A key role for Fut1-regulated angiogenesis and ICAM-1 expression in K/BxN arthritis.

OBJECTIVES: Angiogenesis contributes to the pathogenesis of rheumatoid arthritis. Fucosyltransferases (Futs) are involved in angiogenesis and tumour growth. Here, we examined the role of Fut1 in angiogenesis and K/BxN serum transfer arthritis. METHODS: We examined Fut1 expression in human dermal microvascular endothelial cells (HMVECs) by quantitative PCR. We performed a number of angiogenesis assays to determine the role of Fut1 using HMVECs, Fut1 null (Fut1(-/-)), and wild type (wt) endothelial cells (ECs) and mice. K/BxN serum transfer arthritis was performed to determine the contribution of Fut1-mediated angiogenesis in Fut1(-/-) and wt mice. A static adhesion assay was implemented with RAW264.7 (mouse macrophage cell line) and mouse ECs. Quantitative PCR, immunofluorescence and flow cytometry were performed with Fut1(-/-) and wt ECs for adhesion molecule expression. RESULTS: Tumour necrosis factor-α induced Fut1 mRNA and protein expression in HMVECs. HMVECs transfected with Fut1 antisense oligodeoxynucleotide and Fut1(-/-) ECs formed significantly fewer tubes on Matrigel. Fut1(-/-) mice had reduced angiogenesis in Matrigel plug and sponge granuloma angiogenesis assays compared with wt mice. Fut1(-/-) mice were resistant to K/BxN serum transfer arthritis and had decreased angiogenesis and leucocyte ingress into inflamed joints. Adhesion of RAW264.7 cells to wt mouse ECs was significantly reduced when Fut1 was lacking. Fut1(-/-) ECs had decreased intercellular adhesion molecule-1 (ICAM-1) expression at mRNA and protein levels compared with wt ECs. ICAM-1 was also decreased in Fut1(-/-) arthritic ankle cryosections compared with wt ankles. CONCLUSIONS: Fut1 plays an important role in regulating angiogenesis and ICAM-1 expression in inflammatory arthritis.

Safety and effectiveness assessment of the surpass evolve (SEASE): a post-market international multicenter study.

BACKGROUND: Flow diverters are the first-line treatment for specific intracranial aneurysms (iA). Surpass Evolve (SE) is a new-generation 64-wire flow diverter with a high braid angle. Current literature on the SE is limited. We aimed to report the first international real-world experience evaluating the safety and effectiveness of the SE. METHODS: The Safety and Effectiveness Assessment of the Surpass Evolve (SEASE) was a multicenter retrospective international post-marketing cohort study including consecutive patients treated with SE for iAs between 2020 and 2022. Demographic, clinical, and angiographic data were collected. Primary effectiveness was independent core lab adjudicated complete occlusion rates (Raymond-Roy Class 1) at last follow-up. Primary safety were major ischemic/hemorrhagic events and mortality. RESULTS: In total, 305 patients with 332 aneurysms underwent SE implantation. The patients had a median age of 59 [50-67] years, and 256 (83.9%) were female. The baseline modified Rankin scale score was 0-2 in 291 patients (96.7%). Most aneurysms were unruptured (285, 93.4%) and saccular (309, 93.1%). Previous treatment was present in 76 (22.9%) patients. The median aneurysm size was 5.1 [3.4-9.0] mm, and the median neck width was 3.6 [2.7-5.1] mm. Most aneurysms were in the internal carotid artery C6 ophthalmic segment (126, 38.0%), followed by the communicating segment (58, 17.5%). At median 10.2 [6.4-12.9] months follow-up, 233 (73.0%) aneurysms achieved complete occlusion. After adjusting for confounders, complete occlusion remained consistent. Major stroke and procedure-related mortality were reported in 6 (2%) and 2 (0.7%) cases, respectively. CONCLUSION: These results demonstrate that SE has a consistently high effectiveness and favorable safety for the treatment of iAs.

Treatment of Unruptured Small and Medium-Sized Wide Necked Aneurysms Using the 64-Wire Surpass Evolve: A Subanalysis From the SEASE International Registry.

