CD200 Limits Monopoiesis and Monocyte Recruitment in Atherosclerosis.

[Figure: see text].

Interferon regulatory factor-5-dependent CD11c+ macrophages contribute to the formation of rupture-prone atherosclerotic plaques.

AIMS: Inflammation is a key factor in atherosclerosis. The transcription factor interferon regulatory factor-5 (IRF5) drives macrophages towards a pro-inflammatory state. We investigated the role of IRF5 in human atherosclerosis and plaque stability. METHODS AND RESULTS: Bulk RNA sequencing from the Carotid Plaque Imaging Project biobank were used to mine associations between major macrophage associated genes and transcription factors and human symptomatic carotid disease. Immunohistochemistry, proximity extension assays, and Helios cytometry by time of flight (CyTOF) were used for validation. The effect of IRF5 deficiency on carotid plaque phenotype and rupture in ApoE-/- mice was studied in an inducible model of plaque rupture. Interferon regulatory factor-5 and ITGAX/CD11c were identified as the macrophage associated genes with the strongest associations with symptomatic carotid disease. Expression of IRF5 and ITGAX/CD11c correlated with the vulnerability index, pro-inflammatory plaque cytokine levels, necrotic core area, and with each other. Macrophages were the predominant CD11c-expressing immune cells in the plaque by CyTOF and immunohistochemistry. Interferon regulatory factor-5 immunopositive areas were predominantly found within CD11c+ areas with a predilection for the shoulder region, the area of the human plaque most prone to rupture. Accordingly, an inducible plaque rupture model of ApoE-/-Irf5-/- mice had significantly lower frequencies of carotid plaque ruptures, smaller necrotic cores, and less CD11c+ macrophages than their IRF5-competent counterparts. CONCLUSION: Using complementary evidence from data from human carotid endarterectomies and a murine model of inducible rupture of carotid artery plaque in IRF5-deficient mice, we demonstrate a mechanistic link between the pro-inflammatory transcription factor IRF5, macrophage phenotype, plaque inflammation, and its vulnerability to rupture.

Meta-Analysis of Leukocyte Diversity in Atherosclerotic Mouse Aortas.

The diverse leukocyte infiltrate in atherosclerotic mouse aortas was recently analyzed in 9 single-cell RNA sequencing and 2 mass cytometry studies. In a comprehensive meta-analysis, we confirm 4 known macrophage subsets-resident, inflammatory, interferon-inducible cell, and Trem2 (triggering receptor expressed on myeloid cells-2) foamy macrophages-and identify a new macrophage subset resembling cavity macrophages. We also find that monocytes, neutrophils, dendritic cells, natural killer cells, innate lymphoid cells-2, and CD (cluster of differentiation)-8 T cells form prominent and separate immune cell populations in atherosclerotic aortas. Many CD4 T cells express IL (interleukin)-17 and the chemokine receptor CXCR (C-X-C chemokine receptor)-6. A small number of regulatory T cells and T helper 1 cells is also identified. Immature and naive T cells are present in both healthy and atherosclerotic aortas. Our meta-analysis overcomes limitations of individual studies that, because of their experimental approach, over- or underrepresent certain cell populations. Mass cytometry studies demonstrate that cell surface phenotype provides valuable information beyond the cell transcriptomes. The present analysis helps resolve some long-standing controversies in the field. First, Trem2+ foamy macrophages are not proinflammatory but interferon-inducible cell and inflammatory macrophages are. Second, about half of all foam cells are smooth muscle cell-derived, retaining smooth muscle cell transcripts rather than transdifferentiating to macrophages. Third, Pf4, which had been considered specific for platelets and megakaryocytes, is also prominently expressed in the main population of resident vascular macrophages. Fourth, a new type of resident macrophage shares transcripts with cavity macrophages. Finally, the discovery of a prominent innate lymphoid cell-2 cluster links the single-cell RNA sequencing work to recent flow cytometry data suggesting a strong atheroprotective role of innate lymphoid cells-2. This resolves apparent discrepancies regarding the role of T helper 2 cells in atherosclerosis based on studies that predated the discovery of innate lymphoid cells-2 cells.

