. Results: Technical success in placing the stent-graft and excluding the aneurysm was 100%. An additional vascular intervention was performed in the same session in 5 (24%) cases. In the other 16 patients, local anesthesia was used in 10 (63%). During a median follow-up of 15 months (range 2–37), 5 (22%) of 23 stent-grafts occluded, resulting in a cumulative patency of 74%. All occlusions occurred within 6 months after the intervention; 2 were successfully recanalized, and none of the 3 patients with persisting occlusion required an amputation. Conclusions: The results of this study suggest that endovascular stent-graft repair of popliteal artery aneurysms is feasible. Midterm patency rates are lower compared to traditional surgical repair.

Critical factors in the translation of improved antimicrobial strategies for medical implants and devices

Biomaterials-associated infection incidence represents an increasing clinical challenge as more people gain access to medical device technologies worldwide and microbial resistance to current approaches mounts. Few reported antimicrobial approaches to implanted biomaterials ever get commercialized for physician use and patient benefit. This is not for lack of ideas since many thousands of claims to new approaches to antimicrobial efficacy are reported. Lack of translation of reported ideas into medical products approved for use, results from conflicting goals and purposes between the various participants involved in conception, validation, development, commercialization, safety and regulatory oversight, insurance reimbursement, and legal aspects of medical device innovation. The scientific causes, problems and impressive costs of the limiting clinical options for combating biomaterials-associated infection are well recognized. Demands for improved antimicrobial technologies constantly appear. Yet, the actual human, ethical and social costs and consequences of their occurrence are less articulated. Here, we describe several clinical cases of biomaterials-associated infections to illustrate the often-missing human elements of these infections. We identify the current societal forces at play in translating antimicrobial research concepts into clinical implant use and their often-orthogonal constituencies, missions and policies. We assert that in the current complex environment between researchers, funding agencies, physicians, patients, providers, producers, payers, regulatory agencies and litigators, opportunities for translatable successes are minimized under the various risks assumed in the translation process. This argues for an alternative approach to more effectively introduce new biomaterials and device technologies that can address the clinical issues by providing patients and medical practitioners new options for desperate clinical conditions ineffectively addressed by biomedical innovation.

Periaortic endograft infection due to Listeria monocytogenes treated with graft preservation

A 67-year-old man presented to our hospital with general malaise, fever and diffuse abdominal and lower back pain 7 weeks after endovascular aneurysm repair. Blood samples showed a leukocyte count of 10.9 x 10(9)/l and a C-reactive protein of 239 mg/l. The computed tomography (CT)-scan showed fluid collections behind the proximal part of the endovascular graft and dorsal to the aorta. CT-guided translumbar needle aspiration of these collections yielded growth with Listeria monocytogenes. Prosthetic endograft infection is an extremely rare event, especially when it is caused by L. monocytogenes. Given the scarcity of this complication, no consensus has been reached for its treatment. In the described case, radiological drainage and prolonged antibiotic treatment resulted in favourable outcome at midterm follow-up with preservation of the endograft.