Local gentamicin-collagen sponge reduces cardiovascular implantable electronic device infections and pocket hematoma.

OBJECTIVE: Implantation or replacement of a cardiovascular implantable electronic device (CIED) may be associated with complications, such as pocket hematomas and infections. This study aims to determine whether a lyophilized gentamycin-containing collagen implant (GCCI) reduces major CIED infections and pocket hematomas after implant. SUBJECTS AND METHODS: A retrospective study was conducted among patients who underwent implantation or replacement of CIED at the Tor Vergata Polyclinic (Rome, Italy) between June 2007 and November 2019. The primary combined endpoint was infection and hematoma occurrence through 12 months of follow-up post-procedure. The rate of single infectious complications, pocket hematomas or both were also assessed. RESULTS: We compared 475 patients treated with the GCCI (GCCI group) with 714 patients who did not receive it (control group). Complications occurred in 127 patients (11%); a statistically significant reduction of infections and pocket hematomas in the GCCI group was reported when compared with control patients (1% vs. 17%; p<0.0001). A total of 20 (2%) infectious events were reported, 102 (8%) patients developed a pocket hematoma, and 5 (0.4%) had both. The rate of single complications was significantly lower in GCCI group: infection 0.2% vs. 2.6% (p=0.002), pocket hematoma 0.6% vs. 13.8% (p<0.001). The association between antiplatelet/anticoagulation therapy and hematoma development was not statistically significant. CONCLUSIONS: The GCCI is a medical device that can be used in addition to local hemostasis and prophylactic doses of systemic antibiotics with the aim of reducing infective complications and pocket hematoma after permanent CIED implantation or replacement.

2D/3D accuracies of implant position after guided surgery using different surgical protocols: A retrospective study.

PURPOSE: To compare the 2D and 3D positional accuracy of four guided surgical protocols using an analysis of linear and angular deviations. METHODS: DICOM and .STLs files obtained from a CBCT and a digital impression were superimposed with software to plan implant position. Fifty-six patients were subdivided into 4 groups: FGA group (template support [Ts]: teeth [T]; bed preparation [Bp]: fully guided [FG]; implant insertion [Ii]: 3D template [3Dt]; device [D]: manual adapter [MA], FGM group (Ts: T; Bp: FG; Ii: 3Dt; D: fully guided mounter [FGM]), PG group (Ts: T; Bp: FG; Ii: manual; D: none) and MS group (Ts: mucosa; Bp: FG; Ii: 3Dt; D: FGM). The position of 120 implants was assessed by superimposing the planned and final position recorded with a digital impression. RESULTS: In FGA group, 3D deviations were 0.92 ± 0.52 mm at the implant head and 1.14 ± 0.54 mm at the apex, and the angular deviation (ang. dev.) was 2.45 ± 1.24°. In FGM group, were 0.911 ± 0.44 mm (head) and 1.11 ± 0.54 mm (apex), and the ang. dev. was 2.73 ± 1.96°. In PG group, were 0.95 ± 0.47 mm (head) and 1.17 ± 0.488 mm (apex), and the ang. dev. was 3.71 ± 1.67°. In MS group, were 1.15 ± 0.45 mm (head) and 1.42 ± 0.45 mm (apex), and the ang. dev. was 4.19 ± 2.62°. Ang. dev. of MS group was different from the other groups (P < 0.05). CONCLUSIONS: Guided surgery showed a sufficient accuracy.

In vitro 3D and gravimetric analysis of removed tooth structure for complete and partial preparations.

PURPOSE: To quantify and to compare a gravimetric and three-dimensional (3D) analysis of the removed tooth structure for different complete crown preparations. METHODS: A total of 80 molar resin teeth and 8 preparation finishing lines were chosen: 1 for metal ceramic crowns (MCC); 3 for zirconia all-ceramic crowns: knife edge (ZirKnE), chamfer (ZirCha), and shoulder (ZirSho); 4 for lithium disilicate: light chamfer (LDLCha), chamfer (LDCha), shoulder (LDSho) and table top. Teeth were individually weighed to high precision and then prepared following the preparation guidelines. The teeth were reweighed after preparation, and the amount of structural reduction was calculated. In addition, all teeth were scanned before and after preparation, and the 3D volume of removed dental tissue was calculated, superimposing the two .stl files, as a difference of the volumes before and after the preparation. Kruskal-Wallis statistical analysis was carried out to determine significant differences among the groups with a significance level of p<0.05. RESULTS: Both analyses showed that LDLCha, ZirKnE and table-top preparations produced the smallest amount of removed structure, whereas the preparations for MCC, ZirSho and LDSho were more destructive. For MCC, 2.6 times more tooth structure must be removed than for table top. ZirKnE was 17.82% and LDLCha was 21.51% more conservative than MCC. The data obtained through the volumetric method were similar with those obtained by gravimetric analysis. CONCLUSIONS: ZirKnE, LDLCha, and table-top preparations produced the least amount of tooth tissue removal. Three-dimensional volumetric analysis can be a possible alternative to gravimetric analysis.

