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Introduction: Haemophilia A care has changed with the introduction of emicizumab. Experience on the youngest children is still scarce and clinical practice varies between haemophilia treatment centres. Aim: We aimed to assess the current clinical practice on emicizumab prophylaxis within PedNet, a collaborative research platform for paediatricians treating children with haemophilia. Methods: An electronic survey was sent to all PedNet members (n = 32) between October 2022 and February 2023. The survey included questions on the availability of emicizumab, on the practice of initiating prophylaxis in previously untreated or minimally treated patients (PUPs or MTPs) and emicizumab use in patients with or without inhibitors. Results: All but four centres (28/32; 88%) responded. Emicizumab was available in clinical practice in 25/28 centres (89%), and in 3/28 for selected patients only (e.g. with inhibitors). Emicizumab was the preferred choice for prophylaxis in PUPs or MTPs in 20/25 centres; most (85%) started emicizumab prophylaxis before 1 year of age (30% before 6 months of age) and without concomitant FVIII (16/20; 80%). After the loading dose, 13/28 centres administered the recommended dosing, while the others adjusted the interval of injections to give whole vials. In inhibitor patients, the use of emicizumab during ITI was common, with low‐dose ITI being the preferred protocol. Conclusion: Most centres choose to initiate prophylaxis with emicizumab before 12 months of age and without concomitant FVIII. In inhibitor patients, ITI is mostly given in addition to emicizumab, but there was no common practice on how to proceed after successful ITI. [ABSTRACT FROM AUTHOR]

Reaction of the N‐heterocylic carbene ligand iPrIm (L1) and lithium bis(trimethylsilyl)amide (TMSA) as a base with UCl4 resulted in U(IV) and U(V) complexes. Uranium's +V oxidation state in (HL1)2[U(V)(TMSI)Cl5] (TMSI=trimethylsilylimido) (2) was confirmed by HERFD‐XANES measurements. Solid state characterization by SC‐XRD and geometry optimisation of [U(IV)(L1)2(TMSA)Cl3] (1) indicated a silylamido ligand mediated inverse trans influence (ITI). The ITI was examined regarding different metal oxidation states and was compared to transition metal analogues by theoretical calculations. [ABSTRACT FROM AUTHOR]

Background: Immune tolerance induction (ITI) is the only proven strategy to eradicate factor VIII inhibitors in patients with haemophilia A (HA). Aim: To identify patients and treatment options with the highest chance of inhibitor eradication by primary ITI. Patients and methods: In the frame of the Italian ITI Registry, carried out from 1995 to 2015 (last follow‐up 2018), 137 primary ITI courses in severe HA patients (90/137 with poor prognosis) were analysed for predictors of outcome (complete/partial response or failure). Sixty‐six of them (48%) were prospectively evaluated. Results: ITI was successful in 91/137 patients (66.4%) and 70 (51.1%) achieved complete response within 11 months (median). Historical peak titres ≤200 BU/ml (P =.033), inhibitor titres ≤5 BU/ml at ITI start (P =.001), peak titres ≤100 BU/ml during ITI (P <.001) and missense mutations and small insertions/deletions of FVIII gene (P =.027) predicted complete inhibitor eradication. A score that considers the cumulative number of these variables predicted complete response with positive predictive values up to.81 at ITI start and.91 during ITI, respectively. Patients who had no bleeding (OR, 3.45, 95% CI: 1.4–8.6) nor other adverse events (OR 2.6, 95%CI: 1.3–5.3) during ITI had higher chances of complete response. During the 120‐month follow‐up (median), 2/70 patients who had achieved complete response relapsed (2.9%). Conclusions: This Registry, with a centralized review of outcomes, homogeneous data collection (half of which prospective) and long‐term follow‐up, provides insights for optimizing ITI, with a rationale for further studies in the currently evolving scenario of inhibitor management in HA patients. [ABSTRACT FROM AUTHOR]

Introduction: In good risk patients (historic inhibitor peak < 200BU), the International Immune Tolerance Study demonstrated equal efficacy to induce tolerance between high (200iu/kg/day) and low dose (50iu/kg ×3 times/week) immune tolerance induction (ITI) regimens. However, the trial stopped early on account of the excessive bleed rate in the low dose ITI arm. Methods: United Kingdom Haemophilia Centre Doctors' Organization (UKHCDO) Paediatric and Inhibitor working parties considered available ITI data alongside the bi‐phenotypic antibody emicizumab (Hemlibra®) efficacy and safety data to develop a consensus guideline for the future UK ITI guideline. Results: This revision of UKHCDO ITI guidance incorporates the recommendation to use emicizumab as a prophylaxis haemostatic agent to reduce bleeding rates and to facilitate low dose and reduced frequency of FVIII CFC for ITI in the majority of children. Conclusion: This consensus protocol will facilitate future evaluation of ITI outcomes in the evolving landscape of haemophilia therapeutics and ITI strategies. [ABSTRACT FROM AUTHOR]

