New Perspectives in Overcoming Bulk-Fill Composite Polymerization Shrinkage: The Impact of Curing Mode and Layering.

BACKGROUND: The purpose of this study was to investigate the effect of different light curing modes on the polymerization shrinkage of a bulk-fill composite and to evaluate the impact of two layering techniques on the cuspal deflection. METHODS: Nine different light curing modes were tested on bulk-fill composite samples in aluminum MOD cavities. Intensity, duration, and illumination distance were the factors that changed during the different curing modes. The digital image correlation method was used to visually represent the displacement of carbon particles on the materials' surface caused by shrinkage along both the horizontal and vertical axes. For simulating cuspal deflection, a separate protocol was used, with a bulk and horizontal layering technique. RESULTS: The results showed that the largest horizontal displacements were present in the soft start group (6.00 ± 0.82 µm) and in the X-tra power group (5.67 ± 1.21 µm). The smallest horizontal displacements were detected in normal curing modes (4.00 ± 1.58 µm; 4.00 ± 2.68 µm). The largest vertical displacements, at the bottom layer, were present in the normal curing mode group with a 20 s curing time (5.22 ± 1.56 µm), while the smallest vertical displacements were shown in the X-tra power group (2.89 ± 0.60 µm). The observed particle displacements showing the shrinkage of the composite were correlated with the curing mode. The bulk-fill group showed less cuspal deflection than the horizontal layering group did, but the difference was not statistically significant (p = 0.575). CONCLUSIONS: Within the limitations of this in vitro study, it can be concluded that lower intensities of curing lights (1200 mW/cm2) may perform better from the point of view of material shrinkage than high and extreme light intensities do. The pulse delay mode might be recommended in the case of bulk-fill materials. The number of layers did not significantly affect the cuspal deflection in the case of the studied composite.

Circulating ACE2 activity predicts mortality and disease severity in hospitalized COVID-19 patients.

OBJECTIVES: Angiotensin-converting enzyme 2 (ACE2) represents the primary receptor for SARS-CoV-2 to enter endothelial cells. Here we investigated circulating ACE2 activity to predict the severity and mortality of COVID-19. METHODS: Serum ACE2 activity was measured in COVID-19 (110 critically ill and 66 severely ill subjects at hospital admission and 106 follow-up samples) and in 32 non-COVID-19 severe sepsis patients. Associations between ACE2, inflammation-dependent biomarkers, pre-existing comorbidities, and clinical outcomes were studied. RESULTS: Initial ACE2 activity was significantly higher in critically ill COVID-19 patients (54.4 [36.7-90.8] mU/L) than in severe COVID-19 (34.5 [25.2-48.7] mU/L; P<0.0001) and non-COVID-19 sepsis patients (40.9 [21.4-65.7] mU/L; P=0.0260) regardless of comorbidities. Circulating ACE2 activity correlated with inflammatory biomarkers and was further elevated during the hospital stay in critically ill patients. Based on ROC-curve analysis and logistic regression test, baseline ACE2 independently indicated the severity of COVID-19 with an AUC value of 0.701 (95% CI [0.621-0.781], P<0.0001). Furthermore, non-survivors showed higher serum ACE2 activity vs. survivors at hospital admission (P<0.0001). Finally, high ACE2 activity (≥45.4 mU/L) predicted a higher risk (65 vs. 37%) for 30-day mortality (Log-Rank P<0.0001). CONCLUSIONS: Serum ACE2 activity correlates with COVID-19 severity and predicts mortality.

Prediction of Short- and Medium-term Efficacy of Biosimilar Infliximab Therapy. Do Trough Levels and Antidrug Antibody Levels or Clinical And Biochemical Markers Play the More Important Role?