Influence of preparation design and spacing parameters on the risk of chipping of crowns made with Cerec Bluecam before cementation.

PURPOSE: To evaluate the influence of the preparation design and spacing parameters on the risk of chipping of crowns made by CEREC Bluecam before cementation. METHODS: A knife-edge preparation and a chamfer preparation were made on upper premolars. The teeth were scanned and two Co-Cr alloy replicas were made. Fifteen full crowns were manufactured for four groups using CEREC. The groups differed in type of preparation (knife-edge (KE) or chamfer (CHA)) and spacing parameters: spacer (0 or 150µm), marginal adhesive gap (10 or 50 or 150µm) and margin thickness (0 or 300µm). The four groups were: CHA 150 (spacer)- 50 (marginal adhesive gap)- 0 (margin thickness), KE 150-50-0, KE 150-50-300 and KE 150-150-300. The crowns were loaded before cementation by using an Instron machine to simulate the masticatory load applied during a trial. Differences in means were compared using two-way ANOVA and a post-hoc test (Tukey Test). The level of significance was set at P=0.05. RESULTS: The fracture values, ordered from least to most resistant, were: KE 150-50-300 group, CHA 150-50-0 group, KE 150-50-0 group and KE 150-150-300 group. Two-way ANOVA revealed statistically significant differences between pairs of means (p<0.05). Tukey's test showed that restorations of the KE 150-150-300 group can withstand a load significantly higher than that of other groups (p<0.01). In this group, the failures were mostly minor chippings, while the other groups had mostly major chippings and fractures. CONCLUSIONS: Marginal adhesive gap can affect the trial of a full crown.

Different Methods for Inlay Production: Effect on Internal and Marginal Adaptation, Adjustment Time, and Contact Point.

The aim of this study was to evaluate the effect of different production methods of resin and ceramic inlays on marginal and internal adaptation, adjustment time, and proximal contacts. Forty premolars were selected, embedded (their roots), and prepared to receive inlays that were made as follows (n=10): LaRe-digital impression with a Lava C.O.S. scanner, followed by milling of Lava Ultimate block (composite resin) in a milling center; CeRe-digital impression with a Cerec 3D Bluecam scanner, followed by milling of Lava Ultimate block in Cerec; CeDis-digital impression with a Cerec 3D Bluecam scanner, followed by milling of IPS e.max CAD block (lithium disilicate) in Cerec; and PresDis-impression with polyvinyl siloxane, inlay made using the lost wax technique and IPS e.max Press pressed ceramic (lithium disilicate). Marginal and internal adaptations were measured using the replica technique. The inlay adjustments were performed using diamond burs in a contra-angle hand piece, and the time for adjustment was recorded using a timer, in seconds. The tightness of the proximal contact was measured using standardized metal blades. The statistical analyses for marginal fit data showed that at the cervical edge, CeDis (177.8 µm) had greater misfit than CeRe (116.7 µm), while all the groups had similar adaptation at the occlusal edge. The groups had similar internal fit at the pulpal wall, while LaRe (104.7 µm) > CeDis (66.7 µm) = CeRe (76.7 µm) at the axial wall. The groups restored with lithium disilicate ceramic took more time for adjustment when compared to the resin restorative material. The lowest proximal contact, in micrometers, was seen in the CeRe group (8.8 µm).

Anti-apoA-1 auto-antibodies increase mouse atherosclerotic plaque vulnerability, myocardial necrosis and mortality triggering TLR2 and TLR4.

