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Lameness in pigs is one of the major reasons for culling and early losses in pigs. This can be linked to osteoporosis due to pathologic alterations in bone mineral density (BMD) or bone mineral content (BMC) and may also be linked to the sex. Dealing with the ban on piglet castration without anaesthesia in Germany 2021, we have three male “sex” types: entire boars (EB), immunocastrated boars (IB), and surgically castrated boars (SB). The hypothesis of the present study is that BMC or BMD varies between different male sex types. If sex has an effect on bone mineralization (BMC or BMD) and if this affects leg health, it could result in more lameness and problems during fattening in the negatively affected sex type. The present study evaluated bone mineralization (in terms of BMD and BMC) and body composition traits using dual-energy X-ray absorptiometry (DXA) three times during growth at 30, 50, and 90 kg live body weight. Nine body regions were analysed for bone mineral traits and compared for different male sex types and the fattening season. Significant differences were found regarding BMD (and BMC) among EB, IB, and SB for whole-body BMD (BMC). Additionally significant differences were found in the front and lower hind limbs, where SB showed a significantly higher BMD compared to EB, with IB in between. Additionally regional differences were detected among the groups. Further studies are needed to evaluate the effect of these differences in bone mineralization on leg health.

Objectives The PROSE trial purpose is to investigate whether the incidence of thromboembolic—related complications is reduced with a current generation mechanical prosthesis (On-X Life Technologies/CryoLife Inc.—On-X) compared with a previous generation mechanical prosthesis (St Jude Medical—SJM). The primary purpose of the initial report is to document the preoperative demographics, and the preoperative and operative risk factors by individual prosthesis and by Western and Developing populations. Methods The PROSE study was conducted in 28 worldwide centres and incorporated 855 subjects randomized between 2003 and 2016. The study enrollment was discontinued on August 31, 2016. The preoperative demographics incorporated age, gender, functional class, etiology, prosthetic degeneration, primary rhythm, primary valve lesion, weight, height, BSA and BMI. The preoperative and operative evaluation incorporated 24 risk factors. Results The total patient population (855) incorporated On-X population (462) and the St Jude Medical population (393). There was no significant difference of any of the preoperative demographics between the On-X and SJM groups. The preoperative and operative risk factors evaluation showed there was no significant difference between the On-X and St Jude Medical populations. The preoperative and operative risk factors by valve position (aortic and mitral) also documented no differentiation. The dominant preoperative demographics of the Western world population were older age, male gender, sinus rhythm, aortic stenosis, congenital aortic lesion, and mitral regurgitation. The dominant demographics of the Developing world population were rheumatic etiology, atrial fibrillation, aortic regurgitation, mixed aortic lesions, mitral stenosis and mixed mitral lesions. The Developing world group had only one significant risk factor, congestive heart failure. The majority of the preoperative and operative risk factors were significant in the Western world population. Conclusions The preoperative demographics do not differentiate the prostheses but do differentiate the Western and Developing world populations. The preoperative and operative risk factors do not differentiate the prostheses BUT do differentiate the Western and Developing world populations.

Background The Scepter XC is a dual-lumen balloon catheter that accommodates a 0.014-inch microwire and can be used for balloon-assisted coiling of cerebral aneurysms. We describe our experience with the use of this device. Methods Two high-volume institution neurointerventional databases were retrospectively reviewed for cerebral aneurysms treated with balloon-assisted coiling using the Scepter XC balloon catheter. Patient demographics, aneurysm characteristics, and procedural details were recorded. Major procedure-related neurologic complications were defined as events that caused an increase in modified Rankin Scale that persisted for more than 1 week after the procedure. Follow-up aneurysm occlusion was assessed using the Raymond-Roy classification. Results During the study period, 231 aneurysms were treated in 219 patients (152 women, 67 men) with a mean age of 58.4 ± 12.2 years. Mean aneurysm size was 6.1 ± 3.1 mm, with a mean neck diameter of 3.1 ± 1.3 mm. In total, 77.5% of aneurysms were wide necked, and 39.8% were treated in the setting of subarachnoid hemorrhage. The major complication rate was 0.9% (2/231) per treated aneurysm, including one stroke and one death related to intraoperative aneurysm rupture. Excluding patients who died, angiographic follow up was available for 85.3% (191/224) of aneurysms. During a mean follow up of 17.4 ± 13.0 months (range, 1.7–66.5 months), Raymond-Roy 1 and 2 occlusion rates were 56.5% (108/191) and 35.6% (68/191), respectively. The retreatment rate was 12.6% (24/191). Conclusion Our experience using the coaxial dual-lumen Scepter XC for balloon-assisted coiling demonstrates acceptable aneurysm occlusion and complication rates.

Background: The aim of the current study was to determine whether the time to insulin therapy initiation in patients with type 2 diabetes in primary care in Germany has changed in recent years. Methods: Longitudinal data from general practices in Germany (Disease Analyzer) were analyzed. These data included information of 7128 patients (age: 68.5 [SD: 11.5] years; 54.4% male) receiving incident insulin therapy in 2010/2011 and 8216 patients (age: 69.1 [SD: 11.9] years; 54.9% male) receiving incident insulin therapy in 2016/2017. Changes in time to insulin initiation in the practices and the last HbA1c value before the start of insulin therapy were analyzed, stratified by index date. To analyze the impact of covariables on the time to insulin initiation, a multivariate regression analysis was performed, adjusted for age, sex, diabetologist care, and HbA1c as independent variables. Results: Median time from T2D diagnosis to insulin therapy in the Disease Analyzer database increased from 1717 days in 2010/2011 to 1917 days in 2016/2017 ( P < .001). The proportion of patients with a HbA1c value ≥9% before insulin initiation was high in both groups (2010/2011: 33.0%, 2016/2017: 34.2%, P = .347). The time to insulin initiation in DPP-4i patients was 112 days longer, and in SGLT2 patients 346 days longer than in patients treated with sulfonylurea. Conclusions: The present analysis confirms an increasing delay of the insulin therapy initiation as a consequence of the more frequent use of newer oral antidiabetics. However, the rather moderate increase of time to insulin might display insufficient long-term glycemic control using these agents. Still, more than one-third of patients receive insulin only when HbA1c levels exceed 9%.

Objective First, to determine the number of accident-related complex regional pain syndrome (CRPS) cases from 2008 to 2015 and to identify factors associated with an increased risk for developing CRPS. Second, to analyze the duration of work incapacity and direct health care costs over follow-up periods of two and five years, respectively. Design Retrospective data analysis. Setting Database from the Statistical Service for the Swiss National Accident Insurances covering all accidents insured under the compulsory Swiss Accident Insurance Law. Subjects Subjects were registered after an accident between 2008 and 2015. Methods Cases were retrospectively retrieved from the Statistical Service for the Swiss National Accident Insurances. Cases were identified using the appropriate International Classification of Diseases, 10th Revision, codes. Results CRPS accounted for 0.15% of all accident cases. Age, female gender (odds ratio [OR] = 1.53, 95% confidence interval [CI] = 1.47–1.60), and fracture of the forearm (OR = 38, 95% CI = 35–42) were related to an increased risk of developing CRPS. Over five years, one CRPS case accumulated average insurance costs of $86,900 USD and treatment costs of $23,300 USD. Insurance costs were 19 times and treatment costs 13 times the average costs of accidents without CPRS. Within the first two years after the accident, the number of days lost at work was 20 times higher in patients with CRPS (330 ± 7 days) than in patients without CRPS (16.1 ± 0.1 days). Two-thirds of all CRPS cases developed long-term work incapacity of more than 90 days. Conclusion CRPS is a relatively rare condition but is associated with high direct health care costs and work incapacity.

Background The Pipeline embolization device (PED) has expanded the range of aneurysms amenable to endovascular treatment, including some that were previously untreatable. The PED contains several metals, including nickel, cobalt, chromium, platinum, and tungsten. The safety of PED implantation in patients with cutaneous metal allergy is unknown. The aim of this study was to assess clinical and angiographic outcomes of PED treatment in patients with cutaneous metal allergy. Methods A single-institution neurointerventional database was retrospectively reviewed for patients with documented cutaneous metal allergy who were treated with the PED. Patient, aneurysm, and procedural data were collected, including perioperative and delayed complications. Posttreatment angiograms were reviewed for in-Pipeline stenosis and aneurysm occlusion. Results Twenty patients with metal allergy underwent 23 PED treatments for 26 aneurysms. The cohort was 95% (19/20) female; mean age was 55.7 years. Aneurysms were primarily anterior circulation (92%, 24/26) and saccular (92%; 24/26); mean size was 8.8 mm (range, 2–32 mm). One PED was implanted in 70% (14/20) of patients, 25% (5/20) had 2 devices placed, and 1 patient had 3 devices. One major procedural complication occurred (4.3%, 1/23) in which a stroke was caused by perioperative PED thrombosis. Angiographic follow-up was available for all patients (mean duration 15.7 months; range, 6–64 months), which demonstrated a complete aneurysm occlusion rate of 88% (23/26). Asymptomatic in-Pipeline stenosis occurred in 2 cases, resulting in 65% and 50% parent artery stenosis, respectively. Conclusions Preliminary results suggest that PED implantation in patients with cutaneous metal allergy is safe and effective.

Skeletal disorders, including fractures and osteoporosis, in laying hens cause major welfare and economic problems. Although genetics have been shown to play a key role in bone integrity, little is yet known about the underlying genetic architecture of the traits. This study aimed to identify genes associated with bone breaking strength and bone mineral density of the tibiotarsus and the humerus in laying hens. Potentially informative single nucleotide polymorphisms (SNP) were identified using Random Forests classification. We then searched for genes known to be related to bone stability in close proximity to the SNPs and identified 16 potential candidates. Some of them had human orthologues. Based on our findings, we can support the assumption that multiple genes determine bone strength, with each of them having a rather small effect, as illustrated by our SNP effect estimates. Furthermore, the enrichment analysis showed that some of these candidates are involved in metabolic pathways critical for bone integrity. In conclusion, the identified candidates represent genes that may play a role in the bone integrity of chickens. Although further studies are needed to determine causality, the genes reported here are promising in terms of alleviating bone disorders in laying hens.

