A prospective survey study on the education and awareness about walking exercise amongst inpatients with symptomatic peripheral arterial disease in Germany.

Background: To determine the adherence to supervised exercise training and underlying reasons for non-adherence amongst patients with inpatient treatment of symptomatic lower extremity peripheral arterial disease (PAD). Patients and methods: This was a prospective questionnaire-based survey study of all consecutively treated inpatients with treatment for either intermittent claudication or chronic limb-threatening ischaemia (CLTI) surveyed at sixteen participating centres in Germany. Results: A total of 235 patients (median age 70 years) were included, thereof 29.4% females and 34.6% with CLTI. The median time from first PAD diagnosis was 4 years (IQR: 1-8). Only 11.4% have previously participated in any walking exercise programme before the index treatment, thereby 10.0% in the IC subgroup and 12.0% with CLTI. Amongst all patients, 35.6% responded they were appropriately informed about the necessity and benefits of walking exercise programmes by their hospital physicians (25.8% by general practitioners), and 65.3% agreed that adherence to supervised exercise may improve their pain-free walking distance. A total of 24.5% responded they had access to necessary information concerning local walking exercise programmes. Amongst 127 free text comments on the reasons for non-adherence to supervised exercise training, 64% of the comments contained lack of information or consent on such measures. Conclusions: Less than 12% of the patients enrolled in the current study have ever participated in a walking exercise programme during their life course. Although all practice guidelines contain corresponding class I recommendations, especially for patients suffering from IC, most patients responded that they were not appropriately informed about the necessity of exercise training along with the fact that 65% agreed that exercise may increase the pain-free walking distance. Taken all together, these results emphasise that we miss an important opportunity in the patient-physician communication. Efforts should be made to improve acceptance and application of structured walking-exercise for patients with PAD.

The Role of the Gut Microbiome and Trimethylamine Oxide in Atherosclerosis and Age-Related Disease.

The gut microbiome plays a major role in human health, and gut microbial imbalance or dysbiosis is associated with disease development. Modulation in the gut microbiome can be used to treat or prevent different diseases. Gut dysbiosis increases with aging, and it has been associated with the impairment of gut barrier function leading to the leakage of harmful metabolites such as trimethylamine (TMA). TMA is a gut metabolite resulting from dietary amines that originate from animal-based foods. TMA enters the portal circulation and is oxidized by the hepatic enzyme into trimethylamine oxide (TMAO). Increased TMAO levels have been reported in elderly people. High TMAO levels are linked to peripheral artery disease (PAD), endothelial senescence, and vascular aging. Emerging evidence showed the beneficial role of probiotics and prebiotics in the management of several atherogenic risk factors through the remodeling of the gut microbiota, thus leading to a reduction in TMAO levels and atherosclerotic lesions. Despite the promising outcomes in different studies, the definite mechanisms of gut dysbiosis and microbiota-derived TMAO involved in atherosclerosis remain not fully understood. More studies are still required to focus on the molecular mechanisms and precise treatments targeting gut microbiota and leading to atheroprotective effects.

Cannulation of Visceral Vessels Using a Steerable Sheath in Fenestrated and Branched Aortic Endografts.

BACKGROUND: A critical step in the endovascular treatment of complex aortic aneurysms is the cannulation and stenting of renovisceral vessels, especially in cases with a complex anatomy or atherosclerotic lesions. This study aimed to demonstrate the results of renovisceral vessel cannulation using a steerable sheath in fenestrated or branched endovascular aortic procedures (FB-EVAR). METHODS: Patients undergoing elective FB-EVAR for asymptomatic thoracoabdominal or juxtarenal aneurysm at a single tertiary referral center from 2016 to 2019 were included in this study. Underlying pathologies, renovisceral target vessels (TV), technical success (TS), freedom from reintervention (FFR), and TV patency were assessed. Target vessels were categorized as challenging or nonchallenging TV. RESULTS: Fifty-three patients (median age 73 (Q1, Q3 (68-80)); 43 male (81%)) who underwent elective FB-EVAR were included. Indications comprised thoracoabdominal aneurysms (Crawford I-IV) (n = 26; 49%), juxtarenal aneurysms (n = 23; 43.5%) and penetrating aortic ulcers (PAU) (n = 4; 7.5%). Two patients (4%) had prior open aortic surgery, and three patients (6%) had undergone a failed standard EVAR before. Of the 196 treated TV, 131 (67%) were categorized as challenging. Cannulation was successful in 194 of 196 vessels (99%). A total of 3 TV (1.5%) showed periprocedural complications. No significant difference was found in the rate of intraoperative complications between challenging versus nonchallenging TV (P = 0.457). One patient died within 30 days of the procedure (1.9%). No stroke or intestinal ischemia occurred. After 12, 24, and 36 months, the survival rate was 87%, 87%, and 81%, respectively. Primary patency after 12 months was 98.6%, and 97.9% of vessels remained FFR during follow-up. CONCLUSIONS: Transfemoral, retrograde cannulation of renovisceral vessels using a steerable sheath is feasible and safe and provides good mid-term results, especially in cases with challenging renovisceral vessels. The potential complications of antegrade vascular access can be avoided.