Auto-antibodies to apolipoprotein A-1 (anti-apoA-1 IgG) were shown to promote inflammation and atherogenesis, possibly through innate immune receptors signalling. Here, we aimed at investigating the role of Toll-like receptors (TLR) 2 and 4 on anti-apoA-1 IgG-induced atherosclerotic plaque vulnerability, myocardial necrosis and mortality in mice. Adult male apolipoprotein E knockout (ApoE)-/- (n=72), TLR2-/-ApoE-/- (n=36) and TLR4-/-Apo-/- (n=28) mice were intravenously injected with 50 µg/mouse of endotoxin-free polyclonal anti-apoA-1 IgG or control isotype IgG (CTL IgG) every two weeks for 16 weeks. Atherosclerotic plaque size and vulnerability were assessed by histology. Myocardial ischaemia and necrosis, respectively, were determined by electrocardiographic (ECG) changes assessed by telemetry and serum troponin I (cTnI) measurements. Impact on survival was assessed by Kaplan-Meier analyses. In ApoE-/- mice, anti-apoA-1 IgG passive immunisation enhanced histological features of atherosclerotic plaque vulnerability (increase in neutrophil and MMP-9 and reduction in collagen content), induced a substantial cTnI elevation (p=0.001), and increased mortality rate by 23 % (LogRank, p=0.04) when compared to CTL IgG. On a subgroup of ApoE-/- mice equipped with telemetry (n=4), a significant ST-segment depression was noted in anti-apoA-1 IgG-treated mice when compared to CTL IgG recipients (p< 0.001), and an acute ST-segment elevation myocardial infarction preceding mouse death was observed in one case. The deleterious effects of anti-apoA-1 IgG on atherosclerotic plaque vulnerability, myocardial necrosis and death were partially reversed in TLR2-/-ApoE-/- and TLR4-/-ApoE-/- backgrounds. In conclusion, anti-apoA-1 auto-antibodies seem to be active mediators of atherosclerotic plaque vulnerability, myocardial necrosis, and mortality in mice through TLR2- and TLR4-mediated pathways.

Cardiometabolic and immune factors associated with increased common carotid artery intima-media thickness and cardiovascular disease in patients with systemic lupus erythematosus.

BACKGROUND AND AIM: Patients with systemic lupus erythematosus (SLE) have a higher prevalence of subclinical atherosclerosis and higher risk of cardiovascular (CV) events compared to the general population. The relative contribution of CV-, immune- and disease-related risk factors to accelerated atherogenesis in SLE is unclear. METHODS AND RESULTS: Fifty SLE patients with long-lasting disease (mean age 44 ± 10 years, 86% female) and 50 sex- and age-matched control subjects were studied. Common carotid artery intima-media thickness (CCA-IMT) was used as a surrogate marker of atherosclerosis. We evaluated traditional and immune- and disease-related factors, assessed multiple T-cell subsets by 10-parameter-eight-colour polychromatic flow cytometry and addressed the effect of pharmacological therapies on CCA-IMT. In SLE patients, among several cardiometabolic risk factors, only high-density lipoprotein levels (HDL) and their adenosine triphosphate-binding cassette transporter 1 (ABCA-1)-dependent cholesterol efflux capacity were markedly reduced (p < 0.01), whereas the CCA-IMT was significantly increased (p = 0.03) compared to controls. CCA-IMT correlated with systolic blood pressure, low-density lipoprotein (LDL) cholesterol and body mass index (BMI), but not with disease activity and duration. The activated CD4(+)HLA-DR(+) and CCR5(+) T-cell subsets were expanded in SLE patients. Patients under hydroxychloroquine (HCQ) therapy showed lower CCA-IMT (0.62 ± 0.08 vs. 0.68 ± 0.10 mm; p = 0.03) and better risk-factor profile and presented reduced circulating pro-atherogenic effector memory T-cell subsets and a parallel increased percentage of naïve T-cell subsets. CONCLUSION: HDL represents the main metabolic parameter altered in SLE patients. The increased CCA-IMT in SLE patients may represent the net result of a process in which 'classic' CV risk factors give a continuous contribution, together with immunological factors (CD4(+)HLA-DR(+) T cells) which, on the contrary, could contribute through flares of activity of various degrees over time. Patients under HCQ therapy present a modified metabolic profile, a reduced T-cell activation associated with decreased subclinical atherosclerosis.