Development of inhibitors (alloantibodies to exogenous factor VIII) is the most significant treatment complication in patients with haemophilia A. The only proven way to eradicate inhibitors is through immune tolerance induction ( ITI), while bypassing agents are typically employed to treat or prevent bleeds in patients with high titre inhibitors. Costs of these approaches have not been well studied. The aim of this study was to compare lifetime costs of treating patients with severe haemophilia A with inhibitors using on-demand or prophylaxis treatment with bypassing agents and ITI. A decision-analytic model was developed to compare the treatment costs and outcomes. Quantitation of the reduction in bleeding events for patients on prophylaxis and after eradication of inhibitors when on ITI and relapse of inhibitors was derived from published studies. Costs were obtained from standard US costing sources and are reported in 2014 US dollars. Costs and outcomes were discounted 3% per annum. Lifetime costs of treating patients with inhibitors are lower for ITI vs. on-demand or prophylaxis. Patients are also projected to live longer, have greater quality-adjusted life-years, and have fewer bleeding events than patients treated on-demand. Treating patients via ITI to eradicate inhibitors may result in lower lifetime costs and greater life-years and quality-adjusted life-years than treating with bypassing agents. [ABSTRACT FROM AUTHOR]

An antibody response to therapeutically administered factor VIII (FVIII) can occur in up to 30% of patients with haemophilia, resulting in the production of inhibitors that neutralize FVIII coagulant activity. Immune tolerance induction (ITI) therapy can be used to eradicate inhibitors in these patients, allowing them to continue with factor replacement therapy. Patients with inhibitors (prior to initiation of ITI, while on ITI or those who fail ITI) experience more difficulty in treating bleeds than those patients who do not develop inhibitors. Increasingly, prophylaxis with bypassing therapy is being employed in patients who develop inhibitors. Two bypassing agents, a plasma-derived activated prothrombin complex concentrate [aPCC (FEIBA®; Baxter AG, Vienna, Austria)] and NovoSeven® [recombinant factor VIIa (rFVIIa); NovoNordisk, Denmark] are potentially available for prophylaxis in patients with haemophilia who have developed inhibitors. Results from recent retrospective studies demonstrate the efficacy and safety of both aPCC and rFVIIa in decreasing the frequency of bleeding episodes in patients with haemophilia and inhibitors. In this article, we highlight a number of ongoing studies that aim to identify patients who should be placed on prophylaxis with bypassing agents. [ABSTRACT FROM AUTHOR]

Objectives: The purpose of this study was to investigate an optical solution to eliminate the undesirable shine-through effect of implants on peri-implant mucosa by selecting an optimized implant neck color based on an objective and quantifiable method. Material and methods: The optical effect of color strips on 15 peri-implant mucosal sites of 14 patients with Straumann® single-tooth implant replacements in the maxillary anterior region was analyzed. The color differences between the peri-implant mucosa with insertion of each of eight different color strips (white, black, light pink, pink, light orange, orange, gold, violet) and the gingiva of an adjacent or contralateral tooth without any color strips were compared for the selection of optimal color of implant neck. Spectrophotometric color measurements were performed to compare the color difference index (Δ E) and color coordinates (Δ L*, Δ a*, Δ b* and Δ C*). Results: The colors of the peri-implant mucosa with color strips and the gingiva of natural tooth demonstrated that the test site soft tissue with color strips of light pink, pink, light orange and orange showed a significantly smaller Δ E value ( P<0.05). Moreover, light pink exhibited the lowest mean Δ E value of 2.6±0.6, indicating a clinically indistinguishable color difference. Conclusions: The results suggest that it is possible to improve gingival esthetics by coloring the implant neck, most effectively with light pink, to mask the impact of the underlying titanium implant. The use of implants with optimized neck colors to correct an esthetic deficiency may be a feasible approach to establish improved peri-implant soft tissue esthetics. [ABSTRACT FROM AUTHOR]