BACKGROUND: Flow diversion has revolutionized the management of wide-necked intracranial aneurysms (IAs). We aimed to assess the effectiveness and safety of the new generation 64-wire Surpass Evolve for the treatment of unruptured small/medium-sized IAs. METHODS AND RESULTS: This is a subanalysis from the SEASE (Safety and Effectiveness Assessment of the Surpass Evolve) registry, an observational cohort study including 15 academic institutions in North America and Europe between July 2020 and October 2022. Patients with wide-necked saccular IAs, measuring <12 mm along the internal carotid artery and vertebrobasilar system, and treated with the Surpass Evolve were included. Primary effectiveness was complete occlusion (Raymond-Roy class 1) at follow-up (core laboratory adjudicated), and primary safety was major stroke (ischemic/hemorrhagic) in the territory supplied by the target artery or death. A total of 129 cases with 135 IAs were included (median age 59 years, 85.3% women). Median maximum IAs size and neck size were 5.1 and 3.9 mm, respectively. Most IAs were in the internal carotid artery C6 (65.9%, 89/135) and C7 (14.1%, 19/135) segments. At a median follow-up time of 10.2 months (interquartile range, 6.4-12.8), complete occlusion was 77.1% (101/131), ≥50% in-stent stenosis was 8.8% (11/125), and retreatment was 0.8% (1/125). Major stroke and mortality were reported in 2 (1.6%) patients and 1 (0.8%) patient, respectively. Size was the only factor associated with higher odds of incomplete occlusion (adjusted odds ratio, 1.2 [95% CI, 1.02-1.5]; P=0.03). CONCLUSIONS: Patients with small/medium-sized IAs can be effectively treated using the Surpass Evolve, a new generation, 64-wire, cobalt-chromium flow diverter.

Detection of Malpositioned VP Shunt Catheter by Radionuclide CSF Cisternography.

ABSTRACT: A 37-year-old man presented with a 2-week history of abdominal pain, headaches, nausea, vomiting, and leukocytosis. Medical history includes congenital hydrocephalus, with a ventriculoperitoneal shunt placed several years ago. Radionuclide cerebrospinal fluid cisternography shows curvilinear activity in the abdomen, in the pattern of small and large bowel loops, suggesting that the tip of the catheter is inside a small bowel loop. No activity is seen in the intraperitoneal compartment. CT of the abdomen and pelvis followed by laparoscopic surgery confirmed the findings.

Onyx cast thrombectomy: bailout during thalamic AVM embolization.

Microsurgical resection, radiosurgery, and endovascular embolization are the three different treatment approaches to cerebral arteriovenous malformations (AVMs). Although microsurgical resection remains the most desirable curative option and radiosurgery is often first choice in deep located/eloquent unruptured AVMs, transarterial or transvenous embolization may be pursued for ruptured AVMs not amenable to surgical resection. Most complications during endovascular treatment are related to hemorrhage; however, liquid embolic fragment migration or parent vessel occlusion are also possible and can lead to ischemic events. We present a case of endovascular Onyx (Medtronic, Minnesota, USA) embolization of a ruptured thalamic AVM complicated by Onyx reflux into the proximal posterior cerebral artery causing complete vascular occlusion. We demonstrate a bailout technique1-4 using combined stent-retriever and aspiration catheter to dislodge and retrieve the refluxed Onyx cast while maintaining total occlusion of the initially targeted arterial AVM feeder (video 1).neurintsurg;jnis-2023-020832v1/V1F1V1Video 1.

The Rationale Behind Transcirculation Neuroendovascular Interventions: Literature Review Through a Case-Series Approach.

BACKGROUND: With the development of advanced endovascular techniques and materials, neurointerventionalists can perform challenging and complex cases that were previously difficult to perform. Transcirculation approaches could be a useful tool used in complicated cases, providing access to the target vessel, through the contralateral or opposite circulation, when anterograde access is difficult or nonachievable. OBJECTIVE: To retrospectively review cerebrovascular interventions performed through a transcirculation approach performed by staff at our Institution. METHODS: English-language studies, published until August 2022, reporting transcirculation interventions in the cerebrovascular circulation were retrospectively collected. Type of intervention, number of cases, rationale, and complications were analyzed. Furthermore, similar cases performed by staff currently at our institution were also reviewed and described. RESULTS: Including our cases, a total of 273 transcirculation treatment approaches have been reported. Intracranial aneurysm embolization, stroke thrombectomies, intra-arterial ophthalmic chemotherapy, arteriovenous malformationss, arteriovenous fistulas embolizations, and intracranial angioplasty and stenting are common indications. Reason for using a retrograde approach were stent/balloon-assisted coiling of wide neck aneurysm in 116 cases, difficult angulation of branch in 91 cases, occlusion of parent vessel in 55 cases, and bailout/other in 11 cases. CONCLUSION: Transcirculation approaches can be considered for cases where conventional anterograde treatment options are not feasible or as a bailout strategy in failed or complicated treatment attempts. They represent a strategy to consider when facing challenging cases, and if performed by experienced and dedicated neurointerventionalists, they can represent a safe alternative.