Interferon Regulatory Factor 5 Controls Necrotic Core Formation in Atherosclerotic Lesions by Impairing Efferocytosis.

BACKGROUND: Myeloid cells are central to atherosclerotic lesion development and vulnerable plaque formation. Impaired ability of arterial phagocytes to uptake apoptotic cells (efferocytosis) promotes lesion growth and establishment of a necrotic core. The transcription factor interferon regulatory factor (IRF)-5 is an important modulator of myeloid function and programming. We sought to investigate whether IRF5 affects the formation and phenotype of atherosclerotic lesions. METHODS: We investigated the role of IRF5 in atherosclerosis in 2 complementary models. First, atherosclerotic lesion development in hyperlipidemic apolipoprotein E-deficient (ApoE-/-) mice and ApoE-/- mice with a genetic deletion of IRF5 (ApoE-/-Irf5-/-) was compared and then lesion development was assessed in a model of shear stress-modulated vulnerable plaque formation. RESULTS: Both lesion and necrotic core size were significantly reduced in ApoE-/-Irf5-/- mice compared with IRF5-competent ApoE-/- mice. Necrotic core size was also reduced in the model of shear stress-modulated vulnerable plaque formation. A significant loss of CD11c+ macrophages was evident in ApoE-/-Irf5-/- mice in the aorta, draining lymph nodes, and bone marrow cell cultures, indicating that IRF5 maintains CD11c+ macrophages in atherosclerosis. Moreover, we revealed that the CD11c gene is a direct target of IRF5 in macrophages. In the absence of IRF5, CD11c- macrophages displayed a significant increase in expression of the efferocytosis-regulating integrin-ß3 and its ligand milk fat globule-epidermal growth factor 8 protein and enhanced efferocytosis in vitro and in situ. CONCLUSIONS: IRF5 is detrimental in atherosclerosis by promoting the maintenance of proinflammatory CD11c+ macrophages within lesions and controlling the expansion of the necrotic core by impairing efferocytosis.

Indoleamine 2,3-dioxygenase-1 is protective in atherosclerosis and its metabolites provide new opportunities for drug development.

Atherosclerosis is the major cause of cardiovascular disease (CVD), the leading cause of death worldwide. Despite much focus on lipid abnormalities in atherosclerosis, it is clear that the immune system also has important pro- and antiatherogenic functions. The enzyme indoleamine-2,3-dioxygenase (IDO) catalyses degradation of the essential amino acid tryptophan into immunomodulatory metabolites. How IDO deficiency affects immune responses during atherogenesis is unknown and we explored potential mechanisms in models of murine and human atherosclerosis. IDO deficiency in hypercholesterolemic ApoE(-/-) mice caused a significant increase in lesion size and surrogate markers of plaque vulnerability. No significant changes in cholesterol levels were observed but decreases in IL-10 production were found in the peripheral blood, spleen and lymph node B cells of IDO-deficient compared with IDO-competent ApoE(-/-) mice. 3,4,-Dimethoxycinnamoyl anthranilic acid (3,4-DAA), an orally active synthetic derivative of the tryptophan metabolite anthranilic acid, but not l-kynurenine, enhanced production of IL-10 in cultured splenic B cells. Finally, 3,4-DAA treatment reduced lesion formation and inflammation after collar-induced arterial injury in ApoE(-/-) mice, and reduced cytokine and chemokine production in ex vivo human atheroma cell cultures. Our data demonstrate that endogenous production of tryptophan metabolites via IDO is an essential feedback loop that controls atherogenesis and athero-inflammation. We show that the IDO pathway induces production of IL-10 in B cells in vivo and in vitro, suggesting that IDO may induce immunoregulatory functions of B cells in atherosclerosis. The favorable effects of anthranilic acid derivatives in atherosclerosis indicate a novel approach toward therapy of CVD.

Predictive Factors of Lymph Node Metastasis in Follicular Variant of Papillary Thyroid Carcinoma.

