Infective native aneurysms of the infrapopliteal arteries - A systematic literature review and report of two cases.

Infective native aneurysms (INA) of the infrapopliteal arteries are rare and have previously been poorly described. This systematic review aims to provide an overview of the literature of this entity. Furthermore, two case reports of our own clinical experience are presented. PubMed, ScienceDirect, Cochrane, Ovid Embase, Ovid MEDLINE, and Web of Science were searched for articles on INAs of the infrapopliteal segment from January 1990 to September 2023. Article screening and selection were performed adhering to PRISMA guidelines. A total of 98 articles were screened and 20 were eligible for inclusion, of which all were case reports. In total, 22 patients with 28 infrapopliteal INAs were identified. The majority of INAs were located in the tibioperoneal trunk (n = 10, 36%) followed by the posterior tibial artery (n = 7, 25%). A current, or history of, infective endocarditis (IE) was described in 18 out of 22 patients (82%). Two patients died during hospitalization and one patient required a transfemoral amputation. A conservative antibiotic-only approach was chosen in three out of 28 INAs, two of which were the case reports described in this article; surgical or endovascular intervention was performed in 19 out of 28 aneurysms. No complications occurred in the conservative group, but one complication (transfemoral amputation) occurred in the interventional group. Infrapopliteal INA is a rare entity, and most described cases are precipitated by IE. Surgery or endovascular treatment might be indicated, but more research is warranted to define which patient would benefit and by what surgical approach.

Infective Native Aortic Aneurysm: a Delphi Consensus Document on Treatment, Follow Up, and Definition of Cure.

OBJECTIVE: Evidence is lacking to guide the management of infective native aortic aneurysm (INAA). The aim of this study was to establish expert consensus on surgical and antimicrobial treatment and follow up, and to define when an INAA is considered cured. METHODS: Delphi methodology was used. The principal investigators invited 47 international experts (specialists in infectious diseases, radiology, nuclear medicine, and vascular and cardiothoracic surgery) via email. Four Delphi rounds were performed, three weeks each, using an online questionnaire with initially 28 statements. The panellists rated the statements on a five point Likert scale. Comments on statements were analysed, statements were revised and added or deleted, and the results were presented in the iterative rounds. Consensus was defined as ≥ 75% of the panel rating a statement as strongly agree or agree on the Likert scale, and consensus on the final assessment was defined as Cronbach's alpha > 0.80. RESULTS: All 49 panellists completed all four rounds, resulting in 100% participation. One statement was added based on the results and comments of the panel, resulting in 29 final statements: three on need for consensus, 20 on treatment, five on follow up, and one on definition of cure. All 29 statements reached agreement of ≥ 86%. Cronbach's alpha increased for each consecutive round; round 1, 0.85; round 2, 0.90; round 3, 0.91; and round 4, 0.94. Thus, consensus was reached for all statements. CONCLUSION: INAAs are rare, and high level evidence to guide optimal management is lacking. This consensus document was established with the aim of helping clinicians manage these challenging patients, as a supplement to current guidelines. The presented consensus will need future amendments in accordance with newly acquired knowledge.

Danish Nationwide Study on Surgical Treatment of Infective Native Abdominal Aortic Aneurysms.