Depending on the breed or crossbreed line, cows have to cope with a more or less severe negative energy balance during the period of high milk yields in early lactation, which can be detected by beta-hydroxybutyrate (BHBA) and non-esterified fatty acids (NEFAs) in blood. Preventing cows from undergoing a severe negative energy balance by breeding and/or feeding measures is likely to be supported by the public and may help to improve the sustainability of milk production. The aim was to compare BHBA and NEFA concentrations in the blood of Holstein and Simmental cows and their crosses during the prepartum period until the end of lactation. In total, 164 cows formed five genetic groups according to their theoretic proportion of Holstein and Simmental genes as follows: Holstein (100% Holstein; n = 9), R1-Hol (51–99% Holstein; n = 30), F1 crossbreds (50% Holstein, 50% Simmental; n = 17), R1-Sim (1–49% Holstein; n = 81) and Simmental (100% Simmental; n = 27). NEFA and BHBA were evaluated once a week between April 2018 and August 2019. A mixed model analysis with fixed effects breed, week (relative to calving), the interaction of breed and week, parity, calving year, calving season, milking season, and the repeated measure effect on cows was used. Holstein cows had higher NEFAs (0.196 ± 0.013 mmol/L), and Simmental cows had the lowest NEFA concentrations (0.147 ± 0.008 mmol/L, p = 0.03). R1-Sim, F1 and R1-Hol cows had intermediate values (0.166 ± 0.005, 0.165 ± 0.010, 0.162 ± 0.008 mmol/L; respectively). The highest NEFA value was found in the first week after calving (0.49 ± 0.013 mmol/L). BHBA did not differ among genetic groups (p = 0.1007). There was, however, an interaction between the genetic group and week (p = 0.03). While Simmental, R1-Sim and F1 cows had the highest BHBA value, the second week after calving (0.92 ± 0.07 and 1.05 ± 0.04, and 1.10 ± 0.10 mmol/L, respectively), R1-Hol and Holstein cows showed the BHBA peak at the fourth week after calving (1.16 ± 0.07 and 1.36 ± 0.12 mmol/L, respectively). Unexpectedly, Holstein cows had a high BHBA peak again at week 34 after calving (1.68 ± 0.21 mmol/L). The genetic composition of the cows affects NEFA and BHBA. Simmental and R1-Sim cows mobilize fewer body reserves after calving. Therefore, dairy cows with higher degrees of Simmental origin might be more sustainable in comparison with Holstein genetics in the present study.

Simple Summary Brittle or fractured bones due to continuous demineralisation cause major welfare and economic problems in laying hens. Bone weakness in laying hens is frequently attributed to long-term selection for increased egg production, but this is controversially discussed in the scientific literature. We aimed at characterizing factors influencing the bone breaking strength of laying hens, focusing mainly on the effect of eggshell production. By examining four different chicken layer lines separately, a genetically diverse spectrum of laying hen origins was included in our study. It was shown that bone strength is primarily influenced by bone mineral density. A strong association between bone strength and eggshell production was not observed within each of the lines studied. This applied to all layer lines. Our results suggest that a high egg number does not generally impair bone stability within layer lines. Findings from this study contribute to the discussion on the improvement of bone stability in poultry breeding programs and thus lead to increased animal welfare in egg production. Abstract Impaired animal welfare due to skeletal disorders is likely one of the greatest issues currently facing the egg production industry. Reduced bone stability in laying hens is frequently attributed to long-term selection for increased egg production. The present study sought to analyse the relationship between bone stability traits and egg production. The study comprised four purebred layer lines, differing in their phylogenetic origin and performance level, providing extended insight into the phenotypic variability in bone characteristics in laying hens. Data collection included basic production parameters, bone morphometry, bone mineral density (BMD) and bone breaking strength (BBS) of the tibiotarsus and humerus. Using a multifactorial model and regression analyses, BMD proved to be of outstanding importance for bone stability. Only for the tibiotarsus were morphometric parameters and the bone weight associated with BBS. Within the chicken lines, no effect of total eggshell production on BBS or BMD could be detected, suggesting that a high egg yield itself is not necessarily a risk for poor bone health. Considering the complexity of osteoporosis, the estimated genetic parameters confirmed the importance of genetics in addressing the challenge of improving bone strength in layers.

Aim: To estimate the health economic impact of osteosynthesis (OS) in fracture care over six decades in 17 high-income countries. Patients & methods: Applying a decision tree model, we assumed a hypothetical absence of OS and compared OS (intervention) with conservative treatment (CONS; comparator). We included patients with femur, tibia and radius fractures (age Results: We estimated savings in direct and indirect costs of 855 billion Swiss francs in the working age population in addition to 4.6 million years of life gained. In the elderly population, 69 billion Swiss francs were saved in direct costs of proximal femur fractures in addition to 73 million years of life gained. Conclusion: OS contributed to maximize health gains of society.

The Scepter XC balloon catheter can be used for balloon-assisted coiling (BAC) of cerebral aneurysms but also accommodates delivery of a low-profile visible intraluminal stent (LVIS Jr.). We assessed the safety and effectiveness of BAC using the Scepter XC, with LVIS Jr. stent-assisted coiling (SAC) as a bailout option.A single-institution prospectively maintained neurointerventional database was reviewed for wide-necked (neck width ≥4 mm or dome/neck ratio2) saccular aneurysms treated using the Scepter XC. Complication and angiographic occlusion rates of BAC and SAC procedures were compared. Multivariate logistic regression was used to identify variables predictive of complete aneurysm occlusion.The cohort included 141 wide-necked saccular intracranial aneurysms treated in 135 procedures. SAC was used to treat 30% of aneurysms by deploying the LVIS Jr. through the Scepter XC. The overall procedural complication rate was 8.9%, including a 1.5% rate of symptomatic thromboembolic events and 3.0% rate of hemorrhagic complications, with no significant differences in complications between BAC and SAC procedures (P = 0.27). The overall complete or near-complete aneurysm occlusion rate was 96%, with trends toward higher complete aneurysm occlusion and lower retreatment rates with SAC (78 vs. 57%; P = 0.13; 0 vs. 8.4%, P = 0.13). Multivariate logistic regression identified aneurysm size, procedure technique (BAC or SAC), and duration of follow-up as independent predictors of complete aneurysm occlusion.Use of the Scepter XC for BAC, with LVIS Jr. SAC as a bailout option, shows acceptable angiographic and clinical results.

BACKGROUND AND AIM Frozen shoulder is a poorly understood pathological entity that is characterised by a painful and stiff shoulder. To analyse the socioeconomic impact of frozen shoulder in terms of cost generation and prolonged absence from work, we conducted a retrospective cohort study based on shoulder injuries through accidents in Switzerland. METHODS Data were obtained from the comprehensive database of the Statistical Service for the Swiss National Accident Insurances (SSUV). Cases with shoulder injuries (ICD-10 codes S4* and M84.3*) and/or an additional code of adhesive capsulitis (M75.0) were extracted. Outcomes were work incapacity, with long-term work incapacity defined as absence from work for >90 days and very-long-term cases with >360 days lost. Healthcare and treatment costs as well as total insurance expenses were measured over a 5-year follow-up. Multivariate statistical analyses were used to quantify the effect of the frozen shoulder complication. RESULTS Among all 456,926 patients with a shoulder injury, 5% or a total of 22,228 posttraumatic frozen shoulder cases were observed over the 8-year period. Patients suffering from a frozen shoulder after shoulder injury showed significantly longer sick leave periods with 30.8% long-term and 9.7% very-long-term cases compared with 9.4% and 1.3%, respectively, in the non-frozen shoulder cohort. Overall costs per case for an injured shoulder without developing a frozen shoulder was roughly CHF 8000, whereas expenses for cases with posttraumatic and postoperative frozen shoulder were CHF 34,000 per case. CONCLUSION Developing a frozen shoulder after a shoulder injury is associated with significant longer work incapacities (3.3–7.5 times) and is responsible for costs of CHF 78 million every year. The presented numbers are for cases covered by the compulsory accident insurance only and do not include the even more frequent idiopathic frozen shoulder cases.

PurposeTo report the efficacy of A Direct Aspiration first-Pass Thrombectomy (ADAPT) technique with larger-bore ACE aspiration catheters as first-line treatment for anterior circulation emergent large vessel occlusions (ELVOs), and assess for the presence of a first-pass effect with ADAPT.MethodsWe retrospectively reviewed 152 consecutive patients with anterior circulation ELVOs treated with the ADAPT technique as first-line treatment using ACE60, 64, or 68 at our institution. Baseline characteristics, procedural variables, and modified Rankin Scale (mRS) at 90 days were recorded.ResultsFifty-seven patients were treated with ACE60 (37.5%), 35 with ACE64 (23%), and 60 with ACE68 (39.5%). Median groin puncture to reperfusion time was 30 min with ACE60, 26 min with ACE64, and 19.5 min with ACE68. Successful reperfusion after the first ADAPT pass was 33% with ACE60 and 53% with ACE68 (P=0.04). The stent-retriever rescue rate was 26% with ACE60, 3% with ACE64, and 10% with ACE68 (P=0.004). In multivariate logistic regression analysis, use of the ACE68 aspiration catheter was an independent predictor of successful reperfusion after the first ADAPT pass (P=0.016, OR1.67, 95% CI 1.1 to 2.54), and successful reperfusion after the first ADAPT pass was an independent predictor of good clinical outcome at 90 days (P=0.0004, OR6.2, 95% CI 2.27 to 16.8).ConclusionUse of the larger-bore ACE 68 aspiration catheter was associated with shorter groin puncture to reperfusion time, higher rate of successful reperfusion after the first ADAPT pass, and lower rate of stent-retriever rescue. Further, a first-pass effect was demonstrated in our ADAPT patient cohort.

Objective Laron syndrome (LS) is a rare, autosomal recessive disorder in humans caused by loss-of-function mutations of the growth hormone receptor (GHR) gene. To establish a large animal model for LS, pigs with GHR knockout (KO) mutations were generated and characterized. Methods CRISPR/Cas9 technology was applied to mutate exon 3 of the GHR gene in porcine zygotes. Two heterozygous founder sows with a 1-bp or 7-bp insertion in GHR exon 3 were obtained, and their heterozygous F1 offspring were intercrossed to produce GHR-KO, heterozygous GHR mutant, and wild-type pigs. Since the latter two groups were not significantly different in any parameter investigated, they were pooled as the GHR expressing control group. The characterization program included body and organ growth, body composition, endocrine and clinical-chemical parameters, as well as signaling studies in liver tissue. Results GHR-KO pigs lacked GHR and had markedly reduced serum insulin-like growth factor 1 (IGF1) levels and reduced IGF-binding protein 3 (IGFBP3) activity but increased IGFBP2 levels. Serum GH concentrations were significantly elevated compared with control pigs. GHR-KO pigs had a normal birth weight. Growth retardation became significant at the age of five weeks. At the age of six months, the body weight of GHR-KO pigs was reduced by 60% compared with controls. Most organ weights of GHR-KO pigs were reduced proportionally to body weight. However, the weights of liver, kidneys, and heart were disproportionately reduced, while the relative brain weight was almost doubled. GHR-KO pigs had a markedly increased percentage of total body fat relative to body weight and displayed transient juvenile hypoglycemia along with decreased serum triglyceride and cholesterol levels. Analysis of insulin receptor related signaling in the liver of adult fasted pigs revealed increased phosphorylation of IRS1 and PI3K. In agreement with the loss of GHR, phosphorylation of STAT5 was significantly reduced. In contrast, phosphorylation of JAK2 was significantly increased, possibly due to the increased serum leptin levels and increased hepatic leptin receptor expression and activation in GHR-KO pigs. In addition, increased mTOR phosphorylation was observed in GHR-KO liver samples, and phosphorylation studies of downstream substrates suggested the activation of mainly mTOR complex 2. Conclusion GHR-KO pigs resemble the pathophysiology of LS and are an interesting model for mechanistic studies and treatment trials., Highlights • GHR-deficient pigs reveal postnatal growth retardation, disproportionate organ growth and an increased total body fat content. • GHR-deficient pigs show markedly reduced serum IGF1 and IGFBP3 levels, and transient juvenile hypoglycemia. • Increased expression and phosphorylation of IRS1 in liver of adult GHR-deficient pigs suggest increased insulin sensitivity. • Increased phosphorylation of JAK2 in liver of GHR-deficient pigs may be explained by higher serum leptin levels and activation of hepatic LEPR.

