Harnessing large language models (LLMs) for candidate gene prioritization and selection.

BACKGROUND: Feature selection is a critical step for translating advances afforded by systems-scale molecular profiling into actionable clinical insights. While data-driven methods are commonly utilized for selecting candidate genes, knowledge-driven methods must contend with the challenge of efficiently sifting through extensive volumes of biomedical information. This work aimed to assess the utility of large language models (LLMs) for knowledge-driven gene prioritization and selection. METHODS: In this proof of concept, we focused on 11 blood transcriptional modules associated with an Erythroid cells signature. We evaluated four leading LLMs across multiple tasks. Next, we established a workflow leveraging LLMs. The steps consisted of: (1) Selecting one of the 11 modules; (2) Identifying functional convergences among constituent genes using the LLMs; (3) Scoring candidate genes across six criteria capturing the gene's biological and clinical relevance; (4) Prioritizing candidate genes and summarizing justifications; (5) Fact-checking justifications and identifying supporting references; (6) Selecting a top candidate gene based on validated scoring justifications; and (7) Factoring in transcriptome profiling data to finalize the selection of the top candidate gene. RESULTS: Of the four LLMs evaluated, OpenAI's GPT-4 and Anthropic's Claude demonstrated the best performance and were chosen for the implementation of the candidate gene prioritization and selection workflow. This workflow was run in parallel for each of the 11 erythroid cell modules by participants in a data mining workshop. Module M9.2 served as an illustrative use case. The 30 candidate genes forming this module were assessed, and the top five scoring genes were identified as BCL2L1, ALAS2, SLC4A1, CA1, and FECH. Researchers carefully fact-checked the summarized scoring justifications, after which the LLMs were prompted to select a top candidate based on this information. GPT-4 initially chose BCL2L1, while Claude selected ALAS2. When transcriptional profiling data from three reference datasets were provided for additional context, GPT-4 revised its initial choice to ALAS2, whereas Claude reaffirmed its original selection for this module. CONCLUSIONS: Taken together, our findings highlight the ability of LLMs to prioritize candidate genes with minimal human intervention. This suggests the potential of this technology to boost productivity, especially for tasks that require leveraging extensive biomedical knowledge.

Complex relationships between inflammatory manifestations/type 1 and type 2 symptoms in systemic lupus erythematosus: A narrative literature review.

OBJECTIVE: Recent studies have highlighted that systemic lupus erythematosus (SLE) is characterized by different types of symptoms: type 1 symptoms related to inflammation and disease activity and type 2 symptoms such as fatigue, anxiety-depression, and pain. Our aim was to investigate the relation between type 1 and type 2 symptoms, and their impact on health-related quality of life (HRQoL) in SLE. METHODS: A literature review was conducted about disease activity/type1 and type 2 symptoms. Articles in English published after 2000 were located on Medline via Pubmed. The articles chosen evaluated at least one type 2 symptom or HRQoL using a validated scale in adult patients. RESULTS: Overall, 182 articles were analyzed and 115 were retained including 21 randomized, controlled trials and corresponding to 36 831 patients. We found that in SLE, inflammatory activity/type 1 symptoms were mostly uncorrelated with type 2 symptoms and/or HRQoL. Several studies even showing an inverse relationship. No or weak correlation was observed in 85, 3% (92, 6%), 76, 7% (74, 4%) and 37, 5% (73, 1%) of studies (patients) for fatigue, anxiety-depression, and pain, respectively. For HRQoL, no or weak correlation was observed in 77, 5% of studies (88% of patients). CONCLUSION: Type 2 symptoms are poorly correlated with inflammatory activity/type 1 symptoms in SLE. Possible explanations and implications for clinical care and therapeutic evaluation are discussed.

Mast cells drive pathologic vascular lesions in Takayasu arteritis.

BACKGROUND: Takayasu arteritis (TAK) is a large vessel vasculitis resulting in artery wall remodeling with segmental stenosis and/or aneurysm formation. Mast cells (MCs) are instrumental in bridging cell injury and inflammatory response. OBJECTIVES: This study sought to investigate the contribution of MCs on vessel permeability, angiogenesis, and fibrosis in patients with TAK. METHODS: MC activation and their tissue expression were assessed in sera and in aorta from patients with TAK and from healthy donors (HDs). In vivo permeability was assessed using a modified Miles assay. Subconfluent cultured human umbilic vein endothelial cells and fibroblasts were used in vitro to investigate the effects of MC mediators on angiogenesis and fibrogenesis. RESULTS: This study found increased levels of MC activation markers (histamine and indoleamine 2,3-dioxygenase) in sera of patients with TAK compared with in sera of HDs. Marked expression of MCs was shown in aortic lesions of patients with TAK compared with in those of noninflammatory aorta controls. Using Miles assay, this study showed that sera of patients with TAK significantly increased vascular permeability in vivo as compared with that of HDs. Vessel permeability was abrogated in MC-deficient mice. MCs stimulated by sera of patients with TAK supported neoangiogenesis (increased human umbilic vein endothelial cell proliferation and branches) and fibrosis by inducing increased production of fibronectin, type 1 collagen, and α-smooth muscle actin by fibroblasts as compared to MCs stimulated by sera of HD. CONCLUSIONS: MCs are a key regulator of vascular lesions in patients with TAK and may represent a new therapeutic target in large vessel vasculitis.