BACKGROUND: Compared with conventional papillary thyroid carcinoma (PTC), follicular variant of PTC (FV-PTC) shows less aggressive behavior and better prognosis. Nonetheless, regional lymph node (LN) metastasis was found in 22.8% of FV-PTC patients. Because LN metastasis is a proven predictor of recurrence in PTC, it is important to assess LN metastasis in FV-PTC patients. METHODS: We retrospectively reviewed 134 FV-PTC patients who underwent thyroidectomy with neck dissection. RESULTS: Central LN metastasis (CLNM) and lateral LN metastasis (LLNM) were found in 50 (37.3%) and 16 (11.9%) patients, respectively. In the multivariate analysis for CLNM, male sex (adjusted OR 4.735, p = 0.001), nonencapsulated form (adjusted OR 2.863, p = 0.022), and tumor size >1.0 cm (adjusted OR 3.157, p = 0.008) were independent predictors of high prevalence of CLNM in FV-PTC patients. In the multivariate analysis for LLNM, microscopic extrathyroidal extension (ETE) (adjusted OR 3.939, p = 0.041) and CLNM (adjusted OR 13.340, p = 0.001) were independent predictors of high prevalence of LLNM in FV-PTC patients. CONCLUSIONS: Meticulous perioperative evaluation and prophylactic central neck dissection may be beneficial for FV-PTC patients with male sex, nonencapsulated form, and tumor size >1.0 cm. Moreover, cautious perioperative evaluation of lateral neck LN may be mandatory for FV-PTC patients with microscopic ETE and CLNM.

Computed Tomography-Detected Central Lymph Node Metastasis in Ultrasonography Node-Negative Papillary Thyroid Carcinoma: Is It Really Significant?

BACKGROUND: Because of the limitations in ultrasonography (US), the advantages of computed tomography (CT) for detecting central lymph node (LN) metastasis have been suggested in papillary thyroid carcinoma (PTC). METHODS: First, we compared the diagnostic accuracy of US and CT for detecting central LN metastasis in 6577 central neck levels from 3668 PTC patients. Second, to examine the clinical impact of CT-detected central LN metastasis (CT cN1a) in PTC patients with clinically node negative in US (US cN0), we selected two groups: group I comprised 1245 US cN0 PTC patients who did not have CT scans and did not undergo central neck dissection (CND), while group II comprised 348 US cN0 and CT cN1a PTC patients who underwent CND. After propensity score matching, 254 matched pairs were yielded. RESULTS: For detecting central LN metastasis, CT showed significantly higher sensitivity (38.9 vs. 27.5 %; p < 0.001) and accuracy (66.1 vs. 63.2 %; p < 0.001) than US. Furthermore, US + CT showed significantly higher sensitivity (47.8 vs. 27.5 %; p < 0.001) and accuracy (69.0 vs. 63.2 %; p < 0.001) than US. After matching, radioactive iodine ablation (81.5 vs. 85.8 %; p = 0.235) and locoregional recurrence (p = 0.663) were not significantly different between groups I and II. CONCLUSIONS: Despite the diagnostic advantages of preoperative CT, 'CT-based CND' in US cN0 PTC patients did not significantly influence postoperative management and locoregional recurrence. The strategy for the management of central neck in PTC patients can be sufficiently determined by US only.

Patterns, Predictive Factors, and Prognostic Impact of Contralateral Lateral Lymph Node Metastasis in N1b Papillary Thyroid Carcinoma.

