A short time interval between the neurologic index event and carotid endarterectomy is not a risk factor for carotid surgery.

OBJECTIVE: Current guidelines recommend that carotid endarterectomy (CEA) be performed as early as possible after the neurologic index event in patients with 50% to 99% carotid artery stenosis. However, recent registry data showed that patients treated ≤48 hours had a significantly increased perioperative risk. Therefore, the aim of this single-center study was to determine the effect of the time interval between the neurologic index event and CEA on the periprocedural complication rate at our institution. METHODS: Prospectively collected data for 401 CEAs performed between 2004 and 2014 for symptomatic carotid stenosis were analyzed. Patients were divided into four groups according to the interval between the last neurologic event and surgery: group I, 0 to 2 days; group II, 3 to 7 days; group III, 8 to 14 days; and group IV, 15 to 180 days. The primary end point was the combined rate of in-hospital stroke or mortality. Data were analyzed by way of χ2 tests and multivariable regression analysis. RESULTS: The patients (68% men) had a median age of 70 years (interquartile range, 63-76 years). The index events included transient ischemic attack in 43.4%, amaurosis fugax in 25.4%, and an ipsilateral stroke in 31.2%. CEA was performed using the eversion technique in 61.1% of patients, and 50.1% were treated under locoregional anesthesia. The perioperative combined stroke and mortality rate was 2.5% (10 of 401), representing a perioperative mortality rate of 1.0% and stroke rate of 1.5%. Overall, myocardial infarction, cranial nerve injuries, and postoperative bleeding occurred in 0.7%, 2.2%, and 1.7%, respectively. We detected no significant differences for the combined stroke and mortality rate by time interval: 3% in group I, 3% in group II, 2% in group III, and 2% in group IV. Multivariable regression analysis showed no significant effect of the time interval on the primary end point. CONCLUSIONS: The combined mortality and stroke rate was 2.5% and did not differ significantly between the four different time interval groups. CEA was safe in our cohort, even when performed as soon as possible after the index event.

Determinants of prehospital and in-hospital delay in patients with symptomatic carotid stenosis and their influence on the outcome after elective carotid endarterectomy.

BACKGROUND: This study analyses the determinants of prehospital (index event to admission) and in-hospital delay (admission to carotid endarterectomy (CEA)). In addition, the analysis addresses the association between prehospital or in-hospital delay and outcomes after CEA for symptomatic patients in German hospitals. MATERIALS AND METHODS: This retrospective analysis is based on the nationwide German statutory quality assurance database. 55 437 patients were included in the analysis. Prehospital delay was grouped as follows: 180-15, 14-8, 7-3, 2-0 days or 'in-hospital index event'. In-hospital delay was divided into: 0-1, 2-3 and >3 days. The primary outcome event (POE) was in-hospital stroke or death. Univariate and multivariable regression analyses were performed for statistical analysis. The slope of the linear regression line is given as the ß-value, and the rate parameter of the logistic regression is given as the adjusted OR (aOR). RESULTS: Prehospital delay was 0-2 days in 34.9%, 3-14 days in 29.5% and >14 days in 18.6%. Higher age (ß=-1.08, p<0.001) and a more severe index event (transitory ischaemic attack: ß=-4.41, p<0.001; stroke: ß=-6.05, p<0.001, Ref: amaurosis fugax) were determinants of shorter prehospital delay. Higher age (ß=0.28, p<0.001) and female sex (ß=0.09, p=0.014) were associated with a longer in-hospital delay. Index event after admission (aOR 1.23, 95% CI: 1.04 to 1.47) and an intermediate in-hospital delay of 2-3 days (aOR 1.15, 95% CI: 1.00 to 1.33) were associated with an increased POE risk. CONCLUSIONS: This study revealed that older age, higher American Society of Anesthesiology (ASA) stage, increasing severity of symptoms and ipsilateral moderate stenosis were associated with shorter prehospital delay. Non-specific symptoms were associated with a longer prehospital delay. Regarding in-hospital delay, older age, higher ASA stage, contralateral occlusion, preprocedural examination by a neurologist and admission on Fridays or Saturdays were associated with lagged treatment. A very short (<2 days) prehospital and intermediate in-hospital delay (2-3 days) were associated with increased risk of perioperative stroke or death.

Monocytes do not transdifferentiate into proper osteoblasts.