Flow cytometry improves the diagnostic value of fine needle aspiration cytology in a spleen with neuroendocrine tumor: A case report.

Fine needle aspirations are infrequently performed on the spleen due to concerns for hemorrhagic complications. As a result, splenic lesions can be challenging to diagnose given the limited amount of available specimen. Metastasis to the spleen is rare and metastatic neuroendocrine tumors to the spleen are scarce in literature. The diagnosis of splenic lesions from fine needle aspirate entails processing which prolongs the turnaround time, particularly if the cytomorphology is non-typical and a limited sample can further complicate this process. We describe a case in which flow cytometry performed on fine needle aspiration of a splenic lesion suggested a diagnosis of neuroendocrine neoplasm involving the spleen. Further workup confirmed this diagnosis. Flow cytometry can recognize neuroendocrine tumors involving the spleen in a timely manner so that appropriate immunohistochemistry tests on limited specimens can be performed to aid in their accurate diagnosis.

Validation of an automated machine learning algorithm for the detection and analysis of cerebral aneurysms.

OBJECTIVE: Machine learning algorithms have shown groundbreaking results in neuroimaging. The authors herein evaluated the performance of a newly developed convolutional neural network (CNN) to detect and analyze intracranial aneurysms (IAs) on CTA. METHODS: Consecutive patients with CTA studies between January 2015 and July 2021 at a single center were identified. The ground truth determination of cerebral aneurysm presence or absence was made from the neuroradiology report. The primary outcome was the performance of the CNN in detecting IAs in an external validation set, measured using area under the receiver operating characteristic curve statistics. Secondary outcomes included accuracy for location and size measurement. RESULTS: The independent validation imaging data set consisted of 400 patients with CTA studies, median age 40 years (IQR 34 years) and 141 (35.3%) of whom were male; 193 patients (48.3%) had a diagnosis of IA on neuroradiologist evaluation. The median maximum IA diameter was 3.7 mm (IQR 2.5 mm). In the independent validation imaging data set, the CNN performed well with 93.8% sensitivity (95% CI 0.87-0.98), 94.2% specificity (95% CI 0.90-0.97), and a positive predictive value of 88.2% (95% CI 0.80-0.94) in the subgroup with an IA diameter ≥ 4 mm. CONCLUSIONS: The described Viz.ai Aneurysm CNN performed well in identifying the presence or absence of IAs in an independent validation imaging set. Further studies are necessary to investigate the impact of the software on detection rates in a real-world setting.

Incidence and outcome of perforations during medium vessel occlusion compared with large vessel occlusion thrombectomy.

BACKGROUND: Vessel perforation during thrombectomy is a severe complication and is hypothesized to be more frequent during medium vessel occlusion (MeVO) thrombectomy. The aim of this study was to compare the incidence and outcome of patients with perforation during MeVO and large vessel occlusion (LVO) thrombectomy and to report on the procedural steps that led to perforation. METHODS: In this multicenter retrospective cohort study, data of consecutive patients with vessel perforation during thrombectomy between January 1, 2015 and September 30, 2022 were collected. The primary outcomes were independent functional outcome (ie, modified Rankin Scale 0-2) and all-cause mortality at 90 days. Binomial test, chi-squared test and t-test for unpaired samples were used for statistical analysis. RESULTS: During 25 769 thrombectomies (5124 MeVO, 20 645 LVO) in 25 stroke centers, perforation occurred in 335 patients (1.3%; mean age 72 years, 62% female). Perforation occurred more often in MeVO thrombectomy (2.4%) than in LVO thrombectomy (1.0%, p<0.001). More MeVO than LVO patients with perforation achieved functional independence at 3 months (25.7% vs 10.9%, p=0.001). All-cause mortality did not differ between groups (overall 51.6%). Navigation beyond the occlusion and retraction of stent retriever/aspiration catheter were the two most common procedural steps that led to perforation. CONCLUSIONS: In our cohort, perforation was approximately twice as frequent in MeVO than in LVO thrombectomy. Efforts to optimize the procedure may focus on navigation beyond the occlusion site and retraction of stent retriever/aspiration catheter. Further research is necessary in order to identify thrombectomy candidates at high risk of intraprocedural perforation and to provide data on the effectiveness of endovascular countermeasures.