BACKGROUND: Although the incidence among patients with bilateral lateral lymph node metastasis (LLNM) in N1b papillary thyroid carcinoma (PTC) is reported to be as high as 40%, only a few reports have addressed the characteristics of contralateral LLNM. Therefore, this study aimed to investigate the characteristics of patients with contralateral LLNM in N1b PTC. METHODS: This study retrospectively reviewed 834 patients with N1b PTC who underwent modified radical neck dissection between January 1997 and June 2015. RESULTS: Of the 834 N1b PTC patients, unilateral LLNM was found in 728 patients (87.3%) and bilateral LLNM in 106 patients (12.7%). The independent predictors of contralateral LLNM in N1b PTC patients were male sex (adjusted odds ratio [OR], 1.647; p = 0.039), tumor larger than 4 cm (adjusted OR, 6.700; p < 0.001), multiplicity (adjusted OR, 1.754; p = 0.040), bilobar involvement (adjusted OR, 1.971; p = 0.010), and bilateral central LN metastasis (CLNM) (adjusted OR, 2.829; p = 0.025). Moreover, contralateral LLNM significantly increased the risk of overall (adjusted hazard ratio [HR], 1.943; p = 0.016) and lateral neck (adjusted HR, 2.246; p = 0.015) locoregional recurrence. CONCLUSIONS: In the preoperative period, the meticulous evaluation of contralateral lateral neck may be required for male N1b PTC patients with tumor larger than 4 cm, multiplicity, bilobar involvement, and/or bilateral CLNM. In the postoperative period, N1b PTC patients may be re-stratified according to the contralateral LLNM, and meticulous follow-up assessment is required for N1b PTC patients with contralateral LLNM.

Paenibacillus arcticus sp. nov., isolated from Arctic soil.

A Gram-positive, endospore-forming, strictly aerobic and rod-shaped bacterium, designated strain MME2_R6T, was isolated from Arctic soil, and it was identified by using a polyphasic taxonomic approach. This strain was psychrotolerant, growing at 4‒24 °C. 16S rRNA gene sequence analysis showed that strain MME2_R6T was closest to Paenibacillus swuensis DY6T, with 93.9 % similarity. However, in phylogenetic analysis based on the 16S rRNA gene sequence, strain MME2_R6T showed that it clustered with Paenibacillus contaminans CKOBP-6T and the sequencing similarity between the two species was 93.7 %. Its major cellular fatty acid was anteiso-C15 : 0, like other Paenibacillus species. The major polar lipids were phosphatidylethanolamine, phosphatidylglycerol and diphosphatidylglycerol. The predominant isoprenoid quinone was menaquinone-7. The diagnostic diamino acid in the cell wall was meso-diaminopimelic acid. The genomic DNA G+C content was 44.2 mol%. Based on the results of phenotypic, chemotaxonomic and phylogenetic analyses, a novel species, Paenibacillus arcticus sp. nov., is proposed. The type strain is MME2_R6T (=JCM 30981T=PAMC 28731T).

Nomogram for predicting central node metastasis in papillary thyroid carcinoma.

BACKGROUND: There was a difficulty for detecting Central lymph node metastasis (CLNM) in papillary thyroid carcinoma (PTC) patients. Therefore, the purpose of this study was to design a nomogram for predicting CLNM. METHODS: A total of 10,763 PTC patients who underwent total thyroidectomy with central neck dissection (CND) in Samsung Medical Center were randomly assigned to the training set (n = 7,535) and to the internal validation set (n = 3,228). And, a total of 2,514 PTC patients who underwent total thyroidectomy with CND at Seoul National University Hospital were assigned to the external validation set. RESULTS: The values of the area under the receiver operating characteristic curve in the training set, internal validation set, and external validation set were 0.721 (95% confidence interval [CI], 0.709-0.732), 0.706 (95%CI, 0.688-0.724), and 0.706 (95%CI, 0.685-0.727), respectively. CONCLUSIONS: We recommend the use of our nomogram to enable clinicians and patients to easily personalize and quantify the probability of CLNM during the both pre- and postoperative period. Clinicians may consider the prophylactic CND and meticulous postoperative evaluation in PTC patients with a high nomogram score. J. Surg. Oncol. 2017;115:266-272. © 2016 Wiley Periodicals, Inc.

A novel robotic surgical technique for thyroid surgery: bilateral axillary approach (BAA).