BACKGROUND Tumor-treating fields (TTFields) are a modern anti-mitotic, non-invasive therapy for the treatment of patients with recurrent and newly diagnosed glioblastoma multiforme (GBM). In Europe, Optune® recieved in 2015 the CE certification. TTFields are a low-intensity (1–3 V/cm) approved therapeutic modality using a non-invasive application of intermediate frequency (200 kHz) alternating electric fields through four transducer arrays directly applied to the skin. The EF-14 study has shown that the addition of TTFields to temozolomide chemotherapy in patients with newly diagnosed GBM significantly improved overall survival (OS) and progression-free survival (PFS) without additional adverse events, apart from mild to moderate skin irritations (Stupp et al., JAMA 2017). MATERIAL We retrospectively analyzed data from TTFields-treated patients (2015–2020) that were treated at our department. Patient characteristics such as MGMT promoter methylation status, age, and diagnosis, as well as treatment duration and TTFields therapy usage, were evaluated for this study. RESULTS 29 patients were treated with TTFields therapy between 2015 and 2020 at our hospital. Most patients received TTFields as primary treatment together with temozolomide maintenance therapy. In detail, 48% of patients were diagnosed with newly diagnosed GBM, 41% received TTFields therapy after tumor recurrence and 10% were diagnosed with other high-grade gliomas. In summary, patients could integrate TTFields therapy into their daily life and showed high adherence to the therapy.Particularly, one of our patients (with MGMT-promoter methylation positive) receives TTFields therapy now for almost 1229 days (approx. 41 months) and is still on therapy. Additionally, this patient shows a high usage rate of 86% indicating well integration of the therapy into daily life. CONCLUSION Taken together, our data provided the outcomes of using TTFields together with chemotherapy in the treatment of recurrent and newly diagnosed GBM in our department. Therapy with TTFields has been showing to provide significant clinical benefit for GBM patients.

Mycobacterium avium subsp. paratuberculosis (MAP) is a pathogen causing paratuberculosis in cattle and small ruminants. During the long asymptomatic subclinical stage, high numbers of MAP are excreted and can be transmitted to food for human consumption, where they survive many of the standard techniques of food decontamination. Whether MAP is a human pathogen is currently under debate. The aim of this study was a better understanding of the host-pathogen response by analyzing the interaction of peripheral blood lymphocytes (PBL) from cattle with MAP in their exoproteomes/secretomes to gain more information about the pathogenic mechanisms of MAP. Because in other mycobacterial infections, the immune phenotype correlates with susceptibility, we additionally tested the interaction of MAP with recently detected cattle with a different immune capacity referred as immune deviant (ID) cows. In PBL, different biological pathways were enhanced in response to MAP dependent on the immune phenotype of the host. PBL of control cows activated members of cell activation and chemotaxis of leukocytes pathway as well as IL-12 mediated signaling. In contrast, in ID cows CNOT1 was detected as highly abundant protein, pointing to a different immune response, which could be favorable for MAP. Additionally, MAP exoproteomes differed in either GroEL1 or DnaK abundance, depending on the interacting host immune response. These finding point to an interdependent, tightly regulated response of the bovine immune system to MAP and vise versa.

Mycobacterium avium subsp. paratuberculosis (MAP) is a pathogen causing paratuberculosis in cattle and small ruminants. During the long asymptomatic subclinical stage, high numbers of MAP are excreted and can be transmitted to food, where they survive many of the standard techniques of food decontamination. If these MAP are harmful to the consumers is currently under debate. In general, there is a lack of information regarding interaction of the hosts immune system with MAP.In this study, we tested the interaction of peripheral blood lymphocytes (PBL) from cattle with MAP in their exoproteomes/secretomes. Because in other mycobacterial infections, the immune phenotype correlates with susceptibility, we additionally tested the interaction of MAP with recently detected immune deviant cows.In PBL, different biological pathways were enhanced in response to MAP dependent on the immune phenotype of the host. PBL of control cows activated members of cell activation and chemotaxis of leukocytes pathway as well as IL-12 mediated signaling. In contrast, in ID cows CNOT1 was detected as highly abundant protein, pointing to a different immune response, which could be favorable for MAP. Additionally, MAP reacted different to the hosts. Their exoproteomes differed in either GroEL1 or DnaK abundance, depending on the interacting immune response.These findings point to an interdependent, tightly regulated response of MAP and the immune system.

Background:Activin A and follistatin belong to an anti-inflammatory auto-regulatory cycle. Patients with rheumatoid arthritis (RA) have increased activin A levels in the synovial fluid and tissue. During inflammation, activin A is released systemically, then inducing its antagonist follistatin. This negative feedback is active in different cell types but not RA synovial fibroblasts (SF). Fibroblasts interact with endothelial cells in inflamed tissues inducing angiogenesis.Objectives:Evaluation of the role of activin A and follistatin on RASF and endothelial cell interactions.Methods:RA synovium was used for RASF isolation, HUVEC were commercially obtained. RASF and HUVEC were stimulated in mono- and coculture. Direct: RASF together with HUVEC; indirect: inserts with HUVEC separated by a membrane from RASF. Stimuli: activin A 15ng/ml, follistatin 500ng/ml, IL-1β 1ng/ml. Proliferation was analyzed by BrdU assay. RASF were Calcein-AM stained. Cells were transferred to 24-well plates after 18h stimulation. After adhesion for 1h, non-adherent cells were removed by shaking 3x for 5 min. Afterwards, fluorescent cells were quantified. For the flow-adhesion assay, HUVEC were cultured on rattail collagen coated capillary slides. HUVEC and RASF were stimulated for 4h with TNFα, TNFα+activin A or TNFα+follistatin. After stimulation, 2x10^6 RASF were resuspended in 20ml medium and sent through the capillaries. Two 1min videos were recorded (18.4ml/h, 30.5ml/h). Settings: TNFα-stimulated RASF on HUVEC stimulated wit TNFα or activin A+TNFα or follistatin+ TNFα. For migration assays, 2% FCS medium with 1x10^5 cells were placed in inserts (8µm membrane) into wells with 10% FCS (control: 2%FCS vs. 2%FCS) and stimulated with, IL-1, IL-1+activinA and IL-1+follistatin. After 16h, migrated cells were quantified. For scratch-assay 4x10^5 cells were cultured overnight, then cells were scratched and stimulated, afterwards 3 pictures per scratch were taken at start, after 10h and every 1.5h. Cells migrating into the scratch area were quantified.Results:IL-1 induced activin A in RASF and HUVEC in all settings. IL-1-induced activin A release was reduced by follistatin in HUVEC monoculture and both cocultures compared to IL-1 alone but not in RASF monoculture. IL-1-induced IL-6 release was reduced by activin A in HUVEC and indirect coculture but not in RASF monoculture and direct coculture. Follistatin did not alter IL-6 responses. IL-1 induced VEGF in RASF but not in HUVEC and was not altered by activin A. Short-term adhesion showed no significant influence of activin A or follistatin (n=4). Flow adhesion assay showed reduced adherence/rolling of RASF on HUVEC stimulated with TNFα and activin A (n=4). Migration assays showed that IL-1 decreased migration but without significant difference between the induced effects mediated by IL-1+activinA and IL-1+follistatin (n=4). Scratch assay showed increased migration in dicrect coculture with greater difference between stimulated and unstimulated cells in RASF monoculture and indirect coculture (n=4). Proliferation was not altered by activin A or follistatin.Conclusion:In direct and indirect coculture of HUVEC with RASF the effect on HUVEC was dominant leading to reduced IL-1-induced activin A release. However, the IL-1-induced IL-6 release in RASF or HUVECs was decreased by activin A in HUVEC monoculture and indirect coculture but not during cell-contact between both cell types. The direct interaction of RASF with HUVEC seems to prevent the reducing activin A effect on IL-6 release in HUVECs. Activin A seems to not to have an impact on short-term cell adhesion but first observations show, that activin A alters selectin-mediated adhesion under flow conditions. The migration assay shows that IL-1-induced effects on cell migration were enhanced by activin A and follistatin. Migration assay shows that IL-1-induced decrease on migration more prominent in indirect coculture and RASF monoculture than in direct coculture although in gap migration in the scratch assay was highest in direct coculture.Disclosure of Interests:None declared

Exposure to metal working fluids (MWF) is common in machining processes worldwide and may lead to diseases of the skin and the respiratory tract.The aim of the study was to investigate exposure and diseases due to MWF in Switzerland between 2004 and 2013.We performed descriptive statistics including determination of median and 90th percentile values of MWF concentrations listed in a database of Suva. Moreover, we clustered MWF-induced occupational diseases listed in a database from the Swiss Central Office for Statistics in Accident Insurance, and performed linear regression over time to investigate temporal course of the illnesses.The 90th percentile for MWF air concentration was 8.1 mg (aerosol + vapor)/mThis is the first investigation describing exposure to and diseases due to MWF in Switzerland over a timeframe of 10 years. In general, working conditions in the companies of this investigation were acceptable. Most measured MWF concentrations were below both the Swiss and most international occupational exposure limits of 2014. The percentage of workers declared unfit for work was 17% compared to the average of other occupational diseases (12%).

Background The pathophysiology of delayed cerebral ischemia (DCI) after aneurysmal subarachnoid hemorrhage (aSAH) may include platelet activation and microthrombi formation. Antiplatelet therapy may reduce the incidence of DCI and improve clinical outcomes after aSAH. This study compared outcomes among aSAH patients receiving aspirin monotherapy versus dual antiplatelet therapy (DAPT). Methods Aneurysmal subarachnoid hemorrhage patients treated at a single institution between November 2011 and December 2017 were divided according to whether they received aspirin monotherapy or DAPT after endovascular treatment. Baseline characteristics and outcomes of the groups were compared, including incidences of delayed cerebral ischemia, bleeding complications, symptomatic vasospasm, in-hospital mortality, and functional status 6 months after discharge. Results During the study period, 142 patients met study inclusion criteria, of which 123 were treated with aspirin monotherapy (87 %) and 19 were treated with DAPT (13 %). There was no statistically significant difference between the aspirin monotherapy and DAPT groups with respect to incidences of delayed cerebral ischemia (4.9 vs 10.5 %; p = 0.32), symptomatic vasospasm (13.0 vs 15.8 %; p = 0.74), or good clinical outcome at 6-month follow up (73.3 vs 66.7 %; p = 0.56). The DAPT group experienced a higher incidence of in-hospital mortality (21 vs 5.7 %; p = 0.02), but DAPT did not remain independently predictive of this outcome on regression analysis. There was a trend toward a higher bleeding complication rate in the DAPT group (0.8 vs 5.3 %; p = 0.13). Conclusions DAPT does not reduce the incidence of DCI or improve outcomes in aSAH patients, and may increase the risk of clinically significant bleeding complications.