OBJECTIVE: This study aimed to describe surgical trends, survival, and infection related complications (IRC) in a Danish cohort of patients with infective native aortic aneurysms (INAAs). METHODS: A retrospective nationwide cohort study including all patients in Denmark who were surgically treated for abdominal INAA between 2000 and 2020 was conducted. Patients were identified through the Danish vascular registry, Karbase, which is a database registering all patients treated with vascular surgery in Denmark. Subsequent data on clinical presentation, treatment, all cause mortality, and complications were obtained from the electronic patient charts. RESULTS: Seventy-five patients were included in the study, of whom 60 (80%) were male, with a median age of 69 (IQR 64, 75) years. Open surgical repair (OSR) was performed in 54 (72%) patients and endovascular aortic repair (EVAR) in 21 (28%). Median follow up was 52 (IQR 32, 103) months. Open repair was consistently the most frequent treatment modality throughout the study period, but EVAR became more frequent over time. The 30 day survival of the total cohort was 97% (94 - 100%). Kaplan-Meier survival estimates for the cohort were 92% (95% CI 85 - 98%), 80% (95% CI 71 - 91%), 63% (95% CI 52 - 78%), and 48% (95% CI 35 - 66%) at one, three, five and 10 years, respectively. Patients treated by EVAR had comparable long term survival to patients treated by OSR, with a hazard ratio of 0.35 (95% CI 0.10 - 1.22), but was associated with better short term survival up to five years. The most common cause of death was sepsis. Five (9%) OSR patients had IRC compared with one (5%) EVAR patient. CONCLUSION: In this nationwide study of patients treated for abdominal INAA, an increasing number of patients were surgically treated during the study period. Patients treated by EVAR demonstrated long term survival comparable to OSR. The incidence of post-operative IRC was low. These results should be interpreted with caution and prospective registries are needed.

Contemporary multimodal approach to diagnosis and treatment of vascular graft and endograft infections.

Vascular graft and endograft infections (VGEIs) are a feared complication because of their morbidity, cost, and mortality. Despite broad and varying strategies, as well as limited evidence, societal guidelines do exist. The objective of this review was to supplement current guidelines with emerging and multimodal techniques for treatment. An electronic search was performed using PubMed with specific search terms from 2019 to 2022 in which VGEIs were described or analyzed in the carotid, thoracic aorta, abdominal, or lower extremity arteries. A total of 12 studies were collected from the electronic search. Articles describing all of the anatomic areas were present. The incidence of VGEIs depends on the anatomic location, varying from <1% to 18%. Gram-positive bacteria are the most common organism. Referral of patients with VGEIs to centers of excellence is paramount, as is pathogen identification, preferably from direct sampling techniques. The MAGIC (Management of Aortic Graft Infection Collaboration) criteria have been endorsed for all VGEIs and validated for aortic VGEI. They are well supplemented with additional diagnostic techniques. Treatment must be individualized, although the goal should be the removal of infected material with appropriate revascularization. VGEIs remain a devastating complication, despite changing or improving medical surgical techniques in vascular surgery. Prophylactic measures, early diagnosis, and patient-specific therapy remain the cornerstones of treatment for this feared complication.

Semi-Conservative Treatment Versus Radical Surgery in Abdominal Aortic Graft and Endograft Infections.

OBJECTIVE: Abdominal aortic graft and endograft infections (AGIs) are rare complications following aortic surgery. Radical surgery (RS) with resection of the infected graft and reconstruction with extra-anatomical bypass or in situ reconstruction is the preferred therapy. For patients unfit for RS, a semi-conservative (SC), graft preserving strategy is possible. This paper aimed to compare survival and infection outcomes between RS and SC treatment for AGI in a nationwide cohort. METHODS: Patients with abdominal AGI related surgery in Sweden between January 1995 and May 2017 were identified. The Management of Aortic Graft Infection Collaboration (MAGIC) criteria were used for the definition of AGI. Multivariable regression was performed to identify factors associated with mortality. RESULTS: One hundred and sixty-nine patients with surgically treated abdominal AGI were identified, comprising 43 SC (14 endografts; 53% with a graft enteric fistula [GEF] in total) and 126 RS (26 endografts; 50% with a GEF in total). The SC cohort was older and had a higher frequency of cardiac comorbidities. There was a non-significant trend towards lower Kaplan-Meier estimated five year survival for SC vs. RS (30.2% vs. 48.4%; p = .066). A non-significant trend was identified towards worse Kaplan-Meier estimated five year survival for SC patients with a GEF vs. without a GEF (21.7% vs. 40.1%; p = .097). There were significantly more recurrent graft infections comparing SC with RS (45.4% vs. 19.3%; p < .001). In a Cox regression model adjusting for confounders, there was no difference in five year survival comparing SC vs. RS (HR 1.0, 95% CI 0.6 - 1.5). CONCLUSION: In this national AGI cohort, there was no mortality difference comparing SC and RS for AGI when adjusting for comorbidities. Presence of GEF probably negatively impacts survival outcomes of SC patients. Rates of recurrent infection remain high for SC treated patients.

