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Background: Anterior open treatment of the inguinal hernia with a tension free mesh has reduced the incidence of recurrence and direct postoperative pain. The Lichtenstein procedure rules nowadays as reference technique for hernia treatment. Not recurrences but chronic pain is the main postoperative complication in inguinal hernia repair after Lichtenstein's technique. Preliminary experiences with a soft mesh placed in the preperitoneal space showed good results and less chronic pain.Methods: The TULIP is a double-blind randomised controlled trial in which 300 patients will be randomly allocated to anterior inguinal hernia repair according to Lichtenstein or the transinguinal preperitoneal technique with soft mesh. All unilateral primary inguinal hernia patients eligible for operation who meet inclusion criteria will be invited to participate in this trial. The primary endpoint will be direct postoperative- and chronic pain. Secondary endpoints are operation time, postoperative complications, hospital stay, costs, return to daily activities (e.g. work) and recurrence. Both groups will be evaluated.Success rate of hernia repair and complications will be measured as safeguard for quality.To demonstrate that inguinal hernia repair according to the transinguinal preperitoneal (TIPP) technique reduces postoperative pain to <10%, with alpha = 0,05 and power 80%, a total sample size of 300 patients was calculated.Discussion: The TULIP trial is aimed to show a reduction in postoperative chronic pain after anterior hernia repair according to the transinguinal preperitoneal (TIPP) technique, compared to Lichtenstein.In our hypothesis the TIPP technique reduces chronic pain compared to Lichtenstein.Trial Registration: ISRCTN 93798494. [ABSTRACT FROM AUTHOR]

Objective: The Nellix endovascular aneurysm sealing (EVAS) system was developed as an alternative to conventional endovascular aneurysm repair (EVAR) to minimize endoleaks. A significantly higher failure rate of EVAS may be related to an interaction between the filled endobags and the AAA wall. In general, biological information on aortic remodeling after traditional EVAR is scarce. In this light, we provide here the first histologic evaluation of aneurysm wall morphology after EVAR and EVAS., Methods: Fourteen histological human wall samples of EVAS and EVAR explantation were systematically analysed. Primary open aorta repair samples were included as reference., Results: Compared with primary open aortic repair samples, endovascular repair aortic samples were characterized by more pronounced fibrosis, a greater number of ganglionic structures, decreased cellular inflammation, less calcification, and a lower atherosclerotic load. EVAS was specifically associated with the presence of unstructured elastin deposits., Conclusions: The biological response of the aortic wall after endovascular repair resembles the maturation process of a scar rather than a bona fide healing response. Moreover, the inflammatory response in the aortic wall after placement of endovascular protheses is less prominent than after primary open repair. A specific post-EVAS aortic wall characteristic was unstructured elastin fragments., (© 2023 by the Society for Vascular Surgery. Published by Elsevier Inc.)

Objective: Patients with chronic limb-threatening ischemia (CLTI), the end stage of peripheral artery disease, often present with comorbid depression and anxiety disorders. The prevalence of these comorbidities in the inpatient context over time, and their association with outcomes after revascularization and resource usage is unknown., Methods: Using the 2011 to 2017 National Inpatient Sample, two cohorts were created-CLTI hospitalizations with endovascular revascularization and CLTI hospitalizations with surgical revascularization. Within each cohort, the annual prevalence of depression and anxiety disorder diagnoses was determined, and temporal trends were evaluated using the Cochran-Mantel-Haenszel test. Hierarchical multivariable logistic and linear regression analyses were used to examine the association of depression and anxiety disorder diagnoses with inpatient major amputation, mortality, length of stay (LOS), and cost, adjusting for illness severity, comorbidities, and potential bias in the documentation of depression and anxiety disorder diagnoses stratified by patient sociodemographic data., Results: Across the study period were a total of 245,507 CLTI-related hospitalizations with endovascular revascularization and 138,922 with surgical revascularization. Hospitalizations with a depression or anxiety disorder diagnosis increased from 10.8% in 2011 to 15.3% in 2017 in the endovascular revascularization cohort and from 11.7% in 2011 to 14.4% in 2017 in the surgical revascularization cohort (P trend  < .001). In the endovascular revascularization cohort, depression was associated with higher odds of major amputation (odds ratio, 1.15; 95% confidence interval, 1.03-1.30). In addition, depression (9 vs 8 days [P < .001]; $105,754 vs $102,481 [P = .018]) and anxiety disorder (9 vs 8 days [P < .001]; $109,496 vs $102,324 [P < .001]) diagnoses were associated with a longer median LOS and higher median costs. In the surgical revascularization cohort, depression was associated with a higher odds of major amputation (odds ratio, 1.33; 95% confidence interval, 1.13-1.58) and a longer LOS (median, 9 vs 9 days; P = .004)., Conclusions: Depression and anxiety disorder diagnoses have become increasingly prevalent among CLTI hospitalizations including revascularizations. When present, these psychiatric comorbidities are associated with an increased risk of amputation and greater resource usage., (Copyright © 2022 Society for Vascular Surgery. Published by Elsevier Inc. All rights reserved.)

Background: Peripheral artery disease (PAD) is highly prevalent and associated with poor outcomes. Depression is a risk factor for adverse outcomes in patients with coronary artery disease. Despite evidence showing that depression is common in patients with PAD, less is known about its association with adverse prognostic outcomes. To address this, we conducted a systematic review and meta-analysis to summarize the association between depression and outcomes in patients with PAD., Methods: We performed a systematic search of eight databases to January 2022 including studies that reported a risk estimate for the association of depression or depressive symptoms with all-cause mortality or major adverse limb events (MALE) in patients with PAD and pooled results in a meta-analysis. Risk of bias was assessed using ROBINS-I., Results: Of the 7048 articles screened, 5 observational studies with 119,123 patients were included. A total of 16.2 % had depression or depressive symptoms. Depression was associated with a statistically significant increased risk of all-cause mortality (HR 1.24, confidence interval 1.07-1.25, p = .005). The association between depression and MALE was not significant but trended toward a positive association., Limitations: Due to lack of data, results were limited by a single study with a large sample size, overrepresentation of men, and lack of information of depression severity or treatment status., Conclusion: Depression or depressive symptoms are associated with a 24 % increased risk of all-cause mortality in patients with PAD. Future work should explore the mechanisms and directionality of this association and identify depression as an important comorbidity to address for patients with PAD., Registration: PROSPERO CRD 42021223694., Competing Interests: Conflict of Interest Dr. Mena-Hurtado is a consultant for Abbott, Medtronic, Cook Medical, Cardinal Health, and Optum Labs. Dr. Smolderen reports grant funding from Cardiva, Johnson & Johnson, and Abbott, and she is a consultant for Optum Labs, Abbott Laboratories, and Cook. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Objective: Two consensus histopathological classifications for thoracic aortic aneurysms (TAAs) and inflammatory aortic diseases have been issued to facilitate clinical decision-making and inter-study comparison. However, these consensus classifications do not specifically encompass abdominal aortic aneurysms (AAAs). Given its high prevalence and the existing profound pathophysiologic knowledge gaps, extension of the consensus classification scheme to AAAs would be highly instrumental. The aim of this study was to test the applicability of, and if necessary to adapt, the issued consensus classification schemes for AAAs., Methods: Seventy-two AAA anterolateral wall samples were collected during elective and emergency open aneurysm repair performed between 2002 and 2013. Histologic analysis (hematoxylin and eosin and Movat Pentachrome) and (semi-quantitative and qualitative) grading were performed in order to map the histological aspects of AAA. Immunohistochemistry was performed for visualization of aspects of the adaptive and innate immune system, and for a more detailed analysis of atherosclerotic lesions in AAA., Results: Because the existing consensus classification schemes do not adequately capture the aspects of AAA disease, an AAA-specific 11-point histopathological consensus classification was devised. Systematic application of this classification indicated several universal features for AAA (eg, [almost] complete elastolysis), but considerable variation for other aspects (eg, inflammation and atherosclerotic lesions)., Conclusions: This first multiparameter histopathological AAA consensus classification illustrates the sharp histological contrasts between thoracic and abdominal aneurysms. The value of the proposed scoring system for AAA disease is illustrated by its discriminatory capacity to identify samples from patients with a nonclassical (genetic) variant of AAA disease., (© 2021 by the Society for Vascular Surgery. Published by Elsevier Inc.)