BACKGROUND AND AIMS: Biosimilar infliximab CT-P13 received European Medicines Agency [EMA] approval in June 2013 for all indications of the originator product. In the present study, we aimed to evaluate the predictors of short- and medium-term clinical outcome in patients treated with the biosimilar infliximab at the participating inflammatory bowel disease [IBD] centres in Hungary. METHODS: Demographic data were collected and a harmonised monitoring strategy was applied. Clinical and biochemical activities were evaluated at Weeks 14, 30, and 54. Trough level [TL] and anti-drug antibody [ADA] concentrations were measured by enzyme-linked immunosorbent assay [ELISA] [LT-005, Theradiag, France] at baseline at 14, 30 and 54 weeks and in two centres at Weeks 2 and 6. RESULTS: A total of 291 consecutive IBD patients (184 Crohn's disease [CD] and 107 ulcerative colitis [UC]) were included. In UC, TLs at Week 2 predicted both clinical response and remission at Weeks 14 and 30 (clinical response/remission at Week 14: area under the curve [AUC] = 0.81, p < 0.001, cut-off: 11.5 µg/ml/AUC = 0.79, p < 0.001, cut-off: 15.3µg/ml; clinical response/remission at Week 30: AUC = 0.79, p = 0.002, cut-off: 11.5 µg/ml/AUC = 0.74, p = 0.006, cut-off: 14.5 µg/ml), whereas ADA positivity at Week 14 was inversely associated with clinical response at Week 30 [58.3% vs 84.8% ,p = 0.04]. Previous anti-tumour necrosis factor [TNF] exposure was inversely associated with short-term clinical remission [Week 2: 18.8% vs 47.8%, p = 0.03, at Week 6: 38.9% vs 69.7%, p = 0.013, at Week 14: 37.5% vs 2.5%, p = 0.06]. In CD, TLs at Week 2 predicted short-term [Week 14 response/remission, AUCTLweek2 = 0.715-0.721, p = 0.05/0.005] but not medium-term clinical efficacy. In addition, early ADA status by Week 14 [p = 0.04-0.05 for Weeks 14 and 30], early clinical response [p < 0.001 for Weeks 30/54] and normal C-reactive protein [CRP] at Week 14 [p = 0.005-0.0001] and previous anti-TNF exposure [p = 0.03-0.0001 for Weeks 14, 30, and 54] were associated with short-and medium-term clinical response and remission. CONCLUSIONS: In UC, early TLs were predictive for short- and medium-term clinical efficacy, whereas in CD, Week 2 TLs were associated only with short-term clinical outcomes.

Soluble urokinase plasminogen activator receptor (suPAR) levels in healthy pregnancy and preeclampsia.

BACKGROUND: Preeclampsia is characterized by a maternal systemic inflammatory response and the impairment of maternal immune tolerance present in healthy pregnancy. Soluble urokinase plasminogen activator receptor (suPAR) is a biomarker increasingly used for the monitoring of systemic inflammation. We aimed to assess the levels of suPAR and other markers of systemic inflammation in preeclampsia compared to healthy pregnancy. METHODS: We determined plasma suPAR, IL-6 and high sensitivity C-reactive protein (hs-CRP) levels in plasma samples of 62 healthy pregnant and 41 preeclamptic women in the third trimester of pregnancy. RESULTS: Plasma suPAR levels were elevated in preeclampsia [3.18 (2.30-4.71) ng/mL vs. 2.02 (1.81-2.40) ng/mL, p=0.0001, median (interquartile range)]. IL-6 and hs-CRP levels were also higher compared with healthy pregnancy [5.99 (2.97-18.12) pg/mL vs. 1.41 (1.00-2.70) pg/mL, p=0.0001 and 6.60 (3.55-15.40) mg/L vs. 3.90 (2.10-7.25) mg/L, p=0.006, respectively, median (interquartile range)]. Linear regression analyses revealed an association between individual plasma suPAR and log IL-6 levels as well as log hs-CRP levels. CONCLUSIONS: suPAR levels are elevated in preeclampsia and vary in a narrower range compared with IL-6 and hs-CRP. ROC analysis indicated that monitoring of suPAR levels is a suitable tool for the detection of systemic inflammation in pregnancy.

Effects of bone and mineral metabolism on arterial elasticity in chronic renal failure.

Arterial stiffness (Ast) individually predicts cardiovascular (CV) mortality. Ast increases via vascular calcification and can be characterized by pulse wave velocity (PWV). We assessed the influence of mineral and bone metabolism on Ast in dialyzed (D) and renal transplanted (Tx) children by measuring fetuin-A and bone markers [bone-specific alkaline phosphatase (BALP); beta-CrossLaps (beta)]. Normalized PWV/height (PWV/h) of 11 D and 17 Tx patients was measured by applanation tonometry. Levels of calcium (Ca), phosphate (P), fetuin-A, and bone markers were analyzed. Ca x P/fetuin-A ratio was calculated to characterize the balance of calcification and inhibition. Cumulative dose of calcitriol was also assessed. Fetuin-A was lower in D and Tx compared with healthy controls. Bone markers and Ca x P/ fetuin-A of D were significantly higher than those of Tx and controls. In D PWV/h correlated with Ca x P/fetuin-A and BALP (r=0.8; p=0.005, r=0.6, p=0.05, respectively); BALP correlated with Ca x P/fetuin-A (r=0.7, p=0.01). In Tx, there was a correlation between calcitriol administered before transplantation and PWV/h (r=0.5, p=0.04). Increased bone turnover was coupled with an increased potential of calcium-phosphate precipitation, as shown by the increased Ca x P/fetuin-A. It might explain the connection between disturbed mineral and bone metabolism and Ast. Tx might be beneficial on Ast, though follow-up studies are needed.