Recent publications suggested that monocytes might be an attractive cell type to transdifferentiate into various cellular phenotypes. Aim was, therefore, to evaluate the potential of blood monocytes to transdifferentiate into osteoblasts. Monocytes isolated from peripheral blood were subjected to two previously published treatments to obtain unique, multipotent cell fractions, named programmable cells of monocytic origin (PCMOs) and monocyte-derived mesenchymal progenitor cells (MOMPs). Subsequently, MOMPs and PCMOs were treated with osteogenic differentiation medium (including either vitamin D or dexamethasone) for 14 days. Regarding a variety of surface markers, no differences between MOMPs, PCMOs, and primary monocytes could be detected. The treatment with osteogenic medium neither resulted in loss of hematopoietic markers nor in adoption of mesenchymal phenotype in all cell types. No significant effect was observed regarding the expression of osteogenic transcription factors, bone-related genes, or production of mineralized matrix. Osteogenic medium resulted in activation of monocytes and appearance of osteoclasts. In conclusion, none of the investigated monocyte cell types showed any transdifferentiation characteristics under the tested circumstances. Based on our data, we rather see an activation and maturation of monocytes towards macrophages and osteoclasts.

[Important recommendations of the German-Austrian S3 guidelines on management of extracranial carotid artery stenosis]. / Wichtige Empfehlungen der deutsch-österreichischen S3-Leitlinie zum Management extrakranieller Karotisstenosen.

BACKGROUND: Lesions of the extracranial carotid artery are the cause of 10-15 % of all cases of cerebral ischemia. The aims of the updated S3 guidelines are evidence-based and consensus-based recommendations for action on comprehensive care of patients with extracranial carotid stenosis in Germany and Austria. METHODS: A systematic literature search (1990-2019) and methodical assessment of existing guidelines and systematic reviews were carried out. Consensus answers to 37 key questions with evidence-based recommendations. RESULTS: The prevalence of extracranial carotid stenosis is approximately 4% and increases after the age of 65 years. The most important examination method is duplex sonography. Randomized controlled studies (RCT) have shown that carotid endarterectomy (CEA) of an asymptomatic 60-99% carotid artery stenosis reduces the absolute risk of stroke (absolute risk reduction, ARR) within 5 years in comparison to drug treatment alone by 4.1%. Due to an improved pharmaceutical prevention of arteriosclerosis, the S3 guidelines recommend a prophylactic CEA of a 60-99% stenosis only for patients without an increased surgical risk. Additionally, one or more clinical or imaging results should be present, which indicate an increased risk of carotid-related stroke in the follow-up. For medium-grade (50-69 %) and high-grade (70-99 %) symptomatic stenoses the ARRs after 5 years are 4.6% and 15.6%, respectively. Systematic reviews of RCTs have shown that CEA is associated with a ca. 50% lower periprocedural risk of stroke compared to carotid artery stenting (CAS). There are no differences in the long-term course. The CEA is recommended for high-grade asymptomatic, medium-grade and high-grade symptomatic carotid stenosis as a standard procedure, alternatively CAS can be considered. For both procedures the periprocedural stroke rate/mortality during hospitalization should be a maximum of 2% (asymptomatic stenosis) or 4% (symptomatic stenosis). CONCLUSION: Both CEA and CAS necessitate a critical evaluation of the indications and strict quality criteria. Future studies should evaluate even better selection criteria for an individual, optimal, conservative, operative or endovascular treatment.

The Effects of Minimum Caseload Requirements on Management and Outcome in Abdominal Aortic Aneurysm Repair.