Objective: The new 2019 guideline of the European Society for Vascular Surgery (ESVS) recommends consideration for elective iliac artery aneurysm (eIAA) repair when the iliac diameter exceeds 3.5 cm, as opposed to 3.0 cm previously. The current study assessed diameters at time of eIAA repair and ruptured IAA (rIAA) repair and compared clinical outcomes after open surgical repair (OSR) and endovascular aneurysm repair (EVAR)., Methods: This retrospective observational study used the nationwide Dutch Surgical Aneurysm Audit (DSAA) registry that includes all patients who undergo aorto-iliac aneurysm repair in the Netherlands. All patients who underwent primary IAA repair between 1 January 2014 and 1 January 2018 were included. Diameters at time of eIAA and rIAA repair were compared in a descriptive fashion. The anatomical location of the IAA was not registered in the registry. Patient characteristics and outcomes of OSR and EVAR were compared with appropriate statistical tests., Results: The DSAA registry comprised 974 patients who underwent IAA repair. A total of 851 patients were included after exclusion of patients undergoing revision surgery and patients with missing essential variables. eIAA repair was carried out in 713 patients, rIAA repair in 102, and symptomatic IAA repair in 36. OSR was performed in 205, EVAR in 618, and hybrid repairs and conversions in 28. The median maximum IAA diameter at the time of eIAA and rIAA repair was 43 (IQR 38-50) mm and 68 (IQR 58-85) mm, respectively. Mortality was 1.3% (95% CI 0.7-2.4) after eIAA repair and 25.5% (95% CI 18.0-34.7) after rIAA repair. Mortality was not significantly different between the OSR and EVAR subgroups. Elective OSR was associated with significantly more complications than EVAR (intra-operative: 9.8% vs. 3.6%, post-operative: 34.0% vs. 13.8%, respectively)., Conclusion: In the Netherlands, most eIAA repairs are performed at diameters larger than recommended by the ESVS guideline. These findings appear to support the recent increase in the threshold diameter for eIAA repair., (Copyright © 2020 European Society for Vascular Surgery. Published by Elsevier B.V. All rights reserved.)

Introduction: Despite guideline recommendations advocating conservative management before invasive treatment in intermittent claudication, early revascularisation remains widespread in patients with favourable anatomy. The aim of the Effect of Disease Level on Outcomes of Supervised Exercise in Intermittent Claudication Registry is to determine the effect of the location of stenosis on the outcomes of supervised exercise in patients with intermittent claudication due to peripheral arterial disease., Methods and Analysis: This multicentre prospective cohort study aims to enrol 320 patients in 10 vascular centres across the Netherlands. All patients diagnosed with intermittent claudication (peripheral arterial disease: Fontaine II/Rutherford 1-3), who are considered candidates for supervised exercise therapy by their own physicians are appropriate to participate. Participants will receive standard care, meaning supervised exercise therapy first, with endovascular or open revascularisation in case of insufficient effect (at the discretion of patient and vascular surgeon). For the primary objectives, patients are grouped according to anatomical characteristics of disease (aortoiliac, femoropopliteal or multilevel disease) as apparent on the preferred imaging modality in the participating centre (either duplex, CT angiography or magnetic resonance angiography). Changes in walking performance (treadmill tests, 6 min walk test) and quality of life (QoL; Vascular QoL Questionnaire-6, WHO QoL Questionnaire-Bref) will be compared between groups, after multivariate adjustment for possible confounders. Freedom from revascularisation and major adverse cardiovascular disease events, and attainment of the treatment goal between anatomical groups will be compared using Kaplan-Meier survival curves., Ethics and Dissemination: This study has been exempted from formal medical ethical approval by the Medical Research Ethics Committees United 'MEC-U' (W17.071). Results are intended for publication in peer-reviewed journals and for presentation to stakeholders nationally and internationally., Trial Registration Number: NTR7332; Pre-results., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: The Nellix endovascular aneurysm sealing (EVAS) system is an alternative endovascular treatment option for infrarenal aortic aneurysms (AAAs), with a unique appearance on computed tomography angiography (CTA). Normal evolution of post-EVAS CTA appearance follow-up is still largely unknown and important to timely detect eventual complications. The objective is to assess the normal appearance of CTA images 30 days and 1 year after EVAS in 50 consecutive patients., Methods: Fifty patients treated with Nellix EVAS for an infrarenal AAA were included from 3 hospitals. Using dedicated software, a total of 150 CTA scans were analyzed by predetermined variables per anatomical segment., Results: Thirty days post-EVAS, there was a slight, but not statistically significant, increase in AAA diameter that returned to the preoperative value after 1 year. A shift in total aortic volume distribution was observed without changing aortic diameter, including a trend toward a decreased thrombus volume (85.6 ± 49.1 mL and 78.8 ± 35.5 mL at 30 days and 1 year, respectively, P < 0.242) and a slight, but statistically significant, increase in polymer volume (68.2 ± 34.1 mL and 71.9 ± 35.2 mL at 30 days and 1 year, respectively, P < 0.001). The β-angle (P = 0.06) and iliac artery angulation (P < 0.001) decreased after implant. The latter returned to its original state after 1 year, whereas the neck straightening remained. Over time, there was a significant decrease in radiodensity in the middle of the polymer-filled endobags with an increase at its edges (P < 0.05). Thrombus radiodensity significantly increased over the first year (P < 0.05). Diameters of the infrarenal neck and common iliac arteries remained unchanged, no endoleaks were observed, and the position of the device was stable., Conclusions: Change of CT appearance after EVAS is unique, and as such, the judgment of these images requires experience. The appearance of the endobags in respect to volume and radiodensity differ from classic EVAR. Normal changes over time are observed in aortoiliac angulation, volumes, and radiodensities., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Background: Endovascular aortic sealing (EVAS) with a sac anchoring endoprosthesis excludes abdominal aortic aneurysms based on polymer filling of endobags. Primary objective was to assess the reliability of pre-procedural computed tomography (CT) scans based calculations of required endobag volume in relation to intraoperative volume of the endobags., Methods: Forty elective EVAS patients were included. Pre-procedural estimations of endobag volume were based on CT segmentations of aortic flow lumen volume, including both automated and manually-adjusted segmentations, performed by two experienced users. Additionally, changes in maximum AAA diameter, thrombus volume and total AAA volume were calculated from pre- and post-procedural CT scans., Results: Automatically determined volumes were comparable to manually-adjusted calculations (75.3 vs. 75.7 mL) and inter-observer agreement regarding pre-EVAS calculations of prefill volume appeared almost perfect with an intra-class correlation coefficient of 0.98 (95% CI: 0.96-0.99). The mean pressure of the endobags was 185 mmHg. Manually-adjusted pre-procedural volume calculations underestimated procedural volume of the endobags (-11.3±9.9 mL). Differences between pre-EVAS and procedural volume measurements were independent from endobag pressure (r=-0.06, P=0.72), prepocedural thrombus volume (r=-0.303, P=0.057) and changes in total AAA volume (r=0.02, P=0.91). A significant association was determined between differences in pre-EVAS and endobag volume versus changes in thrombus volume pre- and post-procedural (r=0.39, P=0.01)., Conclusions: In this validation study, pre-procedural volume measurements underestimate the actual fill volume of the endobags. It should be advised to perform a prefill of the endobags during the EVAS procedure.