Risk factors for elective and urgent open conversion after EVAR-a retrospective observational study.

BACKGROUND: Endovascular aortic aneurysm repair (EVAR) has become the standard procedure for treating infrarenal abdominal aortic aneurysms (AAA). Various associated complications can lead to open conversion (OC). Thorough follow-up after the procedure is mandatory for the early detection of complications. Persisting perfusion of the aneurysm, a so-called endoleak (EL), paired with structural instability because of aortic wall atrophy and impaired cell functionality induced by EVAR, results in a high risk for aortic rupture. PURPOSE: The goal of this study was to detect the risk factors for elective and urgent OC as a result of EVAR-induced pathophysiological changes inside the aortic wall. RESEARCH DESIGN: Retrospective data analysis was performed on all open aortic repairs from January 2016 to December 2020. DATA COLLECTION AND ANALYSIS: Fifty patients were identified as treated by OC for failure of an infrarenal EVAR. The patients were divided into two subgroups, here depending on the urgency of surgery. Statistical analysis of patient characteristics and outcomes was performed. RESULTS: The most common indications for OC were various types of EL (74%), resulting in an aortic rupture in 15 patients. Patients with insufficient or absent follow-up were treated more frequently in an emergency setting (16% vs. 63%). The mortality rate was higher in cases of emergency OC (3% vs. 26%). CONCLUSIONS: Particularly in cases of insufficient or absent follow-up, complications such as EL pose an enormous risk for fatal aortic rupture.

Perioperative risk prediction using the POSSUM and V-POSSUM models in symptomatic carotid stenosis.

Background: This study aimed to evaluate risk factors for adverse outcomes and perioperative stroke and death in patients with symptomatic carotid stenosis undergoing open endarterectomy (CEA). The second objective was to assess the predictive value of the POSSUM and V-POSSUM models for predicting morbidity and mortality from CEA in symptomatic carotid stenosis. Patients and methods: A retrospective observational study of all patients admitted to a single center who underwent CEA for symptomatic carotid stenosis was performed. 320 patients from 1999 to 2013 were included. Postoperative complications, 30-day survival, and stroke rates were recorded. The observed outcomes were compared to the POSSUM and V-POSSUM expected mortality (observed to expected ratio (O:E)). Results: The mean age was 68.1±10.0 years. 215 patients were male (67%). Risk factors for surgical complications were: age, with a higher risk in both groups of less than 60 years and more than 75 years of age (p=0.04), a higher ASA score (p=0.04), and hyperlipidemia (p=0.017). Risk factors for the combined endpoint stroke or death were a higher ASA category (p<0.001), stroke as indication for CEA (p 0.022), and a high degree of stenosis (p=0.019). For POSSUM predicted mortality, there was a good O:E ratio in the two lowest risk groups, but a 2-fold overprediction of death or stroke in the two high-risk strata. The area under the curve (AUC) was 0.58 (95% CI: 0.43-0.73). The V-POSSUM showed a better fit in the high-risk groups, but an underprediction of mortality in the low-risk strata. Conclusions: Age and comorbid conditions are risk factors for adverse outcomes after CEA. The V-POSSUM model is better than POSSUM to predict postoperative death and stroke after CEA in patients with symptomatic carotid stenosis and a high preoperative physiological score. In patients with low physiological scores, both POSSUM and V-POSSUM show a limited predictive value.

[Aortic Complications Related to Mycobacterium bovis after Intravesical Bacille Calmette-Guérin Therapy - a Systematic Review]. / Systematische Übersichtsarbeit: aortale Komplikationen nach intravesikaler Bacillus Calmette-Guérin-Behandlung.