Transradial embolization of a life-threatening tooth extraction socket hemorrhage and pseudoaneurysm.

Embolization of oral hemorrhages due to tooth extraction, although rare, has been previously described.1-4 In this video we present a unique case in which a life-threatening tooth extraction hemorrhage was incontrollable with local compression or surgical cauterization. The patient underwent emergent transradial coil embolization5 of the posterior lateral nasal branches of the sphenopalatine artery. However, the patient returned 11 days later with a lower volume bleed at the original site. Computed tomography angiography showed a pseudoaneurysm at the orthognathic surgery crater retrogradely recanalized through the greater palatine arcade. Surgical options were deemed too invasive, and the decision was made to attempt percutaneous direct puncture embolization. This was unsuccessful and repeat embolization with Onyx was performed through the contralateral greater palatine artery. The patient had complete resolution of symptoms.

SOFIA Nonwire Advancement techniKE 35 Technique: A Minimalist Approach to Stroke Thrombectomy.

BACKGROUND: The Soft Torqueable Catheter Optimized for Intracranial Access (SOFIA) is a catheter designed to enable intracranial access, allowing for advancement, at least partially, without a microcatheter by a technique called SOFIA Nonwire Advancement techniKE (SNAKE). We propose a variation of this technique, called SOFIA Nonwire Advancement techniKE 35 (SNAKE35), in which the catheter is navigated by the intracatheter support of a 0.035-inch guidewire, allowing for rapid, distal intracranial access through a biaxial technique. OBJECTIVE: To assess the performance of a modified navigation technique in the setting of acute stroke thrombectomy. METHODS: Consecutive patients who underwent a thrombectomy procedure between January 2017 and February 2019 were retrospectively identified at our institution. The primary end point was defined as successful positioning of the catheter at the proximal end of the occlusion with the sole use of the SNAKE35 technique. Secondary end points were defined as complications, reperfusion times, and thrombolysis in cerebral infarction scores. RESULTS: Among 140 patients, SNAKE35 was attempted in 79 patients (SNAKE35 group), while traditional navigation was used in the remaining 61 patients (conventional group). Of the total 79 cases, SNAKE35 was successful in positioning the catheter at the proximal end of the occlusion in 66 cases (84%). Of these, 54 cases were completed solely with aspiration techniques. Groin puncture to revascularization time averaged 26 minutes in the SNAKE35 group and 37 minutes in the conventional group ( P < .05), despite older age ( P < .001) and increased use of conscious sedation ( P < .001) in the SNAKE35 group. CONCLUSION: SNAKE35 is an effective and safe technique for SOFIA navigation up to the site of intracranial occlusion in the anterior circulation leading to significant decrease of procedural times.

Citrullinated Inhibitor of DNA Binding 1 Is a Novel Autoantigen in Rheumatoid Arthritis.

OBJECTIVE: To explore the intrinsic role of inhibitor of DNA binding 1 (ID-1) in rheumatoid arthritis (RA) fibroblast-like synoviocytes (FLS) and to investigate whether ID-1 is citrullinated and autoantigenic in RA. METHODS: RA patient serum ID-1 levels were measured before and after infliximab treatment. RA FLS were transfected with a clustered regularly interspaced short palindromic repeat (CRISPR)/CRISPR-associated protein 9 construct targeting ID-1 to examine the effects of ID-1 deletion. RA synovial fluid (SF) and homogenized synovial tissue (ST) were immunoprecipitated for ID-1 and measured for citrullinated residues using an enzyme-linked immunosorbent assay and Western blotting. Liquid chromatography tandem mass spectrometry (LC-MS/MS) was performed on in vitro-citrullinated recombinant human ID-1 (cit-ID-1) to localize the sites of citrullination. Normal and RA sera and SF were analyzed by immunodot blotting for anti-citrullinated protein antibodies (ACPAs) to cit-ID-1. RESULTS: RA patient serum ID-1 levels positively correlated with several disease parameters and were reduced after infliximab treatment. RA FLS displayed reduced growth and a robust increase in interleukin-6 (IL-6) and IL-8 production upon deletion of ID-1. ID-1 immunodepletion significantly reduced the levels of citrullinated residues in RA SF, and citrullinated ID-1 was detected in homogenized RA ST (n = 5 samples; P < 0.05). Immunodot blot analyses revealed ACPAs to cit-ID-1 but not to native ID-1, in RA peripheral blood (PB) sera (n = 30 samples; P < 0.001) and SF (n = 18 samples; P < 0.05) but not in normal PB sera. Following analyses of LC-MS/MS results for citrullination sites and corresponding reactivity in immunodot assays, we determined the critical arginines in ID-1 for autoantigenicity: R33, R52, and R121. CONCLUSION: Novel roles of ID-1 in RA include regulation of FLS proliferation and cytokine secretion as well as autoantigenicity following citrullination.