Imaging of the vulnerable carotid plaque: biological targeting of inflammation in atherosclerosis using iron oxide particles and MRI.

OBJECTIVES: Identification of those patients with high-risk asymptomatic carotid plaques remains an elusive but essential step in stroke prevention. Inflammation is a key process in plaque destabilization and the propensity of atherosclerotic lesions to cause clinical sequelae. There is currently no clinical imaging technique available to assess the degree of inflammation associated with plaques. This study aims at visualizing and characterizing atherosclerosis using antibody-conjugated superparamagnetic iron oxide (SPIO) particles as an MRI probe to assess inflammation in human atherosclerotic plaques. METHODS: Atherosclerotic plaques were collected from 20 consecutive patients (n=10 from symptomatic patients, n=10 from asymptomatic patients) undergoing carotid endarterectomy (CEA) for extracranial high-grade internal carotid artery (ICA) stenosis (>70% luminal narrowing). Inflammatory markers on human atherosclerotic plaques were detected and characterized by ex vivo magnetic resonance imaging (MRI) using anti-VCAM-1 antibody and anti-E-selectin antibody-conjugated SPIO with confirmatory immunohistochemistry. RESULTS: Inflammation associated with human ex vivo atherosclerotic plaques could be imaged using dual antibody-conjugated SPIO by MRI. Symptomatic plaques could be distinguished from asymptomatic ones by the degree of inflammation, and the MR contrast effect was significantly correlated with the degree of plaque inflammation (r=.64, p<.001). The asymptomatic plaque population exhibited heterogeneity in terms of inflammation. The dual-targeted SPIO-induced MR signal not only tracked closely with endothelial activation (i.e. endothelial expression of VCAM-1 and E-selectin), but also reflected the macrophage burden within plaque lesions, offering a potential imaging tool for quantitative MRI of inflammatory activity in atherosclerosis. CONCLUSIONS: These functional molecular MRI probes constitute a novel imaging tool for ex vivo characterization of atherosclerosis at a molecular level. Further development and translation into the clinical arena will facilitate more accurate risk stratification in carotid artery disease in the future.

Inhibitory effect of TIMP influences the morphology of varicose veins.

OBJECTIVES: Imbalance of matrix metalloproteinase enzymes (MMP) and their inhibitors (TIMPs) may contribute to the development of varicose veins. We hypothesised that, histological changes in varicose vein wall correlate with alterations in expression of MMP/TIMP. METHODS: Varicose veins (n=26) were compared with great saphenous vein (GSV) segments (n=11) from arterial bypass, and with arm and neck veins from fistula and carotid operations (n=13). Varicose vein wall thickness was measured, enabling categorisation as atrophic and hypertrophic. MMP-2, MT1-MMP, TIMP-2, and TIMP-3 expression were quantitatively analysed by immunohistochemistry. RESULTS: There was significantly higher expression of TIMP-2 (immunopositive area 4.34% versus 0.26%), linked with connective tissue accumulation in the tunica media of varicose veins as compared with arm and neck vein controls. TIMP-2 and TIMP-3 expression was higher in hypertrophic than atrophic segments (3.2% versus 0.99% for TIMP-2, 1.7% versus 0.08% for TIMP-3). Similarly, TIMP-2 and TIMP-3 had elevated expression in the thicker proximal varicose vein segments compared to distal (4.3% versus 1.3% for TIMP-2 and 0.94% versus 0.41% for TIMP-3). CONCLUSIONS: This study linked morphological changes in varicose vein walls with MMP/TIMP balance. A higher TIMP expression favours deposition of connective tissue and thus thicker vein wall, reducing matrix turnover by suppression of protease activity.

The value of laparoscopy in the management of non-palpable testis.