Conservative Management First Strategy in Aortic Vascular Graft and Endograft Infections.

OBJECTIVE: The aim of this study was to describe and present the outcomes of a specific treatment protocol for aortic vascular graft and endograft infections (VGEIs) without explantation of the infected graft. METHODS: This was a retrospective, observational single centre cohort study carried out between 2012 and 2022 at a tertiary hospital. An aortic VGEI was defined according to the Management of Aortic Graft Infection Collaboration (MAGIC) criteria. Fitness for graft excision was assessed by a multidisciplinary team and included an evaluation of the patient's general condition, septic status, and anatomical complexity. Antimicrobial treatments were individualised. The primary outcome was survival at the last available follow up; secondary outcomes were antimicrobial treatment duration, infection eradication, treatment failure despite antimicrobial treatment, and the development of aortic fistulation. RESULTS: Fifty patients were included in the study, of whom 42 (84%) had had previous endovascular repair. The median patient age was 72 years (range 51 - 82 years) and median duration of treatment with antimicrobials was 18 months (range 1 - 164 months). Kaplan-Meier analysis estimated the 30 day survival to be 98% (95% confidence interval [CI] 96 - 100), the one year survival rate to be 88% (95% CI 83.4 - 92.6), and the three year survival rate to be 79% (95% CI 72.7 - 84.7). Twenty-four (48%) patients were able to discontinue antibiotic treatment after a median of 16 months (range 4 - 81 months). When categorised according to infected graft location, deaths occurred in four (40%) patients with thoracic, two (40%) with paravisceral, seven (30%) with infrarenal VGEIs, and in one (25%) patient with an aorto-iliac VGEI; no (0%) patient with a thoraco-abdominal VGEI died. CONCLUSION: Identifying the microbiological aetiology in patients with aortic VGEI enables individualised, specific antibiotic treatment, which may be useful in patients with a VGEI excluded from surgery. This single centre retrospective analysis of patients with VGEIs without fistula selected for conservative treatment suggests that conservative management of aortic VGEIs with targeted antibiotic therapy without graft excision is potentially effective, and that antimicrobial treatment will not necessarily be needed indefinitely.

Artificial Intelligence Outperforms Kaplan-Meier Analyses Estimating Survival after Elective Treatment of Abdominal Aortic Aneurysms.

OBJECTIVE: Long term differences in survival after elective repair of abdominal aortic aneurysms (AAAs) between open surgical repair (OSR) and endovascular aneurysm repair (EVAR) are unclear, and hitherto artificial intelligence has not been used for this purpose. The aim was to compare the precision of survival estimates between the Kaplan-Meier (KM) method and the artificial intelligence derived method Neural Multi-Task Logistic Regression (N-MTLR), and to compare survival estimates as a function of patient age and time since surgery between OSR and EVAR using N-MTLR. METHODS: All AAAs between 2003 and 2018 in Denmark were identified in the Danish vascular registry. Survival was estimated using the KM and N-MTLR methods, and prediction performance was estimated with the Brier score. RESULTS: 7 912 patients were included in the study, n = 6 569 (83%) men, median age 72 years (range 35 - 92), with a median follow-up time of 45.7 months (range 0 - 120). The two treatment cohorts, OSR n = 5 495 (69%), and EVAR n = 2 417 (31%), differed significantly in patient characteristics. The Brier score for KM increased from 0.044 to 0.244, and for N-MTLR from 0.044 to 0.206, from 90 days to 10 years. The N-MTLR method was more accurate than KM from 90 days to 10 years after surgery, p ≤ .025. N-MTLR demonstrated significant increased probability for survival for OSR in patients aged 58 - 76 years at five years, and 65 - 73 at 10 years after surgery, and the opposite was found for the benefit of EVAR in patients aged 72 - 85 years at one year, 85 - 90 years at five years, and for 85 - 90 year olds at 10 years after surgery. CONCLUSION: N-MTLR outperforms KM for the entire post-operative follow-up time. This N-MTLR model has the potential to render more precise patient specific survival estimates and establish survival differences between subgroups of patients that KM is unable to detect, demonstrated here for different age groups.