A Randomized Controlled Trial of Acupressure for the Treatment of Raynaud's Phenomenon: The difficulty of conducting a trial in Raynaud's phenomenon.

OBJECTIVE: To examine the effect of acupressure on Raynaud's phenomenon (RP) in a randomized controlled clinical trial (RCT) and to evaluate the difficulties of conducting a RP RCT. METHODS: A pilot single center RCT of acupressure vs. targeted patient education was conducted for the treatment of RP. Patients with either primary (N = 15) or secondary (N = 8) RP were randomized in an 8-week study. The primary endpoints included a decrease in the frequency and duration of RP. Secondary endpoints included several serum biomarkers including endothelial dysfunction, Raynaud's attack symptoms, Raynaud's Condition Score, and patient and physician global assessments of RP. Primary data analysis was conducted using the last observation carried forward and t-tests or a Wilcoxon rank test was used to compare the two groups. RESULTS: 23 patients were randomized and 7 discontinued prematurely. 78% of patients were female, 96% were Caucasian, and the mean age was 49.8 (SD=16) years. No statistically significant differences were detected between the acupressure vs. education groups in primary and secondary outcomes (p> 0.05). Frequency of attacks decreased by 6.7 attacks (SD=8.8) in the acupressure group vs. 7.2 (SD=12.8) in the education group (p=0.96), and the duration of attacks decreased by 11.4 (SD=19.9) minutes in the acupressure group vs. an increase of 0.8 minutes (SD=11.2) in the education group (p=0.14). There were no adverse events noted in the RCT. CONCLUSION: This pilot study does not support efficacy of acupressure for RP.

Inflammatory properties of inhibitor of DNA binding 1 secreted by synovial fibroblasts in rheumatoid arthritis.

BACKGROUND: Inhibitor of DNA binding 1 (Id1) is a nuclear protein containing a basic helix-loop-helix (bHLH) domain that regulates cell growth by selective binding and prevention of gene transcription. Sources of Id1 production in rheumatoid arthritis synovial tissue (RA ST) and its range of functional effects in RA remain to be clarified. METHODS: We analyzed Id1 produced from synovial fibroblasts and endothelial cells (ECs) with histology and real-time polymerase chain reaction (RT-PCR). Fibroblast supernatants subjected to differential centrifugation to isolate and purify exosomes were measured for Id1 by enzyme-linked immunosorbent assay (ELISA). Western blotting of Id1-stimulated ECs was performed to determine the kinetics of intracellular protein phosphorylation. EC intracellular signaling pathways induced by Id1 were subsequently targeted with silencing RNA (siRNA) for angiogenesis inhibition. RESULTS: By PCR and histologic analysis, we found that the primary source of Id1 in STs is from activated fibroblasts that correlate with inflammatory scores in human RA ST and in joints from K/BxN serum-induced mice. Normal (NL) and RA synovial fibroblasts increase Id1 production with stimulation by transforming growth factor beta (TGF-ß). Most of the Id1 released by RA synovial fibroblasts is contained within exosomes. Endothelial progenitor cells (EPCs) and human dermal microvascular ECs (HMVECs) activate the Jnk signaling pathway in response to Id1, and Jnk siRNA reverses Id1-induced HMVEC vessel formation in Matrigel plugs in vivo. CONCLUSIONS: Id1 is a pleotropic molecule affecting angiogenesis, vasculogenesis, and fibrosis. Our data shows that Id1 is not only an important nuclear protein, but also can be released from fibroblasts via exosomes. The ability of extracellular Id1 to activate signaling pathways expands the role of Id1 in the orchestration of tissue inflammation.