Cerebrovascular Ischemic Events in Patients With Takayasu Arteritis.

BACKGROUND: Takayasu arteritis (TA) is a large vessel vasculitis that may complicate with cerebrovascular ischemic events. The objective was to describe clinical and vascular features of TA patients with cerebrovascular ischemic events and to identify risk factors for these events. METHODS: We analyzed the prevalence and type of stroke/transient ischemic attack (TIA), factors associated with cerebrovascular ischemic events, and stroke-free survival in a large cohort fulfilling the American College of Rheumatology or Ishikawa criteria of TA. RESULTS: Among 320 patients with TA (median age at diagnosis, 36 [25-47] years; 261 [86%] women), 63 (20%) had a stroke (n=41; 65%) or TIA (n=22; 35%). Ischemic event localized in the carotid territory for 55 (87%) patients and the vertebral artery territory in 8 (13%) patients. Multiple stenosis were observed in 33 (52%) patients with a median number of stenosis of 2 (minimum, 0 to maximum, 11), and aneurysms were observed in 10 (16%) patients. A history of stroke or TIA before TA diagnosis (hazard ratio [HR], 4.50 [2.45-8.17]; P<0.0001), smoking (HR, 1.75 [1.01-3.02]; P=0.05), myocardial infarction history (HR, 0.21 [0.05-0.89]; P=0.039), thoracic aorta involvement (HR, 2.05 [1.30-3.75]; P=0.023), time from first symptoms to diagnosis >1 year (HR, 2.22 [1.30-3.80]; P=0.005), and aspirin treatment (HR, 1.82 [1.04-3.19]; P=0.035) were associated with cerebrovascular ischemic event. In multivariate analysis, time from first symptoms to TA diagnosis >1 year (HR, 2.16 [1.27-3.70]; P=0.007) was independently associated with cerebrovascular ischemic events in patients with TA. The HR for cerebrovascular ischemic event in patients who already experienced a stroke/TIA was 5.11 (2.91-8.99; P<0.0001), compared with those who had not. CONCLUSIONS: Carotid stroke/TIA is frequent in TA. We identified factors associated with cerebrovascular ischemic events.

Weaning of maintenance immunosuppressive therapy in lupus nephritis (WIN-Lupus): results of a multicentre randomised controlled trial.

OBJECTIVES: Lupus nephritis (LN) is a frequent complication of systemic lupus erythematosus (SLE). Severe (proliferative) forms of LN are treated with induction immunosuppressive therapy (IST), followed by maintenance IST, to target remission and avoid relapses. The optimal duration of maintenance IST is unknown. The WIN-Lupus trial tested whether IST discontinuation after 2‒3 years was non-inferior to IST continuation for two more years in proliferative LN. METHODS: WIN-Lupus was an investigator-initiated multicentre randomised controlled trial. Patients receiving maintenance IST with azathioprine or mycophenolate mofetil for 2-3 years, and hydroxychloroquine, were randomised (1:1) into two groups: (1) IST continuation and (2) IST discontinuation. The primary endpoint was the relapse rate of proliferative LN at 24 months. Main secondary endpoints were the rate of severe SLE flares, survival without renal relapse or severe flare, adverse events. RESULTS: Between 2011 and 2016, 96 patients (out of 200 planned) were randomised in WIN-Lupus: IST continuation group (n=48), IST discontinuation group (n=48). Relapse of proliferative LN occurred in 5/40 (12.5%) patients with IST continuation and in 12/44 (27.3%) patients with IST discontinuation (difference 14.8% (95% CI -1.9 to 31.5)). Non-inferiority was not demonstrated for relapse rate; time to relapse did not differ between the groups. Severe SLE flares (renal or extrarenal) were less frequent in patients with IST continuation (5/40 vs 14/44 patients; p=0.035). Adverse events did not differ between the groups. CONCLUSIONS: Non-inferiority of maintenance IST discontinuation after 2‒3 years was not demonstrated for renal relapse. IST discontinuation was associated with a higher risk of severe SLE flares. TRIAL REGISTRATION NUMBER: NCT01284725.

Importance of temporality and context in relation to life habit restrictions among patients with systemic lupus erythematosus: A psychosocial qualitative study.