Background: Although patients with peripheral artery disease (PAD) are known to have an increased risk of adverse prognosis, simple techniques to further risk-stratify PAD patients would be clinically useful. A plausible but unexplored factor to predict such risk would be greater disease burden, manifested as multiple lower extremity lesions. The aim of this study was to examine the association between having multiple versus isolated lower extremity PAD lesions and long-term prognosis., Methods and Results: A prospective cohort of 756 newly diagnosed PAD patients underwent duplex ultrasound testing to determine the number of lower extremity lesions. Cox regression models examined the independent association of lesion number (≥3 and 2 versus 1) and adverse prognosis (defined as a composite end point comprising first occurrence of either lower extremity amputation, admission for heart failure, nonfatal stroke, myocardial infarction, or unstable angina or mortality), adjusting for demographic and clinical risk factors. Analyses were replicated using an advanced Cox-based model for multiple events. A total of 173 patients (23%) had ≥3 lesions, 197 (26%) had 2 lesions, and 386 (51%) had 1 lesion. After a median follow-up of 3.2 years, patients with ≥3 lesions had an increased risk of experiencing a first adverse event (adjusted hazard ratio 1.60, 95% CI 1.08-2.38, P=0.020) and an increased risk of having multiple events (adjusted hazard ratio 1.53, 95% CI 1.08-2.18, P=0.018). Patients with 2 lesions had a prognosis similar to those with 1 lesion., Conclusions: Among PAD patients, a greater number of lesions is associated with an increased risk of an adverse prognosis over 3 years of follow-up. Assessing the number of lower extremity lesions might serve as a simple risk-stratification tool at initial PAD diagnosis., (© 2015 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.)

Objective/background: Limited information is available on expected health status gains following invasive treatment in peripheral arterial disease (PAD). One year health status outcomes following invasive treatment for PAD were compared, and whether pre-procedural health status was indicative of 1 year health status gains was evaluated., Methods: Pre-procedural and 1 year health status (Short Form-12, Physical Component Score [PCS]) was prospectively assessed in a cohort of 474 patients, enrolled from 2 Dutch vascular clinics (March 2006-August 2011), with new or exacerbation of PAD symptoms. One year treatment strategy (invasive vs. non-invasive) and clinical information was abstracted. Quartiles of baseline health status scores and mean 1 year health status change scores were compared by invasive treatment for PAD. The numbers needed to treat (NNT) to obtain clinically relevant changes in 1 year health status were calculated. A propensity weight adjusted linear regression analysis was constructed to predict 1 year PCS scores., Results: Invasive treatment was performed in 39% of patients. Patients with baseline health status scores in the lowest quartile undergoing invasive treatment had the greatest improvement (mean invasive 11.3 ± 10.3 vs. mean non-invasive 5.3 ± 8.5 [p = .001, NNT = 3]), whereas those in the highest quartile improved less (.8 ± 6.3 vs. -3.0 ± 8.2 [p = .025, NNT = 90]). Undergoing invasive treatment (p < .0001) and lower baseline health status scores (p < .0001) were independently associated with greater 1 year health status gains., Conclusion: Substantial improvements were found in patients presenting with lower pre-procedural health status scores, whereas patients with higher starting health status levels had less to gain by an invasive strategy., (Copyright © 2015 European Society for Vascular Surgery. Published by Elsevier Ltd. All rights reserved.)

Background: Few studies have examined gender differences in health status and cardiovascular outcomes in patients with peripheral artery disease (PAD). This study assessed (1) self-reported health status at PAD diagnosis and 12-months later, and explored (2) whether outcomes in women with PAD differ with regard to long-term major adverse events., Methods and Results: A total of 816 patients (285 women) with PAD were enrolled from 2 vascular clinics in the Netherlands. Baseline clinical data and subsequent adverse events were recorded and patients completed the Short Form-12 (SF-12, Physical Component Score [PCS] and Mental Component Score [MCS]) upon PAD diagnosis and 12-months later. Women had similar ages and clinical characteristics, but poorer socio-economic status and more depressive symptoms at initial diagnosis, as compared with men. Women also had poorer physical (PCS: 37±10 versus 40±10, P=0.004) and mental (, Mcs: 47±12 versus 49±11, P=0.005) health status at the time of presentation. At 12-months, women still reported a poorer overall PCS score (41±12 versus 46±11, P=0.006) and MCS score (42±14 versus 49±12, P=0.002). Female gender was an independent determinant of a poorer baseline and 12-month PCS and MCS scores. However, there were no significant differences by gender on either mortality (unadjusted hazard ratio [HR]=0.93, 95% CI 0.60;1.44, P=0.74) or major adverse events (unadjusted HR=0.90, 95% CI 0.63;1.29, P=0.57), after a median follow-up of 3.2 years., Conclusions: Women's physical and mental health status is compromised both at initial PAD diagnosis and at 12-month follow-up, despite experiencing a similar magnitude of change in their health scores throughout the first 12-months after diagnosis., (© 2014 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.)

Venous aneurysms have been reported in most major veins and are often asymptomatic but can cause serious complications. Three patients with symptomatic venous aneurysms of the internal jugular vein, portal vein, and popliteal vein are presented, and their treatment and outcomes are discussed. Furthermore, presentation and management of the most frequent venous aneurysms, based on available literature, are evaluated. The literature supports conservative treatment of asymptomatic and nonthrombotic jugular, subclavian, thoracic, and visceral venous aneurysms. Surgery should be considered only for symptomatic venous aneurysms or in case of progressive expansion on follow-up. Prophylactic surgery is recommended for all patients with lower extremity deep venous aneurysms, by means of tangential aneurysmectomy with lateral venorrhaphy, because of the increased risk of pulmonary embolization. Postoperative anticoagulation is recommended for a period of at least 3 months after operative treatment., (Copyright © 2014 Society for Vascular Surgery. Published by Elsevier Inc. All rights reserved.)

Objective: Since it is unknown what factors are weighed in a clinician's decision to refer patients with symptomatic lower extremity peripheral arterial disease (PAD) for invasive treatment, we examined the relationship between health status, lesion location, and site variations and invasive treatment referral ≤1 year following diagnosis in patients with PAD., Methods: This was a prospective observational cohort study on ambulatory patients that presented themselves at two vascular surgery outpatient clinics. A total of 970 patients with new symptoms of PAD or with an exacerbation of existing PAD symptoms that required clinical evaluation and treatment (Rutherford Grade I) were eligible, 884 consented and were included between March 2006 and November 2010. We report on 505 patients in the current study. Prior to patients' initial PAD evaluation, the Short Form-12, Physical Component Scale (PCS) was administered to measure health status. Anatomical lesion location (proximal vs distal) was derived from duplex ultrasounds. PCS scores, lesion location, and site were evaluated as determinants of receiving invasive (endovascular, surgery) vs noninvasive treatment ≤1 year following diagnosis in Poisson regression analyses, adjusting for demographics, ankle-brachial index, and risk factors., Results: Invasive treatment as a first-choice was offered to 167 (33%) patients. While an association between poorer health status and invasive therapy was found in unadjusted analyses (relative risk [RR], 0.98; 95% confidence interval [CI], 0.97-1.00; P = .011), proximal lesion location (RR, 3.66; 95% CI, 2.70-4.96; P < .0001) and site (RR, 1.69; 95% CI, 1.11-2.58; P = .014) were independent predictors of invasive treatment referral in the final model., Conclusions: One-third of patients were treated invasively following PAD diagnosis. Patients' health status was considered in providers' decision to refer patients for invasive treatment, but having a proximal lesion was the strongest predictor. This study also found some important first indications of site variations in offering invasive treatment among patients with PAD. Future work is needed to further document these variations in care., (Copyright © 2014 Society for Vascular Surgery. Published by Mosby, Inc. All rights reserved.)