Expression and function of aminopeptidase N/CD13 produced by fibroblast-like synoviocytes in rheumatoid arthritis: role of CD13 in chemotaxis of cytokine-activated T cells independent of enzymatic activity.

OBJECTIVE: Aminopeptidase N/CD13 (EC 3.4.11.2) is a metalloproteinase expressed by fibroblast-like synoviocytes (FLS). It has been suggested that CD13 can act chemotactically for T cells in rheumatoid arthritis (RA). We undertook this study to measure CD13 in vivo and in vitro in RA samples and to determine whether CD13 could play a role in the homing of T cells to the RA joint. METHODS: Interleukin-17-treated FLS were used to immunize mice, from which a novel anti-human CD13 monoclonal antibody (mAb), 591.1D7.34, was developed. The mAb 591.1D7.34 and a second anti-CD13 mAb, WM15, were used to develop a novel enzyme-linked immunosorbent assay (ELISA) for CD13, and CD13 enzymatic activity was measured in parallel. Chemotaxis of cytokine-activated T cells was measured by a chemotaxis-under-agarose assay. RESULTS: We detected substantial amounts of CD13 in synovial fluid (SF), sera, FLS lysates, and culture supernatants by ELISA, with a significant increase in CD13 in RA SF when compared to osteoarthritis SF. CD13 accounted for most but not all of the CD13-like enzymatic activity in SF. Recombinant human CD13 was chemotactic for cytokine-activated T cells through a G protein-coupled receptor and contributed to the chemotactic properties of SF independently of enzymatic activity. CONCLUSION: CD13 is released from FLS into culture supernatants and is found in SF. CD13 induces chemotaxis of cytokine-activated T cells, a T cell population similar to that found in RA synovium. These data suggest that CD13 could play an important role as a T cell chemoattractant, in a positive feedback loop that contributes to RA synovitis.

Activation of the Thromboxane A2 Receptor by 8-Isoprostane Inhibits the Pro-Angiogenic Effect of Vascular Endothelial Growth Factor in Scleroderma.

The pathogenesis of scleroderma (SSc) includes components of autoimmunity, vascular dysfunction, and accumulation of extracellular matrix. 8-isoprostane, an oxidized lipid created by oxidative stress, activates the thromboxane A2 receptor (TXAR) and the Rho-associated kinase (ROCK) pathway. In this study, we determined whether the TXAR was activated by 8-isoprostane in SSc endothelial cells (ECs) and whether this pathway inhibited VEGF-induced angiogenesis. Elevated 8-isoprostane was observed in plasma and conditioned media from SSc patients. SSc-conditioned media inhibited EC tube formation, whereas addition of vitamin E, by reducing 8-isoprostane, increased tube formation. VEGF did not induce angiogenesis in SSc ECs, but vitamin E or TXAR inhibition restored its effect. The expression of TXAR, RhoA, and ROCK1/2 was elevated in SSc ECs. ROCK activity and 8-isoprostane-induced ROCK activation were significantly higher in SSc ECs, whereas VEGF had no effect. The hyper-activation of the TXAR leads to inhibition of VEGF-induced angiogenesis, as inhibition of the TXAR pathway results in a blockade of 8-isoprostane-induced ROCK activation and restoration of VEGF activity. These results suggest that the TXAR pathway has a crucial role in angiogenesis and that 8-isoprostane is not just a by-product of oxidative stress but also has a significant role in the impaired angiogenesis that characterizes SSc.

The effect of timing of postmastectomy radiation on implant-based breast reconstruction: a retrospective comparison of complication outcomes.

BACKGROUND: The optimal timing of postmastectomy radiation for women undergoing delayed permanent implant exchange continues to remain controversial. The objective of our study is to compare complication rates when tissue expanders are exchanged for permanent implants pre- vs postradiation. METHODS: A retrospective review of 54 consecutive patients who underwent implant-based breast reconstruction and received postmastectomy radiation was conducted. Complications including infection, implant loss, and capsular contracture (measured in Baker score) were compared between the 2 groups. RESULTS: Of the patients studied, 32 patients had radiation before placement of permanent implants, whereas 22 patients received radiation after implant placement. There was no difference in individual complication rates between the 2 groups. CONCLUSIONS: In our study of 54 patients, the timing of radiation did not affect individual complication rates for patients who underwent implant-based breast reconstruction after immediate tissue expander placement.