OBJECTIVE: Life habits (LH) encompass an individual's engagement in daily activities such as nutrition, fitness, personal care, communication, housing, and mobility, along with his/her social role (responsibility, interpersonal relationships, community life, education, employment, and recreation). This qualitative study explores the nature and context of LH restrictions in systemic lupus erythematosus (SLE) individuals across their SLE journey. METHODS: Narrative interviews were conducted with adult SLE patients. Interview transcripts were subjected to a thematic content analysis, using the Disability Creation Process model as a framework. RESULTS: Forty participants were interviewed. Three major themes were highlighted: (1) Temporality, capabilities, and environmental contexts: although all participants experienced LH restrictions at some point, the expression of these limitations depended on the individual's and SLE disease characteristics as well as on temporal (time of life and lupus course) and environmental (material, social, and societal) contexts. (2) Identity issues, illness stigma, and (fear of) discriminations: LH were discussed through the lens of participants' social roles and identities. While illness stigma can influence social relations, it is also expressed at a societal level. (3) Masking and minimizing strategies: due to illness stigma and fear of discrimination, participants developed strategies to manage their relationships, including masking and minimization. Their use was both advantageous and disadvantageous regarding LH. CONCLUSIONS: For individuals with SLE, LH restrictions must be considered as an ongoing process that takes place within specific contexts. Our findings provide many opportunities for interventions that can benefit patients and their families, as well as healthcare providers.

Aortitis is an under-recognized manifestation of antiphospholipid syndrome: A case report and literature review.

Aortitis is a classic manifestation of large vessel vasculitis. Antiphospholipid syndrome (APS), sometimes known as Hughes syndrome, is an acquired autoimmune disorder that manifests clinically as recurrent venous or arterial thrombosis. Patients with APS may also suffer from various underlying diseases, most frequently systemic lupus erythematosus (SLE). Catastrophic antiphospholipid syndrome (CAPS) is a rare but serious complication of APS characterized by failure of several organs due to diffuse microcirculatory thrombi. Its main manifestations involve the kidneys, lungs, heart and central nervous system, and require early diagnosis and rapid therapeutic management. While APS can affect virtually any blood vessel, aortitis is not a known symptom of APS. We report the case of a 36-year-old patient with APS and SLE who presented with CAPS during pregnancy, with no concomitant SLE flare. The first manifestation of CAPS was aortitis, preceding renal, cardiac and haematological manifestations. The outcome was favourable with combined treatment including corticosteroids, anticoagulants, plasma exchange and rituximab. We then carried out a literature search for papers describing the presence of aortitis in APS and/or SLE. In the cases of aortic involvement identified in the literature, including another case of CAPS, the occurrence of aortitis in SLE, often associated with the presence of antiphospholipid antibodies/APS, suggests that aortitis should be considered as an under-recognized manifestation and potential non-criterion feature of APS.

Mycotic/Infective Native Aortic Aneurysms: Results After Preferential Use of Open Surgery and Arterial Allografts.

OBJECTIVE: Mycotic/infective native aortic aneurysms (INAA) are managed heterogeneously. In the context of disparate literature, this study aimed to assess the outcomes of INAA surgical management and provide comprehensive data in alignment with recent suggestions for reporting standards. METHODS: A retrospective review of patients presenting with INAA from September 2002 to March 2020 at two institutions was conducted. In hospital mortality, 90 day mortality, overall mortality, and infection related complications (IRCs) were the study endpoints. Overall survival and IRC free survival were estimated, and predictors of mortality tested using uni- and multivariable analyses. RESULTS: Seventy patients (60 men [86%], median age 68 years [range 59 - 76 years]) were included. Twenty (29%) were ruptured at presentation. INAA location was thoracic in 11 (16%) cases, thoraco-abdominal in seven (10%), and abdominal in 50 (71%). Half of the abdominal INAAs were suprarenal. Two INAAs were concomitantly abdominal and thoracic. Pathogens were identified in 83%. The bacterial spectrum was scattered, with rare Salmonella species (n = 6; 9%). Open surgical repair was performed in 66 (94%) patients, including five conversions of initially attempted endovascular grafts (EVAR), three hybrid procedures, and one palliative EVAR. Vascular substitutes were cryopreserved arterial allografts (n = 67; 96%), prosthesis (n = 2), or femoral veins (n = 1). Kaplan-Meier estimates of overall survival at 30 and 90 days were 87% (95% confidence interval [CI] 76.6 - 93.0) and 71.7% (95% CI 59.2 - 80.9), respectively. The overall in hospital mortality rate was 27.9% (95% CI 1.8 - 66.5). IRCs occurred in seven (10%) patients. The median follow up period was 26.5 months (range 13.0-66.0 months). Chronic kidney disease (CKD) was independently related to in hospital mortality (odds ratio [OR] 20.7, 95% CI 1.8 - 232.7). American Society of Anesthesiologists score of 3 (OR 6.0, 95% CI 1.1 - 33.9), 4 (OR 14.9, 95% CI 1.7 - 129.3), and CKD (OR 32.0, 95% CI 1.2 - 821.5) were related to 90 day mortality. CONCLUSION: Surgical INAA management has significant mortality and a low re-infection rate. EVAR necessitated secondary open repair, but its limited use in this report did not allow conclusions to be drawn.