BACKGROUND: The German quality assurance guideline on abdominal aortic aneurysm (AAA) was implemented by the Joint Federal Committee (Gemeinsamer Bundesausschuss, G-BA) in 2008. The aims of this study were to verify the association between hospital case volume and outcome and to assess the hypothetical effect of minimum caseload requirements. METHODS: The German diagnosis-related groups statistics for the years 2012 to 2016 were scrutinized for AAA (ICD-10 GM I71.3/4) with procedure codes for endo - vascular or open surgical treatment. The primary endpoint was in-hospital mortality. Logistic regression models were used for risk adjustment, and odds ratios (OR) were calculated as a function of the annual hospital-level case volume of AAA. In a hypo - thetical approach, the linear distances for various minimum caseloads (MC) were evaluated to assess accessibility. RESULTS: The mortality of intact AAA (iAAA) was 2.7% (men [M] 2.4%, women [W] 4.2%); ruptured AAA (rAAA), 36.9% (M 36.9%, F 37.5%). An inverse relationship between annual hospital case volume of AAA and mortality was confirmed (iAAA/rAAA: from 3.9%/51% [<10 cases/year] through 3.3%/37% [30-39 cases/year] to 1.9%/28% [≥ 75 cases/year]). For a reference category of 30 AAA procedures/year, the following significant OR were found: 10 AAA cases/year, OR 1.21 (95% confidence interval [1.20; 1.21]); 20 cases, OR 1.09 [1.09; 1.09]; 50 cases, OR 0.89 [0.89; 0.89]; 75 cases, OR 0.82 [0.82; 0.82]. In a hypothetical centralization scenario with assumed MC of 30/year, 86% of the population would have to travel less than 100 km to the nearest hospital; with an MC of 40, this would apply to only 50% (without redistribution effects). CONCLUSION: In the observed period, a significant correlation was confirmed between high annual case volume and low in-hospital mortality. A minimum caseload requirement of 30 AAA operations/year seems reasonable in view of the accessibility of hospitals. Cite this.

Diagnosis, Treatment and Follow-up in Extracranial Carotid Stenosis.

BACKGROUND: Around 15% of cerebral ischemias are caused by lesions of the extracranial carotid artery. The goal of this guideline is to provide evidence- and consensus-based recommendations for the management of patients with extracranial carotid stenoses throughout Germany and Austria. METHODS: A systematic literature search (1990-2019) and methodical assessment of existing guidelines and systematic reviews; consensus-based answers to 37 key questions with evidence-based recommendations. RESULTS: The prevalence of extracranial carotid artery stenoses is around 4% overall, higher from the age of 65 years. The most important examination modality is duplex sonography. Randomized trials have shown that carotid endarterectomy (CEA) significantly reduces the 5-year risk of stroke in patients with 60-99 % asymptomatic stenoses (absolute risk reduction [ARR] 4.1% over 5 years, number needed to treat [NNT] 24) or 50-99% symptomatic stenoses (50-69%: ARR 4.6 % over 5 years, NNT 22; 70-99%: 15.9 % over 5 years, NNT 6). With the aid of intensive conservative treatment, the carotid artery-associated risk of stroke can be reduced to as little as 1% per year. Critical determination of indications and strict quality criteria are therefore necessary for CEA and carotid artery stenting (CAS). Systematic reviews of controlled trials comparing CEA and CAS show that the procedural risk of stroke is higher for CAS (asymptomatic: 2.6% versus 1.3%; symptomatic: 6.2% versus 3.8%). There are no differences in the long term. CEA is recommended as standard procedure for high-grade asymptomatic and moderate to high-grade symptomatic carotid artery stenoses; CAS may be considered as an alternative. For both procedures, the periprocedural combined rate of stroke or death should not exceed 2% for asymptomatic stenoses or 4% for symptomatic stenoses. CONCLUSION: Future studies should evaluate even better selection criteria for optimal individualized treatment, whether conservative, surgical, or endovascular.

The University of Munich lung cancer group database: design, profile of cohort and outcome analysis.

OBJECTIVE: Changes in therapeutic concepts can only be justified by a significant improvement of outcome parameters. Furthermore, detailed statistics of complications are needed to guarantee high quality of treatment. This study describes the new University of Munich Lung Cancer Group Database. METHODS: The MLCG-Database contains all patients who underwent surgery for lung cancer at the Department of Surgery, University of Munich Medical Centre since 1978. Data were database recorded on the patient's ward, or directly imported from other departments performing medical examinations on the patient. Data could be entered online at the time of surgery in the operating room. Relevant information from the Munich Tumour Registry was imported via encrypted data communication. Both epidemiological background and influence of preoperative risk factors on morbidity and mortality as well as on long-term survival were analysed. RESULTS: Median follow-up time was 45 months (1-295 months). Overall 5- and 10-year survival was 36% and 28% respectively. Preoperative risk factors were arterial hypertension in 43% of patients, COPD in 34%, abuse of nicotine in 26% and therapy with corticosteroids in 25%. Surgical procedure consist of lobectomy or bilobectomy in 69%, pneumonectomy in 16% and lesser resections in 15%. Intra- and postoperative complications occurred in 1.4% and 32% of patients, respectively. CONCLUSIONS: This paper provides an overview of our MLCG-Database, which allows performing statistics for outcome analysis and quality management reports as well as medical assessment on a huge collection of patient data on a day-to-day basis. In addition, impact analysis of risk factors on postoperative morbidity and mortality as well as investigation of long-term survival underlines results reported internationally.