INTRODUCTION: Bilateral axillo-breast approach (BABA) robotic thyroidectomy (RT) is proven to be a feasible method for the treatment of well-differentiated thyroid cancers in terms of oncology as well as cosmesis. However, BABA RT causes postoperative sternal discomfort and needs an incision over the nipple areolar area. Here, we suggest a novel robotic surgical technique for thyroid surgery that does not need a breast incision-bilateral axillary approach (BAA). PATIENTS AND METHODS: We recruited 51 patients who were willing to undergo the novel BAA robotic thyroid surgery. We performed a propensity score-matched analysis to compare the BAA robotic thyroid surgery group (BAA group) with the conventional open thyroid surgery group (open group). RESULTS: Mean operation time in the BAA group (129.7 min) was significantly longer than that in the open group (103.1 min) (p < 0.001). However, no significant differences in the mean number of metastatic lymph nodes (LNs), mean number of retrieved LNs, vocal cord palsy, hypoparathyroidism, and mean stimulated thyroglobulin level were observed between the two groups. There was no case of postoperative bleeding or chyle leak. Of the 51 patients who had undergone the BAA procedure, 27 patients answered the questionnaire. The mean scale, ranging from 0 to 10, at postoperative 1 day/2 weeks was as follows: voice change score, 3.0/1.6; swallowing difficulty score, 4.0/2.0; anterior neck pain score, 4.6/3.6; anterior neck numbness score, 5.4/4.3; right chest pain score, 3.8/2.1; left chest pain score, 3.6/2.3; right chest numbness score, 3.2/2.8; left chest numbness score, 2.4/2.7; right breast pain score, 0.9/0; left breast pain score, 1.2/0; right breast numbness score, 1.7/0; and left breast numbness score, 2.6/0, respectively. CONCLUSION: BAA robotic thyroid surgery is a novel, safe, and feasible oncoplastic method, especially for patients who have fear of procedures around the nipple areolar complex.

Propensity score-matched analysis of robotic versus endoscopic bilateral axillo-breast approach (BABA) thyroidectomy in papillary thyroid carcinoma.

PURPOSE: The da Vinci surgical robot system was developed to overcome the weaknesses of endoscopic surgery. However, whether robotic surgery is superior to endoscopic surgery remains uncertain. Therefore, the purpose of this study was to compare the surgical and oncologic outcomes between endoscopic and robotic thyroidectomy using bilateral axillo-breast approach (BABA). METHODS: Between January 2008 and June 2015, papillary thyroid carcinoma patients who underwent thyroidectomy with central neck dissection using endoscopic (n = 480) or robotic (n = 705) BABA were primarily reviewed. We performed 1:1 propensity score matching and 289 matched pairs were yielded. RESULTS: Operation time was significantly longer in the robotic thyroidectomy than in the endoscopic thyroidectomy (184.9 vs. 128.9 min, P < 0.001). A significantly higher number of central lymph nodes (CLNs) were resected in the robotic thyroidectomy than in the endoscopic thyroidectomy (5.3 vs. 4.4, P = 0.003). However, the incidence of other outcomes including hospital stay, postoperative duration, thyroglobulin level, radioactive iodine ablation, hemorrhage, chyle leakage, wound infection, recurrent laryngeal nerve injury, and loco-regional recurrence did not significantly differ between the endoscopic thyroidectomy and the robotic thyroidectomy. CONCLUSIONS: Endoscopic thyroidectomy is comparable with robotic thyroidectomy in view of surgical complications and LRR. Because robotic thyroidectomy resected a larger number of CLNs than did endoscopic thyroidectomy, further long-term follow-up studies will be required to clarify the possible prognostic benefits of robotic thyroidectomy.

Routine Level 2b Dissection may be Recommended Only in N1b Papillary Thyroid Carcinoma with Three- or Four-Level Lateral Lymph Node Metastasis.