The transinguinal preperitoneal (TIPP) technique using a soft mesh with a memory ring was developed recently for inguinal hernia repair. To compare TIPP with the Lichtenstein method, a randomised trial was conducted (ISRCTN93798494). The aim of this study was to perform an economic evaluation of the TIPP modality compared to the Lichtenstein modality from both a hospital and societal perspective alongside the clinical trial. The TULIP study was a double-blind randomised clinical trial comparing two techniques for inguinal hernia repair (TIPP and Lichtenstein). Correct generation of the allocation sequence, allocation concealment, blinding, and follow-up were used/applied according to the recommendations of the Cochrane Handbook. Next to the cost drivers, the short-form-36 health survey (SF-36) data from the TULIP trial was used to determine utility. The SF-36 data from the TULIP trial were revised using the SF-6D algorithm according to Brazier. Two scenarios-a hospital and a societal perspective-were presented. If the analyses showed no difference in effects (on the SF-6D) the cost effectiveness decision rule to cost minimisation was altered. No significant difference in SF-6D utility between both modalities was found (mean difference: 0.888, 95% CI -1.02 to 1.23); consequently, the economic decision rule became cost minimisation. For the hospital perspective no significant differences in costs were found (mean difference: euro -13, 95% CI euro -130 to euro 104). However, when including productivity gains in the analysis, significant differences (P = 0.037) in costs favouring the TIPP modality (mean saving: euro 1,472, 95% CI euro 463- euro 2,714) were found. The results show that TIPP is a cost-saving inguinal hernia repair technique compared to the Lichtenstein modality against equal effectiveness expressed as quality adjusted life week at 1 year given a societal perspective. In the trial, TIPP patients showed on average a quicker recovery of 6.5 days compared to Lichtenstein patients.

Purpose: We performed a retrospective study on hemodialysis fistulae in patients aged 75 years and older., Methods: Dialysis records of 2 hospitals were searched for patients of 75 years and older who had primary autologous radiocephalic arteriovenous fistulae (RCAVFs) and brachiocephalic arteriovenous fistulae (BCAVFs). Outcome measures were primary, primary-assisted, and secondary patency rates. Also, quality of life (QOL) was measured., Results: A total of 107 fistulae were placed in 90 patients; 65 (61%) RCAVFs and 42 (39%) BCAVFs were created. The primary patency rate (P = .026) and the primary-assisted patency rate (P = .016) of BCAVFs were significantly higher than that of RCAVFs. Secondary patency rates at 1 year (P = .01) and 2 years (P = .035) were higher in BCAVFs than in RCAVFs., Conclusions: The BCAVFs give significantly higher primary and primary-assisted patency rates and also significantly higher secondary patency rates at 1 and 2 years. Therefore, we suggest the placement of elbow fistulae in the elderly patients. The QOL was surprisingly high in this population despite a high mortality rate.

Background: The purpose of this study is to evaluate 2 patients who underwent endovascular repair directly after acute life-threatening vascular injury complicating lumbar disc surgery, and to update an overview of the literature from 2002 to gain insights into characteristics, diagnosis, treatment, and outcomes of this rare, life-threatening complication., Methods: PubMed was searched for English language studies on vascular injury (lacerations, arteriovenous fistulas, and pseudoaneurysms) complicating lumbar disc surgery by a posterior approach published from 2002. Two cases from the authors' institute were added to the review. Information on patient characteristics, diagnosis, treatment strategies, and outcomes were extracted by 2 independent reviewers., Case Reports: The first case describes a 54-year-old man who underwent lumbar disc surgery through a posterior approach (L5-S1) and became hypotensive intraoperatively. Angiography revealed an injury of the right internal iliac artery. Bleeding was successfully repaired by endovascular repair (acute balloon occlusion followed by coiling). The second case describes a 51-year-old women who suddenly became hypotensive during L4 through L5 discectomy caused by bleeding from a laceration in the right common iliac artery. Angiography confirmed the diagnosis, and the bleeding was successfully treated through endovascular repair with a covered stent., Results: A total of 56 cases from 34 articles were found in the literature since 2002, including lacerations, arteriovenous fistulas, and pseudoaneurysms. Two cases from the authors' institute were added to the review. Vascular injury was recognized intraoperatively in 36%, and within 24 hours postsurgery in 28%. The common iliac artery was most frequently affected (51%), followed by the iliac vein (23%). All lacerations were detected during surgery, whereas most arteriovenous fistulas and pseudoaneurysms were detected in the long term. Treatment consisted of open surgical repair (57%) or endovascular repair (43%). All patients survived surgery., Conclusions: Publication bias might play a role in the literature of this area because all cases survived surgery, whereas mortality rates for this condition are high. However, early recognition, diagnosis, and prompt surgical repair are essential to prevent fatal outcomes in vascular injuries complicating lumbar disc surgery. Endovascular repair is a minimally invasive, fast, and efficient treatment modality that is increasingly and preferably used because of its low morbidity and mortality., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Background: The Lichtenstein technique is the treatment of first choice according to guidelines for primary inguinal hernia treatment. Postoperative chronic pain has been reported as complication in 15-40 % after Lichtenstein's repair. The postoperative effects on health status after open preperitoneal hernia repair have hardly been examined. Development of an open technique that combines the safe anterior approach of the Lichtenstein with the 'promising' preperitoneal soft mesh position was done; the transinguinal preperitoneal (TIPP) mesh repair. A double-blind prospective randomized controlled trial (TULIP trial, ISRCTN93798494) was conducted to compare different outcome parameters after TIPP or Lichtenstein, one parameter is topic of evaluation in this paper; the health status after TIPP and Lichtenstein for inguinal hernia repair., Methods: The study protocol has been published. It was hypothesized that the health status of inguinal hernia patients would be better after the TIPP repair compared with the Lichtenstein technique. The size of this study was based on chronic pain as primary outcome measure. Three hundred and two patients were randomized. Patients and the outcome assessors were blinded. Follow-up was scheduled after 14 days, 3 months, and 1 year. The three dimensions of possible errors were warranted., Results: With regard to health status, significant differences were found in the dimensions 'physical pain' [difference: 6.1 (95 % CI 2.3-9.9, p = 0.002)] and 'physical functioning' [difference: 3.5 (95 % CI 0.5-6.7, p = 0.023)], favoring the TIPP patients after 1 year., Conclusion: In conclusion, the SF-36 'physical function' and 'physical pain' dimensions after TIPP show significant better patient outcomes at 1 year compared with the Lichtenstein patients in this trial. These differences are in line with reported significant differences in less patients with postoperative chronic pain after TIPP compared with Lichtenstein at 1 year.

Background: Anterior open treatment of the inguinal hernia with a tension-free mesh has reduced the incidence of hernia recurrence. The Lichtenstein procedure is the current reference technique for inguinal hernia treatment. Chronic pain has become the main postoperative complication after surgical inguinal hernia repair, especially following Lichtenstein. Preliminary experiences with a soft mesh positioned in the preperitoneal space (PPS) by transinguinal preperitoneal (TIPP) or total extraperitoneal (TEP) technique, showed promising results considering the reduction of postoperative chronic pain. Evolution of surgical innovations for inguinal hernia repair led to an open, direct approach with preperitoneal mesh position, such as TIPP. Based on the TIPP procedure, another preperitoneal repair has been recently developed, the transrectus sheath preperitoneal (TREPP) mesh repair., Methods: The ENTREPPMENT trial is a multicentre randomized clinical trial. Patients will be randomly allocated to anterior inguinal hernia repair according to the TREPP mesh repair or TIPP procedure. All patients with a primary unilateral inguinal hernia, eligible for operation, will be invited to participate in the trial. The primary outcome measure will be the number of patients with postoperative chronic pain. Secondary outcome measures will be serious adverse events (SAEs), including recurrence, hemorrhage, return to daily activities (for example work), operative time and hospital stay. Alongside the trial health status, an economic evaluation will be performed. To demonstrate that inguinal hernia repair according to the TREPP technique reduces the percentage of patients with postoperative chronic pain from 12% to <6%, a sample size of 800 patients is required (two-sided test, α = 0.05, 80% power).The ENTREPPMENT trial aims to evaluate the TREPP and TIPP procedures from patients' perspective. It is hypothesized that the TREPP technique may reduce the number of patients with any form of postoperative chronic pain by 50% compared to the TIPP procedure., Trial Registration: Current Controlled Trials: ISRCTN18591339.