Editor's Choice - Infective Native Aortic Aneurysms: A Delphi Consensus Document on Terminology, Definition, Classification, Diagnosis, and Reporting Standards.

OBJECTIVE: There is no consensus regarding the terminology, definition, classification, diagnostic criteria, and algorithm, or reporting standards for the disease of infective native aortic aneurysm (INAA), previously known as mycotic aneurysm. The aim of this study was to establish this by performing a consensus study. METHODS: The Delphi methodology was used. Thirty-seven international experts were invited via mail to participate. Four two week Delphi rounds were performed, using an online questionnaire, initially with 22 statements and nine reporting items. The panellists rated the statements on a five point Likert scale. Comments on statements were analysed, statements revised, and results presented in iterative rounds. Consensus was defined as ≥ 75% of the panel selecting "strongly agree" or "agree" on the Likert scale, and consensus on the final assessment was defined as Cronbach's alpha coefficient > .80. RESULTS: All 38 panellists completed all four rounds, resulting in 100% participation and agreement that this study was necessary, and the term INAA was agreed to be optimal. Three more statements were added based on the results and comments of the panel, resulting in a final 25 statements and nine reporting items. All 25 statements reached an agreement of ≥ 87%, and all nine reporting items reached an agreement of 100%. The Cronbach's alpha increased for each consecutive round (round 1 = .84, round 2 = .87, round 3 = .90, and round 4 = .92). Thus, consensus was reached for all statements and reporting items. CONCLUSION: This Delphi study established the first consensus document on INAA regarding terminology, definition, classification, diagnostic criteria, and algorithm, as well as reporting standards. The results of this study create essential conditions for scientific research on this disease. The presented consensus will need future amendments in accordance with newly acquired knowledge.

Predicting Infection Related Complications After Endovascular Repair of Infective Native Aortic Aneurysms.

OBJECTIVE: Endovascular aortic repair (EVAR) as surgical treatment for infective native aortic aneurysm (INAA) is associated with superior survival compared with open surgery, but with the risk of infection related complications (IRCs). This study aimed to assess the association between baseline clinical and computed tomography (CT) features and the risk of post-operative IRCs in patients treated with EVAR for INAA. It also sought to develop a model to predict long term IRCs in patients with abdominal INAA treated with EVAR. METHODS: All initial clinical details and CT examinations of INAAs between 2005 and 2020 at a major referral hospital were reviewed retrospectively. The images were scrutinised according to aneurysm features, as well as peri-aortic and surrounding organ involvement. Data on post-operative IRCs were found in the patient records. Cox regression analysis was used to derive predictors for IRCs and develop a model to predict five year IRCs after EVAR in abdominal INAA. RESULTS: Of 3 780 patients with the diagnosis of aortic aneurysm or aortitis, 98 (3%) patients were treated with EVAR for abdominal INAAs and were thus included. The mean follow up time was 52 months (range 0 ‒ 163). The mean transaxial diameter was 6.5 ± 2.4 cm (range 2.1 ‒14.7). In the enrolled patients, 38 (39%) presented with rupture. The five year IRC rate in abdominal INAAs was 26%. Female sex, renal insufficiency, positive blood culture, aneurysm diameter, and psoas muscle involvement were predictive of five year IRC in abdominal INAA after EVAR. The model had a C-index of 0.76 (95% CI 0.66 - 0.87). CONCLUSION: Pre-operative clinical and CT features have the potential to predict IRC after endovascular aortic repair in INAA patients. These findings stress the importance of rigorous clinical, laboratory, and radiological follow up in these patients.