BACKGROUND: Due to the low incidence of level 2b metastasis and the risk of spinal accessory nerve injury, previous studies have argued against routine level 2b dissection for N1b papillary thyroid carcinoma (PTC). However, other studies have suggested the importance of including level 2b during lateral neck dissection. Therefore, this study aimed to determine the necessity of routine level 2b dissection. METHODS: The study retrospectively reviewed 327 N1b PTC patients who underwent unilateral modified radical neck dissection between January 1997 and May 2016. RESULTS: The incidence of level 2b metastasis was 10.4 %, compared with 53.5 % for level 2a metastasis. The univariate analysis showed that large tumor size (p = 0.027) and simultaneous lateral lymph node metastasis (LLNM) (p = 0.002) were significantly associated with level 2b metastasis. The multivariate analysis showed that three-level (adjusted odds ratio [OR] 6.032; p = 0.020) and four-level (adjusted OR 9.398; p = 0.012) simultaneous LLNM were independent predictors for level 2b metastasis. CONCLUSIONS: Due to the low incidence of level 2b metastasis, routine level 2b dissection may not be necessary for N1b PTC patients. Level 2b dissection may be reserved for patients with more than three-level simultaneous LLNM or clinical/radiological evidence of level 2b metastasis.

Predictive Factors for Lymph Node Metastasis in Papillary Thyroid Microcarcinoma.

BACKGROUND: Because lymph node (LN) metastasis has been proven to be a predictor for locoregional recurrence (LRR) in papillary thyroid microcarcinoma (PTMC), better knowledge about the predictors for LN metastasis in PTMC is required. METHODS: We retrospectively reviewed 5656 PTMC patients who underwent total thyroidectomy and central neck dissection and/or lateral neck dissection between January 1997 and June 2015. RESULTS: Male gender (adjusted odds ratio [OR] 2.332), conventional variant (adjusted OR 4.266), tumor size >0.5 cm (adjusted OR 1.753), multiplicity (adjusted OR 1.168), bilaterality (adjusted OR 1.177), and extrathyroidal extension (ETE) (adjusted OR 1.448) were independent predictors for high prevalence of central LN metastasis (CLNM), whereas per 10-year age increment (adjusted OR 0.760) and chronic lymphocytic thyroiditis (adjusted OR 0.791) were independent predictors for low prevalence of CLNM. In addition, male gender (adjusted OR 1.489), tumor size >0.5 cm (adjusted OR 1.295), multiplicity (adjusted OR 1.801), ETE (adjusted OR 1.659), and CLNM (adjusted OR 4.359) were independent predictors for high prevalence of lateral LN metastasis (LLNM), whereas per 10-year age increment (adjusted OR 0.838) was an independent predictor for low prevalence of LLNM. There was a statistically significant difference in LRR with regard to nodal stage (p < 0.001). CONCLUSIONS: Meticulous perioperative evaluation of LN metastasis is required for PTMC patients with the above predictors.

Thalassobius litorarius sp. nov., isolated from a tidal flat.

A Gram-stain-negative, aerobic, non-motile and rod-shaped bacterium, belonging to the family Rhodobacteraceae, designated strain MME-075T, was isolated from a tidal flat. Strain MME-075T grew with 1-5% (w/v) NaCl at 20-35 °C and at pH 7-9. Optimal growth occurred with 2% (w/v) NaCl at 25-30 °C and at pH 7. The dominant respiratory quinone was ubiquinone-10, whereas summed feature 8 (C18:1ω7c and/or C18:1ω6c), 11-methyl C18:1ω7c, and C16:0 were the major fatty acids. The major polar lipids were phosphatidylcholine, phosphatidylethanolamine, phosphatidylglycerol and an unidentified lipid. The genomic DNA G+C content was 62.1 mol%. The highest 16S rRNA gene sequence similarity values were between strain MME-075T and Thalassobius aestuarii, Thalassococcus lentus, Thalassobius maritimus and Shimia marina and were 97.6, 97.5, 97.2 and 96.2%, respectively. Neighbour-joining, maximum-likelihood and maximum-parsimony phylogenetic trees, based on 16S rRNA gene sequences, revealed that strain MME-075T clustered with species of the genus Thalassobius. Based on phenotypic and phylogenetic taxonomic properties, this strain is proposed as a representative of a novel species of the genus Thalassobius, for which the name Thalassobius litorarius sp. nov. is proposed. The type strain is MME-075T (=KCCM 43143T=JCM 30758T).