BACKGROUND: Aortic complications after intravesical Bacillus Calmette-Guérin (BCG) application are a rare complication of the treatment of non-muscle invasive bladder cancer. The aim of this systematic review was to perform a descriptive analysis of previously published studies and to discuss the particular challenges of diagnosis and treatment of this rare complication. MATERIAL AND METHODS: A literature search was performed in PubMed (1949-2021) and Web of Science (1900-2021) using the search terms "mycobacterium" OR "bovis" OR "BCG" AND "aorta" OR "aneurysm". In a staged review process, publications with the following inclusion criteria were included in data analysis: original paper, full-text availability in English or German and aortic complication after intravesical BCG instillation. We focused on the analysis of BCG-specific medical history data as well as treatment strategies in relation to patient outcome and the occurrence of graft infections during follow-up. RESULTS: A total of 60 individual cases were described in 55 published articles. BCG-induced mycotic aortic aneurysms can occur in all segments of the thoracoabdominal aorta, but the infrarenal aortic segment was most commonly affected (65% of cases). The most common configuration was saccular outpouchings (65%). Concomitant infections in other tissues were typical (65%). Patients with mycotic aneurysm presented with or without consecutive aortic rupture in 28% and 63%, respectively. Diagnosis was based on a combination of pathological and microbiological examinations. A common treatment algorithm was surgical infection treatment (85%) and antitubercular therapy (83%). Performed simultaneously, they resulted in a long-term survival of 81%. Graft infection after initial aortic repair with alloplastic material (n = 40) developed in ten patients (25%) during follow-up. DISCUSSION: Diagnosis of mycotic aneurysms or vascular complications after intravesical BCG application is exceptionally challenging and a high level of suspicion is required. Diagnosis is based on obtaining sample material of affected regions and the combination of patient's history, clinical presentation and pathological or microbiological examinations. Currently, no consensus guideline for optimal medical treatment options of aortic complications secondary to BCG instillation exists. The combination of surgical treatment and supportive antitubercular therapy seems to achieve the best results. Since the risk of prosthetic infection after the use of alloplastic materials remains high (25%), we strongly suggest evaluating autologous or allogenic aortic replacement during initial aortic repair.

Association of simple renal cysts and chronic kidney disease with large abdominal aortic aneurysm.

BACKGROUND: Abdominal aortic aneurysms (AAA) primarily affect men over 65 years old who often have many other diseases, with similar risk factors and pathobiological mechanisms to AAA. The aim of this study was to assess the prevalence of simple renal cysts (SRC), chronic kidney disease (CKD), and other kidney diseases (e.g. nephrolithiasis) among patients presenting with AAA. METHODS: Two groups of patients (97 AAA and 100 controls), with and without AAA, from the Surgical Clinic Charité, Berlin, Germany, were selected for the study. The control group consisted of patients who were evaluated for a kidney donation (n = 14) and patients who were evaluated for an early detection of a melanoma recurrence (n = 86). The AAA and control groups were matched for age and sex. Medical records were analyzed and computed tomography scans were reviewed for the presence of SRC and nephrolithiasis. RESULTS: SRC (74% vs. 57%; p<0.016) and CKD (30% vs. 8%; p<0.001) were both more common among AAA than control group patients. On multivariate analysis, CKD, but not SRC, showed a strong association with AAA. CONCLUSIONS: Knowledge about pathobiological mechanisms and association between CKD and AAA could provide better diagnostic and therapeutic approaches for these patients.

Microarray analysis for delineating the gene expression in biopsies of gastrocnemius muscle of patients with chronic critical limb ischaemia compared with non-ischaemic controls.