Intraoperative Mapping Angiograms of the Parathyroid Glands Using Indocyanine Green During Thyroid Surgery: Results of the Fluogreen Study.

BACKGROUND: During thyroid surgery, preservation of parathyroid gland (PG) feeding vessels is often impossible. The aim of the Fluogreen study was to determine the feasibility of using indocyanine green (ICG)-based intraoperative mapping angiograms of the PG (iMAP) to improve vascular preservation. STUDY DESIGN: This prospective study enrolled all patients undergoing thyroid lobectomy or total thyroidectomy at the Hôpital Européen Marseille between September and December 2018. After exploring the thyroid lobe by autofluorescence to locate the PGs, ICG solution was injected intravenously to locate the PG feeding vessels and guide dissection. A second ICG injection was administered at the end of the lobectomy to assess perfusion of the PGs. The primary outcome was the quality of the angiogram, scaled as iMAP 0 (not informative), iMAP 1 (general vascular pattern visible but no clear vascular pedicle flowing into the PG), or iMAP 2 (clear vascular pedicle flowing into the PG). The secondary outcome was the PG perfusion score at the end of surgery, scaled from ICG 0 (no perfusion) to ICG 2 (intense uptake). RESULTS: A total of 47 adult patients were analyzed, including 34 total thyroidectomies and 13 lobectomies. ICG angiography assessed 76 PGs, which were scored as iMAP 2 in 24 cases (31.6%), iMAP 1 in 46 (60.5%) and iMAP 0 in six (7.9%). At the end of dissection, the ICG perfusion score was significantly better for the PGs with informative angiography (iMAP 1 or 2), than for the PGs with uninformative angiography (iMAP 0), or the PGs not evaluated by vascular angiography (p < 0.05). CONCLUSION: iMAP is feasible and provides direct vascular information in one-third of the cases. Further improvements to this technology are necessary, and the influence of this technique on patient outcomes during thyroidectomy will need to be further evaluated.

Thrombosis of Medium-Sized and Large Arteries During Covid-19 Infection: Results of the COVIVASC Study.

BACKGROUND: COVID-19 infection is associated not only with venous thromboses but also with arterial thromboses (COV-ATs) in relation with an endothelial dysfunction, a coagulopathy and rhythm disorders. The incidence, the topography, and the prognosis of COV-ATs remain poorly known. The objective of this study was to report the overall experience of the Greater Paris University Hospitals (Assistance Publique - Hopitaux de Paris, AP-HP) during the first pandemic wave of COVID-19 infection. METHODS: After approval by the ethics committee, a study using the AP-HP clinical data warehouse was carried out between March and May 2020. Overall, 124,609 patients had a polymerase chain reaction for COVID-19 in our hospitals, of which 25,345 were positive. From 20,710 exploitable stays, patients tested positive for COVID who presented an episode of acute COV-AT (except coronary and intracranial arteries) were selected on the basis of the French medical classification for clinical procedures codes. The data are presented as absolute values with percentages and/or means with standard deviation. RESULTS: Over the studied period, 60 patients (aged 71±14 years, 42 men) presented a COV-AT at the time of their hospitalization, an incidence of 0.2%. The arterial complication occurred 3±7 days after the COVID infection and was inaugural in 30% of the cases (n = 18). The sites of COV-AT were the lower extremities (n = 35%, 58%), the abdominal aorta (n = 10%, 17%), the thoracic aorta (n = 7%, 12%), the upper limbs (n = 7%, 12%), the cerebral arteries (n = 7%, 12%), the digestive arteries (n = 6%, 10%), the renal arteries (n = 2%, 3%), and the ophthalmic artery (n = 1%, 2%). Multiple COV-ATs were observed in 13 patients (22%). At the time of diagnosis, 20 (33%) patients were in intensive care, including six (10%) patients who were intubated. On computed tomography angiography, COVID lesions were classified as moderate and severe in 25 (42%) and 21 (35%) cases, respectively. Revascularization was attempted in 27 patients (45%), by open surgery in 16 cases, using endovascular techniques in 8 cases and with a hybrid approach in three cases. Six patients (22%) required reinterventions. The duration of hospitalization was 12±9 days. Early mortality (in-hospital or at 30 days) was 30% (n = 18). Nine (15%) patients presented severe nonlethal ischemic complications. CONCLUSIONS: Arterial involvement is rare during COVID-19 infection. The aorta and the arteries of the limbs are the privileged sites. The morbi-mortality of these patients is high. Future studies will have to determine if the systematization of anticoagulation therapy decreases the incidence and the severity of the condition.