Coxiella burnetii is a rare cause of vascular infections. Yet, Q fever is endemic in the southern part of The Netherlands. This report describes two patients--from the southern part of The Netherlands--with infected aneurysms of the abdominal aorta caused by Coxiella burnetii. Both patients underwent surgical debridement, in situ reconstruction with a great saphenous vein spiral graft, and a transmesenteric omentumplasty. One patient fully recovered, while the other died due to ischemic complications. A multidisciplinary work-up approach to treat infected abdominal aneurysms is proposed, including adequate surgical treatment and long-term antibiotic administration., (Copyright © 2013 Society for Vascular Surgery. Published by Mosby, Inc. All rights reserved.)

Statins are thought to reduce vascular inflammation through lipid independent mechanisms. Evaluation of such an effect in atherosclerotic disease is complicated by simultaneous effects on lipid metabolism. Abdominal aortic aneurysms (AAA) are part of the atherosclerotic spectrum of diseases. Unlike atherosclerotic occlusive disease, AAA is not lipid driven, thus allowing direct evaluation of putative anti-inflammatory effects. The anti-inflammatory potency of increasing doses (0, 20 or 40 mg/day) simvastatin or atorvastatin was evaluated in 63 patients that were at least 6 weeks on statin therapy and who underwent open AAA repair. A comprehensive analysis using immunohistochemistry, mRNA and protein analyses was applied on aortic wall samples collected during surgery. The effect of statins on AAA growth was analyzed in a separate prospective study in incorporating 142 patients. Both statins equally effectively and dose-dependently reduced aortic wall expression of NFκB regulated mediators (i.e. IL-6 (P<0.001) and MCP-1 (P<0.001)); shifted macrophage polarization towards a M2 phenotype (P<0.0003); selectively reduced macrophage-related markers such as cathepsin K and S (P<0.009 and 0.0027 respectively), and ALOX5 (P<0.0009), and reduced vascular wall NFκB activity (40 mg/day group, P<0.016). No effect was found on other cell types. Evaluation of the clinical efficacy of statins to reduce AAA progression did not indicate an effect of statins on aneurysm growth (P<0.337). Hence, in the context of AAA the clinical relevance of statins pleiotropy appears minimal.

Background: Preliminary experience has suggested that preperitoneal mesh positioning causes less chronic pain than Lichtenstein's technique for inguinal hernia repair. Therefore, a randomized clinical trial was conducted with the aim of evaluating the incidence of postoperative chronic pain after transinguinal preperitoneal (TIPP) mesh repair versus Lichtenstein's technique., Methods: Patients with a primary unilateral inguinal hernia were randomized to either TIPP or Lichtenstein's repair in two training hospitals. The primary outcome was the number of patients with chronic pain after surgery. Secondary outcomes were adverse events. Follow-up was scheduled after 14 days, 3 months and 1 year. Patients and outcome assessors were blinded., Results: A total of 302 patients were randomized to TIPP (143) or Lichtenstein (159) repair. Baseline characteristics were comparable in the two groups. Some 98.0 per cent of the patients were included in the analysis (141 in the TIPP group and 155 in the Lichtenstein group). Significantly fewer patients in the TIPP group had continuous chronic pain 1 year after surgery: five patients (3.5 per cent) versus 20 patients (12.9 per cent) in the Lichtenstein group (P = 0.004). An additional 12 patients (8.5 per cent) in the TIPP group and 60 (38.7 per cent) in the Lichtenstein group experienced pain during activity (P = 0.001). There were two patients with recurrence in the TIPP group and four in the Lichtenstein group, but no significant differences were found in other severe adverse events between the groups., Conclusion: Fewer patients had continuous chronic pain at 1 year after the TIPP mesh inguinal hernia repair compared with Lichtenstein's repair., (Copyright © 2012 British Journal of Surgery Society Ltd. Published by John Wiley & Sons, Ltd.)

Objective: Whether a typical patient and symptom profile is associated with proximal or distal lesions in lower extremity peripheral arterial disease (PAD) is unknown. Knowing which patient characteristics, exertional leg symptoms, and cardiovascular risk profile accompany the anatomic lesion location may facilitate a more tailor-made management of PAD., Methods: This cross-sectional study comprised 701 patients from two vascular surgery outpatient clinics with new-onset symptoms of PAD (Fontaine 2) who underwent duplex ultrasound (DUS) examinations from March 2006 to March 2011. The main outcome measures were patient characteristics, self-reported leg symptoms, and cardiovascular risk factors as documented from questionnaires and medical records. Peripheral lesion information, categorized by proximal and distal lesions, was obtained from DUS examinations. Multivariable logistic regression analyses were performed of proximal vs nonproximal lesions, distal vs nondistal lesions, and proximal and distal vs absence of having both lesions to assess relationships between patient characteristics, leg symptom categories (typical vs atypical leg symptoms), cardiovascular risk factors, and anatomic lesion location., Results: Lesions were proximal in 270 (38.5%), distal in 441 (62.9%), and proximal and distal in 94 (13.4%). Patients with proximal lesions were younger (odds ratio [OR], 0.94; P < .0001) and less likely to be obese (OR, 0.34; P < .0001) than those without proximal lesions. Older age (OR, 1.07; P < .0001), male sex (OR, 1.96; P = .003), being without a partner (OR, 2.24; P = .004), and lower anxiety scores (OR, 0.42; P = .003) were associated with distal lesions. Patients with both lesions were more likely to be single (OR, 2.30; P = .010) and less likely to be obese (OR, 0.24; P = .009). No distinguishing leg symptom pattern was observed for patients with proximal lesions. Intermittent claudication was more frequently reported in those with distal lesions (P = .011). Although buttock and thigh pain seemed to be somewhat more present in proximal lesions (P < .01) and calf pain more in distal lesions (P < .001), patients still reported pain at a variety of levels throughout their legs, regardless of the anatomic lesion location., Conclusions: Two distinctive PAD phenotypes-each with its own characteristics and risk factors-emerged by anatomic lesion location; however, PAD-specific leg symptoms did not always reflect the anatomic lesion location. These findings may open new opportunities to better tailor PAD management to these two PAD subgroups and may raise awareness about not relying on self-reported symptoms to guide further diagnostic imaging and peripheral lesion management., (Copyright © 2012 Society for Vascular Surgery. Published by Mosby, Inc. All rights reserved.)

We describe a 61-year-old patient with an infected aneurysm of the abdominal aorta due to Salmonella sepsis. Treatment was successful and included aneurysm resection, extensive debridement, and reconstruction of the abdominal aorta using the superficial femoral vein, combined with long-term antibiotic therapy., (Copyright © 2012 Annals of Vascular Surgery Inc. Published by Elsevier Inc. All rights reserved.)

Introduction: Standard open anterior inguinal hernia repair is nowadays performed using a soft mesh to prevent recurrence and to minimalize postoperative chronic pain. To further reduce postoperative chronic pain, the use of a preperitoneal placed mesh has been suggested. In extremely large hernias, the lateral side of the mesh can be insufficient to fully embrace the hernial sac. We describe the use of two preperitoneal placed meshes to repair extremely large hernias. This 'Butterfly Technique' has proven to be useful. Hernias were classified according to hernia classification of the European Hernia Society (EHS) during operation. Extremely large indirect hernias were repaired by using two inverted meshes to cover the deep inguinal ring both medial and lateral. Follow up was at least 6 months. VAS pain score was assessed in all patients during follow up. Outcomes of these Butterfly repairs were evaluated. Medical drawings were made to illustrate this technique. A Total of 689 patients underwent anterior hernia repair 2006-2008., Presentation of Case: Seven male patients (1%) presented with extremely large hernial sacs. All these patients were men. Mean age 69.9 years (range: 63-76), EHS classifications of hernias were all unilateral. Follow up was at least 6 months. Recurrence did not occur after repair. Chronic pain was not reported., Discussion: Open preperitoneal hernia repair of extremely large hernias has not been described. The seven patients were trated with this technique uneventfully. No chronic pain occurred., Conclusion: The Butterfly Technique is an easy and safe alternative in anterior preperitoneal repair of extremely large inguinal hernias.