BACKGROUND: Microarray analysis has been carried out in this pilot study to compare delineated gene expression profiles in the biopsies of skeletal muscle taken from patients with chronic critical limb ischaemia (CLI) and non-ischaemic control subjects. PATIENTS AND METHODS: Biopsy of gastrocnemius muscle was obtained from six patients with unreconstructed CLI referred for surgical major amputation. As control, biopsies of six patients undergoing elective knee arthroplasty without evidence of peripheral arterial occlusive disease were taken. The differences in gene expression associated with angiogenic processes in specimens obtained from ischaemic and non-ischaemic skeletal muscle were confirmed by quantitative real-time polymerase chain reaction (PCR) analysis. RESULTS: Compared with non-ischaemic skeletal muscle biopsy of chronic-ischaemic skeletal muscle contained 55 significantly up-regulated and 45 down-regulated genes, out of which 64 genes had a known genetic product. Tissue samples of ischaemic muscle were characterized by increased expression of cell survival factors (e. g. tissue factor pathway inhibitor 2) in combination with reduced expression of cell proliferation effectors (e. g. microfibrillar-associated protein 5 and transferrin receptor). The expression of growth factors (e. g. early growth response 3 and chemokine receptor chemokine C-X-C motif ligand 4) which play a central role in arterial and angiogenic processes and anti-angiogenetic factors (e. g. pentraxin 3) were increased in chronic ischaemic skeletal muscle. An increased expression of extracellular matrix proteins (e. g. cysteine-rich angiogenic inducer 61) was also observed. CONCLUSIONS: Gene expression profiles in biopsies of gastrocnemius muscle in patients with chronic critical limb ischaemia showed an increase in pro-survival factors, extracellular matrix protein deposition, and impaired proliferation, compared with non-ischaemic controls. Further studies are required to analyse the endogenous repair mechanism.

Immunohistochemical analysis of the natural killer cell cytotoxicity pathway in human abdominal aortic aneurysms.

Our previous analysis using genome-wide microarray expression data revealed extreme overrepresentation of immune related genes belonging the Natural Killer (NK) Cell Mediated Cytotoxicity pathway (hsa04650) in human abdominal aortic aneurysm (AAA). We followed up the microarray studies by immunohistochemical analyses using antibodies against nine members of the NK pathway (VAV1, VAV3, PLCG1, PLCG2, HCST, TYROBP, PTK2B, TNFA, and GZMB) and aortic tissue samples from AAA repair operations (n = 6) and control aortae (n = 8) from age-, sex- and ethnicity-matched donors from autopsies. The results confirmed the microarray results. Two different members of the NK pathway, HCST and GRZB, which act at different steps in the NK-pathway, were actively transcribed and translated into proteins in the same cells in the AAA tissue demonstrated by double staining. Furthermore, double staining with antibodies against CD68 or CD8 together with HCST, TYROBP, PTK2B or PLCG2 revealed that CD68 and CD8 positive cells expressed proteins of the NK-pathway but were not the only inflammatory cells involved in the NK-pathway in the AAA tissue. The results provide strong evidence that the NK Cell Mediated Cytotoxicity Pathway is activated in human AAA and valuable insight for future studies to dissect the pathogenesis of human AAA.

[Recommendations for the specialist further training of nursing personnel on intensive care units in the treatment of abdominal aortic aneurysms: results of a modified Delphi procedure with experts]. / Empfehlungen zur Fachweiterbildung von Pflegefachpersonen der Intensivstation bei der Behandlung des Bauchaortenaneurysmas: Ergebnisse eines modifizierten Delphi-Verfahrens mit Expert:innen.

INTRODUCTION: The medical development in the previous 15 years and the changes in treatment reality of the comprehensive elective treatment of abdominal aortic aneurysms necessitate a re-evaluation of the quality assurance guidelines of the Federal Joint Committee in Germany (QBAA-RL). In the current version this requires a specialist further training quota for nursing personnel in intensive care wards of 50%. The quota was determined in 2008 based on expert opinions, although a direct empirical evidence base for this does not exist. METHODS: Representatives from the fields of patient representation, physicians, nursing personnel and other relevant interface areas were invited to participate in a modified Delphi procedure. Following a comprehensive narrative literature search, a survey and focus group discussions with national and international experts, a total of three anonymized online-based voting rounds were carried out for which previously determined key statements were assessed with a 4­point Likert scale (totally disagree up to totally agree). In addition, the expert panel had also defined a recommendation for a minimum quota for the specialist training of nursing personnel on intensive care wards in the treatment of abdominal aortic aneurysms, whereby an a priori agreement of 80% of the participants was defined as the consensus limit. RESULTS: Overall, 37 experts participated in the discussions and three successive voting rounds (participation rate 89%). The panel confirmed the necessity of a re-evaluation of the guideline recommendations and recommended the introduction of a shift-related minimum quota of 30% of the full-time equivalent of nursing personnel on intensive care wards and the introduction of structured promotional programs for long-term elevation of the quota. CONCLUSION: In this national Delphi procedure with medical and nursing experts as well as representatives of patients, the fundamental benefits and needs of professional specialist qualifications in the field of intensive care medicine were confirmed. The corresponding minimum quota for specialist further training of intensive care nursing personnel should generally apply without limitations to specific groups. The expert panel stipulates a shift-related minimum quota for intensive care nursing personnel with specialist training of 30% of the nursing personnel on intensive care wards and the obligatory introduction of structured and transparent promotion programs for the long-term enhancement.