OBJECT: To retrospectively review the value of laparoscopy in the management of impalpable testis. MATERIALS AND METHODS: In 1993-2006, 182 laparoscopies for impalpable testis were performed for a total of 194 testicular units. Five laparoscopic findings were considered: testicular ectopia, intra-abdominal testis, and cord structures that are blind ending, completely absent (agenesis) or entering the internal inguinal ring. RESULTS: In 62 cases an intra-abdominal testis was found; 18 were classified as high and managed by a laparoscopic Fowler-Stephens procedure. Cord structures entering the inguinal ring were observed in 77 patients and 45 underwent an inguinal exploration: a testis was found in 12 cases and in 33 a remnant was excised. In 35 cases, intra-abdominal blind ending vas and vessels were observed and eight showed testicular agenesis. No major surgical complications were recorded. Follow up ranged from 1 to 3 years. CONCLUSIONS: Our study confirms the value of laparoscopy in the management of non-palpable testis, providing a definitive diagnosis by the direct view of spermatic bundle and testis. Ninety-three patients were managed by laparoscopy only, and in 44 it was essential for the subsequent surgical approach. When the internal inguinal ring is patent and/or normal spermatic vessels are present an inguinal exploration is mandatory.

The use of contrast enhanced ultrasound in carotid arterial disease.

Traditionally, stroke risk stratification has centred on the degree of internal carotid artery stenosis, and the presence of focal neurological symptoms. However, degree of stenosis alone is a relatively poor predictor of future stroke in asymptomatic patients; the Asymptomatic Carotid Surgery Trial highlighting the need to identify a subgroup of asymptomatics that may benefit from intervention. Attempting to define this subgroup has inspired imaging research to identify, in vivo, high-risk plaques. In addition to pre-operative risk stratification of carotid stenosis, contrast enhanced ultrasound (CEUS) may be employed in monitoring response to plaque-stabilising therapies. Unlike most contrast agents used for computed tomography and magnetic resonance imaging, microbubbles used in CEUS remain within the vascular space and can hence be used to study the vasculature. In addition to improving current carotid structural scans, CEUS has potential to add extra information on plaque characteristics. Furthermore, by targeting microbubbles to specific ligands expressed on vascular endothelium, CEUS may have the ability to probe plaque biology. This review describes the current carotid ultrasound examination and the need to improve it, rationale for imaging neovascularisation, use of CEUS to image neovascularisation, microbubbles in improving the structural imaging of plaque, potential problems with CEUS, and future directions.

Early biofilm colonization on polished- and glazed-zirconium ceramic surface. Preliminary results.

AIM: The purpose of this study was to evaluate the effect of ceramic surface polishing procedure on the early dental biofilm formation on zirconium ceramics. METHODS: Twenty samples (discs shape) of tetragonal zirconium polycrystal stabilized with yttrium ceramics (Y-TZP) for LAVA system were fabricated (5 mm diameter and 1.5 mm thickness). Two patients with high level of dental hygiene were selected for this study. Oral devices covering the crowns of the upper premolars and molars were fabricated for each participant. Glazed and polished samples of Y-TZP ceramics were fixed on the vestibular and palatal zones of the devices. After 20 min (8 samples) and 1 h (8 samples) in the oral environment, the samples were removed and analyzed in a scanning electron microscope. The surface topographies of 4 ceramic samples (2 glazed and 2 polished) were analyzed (control group: without exposition in oral environment). RESULTS: The glazed samples showed a more irregular surface than polished samples. Deposition of granular aggregates was verified on all the samples in the two times of the study analyzed. This granular material coated more intensely on irregular areas, and its thickness increased after 1 h. No difference was observed as to bacterial morphology in any time of the study. Cocci and rods-shaped prevailed. CONCLUSIONS: Glazed surfaces presented larger tendency to dental biofilm accumulation.

Is NF-kappaB a useful therapeutic target in rheumatoid arthritis?

There is increasing evidence that NF-kappaB is a major, if not the major transcription factor regulating inflammation and immunity. While this implies that blocking NF-kappaB might be therapeutically beneficial, it raises clear questions regarding the balance between efficacy and safety. In this brief review we discuss the effects of NF-kappaB blockade in rheumatoid arthritis, inflammation and immunity, and consider possible therapeutic targets within the NF-kappaB family.

RET/PTC1 oncogene signaling in PC Cl 3 thyroid cells requires the small GTP-binding protein Rho.