Pseudoruegeria aestuarii sp. nov., of the family Rhodobacteraceae, isolated from a tidal flat.

A Gram-stain-negative, non-motile, aerobic and rod-shaped bacterium, designated strain MME-001T, was isolated from the tidal flat of Muui-do in the Republic of Korea. Phylogenetic trees based on the 16S rRNA gene sequence showed that strain MME-001T belonged to the genus Pseudoruegeria in the family Rhodobacteraceae and that it shared the highest 16S rRNA gene sequence similarity with Pseudoruegeria sabulilitoris GJMS-35T (98.0 % similarity of the 16S rRNA gene). Growth of strain MME-001T occurred in the presence of 1.0-7.0 % (w/v) NaCl at 15-40 °C and pH 7.0-9.0, with optimal growth in the presence of 2.0-3.0 % (w/v) NaCl at 25-30 °C and pH 7.0. Ubiquinone-10 was the major respiratory quinone. Major polar lipids were phosphatidylcholine, phosphatidylethanolamine, phosphatidylglycerol and an unidentified lipid. The major cellular fatty acids were C18 : 1ω7c and C16 : 0. The genomic DNA G+C content was 62 mol%. DNA-DNA hybridization values between strain MME-001T and P. sabulilitoris KCTC 42111T, 'Pseudoruegeria limi' KCTC 32460, Pseudoruegeria lutimaris KCTC 22690T, Pseudoruegeria aquimaris KCTC 12737T and Pseudoruegeriahaliotis KACC 17214T was 36±5, 57±7, 34±4, 18±5 and 21±3 %, respectively. Based on the phenotypic and phylogenetic taxonomical properties, this strain MME-001T represents a novel species of the genus Pseudoruegeria, for which the name Pseudoruegeria aestuarii sp. nov. is proposed. The type strain is MME-001T (=KCCM 43133T=JCM 30751T).

Preserving Parathyroid Gland Vasculature to Reduce Post-thyroidectomy Hypocalcemia.

BACKGROUND: The failure to preserve parathyroid function in patients who have undergone total thyroidectomy is of major concern, because hypocalcemia is difficult to prevent and remains a common postoperative complication. Here, we describe procedures designed to preserve the vasculature supplying the parathyroid glands and examine both recent outcomes and retrospective reports of results obtained prior to the application of these preservation techniques. METHODS: Our technique for preserving parathyroid function during thyroidectomy was adopted in 2009 and involves separating a relatively long segment of a vessel distally from the thyroid gland. We reviewed the medical records of 1,411 patients who underwent total thyroidectomy, with or without lateral neck dissection, at the Samsung Medical Center from January 2006 through June 2014 to determine outcomes. Patients were divided into three groups according to the time period during which the surgery took place: Group A, 2006-2008 (before the vasculature-preserving technique was applied); Group B, 2009-2011 (the time when the technique was first adopted); and Group C, 2012-2014 (more recent results of the technique). We analyzed the incidence of hypoparathyroidism in the three groups, as well as risk factors that influenced its development. RESULTS: The rates of transient and permanent hypoparathyroidism in Group A were 25.4 and 4.3 %, respectively. However, the incidence of hypoparathyroidism decreased significantly over time after the vasculature-preserving procedure was adopted. Transient hypoparathyroidism developed in 4.8 % of Group C patients, and only four (0.7 %) of the 565 patients in this group required calcium supplementation, despite the fact that a greater number of patients were included who underwent total thyroidectomy combined with lateral neck dissection. Although female sex and lateral neck dissection tended to increase the rate of transient hypoparathyroidism, multivariate analysis showed that the vasculature-preserving procedure was the only significant risk factor related to postoperative hypoparathyroidism. CONCLUSION: The blood flow of the final branch to the parathyroid gland is mostly in the lateral-to-medial direction; therefore, mobilization and preservation of the vessels lateral to the gland is essential to prevent devascularization of the parathyroid gland.

Low shear stress induces M1 macrophage polarization in murine thin-cap atherosclerotic plaques.