Novel pathways in the pathobiology of human abdominal aortic aneurysms.

OBJECTIVES: Abdominal aortic aneurysm (AAA), a dilatation of the infrarenal aorta, typically affects males >65 years. The pathobiological mechanisms of human AAA are poorly understood. The goal of this study was to identify novel pathways involved in the development of AAAs. METHODS: A custom-designed 'AAA-chip' was used to assay 43 of the differentially expressed genes identified in a previously published microarray study between AAA (n = 15) and control (n = 15) infrarenal abdominal aorta. Protein analyses were performed on selected genes. RESULTS: Altogether 38 of the 43 genes on the 'AAA-chip' showed significantly different expression. Novel validated genes in AAA pathobiology included ADCY7, ARL4C, BLNK, FOSB, GATM, LYZ, MFGE8, PRUNE2, PTPRC, SMTN, TMODI and TPM2. These genes represent a wide range of biological functions, such as calcium signaling, development and differentiation, as well as cell adhesion not previously implicated in AAA pathobiology. Protein analyses for GATM, CD4, CXCR4, BLNK, PLEK, LYZ, FOSB, DUSP6, ITGA5 and PTPRC confirmed the mRNA findings. CONCLUSION: The results provide new directions for future research into AAA pathogenesis to study the role of novel genes confirmed here. New treatments and diagnostic tools for AAA could potentially be identified by studying these novel pathways.

Long-term quality of life of abdominal aortic aneurysm patients under surveillance or after operative treatment.

BACKGROUND: The objective of this study was to determine the long-term quality of life (QOL) in patients with an abdominal aortic aneurysm (AAA) undergoing surveillance or after operative treatment. METHODS: 249 patients with AAAs completed the WHO Quality of Life-BREF (WHOQOL-BREF) test and Short Form (36) Health Survey (SF-36) survey: 78 patients with small AAAs under surveillance, 26 after ruptured AAAs (rAAAs), 47 after endovascular aneurysm repair (EVAR), and 98 after elective open repair. The results were compared with WHOQOL-BREF and SF-36 standard values from a matched German population using the Student's 2-tailed t-test. RESULTS: Long-term results of the WHOQOL-BREF test showed that patients undergoing AAA surveillance had a significantly lower physical QOL (P = 0.04). Patients after EVAR or open repair rated their environmental QOL significantly higher than the age- and sex-matched general population (open repair: P = 0.006; EVAR: P < 0.001). Patients with rAAAs had the same QOL as the matched German population. Long-term results of the QOL SF-36 showed that patients undergoing AAA surveillance rated their QOL significantly lower in the subgroup of role-physical (P = 0.02) and role-emotional (P = 0.003). Patients with rAAAs rated lower scores for role-physical (P = 0.02) and had more bodily pain (P = 0.02). Patients who underwent elective open repair had the same high QOL as the matched German population, whereas patients who underwent EVAR reported significant improvement in vitality (P = 0.002) and mental health (P = 0.03) compared with the matched German population. CONCLUSIONS: Based on measurements from 2 independent QOL tests, the well-established operative treatment of AAAs provided patients with a QOL comparable to that of a matched German population. The electively treated AAA groups rated environmental QOL factors significantly higher than the control group. The impaired physical and emotional QOL of the AAA group under surveillance suggests that more intense patient education could be beneficial.

Systematic review and meta-analysis of cell therapy for COVID-19: global clinical trial landscape, published safety/efficacy outcomes, cell product manufacturing and clinical delivery.