Effect of Tocilizumab on Disease Activity in Patients With Active Polymyalgia Rheumatica Receiving Glucocorticoid Therapy: A Randomized Clinical Trial.

Importance: Few treatments are available for patients with glucocorticoid-dependent polymyalgia rheumatica. IL-6 antagonists may reduce disease activity in patients with active glucocorticoid-dependent polymyalgia rheumatica. Objective: To compare the efficacy of tocilizumab vs placebo in patients with glucocorticoid-dependent polymyalgia rheumatica. Design, Setting, and Participants: This double-blind, parallel-group, placebo-controlled randomized clinical trial enrolled 101 patients with polymyalgia rheumatica at 17 hospitals in France from February 2017 to October 2019. Final follow-up occurred in November 2020. Inclusion criteria were persistent disease activity (polymyalgia rheumatica activity score computed using the C-reactive protein level [CRP PMR-AS] >10) and prednisone dose greater than or equal to 10 mg per day. Interventions: Patients were randomly assigned to receive intravenous tocilizumab (8 mg/kg; n = 51) or placebo (n = 50) every 4 weeks for 24 weeks, combined with predefined standardized tapering of oral prednisone. Main Outcomes and Measures: The primary efficacy end point was CRP PMR-AS less than 10 (range, 0-100; higher values indicate greater activity; no minimal clinically important difference defined) combined with either prednisone dose less than or equal to 5 mg per day or a decrease in prednisone dose greater than or equal to 10 mg from baseline at week 24. There were 11 secondary outcomes assessed at week 24 included in this report, including disease activity (measured by CRP PMR-AS) and the proportion of patients no longer taking prednisone. Results: Of the 101 randomized patients (mean age, 67.2 years; 68 [67.3%] women), 100 (99%) received at least 1 infusion and 100 completed the trial. The primary end point was achieved in 67.3% of patients in the tocilizumab group and 31.4% of patients in the placebo group (adjusted difference, 36.0% [95% CI, 19.4%-52.6%]; adjusted relative risk, 2.3 [95% CI, 1.5-3.6]; P < .001). Of 11 reported secondary end points at 24 weeks, 7 showed significant differences favoring tocilizumab, including mean CRP PMR-AS score (7.5 [95% CI, 5.4-9.6] vs 14.9 [95% CI, 11.4-18.4]; adjusted difference, -7.5 [95% CI, -11.2 to -3.8]; P < .001) and the percentage of patients no longer receiving prednisone (49.0% vs 19.6%; adjusted difference, 29.3% [95% CI, 18.9%-39.7%]; adjusted relative risk, 2.5 [95% CI, 1.8-3.5]; P < .001). The most frequent adverse events were infections, experienced by 23 patients (46.9%) in the tocilizumab group and 20 (39.2%) in the placebo group. Conclusions and Relevance: Among patients with active polymyalgia rheumatica despite prednisone therapy, tocilizumab, compared with placebo, resulted in a significantly greater percentage of patients with a CRP PMR-AS less than 10 with reduced prednisone requirements at week 24. Further research is needed to confirm efficacy and to determine the balance of potential benefits and harms. Trial Registration: ClinicalTrials.gov Identifier: NCT02908217.

Influence of the transcription factor RORgammat on the development of NKp46+ cell populations in gut and skin.

NKp46+CD3- natural killer lymphocytes isolated from blood, lymphoid organs, lung, liver and uterus can produce granule-dependent cytotoxicity and interferon-gamma. Here we identify in dermis, gut lamina propria and cryptopatches distinct populations of NKp46+CD3- cells with a diminished capacity to degranulate and produce interferon-gamma. In the gut, expression of the transcription factor RORgammat, which is involved in the development of lymphoid tissue-inducer cells, defined a previously unknown subset of NKp46+CD3- lymphocytes. Unlike RORgammat- lamina propria and dermis natural killer cells, gut RORgammat+NKp46+ cells produced interleukin 22. Our data show that lymphoid tissue-inducer cells and natural killer cells shared unanticipated similarities and emphasize the heterogeneity of NKp46+CD3- cells in innate immunity, lymphoid organization and local tissue repair.

Results of cryopreserved arterial allograft replacement for thoracic and thoracoabdominal aortic infections.