Thyroid papillary carcinomas are characterized by RET/PTC rearrangements that cause the tyrosine kinase domain of the RET receptor to fuse with N-terminal sequences encoded by heterologous genes. This results in the aberrant expression of a ligand-independent and constitutively active RET kinase. We analysed actin reorganization induced by the RET/PTC1 oncogene in PC Cl 3 rat thyroid epithelial cells. Differently from oncogenes Src, Ras and Raf, RET/PTC1 caused actin filaments to form prominent stress fibers. Moreover, stress fibers were identified in human thyroid papillary carcinoma cell lines harboring RET/PTC1 rearrangements but not in thyroid carcinoma cells negative for RET/PTC rearrangements. RET/MEN 2A, a constitutively active but unrearranged membrane-bound RET oncoprotein, did not induce stress fibers in PC Cl 3 cells. Induction of stress fibers by RET/PTC1 was restricted to thyroid cells; it did not occur in NIH3T3 fibroblasts or MCF7 mammary cells. RET/PTC1-mediated stress fiber formation depended on Rho but not Rac small GTPase activity. In addition, inhibition of Rho, but not of Rac, caused apoptosis of RET/PTC1-expressing thyroid cells. We conclude that Rho is implicated in the actin reorganization and cell survival mediated by the chimeric RET/PTC1 oncogene in thyroid epithelial cells, both phenotypes being cell type- and oncogene type-specific.

RET protein expression has no prognostic impact on the long-term outcome of papillary thyroid carcinoma.

BACKGROUND: RET proto-oncogene rearrangements (RET/PTC) are causative events in the pathogenesis of a subset of papillary thyroid cancer (PTC). The prevalence of RET/PTC varies in different countries and according to specific clinical features: it is higher after radiation exposure and it is claimed to be higher in young patients. Conflicting results are reported regarding the prognostic role of RET/PTC activation. OBJECTIVE: To investigate the prognostic meaning of RET/PTC rearrangement on the long term outcome of PTC. METHODS: We have studied the expression of the RET encoded protein in 127 papillary thyroid carcinomas by immunohistochemistry using a polyclonal antibody against the tyrosine-kinase domain of the RET protein. These cases have been collected during 1970-1985, and have a mean (+/-S.D.) period of follow-up of 18.6+/-3.7 years (range 12-27 years). The results have been compared with the patients' outcome. RESULTS: The tyrosine-kinase domain of RET was expressed in 82 (64.6%) papillary carcinomas. Among them, RET was highly expressed in 65 (51.2%) cases and moderately expressed in 17 (13.4%). RET expression was absent in 45 (35.4%) cases. No correlation was found between RET expression and other parameters such as sex, age at diagnosis, tumor class and histological variant. Follow-up analysis showed no influence of RET expression on patients' outcome. By multivariate analysis, age (>45 years) and tumor class IV, but not sex and RET expression were adverse prognostic indicators of death. CONCLUSION: In conclusion, our analysis indicates that RET expression is frequently found in PTC, and has no influence on tumor outcome.

Autoantibodies against oxidized low density lipoproteins in patients with stable angina, unstable angina or peripheral vascular disease; pathophysiological implications.

BACKGROUND: Antibody antioxidized low density lipoproteins (oxLDL) might play a role both in atherogenesis and in the pathogenesis of acute coronary syndromes. METHODS AND RESULTS: Antibody titres to oxLDL and levels of C-reactive protein were compared in unstable angina, stable angina or peripheral artery disease. Antibody titres to LDL oxidated by CuSO(4)for 2, 4 and 18 h (Cu-oxLDL-Ab(2-4-18)) or by peroxidase (HRP-oxLDL-Ab) were assessed by ELISA. Cu-oxLDL-Ab(2-4-18)were consistently higher in peripheral artery disease than in unstable angina (P<0.001, P<0.001, P=0.01, respectively) or in stable angina (P<0.001, P=0.01, P=ns) but similar in unstable and stable angina. Accordingly, HRP-oxLDL-Ab were higher in peripheral artery disease than in unstable angina (P<0.001) or stable angina (P=0.04) but similar in unstable and stable angina. The number of arterial stenoses was higher in peripheral artery disease than unstable and stable angina (P<0.01). Cu-oxLDL-Ab and HRP-oxLDL-Ab correlated with the severity of atherosclerosis (P<0.01, R=0.4;P=0.02, R=0.3 respectively). Conversely, C-reactive protein levels were higher in unstable than in stable angina (P<0.001) or in peripheral artery disease (P<0.03) but similar in stable angina and peripheral artery disease and did not correlate with the severity of atherosclerosis. CONCLUSION: The autoimmune response to oxLDL is likely to play an important role in atherogenesis but not in precipitating acute coronary syndromes.