During the pandemic of severe respiratory distress syndrome coronavirus 2 (SARS-CoV2), many novel therapeutic modalities to treat Coronavirus 2019 induced disease (COVID-19) were explored. This study summarizes 195 clinical trials of advanced cell therapies targeting COVID-19 that were registered over the two years between January 2020 to December 2021. In addition, this work also analyzed the cell manufacturing and clinical delivery experience of 26 trials that published their outcomes by July 2022. Our demographic analysis found the highest number of cell therapy trials for COVID-19 was in United States, China, and Iran (N=53, 43, and 19, respectively), with the highest number per capita in Israel, Spain, Iran, Australia, and Sweden (N=0.641, 0.232, 0,223, 0.194, and 0.192 trials per million inhabitants). The leading cell types were multipotent mesenchymal stromal/stem cells (MSCs), natural killer (NK) cells, and mononuclear cells (MNCs), accounting for 72%, 9%, and 6% of the studies, respectively. There were 24 published clinical trials that reported on infusions of MSCs. A pooled analysis of these MSC studies found that MSCs provide a relative risk reduction for all-cause COVID-19 mortality of RR=0.63 (95% CI 0.46 to 0.85). This result corroborates previously published smaller meta-analyses, which suggested that MSC therapy demonstrated a clinical benefit for COVID-19 patients. The sources of the MSCs used in these studies and their manufacturing and clinical delivery methods were remarkably heterogeneous, with some predominance of perinatal tissue-derived products. Our results highlight the important role that cell therapy products may play as an adjunct therapy in the management of COVID-19 and its related complications, as well as the importance of controlling key manufacturing parameters to ensure comparability between studies. Thus, we support ongoing calls for a global registry of clinical studies with MSC products that could better link cell product manufacturing and delivery methods to clinical outcomes. Although advanced cell therapies may provide an important adjunct treatment for patients affected by COVID-19 in the near future, preventing pathology through vaccination still remains the best protection to date. We conducted a systematic review and meta-analysis of advanced cell therapy clinical trials as potential novel treatment for COVID-19 (resulting from SARS-CoV-2 coronavirus infection), including analysis of the global clinical trial landscape, published safety/efficacy outcomes (RR/OR), and details on cell product manufacturing and clinical delivery. This study had a 2-year observation interval from start of January 2020 to end of December 2021, including a follow-up period until end of July to identify published outcomes, which covers the most vivid period of clinical trial activity, and is also the longest observation period studied until today. In total, we identified 195 registered advanced cell therapy studies for COVID-19, employing 204 individual cell products. Leading registered trial activity was attributed to the USA, China, and Iran. Through the end of July 2022, 26 clinical trials were published, with 24 out of 26 articles employing intravenous infusions (IV) of mesenchymal stromal/stem cell (MSC) products. Most of the published trials were attributed to China and Iran. The cumulative results from the 24 published studies employing infusions of MSCs indicated an improved survival (RR=0.63 with 95% Confidence Interval 0.46 to 0.85). Our study is the most comprehensive systematic review and meta-analysis on cell therapy trials for COVID-19 conducted to date, clearly identifying the USA, China, and Iran as leading advanced cell therapy trial countries for COVID-19, with further strong contributions from Israel, Spain, Australia and Sweden. Although advanced cell therapies may provide an important adjunct treatment for patients affected by COVID-19 in the future, preventing pathology through vaccination remains the best protection.

Role of complement cascade in abdominal aortic aneurysms.

OBJECTIVE: The goal of this study was to investigate the role of complement cascade genes in the pathobiology of human abdominal aortic aneurysms (AAAs). METHODS AND RESULTS: Results of a genome-wide microarray expression profiling revealed 3274 differentially expressed genes between aneurysmal and control aortic tissue. Interestingly, 13 genes in the complement cascade were significantly differentially expressed between AAA and the controls. In silico analysis of the promoters of the 13 complement cascade genes showed enrichment for transcription factor binding sites for signal transducer and activator of transcription (STAT)5A. Chromatin-immunoprecipitation experiments demonstrated binding of transcription factor STAT5A to the promoters of the majority of the complement cascade genes. Immunohistochemical analysis showed strong staining for C2 in AAA tissues. CONCLUSIONS: These results provide strong evidence that the complement cascade plays a role in human AAA. Based on our microarray studies, the pathway is activated in AAA, particularly via the lectin and classical pathways. The overrepresented binding sites of transcription factor STAT5A in the complement cascade gene promoters suggest a role for STAT5A in the coordinated regulation of complement cascade gene expression.

Comparison of survival rates for abdominal aortic aneurysm treatment methods.