Objectives: The aim of this study was to evaluate patients, who underwent spiral vein reconstruction of the abdominal aorta to repair infected aneurysms or replace infected aortic grafts., Methods: All spiral vein reconstructions between March 2005 and May 2010 because of vascular infections of the abdominal aorta were retrospectively included. Diagnosis was determined by clinical examination, laboratory results, computed tomography (CT) and positron emission tomography (PET) scan, and microbiological tests. Spiral vein reconstruction consisted of harvesting the greater saphenous vein (GSV) and construction into a spiral graft, aortic reconstruction and a transmesenteric omentumplasty. Primary outcomes were survival and limb salvage. Secondary outcomes included technical, clinical and ongoing success, re-infection, ongoing infection and patency., Results: All five patients survived surgery, and there were no in-hospital deaths. Survival and limb salvage were 100% after median follow-up of 13 months (6-67 months). Further, technical, clinical and continuing success was 100%. There were no re-infections or ongoing infections., Conclusions: Spiral vein reconstruction using the GSV showed good short-term survival and limb salvage. It, therefore, might be considered as an attractive treatment method for vascular infections of the abdominal aorta. Still, more follow-up is needed to evaluate long-term results., (Copyright © 2011 European Society for Vascular Surgery. Published by Elsevier Ltd. All rights reserved.)

Background: Chronic pain is the main drawback of the Lichtenstein procedure for inguinal hernia repair, with a reported incidence of 15-40%. The transinguinal pre-peritoneal (TIPP) technique seems to be associated with less chronic pain, comparable to the total extra peritoneal (TEP) technique. The aim of this study was to evaluate 3 years of TIPP and Lichtenstein experience since the start of our Hernia Center Brabant in January 2006., Methods: Patient records of unilateral primary inguinal anterior hernia corrections (TIPP and Lichtenstein) performed since the opening of Hernia Center Brabant (2006-2008) were evaluated in a retrospective study. ASA class 4 and 5, <18 years, recurrences and bilateral hernias were excluded. In the TIPP technique, a Polysoft™ Hernia Patch was placed into the preperitoneal space using an anterior protocol led approach. The Lichtenstein technique was performed as described by Amid [Amid et al (1996) Eur J Surg 162:447-453] and modified with a soft mesh. One of the hernia surgeons decided peroperatively which technique to perform. Baseline characteristics and postoperative complications were assessed retrospectively. The attempted follow up period was 6 months. Chronic pain was assessed in both groups as mild (VAS 1-3), moderate (VAS 4-6) or severe (VAS 7-10). Chronic pain was defined in both groups as any pain sensation lasting longer than 3 months postoperatively, or when local injection of analgesia was necessary. Patients who did not come back because of chronic pain after regular follow up were regarded as free of pain., Results: A total of 496 patients were included in this study; 225 TIPP and 271 Lichtenstein anterior inguinal hernia operations were analyzed. Data from one TIPP-patient were lost. Both groups were comparable with regard to baseline characteristics regarding age (p = 0.059), gender (p = 0.478) and ASA-classification (p = 0.104). TIPP: mean age 52.7 years, ASA-classification I: 54%, II: 36% and III: 5.3%. A total of 7.6% complications were assessed; recurrence (n = 1), bleeding (and re-operation) (n = 4); 10 patients (4.4%) experienced chronic pain. Persisting sensation loss occurred in 0.9%. Lichtenstein: mean age 57.3 years, ASA-classification I: 51%, II: 38% and III: 11%. A total of 8.5% complications were assessed; recurrence (n = 3), bleeding (and re-operation) (n = 3); 11 Lichtenstein patients (4.1%) experienced chronic pain. Persisting sensation loss occurred in 2.2%. Limitations of this retrospective study were incomplete follow up (31.3% had only one post operative visit 14 days after surgery) and these patients were further regarded as free of pain. Therefore, possible under-reporting of chronic pain could be present. The study was not double blind., Conclusion: This retrospective study design revealed no significantly better results for the TIPP procedure as compared to the Lichtenstein technique. The incidence of chronic pain reported in this retrospective study has been low in both groups since the opening of the Hernia Center Brabant. These results form the basis for a prospective randomized clinical trial comparing the TIPP and Lichtenstein techniques.

Objectives: Gender disparities, particularly among young women with cardiovascular disease, are a growing cause for concern. Depression is a prevalent and prognostically important comorbidity in peripheral arterial disease (PAD), but its prevalence has not been described as a function of gender and age. Therefore, we compared depressive symptoms at the time of PAD diagnosis and 6 months later by gender and age in PAD patients., Methods: The study enrolled 444 newly diagnosed patients with PAD (32% women) from two Dutch vascular outpatient clinics. Patients' depressive symptoms were assessed with the 10-item Center for Epidemiological Studies Depression Scale (CES-D) at baseline and 6 months later (CES-D scores >or=4 indicate significant depressive symptoms). Logistic regression models were constructed to evaluate the relationship among four gender-age groups (women <65 and >or=65 years; men <65 and >or=65 years [reference category]) and baseline and 6-month follow-up depressive symptoms., Results: Initially, 33% of women <65 years had significant depressive symptoms, and 6 months later, significant depressive symptoms had developed in 19% of the other younger women. These rates were much higher than other gender-age groups (range at baseline, 11%-16%; 6-month incidence, 6%-10%; P or=65 years, whereas other gender-age groups were not at risk. Additional adjustment for change in the ankle-brachial index did not explain the increased depression risk in younger women (OR, 3.5; 95% CI, 1.2-10.2)., Conclusions: Significant depressive symptoms are more common in younger women with PAD than in other gender-age groups, both at the time of diagnosis and 6 months later. To eradicate gender-based disparities in PAD, depression screening and monitoring in younger women may be an important direction for future research and intervention.

Background: Type D personality refers to the tendency to experience negative emotions and to inhibit self-expression in social interaction and has been shown to be an independent predictor of mortality in cardiac disease. Information about the effects of psychological traits on prognosis is lacking in cases of peripheral arterial disease (PAD)., Objective: To examine whether type D personality predicts all-cause mortality in PAD., Design: Pilot follow-up study., Setting: Vascular surgery department of a teaching hospital., Patients: A total of 184 patients with symptomatic PAD (mean [SD] age, 64.8 [9.8] years) were followed up for 4 years (interquartile range, 3.5-4.5 years)., Main Outcome Measures: Patients completed the type D Scale-14 measure of type D personality at baseline. Information about all-cause mortality was obtained from patient medical files., Results: During 4-year follow-up, 16 patients (8.7%) died. Adjusting for age and sex, type D personality was predictive of mortality (P = .03). Ankle-brachial index (P = .05), age (P = .009), diabetes mellitus (P = .02), pulmonary disease (P = .09), and renal disease (P = .02) were also predictive of mortality. Multivariable logistic regression revealed that age, diabetes, and renal disease were independent predictors of all-cause mortality (odds ratios, 1.1-2.3). After adjustment for these clinical predictors, patients with type D personality still had a more than 3-fold increased risk of death (odds ratio, 3.5; 95% confidence interval, 1.1-11.1; P = .04)., Conclusions: Type D personality predicts an increased risk of all-cause mortality in PAD, above and beyond traditional risk factors. Further research is needed to confirm these findings, but this pilot study suggests that the assessment of type D personality may be useful for detecting high-risk patients with PAD.