Inhibitor of DNA binding 1 as a secreted angiogenic transcription factor in rheumatoid arthritis.

INTRODUCTION: Rheumatoid arthritis (RA) is characterized by enhanced blood vessel development in joint synovium. This involves the recruitment of endothelial progenitor cells (EPCs), allowing for de novo vessel formation and pro-inflammatory cell infiltration. Inhibitor of DNA Binding 1 (Id1) is a transcription factor characteristic of EPCs that influences cell maturation. METHOD: Enzyme-linked immunosorbant assay (ELISA) and polymerase chain reaction (PCR) were used to examine Id1 levels in synovial fluid (SF) and endothelial cells (ECs), respectively. Immunohistology was used to determine the expression of Id1 in synovial tissue (ST). Human dermal microvascular EC (HMVEC) migration and tube forming assays were used to determine if recombinant human Id1 (rhuId1) and/or RA SF immunodepleted Id1 showed angiogenic activity. We also utilized the RA ST severe combined immunodeficient (SCID) mouse chimera to examine if Id1 recruits EPCs to RA synovium. RESULTS: ST samples immunostained for Id1 showed heightened expression in RA compared to osteoarthritis (OA) and normal (NL) ST. By immunofluorescence staining, we found significantly more Id1 in RA compared to OA and NL vasculature, showing that Id1 expressing cells, and therefore EPCs, are most active in vascular remodeling in the RA synovium. We also detected significantly more Id1 in RA compared to OA and other arthritis SFs by ELISA, which correlates highly with Chemokine (C-X-C motif) ligand 16 (CXCL16) levels. In vitro chemotaxis assays showed that Id1 is highly chemotactic for HMVECs and can be attenuated by inhibition of Nuclear Factor κB and phosphoinositide 3-kinase. Using in vitro Matrigel assays, we found that HMVECs form tubes in response to rhuId1 and that Id1 immunodepleted from RA SF profoundly decreases tube formation in Matrigel in vitro. PCR showed that Id1 mRNA could be up-regulated in EPCs compared to HMVECs in response to CXCL16. Finally, using the K/BxN serum induced arthritis model, we found that EC CXCR6 correlated with Id1 expression by immunohistochemistry. CONCLUSIONS: We conclude that Id1 correlates highly with CXCL16 expression, EPC recruitment, and blood vessel formation in the RA joint, and that Id1 is potently angiogenic and can be up-regulated in EPCs by CXCL16.

Fucosyltransferase 1 mediates angiogenesis, cell adhesion and rheumatoid arthritis synovial tissue fibroblast proliferation.

INTRODUCTION: We previously reported that sialyl Lewis(y), synthesized by fucosyltransferases, is involved in angiogenesis. Fucosyltransferase 1 (fut1) is an α(1,2)-fucosyltransferase responsible for synthesis of the H blood group and Lewis(y) antigens. However, the angiogenic involvement of fut 1 in the pathogenesis of rheumatoid arthritis synovial tissue (RA ST) has not been clearly defined. METHODS: Assay of α(1,2)-linked fucosylated proteins in RA was performed by enzyme-linked lectin assay. Fut1 expression was determined in RA ST samples by immunohistological staining. We performed angiogenic Matrigel assays using a co-culture system of human dermal microvascular endothelial cells (HMVECs) and fut1 small interfering RNA (siRNA) transfected RA synovial fibroblasts. To determine if fut1 played a role in leukocyte retention and cell proliferation in the RA synovium, myeloid THP-1 cell adhesion assays and fut1 siRNA transfected RA synovial fibroblast proliferation assays were performed. RESULTS: Total α(1,2)-linked fucosylated proteins in RA ST were significantly higher compared to normal (NL) ST. Fut1 expression on RA ST lining cells positively correlated with ST inflammation. HMVECs from a co-culture system with fut1 siRNA transfected RA synovial fibroblasts exhibited decreased endothelial cell tube formation compared to control siRNA transfected RA synovial fibroblasts. Fut1 siRNA also inhibited myeloid THP-1 adhesion to RA synovial fibroblasts and RA synovial fibroblast proliferation. CONCLUSIONS: These data show that α(1,2)-linked fucosylated proteins are upregulated in RA ST compared to NL ST. We also show that fut1 in RA synovial fibroblasts is important in angiogenesis, leukocyte-synovial fibroblast adhesion, and synovial fibroblast proliferation, all key processes in the pathogenesis of RA.