BACKGROUND: We compared relative survival rates of patients after various operative treatments for abdominal aortic aneurysm (AAA) to those for the general population. We calculated a point of "recovery," defined as the survival rate equal to that of the general population. METHODS: Survival data were collected from patients who underwent open repair for a ruptured AAA (rAAA), elective open repair of an AAA (OPEN), and endovascular repair (EVAR) in our hospital between 1995 and 2005. The cumulative relative survival rate and time-specific relative survival rate were calculated for these patients compared to those for the general population. The point of "recovery" was defined as the cumulative relative survival rate equaling the survival rate for the population, and the time-specific relative survival rate reaching 1.0. RESULTS: The cumulative relative survival rate of the patients immediately after OPEN was lower than for the comparison group at the time the cumulative relative survival rate was regained. The time-specific relative survival rate of the rAAA reached 1.0 at 16 months following emergency surgery, and for OPEN after 10 months. The cumulative relative survival rate in the EVAR group had no impairment following intervention. The relative long-term survival rate in all three surgical groups was the same as that for the general German population. CONCLUSIONS: Patients treated successfully for AAA have the same relative long-term survival as the general population. The time required to reach the same survival, however, differs between the treatment groups and is longest in the group with a rAAA. The variable survival rates should be taken into consideration when treating patients with an AAA.

Stem Cell-Based Therapy: A Promising Treatment for Diabetic Foot Ulcer.

Diabetic foot ulcer (DFU) is a severe complication of diabetes and a challenging medical condition. Conventional treatments for DFU have not been effective enough to reduce the amputation rates, which urges the need for additional treatment. Stem cell-based therapy for DFU has been investigated over the past years. Its therapeutic effect is through promoting angiogenesis, secreting paracrine factors, stimulating vascular differentiation, suppressing inflammation, improving collagen deposition, and immunomodulation. It is controversial which type and origin of stem cells, and which administration route would be the most optimal for therapy. We reviewed the different types and origins of stem cells and routes of administration used for the treatment of DFU in clinical and preclinical studies. Diabetes leads to the impairment of the stem cells in the diseased patients, which makes it less ideal to use autologous stem cells, and requires looking for a matching donor. Moreover, angioplasty could be complementary to stem cell therapy, and scaffolds have a positive impact on the healing process of DFU by stem cell-based therapy. In short, stem cell-based therapy is promising in the field of regenerative medicine, but more studies are still needed to determine the ideal type of stem cells required in therapy, their safety, proper dosing, and optimal administration route.

Effect of Revascularization on Intramuscular Vascular Endothelial Growth Factor Levels in Peripheral Arterial Disease.

Vascular endothelial growth factor (VEGF) is a potent driver of angiogenesis, which may help to relieve ischemia in peripheral arterial disease (PAD). We aimed to investigate the role of intramuscular VEGF in ischemic and non-ischemic skeletal muscle in PAD patients before and after surgical or endovascular revascularization and different stages of PAD. Biopsies of the gastrocnemius and vastus muscles from twenty PAD patients with stenosis or occlusion of the superficial femoral artery were obtained both during revascularization and 8 weeks postoperatively. The gastrocnemius muscle was considered ischemic, while vastus muscle biopsies served as intraindividual controls. The levels of vascular endothelial growth factor in muscle lysates were then determined by ELISA. Preoperative VEGF levels were significantly higher in ischemic muscles compared to the controls (98.07 ± 61.96 pg/mL vs. 55.50 ± 27.33 pg/mL, p = 0.004). Postoperative values decreased significantly (p = 0.010) to 54.83 ± 49.60 pg/mL in gastrocnemius biopsies. No significant change was observed in vastus muscle biopsies, with mean postoperative VEGF values found at 54.16 ± 40.66 pg/mL. Since all patients still had indications for revascularization, impairment of angiogenesis mechanisms can be assumed. More research about angiogenesis in PAD is needed with the ultimate goal to improve conservative treatment.

Distribution of Mobile Health Applications amongst Patients with Symptomatic Peripheral Arterial Disease in Germany: A Cross-Sectional Survey Study.