Macrophages, a significant component of atherosclerotic plaques vulnerable to acute complications, can be pro-inflammatory (designated M1), regulatory (M2), lipid- (Mox) or Heme-induced (Mhem). We showed previously that low (LSS) and oscillatory (OSS) shear stress cause thin-cap fibroatheroma and stable smooth muscle cell-rich plaque formation respectively in ApoE-knockout (ApoE(-/-)) mice. Here we investigated whether different shear stress conditions relate to specific changes in macrophage polarization and plaque morphology by applying a shear stress-altering cast to the carotid arteries of high fat-fed ApoE(-/-) mice. The M1 markers iNOS and IRF5 were highly expressed in macrophage-rich areas of LSS lesions compared to OSS lesions 6weeks after cast placement, while the M2 marker Arginase-1, and Mox/Mhem markers HO-1 and CD163 were elevated in OSS lesions. Our data indicates shear stress could be an important determinant of macrophage polarization in atherosclerosis, with low shear promoting M1 programming.

Improved sedation with dexmedetomidine-remifentanil compared with midazolam-remifentanil during catheter ablation of atrial fibrillation: a randomized, controlled trial.

AIMS: Anaesthesia is required for catheter ablation of atrial fibrillation (A-fib) to achieve patient comfort and immobilization to avoid map shifts. This study compared the analgesic and sedative efficacies of dexmedetomidine-remifentanil with those of midazolam-remifentanil for catheter ablation of A-fib. METHODS AND RESULTS: Ninety patients were randomized to receive either intermittent midazolam boluses (1-2 mg) with 3.6-7.2 µg/kg/h of remifentanil (MR group) or dexmedetomidine 0.2-0.7 µg/kg/h after a loading dose of 1 µg/kg with 1.2-2.4 µg/kg/h of remifentanil (DR group). The sedation level assessed by the Ramsay sedation and bispectral index scores, haemodynamic variables, pain score (10-point numerical scale), and satisfaction levels of the patients and cardiologists (5-point numerical scale) were recorded. The Ramsay sedation score was significantly higher, and the bispectral index score was lower in the DR group (P< 0.001) compared with the MR group starting 10 min after drug administration. The incidence of desaturation (SpO2 < 90%) was significantly greater in the MR group compared with the DR group (15 vs. 1, P < 0.001). The pain score was significantly lower (1.72 ± 1.65 vs. 0.95 ± 1.10, P = 0.021), and the satisfaction levels of interventionists were significantly higher (2.50 ± 0.71 vs. 3.00 ± 0.63, P = 0.001) in the DR group compared with the MR group. CONCLUSION: The combination of dexmedetomidine and remifentanil provided deeper sedation, less respiratory depression, better analgesia, and higher satisfaction for the interventionist during catheter ablation of A-fib compared with midazolam plus remifentanil, even at a lower dose of remifentanil.

Identification of a non-canonical chemokine-receptor pathway suppressing regulatory T cells to drive atherosclerosis.

CCL17 is produced by conventional dendritic cells (cDCs), signals through CCR4 on regulatory T cells (Tregs), and drives atherosclerosis by suppressing Treg functions through yet undefined mechanisms. Here we show that cDCs from CCL17-deficient mice display a pro-tolerogenic phenotype and transcriptome that is not phenocopied in mice lacking its cognate receptor CCR4. In the plasma of CCL17-deficient mice, CCL3 was the only decreased cytokine/chemokine. We found that CCL17 signaled through CCR8 as an alternate high-affinity receptor, which induced CCL3 expression and suppressed Treg functions in the absence of CCR4. Genetic ablation of CCL3 and CCR8 in CD4+ T cells reduced CCL3 secretion, boosted FoxP3+ Treg numbers, and limited atherosclerosis. Conversely, CCL3 administration exacerbated atherosclerosis and restrained Treg differentiation. In symptomatic versus asymptomatic human carotid atheroma, CCL3 expression was increased, while FoxP3 expression was reduced. Together, we identified a non-canonical chemokine pathway whereby CCL17 interacts with CCR8 to yield a CCL3-dependent suppression of atheroprotective Tregs.