BACKGROUND: Primary and secondary thoracic aortic infections are rare but associated with high morbidity and mortality. There is currently no consensus on their optimal treatment. Arterial allografts have been shown to be resistant to bacterial colonization. Complete excision of infected material, especially synthetic grafts, combined with in situ aortic repair is considered the best treatment of abdominal aortic infections. The aim of this study was to assess the management of thoracic and thoracoabdominal aortic infections using arterial allografts. METHODS: Between January 2009 and December 2017, all patients with thoracic and thoracoabdominal aortic native or graft infections underwent complete excision of infected material and in situ arterial allografting. The end points were the early mortality and morbidity rates and early and late rates of reinfection, graft degeneration, and graft-related morbidity. RESULTS: Thirty-five patients with a mean age of 65.6 ± 9.2 years were included. Twenty-one (60%) cases experienced graft infections and 14 (40%) experienced native aortic infections. Eight (22.8%) patients had visceral fistulas: 5 (14.4%) prosthetic-esophageal, 1 (2.8%) prosthetic-bronchial, 1 (2.8%) prosthetic-duodenal, and 1 (2.8%) native aortobronchial. In 12 (34.3%) cases, only the descending thoracic aorta was involved; in 23 (65.7%) cases, the thoracoabdominal aorta was involved. Fifteen (42.8%) patients died during the first month or before discharge: 5 of hemorrhage, 4 of multiorgan failure, 3 of ischemic colitis, 2 of pneumonia, and 1 of anastomotic disruption. Eleven (31.5%) patients required early revision surgery: 6 (17.1%) for nongraft-related hemorrhage, 3 (8.6%) for colectomy, 1 (2.9%) for proximal anastomotic disruption, and 1 (2.9%) for tamponade. One (2.9%) patient who died before discharge experienced paraplegia. One (2.9%) patient experienced stroke. Six (17.1%) patients required postoperative dialysis. Among them, four died before discharge. The mean length of stay in the intensive care unit was 11 ± 10.5 days; the mean length of hospital stay was 32 ± 14 days. During a mean follow-up of 32.3 ± 23.7 months, three allograft-related complications occurred in survivors (15% of late survivors): one proximal and one distal false aneurysm with no evidence of reinfection and one allograft-enteric fistula. The 1-year and 2-year survival rates were 49.3% and 42.5%, respectively. CONCLUSIONS: Although rare, aortic infections are highly challenging. Surgical management includes complete excision of infected tissues or grafts. Allografts offer a promising solution to aortic graft infection because they appear to resist reinfection; however, the grafts must be observed indefinitely because of the risk of late graft complications.

Unsupervised clustering analysis of data from an online community to identify lupus patient profiles with regards to treatment preferences.

OBJECTIVE: Lupus is a chronic complex autoimmune disease. Non-adherence to treatment can affect patient outcomes. Considering patients' preferences into medical decisions may increase acceptance to their medication. The PREFERLUP study used unsupervised clustering analysis to identify profiles of patients with similar treatment preferences in an online community of French lupus patients. METHODS: An online survey was conducted in adult lupus patients from the Carenity community between August 2018 and April 2019. Multiple Correspondence Analysis (MCA) was used with three unsupervised clustering methods (hierarchical, kmeans and partitioning around medoids). Several indicators (measure of connectivity, Dunn index and Silhouette width) were used to select the best clustering algorithm and choose the number of clusters. RESULTS: The 268 participants were mostly female (96%), with a mean age of 44.3 years 83% fulfilled the American College of Rheumatology (ACR) self-reported diagnostic criteria for systemic lupus erythematosus. Overall, the preferred route of administration was oral (62%) and the most important feature of an ideal drug was a low risk of side-effects (32%). Hierarchical clustering identified three clusters. Cluster 1 (59%) comprised patients with few comorbidities and a poor ability to identify oncoming flares; 84% of these patients desired oral treatments with limited side-effects. Cluster 2 (13%) comprised younger patients, who had already participated in a clinical trial, were willing to use implants and valued the compatibility of treatments with pregnancy. Cluster 3 (28%) comprised patients with a longer lupus duration, poorer control of the disease and more comorbidities; these patients mainly valued implants and injections and expected a reduction of corticosteroid intake. CONCLUSIONS: Different profiles of lupus patients were identified according to their drug preferences. These clusters could help physicians tailor their therapeutic proposals to take into account individual patient preferences, which could have a positive impact on treatment acceptance and then adherence. The study highlights the value of data acquired directly from patient communities.

Short and Mid Term Outcomes of Cryopreserved Abdominal Aortic Allografts Used as a Substitute for Infected Prosthetic Grafts in 200 Patients.