HIV-associated infective native aortic aneurysms.

HIV-associated infective native aortic aneurysms (INAA) constitute a subcategory of the disease INAA. This is a very rare group of patients. The aim of this systematic literature review was to compile a description of patient characteristics with HIV-associated INAA. A systematic literature review was performed using the search terms HIV and aortic aneurysm in Ovid MEDLINE and Embase databases, on articles published between 1981 and 2022. Using the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) statement, articles were scrutinized according to a predefined protocol including age, sex, comorbidities, microbiological pathogens, CD4-count, HIV/AIDS state, aortic segment involved, treatment and outcome. Thirty-three studies, all case reports with a total of 39 patients, were included. The median age was 48 years (range 27-79), most were male n = 35 (90%), and the median follow-up was n = 6 months (range 0-63). Cardiovascular comorbidity was present in n = 1 (3%), median CD4-count was 216 (range 6-1236), and n = 12 (31%) had AIDS. The most common microbiological pathogens were Treponema pallidum, n = 12 (31%), Salmonella spp. n = 10 (26%), Mycobacterium species n = 5 (12%) and Staphylococcal spp. n = 5 (13%). The HIV-associated INAAs were localized in the abdominal aorta n = 32 (82%), in the thoracic aorta n = 5 (13%) and in the thoraco-abdominal aorta n = 2 (5%). Open surgery was performed in n = 23 (59%) patients, endovascular aortic repair n = 6 (15%), and n = 7 (18%) did not receive surgery. Infection-related complications were reported in n = 2 (7%) patients, both with postoperative development of fatal sepsis. Patients with HIV-associated INAAs were younger, had lower rate of cardiovascular comorbidity, demonstrated low CD4 counts as a measure of immunosuppression, and demonstrated diverse microbiological pathogens compared with other INAAs. Treponema pallidum and Mycobacterium spp. were common pathogens, which are very rare microbiological pathogens in other INAAs.

Complex Endovascular Repair of Paravisceral Infective Native Aortic Aneurysms.

OBJECTIVE: To report the early and mid-term outcome of complex endovascular repair (EVAR) for paravisceral infective native aortic aneurysms (INAA). METHODS: Interrogation of a prospectively maintained database identified consecutive patients who underwent non-elective complex EVAR for paravisceral INAAs in a single institution between December 2013 and June 2020. All patients were considered to have definite INAAs based on diagnostic criteria. Patients who had prior aortic repair were excluded. RESULTS: A total of 26 patients (19 men; mean age 67 years [SD = 11.4]; median diameter 60 mm [IQR: 55-73]) with acute symptomatic (n = 24) or contained ruptured (n = 2) aneurysms underwent surgeon-modified fenestrated EVAR (SM-FEVAR; n = 24) or chimney-periscope EVAR (CHIMPS; n = 2). Median observed follow-up was 36.2 months (18.3-53.5). Nine patients had positive venous blood cultures and a further seven had recent or concomitant infection. All patients received pre- and post-operative antibiotic therapy and rifampicin-soaked endografts. A total of 95 vessels were targeted for preservation and 86 were stent-grafted. One vessel occluded intra-operatively and a further 3 occluded within 30 days. The 30-day/in-hospital mortality was 11.5% (n = 3), and the estimated 1- and 3-year survival (±SD) was 85% ± 7%. Infection-related complications (IRCs) occurred in two patients: both developed new INAA within 30 days of index repair and were treated by EVAR with no mortality. Estimated 3-year freedom from late re-intervention was 100%. One patient required infrarenal EVAR for a non-infective aneurysm at 43 months. CONCLUSION: Complex EVAR for paravisceral INAAs is associated with acceptable early and mid-term outcomes and is an acceptable alternative to open surgery. We propose that these patients are managed with long-term antimicrobials, impregnation of graft material with rifampicin, and rigorous post-operative surveillance. CLINICAL IMPACT: A multi-disciplinary approach is required to deliver the best possible outcome for patients with this challenging aortic pathology.