Surgical and Endovascular Treatment of Extracranial Carotid Stenosis.

BACKGROUND: Carotid endarterectomy (CEA) and carotid artery stenting (CAS) can be used to prevent stroke due to arteriosclerotic lesions of the carotid artery. In Germany, legally mandated quality assurance (QA) enables the evaluation of outcome quality after CEA and CAS performed under routine conditions. METHODS: We analyzed data on all elective CEA and CAS procedures performed over the periods 2009-2014 and 2012-2014, respectively. The endpoints of the study were the combined in-hospital stroke and death rate, stroke rate and mortality separately, local complications, and other complications. We analyzed the raw data with descriptive statistics and carried out a risk-adjusted analysis of the association of clinically unalterable variables with the risk of stroke and death. All analyses were performed separately for CEA and CAS. RESULTS: Data were analyzed from 142 074 CEA procedures (67.8% of them in men) and 13 086 CAS procedures (69.7% in men). The median age was 72 years (CEA) and 71 years (CAS). The periprocedural rate of stroke and death after CEA was 1.4% for asymptomatic and 2.5% for symptomatic stenoses; the corresponding rates for CAS were 1.7% and 3.7%. Variables associated with increased risk included older age, higher ASA class (ASA = American Society of Anesthesiologists), symptomatic vs. asymptomatic stenosis, 50-69% stenosis, and contralateral carotid occlusion (for CEA only). CONCLUSION: These data reveal a low periprocedural rate of stroke or death for both CEA and CAS. This study does however not permit any conclusions as to the superiority or inferiority of CEA and CAS.

Incidence, Treatment and Mortality in Patients with Abdominal Aortic Aneurysms.

BACKGROUND: Aim of this study was to analyze hospital incidence, type of treatment, and hospital mortality rates of patients with abdominal aortic aneurysm (AAA) in Germany from 2005 to 2014. METHODS: Microdata of the diagnosis-related group (DRG) statistics compiled by the German Federal Statistical Office for the years 2005-2014 were analyzed. Patients who were hospitalized for a ruptured AAA (rAAA, ICD-10 code I71.3, treated either surgically or conservatively) or received surgical treatment for an unruptured AAA (nrAAA, ICD-10-Code I71.4, treated either with open surgery or an endovascular procedure) were included in the analysis. The "European Standard Population 2013" was used for direct standardization of the hospital incidences. In-hospital mortality was calculated with standardization for age and risk. RESULTS: The standardized overall hospital incidence of AAA was 27.9 and 3.3 cases per 100 000 people for men and women, respectively; over the period of the study, the incidence of rAAA fell by 30% in both sexes and that of nrAAA rose by 16% in men and 42% in women. The percentage of patients receiving endovascular treatment rose from 29% to 75% in patients with nrAAA and from 8% to 36% in patients with rAAA. The age- and risk-standardized in-hospital mortality of nrAAA was 3.3% in men and 5.3% in women. The in-hospital mortality of surgically treated rAAA was 39% in men and 48% in women. CONCLUSION: The hospital incidence of AAA rose from 2005 to 2014, while that of rAAA fell. Endovascular treatment became more common for nrAAA as well as rAAA, and in-hospital mortality fell for both.

The diagnosis, treatment and follow-up of extracranial carotid stenosis.