OBJECTIVE: To investigate the use of cryopreserved arterial allografts (CAA) as a substitute for infected infrarenal aortic prostheses, and its outcomes. METHODS: A single centre retrospective study of consecutive patients receiving an abdominal aortic CAA after removal of an infected graft was conducted between January 1997 and December 2013. The primary outcome was the rate of allograft related revision surgery. Secondary outcomes were the 30 day mortality rate, survival, primary patency, limb salvage, and infection recurrence. Allograft ruptures secondary to infection and risk factors for allograft failure were also investigated. RESULTS: Two hundred patients (mean age 64.2 ± 9.4 years) were included. In 56 (28%) cases, infection was related to an enteric fistula. The mean follow up duration was 4.1 years. The 30 day mortality rate was 11%. Early revision surgery was needed in 59 patients (29.5%). Among them, 15 (7.5%) were allograft related and led to the death of three patients (1.5%), corresponding to a 7.5% 30 day allograft related revision surgery rate. During the first six months, 17 (8.5%) patients experienced 21 events with complete or partial rupture (pseudo-aneurysm) of the allograft responsible for five (2.5%) deaths, corresponding to a re-infection rate of 8.5%. The multivariable analysis showed that diabetes and pseudo-aneurysm of the native aorta on presentation were predictive factors for short term allograft rupture. After six months, 25 (12.5%) patients experienced long term allograft complications (rupture, n = 2, 1%; pseudo-aneurysm, n = 6, 3%; aneurysm, n = 2, 1%; thrombosis, n = 11, 5.5%; stenosis, n = 4, 2%;) requiring revision surgery resulting in one death. The five year rates of survival, allograft related revision surgery, limb salvage, primary patency, and infection recurrence were 56%, 30%, 89%, 80%, and 12%, respectively. CONCLUSION: CAAs provide acceptable results to treat aortic graft infection with few early graft related fatal complications. Long term allograft related complications are quite common but are associated with low mortality and amputation rates.

Position Paper on Young Vascular Surgeons Training of the Mediterranean Federation for the Advancing of Vascular Surgery (MeFAVS): State of the Art and Perspectives.

The Mediterranean Federation for the Advancing of Vascular Surgery (MeFAVS) was founded in 2018, with the aim to promote cooperation among vascular professionals within Mediterranean countries. Due to its prominent social and economic impact on national health systems, diabetic peripheral artery was selected as the very first topic to be investigated by the federation. In this second paper, different experiences from delegates of participating countries were shared to define common strategies to harmonize, standardize, and optimize education and training in the Vascular Surgery specialty.

Paradoxical association between blood modular interferon signatures and quality of life in patients with systemic lupus erythematosus.

OBJECTIVES: Blood transcriptomic IFN signature is a hallmark of SLE. The impaired health-related quality of life (HRQOL) observed in SLE is poorly related to disease activity. The aim of this study was to test how IFN signatures were associated with HRQOL in SLE patients. METHODS: Among consecutive patients, blood transcriptomic profiles were analysed with a modular framework comprising 3 IFN modules: M1.2, M3.4 and M5.12. Disease activity was evaluated by the SLEDAI score, and HRQOL was assessed with the SF-36 questionnaire, which includes eight domains: physical function, role physical, bodily pain, general health, vitality, social functioning, role emotional, and mental health (MH) and physical component summary and mental component summary scores. RESULTS: A total of 57 SLE patients were evaluated, among whom 27 (47%) were clinically quiescent, 30 (53%) were flaring, and 19 (33%) had active lupus nephritis. All SF-36 domains were altered in SLE patients compared with the general French population (P < 0.0001). In multivariate analysis, taking into account flares, age, ethnicity, smoking and renal severity, social functioning was independently associated with the IFN score (P = 0.027). Analyses restrained to quiescent patients (n = 27) yielded greater associations between social functioning and the three IFN modules, and between MH and M3.4. Considering all quiescent visits (n = 51), the IFN score was independently correlated with social functioning (P = 0.022) and MH (P = 0.038). CONCLUSION: This unexpected paradoxical association between IFN signature and some specific HRQOL domains argues against a pivotal role of IFNs in the persistently altered HRQOL of SLE patients.

Factors influencing the recurrence of arterial involvement after surgical repair in Behçet disease.

OBJECTIVE: Arterial involvement in Behçet disease (BD) is rare, and its surgical management is a major concern because of its high recurrence rate. This study evaluated the influence of the surgical technique, device, and immunosuppressive treatment used on the postoperative recurrence in patients with non-pulmonary arterial BD. METHODS: A single-center, retrospective study was conducted of 23 patients meeting the international criteria for BD who underwent surgery for arterial involvement between May 1996 and September 2015. Recurrence was defined as the occurrence of arterial aneurysm or thrombosis during follow-up. Perioperative medical treatment and surgical technique used were reported. RESULTS: There were 47 surgical procedures performed in 23 patients. Mean follow-up was 8.4 ± 7.5 years. Initial arterial lesions were aneurysms and thrombosis in 85% and 15% of cases, respectively. Arterial lesions were aortic and peripheral in 48% and 52% of cases. Recurrence rate was 51%. Recurrences developed within <1 year in 24% of cases and at the same anatomic site in 92% of cases. Among the 24 recurrences, 17 were false aneurysms, 6 were thrombosis, and 1 was a true aneurysm in a different arterial site. To treat the arterial lesion, direct anastomosis was performed in 6 cases; bypass using the saphenous vein, graft, or allograft was performed in 6, 27, and 5 cases, respectively; and stent graft was used in 3 cases. Vascular lesions involved the aorta in 19 cases and a peripheral artery in 28 cases. Preoperative medical treatments, including colchicine, steroids, and immunosuppressants, significantly decreased recurrence rate: 28% (7/25) vs 75% (15/20) in untreated patients (P = .002). The recurrence rate was 42.5% (17/40) in patients treated postoperatively vs 80% (4/5) in untreated patients. The nature of the device used (vein, prosthetic graft, allograft, stent graft, or direct anastomosis) did not change the risk of recurrence. When anastomoses were protected using the prosthetic sleeving technique, the recurrence rate was three times lower (P = .08). CONCLUSIONS: Relapse is a main concern after surgical repair of arterial BD. This study suggests the need for targeted perioperative medical management to reduce the risk of arterial recurrence in BD patients. To this end, a multidisciplinary approach is mandatory. The use of sleeve anastomosis is associated with a numerically lower risk of recurrence. However, further studies are needed to confirm this efficacy.