Mycotic aneurysms leading to aortoduodenal fistula (ADF) are associated with high morbidity and mortality. We report a patient with a mycotic aneurysm and ADF who required emergency laparotomy. After excision of the aneurysm, vascular reconstruction was performed using an autologous graft. The left long saphenous vein was harvested and constructed into a spiral graft. The graft was inserted using a standard inlay technique. After 12 months the patient is in good health. No inflammation or dilation of the saphenous vein spiral graft has been noted. We suggest that in the emergency treatment of mycotic abdominal aneurysm, aortic reconstruction with saphenous vein spiral graft is a valuable option.

Background: Acute pancreatitis is a severe disease with unpredictable course and outcomes. It is especially hard to identify early those patients who will have a fulminant course. In a prospective observational study, we tested the hypothesis that the CT Severity Index (CTSI), established within 48hours after admission, is prognostic for morbidity and mortality and can predict the necessity for admission to an ICU., Study Design: From January 1994 to October 2002, all patients with the diagnosis of first time acute pancreatitis underwent spiral CT with intravenous contrast within 48hours of admission. The extent of inflammation and necrosis was assessed to define the CTSI. Patients were initially managed in an ICU in a standardized fashion. Complications and mortality were registered in a systematic manner., Results: Seventy-nine patients were admitted with acute pancreatitis. The overall complication rate was 57%; mortality was 9%. In patients with a CTSI of 0 to 3, these rates were 42% and 2%, respectively; in those with CTSI of 4 to 6, 81% and 19%, respectively; and in those with CTSI of 7 to 10, 100% and 33%, respectively. Outcomes of subsequent CT scans did not alter the initial prognosis. Early CTSI correlated well with the incidence of complications, sepsis, mortality, and necessity for ICU admission., Conclusions: Acute pancreatitis is associated with marked morbidity and mortality. Initial admission to an ICU and standardized conservative treatment are justified for all patients. Early establishment of the CTSI is an excellent prognostic tool for complications and mortality. Patients with a CTSI of 0 to 3 can safely be discharged from the ICU.

Background: In previous studies we have shown that pre-transplant hamster blood transfusion (HBT) can induce non-responsiveness in the T cell independent immunecompartment and result in tolerance towards hamster cardiac xenografts (Xgs) in T cell deficient athymic nude rats. In this study we test the combination of pre-transplant HBT with cyclosporin A (CSA) in immunocompetent Lewis rats., Methods: Before transplantation of a hamster cardiac Xg, 1 ml hamster blood was administered to nude rats or Lewis rats. CSA dissolved in olive oil was given orally at varying doses. Anti-hamster antibodies were measured by flowcytometry., Results: In nude rats HBT 3 days before transplantation resulted in 100% long-term survival >100 days (n=9). In Lewis rats, HBT resulted in hyperacute rejection (HAR) (n=6). Treatment of nude rats with CSA at doses varying from five to 20 mg/kg/day and treatment of Lewis rats with CSA five or 10 mg/kg/day did not effect Xg survival. However, treatment of Lewis rats with CSA 20 mg/kg/day led to long-term survival of five of nine Xgs (p <0.01). Combination of HBT with CSA 10 mg/kg/day in Lewis rats resulted in long-term survival of four of seven Xgs. HBT and CSA 20 mg/kg/day resulted in 100% long-term survival (n=9). Immunoglobulin M (IgM) increased after HBT and CSA in these Lewis rats, but decreased after transplantation and remained low over time. When CSA was discontinued, IgM increased and Xgs were rejected (n=3)., Conclusions: This study confirms that pre-transplant HBT results in long-term survival of hamster cardiac Xgs in nude rats. HBT and CSA have strong synergistic effects in immunocompetent Lewis rats. Combination of HBT with CSA treatment leads to long-term Xg survival in Lewis rats, whereas HBT alone results in HAR. The presence of T cells has a dominant influence on Xg survival after pre-transplant blood transfusion.

Background: Surgeons have become increasingly interested in replacing conventional sutures by means of adhesive bonds for the closure of skin wounds. There are several advantages to the use of adhesive bonds compared with the conventional sutures., Methods: Between January and August 2001, all the wounds in children after groin surgery were closed with an adhesive, N-butylcyanoacrylate (Indermil, Locite Corp, 's-Hertogenbosch, The Netherlands), or with a suture, polyglactin 5-0 (Vicryl), intracutaneously. Fifty Inguinal wounds were treated with Indermil and 50 with Vicryl. Wounds were evaluated for hematoma, infection, dehiscence, or formation of granuloma. A scale from 1 to 10 expressed the cosmesis by patient and surgeon., Results: The most remarkable difference in wound healing was dehiscence of the wound in 26% of cases in the adhesive group and no dehiscence in the suture group. The cosmesis of the wounds was marked with an 8.6 in the suture group and in the adhesive group with a 6.8., Conclusions: Wound dehiscence was seen significantly more frequent in the patients in whom the wound was closed with N-butylcyanoacrylate. The cosmesis of wounds closed with tissue glue was significantly lower then the cosmesis after suturing. Therefore, the authors advise, on the basis of this prospective randomized trial, that surgical wounds in children should be closed with a intracutaneous absorbable suture.

The effects of pre-transplant blood transfusion vary from induction of antibodies and accelerated graft rejection, to prolonged survival and even tolerance. The beneficial 'transfusion effect' in allotransplantation is believed to be merely T-cell mediated. In xenotransplantation, T-cell independent mechanisms form a major hurdle. In this study we investigated the effects of pre-transplant hamster blood transfusion on the survival of hamster cardiac xenografts in T-cell deficient athymic nude rats. Nude rats rejected xenografts after 3.8 +/- 0.5 d (n = 8), and immunocompetent Lewis rats after 4.0 +/- 0.5 d (n = 8), following a similar IgM response (P = NS). Hamster blood transfusion 3 d before transplantation in nude rats led to an IgM response and long-term xenograft survival in 17/20. Timing was of importance: blood transfusion 7 d before transplantation resulted in 45% long-term xenograft survival (n = 20). Injection of purified hamster erythrocytes, leukocytes or minced heart also led to survival of xenografts for > 100 d in nude rats, but not in all cases. Second xenografts transplanted to long-term survivors did not provoke an IigM response, and were accepted for > 100 d (n = 4). Transfer of serum from long-term survivors to untreated nude rats resulted in survival of xenografts for > 100 d (n = 4). In Lewis rats pre-transplant blood transfusion induced hyperacute rejection of xenografts after 158 +/- 128 min (n = 8, P < 0.01). We conclude that pre-transplant hamster blood transfusion can induce long-term survival of hamster cardiac xenografts in T-cell deficient athymic nude rats. This blood transfusion effect is mediated by humoral factors and can be transferred by serum. Elucidation of underlying mechanisms might provide some insight into xenotransplantation nonresponsiveness of T-cell independent immunefactors.

Antibodies play a crucial role in the rejection of xenografts. We tested the hypothesis that xenografts are protected against antibody-mediated attack early after transplantation in a concordant model. We investigated the role of xenoreactive antibodies as a stimulus for protection and the effects of a total blockade of the antibody response by the leflunomide analog malononitrilamide 279. Hamster cardiac xenografts were transplanted to Lewis rat recipients. Second transplants and retransplants of xenografts were performed to untreated rats that had a xenograft in place for 3 d. Untreated rats rejected hamster cardiac xenografts after 4.0 +/- 0.0 d. Significant levels of anti-donor IgM, as measured by flowcytometry, were present on day 3 after transplantation (11.2% +/- 2.8 vs. 1.2% +/- 0.0 on day 0, P < 0.001). 'Fresh' second xenografts transplanted to rats that had a first xenograft in place for 3 d and had anti-hamster antibodies, underwent hyperacute rejection. The first xenografts remained functioning. Xenografts that were removed on day 3 from untreated rats and then retransplanted remained functioning. Xenografts that were removed on d 3 from rats that had been treated with malononitrilamide 279, 15 mg/kg/d and were retransplanted underwent hyperacute rejection. IgM levels at the time of removal were 1.1% +/- 0.5 in these rats and not different from baseline (P = 0.96). We conclude that xenografts are protected against antibody-mediated damage early after transplantation. The presence of anti-donor antibodies might be an essential stimulus for the induction of protection. There seems to be a delicate balance between the injurious and protective effects of antibodies. Treatment strategies that are designed to block antibody formation completely might prevent the induction of protection.