Objectives The correlation between quartz dust concentrations in the Swiss enterprises and the incidence of silicosis and other related diseases acknowledged as occupational diseases (OD) was investigated. Material and methods Quartz dust concentrations were obtained from Suva's databases of occupational health surveillance measurements between 2005 and 2014. Information on quartz dust-related diseases was from medical dossiers of workers with OD acknowledged by Suva between 2005 and 2014. Results The median quartz dust concentration of the 2579 measurements between 2005 and 2014 was 0.09 mg/m3 (alveolar fraction). Out of all measurements, 28% were above the Swiss occupational exposure limit (OEL) of 0.15 mg/m3 (alveolar fraction). One hundred eighty-one individuals suffered from acknowledged quartz dust-related disease (179 silicosis and 2 chronic obstructive pulmonary disease (COPD)). Additionally, 8 out of these workers were diagnosed with lung cancer and 55 with COPD of a non-specified cause. Out of all workers, 46% were exposed to silica dust for the first time before 1975 when the current Swiss OEL was introduced. Out of the foreign workers, 63% began to work abroad, during which they could have at least partly acquired their silicosis. Out of all workers, 75% were ever-smokers. Conclusions The incidence of silicosis decreased drastically from approximately 300 cases/year in the 1970s to fewer than 20 cases/year 20 years ago. Several findings of this study that could help to interpret the ongoing occurrence of the disease include excessive exposure in or outside of Switzerland in former or current times, vulnerability to the development of silicosis due to cigarette smoke, or poor compliance with wearing breathing masks. Int J Occup Med Environ Health 2018;31(5):659-676.

Background The Scepter XC balloon catheter can be used for balloon-assisted coiling (BAC) of cerebral aneurysms, but also accommodates delivery of a low profile visible intraluminal stent (LVIS Jr.). We assessed the safety and effectiveness of BAC using the Scepter XC, with LVIS Jr. stent-assisted coiling (SAC) as a bailout option. Methods A single-institution prospectively-maintained neurointerventional database was retrospectively reviewed for wide-necked (neck width ≥4 mm or dome-to-neck ratio Results The cohort included 169 wide-necked saccular intracranial aneurysms treated in 157 procedures. SAC was used to treat 25% of aneurysms by deploying the LVIS Jr through the Scepter XC. The overall procedural complication rate was 11%, including 3.2% rates of symptomatic thromboembolic and hemorrhagic complications, with no significant differences in complications between BAC and SAC procedures (p=0.26). The overall complete aneurysm occlusion rate was 59%, with trends toward higher complete aneurysm occlusion and lower retreatment rates with SAC (78 vs 54%, p=0.07; 0 vs 9.3%, p=0.10). Multivariate logistic regression identified aneurysm size, procedure technique (BAC or SAC), and duration of follow up as independent predictors of complete aneurysm occlusion. Conclusions Initial experience using the Scepter XC for BAC, with LVIS Jr. SAC as a bailout option, demonstrates acceptable angiographic and clinical results. Disclosures A. Wallace: None. Y. Kayan: 2; C; Medtronic, Penumbra, Microvention. J. Delgado Almandoz: 2; C; Medtronic, Penumbra, Microvention, Accriva. J. Fease: None. A. Milner: None. J. Scholz: None. M. Thomas: None.

Purpose To determine the correlation of serum S100B protein levels with clinical outcome and the presence of DWI abnormalities in acute subarachnoid hemorrhage (SAH). Methods Patients with diffuse SAH at our institution were offered enrollment in a prospective study in which serial MRI, including DWI, FLAIR, PWI, and ASL sequences, was performed at admission, 7 days, 30 days, and upon the development of signs/symptoms of vasospasm. As well, serum S100B levels were measured at the time of each MRI. Patient demographics, Hunt-Hess grade, modified Fisher score, and underlying lesion and treatment technique were recorded. Poor clinical outcome was defined as mRS 3–6 at discharge. Mean S100B levels were compared using Student’s t-test. ROC analyses were performed using MedCalc v18.2.1. p Results Between November 2013 and August 2017, 50 patients were enrolled, 37 women, mean age 58, 20 current smokers. Hunt-Hess grade mean was 3.0. Modified Fisher score mean was 3.5. All underlying vascular lesions were treated endovascularly: 17 ACA aneurysms, 14 ICA aneurysms (including PCOM), 10 MCA aneurysms, 3 basilar tip aneurysms, 1 vertebral aneurysm, 1 posterior fossa AVM, and 4 angiographically-negative SAHs. Mean serum S100B was 73.4 ng/L, 55.1 ng/L and 57.8 ng/L on admission, at 7 days and 30 days, respectively. Overall, serum S100B was significantly higher on admission than at 7 days (p=0.01). Admission serum S100B was significantly higher in patients with poor outcome at discharge (p=0.0003) and in patients with any DWI abnormalities on admission (p=0.0004). The correlation of elevated serum S100B with the presence of DWI abnormalities persisted at 7 days (60.7 ng/L versus 42.8 ng/L, p=0.007). ROC analyses revealed a cutoff of admission S100B>69 ng/L resulting in a sensitivity of 54.8% and a specificity of 94.7% for poor outcome at discharge with an AUC of 0.74 (95% CI 0.60–0.85, p=0.0005), and a cutoff of admission S100B>61 ng/L resulting in a sensitivity of 64.5% and a specificity of 82.4% for the presence of any DWI abnormalities on admission with an AUC of 0.75 (95% CI 0.61–0.86, p=0.0004). Conclusion Admission S100B levels were elevated in setting of acute subarachnoid hemorrhage. Higher S100B levels were associated with poor outcomes at discharge and the presence of DWI abnormalities, both on admission and at 7 days. Disclosures Y. Kayan: 2; C; Medtronic, Penumbra. J. Delgado Almandoz: 2; C; Medtronic, MicroVention, Penumbra. J. Fease: None. A. Wallace: None. J. Scholz: None. A. Milner: None. N. Banerji: None. M. Mulder: None.

Purpose To determine the natural history of diffusion weighted imaging (DWI) abnormalities in early acute subarachnoid hemorrhage (SAH). Methods Patients with diffuse SAH at our institution were offered enrollment in a prospective study in which serial MRI, including DWI, FLAIR, PWI, and ASL sequences, was performed at admission, 7 days, 30 days, and upon the development of signs/symptoms of vasospasm. Patient demographics, Hunt-Hess grade, modified Fisher score, and underlying lesion and treatment technique were recorded. Results Between November 2013 and August 2017, 50 patients were enrolled, 37 women, mean age 58, 20 current smokers. Hunt-Hess grade mean was 3.0. Modified Fisher score mean was 3.5. All underlying vascular lesions were treated endovascularly: 17 ACA aneurysms, 14 ICA aneurysms (including PCOM), 10 MCA aneurysms, 3 basilar tip aneurysms, 1 vertebral aneurysm, 1 posterior fossa AVM, and 4 angiographically-negative SAHs. 31 patients (62%) had DWI abnormalities on their admission scan; all had undergone a catheter angiogram or endovascular treatment of the underlying lesion prior to the MRI. The total number of DWI abnormalities amongst these patients was 250 (214 At 7 days, the total number of DWI abnormalities was 267 (224 Conclusion The acquisition of additional multifocal ischemic injury to the brain is common in early SAH. This phenomenon is independent of cerebral perfusion and large-vessel vasospasm. Disclosures Y. Kayan: 2; C; Medtronic, Penumbra. J. Delgado Almandoz: 2; C; Medtronic, MicroVention, Penumbra. J. Fease: None. A. Wallace: None. J. Scholz: None. A. Milner: None. N. Banerji: None. M. Mulder: None.

Purpose To determine recanalization and post-treatment rupture rates in a large cohort of patients with intracranial aneurysms treated with simple or balloon-assisted coil embolization. Methods We retrospectively reviewed consecutive patients with intracranial aneurysms treated with simple or balloon-assisted coil embolization at our institution from August 8th, 1995 to September 30th, 2017. Baseline aneurysm and patient characteristics, procedural variables and angiographic outcomes were recorded. Aneurysm recanalization was defined as Raymond 3 or Raymond 2 with a neck remnant ≥4 mm or ≥33% of initial aneurysm volume. Multivariate regression analysis was performed to identify independent variables associated with aneurysm recanalization. Results 1634 patients with 1935 intracranial aneurysms were included, 1196 women (73%), mean age 56 years (median 56 years, 8–97 years). 1125 aneurysms were incidental (58.1%), 752 ruptured (38.9%) and 58 symptomatic (3%). Mean aneurysm size 6.3 mm (median 5.5 mm, 1.6–27.9 mm), mean neck 3 mm (median 2.8 mm, 0.6–16.2 mm), mean dome-to-neck ratio 1.7 (median 1.5, 0.7–6.5). Aneurysm locations: 502 ICA (25.9%), 461 Acomm (23.8%), 375 MCA (19.4%), 276 Pcomm (14.3%), 128 basilar tip (6.6%), 79 other ACA (4.1%) and 114 other posterior circulation (5.9%). 749 aneurysms were treated with simple coiling (38.7%) and 1186 with balloon-assisted coiling (61.3%), mean packing density 33.4% (median 31.5%, 6.5%–94.9%). Angiographic follow-up was completed in 1574 of 1730 aneurysms available (91%), mean time to last follow-up 5.3 years (median 4.4 years, 0–20.5 years). Aneurysm occlusion at last follow-up was Raymond 1 in 878 aneurysms (55.8%), Raymond 2 in 496 aneurysms (31.5%), and Raymond 3 in 200 aneurysms (12.7%). There were 254 aneurysm recanalizations at last follow-up (16.1%), and 202 aneurysms were retreated (12.8%). Table 1 summarizes independent predictors of aneurysm recanalization in our cohort. Table 2 summarizes recanalization rates by location and rupture status. 13 aneurysms ruptured after coiling (0.8%), corresponding to an annual post-treatment rupture rate of 0.15%. Mean time from treatment to rupture was 5.8 years (median 4.5 years, 0–12.7 years). Mean time from last angiographic evaluation to rupture was 2.2 years (median 1 year, 0–10.2 years). Aneurysm occlusion at the last angiographic evaluation prior to rupture was Raymond 1 in 4 aneurysms, Raymond 2 in 3 aneurysms, and Raymond 3 in 6 aneurysms. 12 post-treatment ruptures occurred in aneurysms treated before 1/1/2008. Conclusion Endovascular aneurysm treatment with coils alone is associated with relatively high long-term recanalization and post-treatment rupture rates, especially after treatment of ruptured aneurysms. Long-term angiographic follow-up and early retreatment of recanalized aneurysms would be prudent. Disclosures J. Delgado Almandoz: 2; C; Medtronic Neurovascular, Microvention/Terumo, Penumbra, Inc. Y. Kayan: 2; C; Medtronic Neurovascular, Penumbra, Inc. A. Wallace: None. J. Fease: None. J. Scholz: None. A. Milner: None. M. Mulder: None.