Surgical repair of radiation-induced carotid stenosis.

OBJECTIVE: Carotid endarterectomy and carotid artery stenting are both valid therapeutic options for the treatment of radiation-induced carotid stenosis (RICS). The second has the advantage of being less invasive, although it seems to result in more restenosis than the first. Meanwhile, progress in radiation therapy and head and neck surgery has significantly increased the survival of these patients. As a result, treatment of RICS should be considered from a long-term perspective. This works presents perioperative and follow-up outcomes of surgical treatment of RICS. METHODS: This single-center retrospective study included all patients who underwent carotid endarterectomy for RICS from January 1998 to June 2017. Clinical and duplex ultrasound examination-based follow-up was performed postoperatively, at 1 month, 6 months, 12 months, and yearly thereafter. Kaplan-Meier curves were used for survival plots based on a log-rank test. Any abnormal finding led to angio-computed tomography scan and specialized neurovascular examination. RESULTS: Between 1998 and 2017, 128 patients (162 lesions) were treated. The median interval between radiation therapy and surgery was 16 years. Forty-five patients (35%) were symptomatic. The eversion technique was performed in 79 cases (49%), and the patch was favored in 24 cases (15%), prosthetic bypass graft in 51 cases (31%), and a venous bypass graft in 8 cases (5%). Two postoperative deaths (1.5%) (one secondary to massive stroke) were noted. The primary end point of early postoperative cerebrovascular event was 2.5%. Two cervical hematomas (1.2%) required surgical revision and seven cases of permanent cranial nerve injury were recorded. The median follow-up was 29 months (range, 2-199 months). There were no additional strokes. The 3-year primary patency rate was 96% and the 3-year freedom from neurologic event was 98%. CONCLUSIONS: Open surgical treatment of RICS lesions is a safe and durable option. Our results suggest that the outcomes of such treatment are good and in particular that rates of cerebrovascular event and restenosis are low and that cranial nerve injury should not be a concern. As a result, we consider that open surgery for RICS lesions should be offered as a first-line treatment. However, comparative data are mandated to address this issue.

Direct Distal Renal Artery Aneurysm Repair.

OBJECTIVE: Treatment of renal artery aneurysms (RAA) remains controversial. Endovascular treatment has increased for main trunk and for very distal aneurysms, whereas for lesions located at the bifurcation surgical treatment seems to be a valid option. The goal of this study was to describe the technique of direct reconstruction of RAA and to report on outcomes. METHODS: This study comprised single centre prospective collection of data with retrospective analysis (January 2015 to August 2018) of patients operated on for distal RAA using direct reconstruction. RESULTS: A total of 24 RAA in 21 patients (seven men and 14 women, mean age 59 ± 13 years) was included. History of hypertension was found in 15 patients and renal insufficiency was present in one. Mean pre-operative systolic and diastolic blood pressures were 134 ± 21 mmHg and 74 ± 10 mmHg, and mean pre-operative rates of creatinine and glomerular filtration rate were 67 ± 13 µmol/L and 93 ± 49 mL/min/1.73 m2, respectively. Indications for repair were a diameter >20 mm in seven cases (mean diameter = 25 ± 2 mm) or rapid growth in one case, symptomatic aneurysm in 12 cases (hypertension, haematuria, pain), and a concomitant lesion in four cases (splenic aneurysm, abdominal aortic aneurysm, occlusive visceral artery lesions). All lesions were distal, main artery bifurcation in 22 cases and hilar in two cases. The main aetiology was fibromuscular dysplasia (16 cases) followed by atherosclerosis (seven cases) and one case of Ehlers Danlos Syndrome. In situ reconstruction was possible for 22 RAA, while two cases required kidney autotransplantation. The mean renal ischaemia time was 18 ± 5 min. At two years, the patency rate was 100%, and mean systolic blood pressure decreased (134 mmHg-122 mmHg, p = .047). Renal function was stable from 93 ± 49 pre-operatively to 95 ± 35 mL/min/1.73 m2 in the post-operative course (p = .56). CONCLUSION: Direct reconstruction appears to be efficient for most RAA. This technique is complementary to ex vivo autotransplantation and endovascular treatment.