Features of infective native aortic aneurysms on computed tomography.

BACKGROUND: Infective native aortic aneurysm (INAA) is a rare clinical diagnosis. The purpose of this study was to describe the CT findings of INAAs in detail. METHODS: This was a retrospective single-center study of INAA patients at a major referral hospital between 2005 and 2020. All images were reviewed according to a protocol consisting of aneurysm features, periaortic findings, and associated surrounding structures. RESULTS: One hundred and fourteen patients (mean age, 66 years [standard deviation, 11 years]; 91 men) with 132 aneurysms were included. The most common locations were infrarenal (50.8%), aortoiliac (15.2%), and juxtarenal (12.9%). The mean transaxial diameter was 6.2 cm. Most INAAs were saccular (87.9%) and multilobulated (91.7%). Calcified aortic plaque was present in 93.2% and within the aneurysm in 51.5%. INAA instability was classified as contained rupture (27.3%), impending rupture (26.5%), and free rupture (3.8%). Rapid expansion was demonstrated in 13 of 14 (92.9%) aneurysms with sequential CT studies. Periaortic inflammation was demonstrated as periaortic enhancement (94.7%), fat stranding (93.9%), soft-tissue mass (92.4%), and lymphadenopathy (62.1%). Surrounding involvement included psoas muscle (17.8%), spondylitis (11.4%), and perinephric region (2.8%). Twelve patients demonstrated thoracic and abdominal INAA complications: fistulas to the esophagus (20%), bronchus (16%), bowel (1.9%), and inferior vena cava (IVC) (0.9%). CONCLUSION: The most common CT features of INAA were saccular aneurysm, multilobulation, and calcified plaques. The most frequent periaortic findings were enhancement, fat stranding, and soft-tissue mass. Surrounding involvement, including psoas muscle, IVC, gastrointestinal tract, and bronchi, was infrequent but may develop as critical INAA complications.

The Microbiology of Infective Native Aortic Aneurysms in a Population-Based Setting.

OBJECTIVE: The aim was to describe the microbiology of surgically treated infective native (mycotic) aortic aneurysms (INAAs), and associated survival and development of infection-related complications (IRCs). METHODS: Data were pooled from 2 nationwide studies on surgically treated patients with INAAs in Sweden, between 1994 - 2016. Patients were grouped and analyzed according to culture results: 1) Staphylococcus aureus, 2) Streptococcus species (sp.), 3) Salmonella sp., 4) Enterococcus sp., 5) Gram-negative intestinal bacteria, 6) Other sp. (all other species found in culture), and 7) Negative cultures. RESULTS: A sum of 182 patients were included, mean age 71 years (standard deviation; SD: 8.9). The median follow-up was 50.3 months (range 0 - 360). 128 (70.3%) patients had positive blood and/or tissue culture; Staphylococcus aureus n = 38 (20.9%), Streptococcus sp. n = 37 (20.3%), Salmonella sp. n = 19 (10.4%), Enterococcus sp. n = 16 (8.8%), Gram-negative intestinal bacteria n = 6, (3.3%), Other sp. n = 12 (6.6%) and Negative cultures n = 54 (29.7%). The estimated survival for the largest groups at 2-years after surgery was: Staphylococcus aureus 62% (95% Confidence interval 53.9 - 70.1), Streptococcus sp. 74.7% (67.4 - 82.0), Salmonella sp. 73.7% (63.6 - 83.8), Enterococcus sp. 61.9% (49.6 - 74.2), and Negative cultures 89.8% (85.5 - 94.1), P = .051. There were 37 IRCs (20.3%), and 19 (51.4%) were fatal, the frequency was insignificant between the groups. The majority of IRCs, 30/37 (81%), developed during the first postoperative year. CONCLUSION: In this assessment of microbiological findings of INAAs in Sweden, 50% of the pathogens were Staphylococcus aureus, Streptococcus sp., or Salmonella sp.. The overall 20%-frequency of IRCs, and its association with high mortality, motivates long-term antibiotic treatment regardless of microbial findings.