Introduction Balloon-assisted coiling (BAC) is a well-established technique for treatment of wide-necked cerebral aneurysms. The Scepter XC (Microvention, Tustin, California, USA) is a dual-lumen balloon catheter that can be used for aneurysm-neck remodeling, protection of branch vessels arising from or near the aneurysm neck, and stabilization of the microcatheter during coil deployment. The lumen also accommodates a 0.014 inch microwire. We describe our initial experience with the use of this device for BAC of cerebral aneurysms. Methods Two high-volume institution neurointerventional databases were retrospectively reviewed for cerebral aneurysms treated with BAC using the Scepter XC balloon catheter. Wide-neck aneurysms were defined as those with a neck width ≥4 mm or a dome-to-neck ratio 10 mm, or DSA and rated using the Raymond-Roy classification. Results During the study period, 231 aneurysms were treated in 219 patients (152 women, 67 men) with a mean age of 58.4±12.2 years. Mean aneurysm size was 6.1±3.1 mm, with a mean neck diameter of 3.1±1.3 mm. 77.9% (180/231) of aneurysms were wide-necked, and 39.8% (92/231) were acutely ruptured at the time of treatment. The overall complication rate was 12.1% (28/231) per treated aneurysm, including a 4.8% (11/231) rate of symptomatic thromboembolic events, 8.6% (8/92) rate of intraoperative rupture when treating acutely ruptured aneurysms, and 1.4% (2/139) rate of intraoperative aneurysm rupture in elective cases. Excluding patients who died, DSA or MRA follow up was available for 85.3% (191/224) of aneurysms. During a mean follow-up of 17.4±13.0 months (range, 1.7–66.5 months), Raymond-Roy 1oc and 2oc clusion rates were 56.5% (108/191) and 35.6% (68/191), respectively. The retreatment rate was 13% (24/191). Conclusions Balloon-assisted coiling using the dual coaxial lumen Scepter XC demonstrates acceptable aneurysm occlusion and complication rates. Disclosures A. Wallace: None. E. Samaniego: 2; C; Medtronic, Microvention. Y. Kayan: 2; C; Medtronic, Penumbra, Microvention. C. Derdeyn: None. J. Delgado: 2; C; Medtronic, Penumbra, Microvention, Accriva. B. Zheng: None. J. Fease: None. M. Thomas: None. J. Scholz: None. A. Milner:None. S. Ortega: 2; C; Stryker Neurovascular, Medtronic.

Purpose To evaluate the safety and efficacy of the Low-profile Visualized Intraluminal Support (LVIS) Jr stent for treatment of intracranial aneurysms. Methods We conducted a retrospective review of all consecutive patients with intracranial aneurysms treated with the LVIS Jr stent between June 4th, 2014 and March 31 st, 2018 at our institution. Baseline patient and aneurysm characteristics, procedural variables, complications and aneurysm occlusion at follow-up were recorded. Results 81 patients underwent 91 procedures to treat 95 intracranial aneurysms using the LVIS Jr stent, 59 women (73%), mean age 59.1 years (median 60 years, 32–83 years). 42 aneurysms were incidental (44%), 41 recurrent (43%), 9 ruptured (10%), and 3 symptomatic (3%). Mean aneurysm size was 6.3 mm (median 5.2 mm, 1.5–31.3 mm), mean neck 3.8 mm (median 2.9 mm, 0.9–13.7 mm), mean dome-to-neck ratio 1.4 (median 1.3, 0.6–2.7). Aneurysm locations were: 36 anterior communicating artery, 26 middle cerebral artery (MCA), 12 basilar tip, 10 anterior cerebral artery, 4 internal carotid artery, 2 posterior communicating artery, 2 vertebral artery and 1 each posterior inferior cerebellar, superior cerebellar and posterior cerebral arteries. Aneurysm embolization techniques were: 91 stent-assisted coiling (96%) and 4 flow diversion (4%). Y-stenting was used for 13 aneurysms (14%), T-stenting for 2 aneurysms (2%) and X-stenting for 1 aneurysm (1%). The LVIS Jr was deployed via a Scepter XC balloon in 49 procedures (54%). Mean packing density was 40% (median 38.5%, 8.8%–90.9%), mean procedure time was 83 min (median 74 min, 35–201 min). The table summarizes treatment-related complications in our cohort. There were no intra-procedural aneurysm/vessel perforations. There were 4 treatment-related complications resulting in a disabling neurological deficit or death (modified Rankin Scale>2, 4.4%). These were 1 MCA perforator infarction on post-operative day (POD) 0; 1 subacute T-stent thrombosis on POD 4; 1 rectus sheath hematoma after percutaneous feeding tube placement leading to severe anemia, hypotension and left MCA territorial infarction on POD 21 in a patient with a ruptured aneurysm; and 1 delayed basilar artery perforator infarction 7 months after Y-stenting of a recurrent giant basilar tip aneurysm. Treatment-related mortality was 2.5%, overall neurological mortality 6.2%. Angiographic follow-up was performed in 58 aneurysms (66%, 30 aneurysms pending follow-up). Follow-up was completed with MR angiography in 54 aneurysms (93%) and catheter angiography in 4 aneurysms (7%). Mean time to last follow-up was 14.1 months (median 6.5 months, 2.9–38.4 months). At last follow-up, 41 aneurysms were completely occluded (70.7%, Raymond 1), 12 had residual neck (20.7%, Raymond 2) and 5 had residual aneurysm (8.6%, Raymond 3). 5 aneurysms were retreated (8.6%). Conclusion The LVIS Jr stent is a safe and effective tool for the treatment of intracranial aneurysms, achieving high medium-term complete/near complete aneurysm occlusion rates with low treatment-related morbidity and mortality and low re-treatment rates. Disclosures J. Delgado Almandoz: 2; C; Microvention/Terumo. Y. Kayan: None. A. Wallace: None. J. Scholz: None. A. Milner: None. J. Fease: None. M. Mulder: None.

Introduction The Pipeline Embolization Device (PED; Medtronic Neurovascular, Irvine, CA) has expanded the spectrum of aneurysms amenable to endovascular treatment. The device is a braided mesh cylinder composed of 48 strands of 25% platinum and 75% cobalt-nickel alloy. An estimated 17% of women and 3% of men are allergic to nickel, and the safety PED implantation in these patients is a concern. The purpose of this study was to assess the clinical and angiographic outcomes of PED treatment in patients with nickel allergy. Methods A single institution neurointerventional database was retrospectively reviewed for patients treated with the PED who had a documented nickel allergy. In some patients patch testing was performed preoperatively, consisting of taping a PED to the patient’s skin for 1 week. Patient demographics, aneurysm characteristics, and procedural details were recorded. All patients received dual antiplatelet therapy for approximately 17 days before treatment, and response was assessed with VerifyNow (Accriva Diagnostics; San Diego, CA). Follow-up digital subtraction angiography was performed 6 months post procedure. Longer-term follow up was performed with CT angiography when PED alone was used or MRA with and without contrast when adjunctive coiling was performed. Follow-up functional status was graded using the modified Rankin Scale (mRS). Good clinical outcome was defined as mRS ≤2 at last clinical follow up. Results During the study period, 22 patients with documented nickel contact dermatitis underwent 23 PED treatments for 29 aneurysms. Patch testing was performed in 55% (12/22) of patients, none of whom experienced a skin reaction. The cohort included 21 women and 1 man with a mean age of 53.6±14 years. Patient medical comorbidities were as follows: hypertension, 40.9%; hyperlipidemia, 9.1%; type 2 diabetes mellitus, 0%. 36% (8/22) of patients actively smoked at the time of treatment. Mean aneurysm size was 8.8±8.1 mm (range, 2.0–32.0 mm), with 93% (27/29) located in the anterior circulation and 7% (2/29) in the posterior circulation. No aneurysms were treated in the setting of subarachnoid hemorrhage. Most patients were treated with a single PED (79.3%, 23/29). Five patients were treated with two PEDs and one was treated with three PEDs. 28% (8/29) of aneurysms were treated with adjunctive coiling. 18% (4/22) of patients experienced a symptomatic complication, all of which were thromboembolic, but all patients (100%, 22/22) had a good clinical outcome. During a mean angiographic follow-up of 16.2±13.0 months (range, 3–64 months), complete and near-complete (>90%) occlusion rates were 77% (20/26) and 4% (1/26), respectively. Endothelial hyperplasia occurred in one case (3%), which resulted in approximately 65% asymptomatic parent artery stenosis. Conclusion All patients with nickel allergy treated with the PED had a good clinical outcome, but the thromboembolic complication rate was higher than typically reported for PED series. Further research is needed to determine if nickel allergy is an independent risk factor for procedural complications. Disclosures A. Wallace: None. J. Delagado Almandoz: 2; C; Medtronic, Penumbra, Accriva, Microvention. Y. Kayan: 2; C; Medtronic, Penumbra, Microvention. J. Fease: None. M. Thomas: None. J. Scholz: None. A. Milner: None.

Delayed ipsilateral intraparenchymal hemorrhage (IPH) has been reported following technically successful treatment of intracranial aneurysms using flow-diverting stents in up to 8.5 % of patients. We report a similar, though less frequent phenomenon in the setting of stent-assisted coil embolization. Institutional review board approval was obtained. A retrospective analysis of a prospective neurointerventional procedure registry was performed to review all IPHs that occurred in aneurysm patients within 90 days of endovascular treatment performed between November 2002 and November 2014 at one institution. Age, sex, hypertension, dual antiplatelet therapy, and technical details of the procedure were recorded. A total of 1697 patients underwent endovascular treatment of an intracranial aneurysm without a flow diverter at our institution during the study period. Among these, 138 patients underwent stent-assisted coiling (8.1 %). Of these, three patients (2.2 %) suffered a delayed IPH within the vascular territory distal to the treated lesion (one woman, median age 60 years). Recently described in the setting of flow diversion, delayed ipsilateral IPH is not limited to flow-diverting stents. Though less frequent, a potential for this complication may exist following any intracranial stenting procedure, possibly related to hemorrhagic conversion of microembolic phenomena in the setting of dual antiplatelet or anticoagulation therapy.

Femoral cannulation during cardiopulmonary bypass has become a common approach for many cardiac procedures and serves as an important access option, especially during minimally invasive cardiac surgery. Opponents, however, argue that there is significant risk, including site-specific and overall morbidity, which makes the use of this modality dangerous compared to conventional aortoatrial cannulation techniques. We analyzed our institutional experience to elucidate the safety and efficacy of femoral cannulation. All data were collected from a single hospital’s cardiac surgery database. A total of 346 cardiac surgeries were evaluated from September 2012 to September 2013, of which 85/346 (24.6%) utilized a minimally invasive approach. Of the 346 operations performed, 72/346 (20.8%) utilized femoral cannulation while 274/346 (79.2%) used aortoatrial cannulation. Stroke occurred in 1/72 (1.39%) after femoral cannulation, specifically, in a conventional sternotomy patient, while it occurred in 6/274 (2.19%) [p=0.67] after aortoatrial cannulation. When comparing postoperative complications between the femoral cannulation and aortoatrial cannulation groups, the rates of atrial fibrillation [10/72 (13.9%) versus 46/274 (16.8%), p=0.55], renal failure [2/72 (2.78%) versus 11/274 (4.01%), p=0.62], prolonged ventilation time [4/72 (5.56%) versus 27/274 (9.85%), p=0.26] and re-operation for bleeding [3/72 (4.17%) versus 13/274 (4.74%), p=0.84] showed no significant difference. Selective femoral cannulation provides a safe alternative to aortoatrial cannulation for cardiopulmonary bypass and is especially important when performing minimally invasive cardiac surgery. When comparing aortoatrial and femoral cannulation, we found no significant difference in the postoperative complication rates and overall mortality.