Objectives: The purpose of this study was to investigate the difference in optical appearance of the soft tissues labial to dental implants and to analyze the effects of titanium implant neck colors transmitted through the marginal mucosa. Materials and methods: Fourteen patients with 15 Straumann® single implant replacements in the maxillary anterior region were recruited. Color measurements of the peri-implant mucosa of test sites and the gingivae of contralateral or adjacent natural teeth as controls were made at the facial aspect of the teeth using a spectrophotometer. The color data (CIELAB color coordinates; L*, a*, b* and C*) in five incremental areas of 1 × 2 mm from the gingival margin toward the apical direction were obtained. Results: A significant difference existed ( P<0.01) between the test site and the control site on the mean L* and b* values in all five incremental areas (area 1–5). In contrast, there was no significant difference in the mean a* values. Discrepancies between color distributions of soft tissues were stronger in areas close to the gingival margin and decreased toward the apical direction. The mean color difference Δ E between the test site and the control site was 7.7 in area 1 and decreased toward area 5 with a value of 6.5. However, there was no statistical difference in each of the mean values of differences in optical data, Δ L*, Δ a* and Δ b*, when five incremental areas of the control and the test sites were compared. Conclusion: It was observed that the color of soft tissue around the titanium implant was significantly different compared with the gingiva of natural teeth. Significantly lower values of CIELAB color coordinates, L* and b* were found in the peri-implant soft tissue. [ABSTRACT FROM AUTHOR]

Objective: The purpose of this study was to test the retention of metal copings fabricated to fit on the one-groove, one flat-sided solid titanium abutment using six different cements. Materials and methods: Ten hollow screw 3.8 mm ITI implants were mounted in acrylic resin blocks. A solid titanium abutment was placed on each implant and torqued at 35 Ncm. Prefabricated burn-out caps were placed on the titanium abutment and wax loops added to the occlusal surface to allow for subsequent retention testing. All plastic caps were embedded in phosphate-bonded investment and cast with noble alloy. Castings were inspected for surface irregularities using a stereomicroscope at 10× magnification. The six cements were: 1) eugenol-free zinc oxide (Temp Bond NE); 2) zinc-oxide eugenol (IRM); 3) zinc phosphate (Hy-Bond); 4) resin-modified glass ionomer (Protec Cem); 5) zinc polycarboxylate (Durelon) and 6) 10-methacryloyloxydecyl dihydrogen phosphate resin (Panavia 21). After cementation, implant–abutment–casting assemblies were stored for 24 h in 100% humidity. Samples were subjected to a pull-out test using an Instron universal testing machine at a crosshead speed of 0.5 mm/min. The load required to de-cement each coping was recorded and mean values for each group calculated. Means and standard deviations of loads at failure were analyzed using ANOVA and a Tukey studentized test. Statistical significance was set at P ≤ 0.05. Results: The mean values (± SD) of loads in kilograms at failure (n = 10) for the various cements were as follows: Temp Bond 3.18 ( ± 1.1) (Tukey group D), IRM 9.25 (± 3.83) (Tukey group CD), HY-Bond 10.9 (± 6.52) (Tukey group C), Protec Cem 18.98 (± 6.23) (Tukey group B), Durelon 23.55 (± 4.29) (Tukey group B) and Panavia 21, 36.53 (± 8.1) (Tukey group A). Means with the same letter in the Tukey grouping are not significantly different. Conclusions: The retention values of castings... [ABSTRACT FROM AUTHOR]

In the present report a repair set to retrieve fractured abutments remaining in the implants of the ITI® Dental Implant System is presented. In 1 case in which such fractures occurred, the repair set was successfully applied. After removal of all particles of the fractured prosthetic abutments and recutting the threads, new abutments were used, and the original suprastructure could be reinserted. The causes for such technical failures are discussed considering the relatively sparse information in the literature on that topic. [ABSTRACT FROM AUTHOR]

The article focuses on the Infaunal Trophic Index (ITI) and its suitability for marine environmental monitoring. Topics discussed include using macrobenthic invertebrate data from the San Pedro Shelf, California; community response to organic material in the water column, and effect on ITI due to water depth, granulometry, and distance from an outfall of wastewater to the ocean.

The aim of this prospective comparative study was to evaluate the condition of the peri-implant tissues of three different implant systems supporting a mandibular overdenture. Ninety edentulous patients (Cawood class V–VI) participated in this study. After randomization, 30 patients were treated with 2 Brånemark implants, 30 patients with 2 IMZ implants and 30 patients with 2 ITI implants. The implants were inserted in the canine region of the mandible. After 3 months overdentures were fabricated supported by a round bar and clip attachment. A standardized clinical and radiographic evaluation was performed 0,6 and 12 months after insertion of the denture. The intra-oral radiographs were made, using the long-cone technique with an aiming device. Two implants were lost (1 Brånemark, 1 IMZ) during the healing period. None of the patients showed any sensory change in lip or chin region. The pocket depth in the Brinemark group decreased significantly whereas the mucosa recession increased significantly in both the Brånemark as well as in the IMZ group. After 12 months, there was significantly less bone loss in the ITI group. From our study it was concluded that 2 (Brånemark, IMZ or ITI) implants placed in the interforaminal region connected with a bar supply a proper base for the support of a mandibular overdenture in the (Cawood V–VI) edentulous patient. The ITI implant appears to be the implant of choice for mandibular overdenture therapy. because only one operation is required for a comparable result. [ABSTRACT FROM AUTHOR]