Background: Our purpose was to optimize hyperbaric pressure as a vector for ex vivo transfection of antisense oligodeoxynucleotides (AS-ODN) to intercellular adhesion molecule-1 to limit reperfusion injury (RI) in cardiac allografts. We investigated the effects of increased pressure, incubation time, and AS-ODN concentrations on transfection efficiency and toxicity., Methods and Results: PVG (RT1c) donor hearts were heterotopically transplanted to ACI (RT1a) recipients. Donor hearts were harvested and the various groups were treated at: (1) different pressure (1-9 atm) for 45 min with 80 micromol/liter AS-ODN; (2) different incubation times (15 min to 6 hr) at 5 atm with 80 micromol/liter AS-ODN; 3) different AS-ODN concentrations (80-240 micromol/liter) at 5 atm for 45 min. Hearts were procured 24 or 72 hr after transplantation. Transfection efficiency was determined with fluorescein-labeled AS-ODN. The degree of RI was determined with biochemical and histological analysis. Increasing pressure from ambient (1 atm) pressure to pressures as high as 9 atm leads to a increase in transfection efficiency from 1.7+/-.5 to 62+/-3.9% and a reduction in RI. Increased incubation time up to 45 min increased transfection efficiency and reduced RI, but longer incubation times induced significant toxicity to the allograft. Increased AS-ODN concentrations improved transfection and reduced RI., Conclusions: Hyperbaric pressure is a safe and effective vector for the ex vivo delivery of AS-ICAM-1-ODN to rodent cardiac allografts and results in a reduction in reperfusion injury.

Study Objectives: Early detection and treatment of lung transplant rejection is critical for preservation of pulmonary graft function. Damage to pulmonary allografts is mediated by apoptotic cell death induced by the alloreactive T lymphocytes that infiltrate lung grafts. Previous studies demonstrate that acute cardiac allograft rejection can be visualized using radiolabeled annexin V. This study was done to determine whether this technique could visualize acute rejection in a rodent model of unilateral orthotopic lung transplantation., Design: Eighteen Sprague-Dawley ACI rats underwent removal of their left lung followed by orthotopic transplant of either an allogeneic (PVG, immunologically mismatched; N = 10) or a syngeneic (ACI, immunologically matched) pulmonary graft (N = 8). Animals were imaged 1 h after IV injection of 1 mCi (37.0 MBq) of (99m)Tc-annexin V 1 to 7 days after transplantation., Results: Lungs receiving the allograft demonstrated moderate to marked mononuclear infiltration of the perivascular, interstitial, and peribronchial tissues. No mononuclear infiltrates were noted in the native right lungs nor in the syngeneic transplants. Region of interest image analysis revealed significant (p < 0.0005) increases of transplant to normal lung activity ratios 3 to 7 days after allograft surgery. The increased annexin V uptake in these lungs was confirmed at biodistribution assay (allograft 151% greater than isograft activity, p < 0.005)., Conclusions: Acute experimental lung transplant rejection can be noninvasively identified using (99m)Tc-annexin V. Radiolabeled annexin V may be a clinically useful noninvasive screening tool for acute rejection.

Objective: Apoptosis, or programmed cell death, has been suggested as a mechanism of immunologic injury during cardiac allograft rejection. We tested the hypothesis that technetium Tc 99m annexin V, a novel radiopharmaceutical used to detect apoptosis, can be used to detect cardiac allograft rejection by nuclear imaging., Methods: Untreated ACI rats served as recipients of allogeneic PVG rat (n = 66) or syngeneic ACI rat (n = 30) cardiac grafts. Untreated recipient animals underwent 99mTc-annexin V imaging daily for 7 days. Region of interest analysis was used to quantify the uptake of 99mTc-annexin V. Immediately after imaging grafts were procured for histopathologic analysis and terminal deoxynucleotidyltransferase-mediated deoxyuridine triphosphate-biotin nick-end labeling of apoptotic nuclei. One group was treated with 10 mg/kg/d cyclosporine (INN: ciclosporin) commencing on day 4 after transplantation (n = 6)., Results: Untreated allografts showed histologic signs of rejection 4 days after transplantation. Apoptotic nuclei could be demonstrated in myocytes, endothelial cells, and graft-infiltrating cells of all rejecting allografts. Nuclear imaging revealed a significantly greater uptake of 99mTc-annexin V in rejecting allogeneic grafts than in syngeneic grafts on day 4 (P = .05), day 5 (P < .001), day 6 (P < .001), and day 7 (P = .013) after transplantation. A correlation between the histologic grade of acute rejection and uptake of 99mTc-annexin V was observed (r2 = 0.87). After treatment of rejection with cyclosporine, no apoptotic nuclei could be identified in allografts and uptake of 99mTc-annexin V decreased to baseline., Conclusions: Apoptosis occurs during acute cardiac allograft rejection and disappears after treatment of rejection. 99mTc-annexin V can be used to detect and monitor cardiac allograft rejection.

Cellular mechanisms responsible for maintenance of peripheral transplant tolerance in a rodent model were evaluated. Donor-specific tolerance was established in ACI rats given a vascularized heterotopic cardiac allograft followed by a 10-day course of cyclosporine. Tolerance was associated with a reduction in donor-specific cytotoxic T lymphocyte precursors and the presence within the spleen of cells capable of transferring suppression in adoptive transfer assays. Experiments using thymectomized animals revealed that the establishment and maintenance of tolerance occurred peripherally, independently of the thymus. Adoptive transfer experiments demonstrated that ongoing graft tolerance was mediated by suppressor cells that were antigen-restricted, radiosensitive, and capable of preventing allograft rejection by naive as well as sensitized cells in vivo. Studies designed to disrupt tolerance demonstrated a remarkable durability of graft protection once established, and give insight into the identity and mechanism of action of suppressor cells generated in this model.

With the increasing frequency of transplantation of two or more organs into a single recipient, it has become evident that different organs are rejected with different kinetics. In this study the kinetics of skin, lung, and heart allograft rejection were compared in a rodent model. To study the influence of different allografts on the recipient's immune system, simultaneous or sequential skin, lung, or heart transplants were performed in various combinations, using DA rats as recipients for PVG allografts. Recipients receiving primary allografts were treated postoperatively with ten doses of cyclosporine (CsA) or preoperatively with 4 doses of rabbit antirat thymocyte globulin (ATG). Subsequent transplants were performed a minimum of 40 days later without additional immunosuppression. All primary skin allografts and 60% of primary lung allografts were rejected, while 100% of the heart allografts were accepted indefinitely. Recipients of primary skin allografts rejected subsequent skin, lung, or heart allografts with accelerated kinetics. Recipients of primary heart allografts accepted subsequent skin, lung, and heart allografts indefinitely without further immunosuppression. Surprisingly, animals that had rejected a primary lung allograft accepted subsequent skin or heart allografts indefinitely. Simultaneously transplanted skin and lung allografts were concordantly rejected. However, these animals accepted a subsequent heart allograft indefinitely, suggesting a strong tolerizing effect of lung allografts. Our results indicate that tissue-specific differences are critical, not only in determining acceptance or rejection of a primary allograft but also in determining the fate of subsequent allografts.