Background Although a relationship between elevated triglycerides (TG) and cardiovascular diseases is generally accepted, its extent is still discussed. This retrospective study analyzed the incidence of cardiovascular events (CVE) and pancreatitis as well as the therapeutic regimen in patients being treated for hypertriglyceridemia (HTG) at an outpatient department. Methods The cohort included 183 patients with mild and 49 patients with severe HTG; subgroups were formed and compared according to gender, presence of metabolic vascular syndrome (MVS) and lipid values. Results Patients in this study seem to have had CVE at younger age than reported event rates in the general population. TG levels, rates of CVE and pancreatitis were reduced in all groups during therapy, which could be linked to use of omega-3 fatty acids and fibrates. Patients with persisting severe HTG as a result of incompliance showed massive risk for pancreatitis. Conclusion Although no significant association between TG levels and CVE could be established, the combination of HTG and other cardiovascular risk factors such as MVS seems to be especially dangerous. The lipid-lowering drug therapy appeared to be effective with respect to CVE and pancreatitis incidence.

Clostridium difficile (CD) is a common cause of healthcare-associated infectious colitis that complicates about 1% of all hospital stays in the U.S. The impact of CD on outcomes after coronary artery bypass grafting (CABG) and valvular surgery (VS) is not well known.The Nationwide Inpatient Sample (2002-2009) was queried to identify CABG and VS patients utilizing International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) diagnosis codes. Rates of CD, post-operative endocarditis and mediastinitis, hospital mortality rate, and resource utilization were evaluated.We identified 421,294 and 90,923 patients of age 40 yrs and older who underwent CABG and VS, respectively. The CD infection was more likely to develop in patients undergoing VS than in those having CABG (odds ratio [OR] 1.8; 95% confidence interval [CI] 1.64-1.92) and was more likely after urgent or emergency admission than after elective admission (OR 1.8; 95% CI 1.68-1.94). There was a greater likelihood of mediastinitis in patients with CD after CABG than in non-complicated cases without CD, both by univariable (OR 6.0; 95% CI 3.07-11.62) and multivariable analysis with adjustment for patient age, gender, race, type of admission, and co-morbidities (OR 3.1; 95% CI 1.49-6.51). The infection thus was most likely a result of the antibiotics used to treat mediastinitis, as the patients treated for mediastinitis were most likely to develop CD. There was a significant association in patients with CD and endocarditis who underwent VS but not in patients who did not have CD. The CD infection in these patients thus was most likely a result of the antibiotics used to treat endocarditis. Endocarditis and CD developed 3.2 times (95% CI 2.65-3.97) as often as in patients without CD, a finding that was confirmed by multivariable analysis (OR 2.2; 95% CI 1.70-2.84). At the same time, in patients having VS, there was no significant association of CD and mediastinitis. Clostridium difficile infection affected the hospital mortality rate significantly after both CABG (OR 2.0; 95% CI 1.65-2.35) and VS (OR 1.9; 95% CI 1.51-2.39). Development of CD increased median hospital length of stay and cost dramatically after both CABG (from 7 d to 19 d and from $33,105 to $65,535, respectively; p0.0001 for both) and VS (from 8 d to 24 d and from $41,876 to $95,699, respectively; p0.0001 for both).The development of CD worsened significantly the outcomes of adult patients undergoing cardiac surgery. There was a greater risk of CD in patients with either mediastinitis or endocarditis. The infection was associated with a higher hospital mortality rate, longer hospital stays, and greater cost after both CABG and VS.

Objective: The worldwide prevalence of obesity has increased to 10% in men and 15% in women and is associated with severe comorbidities such as diabetes, cancer, and cardiovascular disease. Animal models of obesity are central to experimental studies of disease mechanisms and therapeutic strategies. Diet-induced obesity (DIO) models in rodents have provided important insights into the pathophysiology of obesity and, in most instances, are the first in line for exploratory pharmacology studies. To deepen the relevance towards translation to human patients, we established a corresponding DIO model in Göttingen minipigs (GM). Methods: Young adult female ovariectomized GM were fed a high-fat/high-energy diet for a period of 70 weeks. The ration was calculated to meet the requirements and maintain body weight (BW) of lean adult minipigs (L-GM group) or increased stepwise to achieve an obese state (DIO-GM group). Body composition, blood parameters and intravenous glucose tolerance were determined at regular intervals. A pilot chronic treatment trial with a GLP1 receptor agonist was conducted in DIO-GM. At the end of the study, the animals were necropsied and a biobank of selected tissues was established. Results: DIO-GM developed severe subcutaneous and visceral adiposity (body fat >50% of body mass vs. 22% in L-GM), increased plasma cholesterol, triglyceride, and free fatty acid levels, insulin resistance (HOMA-IR >5 vs. 2 in L-GM), impaired glucose tolerance and increased heart rate when resting and active. However, fasting glucose concentrations stayed within normal range throughout the study. Treatment with a long-acting GLP1 receptor agonist revealed substantial reduction of food intake and body weight within four weeks, with increased drug sensitivity relative to observations in other DIO animal models. Extensive adipose tissue inflammation and adipocyte necrosis was observed in visceral, but not subcutaneous, adipose tissue of DIO-GM. Conclusions: The Munich DIO-GM model resembles hallmarks of the human metabolic syndrome with extensive adipose tissue inflammation and adipocyte necrosis reported for the first time. DIO-GM may be used for evaluating novel treatments of obesity and associated comorbidities. They may help to identify triggers and mechanisms of fat tissue inflammation and mechanisms preventing complete metabolic decompensation despite morbid obesity. Keywords: Pig, High fat diet, Obesity, Diabetes, Metabolic syndrome, Adipose tissue inflammation

Purpose This study9s goal is to evaluate the safety and efficacy of the Axium Prime Extra Soft (ES) coil for treatment of intracranial aneurysms. Methods We conducted a retrospective review of all consecutive patients with intracranial aneurysms treated with Axium Prime ES coils at a single center between January 26th, 2016 and March 28th, 2017. Baseline patient and aneurysm characteristics, procedural variables and complications were recorded. Aneurysm occlusion at angiographic follow-up was determined using the Roy-Raymond scale. Aneurysm retreatment was recorded. Results 45 patients with 48 intracranial aneurysms were included, 36 women (80%). Mean age was 58.2 years (median 58 years, 36–92 years). 47 aneurysms were treated successfully with coils (98%). 17 aneurysms were ruptured (35%), 8 recurrent (17%) and 3 symptomatic (6%). Mean maximum aneurysm size was 5.7mm (median 5.2mm, 2.2-26.2mm), mean neck 2.8mm (median 2.6mm, 1-6.2mm), mean dome to neck ratio 1.7 (median 1.4, 0.9-11.5). Aneurysm locations were: 13 anterior communicating artery, 11 middle cerebral artery, 10 internal carotid artery, 5 anterior cerebral artery, 4 posterior communicating artery, 1 basilar tip, and 1 each posterior inferior cerebellar, superior cerebellar, posterior cerebral and persistent hypoglossal arteries. Aneurysm embolization techniques were: 23 balloon-assisted coiling (48%), 11 stent-assisted coiling (23%), 10 simple coiling (21%), 3 Pipeline/coiling (6%), and 1 aneurysm was treated with flow diversion after attempted coiling (2%). Mean total number of coils deployed per aneurysm was 3.5mm (median 3, 1-14). Mean number of Axium Prime ES coils deployed per aneurysm was 2.1mm (median 2, 1-7). Mean Axium Prime ES coil length as total coil length percentage was 55.1% (median 42%, 11.1-100%). Mean packing density was 35.2% (median 35.7%, 1.6-63%). There were 6 peri-procedural complications: 3 coil herniations during balloon-assisted coiling requiring stenting (6%), 1 intra-operative aneurysm re-rupture controlled with balloon inflation (2%), 1 small peripheral subarachnoid hemorrhage on post-operative day 1 (2%), and 1 subacute stent thrombosis on post-operative day 4 (2%). The subacute stent thrombosis resulted in the patient’s death (2.2%). No other treatment-related complication resulted in a permanent neurological deficit or death. Overall mortality was 4.4%. Angiographic follow-up was performed in 19 aneurysms (42%, 26 aneurysms currently pending follow-up). Follow-up was completed with MR angiography in 17 aneurysms (90%) and catheter angiography in 2 aneurysms (10%). Mean time to follow-up was 6.3 months (median 6.1 months, 5.9-7.6 months). At follow-up, 14 aneurysms were completely occluded (74%, Raymond 1) and 5 showed residual neck (26%, Raymond 2). There were no residual aneurysms at follow-up (Raymond 3). No aneurysms were retreated. Conclusion The Axium Prime ES coil is safe and effective for the treatment of intracranial aneurysms, achieving high packing densities, low risk of major treatment-related complications, high medium-term complete/near-complete aneurysm occlusion rates, and low re-treatment rates. Disclosures: J. Delgado Almandoz: 2; C; Medtronic Neurovascular. Y. Kayan: 2; C; Medtronic Neurovascular. J. Scholz: None. A. Milner: None. A. Wallace: None. J. Fease: None. M. Mulder: None.

Purpose To examine clinical and angiographic outcomes in a cohort of consecutive patients with posterior circulation intracranial aneurysms treated with the Pipeline Embolization Device (PED) at a referral center. Methods We conducted a retrospective review of all patients with posterior circulation intracranial aneurysms treated with the PED in our center between January 23 rd , 2012 and January 24 th , 2017. Baseline patient and aneurysm characteristics, intra-­operative, peri-­operative and delayed complications were recorded. Aneurysm volumes in initial and follow-­up angiographic studies were calculated using AngioCalc. Clinical outcomes were categorized using the modified Rankin Scale (mRS). Results 17 patients underwent 18 PED procedures to treat 19 posterior circulation intracranial aneurysms during the study period. 12 patients were women (71%) and 5 men (29%). Mean age was 60 years (range 13-­80 years). 16 patients were premedicated with aspirin/clopidogrel with VerifyNow testing (94%), and 1 with aspirin/ticagrelor without VerifyNow testing (6%). 8 aneurysms were incidental (42%), 5 symptomatic (26%, 2 from mass effect), 4 recurrent (21%) and 3 ruptured (16%). 6 aneurysms were fusiform (32%), 3 dissecting (16%) and 2 blister (11%). 7 aneurysms were located in the basilar trunk (37%), 4 in the posterior inferior cerebellar artery (21%), 2 in the superior cerebellar artery (10.5%), 2 in the posterior cerebral artery (10.5%), 2 in the vertebral artery (10.5%), 1 in the basilar tip (5%) and 1 in a basilar perforator artery (5%). Mean aneurysm size was 8.8mm (1.7-34mm), mean neck was 6.7mm (0.6-32.6mm), mean dome-­to-­neck ratio was 1.3 (0.2-2.9). 12 aneurysms were wide-neck (≥4mm, 63%). Mean number of PEDs deployed per aneurysm was 1.3. Adjunctive coiling was performed in 4 aneurysms (21%). There were 2 intra-operative (11%), 3 peri-operative (17%) and 1 delayed (5.6%) complications, none led to a disabling neurological deficit (mRS≥3). There was no treatment-related mortality. There were no post-­operative aneurysm ruptures. Overall mortality was 5.9%. Angiographic follow-­up was available in 15 aneurysms (79%, 3 follow-ups currently pending), with a mean time to last angiographic follow-­up of 23.7 months (median 11 months, range 3.3-61.3 months). At last follow­-up, 11 aneurysms were completely occluded (73%), 3 aneurysms had incomplete occlusion (20%, mean 59.2% volume reduction), and 1 aneurysm had volume increase (7%, 166% increase). The enlarging aneurysm was re-treated with parent artery sacrifice (7%). Conclusion The PED is a safe and effective treatment for wide-neck posterior circulation intracranial aneurysms, with high long-term complete aneurysm occlusion rates, low re-­treatment rates, and a low rate of major treatment-related complications. Disclosures: J. Delgado Almandoz: 2; C; Medtronic Neurovascular, Accriva Diagnostics. Y. Kayan: 2; C; Medtronic Neurovascular. J. Scholz: None. K. Uittenbogaard: None. A. Milner: None. J. Fease: None. A. Wallace: None. K. Nelson: None. M. Mulder: None.