BACKGROUND: Extracranial atherosclerotic lesions of the carotid bifurcation cause 10% to 20% of all cases of cerebral ischemia. Until now, there have been no comprehensive evidence- and consensus-based recommendations for the management of patients with extracranial carotid stenosis in Germany and Austria. METHODS: The literature was systematically searched for pertinent publications (1990-2011). On the basis of 182 randomized clinical trials (RCTs) and 308 systematic reviews, 30 key questions were answered and evidence-based recommendations were issued. RESULTS: The prevalence of extracranial carotid stenosis is more than 5% from age 65 onward. Men are affected twice as frequently as women. The most important diagnostic technique is Doppler- and color-coded duplex ultrasonography. RCTs have shown that the treatment of high-grade asymptomatic carotid stenosis with carotid endarterectomy (CEA) can lower the 5-year risk of stroke from 11% to 5%. Intensive conservative treatment may lower the stroke risk still further. Moreover, RCTs have shown that CEA for symptomatic 50% to 99% carotid stenosis lowers the 5-year stroke risk by 5% to 16%. Meta-analyses of the 13 available RCTs comparing carotid artery stenting (CAS) with CEA have shown that CAS is associated with a 2% to 2.5% higher risk of periprocedural stroke or death and with a 0.5% to 1% lower risk of periprocedural myocardial infarction. If no particular surgical risk factors are present, CEA is the standard treatment for high-grade carotid stenosis. CAS may be considered as an alternative to CEA if the rate of procedure-related stroke or death can be kept below 3% or 6% for asymptomatic and symptomatic stenosis, respectively. CONCLUSION: Further studies are needed so that better selection criteria can be developed for individually tailored treatment.

Surgical and endovascular treatment of symptomatic aberrant right subclavian artery (arteria lusoria).

Right aberrant subclavian artery, also called arteria lusoria, is one of the most common intrathoracic arterial anomalies. Although mostly asymptomatic, the retroesophageal and retrotracheal course of the lusorian artery might result in unspecific thoracic pain, dysphagia, dyspnea, arterioesophageal or arteriotracheal fistulae with hematemesis or hemoptysis, and aneurysmal formation with relevant risk of rupture. The purpose was to present our experience with six patients with a symptomatic aberrant right subclavian artery, two patients with dysphagia or dyspnea caused by a nonaneurysmal lusorian artery, and four patients with arteria lusoria aneurysms. The operative procedures performed are described and discussed in view of the data reported in the literature. According to the classification of the lusorian artery pathology, a combined intervention with right subclavian artery transposition, distal or proximal lusorian artery ligation or proximal endovascular occlusion for nonaneurysmal disease, or endovascular thoracic aortic stent graft implantation for lusorian artery aneurysms seems to be an additional and minimally invasive approach with promising midterm results.

C-type natriuretic peptide inhibits constrictive remodeling without compromising re-endothelialization in balloon-dilated renal arteries.

PURPOSE: To investigate the long-term effect of local, liposome-mediated gene transfer of C-type natriuretic peptide (CNP) plasmid versus CNP protein on restenosis in porcine renal arteries following balloon angioplasty. METHODS: The renal arteries of 15 pigs were dilated and the adventitia at the site of balloon injury injected with CNP protein, pCR3.1 plasmid encoding CNP, or the beta-galactosidase gene (control) via a needle injection catheter. Five animals receiving the CNP and control genes in dilated arteries were sacrificed after 3 weeks to analyze re-endothelialization, proliferation, and early CNP expression. Ten animals designated for the long-term experiments (3 months) were treated with the CNP gene versus CNP protein (n=3), the CNP gene versus the control gene (n=3), and the CNP protein versus the control gene (n=3). One animal served as a dilated non-treated control. Transfection and expression of CNP and beta-galactosidase were measured by polymerase chain reaction (PCR) and reverse transcription PCR. Renal arterial lumen narrowing was measured with angiography and histology. Endothelialization was assessed using Evans blue stain; vWF, CD31, factor VIII, and Ki67 were markers for immunohistochemical analysis. RESULTS: An intact endothelial layer was seen at 3 weeks following angioplasty in all transfected arteries. Three months following treatment, computer-assisted morphometric analysis revealed significant enlargement of the arterial cross-sectional areas in CNP plasmid- treated vessels compared to dilated but untreated arteries (CNP plasmid +34.8%+/-13.9% versus CNP protein -1.75%+/-19.9% versus beta-galactosidase -47.0%+/-13.9%, p<0.01). Angiographic analysis showed significant enlargement of the arterial diameter compared to dilated, untreated arteries (CNP plasmid +20.8%+/-6.8% versus CNP protein +5.7%+/-6.0% versus beta-galactosidase -24.5%+/-10.2%, p<0.01). CONCLUSIONS: Local application of CNP plasmid proved superior to CNP protein in producing rapid re-endothelialization and significantly enlarging the renal arterial lumen following dilation.