BACKGROUND: Broadly available digital and mobile health applications (also known as mHealth) have recently gained increasing attention by the vascular community, but very little is known about the dissemination and acceptance of such technologies in certain target populations. The current study aimed to determine the user behaviour and acceptance of such digital technologies amongst patients with peripheral arterial disease (PAD). METHODS: A cross-sectional survey of consecutively treated inpatients at 12 university institutions, as well as one non-university institution, was conducted. All admitted patients with symptomatic PAD were surveyed for 30 consecutive days within a flexible timeframe between 1 July and 30 September 2021. The factors associated with smartphone use were estimated via backward selection within a logistic regression model with clustered standard errors. RESULTS: A total of 326 patients participated (response rate 96.3%), thereof 102 (34.0%) were treated for intermittent claudication (IC, 29.2% women, 70 years in median) and 198 were treated for chronic limb-threatening ischaemia (CLTI, 29.5% women, 70 years in median). Amongst all of the patients, 46.6% stated that they had not changed their lifestyle and health behaviour since the index diagnosis (four years in median), and 33.1% responded that they were not aware of the reasons for all of their medication orders. Amongst all those surveyed, 66.8% owned a smartphone (IC: 70.6%, CLTI: 64.1%), thereof 27.9% needed regular user support. While 42.5% used smartphone apps, only 15.0% used mobile health applications, and 19.0% owned wearables. One out of five patients agreed that such technologies could help to improve their healthy lifestyle. Only higher age was inversely associated with smartphone possession. CONCLUSIONS: The current survey showed that smartphones are prevalent amongst patients with peripheral arterial disease, but only a small proportion used mobile health applications and a considerable number of patients needed regular user support. Almost half of the patients did not change their lifestyle and one third were not aware of the reasons for their medication orders, emphasising room for improvement. These findings can further help to guide future projects using such applications to identify those target populations that are reachable with digital interventions.

Genes and abdominal aortic aneurysm.

Abdominal aortic aneurysm (AAA) is a multifactorial disease with a strong genetic component. Since the first candidate gene studies were published 20 years ago, approximately 100 genetic association studies using single nucleotide polymorphisms (SNPs) in biologically relevant genes have been reported on AAA. These studies investigated SNPs in genes of the extracellular matrix, the cardiovascular system, the immune system, and signaling pathways. Very few studies were large enough to draw firm conclusions and very few results could be replicated in another sample set. The more recent unbiased approaches are family-based DNA linkage studies and genome-wide genetic association studies, which have the potential of identifying the genetic basis for AAA, only when appropriately powered and well-characterized large AAA cohorts are used. SNPs associated with AAA have already been identified in these large multicenter studies. One significant association was of a variant in a gene called contactin-3, which is located on chromosome 3p12.3. However, two follow-up studies could not replicate this association. Two other SNPs, which are located on chromosome 9p21 and 9q33, were replicated in other samples. The two genes with the strongest supporting evidence of contribution to the genetic risk for AAA are the CDKN2BAS gene, also known as ANRIL, which encodes an antisense ribonucleic acid that regulates expression of the cyclin-dependent kinase inhibitors CDKN2A and CDKN2B, and DAB2IP, which encodes an inhibitor of cell growth and survival. Functional studies are now needed to establish the mechanisms by which these genes contribute toward AAA pathogenesis.

Do Hernias Contribute to Increased Severity of Aneurysmal Disease among Abdominal Aortic Aneurysm Patients?

BACKGROUND: Connective tissue disorders could contribute to the pathogenesis of both abdominal aortic aneurysms (AAA) and hernias. We tested the hypothesis that hernias in AAA patients contribute to increased severity of the aneurysmal disease. METHODS: A questionnaire was used to collect information from 195 AAA patients divided into four groups: (1) survivors (n = 22) of ruptured AAA, (2) patients (n = 90) after elective open repair, (3) patients (n = 43) after elective endovascular repair (EVAR), and (4) patients (n = 40) under surveillance of AAA. The control group consisted of 100 patients without AAA whose abdominal computed tomography (CT) scans were examined for the presence of hernias. Mann-Whitney U-test, Chi-squared (χ 2) test, or Fisher's exact test (as appropriate) were used for statistical analyses. Multivariate logistic regression was used to control for potential confounding variables such as sex and age. RESULTS: The prevalence of inguinal hernias was significantly higher in the AAA than the control group (25 vs. 9%, p = 0.001) and did not differ between the AAA subgroups (9, 24, 35, and 23% in subgroups 1 through 4, respectively, p = 0.15) based on univariate analysis. The prevalence of inguinal hernias did not differ (p = 0.15) between the two open surgery groups (groups 1 and 2), or when comparing all three operative procedures as a combined group to group 4 (p = 0.73). The prevalences of incisional hernias were 18 and 24% for groups 1 and 2, respectively, with no significant difference (p = 0.39). Inguinal hernia demonstrated a significant association with AAA on multivariate analysis (p = 0.006; odds ratio [OR] = 4.00; 95% confidence interval [CI] = 1.49-10.66). CONCLUSIONS: Our study confirms previous observations that patients with AAA have a high prevalence of hernias. Our results suggest that hernias do not contribute to increased severity of the aneurysmal disease.