Purpose The Penumbra Coil 400 System (PC400) was designed with increased coil diameter to enhance filling efficiency in large intracranial aneurysms. This study9s goal is to evaluate the safety and efficacy of the PC400 coils to treat large intracranial aneurysms. Methods We conducted a retrospective review of all consecutive patients with intracranial aneurysms treated with PC400 coils at a single center. Baseline patient and aneurysm characteristics, procedural variables and treatment-related complications were recorded. Aneurysm occlusion at the time of last angiographic follow-up was determined using the Roy-Raymond scale. Aneurysm retreatment was recorded. Results 57 consecutive patients with 60 intracranial aneurysms were included, 44 women (77%). Mean age was 60.7 years (median 60 years, 28–89 years). 12 aneurysms were ruptured (20%). Mean maximum aneurysm size was 12mm (median 10.5mm, 5.2-22mm), mean neck size was 5mm (median 4.1mm, 1.9-15mm), mean dome to neck ratio was 2 (median 1.9, 0.8-4.2). Aneurysm locations were: 27 internal carotid artery, 10 middle cerebral artery, 8 posterior communicating artery, 6 basilar tip, 5 anterior communicating artery, and 1 each posterior inferior cerebellar, superior cerebellar, posterior cerebral and anterior cerebral arteries. Aneurysm embolization techniques were: 30 balloon-assisted coiling (50%), 18 simple coiling (30%), 8 Pipeline/coiling (13%), 3 stent-assisted coiling (5%), and 1 parent artery sacrifice (2%). 49 aneurysms were treated with PC400 coils only (82%). Mean number of PC400 coils deployed was 5.1 (median 4, 1-23), mean packing density was 34% (median 33.5%, 7-68%). Mean procedure time was 64 minutes (median 53 minutes, 23–186 minutes). There were 6 peri-procedural complications: 2 intra-operative aneurysm ruptures (3.3%), 1 coil herniation requiring stenting (1.7%), and 3 post-operative infarctions with permanent deficits (5%). Angiographic follow-up was available in 54 aneurysms (90%), mean time to last follow-up 12.2 months (median 6.5 months, 3.3-33.4 months). At last follow-up, 25 aneurysms were completely occluded (46%, Raymond 1), 20 showed residual neck (37%, Raymond 2), and 9 demonstrated residual aneurysm (17%, Raymond 3). Nine aneurysms were retreated (17%), 6 with flow-diversion and 3 with stent assisted-coiling. Compared to a prior study examining 84 large aneurysms treated with conventional coils, treatment with PC400 coils resulted in higher packing densities, faster procedure times, lower procedural complications and lower retreatment rates (Tables 1 and 2). Conclusion The PC400 system is safe and effective for the treatment of large wide-neck intracranial aneurysms, achieving high packing densities, fast procedural times, favorable safety profile and low re-treatment rates compared to conventional coiling. Disclosures: J. Delgado Almandoz: 2; C; Penumbra, Inc. Y. Kayan: 2; C; Penumbra, Inc. J. Fease: None. J. Scholz: None. A. Milner: None. A. Wallace: None. M. Mulder: None.

Purpose To examine clinical and angiographic outcomes in a cohort of consecutive patients with recurrent intracranial aneurysms treated with the Pipeline Embolization Device (PED) at a referral center. Methods We conducted a retrospective review of all patients with recurrent intracranial aneurysms treated with the PED in our center center between December 13 th , 2011 and March 29 th , 2017. Baseline patient and aneurysm characteristics, intra-­operative, peri-­operative and delayed complications were recorded. Aneurysm volumes in initial and follow-­up angiographic studies were calculated using AngioCalc. Clinical outcomes were categorized using the modified Rankin Scale (mRS). Results 50 patients underwent 53 PED procedures to treat 56 recurrent intracranial aneurysms during the study period. 36 patients were women (72%) and 14 men (28%). Mean age was 58 years (range 29–­77 years). 23 patients were active smokers (46%) and 26 had a prior history of subarachnoid hemorrhage (52%). 46 patients were premedicated with aspirin/clopidogrel (92%), 3 with aspirin/prasugrel (6%) and 1 with warfarin/clopidogrel (2%). All patients underwent pre-procedure VerifyNow testing. 46 aneurysms were recurrent after simple coiling (82%), 5 after PED embolization (9%, 1 after PED/coiling), 3 after stent-assisted coiling (5%), 1 after Onyx HD500 embolization (2%) and 1 after surgical clipping (2%). 4 aneurysms were symptomatic from mass effect (7%) and 1 was acutely ruptured (2%). 3 aneurysms were fusiform (5%) and 1 blister (2%). 39 aneurysms were located in the internal carotid artery (70%), 8 in the middle cerebral artery (14%), 5 in the anterior cerebral artery (9%), 3 in the posterior inferior cerebellar artery (5%) and 1 in the basilar tip (2%). 30 aneurysms had a vessel arising from the aneurysm dome/neck (54%), 14 of which were the posterior communicating artery (47%). Mean aneurysm size was 6.2 mm (1.5–26.2 mm), mean neck was 3.9 mm (0.5–9.3 mm), mean dome-­to-­neck ratio was 1.6 (0.6–11.5). 24 aneurysms were wide-neck (≥4 mm, 43%). Mean number of PEDs deployed per aneurysm was 0.9. Adjunctive coiling was performed in 7 aneurysms (12.5%, mean 4.7 coils deployed). 28 aneurysms were treated with PED Flex (50%). There were 4 intra-operative (7.5%), 15 peri-operative (28%) and 3 delayed (5.7%) complications. 1 peri-operative complication, an ipsilateral intracerebral hemorrhage on post-operative day 4 in a patient with P2Y12 reception over-inhibition at the time of the hemorrhage, resulted in the patient’s death (1.9%). No other treatment-related complication led to a disabling neurological deficit or death (mRS ≥3). Treatment-related mortality was 2%. There were no post-­operative aneurysm ruptures. Angiographic follow-­up was available in 47 aneurysms (86%, 8 follow-ups currently pending), with a mean time to last angiographic follow-­up of 20 months. At last follow­-up, 36 aneurysms were completely occluded (77%), 2 aneurysms had near-completed occlusion (4%, mean 97.3% vol reduction), and 9 aneurysms had incomplete occlusion (19%, mean 68.7% vol reduction). No aneurysms required retreatment. Conclusion The PED is a safe and effective treatment for recurrent intracranial aneurysms, with high long-term complete aneurysm occlusion rates, low re-­treatment rates, and a low rate of major treatment-related complications. Disclosures J. Delgado Almandoz: 2; C; Medtronic Neurovascular, Accriva Diagnostics. Y. Kayan: 2; C; Medtronic Neurovascular. J. Fease: None. K. Uittenbogaard: None. J. Scholz: None. A. Milner: None. K. Nelson: None. A. Wallace: None. M. Mulder: None.

Flow diversion constitutes a pivotal advancement in endovascular intracranial aneurysm treatment, but requires development of a new skill set. The aim of this study is to determine whether outcomes after treatment with the Pipeline Embolization Device improve with experience. We retrospectively reviewed all patients with intracranial aneurysms treated with Pipeline at two centers over a 4.5-year period. Baseline patient and aneurysm characteristics, complications, and angiographic outcomes were analyzed. One hundred forty patients underwent 150 Pipeline procedures to treat 167 intracranial aneurysms during the study period, 109 women, mean age 55.4 years. One hundred twenty-six aneurysms were ICA, mean size 10.2 mm and mean neck 6.4 mm. Intra-procedural technical difficulties were higher during the first 75 procedures compared with the subsequent 75 (13.3 vs 2.7%; p = 0.03), as combined major morbidity and neurological mortality (14.7 vs 4%; p = 0.046). In multivariate regression analysis, increased operator experience with Pipeline remained an independent predictor of intra-procedural technical difficulties (p = 0.02, odds ratio (OR) 0.015, 95% CI 0.0004–0.55) and combined major morbidity and neurological mortality (p = 0.03, OR 0.16, 95% CI 0.03–0.84). At last follow-up, 123 aneurysms were completely occluded (81.5%, mean 24 months). In our cohort, age ≤ 53 years was an independent predictor of complete aneurysm occlusion at last follow-up (p = 0.001, OR 0.92, 95% CI 0.88–0.97). Five aneurysms were retreated (3.3%). The Pipeline embolization device is an effective treatment for intracranial aneurysms. The risk of intra-procedural technical difficulties and combined major morbidity and neurological mortality decreases significantly with increased operator experience in Pipeline deployment and patient management.

Objective: To determine whether functional capacity evaluation (FCE) tests predict future work capacity (WC) of patients with whiplash-associated disorders (WADs) grades I and II who did not regain full WC 6 to 12 weeks after injury.Design: Prospective cohort study.Setting: Rehabilitation center.Participants: Workers (N=267) listed on workers' compensation with grade I or El WADs 6 to 12 weeks after injury.Interventions: Patients performed 8 work-related FCE tests.Main Outcome Measures: WC (0-100%) measured at baseline and 1, 3, 6, and 12 months after testing. Correlation coefficients between FCE tests and WC were calculated. A linear mixed-model analysis was used to assess the association between FCE and future WC.Results: Mean +/- SD WC increased over time from 20.8%+/- 27.6% at baseline to 32.3%+/- 38.4%, 51.3%+/- 42.8%, 65.6%+/- 42.2%, and 83.2%+/- 35.0% at the 1-, 3-, 6-, and 12-month follow-ups, respectively. Correlation coefficients between FCE tests and WC ranged from r=.06 (lifting low at 12-mo follow-up) to r=.39 (walking speed at 3mo). Strength of the correlations decreased over time. FCE tests did not predict WC at follow-up. The predictors of WC were ln (time) (beta=23.74), mother language (beta=5.49), WC at baseline (beta=1.01), and self-reported disability (beta=-.20). Two interaction terms, ln (time) x WC (beta=-.19) and ln (time) x self-reported disability (beta=-.21), were significant predictors of WC.Conclusions: FCE tests performed within 6 to 12 weeks after WADs injury grades I and II are associated with WC at baseline but do not predict future WC, whereas time course, mother language, WC at baseline, and self-reported disability do predict future WC. Additionally, the interaction between time course WC at baseline and self-reported disability predicted future WC. (C) 2014 by the American Congress of Rehabilitation Medicine

Background. Acute cardiogenic shock is associated with high mortality rates. Mechanical circulatory devices have been increasingly used in this setting for hemodynamic support. The Impella device (Abiomed Inc, Danvers, MA) is a microaxial left ventricular assist device that can be inserted using a less invasive technique. This study was conducted to determine the outcome of patients who have undergone placement of the Impella device for acute cardiogenic shock in our institution. Methods. A retrospective record review of 47 patients who underwent placement of the Impella device was performed from January 1, 2006, to December 31, 2011. Records were evaluated for demographics, operative details, and postoperative outcomes. Operative mortality was defined as death within 30 days of the operation. Results. The patients (33 male) were an average age of 60.23 ±13 years. The indication for placement of the Impella device included cardiogenic shock in 15 patients (32%) and postcardiotomy cardiogenic shock in 32 (68%). Of the 47 patients, 38 (80%) received the Impella 5.0 and the rest the 2.5 device. Ventricular function recovered in 34 of 47 patients (72%), and the device was removed, with 4 patients (8%) transitioned to long-term ventricular assist devices. The 30-day mortality was 25% (12 of 47 patients). Complications occurred in 14 patients (30%), consisting of device malfunction, high purge pressures, tube fracture, and groin hematoma. Conclusions. This is one of the largest series of patients undergoing placement of the Impella device for acute cardiogenicshock.Ouroutcomesshowed improved results compared with historical data. Myocardial recovery was accomplished in most patients. Finally, the 30-day mortality and complication rate was acceptable in these critical patients. These benefits were all achieved with the Impella device in a less invasive method.

Variability in response to clopidogrel therapy is increasingly being recognized as an important factor in thromboembolic and hemorrhagic complications encountered after neurointerventional procedures. This study aims to determine the variability in response to clopidogrel therapy and associated complications in patients undergoing endovascular treatment of unruptured cerebral aneurysms.We recorded baseline patient characteristics, co-administered medications, P2Y12 reaction units (PRU) values with VerifyNow, clopidogrel dosing, and thromboembolic and hemorrhagic complications in patients undergoing endovascular treatment of unruptured cerebral aneurysms at our institution during a 19 month period.100 patients were included in the study, 76 women and 24 men, mean age 57.3 years. 15 patients exhibited an initial clopidogrel hypo-response (PRU240) and 21 patients an initial clopidogrel hyper-response (PRU60). 36 patients had a follow-up VerifyNow test performed without changes to the standard 75 mg daily clopidogrel dose, which demonstrated that 59% of patients who had initially been within the target 60-240 PRU range exhibited a delayed conversion to clopidogrel hyper-response. In our cohort, a clopidogrel hypo-response was associated with a significantly increased risk of thromboembolic complications in patients undergoing cerebral aneurysm treatment with stent assistance or the pipeline embolization device (60%, p=0.003), while a clopidogrel hyper-response was associated with a significantly increased risk of major hemorrhagic complications in all patients undergoing endovascular treatment of cerebral aneurysms (11%, p=0.016).We found wide and dynamic variability in response to clopidogrel therapy in patients undergoing endovascular treatment of unruptured cerebral aneurysms, which was significantly associated with thromboembolic and major hemorrhagic complications in our cohort.

BACKGROUND AND PURPOSE: A recent study identified a preprocedural P2Y12 reaction units value of 240 as a strong independent predictor of perioperative thromboembolic and hemorrhagic complications after treatment of cerebral aneurysms with the Pipeline Embolization Device. This study aimed to determine whether a last-recorded P2Y12 reaction units value of 240 predicts thromboembolic and hemorrhagic complications up to 6 months after treatment of cerebral aneurysms with the Pipeline Embolization Device in the same patient cohort. MATERIALS AND METHODS: We recorded patient and aneurysm characteristics, P2Y12 receptor antagonist administered, P2Y12 reaction units value with VerifyNow, procedural variables, and thromboembolic and hemorrhagic complications up to 6 months after Pipeline Embolization Device procedures at our institution during an 8-month period. Complications causing a permanent disabling neurologic deficit or death were considered major. Multivariate regression analysis was performed to identify independent predictors of thromboembolic and hemorrhagic complications. RESULTS: Forty-four patients underwent 48 Pipeline Embolization Device procedures at our institution during the study period. There were 11 thromboembolic and hemorrhagic complications up to 6 months after treatment in our cohort (22.9%), 5 of which were major (10.4%). A last-recorded P2Y12 reaction units value of 240 was the only independent predictor of all (P = .002) and major (P = .03) thromboembolic and hemorrhagic complications in our cohort. Most patients (71%) required, on average, 2 adjustments to the dose or type of P2Y12 receptor antagonist to remain within the 60–240 target P2Y12 reaction units range. CONCLUSIONS: In our cohort, a last-recorded P2Y12 reaction units value of 240 was the only independent predictor of all and major thromboembolic and hemorrhagic complications up to 6 months after Pipeline Embolization Device procedures.

In addition to their established roles in host defence, Toll-like Receptors (TLRs) have emerging roles in control of homeostasis, injury and wound repair. The dsRNA-sensing receptor, TLR3, has been particularly implicated in such processes in several different tissues including the skin, intestine and liver, as well as in the control of reparative mechanisms in the brain, heart and kidneys, following ischemia reperfusion injury. In this review, we provide an overview of TLR3 signalling and functions in inflammation, tissue damage and repair processes, as well as therapeutic opportunities that may arise in the future from knowledge of such pathways.

BACKGROUND AND PURPOSE: The yield of DSA in patients with SAH and negative initial noninvasive neurovascular examinations (CTA or MRA) is not well-understood. This study aimed to determine the yield of DSA for the detection of causative vascular lesions in this clinical scenario. MATERIALS AND METHODS: We examined the yield of DSA for the detection of causative vascular lesions in a cohort of patients presenting to our institution with SAH and negative initial noninvasive neurovascular examinations during a 5-year period. Two experienced neuroradiologists independently evaluated the NCCT to determine the SAH pattern (diffuse, perimesencephalic, or peripheral sulcal) and the catheter angiograms to assess the presence of a causative vascular lesion. RESULTS: Fifty-five patients were included in the study, with a mean age of 58.2 years (median, 58 years; range, 25–88 years). Twenty-eight patients were men (50.9%), and 27 were women (49.1%). The initial noninvasive examination was a CTA in 47 patients (85.5%) and an MRA in 8 patients (14.5%). Thirty-three patients had diffuse SAH (60%); 11, perimesencephalic SAH (20%); and 11, peripheral sulcal SAH (20%). DSA demonstrated a causative vascular lesion in 6 patients (10.9%), 5 of whom had diffuse SAH (yield of 15.2%) and 1 of whom had peripheral sulcal SAH (yield of 9.1%). No causative vascular lesions were found in patients with perimesencephalic SAH. CONCLUSIONS: DSA is a valuable tool in the evaluation of patients with diffuse and peripheral sulcal SAH who have negative initial noninvasive neurovascular examinations, demonstrating a causative vascular lesion in 15.2% and 9.1% of patients, respectively.

Ein Zyklisches Erbrechenssyndrom (englisch: cyclic vomiting syndrome [CVS]) ist eine funktionelle Storung, die in allen Altersgruppen vorkommen kann. Manifestiert sich die Erkrankung erst im Erwachsenenalter, entwickelt sich das CVS meist um das 35. Lebensjahr. Das CVS besteht aus immer wiederkehrenden, weitgehend stereotypen Erbrechensepisoden, die Stunden bis Tage anhalten. Zwischen diesen Erbrechensphasen liegen typischerweise symptomfreie Intervalle von Wochen bis Monaten. Mit seinen Hauptsymptomen aus Ubelkeit, Erbrechen und haufig zusatzlichen abdominellen Schmerzen ist es oft nicht einfach, ein CVS von einer Vielzahl anderer Erkrankungen abzugrenzen. Oft dauert es mehrere Monate bis Jahre, bis die definitive Diagnose eines CVS gestellt wird und die Patienten einer adaquaten Therapie zugefuhrt werden konnen. Es existiert kein spezifischer Test, um ein CVS nachzuweisen. Die Diagnose eines CVS erfolgt anhand der anamnestischen Schilderungen der Patienten nach Ausschluss anderer Ursachen eines rezidivierenden Erbrechens. Es gibt bisher keine evidenzbasierten Standardbehandlungsregime eines CVS, weder zur Akutbehandlung der Erbrechensphase noch zur Prophylaxe. Die meisten in der Literatur beschriebenen Behandlungsstrategien basieren auf kleinen Fallzahlen und Erfahrungsberichten. Zur Akutbehandlung einer Erbrechensphase kommen Antiemetika, Sedativa und Migranetherapeutika zum Einsatz. Die am haufigsten eingesetzten Wirkstoffe fur eine CVS-Prophylaxe sind Amitriptylin und Propranolol.

Objective In clinical practice, reperfusion of ischemic myocardium usually occurs under high arterial oxygen levels. However, this might aggravate cardiac ischemia–reperfusion injury caused by excessive oxidative stress. In an experimental in vivo study, the cardioprotective role of hypoxic reoxygenation during initial reperfusion was assessed. Methods Twenty-one adult pigs were started on cardiopulmonary bypass with aortic crossclamping (90 minutes) and cardioplegic arrest. During initial reperfusion, 10 pigs underwent standard hypoxic reoxygenation (Pao 2 , 250–350 mm Hg), whereas gradual reoxygenation (Pao 2 , 40–90 mm Hg) was performed in 11 pigs. Cardiac function was analyzed by means of the thermodilution method and conductance catheter technique. Results In both groups cardiac index was decreased 10 minutes after cardiopulmonary bypass compared with preoperative values. Sixty minutes after cardiopulmonary bypass, cardiac index improved significantly after gradual reoxygenation compared with that after hypoxic reoxygenation (3.2 ± 0.6 vs 2.5 ± 0.5 L · min −1 · m −2 , P = .04). Correspondingly, end-systolic pressure–volume relationship and peak left ventricular pressure increase were significantly less decreased in the gradual reoxygenation group. During and after reperfusion, malondialdehyde and troponin T values within the coronary sinus were significantly lower after gradual reoxygenation (60 minutes after declamping: malondialdehyde, 7.6 ± 0.8 vs 4.6 ± 0.5 μmol/L [ P = .007]; troponin, 0.12 ± 0.02 vs 0.41 ± 0.12 ng/mL [ P = .02]). Conclusion Hypoxic reoxygenation at the onset of reperfusion attenuates myocardial ischemia–reperfusion injury and helps to preserve cardiac performance after myocardial ischemia in a pig model.

We hypothesized that myocardial stunning would be reversed through increased cyclic GMP caused by nitroprusside, and that this would be accomplished through a decreased proportion of regional work during diastole. Hearts were instrumented to measure left ventricular pressure, and regional myocardial mechanics were recorded using a miniature force transducer and ultrasonic dimension crystals in eight open-chest anesthetized dogs. Following baseline (CON), the left anterior descending coronary artery (LAD) was occluded for 15 min, followed by a 30-min recovery (STUN). Then intracoronary LAD infusion of sodium nitroprusside (NP) (4 μg/kg/min) was begun. The time delay (msec) to regional shortening increased significantly from 18 ± 13 to 73 ± 13 following stunning, but was reduced to 49 ± 18 by NP. Total regional work (g*mm/min) at baseline (1368 ± 401 CON) was unchanged with stunning (1320 ± 333 STUN), but reduced (961 ± 240) following NP. Time to peak force development (msec) increased significantly with st...

This case report describes the first implantation of an expandable cage into the lumbar spine of a 2-year-old boy. Due to incomplete remission of a teratoma, it was necessary to replace the second lumbar vertebral body with an expandable cage implantation and subsequent dorsoventral stabilization. During the follow-up period with annual x-ray examinations, a loss of correction without increased pain or neurological deficits could be shown in the now 9-year-old boy.